alon-albalak/licensed_pubmed · Datasets at Hugging Face

id stringlengths 9 10	text stringlengths 1 3.07M	source stringclasses 1 value	added stringlengths 26 26	created stringlengths 8 19	metadata dict
PMC3052094	Related literature {#sec1} ================== For background literature concerning compounds of alkyl carboxylic acids and primary alkyl amines, see: Backlund et al. (1994[@bb3], 1997[@bb2]); Karlsson et al. (2000[@bb6], 2001[@bb7]); Kohler et al. (1972[@bb10]); Kohler, Atrops, et al. (1981[@bb8]); Kohler, Gopal, et al. (1981[@bb9]). For a description of the 'subcell' associated with the packing of the n-alkyl chains, see: Dorset (2005[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~24~N^+^·C~8~H~15~O~2~ ^−^M ~r~ = 301.50Monoclinic,a = 5.5526 (2) Åb = 44.489 (2) Åc = 8.0931 (4) Åβ = 100.788 (3)°V = 1963.90 (15) Å^3^Z = 4Mo Kα radiationμ = 0.06 mm^−1^T = 180 K0.35 × 0.18 × 0.02 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (SORTAV; Blessing, 1995[@bb4]) T ~min~ = 0.773, T ~max~ = 1.0005524 measured reflections2233 independent reflections1438 reflections with I \> 2σ(I)R ~int~ = 0.053θ~max~ = 22.0° ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.051wR(F ^2^) = 0.128S = 1.022233 reflections202 parameters3 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.13 e Å^−3^Δρ~min~ = −0.17 e Å^−3^ {#d5e536} Data collection: COLLECT (Nonius, 1998[@bb12]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[@bb13]); data reduction: DENZO (Otwinowski & Minor, 1997[@bb13]) and SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994[@bb1]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb14]); molecular graphics: Mercury (Macrae et al., 2008[@bb11]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005125/lh5207sup1.cif](http://dx.doi.org/10.1107/S1600536811005125/lh5207sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005125/lh5207Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005125/lh5207Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5207&file=lh5207sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5207sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5207&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5207](http://scripts.iucr.org/cgi-bin/sendsup?lh5207)). We thank the Department of Chemistry and the BP Institute for financial and technical assistance, and Dr John E. Davies for collecting the X-ray data. Comment ======= The combination of alkyl carboxylic acids and primary alkyl amines is of continuing interest both in the bulk and in adsorbed monolayers. There is mainly spectroscopic evidence that a number of stoichiometric complexes can form, depending upon the molecular structure: combinations AB (1 acid: 1 amine), A~2~B and A~3~B have been reported (Backlund et al., 1994; Backlund et al., 1997; Karlsson et al., 2000; Karlsson et al., 2001; Kohler, Atrops et al., 1981; Kohler, Gopal et al., 1981; Kohler et al., 1972). Interestingly, similar complexes have not been reported on the amine-rich side of the phase diagram. The precise nature of the complexation is still a matter of debate, but hydrogen bonding between the species is obviously strongly implicated and different structures have been proposed on this basis. However, we are not aware of any single-crystal diffraction studies for these materials. The absence of reported single-crystal data for this class of complexes is probably attributable to difficulties in obtaining suitable crystals. Our various crystallization attempts have consistently failed, and our discovery of the crystal used for this study was serendipitous. The crystal was a thin plate that diffracted weakly, and data could be measured only to 0.95 Å resolution. Nonetheless, the data are adequate to localize the H atoms associated with the ammonium group, and these H atoms could be refined satisfactorily with restrained N---H bond lengths and individual isotropic displacement parameters. The C---O bond lengths of 1.269 (3) and 1.253 (3) Å are also consistent with proton transfer to yield a carboxylate anion. Both molecules adopt essentially fully extended conformations (i.e. the torsion angles along the main chain are all close to 180°), although the decylammonium chain is clearly disorted from planarity (Fig. 1). As a measure of this distortion, we note that the terminal C atom of the chain (C10) lies 1.43 (1) Å from the mean plane defined by atoms C1, C2 and C3. As might be expected, the crystal structure is layered, with the hydrophilic sections accommodated around the glide planes parallel to (010) at y = 1/4 and 3/4 (Fig. 2). The hydrogen bonding between the ammonium groups and carboxylate anions (Table 1) defines a 2-D network comprising 6-membered rings (Fig. 3). Projection along the n-alkyl chains of the molecules reveals an approximately orthorhombic \"subcell\" with approximate dimensions 5.1 × 7.3 Å (the third dimension being the translation of ca 2.54 Å along the n-alkyl chain). The plane through the C atoms of the n-alkyl chain of each octanoate anion lies almost perpendicular to the planes of the n-alkyl chains of the ammonium cations (Fig. 4). This is a common subcell arrangement for long-chain n-alkyl compounds (Dorset, 2005). The distortion from planarity of the n-alkyl chain in the decylammonium cation serves to accommodate it between two neighbouring octanoic acid molecules \[symmetry codes: 1 + x,0.5 - y,-1/2 + z and 1 + x,0.5 - y,1/2 + z\], optimizing dispersion interactions along the length of the n-alkyl chains within the constraints imposed by the hydrogen-bonding geometry. At the interface between layers (i.e. in the (020) planes of the structure) the methyl groups of the decylammonium cations meet the methyl groups of the octanoate anions to form C···C contacts of 3.972 (4) Å, with the H atoms approximately eclipsed. Experimental {#experimental} ============ Octanoic acid (99%) and decylamine (99.5%) were obtained from Sigma Aldrich and used without further purification. A number of solution and melt methods were attempted to grow a single-crystal of sufficient dimensions and quality, but all were unsuccessful. A crystal was finally obtained serendipidously by growth from the vapour when poorly sealed vessels containing each of the individual components were stored together inside a small container (1 litre volume) in a glove bag initially purged with N~2~ and left undisturbed for a number of weeks. Crystal growth was observed on most of the plastic surfaces inside the storage container but principally on the polypropylene cap of the decylamine bottle. Elemental analysis found for the bulk sample: C 72.4, H 13.1, N, 4.8%; calculated C 71.7, H 13.0, N 4.7%. Refinement {#refinement} ========== The crystal diffracted relatively weakly, and data were collected to a maximum θ of 22° (0.95 Å resolution). Approximately 65% of data were observed at the 2σ level to this limit. The data are adequate to support location and refinement of the H atoms associated with the ammonium group. These were refined with N---H distances restrained to 0.91 (1) Å, and with individual U~iso~ values refined in the range 0.061 (10)--0.064 (10) Å^2^. All other H atoms were placed geometrically and refined as riding with C---H = 0.99 (CH~2~) or 0.98 (CH~3~) Å, and with U~iso~(H) = 1.2 or 1.5U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure with displacement ellipsoids drawn at 50% probability for non-H atoms. ::: ![](e-67-0o655-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Projection along the c axis showing the layered structure. H atoms are omitted and the N atoms of the NH3+ groups are highlighted as spheres. ::: ![](e-67-0o655-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Section of the structure projected along the c axis, showing the hydrogen-bond topology (dashed lines). Only the C---CO2- and C---NH3+ groups are shown. All other C and H atoms are omitted. ::: ![](e-67-0o655-fig3) ::: ::: {#Fap4 .fig} Fig. 4. ::: {.caption} ###### Section of the structure projected approximately along the long axes of the n-alkyl chains, showing the orthorhombic \"subcell\" packing. The dimensions indicated for the subcell are approximate. The third dimension of the subcell refers to the translational repeat of ca 2.54 Å along the n-alkyl chain. See Dorset (2005). ::: ![](e-67-0o655-fig4) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e258 .table-wrap} --------------------------------- ---------------------------------------- C~10~H~24~N^+^·C~8~H~15~O~2~^−^ F(000) = 680 M~r~ = 301.50 D~x~ = 1.020 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 29938 reflections a = 5.5526 (2) Å θ = 1.0--22.0° b = 44.489 (2) Å µ = 0.06 mm^−1^ c = 8.0931 (4) Å T = 180 K β = 100.788 (3)° Block, colourless V = 1963.90 (15) Å^3^ 0.35 × 0.18 × 0.02 mm Z = 4 --------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e398 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 1438 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.053 ω and φ scans θ~max~ = 22.0°, θ~min~ = 3.7° Absorption correction: multi-scan (SORTAV; Blessing, 1995) h = −5→5 T~min~ = 0.773, T~max~ = 1.000 k = −46→46 5524 measured reflections l = −8→8 2233 independent reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e514 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.051 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.128 H atoms treated by a mixture of independent and constrained refinement S = 1.02 w = 1/\[σ^2^(F~o~^2^) + (0.0647P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 2233 reflections (Δ/σ)~max~ \< 0.001 202 parameters Δρ~max~ = 0.13 e Å^−3^ 3 restraints Δρ~min~ = −0.17 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e668 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e767 .table-wrap} ------ ------------- ------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ N1 0.6509 (4) 0.23800 (6) 0.6408 (3) 0.0368 (6) H1A 0.797 (3) 0.2475 (6) 0.635 (3) 0.064 (10)\ H1B 0.552 (4) 0.2520 (5) 0.681 (3) 0.061 (10)\* H1C 0.564 (4) 0.2308 (6) 0.540 (2) 0.063 (10)\* C1 0.7131 (5) 0.21366 (6) 0.7683 (3) 0.0376 (7) H1D 0.7889 0.2226 0.8776 0.045\* H1E 0.8346 0.2000 0.7330 0.045\* C2 0.4907 (5) 0.19598 (6) 0.7896 (3) 0.0443 (8) H2A 0.4128 0.1875 0.6794 0.053\* H2B 0.3712 0.2097 0.8271 0.053\* C3 0.5494 (5) 0.17059 (6) 0.9156 (3) 0.0453 (8) H3A 0.6910 0.1591 0.8902 0.054\* H3B 0.5984 0.1793 1.0296 0.054\* C4 0.3373 (5) 0.14915 (6) 0.9157 (3) 0.0479 (8) H4A 0.1991 0.1606 0.9465 0.057\* H4B 0.2827 0.1415 0.7999 0.057\* C5 0.3925 (5) 0.12257 (7) 1.0335 (3) 0.0469 (8) H5A 0.4359 0.1301 1.1504 0.056\* H5B 0.5369 0.1118 1.0077 0.056\* C6 0.1810 (5) 0.10059 (6) 1.0222 (3) 0.0466 (8) H6A 0.0387 0.1113 1.0520 0.056\* H6B 0.1335 0.0938 0.9042 0.056\* C7 0.2351 (5) 0.07329 (7) 1.1342 (4) 0.0511 (8) H7A 0.2901 0.0801 1.2516 0.061\* H7B 0.3725 0.0621 1.1009 0.061\* C8 0.0211 (5) 0.05205 (6) 1.1290 (4) 0.0505 (8) H8A −0.1158 0.0633 1.1630 0.061\* H8B −0.0345 0.0453 1.0114 0.061\* C9 0.0743 (6) 0.02465 (7) 1.2396 (4) 0.0648 (10) H9A 0.1386 0.0313 1.3563 0.078\* H9B 0.2044 0.0128 1.2015 0.078\* C10 −0.1459 (6) 0.00445 (7) 1.2403 (4) 0.0763 (11) H10A −0.0969 −0.0128 1.3145 0.114\* H10B −0.2086 −0.0027 1.1258 0.114\* H10C −0.2744 0.0158 1.2809 0.114\* O1 0.4243 (3) 0.28030 (4) 0.81491 (19) 0.0384 (5) O2 0.1023 (3) 0.26380 (4) 0.6328 (2) 0.0424 (5) C11 0.1952 (5) 0.27876 (6) 0.7601 (3) 0.0333 (7) C12 0.0316 (4) 0.29610 (6) 0.8566 (3) 0.0358 (7) H12A 0.0647 0.2891 0.9748 0.043\* H12B −0.1413 0.2912 0.8086 0.043\* C13 0.0628 (5) 0.33012 (6) 0.8553 (3) 0.0368 (7) H13A 0.2345 0.3353 0.9050 0.044\* H13B 0.0292 0.3374 0.7376 0.044\* C14 −0.1081 (5) 0.34575 (6) 0.9533 (3) 0.0400 (7) H14A −0.0733 0.3381 1.0702 0.048\* H14B −0.2785 0.3400 0.9038 0.048\* C15 −0.0940 (5) 0.37981 (6) 0.9594 (3) 0.0419 (8) H15A 0.0749 0.3859 1.0110 0.050\* H15B −0.1288 0.3877 0.8431 0.050\* C16 −0.2713 (5) 0.39370 (6) 1.0579 (3) 0.0447 (8) H16A −0.2394 0.3851 1.1728 0.054\* H16B −0.4400 0.3879 1.0041 0.054\* C17 −0.2585 (5) 0.42763 (6) 1.0715 (4) 0.0527 (8) H17A −0.2878 0.4363 0.9568 0.063\* H17B −0.0911 0.4335 1.1277 0.063\* C18 −0.4416 (5) 0.44107 (7) 1.1682 (4) 0.0704 (10) H18A −0.4233 0.4630 1.1721 0.106\* H18B −0.4115 0.4330 1.2830 0.106\* H18C −0.6084 0.4359 1.1119 0.106\* ------ ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1576 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ N1 0.0325 (15) 0.0405 (16) 0.0377 (16) −0.0004 (14) 0.0076 (13) −0.0051 (14) C1 0.0383 (16) 0.0406 (18) 0.0332 (15) 0.0040 (15) 0.0051 (12) 0.0004 (15) C2 0.0379 (17) 0.051 (2) 0.0441 (17) −0.0020 (16) 0.0070 (13) 0.0085 (16) C3 0.0410 (17) 0.052 (2) 0.0412 (17) −0.0032 (16) 0.0038 (14) 0.0024 (16) C4 0.0411 (17) 0.059 (2) 0.0427 (18) −0.0047 (17) 0.0053 (14) 0.0068 (17) C5 0.0435 (18) 0.052 (2) 0.0449 (17) −0.0015 (16) 0.0069 (14) 0.0087 (17) C6 0.0470 (18) 0.048 (2) 0.0448 (18) 0.0012 (16) 0.0081 (14) 0.0064 (16) C7 0.0499 (19) 0.049 (2) 0.0553 (19) 0.0005 (16) 0.0115 (15) 0.0081 (17) C8 0.0524 (19) 0.045 (2) 0.056 (2) −0.0044 (17) 0.0152 (15) 0.0033 (17) C9 0.067 (2) 0.056 (2) 0.076 (2) −0.001 (2) 0.0242 (18) 0.013 (2) C10 0.080 (3) 0.057 (2) 0.100 (3) −0.010 (2) 0.036 (2) 0.007 (2) O1 0.0247 (11) 0.0510 (13) 0.0390 (10) 0.0009 (9) 0.0048 (8) −0.0016 (10) O2 0.0360 (11) 0.0542 (14) 0.0364 (11) −0.0062 (10) 0.0049 (9) −0.0129 (11) C11 0.0300 (17) 0.0360 (18) 0.0349 (16) 0.0013 (15) 0.0084 (13) 0.0116 (16) C12 0.0306 (15) 0.0392 (18) 0.0381 (16) −0.0013 (14) 0.0080 (13) −0.0008 (14) C13 0.0333 (15) 0.0378 (18) 0.0392 (16) −0.0006 (14) 0.0065 (12) 0.0036 (14) C14 0.0389 (16) 0.039 (2) 0.0441 (16) 0.0028 (15) 0.0124 (13) 0.0000 (15) C15 0.0389 (17) 0.041 (2) 0.0472 (17) 0.0004 (15) 0.0105 (14) −0.0029 (15) C16 0.0452 (18) 0.040 (2) 0.0492 (18) 0.0021 (16) 0.0095 (14) −0.0030 (16) C17 0.0494 (19) 0.045 (2) 0.063 (2) 0.0036 (17) 0.0077 (16) −0.0066 (17) C18 0.065 (2) 0.059 (2) 0.088 (3) 0.0103 (19) 0.0179 (19) −0.015 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1975 .table-wrap} -------------------- ------------ ----------------------- ------------ N1---C1 1.491 (3) C9---H9A 0.990 N1---H1A 0.92 (1) C9---H9B 0.990 N1---H1B 0.93 (1) C10---H10A 0.980 N1---H1C 0.92 (1) C10---H10B 0.980 C1---C2 1.501 (3) C10---H10C 0.980 C1---H1D 0.990 O1---C11 1.268 (3) C1---H1E 0.990 O2---C11 1.253 (3) C2---C3 1.516 (3) C11---C12 1.515 (3) C2---H2A 0.990 C12---C13 1.524 (3) C2---H2B 0.990 C12---H12A 0.990 C3---C4 1.516 (3) C12---H12B 0.990 C3---H3A 0.990 C13---C14 1.515 (3) C3---H3B 0.990 C13---H13A 0.990 C4---C5 1.514 (4) C13---H13B 0.990 C4---H4A 0.990 C14---C15 1.517 (3) C4---H4B 0.990 C14---H14A 0.990 C5---C6 1.518 (3) C14---H14B 0.990 C5---H5A 0.990 C15---C16 1.510 (3) C5---H5B 0.990 C15---H15A 0.990 C6---C7 1.511 (4) C15---H15B 0.990 C6---H6A 0.990 C16---C17 1.514 (4) C6---H6B 0.990 C16---H16A 0.990 C7---C8 1.513 (4) C16---H16B 0.990 C7---H7A 0.990 C17---C18 1.517 (4) C7---H7B 0.990 C17---H17A 0.990 C8---C9 1.508 (4) C17---H17B 0.990 C8---H8A 0.990 C18---H18A 0.980 C8---H8B 0.990 C18---H18B 0.980 C9---C10 1.518 (4) C18---H18C 0.980 C1---N1---H1A 105.9 (17) C8---C9---H9B 108.7 C1---N1---H1B 108.7 (18) C10---C9---H9B 108.7 H1A---N1---H1B 107 (3) H9A---C9---H9B 107.6 C1---N1---H1C 111.8 (18) C9---C10---H10A 109.5 H1A---N1---H1C 116 (2) C18^i^---C10---H10A 53.7 H1B---N1---H1C 107 (2) C9---C10---H10B 109.5 N1---C1---C2 111.8 (2) C18^i^---C10---H10B 79.7 N1---C1---H1D 109.3 H10A---C10---H10B 109.5 C2---C1---H1D 109.3 C9---C10---H10C 109.5 N1---C1---H1E 109.3 H10A---C10---H10C 109.5 C2---C1---H1E 109.3 H10B---C10---H10C 109.5 H1D---C1---H1E 107.9 O2---C11---O1 123.2 (2) C1---C2---C3 112.9 (2) O2---C11---C12 120.0 (2) C1---C2---H2A 109.0 O1---C11---C12 116.8 (3) C3---C2---H2A 109.0 C11---C12---C13 115.0 (2) C1---C2---H2B 109.0 C11---C12---H12A 108.5 C3---C2---H2B 109.0 C13---C12---H12A 108.5 H2A---C2---H2B 107.8 C11---C12---H12B 108.5 C4---C3---C2 113.6 (2) C13---C12---H12B 108.5 C4---C3---H3A 108.9 H12A---C12---H12B 107.5 C2---C3---H3A 108.9 C14---C13---C12 111.7 (2) C4---C3---H3B 108.9 C14---C13---H13A 109.3 C2---C3---H3B 108.9 C12---C13---H13A 109.3 H3A---C3---H3B 107.7 C14---C13---H13B 109.3 C5---C4---C3 115.2 (2) C12---C13---H13B 109.3 C5---C4---H4A 108.5 H13A---C13---H13B 107.9 C3---C4---H4A 108.5 C13---C14---C15 116.2 (2) C5---C4---H4B 108.5 C13---C14---H14A 108.2 C3---C4---H4B 108.5 C15---C14---H14A 108.2 H4A---C4---H4B 107.5 C13---C14---H14B 108.2 C4---C5---C6 113.7 (2) C15---C14---H14B 108.2 C4---C5---H5A 108.8 H14A---C14---H14B 107.4 C6---C5---H5A 108.8 C16---C15---C14 113.0 (2) C4---C5---H5B 108.8 C16---C15---H15A 109.0 C6---C5---H5B 108.8 C14---C15---H15A 109.0 H5A---C5---H5B 107.7 C16---C15---H15B 109.0 C7---C6---C5 114.6 (2) C14---C15---H15B 109.0 C7---C6---H6A 108.6 H15A---C15---H15B 107.8 C5---C6---H6A 108.6 C15---C16---C17 114.8 (2) C7---C6---H6B 108.6 C15---C16---H16A 108.6 C5---C6---H6B 108.6 C17---C16---H16A 108.6 H6A---C6---H6B 107.6 C15---C16---H16B 108.6 C6---C7---C8 114.7 (2) C17---C16---H16B 108.6 C6---C7---H7A 108.6 H16A---C16---H16B 107.5 C8---C7---H7A 108.6 C16---C17---C18 113.8 (2) C6---C7---H7B 108.6 C16---C17---H17A 108.8 C8---C7---H7B 108.6 C18---C17---H17A 108.8 H7A---C7---H7B 107.6 C16---C17---H17B 108.8 C9---C8---C7 115.0 (2) C18---C17---H17B 108.8 C9---C8---H8A 108.5 H17A---C17---H17B 107.7 C7---C8---H8A 108.5 C17---C18---H18A 109.5 C9---C8---H8B 108.5 C17---C18---H18B 109.5 C7---C8---H8B 108.5 H18A---C18---H18B 109.5 H8A---C8---H8B 107.5 C17---C18---H18C 109.5 C8---C9---C10 114.3 (3) H18A---C18---H18C 109.5 C8---C9---H9A 108.7 H18B---C18---H18C 109.5 C10---C9---H9A 108.7 N1---C1---C2---C3 178.6 (2) O2---C11---C12---C13 −115.7 (3) C1---C2---C3---C4 −169.5 (2) O1---C11---C12---C13 64.4 (3) C2---C3---C4---C5 177.0 (2) C11---C12---C13---C14 179.6 (2) C3---C4---C5---C6 −176.4 (2) C12---C13---C14---C15 −179.6 (2) C4---C5---C6---C7 177.9 (2) C13---C14---C15---C16 179.4 (2) C5---C6---C7---C8 177.4 (2) C14---C15---C16---C17 178.3 (2) C6---C7---C8---C9 179.6 (2) C15---C16---C17---C18 178.9 (2) C7---C8---C9---C10 176.8 (3) -------------------- ------------ ----------------------- ------------ ::: Symmetry codes: (i) −x−1, y−1/2, −z+5/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2878 .table-wrap} -------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1B···O1 0.93 (1) 1.89 (1) 2.788 (3) 164 (2) N1---H1C···O1^ii^ 0.92 (1) 1.91 (1) 2.821 (3) 170 (2) N1---H1A···O2^iii^ 0.92 (1) 1.85 (1) 2.768 (3) 175 (3) -------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (ii) x, −y+1/2, z−1/2; (iii) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- ---------- ---------- ----------- ------------- N1---H1B⋯O1 0.93 (1) 1.89 (1) 2.788 (3) 164 (2) N1---H1C⋯O1^i^ 0.92 (1) 1.91 (1) 2.821 (3) 170 (2) N1---H1A⋯O2^ii^ 0.92 (1) 1.85 (1) 2.768 (3) 175 (3) Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.396533	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052094/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o655", "authors": [ { "first": "Andrew E.", "last": "Jefferson" }, { "first": "Chenguang", "last": "Sun" }, { "first": "Andrew D.", "last": "Bond" }, { "first": "Stuart M.", "last": "Clarke" } ] }
PMC3052095	Related literature {#sec1} ================== For related structures with an indane group linked to a pyridine derivative through a C---O---C bridge, see: Dinçer et al. (2004[@bb3]); Lifshits et al. (2008[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~13~BrN~2~OM ~r~ = 305.17Monoclinic,a = 11.3944 (18) Åb = 9.4515 (15) Åc = 12.438 (2) Åβ = 110.678 (2)°V = 1253.2 (3) Å^3^Z = 4Mo Kα radiationμ = 3.27 mm^−1^T = 100 K0.21 × 0.16 × 0.08 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2001[@bb1]) T ~min~ = 0.547, T ~max~ = 0.78023669 measured reflections2942 independent reflections2595 reflections with I \> 2σ(I)R ~int~ = 0.046 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.023wR(F ^2^) = 0.054S = 1.032942 reflections163 parametersH-atom parameters constrainedΔρ~max~ = 0.38 e Å^−3^Δρ~min~ = −0.30 e Å^−3^ {#d5e405} Data collection: APEX2 (Bruker, 2007[@bb2]); cell refinement: SAINT (Bruker, 2007[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb5]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005332/rz2555sup1.cif](http://dx.doi.org/10.1107/S1600536811005332/rz2555sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005332/rz2555Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005332/rz2555Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2555&file=rz2555sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2555sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2555&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2555](http://scripts.iucr.org/cgi-bin/sendsup?rz2555)). Comment ======= The present study confirmed the expected structure of the title compound, the product of reaction between indan-1-yl methanesulfonate and 2-amino-5-bromopyridin-3-ol in the presence of caesium carbonate (Fig. 1). All C atoms of the indane fragment with the exception of C7 are coplanar within 0.03 Å; the latter atom is displaced by 0.206 (2) Å from the mean plane based on all the remaining atoms of the bicyclic system. The O1 atom deviates from this plane by 1.008 (2) Å in the same direction as the C7 atom. The central C2---O1---C6 bridge is in fact coplanar with the pyridine ring so that the N1/C1/C2/C3/C3/C4/C5/O1/C6 fragment is planar within 0.01 Å and its plane forms the dihedral angle of 57.6 (3)° with the above mentioned indane plane. It is noteworthy, that general conformations of a few other structurally studied molecules featuring indane group linked to pyridine derivatives through the C---O---C bridge (Dinçer et al., 2004; Lifshits et al., 2008) bear close resemblance to that of the molecule of the title compound. The N2---H2NA···N1^i^ bonds \[symmetry code (i): 2 - x, 1 - y, 2 - z\] (Table 1) link molecules in the crystal of the title compounds into centrosymmetric dimers (Fig. 2). One more intermolecular contact N2---H2NB···Br1^ii^ \[symmetry code (ii): x - 1/2, 1.5 - y, z - 1/2\] may also play certain role in the stability of the packing, although corresponding interaction seems to be too weak to be qualified as one more independent H-bond. Experimental {#experimental} ============ To a solution of 2-amino-5-bromopyridin-3-ol (1.640 g, 8.48 mmol) in 42 ml of DMF was added 2,3-dihydro-1H-inden-1-yl methanesulfonate (0.9 g, 4.24 mmol) and caesium carbonate (1.380 g, 4.24 mmol) and heated to 60°C overnight. The reaction mixture was quenched with water and the aqueous layer was extracted with EtOAc (3 x 20 ml). The organic layers were combined, dried over MgSO~4~, filtered and concentrated. The product was purified by flash chromatography (silica gel, 10--50% EtOAc/heptane) to give 525 mg (46%) 5-bromo-3-(2,3-dihydro-1H-inden-1-yloxy)pyridin-2-amine as a white solid. The colorless crystals were grown by slow cooling of the solution of the title compound in boiling dichloroetane. Refinement {#refinement} ========== All H atoms were placed in geometrically calculated positions (N---H 0.88 Å, C---H 0.95 Å, 0.99 Å and 1.00 Å for aromatic, methylene and methine groups respectively) and included in the refinement in the riding motion approximation. The U~iso~(H) were set to 1.2U~eq~ of the carrying atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound, showing 50% probability displacement ellipsoids. H atoms are drawn as circles of arbitrary small radius. ::: ![](e-67-0o650-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Packing diagram of the title compound viewed down the b axis. H-bonds are shown as dashed lines. ::: ![](e-67-0o650-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e157 .table-wrap} ------------------------- --------------------------------------- C~14~H~13~BrN~2~O F(000) = 616 M~r~ = 305.17 D~x~ = 1.617 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 9797 reflections a = 11.3944 (18) Å θ = 2.8--27.7° b = 9.4515 (15) Å µ = 3.27 mm^−1^ c = 12.438 (2) Å T = 100 K β = 110.678 (2)° Block, colorless V = 1253.2 (3) Å^3^ 0.21 × 0.16 × 0.08 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e285 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2942 independent reflections Radiation source: fine-focus sealed tube 2595 reflections with I \> 2σ(I) graphite R~int~ = 0.046 φ and ω scans θ~max~ = 28.3°, θ~min~ = 2.1° Absorption correction: multi-scan (SADABS; Bruker, 2001) h = −15→14 T~min~ = 0.547, T~max~ = 0.780 k = −12→12 23669 measured reflections l = −16→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e402 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.023 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.054 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0191P)^2^ + 0.7815P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2942 reflections (Δ/σ)~max~ = 0.001 163 parameters Δρ~max~ = 0.38 e Å^−3^ 0 restraints Δρ~min~ = −0.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e559 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e658 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 1.235622 (16) 1.080477 (17) 1.070416 (15) 0.02063 (6) O1 0.95752 (11) 0.77404 (12) 0.71352 (10) 0.0192 (3) N1 1.06647 (13) 0.68706 (14) 1.01301 (12) 0.0179 (3) N2 0.95112 (15) 0.56292 (15) 0.84811 (13) 0.0227 (3) H2NA 0.9477 0.4894 0.8903 0.027\ H2NB 0.9150 0.5591 0.7729 0.027\* C1 1.01219 (16) 0.68247 (17) 0.89913 (14) 0.0163 (3) C2 1.01793 (15) 0.79884 (17) 0.82822 (14) 0.0165 (3) C3 1.08206 (16) 0.91835 (17) 0.87805 (15) 0.0171 (3) H3 1.0868 0.9979 0.8331 0.020\* C4 1.14048 (16) 0.91900 (16) 0.99797 (15) 0.0161 (3) C5 1.13089 (16) 0.80499 (17) 1.06228 (15) 0.0180 (3) H5 1.1704 0.8086 1.1435 0.022\* C6 0.95743 (16) 0.88611 (17) 0.63483 (14) 0.0168 (3) H6 1.0431 0.9283 0.6559 0.020\* C7 0.85977 (17) 1.00246 (18) 0.62819 (15) 0.0209 (4) H7A 0.8003 0.9696 0.6647 0.025\* H7B 0.9019 1.0892 0.6681 0.025\* C8 0.78992 (16) 1.03247 (17) 0.49914 (15) 0.0184 (3) H8A 0.6983 1.0385 0.4815 0.022\* H8B 0.8193 1.1220 0.4759 0.022\* C9 0.82218 (16) 0.90756 (16) 0.43914 (15) 0.0164 (3) C10 0.91601 (15) 0.82524 (17) 0.51553 (14) 0.0163 (3) C11 0.96492 (16) 0.70772 (17) 0.47841 (15) 0.0200 (4) H11 1.0284 0.6517 0.5316 0.024\* C12 0.91930 (17) 0.67388 (18) 0.36230 (16) 0.0225 (4) H12 0.9523 0.5947 0.3353 0.027\* C13 0.82497 (17) 0.75614 (19) 0.28514 (15) 0.0224 (4) H13 0.7942 0.7322 0.2059 0.027\* C14 0.77560 (17) 0.87233 (18) 0.32274 (15) 0.0204 (4) H14 0.7109 0.9272 0.2699 0.025\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1068 .table-wrap} ----- -------------- ------------- -------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.02147 (10) 0.01833 (9) 0.01970 (10) −0.00397 (7) 0.00432 (7) −0.00082 (6) O1 0.0247 (7) 0.0182 (6) 0.0125 (6) −0.0039 (5) 0.0038 (5) 0.0033 (4) N1 0.0195 (7) 0.0179 (7) 0.0156 (7) −0.0011 (6) 0.0055 (6) 0.0024 (5) N2 0.0298 (9) 0.0198 (7) 0.0140 (7) −0.0074 (6) 0.0021 (6) 0.0035 (6) C1 0.0150 (8) 0.0174 (7) 0.0168 (8) 0.0007 (6) 0.0058 (7) 0.0029 (6) C2 0.0149 (8) 0.0209 (8) 0.0137 (8) 0.0019 (6) 0.0052 (6) 0.0030 (6) C3 0.0178 (8) 0.0168 (8) 0.0172 (9) 0.0013 (6) 0.0070 (7) 0.0039 (6) C4 0.0141 (8) 0.0155 (7) 0.0184 (8) −0.0002 (6) 0.0053 (7) −0.0013 (6) C5 0.0187 (9) 0.0201 (8) 0.0145 (8) 0.0009 (7) 0.0049 (7) 0.0003 (6) C6 0.0195 (9) 0.0169 (7) 0.0140 (8) −0.0022 (6) 0.0057 (7) 0.0033 (6) C7 0.0257 (10) 0.0202 (8) 0.0161 (9) 0.0025 (7) 0.0067 (7) 0.0009 (7) C8 0.0184 (9) 0.0171 (8) 0.0180 (9) 0.0002 (6) 0.0045 (7) 0.0020 (6) C9 0.0170 (8) 0.0158 (7) 0.0166 (8) −0.0037 (6) 0.0062 (7) 0.0018 (6) C10 0.0159 (8) 0.0177 (8) 0.0158 (8) −0.0032 (6) 0.0061 (7) 0.0012 (6) C11 0.0179 (9) 0.0193 (8) 0.0225 (9) −0.0002 (7) 0.0067 (7) 0.0013 (7) C12 0.0233 (9) 0.0200 (8) 0.0262 (10) −0.0048 (7) 0.0113 (8) −0.0068 (7) C13 0.0256 (10) 0.0258 (9) 0.0154 (9) −0.0086 (7) 0.0066 (7) −0.0050 (7) C14 0.0213 (9) 0.0199 (8) 0.0169 (9) −0.0040 (7) 0.0028 (7) 0.0029 (7) ----- -------------- ------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1416 .table-wrap} ------------------ ------------- ----------------- ------------- Br1---C4 1.9044 (16) C7---C8 1.545 (2) O1---C2 1.368 (2) C7---H7A 0.9900 O1---C6 1.4419 (19) C7---H7B 0.9900 N1---C1 1.331 (2) C8---C9 1.510 (2) N1---C5 1.356 (2) C8---H8A 0.9900 N2---C1 1.361 (2) C8---H8B 0.9900 N2---H2NA 0.8800 C9---C10 1.391 (2) N2---H2NB 0.8800 C9---C14 1.395 (2) C1---C2 1.426 (2) C10---C11 1.393 (2) C2---C3 1.369 (2) C11---C12 1.388 (3) C3---C4 1.402 (2) C11---H11 0.9500 C3---H3 0.9500 C12---C13 1.397 (3) C4---C5 1.369 (2) C12---H12 0.9500 C5---H5 0.9500 C13---C14 1.388 (3) C6---C10 1.504 (2) C13---H13 0.9500 C6---C7 1.546 (2) C14---H14 0.9500 C6---H6 1.0000 C2---O1---C6 117.49 (13) C6---C7---H7A 110.4 C1---N1---C5 118.79 (14) C8---C7---H7B 110.4 C1---N2---H2NA 120.0 C6---C7---H7B 110.4 C1---N2---H2NB 120.0 H7A---C7---H7B 108.6 H2NA---N2---H2NB 120.0 C9---C8---C7 104.11 (13) N1---C1---N2 119.49 (15) C9---C8---H8A 110.9 N1---C1---C2 121.84 (15) C7---C8---H8A 110.9 N2---C1---C2 118.66 (15) C9---C8---H8B 110.9 O1---C2---C3 127.25 (15) C7---C8---H8B 110.9 O1---C2---C1 113.39 (14) H8A---C8---H8B 109.0 C3---C2---C1 119.35 (15) C10---C9---C14 119.63 (16) C2---C3---C4 117.53 (15) C10---C9---C8 111.25 (15) C2---C3---H3 121.2 C14---C9---C8 129.04 (16) C4---C3---H3 121.2 C9---C10---C11 121.40 (16) C5---C4---C3 120.80 (15) C9---C10---C6 110.97 (14) C5---C4---Br1 120.25 (13) C11---C10---C6 127.55 (15) C3---C4---Br1 118.94 (12) C12---C11---C10 118.81 (16) N1---C5---C4 121.67 (16) C12---C11---H11 120.6 N1---C5---H5 119.2 C10---C11---H11 120.6 C4---C5---H5 119.2 C11---C12---C13 120.06 (16) O1---C6---C10 108.27 (13) C11---C12---H12 120.0 O1---C6---C7 112.76 (14) C13---C12---H12 120.0 C10---C6---C7 104.49 (14) C14---C13---C12 120.92 (16) O1---C6---H6 110.4 C14---C13---H13 119.5 C10---C6---H6 110.4 C12---C13---H13 119.5 C7---C6---H6 110.4 C13---C14---C9 119.18 (16) C8---C7---C6 106.45 (14) C13---C14---H14 120.4 C8---C7---H7A 110.4 C9---C14---H14 120.4 ------------------ ------------- ----------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1844 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N2---H2NA···N1^i^ 0.88 2.10 2.975 (2) 178 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+2, −y+1, −z+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- --------- ------- ----------- ------------- N2---H2NA⋯N1^i^ 0.88 2.10 2.975 (2) 178 Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.402344	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052095/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o650", "authors": [ { "first": "Sujin", "last": "Cho-Schultz" }, { "first": "John C.", "last": "Kath" }, { "first": "Curtis", "last": "Moore" }, { "first": "Arnold L.", "last": "Rheingold" }, { "first": "Alex", "last": "Yanovsky" } ] }
PMC3052096	Related literature {#sec1} ================== For other inorganic--organic hybrid materials based on polyoxidometalates with organic cations, see: Alizadeh et al. (2008a [@bb3],b [@bb2]); Nikpour et al. (2009[@bb8], 2010[@bb7]). For details of (H~2~O)~n~ cluster analysis, see: Aghabozorg et al. (2010[@bb1]). For background to pseudopolymorphism, see: Desiraju (2003[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~6~H~12~N~5~O)~3~\[W~12~(PO~4~)O~36~\]·6H~2~OM ~r~ = 3495.88Orthorhombic,a = 14.616 (3) Åb = 15.213 (3) Åc = 26.735 (6) ÅV = 5944 (2) Å^3^Z = 4Mo Kα radiationμ = 23.27 mm^−1^T = 100 K0.12 × 0.11 × 0.06 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2005[@bb4]) T ~min~ = 0.078, T ~max~ = 0.24659635 measured reflections12321 independent reflections9617 reflections with I \> 2σ(I)R ~int~ = 0.159 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.052wR(F ^2^) = 0.104S = 1.0012321 reflections446 parameters6 restraintsH-atom parameters constrainedΔρ~max~ = 2.80 e Å^−3^Δρ~min~ = −2.72 e Å^−3^Absolute structure: Flack (1983[@bb6]), 5544 Friedel pairsFlack parameter: −0.041 (19) {#d5e926} Data collection: APEX2 (Bruker, 2005[@bb4]); cell refinement: SAINT (Bruker, 2005[@bb4]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: publCIF (Westrip, 2010[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003734/wm2435sup1.cif](http://dx.doi.org/10.1107/S1600536811003734/wm2435sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003734/wm2435Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003734/wm2435Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2435&file=wm2435sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2435sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2435&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2435](http://scripts.iucr.org/cgi-bin/sendsup?wm2435)). The Islamic Azad University, Quchan Branch, Quchan, Iran is gratefully acknowledged for financial support of this research paper. Comment ======= In continuation of our previous studies of inorganic-organic hybrid materials based on polyoxidometalates (Alizadeh et al., 2008a,b; Nikpour et al., 2009), we report here on the structure of the title compound, \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^6H~2~O, (I), as a pseudopolymorph (different number of crystal water molecules; Desiraju, 2003) of \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^5H~2~O as reported by us previously (Nikpour et al., 2010). The structure of (I) consists of one discrete anion \[(PO~4~)W~12~O~36~\]^3-^, three \[C~6~H~12~N~5~O\]^+^ cations and six water molecules of crystallisation. (Fig. 1). The anion in the title compound is of the well-known α-Keggin type consisting of four groups of W~3~O~10~ units. Each WO~6~ octahedron in such a unit shares edges with its neighbours. Four W~3~O~10~ units are linked together via corner-sharing WO~6~ octahedra to form a cage with a P atom located in the tetrahedrally surrounded centre. There are four kinds of oxygen atoms in the heteropolyanion, viz. four O atoms (O1c, O5c, O9c, O13c) that are bonded to the P atom and to three W atoms, twelve corner-sharing atoms Oc atom that bridge the different W~3~O~13~ units, twelve edge-sharing atoms Ob that bridge within the W~3~O~13~ units, and twelve terminal oxygen atoms Ot. In the organic cation, the 1H-tetrazole ring and the methylcarbon atom lie approximately in the same plane and the morpholine ring is in a chair configuration. In (I), all bond lengths and angles are normal and comparable with those observed in the pseudopolymorph with 5 crystal water molecules (Nikpour et al., 2010)). The three organic cations in (I) show only minor differences with respect to bond lengths and angles. The molecular entities are linked together via an extensive network of N---H···O, N---H···N, O---H···O and O---H···N hydrogen bonding interactions (Fig. 2). The charge-compensating cations \[C~6~H~12~N~5~O\]^+^ can be considered as the space-filling structural subunits and are connected to one side of the α-\[(PO~4~)W~12~O~36~\]^3-^ anion by the aforementioned multiple hydrogen-bonding interactions. Since \[C~6~H~12~N~5~O\]^+^ cations lie at one side of the anion, the inorganic anions are well-separated by \[C~6~H~12~N~5~O\]^+^ cations and by additional water molecules of crystallisation. In recent years, there has been increasing interest in the experimental and theoretical study of water clusters (H~2~O)~n~ because these water assemblies might provide an insight into some of the unexplained properties of bulk water, namely into the processes that occur at the ice-liquid, ice-air, and liquid-air interfaces, and into the nature of water-water and water-solute interactions (Aghabozorg et al. 2010). In the network of (I), six uncoordinated water molecules increase the number of O---H···O hydrogen bonds and thus lead to the formation of (H~2~O)~∞~ clusters. Indeed, these units were found to act as a \'supramolecular glue\' in the aggregation of \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^6H~2~O and hence support the consolidation of the three-dimensional network. Experimental {#experimental} ============ A solution of ((1H-tetrazole-5-yl)methyl)morpholine (0.14 g, 0.82 mmol) in 30 ml of distilled water was added with vigorous stirring to a solution of α-H~3~\[(PO~4~)W~12~O~36~\]^.^21H~2~O (0.50 g, 0.27 mmol) in 25 ml of distilled water. A colorless precipitate was formed after five hours. The solid was filtered off, washed with DMF and dried at room temperature. The precipitate was then re-dissolved in acetonitrile and the solution was cooled to ambient temperature; colorless block-shaped crystals were obtained, filtered off, washed several times with distilled water, and dried in air (yield 30% based on W) and characterized by spectroscopy and X-ray crystallography methods. ^1^H NMR in D~2~O:d 2.65 (t, 4H, (CH~2~)~2~N), 3.80 (t,4H, (CH~2~)~2~O), 4.15 (s, 2H, CH~2~-(N(CH~2~)~2~)).Anal. calcd. for C~18~H~45~N~15~O~49~PW~12~:C, 6.19; H, 1.30; N, 6.02; P, 0.90; W, 63.20. Found: C, 6.41; H, 1.41; N, 5.88; P, 0.85; W, 63.00. Refinement {#refinement} ========== Only heavy atoms (P and W) were refined anisotropically. Refinement in anisotropic approximation for all atoms was unstable due to the limited scattering powder of the crystal and absorption effects which could not be completely corrected. The highest peak and the deepest hole in the final Fourier map are 0.86 Å and 0.91 Å away from atoms W8 and W3, respectively. Positions of hydrogen atoms were calculated. All hydrogen atoms were treated in the riding model approximation with the U~iso~(H) parameters equal to 1.2 U~eq~(Ci), where U~eq~(C) are the equivalent temperature factors of the atoms to which corresponding H atoms are bonded. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of \[C6H12N5O\]3\[W12(PO4)O36\].6H2O, with displacement ellipsoids drawn at the 50% probability level. ::: ![](e-67-0m301-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of (I) in a projection along a, emphasizing the three-dimensional H-bonded network (dashed lines). ::: ![](e-67-0m301-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e472 .table-wrap} ------------------------------------------------- -------------------------------------- (C~6~H~12~N~5~O)~3~\[W~12~(PO~4~)O~36~\]·6H~2~O F(000) = 6224 M~r~ = 3495.88 D~x~ = 3.906 Mg m^−3^ Orthorhombic, P2~1~2~1~2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 846 reflections a = 14.616 (3) Å θ = 2.4--24.2° b = 15.213 (3) Å µ = 23.27 mm^−1^ c = 26.735 (6) Å T = 100 K V = 5944 (2) Å^3^ Plate, colourless Z = 4 0.12 × 0.11 × 0.06 mm ------------------------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e613 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD area-detector diffractometer 12321 independent reflections Radiation source: fine-focus sealed tube 9617 reflections with I \> 2σ(I) graphite R~int~ = 0.159 ω scans θ~max~ = 26.5°, θ~min~ = 1.5° Absorption correction: multi-scan (SADABS; Bruker, 2005) h = −18→18 T~min~ = 0.078, T~max~ = 0.246 k = −19→19 59635 measured reflections l = −33→33 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e727 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------ Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.052 H-atom parameters constrained wR(F^2^) = 0.104 w = 1/\[σ^2^(F~o~^2^) + (0.015P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.00 (Δ/σ)~max~ = 0.001 12321 reflections Δρ~max~ = 2.80 e Å^−3^ 446 parameters Δρ~min~ = −2.72 e Å^−3^ 6 restraints Absolute structure: Flack (1983), 5544 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.041 (19) ---------------------------------------------------------------- ------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e889 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e988 .table-wrap} ------ -------------- -------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ W1 0.13685 (6) 0.08083 (6) 0.78414 (3) 0.0071 (2) W2 0.12581 (6) −0.11475 (6) 0.84527 (3) 0.00680 (19) W3 −0.01178 (6) 0.05564 (6) 0.88273 (3) 0.00663 (19) W4 0.23993 (6) 0.27465 (6) 0.84686 (3) 0.0063 (2) W5 0.32328 (6) 0.25584 (6) 0.96592 (3) 0.00742 (19) W6 0.09215 (6) 0.24836 (6) 0.94429 (3) 0.00671 (19) W7 0.38668 (6) 0.08881 (6) 0.80600 (3) 0.0069 (2) W8 0.46950 (6) 0.07104 (6) 0.92481 (3) 0.0077 (2) W9 0.37534 (7) −0.10728 (6) 0.86647 (3) 0.0078 (2) W10 0.21725 (7) −0.13462 (6) 0.97307 (3) 0.0076 (2) W11 0.08109 (6) 0.03551 (6) 1.01029 (3) 0.0071 (2) W12 0.31213 (6) 0.04266 (6) 1.03168 (3) 0.0075 (2) P1 0.2295 (4) 0.0669 (4) 0.9062 (2) 0.0048 (11) O1B 0.1641 (10) 0.1949 (9) 0.8099 (5) 0.004 (3)\ O2B 0.2655 (11) 0.0633 (9) 0.7824 (5) 0.010 (3)\* O3B 0.2554 (11) −0.1191 (10) 0.8382 (6) 0.015 (4)\* O4B 0.1447 (10) −0.1393 (10) 0.9133 (5) 0.009 (3)\* O5B 0.0152 (10) 0.0215 (9) 0.9489 (5) 0.006 (3)\* O6B 0.0257 (11) 0.1702 (9) 0.9025 (5) 0.009 (3)\* O7B 0.3371 (11) 0.1990 (10) 0.8259 (6) 0.011 (4)\* O8B 0.4150 (11) 0.1809 (9) 0.9367 (5) 0.009 (3)\* O9B 0.3045 (11) 0.1634 (9) 1.0121 (5) 0.007 (3)\* O10B 0.0901 (11) 0.1564 (10) 0.9929 (6) 0.013 (4)\* O11B 0.4062 (11) 0.0320 (10) 0.9827 (5) 0.012 (3)\* O12B 0.3195 (10) −0.1331 (9) 0.9280 (5) 0.008 (3)\* O1C 0.1542 (10) 0.0355 (9) 0.8695 (5) 0.006 (3)\* O2C 0.1237 (10) −0.0454 (9) 0.7853 (5) 0.009 (3)\* O3C 0.0181 (10) 0.0886 (9) 0.8151 (5) 0.006 (3)\* O4C 0.0105 (10) −0.0617 (9) 0.8616 (5) 0.009 (3)\* O5C 0.2234 (11) 0.1677 (9) 0.9125 (5) 0.010 (4)\* O6C 0.1364 (11) 0.3072 (9) 0.8851 (5) 0.008 (3)\* O7C 0.3141 (10) 0.3122 (9) 0.9011 (5) 0.002 (3)\* O8C 0.1998 (10) 0.2924 (9) 0.9769 (5) 0.004 (3)\* O9C 0.3222 (11) 0.0400 (10) 0.8850 (5) 0.009 (3)\* O10C 0.4081 (11) −0.0347 (10) 0.8101 (5) 0.012 (3)\* O11C 0.4790 (11) 0.1034 (10) 0.8545 (5) 0.012 (3)\* O12C 0.4726 (12) −0.0506 (11) 0.9018 (6) 0.017 (4)\* O13C 0.2162 (10) 0.0225 (9) 0.9574 (5) 0.004 (3)\* O14C 0.2926 (10) −0.0796 (9) 1.0242 (5) 0.005 (3)\* O15C 0.1137 (11) −0.0849 (10) 1.0077 (5) 0.012 (3)\* O16C 0.1849 (11) 0.0503 (10) 1.0520 (6) 0.014 (4)\* O1T 0.1113 (11) 0.1009 (9) 0.7229 (5) 0.008 (3)\* O2T 0.0886 (12) −0.2120 (11) 0.8230 (6) 0.021 (4)\* O3T −0.1262 (11) 0.0627 (10) 0.8820 (5) 0.009 (3)\* O4T 0.2503 (11) 0.3612 (9) 0.8069 (6) 0.011 (3)\* O5T 0.3826 (11) 0.3329 (10) 0.9988 (6) 0.013 (4)\* O6T 0.0161 (12) 0.3183 (10) 0.9630 (6) 0.015 (4)\* O7T 0.4435 (10) 0.1134 (10) 0.7519 (5) 0.008 (3)\* O8T 0.5799 (10) 0.0855 (10) 0.9435 (5) 0.009 (3)\* O9T 0.4278 (10) −0.2028 (9) 0.8515 (5) 0.008 (3)\* O10T 0.2142 (10) −0.2426 (9) 0.9929 (5) 0.007 (3)\* O11T −0.0015 (10) 0.0336 (9) 1.0544 (5) 0.007 (3)\* O12T 0.3661 (11) 0.0419 (10) 1.0867 (5) 0.010 (3)\* O1 −0.0329 (11) 0.6253 (10) 0.9033 (6) 0.014 (4)\* O2 0.3910 (12) 0.1840 (10) 0.6455 (6) 0.014 (4)\* O3 0.7992 (11) 0.3157 (10) 0.8498 (6) 0.013 (4)\* N1A 0.2428 (14) 0.5669 (13) 1.0482 (7) 0.016 (5)\* N2A 0.3121 (13) 0.6174 (12) 1.0671 (6) 0.010 (4)\* N3A 0.3715 (13) 0.6348 (12) 1.0333 (7) 0.012 (4)\* N4A 0.3446 (13) 0.5980 (12) 0.9905 (7) 0.014 (4)\* H4A 0.3725 0.6005 0.9614 0.017\* N5A 0.1426 (13) 0.5627 (13) 0.9376 (7) 0.014 (4)\* H5A 0.1673 0.5989 0.9147 0.017\* N1B 0.1622 (12) 0.4400 (11) 0.7087 (6) 0.006 (4)\* N2B 0.1362 (15) 0.4894 (13) 0.7487 (7) 0.019 (5)\* N3B 0.0718 (14) 0.4460 (13) 0.7736 (7) 0.017 (5)\* N4B 0.0632 (13) 0.3681 (12) 0.7506 (6) 0.009 (4)\* H4B 0.0263 0.3256 0.7601 0.010\* N5B 0.2227 (13) 0.2763 (12) 0.6584 (7) 0.010 (4)\* H5B 0.2237 0.3313 0.6460 0.012\* N1C 0.4485 (14) 0.3858 (13) 0.7645 (7) 0.015 (5)\* N2C 0.4037 (14) 0.4569 (13) 0.7477 (7) 0.015 (4)\* N3C 0.3909 (14) 0.5159 (13) 0.7846 (7) 0.017 (5)\* N4C 0.4281 (14) 0.4820 (13) 0.8246 (7) 0.017 (5)\* H4C 0.4293 0.5058 0.8546 0.020\* N5C 0.6017 (12) 0.3217 (11) 0.8337 (6) 0.005 (4)\* H5C 0.6146 0.3135 0.8023 0.006\* C1A 0.2647 (16) 0.5557 (14) 1.0014 (8) 0.013 (5)\* C2A 0.2074 (16) 0.5054 (14) 0.9619 (8) 0.012 (5)\* H2A 0.2489 0.4797 0.9365 0.014\* H2B 0.1742 0.4566 0.9784 0.014\* C3A 0.0767 (16) 0.6076 (15) 0.9709 (9) 0.014 (5)\* H3A 0.1105 0.6373 0.9981 0.017\* H3B 0.0358 0.5633 0.9863 0.017\* C4A 0.0184 (18) 0.6757 (15) 0.9428 (8) 0.016 (5)\* H4D −0.0247 0.7050 0.9660 0.019\* H4E 0.0579 0.7210 0.9273 0.019\* C5A 0.0289 (14) 0.5823 (13) 0.8701 (7) 0.004 (4)\* H5D 0.0670 0.6270 0.8531 0.005\* H5E −0.0066 0.5507 0.8442 0.005\* C6A 0.0924 (15) 0.5159 (13) 0.8974 (7) 0.004 (4)\* H6A 0.0556 0.4676 0.9119 0.004\* H6B 0.1364 0.4901 0.8733 0.004\* C1B 0.1192 (16) 0.3644 (14) 0.7108 (8) 0.011 (5)\* C2B 0.1251 (15) 0.2898 (13) 0.6748 (7) 0.006 (4)\* H2C 0.0864 0.3024 0.6452 0.007\* H2D 0.1020 0.2355 0.6908 0.007\* C3B 0.2338 (17) 0.2013 (14) 0.6242 (9) 0.013 (5)\* H3C 0.2175 0.1464 0.6420 0.016\* H3D 0.1910 0.2080 0.5957 0.016\* C4B 0.3270 (17) 0.1938 (16) 0.6050 (9) 0.017 (6)\* H4F 0.3313 0.1422 0.5825 0.021\* H4G 0.3424 0.2469 0.5853 0.021\* C5B 0.3838 (16) 0.2549 (14) 0.6768 (8) 0.011 (5)\* H5F 0.3981 0.3090 0.6578 0.013\* H5G 0.4299 0.2491 0.7038 0.013\* C6B 0.2899 (14) 0.2648 (13) 0.7004 (7) 0.006 (5)\* H6C 0.2746 0.2118 0.7202 0.007\* H6D 0.2886 0.3165 0.7228 0.007\* C1C 0.4646 (16) 0.4033 (15) 0.8114 (8) 0.013 (5)\* C2C 0.5061 (16) 0.3423 (15) 0.8466 (8) 0.013 (5)\* H2E 0.4701 0.2872 0.8472 0.016\* H2F 0.5040 0.3682 0.8806 0.016\* C3C 0.6655 (15) 0.3995 (14) 0.8253 (8) 0.007 (5)\* H3E 0.6405 0.4372 0.7983 0.008\* H3F 0.6691 0.4351 0.8562 0.008\* C4C 0.7572 (18) 0.3700 (16) 0.8114 (9) 0.019 (6)\* H4H 0.7536 0.3361 0.7799 0.022\* H4I 0.7964 0.4220 0.8052 0.022\* C5C 0.7445 (17) 0.2421 (15) 0.8584 (9) 0.015 (5)\* H5H 0.7725 0.2068 0.8855 0.018\* H5I 0.7439 0.2054 0.8278 0.018\* C6C 0.6498 (17) 0.2625 (16) 0.8723 (8) 0.015 (5)\* H6E 0.6495 0.2922 0.9053 0.019\* H6F 0.6150 0.2069 0.8757 0.019\* O1W 0.9409 (11) 0.2541 (10) 0.7904 (5) 0.013 (4)\* H1W 0.9675 0.2096 0.8030 0.016\* H2W 0.8972 0.2730 0.8085 0.016\* O2W 0.4266 (11) 0.6202 (10) 0.8979 (5) 0.014 (4)\* H35 0.4805 0.6109 0.9087 0.017\* H36 0.4465 0.6690 0.8867 0.017\* O3W 0.3234 (12) 0.4705 (11) 0.6534 (7) 0.027 (4)\* H5W 0.3264 0.4896 0.6236 0.033\* H6W 0.3570 0.4951 0.6752 0.033\* O4W 0.6176 (14) 0.2121 (12) 0.7543 (6) 0.029 (5)\* H7W 0.5676 0.1836 0.7536 0.035\* H8W 0.6645 0.1847 0.7436 0.035\* O5W 0.2453 (12) 0.6697 (10) 0.8761 (6) 0.018 (4)\* H9W 0.2960 0.6448 0.8824 0.022\* H10W 0.2317 0.6666 0.8452 0.022\* O6W 0.2054 (12) 0.6585 (11) 0.7745 (6) 0.020 (4)\* H71 0.1806 0.6207 0.7554 0.024\* H72 0.1714 0.7033 0.7707 0.024\* ------ -------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2795 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ W1 0.0073 (5) 0.0071 (4) 0.0068 (4) −0.0005 (4) −0.0002 (4) −0.0001 (4) W2 0.0071 (5) 0.0054 (4) 0.0079 (4) 0.0006 (4) −0.0003 (4) −0.0009 (4) W3 0.0049 (5) 0.0065 (4) 0.0085 (4) 0.0006 (4) 0.0000 (4) −0.0006 (4) W4 0.0061 (5) 0.0051 (4) 0.0077 (5) −0.0002 (4) 0.0001 (4) 0.0006 (4) W5 0.0080 (5) 0.0055 (4) 0.0088 (5) −0.0005 (4) −0.0015 (4) 0.0001 (4) W6 0.0060 (5) 0.0051 (4) 0.0091 (4) 0.0001 (4) 0.0014 (4) −0.0003 (4) W7 0.0050 (5) 0.0068 (4) 0.0090 (4) 0.0005 (4) 0.0007 (4) 0.0007 (4) W8 0.0061 (5) 0.0076 (4) 0.0094 (4) −0.0004 (4) −0.0014 (4) 0.0007 (4) W9 0.0058 (5) 0.0061 (4) 0.0114 (5) 0.0012 (4) 0.0015 (4) −0.0002 (4) W10 0.0088 (5) 0.0052 (4) 0.0088 (5) −0.0003 (4) −0.0004 (4) 0.0008 (4) W11 0.0070 (5) 0.0068 (4) 0.0076 (5) 0.0000 (4) 0.0010 (4) 0.0009 (4) W12 0.0089 (5) 0.0073 (4) 0.0064 (5) 0.0002 (4) −0.0008 (4) 0.0008 (4) P1 0.0043 (18) 0.0060 (17) 0.0042 (17) −0.0007 (15) −0.0014 (15) 0.0003 (15) ----- ------------- ------------- ------------- -------------- -------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3072 .table-wrap} ----------------------- ------------- ----------------------- ------------- W1---O1T 1.706 (14) N1A---C1A 1.30 (3) W1---O2B 1.900 (16) N1A---N2A 1.37 (3) W1---O1B 1.909 (14) N2A---N3A 1.28 (2) W1---O3C 1.926 (15) N3A---N4A 1.33 (2) W1---O2C 1.930 (14) N4A---C1A 1.37 (3) W1---O1C 2.396 (14) N4A---H4A 0.8800 W2---O2T 1.685 (17) N5A---C2A 1.44 (3) W2---O4B 1.878 (14) N5A---C6A 1.48 (3) W2---O3B 1.905 (17) N5A---C3A 1.48 (3) W2---O2C 1.920 (14) N5A---H5A 0.8997 W2---O4C 1.919 (15) N1B---C1B 1.31 (3) W2---O1C 2.412 (14) N1B---N2B 1.36 (3) W3---O3T 1.676 (15) N2B---N3B 1.33 (3) W3---O5B 1.886 (14) N3B---N4B 1.34 (3) W3---O4C 1.900 (14) N4B---C1B 1.34 (3) W3---O6B 1.902 (15) N4B---H4B 0.8800 W3---O3C 1.925 (13) N5B---C3B 1.47 (3) W3---O1C 2.471 (15) N5B---C6B 1.50 (3) W4---O4T 1.703 (15) N5B---C2B 1.51 (3) W4---O6C 1.893 (15) N5B---H5B 0.9000 W4---O7C 1.899 (14) N1C---C1C 1.30 (3) W4---O7B 1.912 (16) N1C---N2C 1.34 (3) W4---O1B 1.917 (14) N2C---N3C 1.35 (3) W4---O5C 2.405 (14) N3C---N4C 1.31 (3) W5---O5T 1.702 (16) N4C---C1C 1.36 (3) W5---O9B 1.892 (14) N4C---H4C 0.8800 W5---O8C 1.911 (15) N5C---C2C 1.47 (3) W5---O8B 1.925 (15) N5C---C3C 1.52 (3) W5---O7C 1.938 (13) N5C---C6C 1.54 (3) W5---O5C 2.444 (15) N5C---H5C 0.8698 W6---O6T 1.619 (16) C1A---C2A 1.55 (3) W6---O6B 1.898 (15) C2A---H2A 0.9900 W6---O10B 1.910 (15) C2A---H2B 0.9900 W6---O8C 1.919 (14) C3A---C4A 1.54 (3) W6---O6C 1.928 (14) C3A---H3A 0.9900 W6---O5C 2.430 (15) C3A---H3B 0.9900 W7---O7T 1.710 (14) C4A---H4D 0.9900 W7---O11C 1.884 (15) C4A---H4E 0.9900 W7---O7B 1.902 (15) C5A---C6A 1.55 (3) W7---O10C 1.908 (15) C5A---H5D 0.9900 W7---O2B 1.920 (15) C5A---H5E 0.9900 W7---O9C 2.428 (14) C6A---H6A 0.9900 W8---O8T 1.704 (15) C6A---H6B 0.9900 W8---O8B 1.879 (15) C1B---C2B 1.49 (3) W8---O11B 1.900 (15) C2B---H2C 0.9900 W8---O12C 1.950 (16) C2B---H2D 0.9900 W8---O11C 1.949 (14) C3B---C4B 1.46 (3) W8---O9C 2.448 (15) C3B---H3C 0.9900 W9---O9T 1.691 (14) C3B---H3D 0.9900 W9---O12B 1.878 (15) C4B---H4F 0.9900 W9---O12C 1.913 (17) C4B---H4G 0.9900 W9---O3B 1.918 (17) C5B---C6B 1.52 (3) W9---O10C 1.928 (15) C5B---H5F 0.9900 W9---O9C 2.423 (15) C5B---H5G 0.9900 W10---O10T 1.727 (14) C6B---H6C 0.9900 W10---O12B 1.920 (15) C6B---H6D 0.9900 W10---O4B 1.918 (14) C1C---C2C 1.46 (3) W10---O15C 1.929 (15) C2C---H2E 0.9900 W10---O14C 1.944 (14) C2C---H2F 0.9900 W10---O13C 2.427 (13) C3C---C4C 1.46 (3) W11---O11T 1.687 (14) C3C---H3E 0.9900 W11---O15C 1.895 (15) C3C---H3F 0.9900 W11---O16C 1.897 (16) C4C---H4H 0.9900 W11---O10B 1.901 (15) C4C---H4I 0.9900 W11---O5B 1.914 (14) C5C---C6C 1.47 (3) W11---O13C 2.437 (14) C5C---H5H 0.9900 W12---O12T 1.668 (14) C5C---H5I 0.9900 W12---O14C 1.892 (13) C6C---H6E 0.9900 W12---O11B 1.904 (15) C6C---H6F 0.9900 W12---O9B 1.913 (14) O1W---H1W 0.8498 W12---O16C 1.941 (16) O1W---H2W 0.8501 W12---O13C 2.451 (14) O2W---H35 0.8500 P1---O9C 1.525 (16) O2W---H36 0.8500 P1---O13C 1.538 (14) O3W---H5W 0.8498 P1---O5C 1.545 (15) O3W---H6W 0.8501 P1---O1C 1.550 (15) O4W---H7W 0.8500 O1---C5A 1.43 (2) O4W---H8W 0.8500 O1---C4A 1.51 (3) O5W---H9W 0.8499 O2---C5B 1.37 (2) O5W---H10W 0.8500 O2---C4B 1.44 (3) O6W---H71 0.8500 O3---C5C 1.40 (3) O6W---H72 0.8499 O3---C4C 1.45 (3) O1T---W1---O2B 102.6 (7) W2---O4B---W10 151.7 (9) O1T---W1---O1B 103.2 (6) W3---O5B---W11 151.5 (8) O2B---W1---O1B 86.0 (6) W6---O6B---W3 152.2 (9) O1T---W1---O3C 101.8 (7) W7---O7B---W4 153.5 (9) O2B---W1---O3C 155.6 (6) W8---O8B---W5 153.0 (9) O1B---W1---O3C 88.7 (6) W5---O9B---W12 152.2 (8) O1T---W1---O2C 99.9 (6) W11---O10B---W6 151.1 (9) O2B---W1---O2C 87.7 (6) W8---O11B---W12 152.3 (9) O1B---W1---O2C 156.8 (6) W9---O12B---W10 152.9 (9) O3C---W1---O2C 87.9 (6) P1---O1C---W1 126.1 (8) O1T---W1---O1C 171.0 (6) P1---O1C---W2 125.7 (8) O2B---W1---O1C 83.0 (6) W1---O1C---W2 90.0 (5) O1B---W1---O1C 84.0 (5) P1---O1C---W3 124.6 (8) O3C---W1---O1C 72.7 (5) W1---O1C---W3 89.8 (5) O2C---W1---O1C 73.1 (5) W2---O1C---W3 89.3 (5) O2T---W2---O4B 102.4 (7) W2---O2C---W1 124.0 (7) O2T---W2---O3B 104.8 (8) W1---O3C---W3 126.3 (7) O4B---W2---O3B 86.7 (7) W3---O4C---W2 127.8 (8) O2T---W2---O2C 100.5 (7) P1---O5C---W4 125.9 (8) O4B---W2---O2C 157.1 (6) P1---O5C---W6 125.8 (9) O3B---W2---O2C 87.3 (7) W4---O5C---W6 89.6 (5) O2T---W2---O4C 99.5 (8) P1---O5C---W5 125.0 (9) O4B---W2---O4C 89.6 (6) W4---O5C---W5 89.7 (5) O3B---W2---O4C 155.6 (6) W6---O5C---W5 89.4 (5) O2C---W2---O4C 86.8 (6) W4---O6C---W6 126.2 (8) O2T---W2---O1C 169.3 (7) W4---O7C---W5 126.1 (7) O4B---W2---O1C 84.5 (6) W5---O8C---W6 127.1 (7) O3B---W2---O1C 83.6 (6) P1---O9C---W9 127.5 (9) O2C---W2---O1C 72.9 (5) P1---O9C---W7 125.9 (8) O4C---W2---O1C 72.0 (6) W9---O9C---W7 88.9 (5) O3T---W3---O5B 103.7 (7) P1---O9C---W8 124.6 (8) O3T---W3---O4C 103.1 (7) W9---O9C---W8 89.1 (5) O5B---W3---O4C 89.1 (6) W7---O9C---W8 88.7 (5) O3T---W3---O6B 103.4 (7) W7---O10C---W9 124.6 (8) O5B---W3---O6B 86.1 (6) W7---O11C---W8 125.6 (8) O4C---W3---O6B 153.4 (7) W9---O12C---W8 124.5 (9) O3T---W3---O3C 101.5 (7) P1---O13C---W10 125.8 (8) O5B---W3---O3C 154.8 (6) P1---O13C---W11 125.7 (8) O4C---W3---O3C 85.8 (6) W10---O13C---W11 89.1 (5) O6B---W3---O3C 87.5 (6) P1---O13C---W12 126.4 (8) O3T---W3---O1C 170.4 (6) W10---O13C---W12 88.8 (4) O5B---W3---O1C 84.0 (6) W11---O13C---W12 89.0 (4) O4C---W3---O1C 70.9 (6) W12---O14C---W10 125.7 (7) O6B---W3---O1C 82.6 (6) W11---O15C---W10 126.4 (8) O3C---W3---O1C 71.0 (5) W11---O16C---W12 126.5 (8) O4T---W4---O6C 102.0 (7) C5A---O1---C4A 110.7 (17) O4T---W4---O7C 101.3 (7) C5B---O2---C4B 109.3 (17) O6C---W4---O7C 88.0 (6) C5C---O3---C4C 109.4 (18) O4T---W4---O7B 102.4 (7) C1A---N1A---N2A 104.3 (19) O6C---W4---O7B 155.5 (6) N3A---N2A---N1A 110.9 (17) O7C---W4---O7B 88.9 (6) N2A---N3A---N4A 108.6 (18) O4T---W4---O1B 102.5 (7) N3A---N4A---C1A 105.5 (18) O6C---W4---O1B 89.0 (6) N3A---N4A---H4A 127.3 O7C---W4---O1B 156.1 (6) C1A---N4A---H4A 127.3 O7B---W4---O1B 84.1 (6) C2A---N5A---C6A 111.2 (17) O4T---W4---O5C 171.9 (6) C2A---N5A---C3A 115.9 (18) O6C---W4---O5C 72.7 (6) C6A---N5A---C3A 109.6 (18) O7C---W4---O5C 72.8 (5) C2A---N5A---H5A 114.4 O7B---W4---O5C 83.2 (6) C6A---N5A---H5A 89.9 O1B---W4---O5C 83.7 (5) C3A---N5A---H5A 112.8 O5T---W5---O9B 104.5 (7) C1B---N1B---N2B 108.5 (18) O5T---W5---O8C 101.7 (7) N3B---N2B---N1B 108.5 (18) O9B---W5---O8C 88.8 (6) N2B---N3B---N4B 106.0 (18) O5T---W5---O8B 105.2 (7) N3B---N4B---C1B 110.1 (19) O9B---W5---O8B 85.7 (6) N3B---N4B---H4B 124.9 O8C---W5---O8B 153.1 (6) C1B---N4B---H4B 124.9 O5T---W5---O7C 101.1 (6) C3B---N5B---C6B 107.6 (17) O9B---W5---O7C 154.5 (6) C3B---N5B---C2B 113.0 (17) O8C---W5---O7C 86.7 (6) C6B---N5B---C2B 114.7 (16) O8B---W5---O7C 87.0 (6) C3B---N5B---H5B 119.4 O5T---W5---O5C 169.7 (6) C6B---N5B---H5B 111.8 O9B---W5---O5C 83.5 (6) C2B---N5B---H5B 89.8 O8C---W5---O5C 71.6 (6) C1C---N1C---N2C 104.1 (19) O8B---W5---O5C 81.6 (6) N1C---N2C---N3C 111.2 (18) O7C---W5---O5C 71.3 (5) N4C---N3C---N2C 106.2 (19) O6T---W6---O6B 104.1 (8) N3C---N4C---C1C 107.4 (19) O6T---W6---O10B 105.1 (7) N3C---N4C---H4C 126.3 O6B---W6---O10B 86.2 (6) C1C---N4C---H4C 126.3 O6T---W6---O8C 101.1 (7) C2C---N5C---C3C 116.8 (16) O6B---W6---O8C 154.8 (6) C2C---N5C---C6C 113.6 (17) O10B---W6---O8C 87.7 (6) C3C---N5C---C6C 105.9 (16) O6T---W6---O6C 100.3 (7) C2C---N5C---H5C 117.6 O6B---W6---O6C 88.8 (6) C3C---N5C---H5C 80.4 O10B---W6---O6C 154.6 (7) C6C---N5C---H5C 117.6 O8C---W6---O6C 86.3 (6) N1A---C1A---N4A 111 (2) O6T---W6---O5C 169.2 (7) N1A---C1A---C2A 126 (2) O6B---W6---O5C 83.2 (6) N4A---C1A---C2A 123 (2) O10B---W6---O5C 83.1 (6) N5A---C2A---C1A 111.3 (18) O8C---W6---O5C 71.8 (5) N5A---C2A---H2A 109.4 O6C---W6---O5C 71.5 (6) C1A---C2A---H2A 109.4 O7T---W7---O11C 102.0 (7) N5A---C2A---H2B 109.4 O7T---W7---O7B 103.2 (7) C1A---C2A---H2B 109.4 O11C---W7---O7B 88.6 (7) H2A---C2A---H2B 108.0 O7T---W7---O10C 100.6 (7) N5A---C3A---C4A 112.2 (18) O11C---W7---O10C 87.6 (6) N5A---C3A---H3A 109.2 O7B---W7---O10C 156.1 (7) C4A---C3A---H3A 109.2 O7T---W7---O2B 102.4 (7) N5A---C3A---H3B 109.2 O11C---W7---O2B 155.6 (6) C4A---C3A---H3B 109.2 O7B---W7---O2B 85.4 (6) H3A---C3A---H3B 107.9 O10C---W7---O2B 88.4 (6) O1---C4A---C3A 106.0 (18) O7T---W7---O9C 172.4 (6) O1---C4A---H4D 110.5 O11C---W7---O9C 73.5 (6) C3A---C4A---H4D 110.5 O7B---W7---O9C 83.0 (6) O1---C4A---H4E 110.5 O10C---W7---O9C 73.3 (6) C3A---C4A---H4E 110.5 O2B---W7---O9C 82.3 (6) H4D---C4A---H4E 108.7 O8T---W8---O8B 103.7 (7) O1---C5A---C6A 112.7 (16) O8T---W8---O11B 105.2 (7) O1---C5A---H5D 109.1 O8B---W8---O11B 86.2 (6) C6A---C5A---H5D 109.1 O8T---W8---O12C 101.1 (7) O1---C5A---H5E 109.1 O8B---W8---O12C 155.2 (7) C6A---C5A---H5E 109.1 O11B---W8---O12C 88.4 (6) H5D---C5A---H5E 107.8 O8T---W8---O11C 100.6 (7) N5A---C6A---C5A 108.9 (16) O8B---W8---O11C 88.2 (6) N5A---C6A---H6A 109.9 O11B---W8---O11C 154.2 (7) C5A---C6A---H6A 109.9 O12C---W8---O11C 86.2 (6) N5A---C6A---H6B 109.9 O8T---W8---O9C 170.3 (6) C5A---C6A---H6B 109.9 O8B---W8---O9C 82.7 (6) H6A---C6A---H6B 108.3 O11B---W8---O9C 82.3 (6) N1B---C1B---N4B 106.8 (19) O12C---W8---O9C 72.6 (6) N1B---C1B---C2B 128 (2) O11C---W8---O9C 72.0 (6) N4B---C1B---C2B 125 (2) O9T---W9---O12B 102.9 (7) C1B---C2B---N5B 110.3 (18) O9T---W9---O12C 99.6 (7) C1B---C2B---H2C 109.6 O12B---W9---O12C 89.1 (6) N5B---C2B---H2C 109.6 O9T---W9---O3B 103.9 (7) C1B---C2B---H2D 109.6 O12B---W9---O3B 85.9 (7) N5B---C2B---H2D 109.6 O12C---W9---O3B 156.4 (7) H2C---C2B---H2D 108.1 O9T---W9---O10C 101.2 (7) C4B---C3B---N5B 112 (2) O12B---W9---O10C 155.8 (6) C4B---C3B---H3C 109.1 O12C---W9---O10C 86.7 (7) N5B---C3B---H3C 109.1 O3B---W9---O10C 88.5 (7) C4B---C3B---H3D 109.1 O9T---W9---O9C 171.3 (6) N5B---C3B---H3D 109.1 O12B---W9---O9C 82.9 (6) H3C---C3B---H3D 107.8 O12C---W9---O9C 73.8 (6) O2---C4B---C3B 110.5 (19) O3B---W9---O9C 82.8 (6) O2---C4B---H4F 109.5 O10C---W9---O9C 73.1 (6) C3B---C4B---H4F 109.5 O10T---W10---O12B 102.9 (6) O2---C4B---H4G 109.5 O10T---W10---O4B 101.9 (6) C3B---C4B---H4G 109.5 O12B---W10---O4B 84.7 (6) H4F---C4B---H4G 108.1 O10T---W10---O15C 101.9 (7) O2---C5B---C6B 113.7 (19) O12B---W10---O15C 155.2 (6) O2---C5B---H5F 108.8 O4B---W10---O15C 88.9 (6) C6B---C5B---H5F 108.8 O10T---W10---O14C 102.1 (6) O2---C5B---H5G 108.8 O12B---W10---O14C 89.7 (6) C6B---C5B---H5G 108.8 O4B---W10---O14C 156.1 (6) H5F---C5B---H5G 107.7 O15C---W10---O14C 86.5 (6) N5B---C6B---C5B 107.0 (16) O10T---W10---O13C 171.9 (6) N5B---C6B---H6C 110.3 O12B---W10---O13C 83.4 (6) C5B---C6B---H6C 110.3 O4B---W10---O13C 83.6 (6) N5B---C6B---H6D 110.3 O15C---W10---O13C 72.1 (6) C5B---C6B---H6D 110.3 O14C---W10---O13C 72.6 (5) H6C---C6B---H6D 108.6 O11T---W11---O15C 100.9 (7) N1C---C1C---N4C 111 (2) O11T---W11---O16C 99.4 (7) N1C---C1C---C2C 125 (2) O15C---W11---O16C 86.3 (7) N4C---C1C---C2C 124 (2) O11T---W11---O10B 103.7 (7) C1C---C2C---N5C 112.3 (19) O15C---W11---O10B 155.4 (7) C1C---C2C---H2E 109.1 O16C---W11---O10B 88.5 (7) N5C---C2C---H2E 109.1 O11T---W11---O5B 103.7 (7) C1C---C2C---H2F 109.1 O15C---W11---O5B 89.3 (6) N5C---C2C---H2F 109.1 O16C---W11---O5B 156.9 (6) H2E---C2C---H2F 107.9 O10B---W11---O5B 86.2 (6) C4C---C3C---N5C 111.2 (18) O11T---W11---O13C 169.7 (6) C4C---C3C---H3E 109.4 O15C---W11---O13C 72.4 (6) N5C---C3C---H3E 109.4 O16C---W11---O13C 72.7 (6) C4C---C3C---H3F 109.4 O10B---W11---O13C 83.1 (6) N5C---C3C---H3F 109.4 O5B---W11---O13C 84.3 (5) H3E---C3C---H3F 108.0 O12T---W12---O14C 99.1 (7) O3---C4C---C3C 112.5 (19) O12T---W12---O11B 105.3 (7) O3---C4C---H4H 109.1 O14C---W12---O11B 87.2 (6) C3C---C4C---H4H 109.1 O12T---W12---O9B 106.0 (7) O3---C4C---H4I 109.1 O14C---W12---O9B 154.9 (6) C3C---C4C---H4I 109.1 O11B---W12---O9B 86.3 (6) H4H---C4C---H4I 107.8 O12T---W12---O16C 101.9 (7) O3---C5C---C6C 114 (2) O14C---W12---O16C 86.8 (6) O3---C5C---H5H 108.7 O11B---W12---O16C 152.8 (6) C6C---C5C---H5H 108.7 O9B---W12---O16C 87.9 (7) O3---C5C---H5I 108.7 O12T---W12---O13C 169.7 (6) C6C---C5C---H5I 108.7 O14C---W12---O13C 72.8 (5) H5H---C5C---H5I 107.6 O11B---W12---O13C 81.1 (6) C5C---C6C---N5C 112.7 (19) O9B---W12---O13C 82.2 (5) C5C---C6C---H6E 109.1 O16C---W12---O13C 71.7 (6) N5C---C6C---H6E 109.1 O9C---P1---O13C 109.0 (9) C5C---C6C---H6F 109.1 O9C---P1---O5C 111.0 (9) N5C---C6C---H6F 109.1 O13C---P1---O5C 109.3 (8) H6E---C6C---H6F 107.8 O9C---P1---O1C 108.2 (8) H1W---O1W---H2W 112.9 O13C---P1---O1C 109.8 (8) H35---O2W---H36 87.1 O5C---P1---O1C 109.5 (9) H5W---O3W---H6W 117.6 W1---O1B---W4 151.8 (8) H7W---O4W---H8W 115.8 W1---O2B---W7 151.2 (8) H9W---O5W---H10W 111.9 W2---O3B---W9 150.1 (9) H71---O6W---H72 102.9 C1A---N1A---N2A---N3A 0(2) N1B---C1B---C2B---N5B 41 (3) N1A---N2A---N3A---N4A 1(2) N4B---C1B---C2B---N5B −143 (2) N2A---N3A---N4A---C1A −1(2) C3B---N5B---C2B---C1B 177.8 (18) C1B---N1B---N2B---N3B −4(3) C6B---N5B---C2B---C1B 54 (2) N1B---N2B---N3B---N4B 4(2) C6B---N5B---C3B---C4B −58 (2) N2B---N3B---N4B---C1B −2(2) C2B---N5B---C3B---C4B 174.7 (18) C1C---N1C---N2C---N3C −2(3) C5B---O2---C4B---C3B −58 (2) N1C---N2C---N3C---N4C 0(3) N5B---C3B---C4B---O2 59 (3) N2C---N3C---N4C---C1C 1(3) C4B---O2---C5B---C6B 61 (2) N2A---N1A---C1A---N4A −1(2) C3B---N5B---C6B---C5B 55 (2) N2A---N1A---C1A---C2A −178 (2) C2B---N5B---C6B---C5B −178.3 (17) N3A---N4A---C1A---N1A 1(3) O2---C5B---C6B---N5B −60 (2) N3A---N4A---C1A---C2A 178.3 (19) N2C---N1C---C1C---N4C 2(3) C6A---N5A---C2A---C1A 176.0 (18) N2C---N1C---C1C---C2C 175 (2) C3A---N5A---C2A---C1A −58 (3) N3C---N4C---C1C---N1C −2(3) N1A---C1A---C2A---N5A 88 (3) N3C---N4C---C1C---C2C −175 (2) N4A---C1A---C2A---N5A −89 (3) N1C---C1C---C2C---N5C 66 (3) C2A---N5A---C3A---C4A 172.9 (19) N4C---C1C---C2C---N5C −122 (2) C6A---N5A---C3A---C4A −60 (2) C3C---N5C---C2C---C1C 52 (2) C5A---O1---C4A---C3A −60 (2) C6C---N5C---C2C---C1C 176.0 (18) N5A---C3A---C4A---O1 61 (2) C2C---N5C---C3C---C4C −178.4 (19) C4A---O1---C5A---C6A 60 (2) C6C---N5C---C3C---C4C 54 (2) C2A---N5A---C6A---C5A −176.0 (17) C5C---O3---C4C---C3C 59 (2) C3A---N5A---C6A---C5A 55 (2) N5C---C3C---C4C---O3 −60 (2) O1---C5A---C6A---N5A −56 (2) C4C---O3---C5C---C6C −56 (3) N2B---N1B---C1B---N4B 3(2) O3---C5C---C6C---N5C 55 (3) N2B---N1B---C1B---C2B 179 (2) C2C---N5C---C6C---C5C 179.4 (19) N3B---N4B---C1B---N1B 0(3) C3C---N5C---C6C---C5C −51 (2) N3B---N4B---C1B---C2B −177 (2) ----------------------- ------------- ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5871 .table-wrap} ---------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N4A---H4A···O2W 0.88 1.90 2.77 (2) 173 N5A---H5A···O5W 0.90 1.88 2.76 (3) 166 N4B---H4B···O1W^i^ 0.88 1.84 2.71 (2) 168 N5B---H5B···N2A^ii^ 0.90 2.31 2.97 (2) 130 N4C---H4C···O2W 0.88 2.09 2.87 (3) 149 N5C---H5C···O4W 0.87 2.01 2.71 (2) 137 O1W---H1W···O3C^iii^ 0.85 2.01 2.84 (2) 164 O1W---H2W···O3 0.85 1.92 2.77 (2) 180 O2W---H3W···O11T^iv^ 0.85 2.43 2.87 (2) 113 O2W---H4W···O9T^v^ 0.85 2.18 2.96 (2) 153 O2W---H4W···O2^vi^ 0.85 2.54 3.06 (2) 121 O3W---H5W···N1A^ii^ 0.85 2.41 3.03 (3) 130 O3W---H6W···N2C 0.85 2.14 2.79 (3) 134 O4W---H7W···O7T 0.85 2.11 2.96 (2) 180 O4W---H8W···O6W^vii^ 0.85 2.00 2.82 (2) 161 O5W---H9W···O2W 0.85 1.99 2.82 (2) 164 O5W---H10W···O6W 0.85 1.93 2.78 (2) 178 O6W---H11W···N2B 0.85 2.11 2.85 (2) 146 O6W---H12W···O2T^v^ 0.85 2.25 2.91 (2) 134 O6W---H12W···O1W^vi^ 0.85 2.44 3.11 (2) 137 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x−1, y, z; (ii) −x+1/2, −y+1, z−1/2; (iii) x+1, y, z; (iv) x+1/2, −y+1/2, −z+2; (v) x, y+1, z; (vi) −x+1, y+1/2, −z+3/2; (vii) −x+1, y−1/2, −z+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------------- --------- ------- ---------- ------------- N4A---H4A⋯O2W 0.88 1.90 2.77 (2) 173 N5A---H5A⋯O5W 0.90 1.88 2.76 (3) 166 N4B---H4B⋯O1W^i^ 0.88 1.84 2.71 (2) 168 N5B---H5B⋯N2A^ii^ 0.90 2.31 2.97 (2) 130 N4C---H4C⋯O2W 0.88 2.09 2.87 (3) 149 N5C---H5C⋯O4W 0.87 2.01 2.71 (2) 137 O1W---H1W⋯O3C^iii^ 0.85 2.01 2.84 (2) 164 O1W---H2W⋯O3 0.85 1.92 2.77 (2) 180 O2W---H3W⋯O11T^iv^ 0.85 2.43 2.87 (2) 113 O2W---H4W⋯O9T^v^ 0.85 2.18 2.96 (2) 153 O2W---H4W⋯O2^vi^ 0.85 2.54 3.06 (2) 121 O3W---H5W⋯N1A^ii^ 0.85 2.41 3.03 (3) 130 O3W---H6W⋯N2C 0.85 2.14 2.79 (3) 134 O4W---H7W⋯O7T 0.85 2.11 2.96 (2) 180 O4W---H8W⋯O6W^vii^ 0.85 2.00 2.82 (2) 161 O5W---H9W⋯O2W 0.85 1.99 2.82 (2) 164 O5W---H10W⋯O6W 0.85 1.93 2.78 (2) 178 O6W---H11W⋯N2B 0.85 2.11 2.85 (2) 146 O6W---H12W⋯O2T^v^ 0.85 2.25 2.91 (2) 134 O6W---H12W⋯O1W^vi^ 0.85 2.44 3.11 (2) 137 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) . :::	PubMed Central	2024-06-05T04:04:18.406162	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052096/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):m301-m302", "authors": [ { "first": "Babak", "last": "Feizyzadeh" }, { "first": "Masoud", "last": "Mirzaei" }, { "first": "Hossein", "last": "Eshtiagh-Hosseini" }, { "first": "Ahmad", "last": "Gholizadeh" } ] }
PMC3052097	Related literature {#sec1} ================== For related compounds, see: Berrah et al. (2005a [@bb3],b [@bb2], 2011[@bb4]); Bouacida et al. (2005[@bb6], 2009[@bb5]); Dobson & Gerkin (1996[@bb11]). For hydrogen-bond motifs, see: Bernstein et al. (1995[@bb1]); Etter et al. (1990[@bb13]). For similar intermolecular interactions, see: Dorn et al. (2005[@bb12]), Janiak (2000[@bb16]); Desiraju (2003[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} 2C~5~H~6~N~3~O~2~ ^+^·SO~4~ ^2−^·2H~2~OM ~r~ = 412.36Monoclinic,a = 7.7214 (4) Åb = 20.7043 (14) Åc = 10.6398 (7) Åβ = 109.299 (2)°V = 1605.36 (17) Å^3^Z = 4Mo Kα radiationμ = 0.27 mm^−1^T = 150 K0.55 × 0.36 × 0.15 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 2002[@bb17]) T ~min~ = 0.708, T ~max~ = 0.96013466 measured reflections3675 independent reflections3146 reflections with I \> 2σ(I)R ~int~ = 0.039 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.035wR(F ^2^) = 0.096S = 1.033675 reflections246 parametersH-atom parameters constrainedΔρ~max~ = 0.47 e Å^−3^Δρ~min~ = −0.48 e Å^−3^ {#d5e799} Data collection: APEX2 (Bruker, 2001[@bb8]); cell refinement: SAINT (Bruker, 2001[@bb8]); data reduction: SAINT; program(s) used to solve structure: SIR2002 (Burla et al., 2003[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb18]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb14]) and DIAMOND (Brandenburg & Berndt, 2001[@bb7]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb15]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005824/dn2656sup1.cif](http://dx.doi.org/10.1107/S1600536811005824/dn2656sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005824/dn2656Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005824/dn2656Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?dn2656&file=dn2656sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?dn2656sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?dn2656&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DN2656](http://scripts.iucr.org/cgi-bin/sendsup?dn2656)). We are grateful to the LCATM laboratory, Université Larbi Ben M'Hidi, Oum El Bouaghi, Algeria, for financial support. Comment ======= Hydrogen bonds are object of several studies, that aim at elucidate their influence on crystal construction and compounds properties (Desiraju, 2003). N-heterocyclic compounds such as pyrazine and its derivatives may be interesting units to built new edifices involving original hydrogen-bonding scheme since they include a variety of potential hydrogen donors and acceptors. In this perspective and as a part of our search for new hybrid compounds based on protonated amines and imines (Berrah et al. 2011, 2005a,b; Bouacida et al. 2005,2009), we present here the structure of Bis (2-Amino-3-carboxypyrazin-1-ium) sulfate dihydrate. The asymmetric units of (I) includes two symmetry- independent cations and water molecules, and one sulfate anion. Cations and anions are interconnected to form R~3~^3^(10) and R~2~^2^(8) ring motifs (Etter et al., 1990; Bernstein et al., 1995) (Fig 1). Bond lengths and angles are as expected (Berrah et al. 2011; Dobson & Gerkin, 1996). The three-dimensional structure of (I), results from undulating sheets of cations dimmers parallel to (011) plane(Fig.2 and Fig.3 )and sulfate-water chains extending along \[100\](Fig.3). An interesting hydrogen bonds network, in which all potential donors and acceptors are involved, and especially marked by the presence of R~6~^6^(26)and R~2~^3^(10) set-graph motifs (Etter et al., 1990; Bernstein et al., 1995), ensures the coherence of the structure(Fig.2 and Fig.3, table 1). This later is reinforced by the contribution of π-π, S---O··· π and C---O··· π interactions (Dorn et al. 2005; Janiak, 2000) (table 2,3). Experimental {#experimental} ============ The title compound was synthesized by reacting 3-amino-pyrazine 2- carboxylic acid with some excess of sulphiric acid in aqueous solution. Slow evaporation leads to well crystallized yellow needles. Refinement {#refinement} ========== All non-H atoms were refined with anisotropic atomic displacement parameters. H atoms of water molecule were located in difference Fourier maps and treated as riding on their parent oxygen atoms with O---H = 0.85, H···H = 1.40 and U~iso~(H) = 1.5U~eq~(O). The remaining H atoms were localized on Fourier maps but introduced in calculated positions and treated as riding on their parent atoms (C, N or O) with C---H = 0.95 Å, O---H = 0.84 Å and N---H = 0.88 Å with U~iso~(H) = 1.2U~eq~(C or N) and U~iso~(H = 1.5 U~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound with the atomic labelling scheme.Displacement are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o677-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing view showing undulating sheets parallel to (011) plane and R66(26) rings set motif. Hydrogen bonds are shown as dashed lines. Hydrogen atoms not involved in H-bonds have been omitted for clarity ::: ![](e-67-0o677-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Partial packing view showing sulfate-water chains extending along \[100\] direction and undulating sheets. Hydrogen bonds are shown as dashed lines.Hydrogen atoms not involved in H-bonds have been omitted for clarity. ::: ![](e-67-0o677-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e216 .table-wrap} --------------------------------------- --------------------------------------- 2C~5~H~6~N~3~O~2~^+^·SO~4~^2−^·2H~2~O F(000) = 856 M~r~ = 412.36 D~x~ = 1.706 Mg m^−3^ Monoclinic, P2~1~/a Mo Kα radiation, λ = 0.71073 Å a = 7.7214 (4) Å Cell parameters from 5179 reflections b = 20.7043 (14) Å θ = 2.8--27.5° c = 10.6398 (7) Å µ = 0.27 mm^−1^ β = 109.299 (2)° T = 150 K V = 1605.36 (17) Å^3^ Prism, yellow Z = 4 0.55 × 0.36 × 0.15 mm --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e357 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII diffractometer 3146 reflections with I \> 2σ(I) graphite R~int~ = 0.039 CCD rotation images, thin slices scans θ~max~ = 27.6°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Sheldrick, 2002) h = −8→9 T~min~ = 0.708, T~max~ = 0.960 k = −26→26 13466 measured reflections l = −13→13 3675 independent reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e468 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.035 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.096 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0491P)^2^ + 0.7394P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3675 reflections (Δ/σ)~max~ = 0.001 246 parameters Δρ~max~ = 0.47 e Å^−3^ 0 restraints Δρ~min~ = −0.48 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e625 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e724 .table-wrap} ------ --------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O5A 0.17659 (16) 0.04617 (6) 0.03501 (11) 0.0221 (3) H5A 0.1515 0.0732 −0.0273 0.033\ O6A 0.03846 (18) 0.11842 (6) 0.12557 (11) 0.0258 (3) N1A 0.0567 (2) 0.10587 (7) 0.37979 (13) 0.0231 (3) H1A1 0.0399 0.1167 0.4549 0.028\* H1A2 0.0122 0.1303 0.3087 0.028\* N2A 0.21592 (19) 0.01604 (6) 0.48490 (13) 0.0195 (3) H2A 0.1989 0.0288 0.5588 0.023\* N3A 0.27826 (19) −0.02410 (6) 0.25952 (13) 0.0194 (3) C1A 0.1266 (2) 0.06905 (7) 0.13275 (15) 0.0185 (3) C2A 0.1875 (2) 0.02980 (7) 0.25829 (15) 0.0177 (3) C3A 0.1485 (2) 0.05305 (7) 0.37379 (15) 0.0183 (3) C4A 0.3079 (2) −0.03946 (8) 0.48622 (16) 0.0207 (3) H4A 0.3518 −0.0644 0.5654 0.025\* C5A 0.3374 (2) −0.05941 (8) 0.37264 (16) 0.0214 (3) H5C 0.4006 −0.0988 0.3731 0.026\* O5B −0.03794 (19) 0.32977 (6) 1.37046 (12) 0.0273 (3) H5B −0.0768 0.3055 1.4185 0.041\* O6B −0.03786 (17) 0.23824 (5) 1.25812 (11) 0.0241 (3) N1B 0.0619 (2) 0.24559 (7) 1.03668 (14) 0.0238 (3) H1B1 0.0821 0.2313 0.9649 0.029\* H1B2 0.0315 0.2184 1.0895 0.029\* N2B 0.12393 (19) 0.34886 (7) 0.98346 (13) 0.0205 (3) H2B 0.1422 0.3332 0.912 0.025\* N3B 0.07073 (19) 0.39911 (6) 1.20349 (13) 0.0206 (3) C1B −0.0126 (2) 0.29617 (8) 1.27448 (15) 0.0196 (3) C2B 0.0482 (2) 0.33663 (7) 1.17934 (14) 0.0178 (3) C3B 0.0773 (2) 0.30786 (8) 1.06522 (15) 0.0187 (3) C4B 0.1438 (2) 0.41269 (8) 1.00633 (16) 0.0227 (3) H4B 0.1752 0.4403 0.9458 0.027\* C5B 0.1180 (2) 0.43737 (8) 1.11810 (16) 0.0233 (3) H5D 0.1338 0.4824 1.1357 0.028\* S1 0.15317 (5) 0.131125 (18) 0.73117 (4) 0.01813 (11) O1 0.2146 (2) 0.06509 (6) 0.71883 (12) 0.0337 (3) O2 0.09536 (18) 0.13565 (6) 0.85065 (12) 0.0262 (3) O3 0.30149 (17) 0.17773 (7) 0.74478 (12) 0.0306 (3) O4 −0.00482 (16) 0.14708 (6) 0.61180 (11) 0.0236 (3) O1W 0.23309 (17) 0.30737 (6) 0.78406 (12) 0.0262 (3) H1W 0.2465 0.2676 0.7697 0.039\* H2W 0.3352 0.3253 0.7903 0.039\* O2W −0.15818 (19) 0.26453 (6) 1.52193 (12) 0.0296 (3) H3W −0.1068 0.2285 1.5511 0.044\* H4W −0.1653 0.2863 1.5886 0.044\* ------ --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1307 .table-wrap} ----- ------------ -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O5A 0.0332 (7) 0.0213 (6) 0.0140 (5) 0.0044 (5) 0.0109 (5) 0.0030 (4) O6A 0.0400 (7) 0.0206 (6) 0.0184 (6) 0.0076 (5) 0.0115 (5) 0.0036 (4) N1A 0.0340 (8) 0.0227 (7) 0.0140 (6) 0.0063 (6) 0.0100 (6) 0.0012 (5) N2A 0.0269 (7) 0.0193 (6) 0.0128 (6) −0.0002 (5) 0.0072 (5) 0.0001 (5) N3A 0.0253 (7) 0.0168 (6) 0.0158 (6) −0.0013 (5) 0.0063 (5) −0.0003 (5) C1A 0.0232 (8) 0.0172 (7) 0.0153 (7) −0.0026 (6) 0.0065 (6) −0.0007 (6) C2A 0.0225 (8) 0.0159 (7) 0.0154 (7) −0.0020 (6) 0.0072 (6) −0.0008 (6) C3A 0.0229 (8) 0.0175 (7) 0.0144 (7) −0.0027 (6) 0.0062 (6) −0.0007 (6) C4A 0.0259 (8) 0.0177 (7) 0.0168 (7) −0.0016 (6) 0.0048 (6) 0.0035 (6) C5A 0.0279 (9) 0.0163 (7) 0.0186 (7) 0.0011 (6) 0.0056 (6) 0.0000 (6) O5B 0.0480 (8) 0.0198 (6) 0.0201 (6) −0.0009 (5) 0.0194 (5) −0.0004 (5) O6B 0.0355 (7) 0.0185 (6) 0.0193 (6) −0.0015 (5) 0.0104 (5) 0.0003 (4) N1B 0.0372 (8) 0.0188 (7) 0.0167 (6) −0.0035 (6) 0.0105 (6) −0.0037 (5) N2B 0.0267 (7) 0.0221 (7) 0.0128 (6) −0.0027 (5) 0.0069 (5) −0.0024 (5) N3B 0.0267 (7) 0.0172 (6) 0.0167 (6) 0.0005 (5) 0.0056 (5) −0.0008 (5) C1B 0.0231 (8) 0.0198 (8) 0.0141 (7) 0.0019 (6) 0.0039 (6) 0.0008 (6) C2B 0.0216 (8) 0.0173 (7) 0.0127 (7) 0.0005 (6) 0.0033 (6) 0.0001 (5) C3B 0.0203 (8) 0.0194 (7) 0.0142 (7) −0.0010 (6) 0.0029 (6) −0.0014 (6) C4B 0.0276 (9) 0.0201 (8) 0.0195 (7) −0.0035 (6) 0.0068 (6) 0.0020 (6) C5B 0.0324 (9) 0.0177 (7) 0.0193 (7) −0.0019 (6) 0.0077 (7) 0.0004 (6) S1 0.0259 (2) 0.01758 (19) 0.01276 (18) 0.00290 (14) 0.00883 (15) 0.00224 (13) O1 0.0605 (9) 0.0245 (6) 0.0186 (6) 0.0188 (6) 0.0163 (6) 0.0047 (5) O2 0.0429 (7) 0.0230 (6) 0.0193 (6) 0.0051 (5) 0.0192 (5) 0.0035 (5) O3 0.0291 (7) 0.0384 (7) 0.0238 (6) −0.0067 (5) 0.0080 (5) 0.0029 (5) O4 0.0266 (6) 0.0246 (6) 0.0179 (6) 0.0031 (5) 0.0049 (5) 0.0017 (4) O1W 0.0294 (6) 0.0273 (6) 0.0252 (6) −0.0009 (5) 0.0136 (5) −0.0005 (5) O2W 0.0460 (8) 0.0244 (6) 0.0229 (6) 0.0086 (5) 0.0174 (6) 0.0061 (5) ----- ------------ -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1809 .table-wrap} ----------------------- -------------- ----------------------- -------------- O5A---C1A 1.3116 (19) N1B---H1B1 0.88 O5A---H5A 0.84 N1B---H1B2 0.88 O6A---C1A 1.216 (2) N2B---C4B 1.343 (2) N1A---C3A 1.316 (2) N2B---C3B 1.347 (2) N1A---H1A1 0.88 N2B---H2B 0.88 N1A---H1A2 0.88 N3B---C2B 1.319 (2) N2A---C4A 1.349 (2) N3B---C5B 1.344 (2) N2A---C3A 1.360 (2) C1B---C2B 1.503 (2) N2A---H2A 0.88 C2B---C3B 1.435 (2) N3A---C2A 1.315 (2) C4B---C5B 1.368 (2) N3A---C5A 1.352 (2) C4B---H4B 0.95 C1A---C2A 1.500 (2) C5B---H5D 0.95 C2A---C3A 1.442 (2) S1---O1 1.4670 (12) C4A---C5A 1.365 (2) S1---O3 1.4677 (13) C4A---H4A 0.95 S1---O4 1.4786 (12) C5A---H5C 0.95 S1---O2 1.4831 (12) O5B---C1B 1.3028 (19) O1W---H1W 0.8491 O5B---H5B 0.84 O1W---H2W 0.8542 O6B---C1B 1.218 (2) O2W---H3W 0.8543 N1B---C3B 1.321 (2) O2W---H4W 0.8582 C1A---O5A---H5A 109.5 C4B---N2B---C3B 122.81 (14) C3A---N1A---H1A1 120 C4B---N2B---H2B 118.6 C3A---N1A---H1A2 120 C3B---N2B---H2B 118.6 H1A1---N1A---H1A2 120 C2B---N3B---C5B 119.63 (14) C4A---N2A---C3A 122.57 (14) O6B---C1B---O5B 125.38 (15) C4A---N2A---H2A 118.7 O6B---C1B---C2B 121.55 (14) C3A---N2A---H2A 118.7 O5B---C1B---C2B 113.05 (14) C2A---N3A---C5A 119.32 (14) N3B---C2B---C3B 121.62 (14) O6A---C1A---O5A 123.99 (14) N3B---C2B---C1B 117.76 (14) O6A---C1A---C2A 121.03 (14) C3B---C2B---C1B 120.62 (14) O5A---C1A---C2A 114.98 (13) N1B---C3B---N2B 119.31 (15) N3A---C2A---C3A 122.39 (14) N1B---C3B---C2B 124.91 (15) N3A---C2A---C1A 118.54 (14) N2B---C3B---C2B 115.78 (14) C3A---C2A---C1A 119.06 (14) N2B---C4B---C5B 118.98 (15) N1A---C3A---N2A 118.94 (14) N2B---C4B---H4B 120.5 N1A---C3A---C2A 125.91 (14) C5B---C4B---H4B 120.5 N2A---C3A---C2A 115.15 (14) N3B---C5B---C4B 121.17 (15) N2A---C4A---C5A 119.33 (14) N3B---C5B---H5D 119.4 N2A---C4A---H4A 120.3 C4B---C5B---H5D 119.4 C5A---C4A---H4A 120.3 O1---S1---O3 110.91 (9) N3A---C5A---C4A 121.21 (15) O1---S1---O4 109.31 (7) N3A---C5A---H5C 119.4 O3---S1---O4 109.46 (7) C4A---C5A---H5C 119.4 O1---S1---O2 109.47 (7) C1B---O5B---H5B 109.5 O3---S1---O2 108.66 (7) C3B---N1B---H1B1 120 O4---S1---O2 109.00 (7) C3B---N1B---H1B2 120 H1W---O1W---H2W 105.7 H1B1---N1B---H1B2 120 H3W---O2W---H4W 108 C5A---N3A---C2A---C3A 0.1 (2) C5B---N3B---C2B---C3B 1.6 (2) C5A---N3A---C2A---C1A 178.70 (14) C5B---N3B---C2B---C1B −177.43 (14) O6A---C1A---C2A---N3A 178.18 (15) O6B---C1B---C2B---N3B 179.35 (15) O5A---C1A---C2A---N3A −2.2 (2) O5B---C1B---C2B---N3B 0.9 (2) O6A---C1A---C2A---C3A −3.2 (2) O6B---C1B---C2B---C3B 0.3 (2) O5A---C1A---C2A---C3A 176.41 (14) O5B---C1B---C2B---C3B −178.12 (14) C4A---N2A---C3A---N1A 178.56 (15) C4B---N2B---C3B---N1B −179.42 (15) C4A---N2A---C3A---C2A −1.9 (2) C4B---N2B---C3B---C2B 0.5 (2) N3A---C2A---C3A---N1A −179.04 (16) N3B---C2B---C3B---N1B 178.17 (15) C1A---C2A---C3A---N1A 2.4 (2) C1B---C2B---C3B---N1B −2.9 (2) N3A---C2A---C3A---N2A 1.5 (2) N3B---C2B---C3B---N2B −1.7 (2) C1A---C2A---C3A---N2A −177.09 (13) C1B---C2B---C3B---N2B 177.27 (14) C3A---N2A---C4A---C5A 0.8 (2) C3B---N2B---C4B---C5B 0.8 (2) C2A---N3A---C5A---C4A −1.4 (2) C2B---N3B---C5B---C4B −0.2 (3) N2A---C4A---C5A---N3A 0.9 (2) N2B---C4B---C5B---N3B −1.0 (3) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2424 .table-wrap} ---------------------- --------- --------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1A---H1A1···O4 0.88 1.92 2.7970 (18) 175. N1A---H1A2···O6A 0.88 2.04 2.6741 (18) 128. N1A---H1A2···O6B^i^ 0.88 2.30 3.0158 (18) 138. N2A---H2A···O1 0.88 1.83 2.6915 (18) 167. N1B---H1B1···O2 0.88 2.34 3.0827 (18) 142. N1B---H1B2···O6B 0.88 2.08 2.7144 (19) 129. N1B---H1B2···O6A^ii^ 0.88 2.10 2.8237 (18) 139. N2B---H2B···O1W 0.88 1.81 2.6705 (18) 167. O5B---H5B···O2W 0.84 1.67 2.5046 (17) 174. O5A---H5A···O2^i^ 0.84 1.78 2.6192 (16) 175. O1W---H1W···O3 0.85 1.95 2.7934 (19) 175. O1W---H2W···O2^iii^ 0.85 2.06 2.8996 (18) 167 O1W---H2W···O4^iii^ 0.85 2.65 3.2856 (17) 133. O2W---H3W···O4^ii^ 0.85 1.88 2.7351 (17) 177. O2W---H4W···O3^iv^ 0.86 1.91 2.7633 (17) 171. C4A---H4A···O5B^v^ 0.95 2.58 3.320 (2) 134. C4A---H4A···N3B^v^ 0.95 2.45 3.369 (2) 163. C4B---H4B···O5A^vi^ 0.95 2.45 3.187 (2) 134. C4B---H4B···N3A^vi^ 0.95 2.44 3.347 (2) 159 C5A---H5C···O1W^vii^ 0.95 2.55 3.175 (2) 124. C5B---H5D···O1^viii^ 0.95 2.35 3.192 (2) 148. ---------------------- --------- --------- ------------- --------------- ::: Symmetry codes: (i) x, y, z−1; (ii) x, y, z+1; (iii) x+1/2, −y+1/2, z; (iv) x−1/2, −y+1/2, z+1; (v) −x+1/2, y−1/2, −z+2; (vi) −x+1/2, y+1/2, −z+1; (vii) −x+1/2, y−1/2, −z+1; (viii) −x+1/2, y+1/2, −z+2. Table 2 π--π stacking interactions (Å, °) {#d1e2805} ========================================= Cg1 is the centroid of the N2A--C4A ring. ::: {#d1e2827 .table-wrap} ----- -------- -------------- --- ------- ------- --------------- --------------- ---------- CgI CgJ CgI···CgJ^a^ α β γ CgI···P(J)^b^ CgJ···P(I)^c^ Slippage Cg1 Cg1^i^ 3.9678 (9) 0 34.94 34.94 3.2528 (6) 3.2527 (6) 2.272 ----- -------- -------------- --- ------- ------- --------------- --------------- ---------- ::: Symmetry codes: (i)1-x,-y,1-z Notes: a : Distance between centroids b : Perpendicular distance of CgI on ring plan J c : Perpendicular distance of CgJ on ring plan I α = Dihedral Angle between the ring planes β = Angle between the centroid vector CgI···CgJ and the normal to the plane I. γ = Angle between the centroid vector CgI···CgJ and the normal to the plane J. Slippage = vertical displacement between ring centroids. Table 3 S---O···π and C---O···π interactions (Å, °). {#d1e2891} ==================================================== Cg1 and Cg2 are the centroids of the N2A--C4A and N2B--C4B rings, respectively. ::: {#d1e2914 .table-wrap} ----- ----- ---------- ------------- ------------- ------------- X I J I···J X--I···J X···J S1 O1 Cg1^i^ 3.5922 (17) 91.83 (7) 3.9233 (8) S1 O2 Cg1^i^ 3.9845 (14) 76.88 (5) 3.9233 (8) S1 O2 Cg2^ii^ 3.8831 (15) 92.77 (6) 4.2231 (8) C1A O6A Cg2^iii^ 3.3136 (16) 125.62 (11) 4.1418 (18) ----- ----- ---------- ------------- ------------- ------------- ::: Symmetry codes: (i) -x, -y, 1-z; (ii) x, y, 1+z; (iii) x-1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------------- --------- ------- ------------- ------------- N1A---H1A1⋯O4 0.88 1.92 2.7970 (18) 175 N1A---H1A2⋯O6A 0.88 2.04 2.6741 (18) 128 N1A---H1A2⋯O6B^i^ 0.88 2.30 3.0158 (18) 138 N2A---H2A⋯O1 0.88 1.83 2.6915 (18) 167 N1B---H1B1⋯O2 0.88 2.34 3.0827 (18) 142 N1B---H1B2⋯O6B 0.88 2.08 2.7144 (19) 129 N1B---H1B2⋯O6A^ii^ 0.88 2.10 2.8237 (18) 139 N2B---H2B⋯O1W 0.88 1.81 2.6705 (18) 167 O5B---H5B⋯O2W 0.84 1.67 2.5046 (17) 174 O5A---H5A⋯O2^i^ 0.84 1.78 2.6192 (16) 175 O1W---H1W⋯O3 0.85 1.95 2.7934 (19) 175 O1W---H2W⋯O2^iii^ 0.85 2.06 2.8996 (18) 167 O1W---H2W⋯O4^iii^ 0.85 2.65 3.2856 (17) 133 O2W---H3W⋯O4^ii^ 0.85 1.88 2.7351 (17) 177 O2W---H4W⋯O3^iv^ 0.86 1.91 2.7633 (17) 171 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::	PubMed Central	2024-06-05T04:04:18.420014	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052097/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o677-o678", "authors": [ { "first": "Fadila", "last": "Berrah" }, { "first": "Amira", "last": "Ouakkaf" }, { "first": "Sofiane", "last": "Bouacida" }, { "first": "Thierry", "last": "Roisnel" } ] }
PMC3052098	Related literature {#sec1} ================== For the synthesis, see: Couldwell & House (1972[@bb8]); House (1970[@bb9]). For related structures, see: Choi et al. (2002[@bb7], 2007[@bb5], 2008[@bb6], 2010[@bb4]); Vaughn & Rogers (1985[@bb14]); Kou et al. (2001[@bb10]). For tn ligand geometry, see: Vaughn (1981[@bb13]). For the standard Cambridge Structural Database description, see: Allen (2002[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[CrCl~2~(C~3~H~10~N~2~)~2~\]ClO~4~M ~r~ = 370.61Monoclinic,a = 6.4306 (5) Åb = 17.2588 (15) Åc = 13.0235 (11) Åβ = 92.840 (4)°V = 1443.6 (2) Å^3^Z = 4Mo Kα radiationμ = 1.36 mm^−1^T = 173 K0.16 × 0.08 × 0.05 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (TWINABS; Sheldrick, 2008a [@bb11]) T ~min~ = 0.815, T ~max~ = 0.93028308 measured reflections6269 independent reflections5585 reflections with I \> 2σ(I)R ~int~ = 0.039 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.028wR(F ^2^) = 0.075S = 1.076269 reflections245 parametersAll H-atom parameters refinedΔρ~max~ = 0.36 e Å^−3^Δρ~min~ = −0.32 e Å^−3^ {#d5e576} Data collection: APEX2 (Bruker, 2010[@bb3]); cell refinement: SAINT (Bruker, 2010[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008b [@bb12]); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg, 2010[@bb2]); software used to prepare material for publication: SHELXTL and local programs. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006349/nk2086sup1.cif](http://dx.doi.org/10.1107/S1600536811006349/nk2086sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006349/nk2086Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006349/nk2086Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?nk2086&file=nk2086sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?nk2086sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?nk2086&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NK2086](http://scripts.iucr.org/cgi-bin/sendsup?nk2086)). This work was supported by a grant from the 2010 Research Fund of Andong National University. Comment ======= The \[Cr(tn)~2~L~2~\]^+^ cation (tn = propane-1,3-diamine, L = monodentate ligand) can exist as trans and cis geometric isomers. There are also two possible conformations with respect to the six-membered chelate rings (present as chairs) in the trans geometric isomer: the carbon atoms of these rings in the two tn ligands can be located on the same side (syn conformer) or on opposite side (anti conformer) of the equatorial plane. In the crystal structures of trans-\[Cr(Me~2~tn)~2~Cl~2~\]Cl and trans-\[Cr(Me~2~tn)~2~Br~2~\]~2~Br~2~.HClO~4~.6H~2~O (Me~2~tn = 2,2-dimethylpropane-1,3-diamine), both syn and anti conformational isomers are found together (Choi et al., 2002; Choi et al., 2007), while trans-\[Cr(Me~2~tn)~2~Cl~2~\]ClO~4~ (Choi et al., 2008) has only the anti conformer, as do trans-\[Cr(tn)~2~F~2~\]ClO~4~ (Vaughn & Rogers, 1985) and trans-\[Cr(tn)~2~Cl~2~\]~3~\[Fe(CN)~6~.6H~2~O (Kou et al., 2001). The preference for syn or anti conformation of chelate rings in trans complex cations with tn or Me~2~tn ligands is thus subtle and worthy of further study. Infrared and electronic absorption spectroscopic methods are not useful in distinguishing such syn and anti conformations in these metal complexes. Structural studies of bromido-containing chromium(III) complexes are relatively rare compared to those with chlorido ligands. Therefore we attempted to prepare trans-\[Cr(tn)~2~Br~2~\]ClO~4~ by a literature method (Couldwell & House, 1972); its UV-visible and IR spectra are nearly the same as those of trans-\[Cr(tn)~2~Cl~2~\]ClO~4~ (House, 1970), and it was only with a crystal structure analysis that we established that the product was actually the dichlorido rather than the dibromido complex. We report here the structure of trans-\[Cr(tn)~2~Cl~2~\]ClO~4~ (I) which provides further information on the conformation of the two six-membered chelate rings. In the title complex (I), the chromium(III) ion is coplanar with the four coordinating N atoms and adopts an octahedral geometry, in which the four nitrogen atoms of two tn ligands occupy the equatorial sites and the two chlorine atoms coordinate axially in a trans configuration. The two six-membered rings have their usual stable chair conformations, and they are exclusively in the anti conformation with respect to each other in the unique cation of the asymmetric unit (Fig. 1). The Cr---N distances (Table 1) are in the range 2.0831 (18)--2.0917 (19) Å, typical for Cr---N bonds involving primary amines (Choi et al., 2002; Choi et al., 2007). The Cr---Cl distances \[2.3135 (6) and 2.3148 (6) Å\] are very close to the values 2.3179 (9) and 2.3212 (4) Å found in trans-\[Cr(Me~2~tn)~2~Cl~2~\]ClO~4~ (Choi et al., 2008), and typical generally of Cr---Cl bond lengths in the Cambridge Structural Database (Allen, 2002), but shorter than the 2.4743 (10) Å for Cr---Br bond lengths in trans-\[Cr(en)~2~Br~2~\]ClO~4~ (Choi et al., 2010). The assignment of the axial ligands as Cl rather than the Br intended and expected from the synthesis is also clearly correct from the satisfactory refinement of anisotropic displacement parameters, demonstrating an appropriate electron density. The internal geometry of the tn ligands is typical for these in chair conformations (Vaughn, 1981). The uncoordinated ClO~4~^-^ anion shows an essentially tetrahedral arrangement with Cl---O distances in the range 1.4268 (19)--1.4380 (19) Å and the angles at Cl ranging from 108.32 (11) to 110.48 (13)°. There is an extensive weak hydrogen bonding network involving the oxygen atoms of the anions, chlorido ligands, and the N---H groups of the tn ligands (Table 2), which supports the main ionic interactions in this complex salt. Experimental {#experimental} ============ The ligand propane-1,3-diamine was obtained from Aldrich Chemical Co. and was used as supplied. All other chemicals were reagent grade materials and were used without further purification. We intended to prepare trans-\[Cr(tn)~2~Br~2~\]ClO~4~ as described in the literature (Couldwell & House, 1972) but obtained instead trans-\[Cr(tn)~2~Cl~2~\]ClO~4~, as demonstrated by this crystal structure analysis. CrCl~3~.6H~2~O (5.4 g) was dissolved in DMSO (25 ml) and the solution was boiled for 10 min. A mixture of 1,3-propanediamine (3 ml) and DMSO (15 ml) was added and boiling was continued for 2 min. After cooling to 60°C, the solution was poured into well stirred acetone (300 ml). The precipitate was filtered off and washed with acetone, then dissolved in aqueous HBr (20 ml, 48%) and the solution was heated on a steam bath for 15 min. and filtered. The filtrate was heated on a steam bath for a further 15 min. Aqueous HClO~4~ (5 ml, 60%) was added to the solution. The resulting green crystals were collected and washed with ethanol. The infrared spectrum (nujol) was consistent with the crystallographically determined structure. The chloro ligands in the title compound are clearly retained from the chromium(III) chloride starting material, and were not substituted as intended by Br in the reaction with HBr. Refinement {#refinement} ========== The crystal was a non-merohedral twin with a 23.45 (6)% contribution of the minor component according to the refinement; because of the twinning, merging of symmetry-equivalent data could not be performed prior to refinement. The twin law is 1 0 0 / 0 - 1 0 / -0.2 0 - 1, corresponding to a 180° rotation about the a axis. Hydrogen atoms were located in a difference map and refined freely with individual isotropic displacement parameters. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the complex cation and anion (displacement ellipsoids are drawn at the 50% probability level). ::: ![](e-67-0m381-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e380 .table-wrap} ------------------------------------- --------------------------------------- \[CrCl~2~(C~3~H~10~N~2~)~2~\]ClO~4~ F(000) = 764 M~r~ = 370.61 D~x~ = 1.705 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 6530 reflections a = 6.4306 (5) Å θ = 2.8--28.3° b = 17.2588 (15) Å µ = 1.36 mm^−1^ c = 13.0235 (11) Å T = 173 K β = 92.840 (4)° Block, green V = 1443.6 (2) Å^3^ 0.16 × 0.08 × 0.05 mm Z = 4 ------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e517 .table-wrap} ----------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 6269 independent reflections Radiation source: sealed tube 5585 reflections with I \> 2σ(I) graphite R~int~ = 0.039 Thin--slice ω scans θ~max~ = 28.4°, θ~min~ = 2.0° Absorption correction: multi-scan (TWINABS; Sheldrick, 2008a) h = −8→8 T~min~ = 0.815, T~max~ = 0.930 k = 0→23 28308 measured reflections l = 0→17 ----------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e626 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.028 All H-atom parameters refined wR(F^2^) = 0.075 w = 1/\[σ^2^(F~o~^2^) + (0.0391P)^2^ + 1.9009P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.07 (Δ/σ)~max~ = 0.001 6269 reflections Δρ~max~ = 0.36 e Å^−3^ 245 parameters Δρ~min~ = −0.32 e Å^−3^ 0 restraints Extinction correction: SHELXTL (Sheldrick, 2008a), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0011 (6) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e807 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e906 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cr 0.49360 (5) 0.396455 (18) 0.29650 (2) 0.01236 (9) Cl1 0.24916 (7) 0.41493 (3) 0.41882 (4) 0.01906 (12) Cl2 0.74177 (7) 0.37755 (3) 0.17627 (4) 0.01921 (12) N1 0.7262 (3) 0.42985 (10) 0.40534 (14) 0.0149 (3) H1A 0.840 (4) 0.4296 (16) 0.375 (2) 0.026 (7)\ H1B 0.707 (4) 0.4791 (15) 0.4214 (19) 0.015 (6)\* N2 0.5301 (3) 0.28012 (11) 0.33866 (15) 0.0177 (4) H2A 0.619 (5) 0.2656 (17) 0.301 (2) 0.028 (8)\* H2B 0.417 (5) 0.2552 (18) 0.321 (2) 0.039 (8)\* N3 0.2572 (3) 0.36594 (12) 0.18892 (14) 0.0182 (4) H3A 0.258 (4) 0.3159 (17) 0.182 (2) 0.027 (7)\* H3B 0.138 (5) 0.3757 (16) 0.219 (2) 0.030 (8)\* N4 0.4523 (3) 0.51159 (11) 0.25055 (15) 0.0194 (4) H4A 0.556 (4) 0.5348 (16) 0.271 (2) 0.024 (7)\* H4B 0.356 (5) 0.5272 (16) 0.284 (2) 0.029 (8)\* C1 0.7561 (3) 0.38579 (13) 0.50303 (17) 0.0190 (4) H1C 0.872 (4) 0.4054 (15) 0.543 (2) 0.022 (7)\* H1D 0.634 (4) 0.3944 (13) 0.5441 (19) 0.011 (6)\* C2 0.7850 (4) 0.29977 (13) 0.48554 (19) 0.0236 (5) H2C 0.894 (4) 0.2925 (15) 0.439 (2) 0.022 (7)\* H2D 0.821 (4) 0.2755 (17) 0.550 (2) 0.034 (8)\* C3 0.5888 (4) 0.25891 (13) 0.44656 (18) 0.0222 (5) H3C 0.605 (4) 0.2040 (16) 0.450 (2) 0.024 (7)\* H3D 0.476 (4) 0.2728 (15) 0.490 (2) 0.023 (7)\* C4 0.2446 (4) 0.40246 (14) 0.08533 (18) 0.0232 (5) H4C 0.366 (4) 0.3889 (15) 0.051 (2) 0.022 (7)\* H4D 0.121 (4) 0.3793 (15) 0.045 (2) 0.021 (6)\* C5 0.2255 (4) 0.48944 (15) 0.09247 (19) 0.0244 (5) H5C 0.203 (4) 0.5077 (16) 0.021 (2) 0.032 (8)\* H5D 0.104 (4) 0.5017 (16) 0.129 (2) 0.029 (7)\* C6 0.4160 (4) 0.52997 (14) 0.13932 (19) 0.0242 (5) H6C 0.542 (4) 0.5136 (15) 0.106 (2) 0.021 (6)\* H6D 0.403 (4) 0.5848 (17) 0.135 (2) 0.029 (7)\* Cl3 0.07592 (8) 0.14746 (3) 0.25004 (4) 0.01984 (12) O1 0.1011 (3) 0.06757 (10) 0.22292 (16) 0.0363 (4) O2 0.1833 (3) 0.19442 (11) 0.17838 (16) 0.0384 (5) O3 −0.1425 (3) 0.16517 (11) 0.24445 (15) 0.0358 (4) O4 0.1632 (3) 0.16154 (14) 0.35117 (15) 0.0475 (5) ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1403 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cr 0.00998 (15) 0.01357 (16) 0.01352 (17) −0.00015 (11) 0.00047 (11) −0.00070 (12) Cl1 0.0142 (2) 0.0238 (3) 0.0196 (3) 0.00007 (18) 0.00468 (18) −0.00218 (19) Cl2 0.0131 (2) 0.0257 (3) 0.0190 (3) 0.00135 (18) 0.00347 (18) −0.00246 (19) N1 0.0135 (8) 0.0154 (9) 0.0160 (9) −0.0014 (6) 0.0014 (6) −0.0011 (7) N2 0.0171 (8) 0.0166 (9) 0.0192 (9) −0.0015 (7) −0.0009 (7) −0.0017 (7) N3 0.0133 (8) 0.0238 (10) 0.0175 (9) −0.0010 (7) −0.0003 (7) −0.0028 (7) N4 0.0197 (9) 0.0179 (9) 0.0206 (10) 0.0006 (7) 0.0006 (8) 0.0014 (7) C1 0.0222 (10) 0.0194 (10) 0.0150 (10) −0.0019 (8) −0.0024 (8) −0.0007 (8) C2 0.0281 (12) 0.0194 (11) 0.0226 (12) 0.0020 (9) −0.0065 (10) 0.0011 (9) C3 0.0310 (12) 0.0155 (10) 0.0201 (11) −0.0035 (9) −0.0004 (9) 0.0030 (8) C4 0.0191 (10) 0.0338 (13) 0.0164 (11) 0.0023 (9) −0.0017 (8) −0.0017 (9) C5 0.0210 (11) 0.0329 (13) 0.0193 (11) 0.0081 (9) 0.0005 (9) 0.0048 (9) C6 0.0269 (11) 0.0243 (12) 0.0216 (11) 0.0040 (9) 0.0031 (9) 0.0080 (9) Cl3 0.0206 (2) 0.0175 (2) 0.0210 (3) −0.00116 (19) −0.00290 (19) −0.00153 (19) O1 0.0380 (10) 0.0179 (8) 0.0530 (13) 0.0042 (7) 0.0012 (9) −0.0030 (8) O2 0.0452 (11) 0.0343 (10) 0.0364 (11) −0.0138 (9) 0.0092 (9) 0.0050 (8) O3 0.0246 (9) 0.0394 (10) 0.0434 (12) 0.0087 (8) 0.0019 (8) −0.0052 (9) O4 0.0523 (13) 0.0653 (15) 0.0235 (10) −0.0131 (11) −0.0121 (9) −0.0053 (10) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1777 .table-wrap} -------------------- -------------- -------------------- -------------- Cr---Cl1 2.3148 (6) C1---H1D 0.98 (2) Cr---Cl2 2.3135 (6) C1---C2 1.515 (3) Cr---N1 2.0903 (18) C2---H2C 0.95 (3) Cr---N2 2.0917 (19) C2---H2D 0.96 (3) Cr---N3 2.0831 (18) C2---C3 1.511 (3) Cr---N4 2.0884 (19) C3---H3C 0.95 (3) N1---H1A 0.85 (3) C3---H3D 0.97 (3) N1---H1B 0.89 (3) C4---H4C 0.95 (3) N1---C1 1.486 (3) C4---H4D 1.02 (3) N2---H2A 0.81 (3) C4---C5 1.510 (3) N2---H2B 0.86 (3) C5---H5C 0.99 (3) N2---C3 1.483 (3) C5---H5D 0.95 (3) N3---H3A 0.87 (3) C5---C6 1.513 (3) N3---H3B 0.89 (3) C6---H6C 0.98 (3) N3---C4 1.488 (3) C6---H6D 0.95 (3) N4---H4A 0.81 (3) Cl3---O1 1.4346 (18) N4---H4B 0.82 (3) Cl3---O2 1.4380 (19) N4---C6 1.490 (3) Cl3---O3 1.4360 (18) C1---H1C 0.95 (3) Cl3---O4 1.4268 (19) Cl1---Cr---Cl2 179.11 (2) N1---C1---C2 112.60 (19) Cl1---Cr---N1 89.02 (5) H1C---C1---H1D 106 (2) Cl1---Cr---N2 91.31 (6) H1C---C1---C2 109.5 (15) Cl1---Cr---N3 90.00 (6) H1D---C1---C2 109.7 (13) Cl1---Cr---N4 89.14 (6) C1---C2---H2C 108.8 (16) Cl2---Cr---N1 90.19 (5) C1---C2---H2D 108.8 (18) Cl2---Cr---N2 88.28 (6) C1---C2---C3 113.6 (2) Cl2---Cr---N3 90.80 (6) H2C---C2---H2D 110 (2) Cl2---Cr---N4 91.29 (6) H2C---C2---C3 110.8 (16) N1---Cr---N2 91.11 (7) H2D---C2---C3 104.7 (17) N1---Cr---N3 178.42 (8) N2---C3---C2 111.85 (19) N1---Cr---N4 90.49 (7) N2---C3---H3C 108.4 (16) N2---Cr---N3 90.15 (8) N2---C3---H3D 108.9 (16) N2---Cr---N4 178.34 (8) C2---C3---H3C 111.0 (16) N3---Cr---N4 88.26 (8) C2---C3---H3D 109.1 (16) Cr---N1---H1A 106.5 (19) H3C---C3---H3D 107 (2) Cr---N1---H1B 108.7 (16) N3---C4---H4C 108.4 (16) Cr---N1---C1 119.81 (13) N3---C4---H4D 108.1 (15) H1A---N1---H1B 104 (2) N3---C4---C5 111.49 (19) H1A---N1---C1 108.7 (19) H4C---C4---H4D 107 (2) H1B---N1---C1 107.6 (16) H4C---C4---C5 110.2 (16) Cr---N2---H2A 102 (2) H4D---C4---C5 111.1 (14) Cr---N2---H2B 109 (2) C4---C5---H5C 105.6 (16) Cr---N2---C3 120.38 (14) C4---C5---H5D 108.8 (17) H2A---N2---H2B 107 (3) C4---C5---C6 114.71 (19) H2A---N2---C3 110 (2) H5C---C5---H5D 108 (2) H2B---N2---C3 108 (2) H5C---C5---C6 108.0 (16) Cr---N3---H3A 108.3 (19) H5D---C5---C6 111.2 (17) Cr---N3---H3B 105.8 (19) N4---C6---C5 112.24 (19) Cr---N3---C4 120.53 (14) N4---C6---H6C 106.3 (15) H3A---N3---H3B 104 (3) N4---C6---H6D 106.0 (17) H3A---N3---C4 109.2 (19) C5---C6---H6C 110.9 (15) H3B---N3---C4 107.9 (19) C5---C6---H6D 111.8 (17) Cr---N4---H4A 107 (2) H6C---C6---H6D 109 (2) Cr---N4---H4B 104 (2) O1---Cl3---O2 108.55 (12) Cr---N4---C6 119.53 (15) O1---Cl3---O3 108.32 (11) H4A---N4---H4B 107 (3) O1---Cl3---O4 110.29 (13) H4A---N4---C6 108 (2) O2---Cl3---O3 110.30 (12) H4B---N4---C6 111 (2) O2---Cl3---O4 108.88 (13) N1---C1---H1C 110.3 (16) O3---Cl3---O4 110.48 (13) N1---C1---H1D 108.4 (14) Cl1---Cr---N1---C1 59.00 (15) Cl1---Cr---N4---C6 −130.76 (17) Cl2---Cr---N1---C1 −120.57 (15) Cl2---Cr---N4---C6 50.02 (17) N2---Cr---N1---C1 −32.28 (16) N1---Cr---N4---C6 140.22 (17) N4---Cr---N1---C1 148.14 (16) N3---Cr---N4---C6 −40.74 (17) Cl1---Cr---N2---C3 −56.16 (16) Cr---N1---C1---C2 53.7 (2) Cl2---Cr---N2---C3 123.04 (16) N1---C1---C2---C3 −71.2 (3) N1---Cr---N2---C3 32.88 (17) Cr---N2---C3---C2 −54.3 (2) N3---Cr---N2---C3 −146.17 (17) C1---C2---C3---N2 71.1 (3) Cl1---Cr---N3---C4 130.33 (16) Cr---N3---C4---C5 −58.4 (2) Cl2---Cr---N3---C4 −50.08 (16) N3---C4---C5---C6 67.0 (3) N2---Cr---N3---C4 −138.36 (17) Cr---N4---C6---C5 58.4 (2) N4---Cr---N3---C4 41.19 (17) C4---C5---C6---N4 −67.7 (3) -------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2479 .table-wrap} --------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···Cl1^i^ 0.85 (3) 2.68 (3) 3.3684 (19) 139 (2) N1---H1B···Cl1^ii^ 0.89 (3) 2.77 (3) 3.5229 (19) 143 (2) N2---H2A···O3^i^ 0.81 (3) 2.45 (3) 3.182 (3) 151 (3) N2---H2A···Cl2 0.81 (3) 2.67 (3) 3.072 (2) 112 (2) N2---H2B···O4 0.86 (3) 2.35 (3) 3.134 (3) 151 (3) N2---H2B···O2 0.86 (3) 2.56 (3) 3.326 (3) 149 (3) N3---H3A···O2 0.87 (3) 2.15 (3) 3.000 (3) 166 (3) N3---H3B···Cl2^iii^ 0.89 (3) 2.58 (3) 3.3168 (19) 140 (2) N4---H4A···O1^iv^ 0.81 (3) 2.28 (3) 3.033 (3) 156 (3) --------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y+1, −z+1; (iii) x−1, y, z; (iv) −x+1, y+1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- ---------- ---------- ------------- ------------- N1---H1A⋯Cl1^i^ 0.85 (3) 2.68 (3) 3.3684 (19) 139 (2) N1---H1B⋯Cl1^ii^ 0.89 (3) 2.77 (3) 3.5229 (19) 143 (2) N2---H2A⋯O3^i^ 0.81 (3) 2.45 (3) 3.182 (3) 151 (3) N2---H2A⋯Cl2 0.81 (3) 2.67 (3) 3.072 (2) 112 (2) N2---H2B⋯O4 0.86 (3) 2.35 (3) 3.134 (3) 151 (3) N2---H2B⋯O2 0.86 (3) 2.56 (3) 3.326 (3) 149 (3) N3---H3A⋯O2 0.87 (3) 2.15 (3) 3.000 (3) 166 (3) N3---H3B⋯Cl2^iii^ 0.89 (3) 2.58 (3) 3.3168 (19) 140 (2) N4---H4A⋯O1^iv^ 0.81 (3) 2.28 (3) 3.033 (3) 156 (3) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::	PubMed Central	2024-06-05T04:04:18.426484	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052098/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m381", "authors": [ { "first": "Jong-Ha", "last": "Choi" }, { "first": "William", "last": "Clegg" } ] }
PMC3052099	Related literature {#sec1} ================== For background to the chemistry of α-tocopherol \[systematic name 2,7,8-trimethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-ol\] and its derivatives and their applications, see: Dubbs & Gupta (1998[@bb3]); Azzi & Stoker (2000[@bb1]); Traber & Atkinson (2007[@bb8]). For the preparation, see: Witkowski & Walejko (2002[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~28~H~38~O~11~M ~r~ = 550.58Triclinic,a = 8.66 (1) Åb = 11.30 (1) Åc = 14.55 (1) Åα = 85.74 (5)°β = 89.13 (5)°γ = 88.16 (5)°V = 1419 (2) Å^3^Z = 2Synchrotron radiationλ = 0.59040 Åμ = 0.06 mm^−1^T = 100 K0.25 × 0.15 × 0.09 mm ### Data collection {#sec2.1.2} Mar Research MAR315 CCD diffractometerAbsorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 2003[@bb5]) T ~min~ = 0.985, T ~max~ = 0.9958538 measured reflections5956 independent reflections5260 reflections with I \> 2σ(I)R ~int~ = 0.023 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.045wR(F ^2^) = 0.118S = 0.995956 reflections795 parameters752 restraintsH-atom parameters constrainedΔρ~max~ = 0.21 e Å^−3^Δρ~min~ = −0.23 e Å^−3^ {#d5e353} Data collection: NECAT APS beamline software (unpublished); cell refinement: HKL-2000 (Otwinowski & Minor, 1997[@bb6]); data reduction: HKL-2000; program(s) used to solve structure: SHELXD (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb4]) and pyMOL (DeLano, 2002[@bb2]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100626X/gk2341sup1.cif](http://dx.doi.org/10.1107/S160053681100626X/gk2341sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100626X/gk2341Isup2.hkl](http://dx.doi.org/10.1107/S160053681100626X/gk2341Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2341&file=gk2341sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2341sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2341&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2341](http://scripts.iucr.org/cgi-bin/sendsup?gk2341)). This work was in part supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. X-ray data were collected at the NECAT 24ID-C beamline of the Advanced Photon Source, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy under contract No. W-31--109-Eng-38. Comment ======= α-Tocopherol (vitamin E) is a lipophilic compound, poorly soluble in water (Dubbs & Gupta, 1998). It is also poorly absorbed after oral administration. 2,2,5,7,8-Pentamethyl-6-hydroxychroman in which the lipophylic phytyl chain was replaced with a methyl group is often used as a model compound for structural and biological investigations. Enhancing of aqueous solubility is of interest because of challenges in supplying the vitamin E preparations. In order to improve pharmacological properties, the model compound was converted into the water-soluble glucoside which is easy cleavable by the appropriate enzymes or acidic medium (Witkowski & Walejko, 2002). In both symmetrically independent molecules, the heterocyclic ring of chroman system exists in the approximate half-chair conformation with two possible alternative positions, exo or endo, of the out of plane atom C03 (C53), as illustrated in the packing diagram, Fig. 2. As a consequence, there are also two alternative positions of the methyl substituents at C02 (C52) atoms. The occupancy ratio is 0.858:0.142 (0.005) and 0.523:0.477 (0.005), in the first and the second molecule, respectively. Two independent molecules in the cell are in the relation resembling the 2~1~ axis parallel to a direction, Fig. 2. This effect is emphasized by the β and γ unit-cell angles being close to 90°. Experimental {#experimental} ============ The title glucoside was synthesized by a modified Helferich method according to the published procedure (Witkowski & Walejko, 2002). The crystallization was carried out at room temperature by slow evaporation of 2,2,5,7,8-pentamethyl-6-hydroxychromanyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside solution in ethanol. Refinement {#refinement} ========== Fridel related reflections were averaged. The D configuration and anomeric state of the sugar moiety has been attributed according to synthesis and NMR studies (Witkowski & Walejko, 2002). Distance and angle restraints were only applied to the disordered parts of chroman moieties. All hydrogen atoms were constrained to idealized positions with C---H distances fixed at 0.98--1.00 Å and U~iso~(H) = 1.5U~eq~(C) for methyl hydrogen atoms and 1.2U~eq~(C) for others. The sum of occupancies of alternative positions of disordered atoms of was constrained to unity. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. For clarity, two symmetrically independent molecules are shown separately (a and b) with hydrogen atoms omitted. Carbon atoms of the chroman systems which adopt two different conformations, are shown in green and blue, respectively. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o718-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram viewed along a axis. Only non-hydrogen atoms are shown. ::: ![](e-67-0o718-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e145 .table-wrap} --------------------- --------------------------------------- C~28~H~38~O~11~ Z = 2 M~r~ = 550.58 F(000) = 588 Triclinic, P1 D~x~ = 1.289 Mg m^−3^ Hall symbol: P 1 Synchrotron radiation, λ = 0.59040 Å a = 8.66 (1) Å Cell parameters from 5956 reflections b = 11.30 (1) Å θ = 1.5--22.6° c = 14.55 (1) Å µ = 0.06 mm^−1^ α = 85.74 (5)° T = 100 K β = 89.13 (5)° Needle, colourless γ = 88.16 (5)° 0.25 × 0.15 × 0.09 mm V = 1419 (2) Å^3^ --------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e272 .table-wrap} ---------------------------------------------------------------------------- -------------------------------------- Mar Research MAR315 CCD diffractometer 5956 independent reflections Radiation source: NECAT 24ID-C synchrotron beamline APS, USA 5260 reflections with I \> 2σ(I) Si111 double crystal R~int~ = 0.023 ω scans θ~max~ = 22.6°, θ~min~ = 1.5° Absorption correction: multi-scan (SCALEPACK; Otwinowski et al., 2003) h = 0→11 T~min~ = 0.985, T~max~ = 0.995 k = −14→14 8538 measured reflections l = −18→18 ---------------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e386 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.118 H-atom parameters constrained S = 0.99 w = 1/\[σ^2^(F~o~^2^) + (0.0671P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 5956 reflections (Δ/σ)~max~ \< 0.001 795 parameters Δρ~max~ = 0.21 e Å^−3^ 752 restraints Δρ~min~ = −0.23 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e540 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The crystal was mounted with vaseline on a pin attached capillary. Upon mounting, the crystal was quenched to 100 K in a nitrogen-gas stream supplied by an Oxford Cryo-Jet. Diffraction data were measured at the station 24-ID---C of the APS synchrotron by rotation method. Geometry. All e.s.d.\'s are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. Refinement. Refinement of F^2^ against all reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e641 .table-wrap} ------- ------------- --------------- --------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) O01 0.7561 (2) 0.6151 (2) 0.69759 (14) 0.0488 (5) C02A 0.9136 (8) 0.6057 (5) 0.7333 (3) 0.0389 (13) 0.858 (5) C03A 1.0148 (4) 0.5345 (3) 0.6699 (2) 0.0389 (8) 0.858 (5) HA03A 0.9747 0.4536 0.6689 0.047\ 0.858 (5) HA03B 1.1210 0.5272 0.6944 0.047\* 0.858 (5) C04A 1.0197 (5) 0.5922 (4) 0.5721 (4) 0.0409 (10) 0.858 (5) HA04A 1.0866 0.6618 0.5697 0.049\* 0.858 (5) HA04B 1.0647 0.5350 0.5301 0.049\* 0.858 (5) C02B 0.885 (5) 0.612 (2) 0.7368 (19) 0.051 (9) 0.142 (5) C03B 1.013 (3) 0.672 (2) 0.6797 (13) 0.064 (6) 0.142 (5) HB03A 1.1138 0.6506 0.7090 0.077\* 0.142 (5) HB03B 0.9975 0.7594 0.6803 0.077\* 0.142 (5) C04B 1.020 (2) 0.639 (3) 0.5796 (15) 0.048 (6) 0.142 (5) HB04A 1.0786 0.6992 0.5417 0.058\* 0.142 (5) HB04B 1.0758 0.5614 0.5765 0.058\* 0.142 (5) C05 0.8296 (3) 0.6572 (2) 0.4453 (2) 0.0394 (6) C06 0.6793 (3) 0.6888 (2) 0.41880 (19) 0.0353 (5) C07 0.5552 (3) 0.6891 (2) 0.48235 (19) 0.0366 (6) C08 0.5853 (3) 0.6646 (2) 0.5762 (2) 0.0392 (6) C09 0.7371 (3) 0.6387 (2) 0.6032 (2) 0.0400 (6) C10 0.8588 (3) 0.6314 (3) 0.5404 (2) 0.0415 (6) C11A 0.9684 (4) 0.7319 (3) 0.7378 (3) 0.0473 (9) 0.858 (5) HA11A 0.9710 0.7715 0.6756 0.071\* 0.858 (5) HA11B 1.0722 0.7295 0.7639 0.071\* 0.858 (5) HA11C 0.8972 0.7758 0.7768 0.071\* 0.858 (5) C12A 0.8999 (4) 0.5440 (4) 0.8282 (3) 0.0474 (9) 0.858 (5) HA12A 0.8627 0.4637 0.8235 0.071\* 0.858 (5) HA12B 0.8267 0.5888 0.8653 0.071\* 0.858 (5) HA12C 1.0013 0.5394 0.8574 0.071\* 0.858 (5) C11B 0.902 (3) 0.4772 (19) 0.7345 (14) 0.051 (6) 0.142 (5) HB11A 0.8710 0.4392 0.7943 0.077\* 0.142 (5) HB11B 1.0103 0.4552 0.7214 0.077\* 0.142 (5) HB11C 0.8365 0.4507 0.6862 0.077\* 0.142 (5) C12B 0.892 (3) 0.646 (3) 0.8367 (16) 0.061 (7) 0.142 (5) HB12A 0.9000 0.7324 0.8372 0.092\* 0.142 (5) HB12B 0.9819 0.6067 0.8669 0.092\* 0.142 (5) HB12C 0.7975 0.6213 0.8699 0.092\* 0.142 (5) C13 0.9577 (3) 0.6458 (3) 0.3752 (2) 0.0443 (7) H13A 0.9135 0.6440 0.3137 0.066\* H13B 1.0181 0.5722 0.3901 0.066\* H13C 1.0250 0.7138 0.3761 0.066\* O14 0.6441 (2) 0.71514 (15) 0.32506 (13) 0.0379 (4) C15 0.3903 (3) 0.7082 (2) 0.4519 (2) 0.0403 (6) H15A 0.3880 0.7258 0.3850 0.060\* H15B 0.3428 0.7750 0.4824 0.060\* H15C 0.3327 0.6364 0.4685 0.060\* C16 0.4554 (4) 0.6646 (3) 0.6465 (2) 0.0442 (6) H16A 0.4985 0.6602 0.7086 0.066\* H16B 0.3913 0.5958 0.6401 0.066\* H16C 0.3921 0.7377 0.6364 0.066\* C17 0.7064 (3) 0.8206 (2) 0.28211 (18) 0.0366 (6) H17A 0.7912 0.8480 0.3205 0.044\* C18 0.5803 (3) 0.9181 (2) 0.26962 (19) 0.0370 (6) H18A 0.6253 0.9914 0.2387 0.044\* C19 0.4521 (3) 0.8772 (2) 0.21147 (19) 0.0376 (6) H19A 0.4010 0.8078 0.2443 0.045\* C20 0.5187 (3) 0.8427 (2) 0.11993 (19) 0.0367 (6) H20A 0.5521 0.9145 0.0813 0.044\* C21 0.6533 (3) 0.7531 (2) 0.13481 (19) 0.0369 (6) H21A 0.6143 0.6762 0.1632 0.044\* C22 0.7377 (3) 0.7323 (2) 0.0457 (2) 0.0412 (6) H22A 0.6662 0.6991 0.0026 0.049\* H22B 0.7735 0.8089 0.0170 0.049\* O23 0.7644 (2) 0.79836 (16) 0.19401 (13) 0.0378 (4) O24 0.5137 (2) 0.94463 (16) 0.35732 (13) 0.0395 (4) C25 0.5971 (3) 1.0157 (2) 0.4072 (2) 0.0409 (6) O26 0.7141 (2) 1.05995 (18) 0.37950 (15) 0.0467 (5) C27 0.5227 (4) 1.0309 (3) 0.4989 (2) 0.0516 (8) H27A 0.4863 0.9542 0.5250 0.077\* H27B 0.4350 1.0876 0.4915 0.077\* H27C 0.5981 1.0609 0.5403 0.077\* O28 0.3402 (2) 0.97388 (16) 0.19391 (13) 0.0397 (4) C29 0.1984 (3) 0.9609 (2) 0.2340 (2) 0.0419 (6) O30 0.1621 (3) 0.8758 (2) 0.28195 (16) 0.0535 (5) C31 0.0959 (4) 1.0682 (3) 0.2114 (3) 0.0538 (8) H31A 0.1392 1.1373 0.2374 0.081\* H31B −0.0074 1.0546 0.2378 0.081\* H31C 0.0888 1.0828 0.1444 0.081\* O32 0.3995 (2) 0.78273 (16) 0.07392 (13) 0.0403 (4) C33 0.3230 (4) 0.8441 (3) 0.0039 (2) 0.0435 (6) C34 0.1947 (4) 0.7725 (3) −0.0281 (3) 0.0618 (9) H34A 0.1207 0.8249 −0.0630 0.093\* H34B 0.1423 0.7331 0.0254 0.093\* H34C 0.2371 0.7125 −0.0677 0.093\* O35 0.3556 (3) 0.94005 (19) −0.02650 (15) 0.0519 (5) O36 0.8680 (2) 0.65193 (17) 0.06139 (14) 0.0443 (5) C37 0.8400 (4) 0.5356 (3) 0.0729 (2) 0.0458 (7) C38 0.9850 (4) 0.4649 (3) 0.0940 (3) 0.0607 (9) H38A 1.0619 0.4824 0.0452 0.091\* H38B 0.9632 0.3801 0.0976 0.091\* H38C 1.0252 0.4856 0.1532 0.091\* O39 0.7119 (3) 0.49706 (19) 0.06786 (16) 0.0533 (5) O51 0.2336 (2) 0.3517 (3) 0.28927 (15) 0.0623 (7) C52A 0.371 (2) 0.3815 (16) 0.2494 (14) 0.037 (3) 0.523 (5) C53A 0.5086 (7) 0.3217 (6) 0.3023 (4) 0.0447 (14) 0.523 (5) HA53A 0.5085 0.2348 0.2971 0.054\* 0.523 (5) HA53B 0.6064 0.3518 0.2750 0.054\* 0.523 (5) C54A 0.4982 (11) 0.3477 (8) 0.4039 (6) 0.0405 (19) 0.523 (5) HA54A 0.5682 0.2912 0.4395 0.049\* 0.523 (5) HA54B 0.5352 0.4287 0.4102 0.049\* 0.523 (5) C52B 0.398 (2) 0.377 (2) 0.2549 (13) 0.038 (3) 0.477 (5) C53B 0.4895 (7) 0.4495 (5) 0.3180 (4) 0.0389 (14) 0.477 (5) HB53A 0.5959 0.4585 0.2932 0.047\* 0.477 (5) HB53B 0.4405 0.5297 0.3197 0.047\* 0.477 (5) C54B 0.4957 (11) 0.3904 (7) 0.4148 (7) 0.0355 (19) 0.477 (5) HB54A 0.5254 0.4491 0.4581 0.043\* 0.477 (5) HB54B 0.5755 0.3255 0.4173 0.043\* 0.477 (5) C55 0.3091 (3) 0.3160 (2) 0.53997 (19) 0.0365 (6) C56 0.1604 (3) 0.2858 (2) 0.56897 (18) 0.0345 (5) C57 0.0357 (3) 0.2893 (2) 0.50902 (19) 0.0342 (5) C58 0.0645 (3) 0.3129 (2) 0.41409 (19) 0.0366 (6) C59 0.2153 (3) 0.3346 (3) 0.3839 (2) 0.0437 (6) C60 0.3370 (3) 0.3390 (3) 0.4452 (2) 0.0441 (7) C61A 0.3660 (7) 0.5140 (5) 0.2516 (4) 0.0457 (14) 0.523 (5) HA61A 0.3073 0.5496 0.1990 0.069\* 0.523 (5) HA61B 0.4715 0.5429 0.2484 0.069\* 0.523 (5) HA61C 0.3159 0.5360 0.3091 0.069\* 0.523 (5) C62A 0.3814 (7) 0.3441 (6) 0.1501 (4) 0.0449 (14) 0.523 (5) HA62A 0.3859 0.2573 0.1510 0.067\* 0.523 (5) HA62B 0.4749 0.3759 0.1201 0.067\* 0.523 (5) HA62C 0.2904 0.3752 0.1160 0.067\* 0.523 (5) C61B 0.4591 (8) 0.2526 (6) 0.2504 (5) 0.0485 (16) 0.477 (5) HB61A 0.5649 0.2534 0.2256 0.073\* 0.477 (5) HB61B 0.3936 0.2104 0.2103 0.073\* 0.477 (5) HB61C 0.4589 0.2123 0.3124 0.073\* 0.477 (5) C62B 0.3773 (8) 0.4428 (7) 0.1606 (4) 0.0498 (17) 0.477 (5) HB62A 0.3323 0.5223 0.1681 0.075\* 0.477 (5) HB62B 0.3082 0.3989 0.1237 0.075\* 0.477 (5) HB62C 0.4779 0.4498 0.1292 0.075\* 0.477 (5) C63 0.4369 (3) 0.3278 (2) 0.60830 (19) 0.0404 (6) H63A 0.4980 0.3969 0.5887 0.061\* H63B 0.5037 0.2560 0.6109 0.061\* H63C 0.3916 0.3380 0.6694 0.061\* O64 0.1302 (2) 0.25883 (15) 0.66386 (12) 0.0352 (4) C65 −0.1279 (3) 0.2750 (2) 0.5431 (2) 0.0383 (6) H65A −0.1896 0.3467 0.5242 0.058\* H65B −0.1291 0.2627 0.6104 0.058\* H65C −0.1717 0.2063 0.5167 0.058\* C66 −0.0684 (3) 0.3201 (3) 0.3479 (2) 0.0418 (6) H66A −0.1293 0.2486 0.3580 0.063\* H66B −0.0282 0.3261 0.2845 0.063\* H66C −0.1340 0.3902 0.3583 0.063\* C67 0.1988 (3) 0.1507 (2) 0.70335 (19) 0.0370 (6) H67A 0.2818 0.1218 0.6613 0.044\* C68 0.0754 (3) 0.0573 (2) 0.71880 (18) 0.0358 (5) H68A 0.1241 −0.0177 0.7474 0.043\* C69 −0.0498 (3) 0.1007 (2) 0.78254 (19) 0.0368 (6) H69A −0.1018 0.1741 0.7533 0.044\* C70 0.0221 (3) 0.1284 (2) 0.87262 (19) 0.0360 (6) H70A 0.0622 0.0535 0.9061 0.043\* C71 0.1532 (3) 0.2149 (2) 0.85451 (18) 0.0359 (6) H71A 0.1100 0.2939 0.8300 0.043\* C72 0.2424 (3) 0.2292 (2) 0.9411 (2) 0.0404 (6) H72A 0.1761 0.2712 0.9851 0.049\* H72B 0.2713 0.1499 0.9705 0.049\* O73 0.2619 (2) 0.16994 (16) 0.78913 (12) 0.0373 (4) O74 0.0062 (2) 0.03338 (16) 0.63368 (13) 0.0390 (4) C75 0.0909 (3) −0.0373 (2) 0.5785 (2) 0.0402 (6) O76 0.2155 (2) −0.07916 (18) 0.60091 (15) 0.0470 (5) C77 0.0086 (4) −0.0553 (3) 0.4925 (2) 0.0510 (7) H77A 0.0792 −0.0936 0.4497 0.077\* H77B −0.0280 0.0217 0.4642 0.077\* H77C −0.0797 −0.1058 0.5066 0.077\* O78 −0.1617 (2) 0.01101 (16) 0.80209 (13) 0.0386 (4) C79 −0.3014 (3) 0.0277 (3) 0.7598 (2) 0.0439 (6) O80 −0.3347 (2) 0.1129 (2) 0.71021 (16) 0.0539 (6) C81 −0.4040 (4) −0.0740 (3) 0.7847 (3) 0.0565 (8) H81A −0.5076 −0.0436 0.8001 0.085\* H81B −0.3616 −0.1218 0.8380 0.085\* H81C −0.4098 −0.1234 0.7323 0.085\* O82 −0.0937 (2) 0.18503 (15) 0.92817 (13) 0.0384 (4) C83 −0.1639 (3) 0.1161 (2) 0.9962 (2) 0.0396 (6) C84 −0.2941 (4) 0.1831 (3) 1.0383 (2) 0.0542 (8) H84A −0.2727 0.2679 1.0334 0.081\* H84B −0.3057 0.1552 1.1034 0.081\* H84C −0.3898 0.1701 1.0058 0.081\* O85 −0.1246 (3) 0.01617 (18) 1.01807 (15) 0.0516 (5) O86 0.3803 (2) 0.2954 (2) 0.92082 (15) 0.0484 (5) C87 0.3644 (4) 0.4134 (3) 0.9065 (2) 0.0524 (8) C88 0.5135 (5) 0.4673 (5) 0.8774 (3) 0.0841 (14) H88A 0.4979 0.5534 0.8660 0.126\* H88B 0.5514 0.4336 0.8209 0.126\* H88C 0.5895 0.4504 0.9263 0.126\* O89 0.2423 (3) 0.4656 (2) 0.91500 (18) 0.0616 (6) ------- ------------- --------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e3044 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O01 0.0416 (11) 0.0643 (14) 0.0400 (12) −0.0051 (10) −0.0039 (9) 0.0009 (10) C02A 0.038 (2) 0.040 (3) 0.039 (2) 0.0009 (18) −0.0043 (16) −0.0008 (19) C03A 0.0435 (17) 0.0315 (15) 0.0412 (18) 0.0003 (13) −0.0014 (13) −0.0001 (13) C04A 0.042 (2) 0.033 (2) 0.047 (2) −0.0019 (15) 0.0032 (15) −0.0004 (17) C02B 0.057 (17) 0.030 (13) 0.066 (16) 0.002 (12) −0.010 (13) −0.005 (12) C03B 0.085 (13) 0.051 (11) 0.053 (12) 0.023 (11) 0.001 (11) 0.009 (10) C04B 0.041 (11) 0.077 (16) 0.024 (10) 0.000 (12) −0.009 (8) 0.011 (11) C05 0.0466 (15) 0.0285 (12) 0.0431 (16) −0.0058 (11) 0.0021 (12) −0.0003 (11) C06 0.0421 (14) 0.0265 (12) 0.0371 (14) −0.0025 (10) −0.0029 (11) −0.0007 (10) C07 0.0447 (14) 0.0275 (12) 0.0380 (14) −0.0052 (10) −0.0005 (11) −0.0021 (10) C08 0.0497 (16) 0.0302 (13) 0.0375 (15) −0.0053 (11) −0.0005 (12) −0.0001 (11) C09 0.0454 (15) 0.0340 (13) 0.0403 (16) −0.0042 (11) 0.0002 (12) 0.0005 (11) C10 0.0426 (14) 0.0377 (14) 0.0440 (16) −0.0010 (11) −0.0049 (12) −0.0010 (12) C11A 0.055 (2) 0.0369 (17) 0.052 (2) −0.0079 (15) −0.0018 (16) −0.0083 (15) C12A 0.0456 (19) 0.051 (2) 0.045 (2) 0.0000 (16) −0.0002 (15) 0.0025 (16) C11B 0.065 (14) 0.054 (13) 0.031 (10) 0.025 (10) 0.007 (9) 0.006 (9) C12B 0.042 (11) 0.086 (18) 0.056 (14) 0.011 (12) 0.005 (10) −0.015 (13) C13 0.0491 (16) 0.0374 (15) 0.0459 (17) −0.0032 (12) 0.0016 (13) −0.0006 (12) O14 0.0472 (10) 0.0316 (9) 0.0348 (10) −0.0071 (8) −0.0001 (8) 0.0004 (8) C15 0.0444 (15) 0.0362 (14) 0.0404 (15) −0.0043 (11) 0.0011 (11) −0.0023 (11) C16 0.0495 (16) 0.0403 (15) 0.0428 (16) −0.0012 (12) 0.0008 (12) −0.0034 (12) C17 0.0456 (15) 0.0307 (13) 0.0330 (14) −0.0055 (11) 0.0003 (11) 0.0019 (10) C18 0.0435 (14) 0.0319 (13) 0.0359 (14) −0.0055 (11) 0.0020 (11) −0.0025 (11) C19 0.0430 (14) 0.0287 (12) 0.0410 (15) −0.0021 (11) −0.0035 (11) −0.0008 (11) C20 0.0449 (15) 0.0286 (13) 0.0371 (14) −0.0070 (11) −0.0059 (11) −0.0019 (10) C21 0.0412 (14) 0.0336 (13) 0.0360 (14) −0.0042 (11) −0.0011 (11) −0.0009 (11) C22 0.0487 (16) 0.0344 (14) 0.0402 (15) −0.0017 (12) 0.0022 (12) −0.0022 (11) O23 0.0419 (10) 0.0358 (10) 0.0361 (10) −0.0060 (8) 0.0008 (8) −0.0039 (8) O24 0.0487 (11) 0.0308 (9) 0.0398 (11) −0.0077 (8) 0.0009 (8) −0.0065 (8) C25 0.0525 (16) 0.0282 (13) 0.0427 (16) −0.0037 (12) −0.0019 (12) −0.0056 (11) O26 0.0496 (12) 0.0398 (11) 0.0516 (13) −0.0096 (9) −0.0027 (9) −0.0066 (9) C27 0.068 (2) 0.0439 (17) 0.0453 (17) −0.0103 (15) 0.0048 (15) −0.0139 (13) O28 0.0440 (10) 0.0308 (9) 0.0439 (11) −0.0009 (8) −0.0013 (8) 0.0001 (8) C29 0.0472 (15) 0.0375 (15) 0.0421 (16) −0.0078 (12) −0.0043 (12) −0.0062 (12) O30 0.0516 (12) 0.0491 (12) 0.0587 (14) −0.0070 (10) 0.0070 (10) 0.0045 (10) C31 0.0489 (17) 0.0507 (18) 0.062 (2) 0.0046 (14) −0.0029 (14) −0.0087 (15) O32 0.0483 (11) 0.0307 (9) 0.0423 (11) −0.0031 (8) −0.0080 (8) −0.0026 (8) C33 0.0524 (16) 0.0374 (15) 0.0408 (15) 0.0018 (12) −0.0064 (12) −0.0027 (12) C34 0.060 (2) 0.0548 (19) 0.071 (2) −0.0059 (16) −0.0217 (17) −0.0072 (17) O35 0.0635 (14) 0.0443 (12) 0.0470 (13) −0.0027 (10) −0.0102 (10) 0.0049 (10) O36 0.0431 (10) 0.0422 (11) 0.0478 (12) −0.0019 (9) 0.0010 (8) −0.0047 (9) C37 0.0570 (18) 0.0419 (16) 0.0381 (16) −0.0010 (14) 0.0017 (13) −0.0007 (12) C38 0.065 (2) 0.060 (2) 0.055 (2) 0.0152 (17) 0.0055 (16) 0.0012 (16) O39 0.0559 (13) 0.0428 (12) 0.0616 (15) −0.0070 (10) 0.0014 (10) −0.0045 (10) O51 0.0351 (11) 0.112 (2) 0.0362 (12) −0.0017 (12) 0.0016 (9) 0.0153 (12) C52A 0.031 (7) 0.029 (4) 0.051 (5) 0.000 (4) −0.005 (4) −0.003 (3) C53A 0.041 (3) 0.057 (4) 0.036 (3) −0.005 (3) −0.003 (2) 0.000 (3) C54A 0.040 (4) 0.042 (5) 0.039 (4) −0.007 (4) 0.002 (3) −0.002 (3) C52B 0.027 (6) 0.050 (6) 0.037 (6) −0.009 (4) 0.010 (4) 0.001 (4) C53B 0.038 (3) 0.034 (3) 0.044 (3) −0.010 (2) 0.000 (2) 0.000 (2) C54B 0.032 (3) 0.032 (4) 0.042 (4) −0.004 (3) −0.001 (3) −0.003 (3) C55 0.0381 (13) 0.0325 (13) 0.0382 (15) −0.0011 (10) −0.0034 (11) 0.0033 (11) C56 0.0429 (14) 0.0275 (12) 0.0325 (14) −0.0001 (10) 0.0016 (11) 0.0018 (10) C57 0.0375 (13) 0.0279 (12) 0.0366 (14) −0.0020 (10) 0.0017 (10) 0.0023 (10) C58 0.0370 (14) 0.0347 (13) 0.0376 (15) −0.0029 (11) 0.0001 (10) 0.0020 (11) C59 0.0416 (14) 0.0523 (17) 0.0353 (15) 0.0005 (13) −0.0034 (11) 0.0088 (12) C60 0.0378 (14) 0.0516 (17) 0.0410 (16) −0.0032 (12) 0.0001 (11) 0.0100 (13) C61A 0.053 (3) 0.039 (3) 0.046 (3) −0.017 (2) −0.003 (3) −0.003 (2) C62A 0.041 (3) 0.061 (4) 0.033 (3) −0.009 (3) 0.001 (2) −0.004 (3) C61B 0.053 (4) 0.044 (3) 0.050 (4) −0.003 (3) 0.003 (3) −0.012 (3) C62B 0.055 (4) 0.057 (4) 0.038 (3) −0.018 (3) 0.001 (3) −0.001 (3) C63 0.0436 (15) 0.0379 (14) 0.0394 (15) −0.0039 (12) −0.0051 (11) 0.0004 (11) O64 0.0412 (10) 0.0301 (9) 0.0337 (10) 0.0015 (7) 0.0003 (7) 0.0004 (7) C65 0.0382 (13) 0.0368 (14) 0.0396 (15) −0.0026 (11) 0.0019 (11) 0.0002 (11) C66 0.0377 (14) 0.0443 (15) 0.0429 (16) −0.0021 (12) −0.0041 (11) 0.0015 (12) C67 0.0443 (15) 0.0299 (13) 0.0362 (14) 0.0023 (11) 0.0001 (11) −0.0001 (11) C68 0.0440 (14) 0.0302 (12) 0.0328 (14) −0.0004 (10) 0.0004 (11) −0.0005 (10) C69 0.0436 (14) 0.0277 (12) 0.0386 (15) −0.0018 (10) 0.0046 (11) −0.0009 (10) C70 0.0408 (14) 0.0288 (12) 0.0378 (14) 0.0025 (10) 0.0061 (11) −0.0025 (10) C71 0.0400 (14) 0.0298 (13) 0.0377 (15) 0.0006 (11) 0.0028 (11) −0.0030 (10) C72 0.0474 (15) 0.0350 (14) 0.0386 (15) −0.0035 (12) −0.0005 (12) 0.0001 (11) O73 0.0394 (10) 0.0377 (10) 0.0345 (10) 0.0022 (8) 0.0005 (8) −0.0023 (8) O74 0.0472 (10) 0.0335 (9) 0.0364 (10) 0.0013 (8) 0.0014 (8) −0.0056 (8) C75 0.0511 (17) 0.0276 (13) 0.0419 (16) −0.0015 (12) 0.0079 (12) −0.0037 (11) O76 0.0495 (12) 0.0390 (11) 0.0528 (13) 0.0044 (9) 0.0010 (9) −0.0087 (9) C77 0.064 (2) 0.0446 (16) 0.0454 (18) 0.0022 (14) −0.0022 (14) −0.0091 (14) O78 0.0425 (10) 0.0315 (9) 0.0415 (11) −0.0038 (8) −0.0005 (8) 0.0009 (8) C79 0.0415 (15) 0.0460 (16) 0.0438 (16) −0.0025 (12) −0.0012 (12) 0.0000 (13) O80 0.0455 (12) 0.0523 (13) 0.0617 (14) 0.0003 (10) −0.0047 (10) 0.0104 (11) C81 0.0499 (17) 0.0492 (18) 0.070 (2) −0.0116 (15) −0.0026 (15) 0.0007 (16) O82 0.0431 (10) 0.0305 (9) 0.0413 (11) 0.0005 (8) 0.0068 (8) −0.0023 (8) C83 0.0434 (14) 0.0361 (14) 0.0395 (15) −0.0072 (12) 0.0023 (11) −0.0032 (11) C84 0.0579 (19) 0.0458 (17) 0.058 (2) −0.0022 (14) 0.0196 (15) −0.0041 (14) O85 0.0649 (14) 0.0396 (11) 0.0483 (13) 0.0003 (10) 0.0079 (10) 0.0064 (9) O86 0.0447 (11) 0.0559 (13) 0.0455 (12) −0.0094 (10) −0.0035 (9) −0.0048 (10) C87 0.058 (2) 0.057 (2) 0.0420 (17) −0.0141 (16) −0.0108 (14) 0.0056 (14) C88 0.075 (3) 0.113 (4) 0.063 (3) −0.049 (3) −0.016 (2) 0.019 (2) O89 0.0707 (17) 0.0452 (13) 0.0693 (17) −0.0071 (12) −0.0181 (12) −0.0014 (11) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e4737 .table-wrap} --------------------------- ------------- --------------------------- -------------- O01---C02B 1.26 (4) O51---C52A 1.36 (2) O01---C09 1.390 (4) O51---C59 1.383 (4) O01---C02A 1.465 (7) O51---C52B 1.53 (2) C02A---C12A 1.504 (6) C52A---C61A 1.499 (19) C02A---C03A 1.518 (6) C52A---C62A 1.53 (2) C02A---C11A 1.524 (7) C52A---C53A 1.541 (15) C03A---C04A 1.521 (6) C53A---C54A 1.529 (9) C03A---HA03A 0.9900 C53A---HA53A 0.9900 C03A---HA03B 0.9900 C53A---HA53B 0.9900 C04A---C10 1.517 (5) C54A---C60 1.515 (9) C04A---HA04A 0.9900 C54A---HA54A 0.9900 C04A---HA04B 0.9900 C54A---HA54B 0.9900 C02B---C11B 1.526 (19) C52B---C61B 1.49 (2) C02B---C03B 1.526 (19) C52B---C53B 1.521 (16) C02B---C12B 1.535 (19) C52B---C62B 1.52 (2) C03B---C04B 1.532 (17) C53B---C54B 1.514 (11) C03B---HB03A 0.9900 C53B---HB53A 0.9900 C03B---HB03B 0.9900 C53B---HB53B 0.9900 C04B---C10 1.525 (17) C54B---C60 1.554 (10) C04B---HB04A 0.9900 C54B---HB54A 0.9900 C04B---HB04B 0.9900 C54B---HB54B 0.9900 C05---C06 1.391 (4) C55---C56 1.394 (4) C05---C10 1.417 (4) C55---C60 1.403 (4) C05---C13 1.504 (4) C55---C63 1.514 (4) C06---O14 1.410 (3) C56---C57 1.396 (4) C06---C07 1.407 (4) C56---O64 1.414 (3) C07---C08 1.400 (4) C57---C58 1.407 (4) C07---C15 1.506 (4) C57---C65 1.504 (4) C08---C09 1.394 (4) C58---C59 1.395 (4) C08---C16 1.508 (4) C58---C66 1.508 (4) C09---C10 1.389 (4) C59---C60 1.396 (4) C11A---HA11A 0.9800 C61A---HA61A 0.9800 C11A---HA11B 0.9800 C61A---HA61B 0.9800 C11A---HA11C 0.9800 C61A---HA61C 0.9800 C12A---HA12A 0.9800 C62A---HA62A 0.9800 C12A---HA12B 0.9800 C62A---HA62B 0.9800 C12A---HA12C 0.9800 C62A---HA62C 0.9800 C11B---HB11A 0.9800 C61B---HB61A 0.9800 C11B---HB11B 0.9800 C61B---HB61B 0.9800 C11B---HB11C 0.9800 C61B---HB61C 0.9800 C12B---HB12A 0.9800 C62B---HB62A 0.9800 C12B---HB12B 0.9800 C62B---HB62B 0.9800 C12B---HB12C 0.9800 C62B---HB62C 0.9800 C13---H13A 0.9800 C63---H63A 0.9800 C13---H13B 0.9800 C63---H63B 0.9800 C13---H13C 0.9800 C63---H63C 0.9800 O14---C17 1.422 (3) O64---C67 1.426 (3) C15---H15A 0.9800 C65---H65A 0.9800 C15---H15B 0.9800 C65---H65B 0.9800 C15---H15C 0.9800 C65---H65C 0.9800 C16---H16A 0.9800 C66---H66A 0.9800 C16---H16B 0.9800 C66---H66B 0.9800 C16---H16C 0.9800 C66---H66C 0.9800 C17---O23 1.407 (3) C67---O73 1.404 (3) C17---C18 1.530 (4) C67---C68 1.529 (4) C17---H17A 1.0000 C67---H67A 1.0000 C18---O24 1.440 (3) C68---O74 1.432 (3) C18---C19 1.510 (4) C68---C69 1.510 (3) C18---H18A 1.0000 C68---H68A 1.0000 C19---O28 1.447 (3) C69---O78 1.435 (3) C19---C20 1.516 (4) C69---C70 1.517 (4) C19---H19A 1.0000 C69---H69A 1.0000 C20---O32 1.451 (3) C70---O82 1.442 (3) C20---C21 1.526 (4) C70---C71 1.530 (4) C20---H20A 1.0000 C70---H70A 1.0000 C21---O23 1.433 (3) C71---O73 1.436 (3) C21---C22 1.508 (4) C71---C72 1.509 (4) C21---H21A 1.0000 C71---H71A 1.0000 C22---O36 1.435 (4) C72---O86 1.445 (4) C22---H22A 0.9900 C72---H72A 0.9900 C22---H22B 0.9900 C72---H72B 0.9900 O24---C25 1.354 (3) O74---C75 1.364 (3) C25---O26 1.196 (3) C75---O76 1.204 (4) C25---C27 1.491 (4) C75---C77 1.480 (4) C27---H27A 0.9800 C77---H77A 0.9800 C27---H27B 0.9800 C77---H77B 0.9800 C27---H27C 0.9800 C77---H77C 0.9800 O28---C29 1.359 (4) O78---C79 1.367 (3) C29---O30 1.193 (3) C79---O80 1.190 (4) C29---C31 1.499 (4) C79---C81 1.495 (4) C31---H31A 0.9800 C81---H81A 0.9800 C31---H31B 0.9800 C81---H81B 0.9800 C31---H31C 0.9800 C81---H81C 0.9800 O32---C33 1.358 (4) O82---C83 1.361 (3) C33---O35 1.181 (4) C83---O85 1.190 (4) C33---C34 1.496 (5) C83---C84 1.488 (4) C34---H34A 0.9800 C84---H84A 0.9800 C34---H34B 0.9800 C84---H84B 0.9800 C34---H34C 0.9800 C84---H84C 0.9800 O36---C37 1.342 (4) O86---C87 1.337 (4) C37---O39 1.211 (4) C87---O89 1.204 (4) C37---C38 1.490 (5) C87---C88 1.488 (5) C38---H38A 0.9800 C88---H88A 0.9800 C38---H38B 0.9800 C88---H88B 0.9800 C38---H38C 0.9800 C88---H88C 0.9800 C02B---O01---C09 123.9 (11) C52A---O51---C59 122.0 (7) C02B---O01---C02A 6.8 (12) C52A---O51---C52B 7.3 (13) C09---O01---C02A 118.2 (3) C59---O51---C52B 115.5 (6) O01---C02A---C12A 105.5 (4) O51---C52A---C61A 102.3 (13) O01---C02A---C03A 109.1 (4) O51---C52A---C62A 111.0 (10) C12A---C02A---C03A 111.8 (4) C61A---C52A---C62A 111.4 (14) O01---C02A---C11A 106.9 (4) O51---C52A---C53A 112.0 (14) C12A---C02A---C11A 111.0 (4) C61A---C52A---C53A 112.7 (10) C03A---C02A---C11A 112.1 (4) C62A---C52A---C53A 107.5 (13) C02A---C03A---C04A 112.0 (3) C54A---C53A---C52A 110.2 (9) C02A---C03A---HA03A 109.2 C54A---C53A---HA53A 109.6 C04A---C03A---HA03A 109.2 C52A---C53A---HA53A 109.6 C02A---C03A---HA03B 109.2 C54A---C53A---HA53B 109.6 C04A---C03A---HA03B 109.2 C52A---C53A---HA53B 109.6 HA03A---C03A---HA03B 107.9 HA53A---C53A---HA53B 108.1 C10---C04A---C03A 110.8 (3) C60---C54A---C53A 114.0 (6) C10---C04A---HA04A 109.5 C60---C54A---HA54A 108.8 C03A---C04A---HA04A 109.5 C53A---C54A---HA54A 108.8 C10---C04A---HA04B 109.5 C60---C54A---HA54B 108.8 C03A---C04A---HA04B 109.5 C53A---C54A---HA54B 108.8 HA04A---C04A---HA04B 108.1 HA54A---C54A---HA54B 107.6 O01---C02B---C11B 92.6 (19) C61B---C52B---O51 99.3 (13) O01---C02B---C03B 114 (2) C61B---C52B---C53B 113.7 (12) C11B---C02B---C03B 110 (2) O51---C52B---C53B 114.0 (14) O01---C02B---C12B 119 (2) C61B---C52B---C62B 113.4 (13) C11B---C02B---C12B 110 (2) O51---C52B---C62B 104.6 (11) C03B---C02B---C12B 110 (2) C53B---C52B---C62B 111.0 (14) C02B---C03B---C04B 113.4 (18) C54B---C53B---C52B 111.1 (9) C02B---C03B---HB03A 108.9 C54B---C53B---HB53A 109.4 C04B---C03B---HB03A 108.9 C52B---C53B---HB53A 109.4 C02B---C03B---HB03B 108.9 C54B---C53B---HB53B 109.4 C04B---C03B---HB03B 108.9 C52B---C53B---HB53B 109.4 HB03A---C03B---HB03B 107.7 HB53A---C53B---HB53B 108.0 C10---C04B---C03B 111.4 (16) C53B---C54B---C60 111.2 (7) C10---C04B---HB04A 109.3 C53B---C54B---HB54A 109.4 C03B---C04B---HB04A 109.3 C60---C54B---HB54A 109.4 C10---C04B---HB04B 109.3 C53B---C54B---HB54B 109.4 C03B---C04B---HB04B 109.3 C60---C54B---HB54B 109.4 HB04A---C04B---HB04B 108.0 HB54A---C54B---HB54B 108.0 C06---C05---C10 118.3 (3) C56---C55---C60 118.2 (2) C06---C05---C13 121.3 (3) C56---C55---C63 121.5 (2) C10---C05---C13 120.3 (3) C60---C55---C63 120.3 (2) C05---C06---O14 120.6 (2) C55---C56---C57 122.8 (2) C05---C06---C07 122.2 (3) C55---C56---O64 119.3 (2) O14---C06---C07 117.1 (2) C57---C56---O64 117.7 (2) C08---C07---C06 119.0 (3) C56---C57---C58 118.4 (2) C08---C07---C15 119.0 (2) C56---C57---C65 122.2 (2) C06---C07---C15 121.9 (2) C58---C57---C65 119.3 (2) C09---C08---C07 118.7 (3) C59---C58---C57 118.9 (2) C09---C08---C16 120.8 (3) C59---C58---C66 121.4 (3) C07---C08---C16 120.5 (3) C57---C58---C66 119.6 (2) O01---C09---C10 122.6 (3) O51---C59---C58 114.8 (2) O01---C09---C08 114.7 (2) O51---C59---C60 123.2 (3) C10---C09---C08 122.6 (3) C58---C59---C60 122.0 (3) C09---C10---C05 119.0 (3) C59---C60---C55 119.3 (3) C09---C10---C04A 120.8 (3) C59---C60---C54A 117.0 (4) C05---C10---C04A 120.1 (3) C55---C60---C54A 122.8 (4) C09---C10---C04B 115.9 (9) C59---C60---C54B 122.1 (4) C05---C10---C04B 121.7 (10) C55---C60---C54B 117.6 (4) C04A---C10---C04B 20.7 (12) C54A---C60---C54B 19.4 (3) C02A---C11A---HA11A 109.5 C52A---C61A---HA61A 109.5 C02A---C11A---HA11B 109.5 C52A---C61A---HA61B 109.5 HA11A---C11A---HA11B 109.5 HA61A---C61A---HA61B 109.5 C02A---C11A---HA11C 109.5 C52A---C61A---HA61C 109.5 HA11A---C11A---HA11C 109.5 HA61A---C61A---HA61C 109.5 HA11B---C11A---HA11C 109.5 HA61B---C61A---HA61C 109.5 C02A---C12A---HA12A 109.5 C52A---C62A---HA62A 109.5 C02A---C12A---HA12B 109.5 C52A---C62A---HA62B 109.5 HA12A---C12A---HA12B 109.5 HA62A---C62A---HA62B 109.5 C02A---C12A---HA12C 109.5 C52A---C62A---HA62C 109.5 HA12A---C12A---HA12C 109.5 HA62A---C62A---HA62C 109.5 HA12B---C12A---HA12C 109.5 HA62B---C62A---HA62C 109.5 C02B---C11B---HB11A 109.5 C52B---C61B---HB61A 109.5 C02B---C11B---HB11B 109.5 C52B---C61B---HB61B 109.5 HB11A---C11B---HB11B 109.5 HB61A---C61B---HB61B 109.5 C02B---C11B---HB11C 109.5 C52B---C61B---HB61C 109.5 HB11A---C11B---HB11C 109.5 HB61A---C61B---HB61C 109.5 HB11B---C11B---HB11C 109.5 HB61B---C61B---HB61C 109.5 C02B---C12B---HB12A 109.5 C52B---C62B---HB62A 109.5 C02B---C12B---HB12B 109.5 C52B---C62B---HB62B 109.5 HB12A---C12B---HB12B 109.5 HB62A---C62B---HB62B 109.5 C02B---C12B---HB12C 109.5 C52B---C62B---HB62C 109.5 HB12A---C12B---HB12C 109.5 HB62A---C62B---HB62C 109.5 HB12B---C12B---HB12C 109.5 HB62B---C62B---HB62C 109.5 C05---C13---H13A 109.5 C55---C63---H63A 109.5 C05---C13---H13B 109.5 C55---C63---H63B 109.5 H13A---C13---H13B 109.5 H63A---C63---H63B 109.5 C05---C13---H13C 109.5 C55---C63---H63C 109.5 H13A---C13---H13C 109.5 H63A---C63---H63C 109.5 H13B---C13---H13C 109.5 H63B---C63---H63C 109.5 C06---O14---C17 116.4 (2) C56---O64---C67 116.09 (18) C07---C15---H15A 109.5 C57---C65---H65A 109.5 C07---C15---H15B 109.5 C57---C65---H65B 109.5 H15A---C15---H15B 109.5 H65A---C65---H65B 109.5 C07---C15---H15C 109.5 C57---C65---H65C 109.5 H15A---C15---H15C 109.5 H65A---C65---H65C 109.5 H15B---C15---H15C 109.5 H65B---C65---H65C 109.5 C08---C16---H16A 109.5 C58---C66---H66A 109.5 C08---C16---H16B 109.5 C58---C66---H66B 109.5 H16A---C16---H16B 109.5 H66A---C66---H66B 109.5 C08---C16---H16C 109.5 C58---C66---H66C 109.5 H16A---C16---H16C 109.5 H66A---C66---H66C 109.5 H16B---C16---H16C 109.5 H66B---C66---H66C 109.5 O23---C17---O14 109.6 (2) O73---C67---O64 109.6 (2) O23---C17---C18 107.5 (2) O73---C67---C68 108.2 (2) O14---C17---C18 110.4 (2) O64---C67---C68 109.7 (2) O23---C17---H17A 109.8 O73---C67---H67A 109.8 O14---C17---H17A 109.8 O64---C67---H67A 109.8 C18---C17---H17A 109.8 C68---C67---H67A 109.8 O24---C18---C19 107.6 (2) O74---C68---C69 108.4 (2) O24---C18---C17 110.7 (2) O74---C68---C67 111.1 (2) C19---C18---C17 109.9 (2) C69---C68---C67 109.9 (2) O24---C18---H18A 109.5 O74---C68---H68A 109.1 C19---C18---H18A 109.5 C69---C68---H68A 109.1 C17---C18---H18A 109.5 C67---C68---H68A 109.1 O28---C19---C18 109.2 (2) O78---C69---C68 110.5 (2) O28---C19---C20 108.5 (2) O78---C69---C70 108.4 (2) C18---C19---C20 109.3 (2) C68---C69---C70 109.1 (2) O28---C19---H19A 109.9 O78---C69---H69A 109.6 C18---C19---H19A 109.9 C68---C69---H69A 109.6 C20---C19---H19A 109.9 C70---C69---H69A 109.6 O32---C20---C19 107.5 (2) O82---C70---C69 108.8 (2) O32---C20---C21 106.5 (2) O82---C70---C71 107.7 (2) C19---C20---C21 110.7 (2) C69---C70---C71 110.4 (2) O32---C20---H20A 110.7 O82---C70---H70A 110.0 C19---C20---H20A 110.7 C69---C70---H70A 110.0 C21---C20---H20A 110.7 C71---C70---H70A 110.0 O23---C21---C22 106.2 (2) O73---C71---C72 106.5 (2) O23---C21---C20 109.8 (2) O73---C71---C70 110.1 (2) C22---C21---C20 111.7 (2) C72---C71---C70 111.3 (2) O23---C21---H21A 109.7 O73---C71---H71A 109.6 C22---C21---H21A 109.7 C72---C71---H71A 109.6 C20---C21---H21A 109.7 C70---C71---H71A 109.6 O36---C22---C21 111.0 (2) O86---C72---C71 111.0 (2) O36---C22---H22A 109.4 O86---C72---H72A 109.4 C21---C22---H22A 109.4 C71---C72---H72A 109.4 O36---C22---H22B 109.4 O86---C72---H72B 109.4 C21---C22---H22B 109.4 C71---C72---H72B 109.4 H22A---C22---H22B 108.0 H72A---C72---H72B 108.0 C17---O23---C21 114.2 (2) C67---O73---C71 114.6 (2) C25---O24---C18 115.6 (2) C75---O74---C68 116.2 (2) O26---C25---O24 123.3 (3) O76---C75---O74 121.9 (3) O26---C25---C27 125.7 (3) O76---C75---C77 126.6 (3) O24---C25---C27 111.1 (3) O74---C75---C77 111.5 (3) C25---C27---H27A 109.5 C75---C77---H77A 109.5 C25---C27---H27B 109.5 C75---C77---H77B 109.5 H27A---C27---H27B 109.5 H77A---C77---H77B 109.5 C25---C27---H27C 109.5 C75---C77---H77C 109.5 H27A---C27---H27C 109.5 H77A---C77---H77C 109.5 H27B---C27---H27C 109.5 H77B---C77---H77C 109.5 C29---O28---C19 116.9 (2) C79---O78---C69 117.1 (2) O30---C29---O28 124.1 (3) O80---C79---O78 123.5 (3) O30---C29---C31 124.9 (3) O80---C79---C81 125.5 (3) O28---C29---C31 111.1 (2) O78---C79---C81 111.0 (2) C29---C31---H31A 109.5 C79---C81---H81A 109.5 C29---C31---H31B 109.5 C79---C81---H81B 109.5 H31A---C31---H31B 109.5 H81A---C81---H81B 109.5 C29---C31---H31C 109.5 C79---C81---H81C 109.5 H31A---C31---H31C 109.5 H81A---C81---H81C 109.5 H31B---C31---H31C 109.5 H81B---C81---H81C 109.5 C33---O32---C20 118.1 (2) C83---O82---C70 117.3 (2) O35---C33---O32 123.9 (3) O85---C83---O82 123.9 (3) O35---C33---C34 125.9 (3) O85---C83---C84 125.5 (3) O32---C33---C34 110.2 (3) O82---C83---C84 110.6 (2) C33---C34---H34A 109.5 C83---C84---H84A 109.5 C33---C34---H34B 109.5 C83---C84---H84B 109.5 H34A---C34---H34B 109.5 H84A---C84---H84B 109.5 C33---C34---H34C 109.5 C83---C84---H84C 109.5 H34A---C34---H34C 109.5 H84A---C84---H84C 109.5 H34B---C34---H34C 109.5 H84B---C84---H84C 109.5 C37---O36---C22 117.4 (2) C87---O86---C72 117.7 (3) O39---C37---O36 122.8 (3) O89---C87---O86 122.5 (3) O39---C37---C38 126.3 (3) O89---C87---C88 126.2 (4) O36---C37---C38 110.9 (3) O86---C87---C88 111.2 (4) C37---C38---H38A 109.5 C87---C88---H88A 109.5 C37---C38---H38B 109.5 C87---C88---H88B 109.5 H38A---C38---H38B 109.5 H88A---C88---H88B 109.5 C37---C38---H38C 109.5 C87---C88---H88C 109.5 H38A---C38---H38C 109.5 H88A---C88---H88C 109.5 H38B---C38---H38C 109.5 H88B---C88---H88C 109.5 C02B---O01---C02A---C12A 48 (11) C59---O51---C52A---C61A −85.3 (10) C09---O01---C02A---C12A −162.9 (3) C52B---O51---C52A---C61A −114 (12) C02B---O01---C02A---C03A 169 (12) C59---O51---C52A---C62A 155.7 (7) C09---O01---C02A---C03A −42.6 (5) C52B---O51---C52A---C62A 127 (12) C02B---O01---C02A---C11A −70 (11) C59---O51---C52A---C53A 35.6 (15) C09---O01---C02A---C11A 78.9 (4) C52B---O51---C52A---C53A 7(11) O01---C02A---C03A---C04A 59.6 (5) O51---C52A---C53A---C54A −53.6 (13) C12A---C02A---C03A---C04A 175.9 (4) C61A---C52A---C53A---C54A 61.1 (17) C11A---C02A---C03A---C04A −58.6 (5) C62A---C52A---C53A---C54A −175.7 (9) C02A---C03A---C04A---C10 −45.5 (5) C52A---C53A---C54A---C60 42.3 (12) C09---O01---C02B---C11B −95.5 (14) C52A---O51---C52B---C61B −120 (12) C02A---O01---C02B---C11B −62 (11) C59---O51---C52B---C61B 86.5 (9) C09---O01---C02B---C03B 18 (3) C52A---O51---C52B---C53B 118 (12) C02A---O01---C02B---C03B 52 (10) C59---O51---C52B---C53B −34.8 (16) C09---O01---C02B---C12B 150.1 (16) C52A---O51---C52B---C62B −3(11) C02A---O01---C02B---C12B −176 (13) C59---O51---C52B---C62B −156.2 (7) O01---C02B---C03B---C04B −46 (3) C61B---C52B---C53B---C54B −56.8 (17) C11B---C02B---C03B---C04B 56 (3) O51---C52B---C53B---C54B 56.1 (16) C12B---C02B---C03B---C04B 178 (2) C62B---C52B---C53B---C54B 173.9 (11) C02B---C03B---C04B---C10 40 (3) C52B---C53B---C54B---C60 −41.4 (12) C10---C05---C06---O14 −179.9 (2) C60---C55---C56---C57 −6.7 (4) C13---C05---C06---O14 −2.2 (4) C63---C55---C56---C57 171.5 (2) C10---C05---C06---C07 −3.9 (4) C60---C55---C56---O64 178.2 (2) C13---C05---C06---C07 173.9 (2) C63---C55---C56---O64 −3.7 (4) C05---C06---C07---C08 4.5 (4) C55---C56---C57---C58 6.4 (4) O14---C06---C07---C08 −179.3 (2) O64---C56---C57---C58 −178.4 (2) C05---C06---C07---C15 −172.1 (2) C55---C56---C57---C65 −170.3 (2) O14---C06---C07---C15 4.1 (3) O64---C56---C57---C65 4.9 (4) C06---C07---C08---C09 −1.2 (4) C56---C57---C58---C59 −1.4 (4) C15---C07---C08---C09 175.5 (2) C65---C57---C58---C59 175.4 (3) C06---C07---C08---C16 179.7 (2) C56---C57---C58---C66 −178.5 (2) C15---C07---C08---C16 −3.5 (4) C65---C57---C58---C66 −1.7 (4) C02B---O01---C09---C10 16.6 (15) C52A---O51---C59---C58 175.5 (9) C02A---O01---C09---C10 12.4 (4) C52B---O51---C59---C58 179.4 (9) C02B---O01---C09---C08 −166.3 (15) C52A---O51---C59---C60 −4.2 (10) C02A---O01---C09---C08 −170.5 (3) C52B---O51---C59---C60 −0.3 (10) C07---C08---C09---O01 −179.7 (2) C57---C58---C59---O51 177.2 (3) C16---C08---C09---O01 −0.7 (4) C66---C58---C59---O51 −5.7 (4) C07---C08---C09---C10 −2.7 (4) C57---C58---C59---C60 −3.1 (4) C16---C08---C09---C10 176.4 (3) C66---C58---C59---C60 174.0 (3) O01---C09---C10---C05 −179.9 (2) O51---C59---C60---C55 −177.5 (3) C08---C09---C10---C05 3.3 (4) C58---C59---C60---C55 2.8 (5) O01---C09---C10---C04A 2.4 (4) O51---C59---C60---C54A −7.9 (6) C08---C09---C10---C04A −174.5 (3) C58---C59---C60---C54A 172.5 (5) O01---C09---C10---C04B −20.6 (15) O51---C59---C60---C54B 13.7 (6) C08---C09---C10---C04B 162.6 (15) C58---C59---C60---C54B −165.9 (4) C06---C05---C10---C09 0.0 (4) C56---C55---C60---C59 1.9 (4) C13---C05---C10---C09 −177.8 (3) C63---C55---C60---C59 −176.2 (3) C06---C05---C10---C04A 177.8 (3) C56---C55---C60---C54A −167.1 (4) C13---C05---C10---C04A 0.0 (4) C63---C55---C60---C54A 14.7 (6) C06---C05---C10---C04B −158.1 (15) C56---C55---C60---C54B 171.2 (4) C13---C05---C10---C04B 24.2 (15) C63---C55---C60---C54B −6.9 (5) C03A---C04A---C10---C09 14.9 (5) C53A---C54A---C60---C59 −13.4 (8) C03A---C04A---C10---C05 −162.8 (3) C53A---C54A---C60---C55 155.9 (5) C03A---C04A---C10---C04B 97 (3) C53A---C54A---C60---C54B −124 (2) C03B---C04B---C10---C09 −9(3) C53B---C54B---C60---C59 8.7 (8) C03B---C04B---C10---C05 150.0 (15) C53B---C54B---C60---C55 −160.2 (4) C03B---C04B---C10---C04A −118 (4) C53B---C54B---C60---C54A 89 (2) C05---C06---O14---C17 −68.2 (3) C55---C56---O64---C67 −69.3 (3) C07---C06---O14---C17 115.6 (3) C57---C56---O64---C67 115.3 (3) C06---O14---C17---O23 137.0 (2) C56---O64---C67---O73 136.3 (2) C06---O14---C17---C18 −104.8 (3) C56---O64---C67---C68 −105.0 (2) O23---C17---C18---O24 179.22 (19) O73---C67---C68---O74 −179.99 (19) O14---C17---C18---O24 59.8 (3) O64---C67---C68---O74 60.5 (3) O23---C17---C18---C19 60.5 (3) O73---C67---C68---C69 60.0 (3) O14---C17---C18---C19 −59.0 (3) O64---C67---C68---C69 −59.4 (3) O24---C18---C19---O28 64.1 (3) O74---C68---C69---O78 61.9 (3) C17---C18---C19---O28 −175.3 (2) C67---C68---C69---O78 −176.5 (2) O24---C18---C19---C20 −177.3 (2) O74---C68---C69---C70 −179.1 (2) C17---C18---C19---C20 −56.7 (3) C67---C68---C69---C70 −57.5 (3) O28---C19---C20---O32 −71.9 (2) O78---C69---C70---O82 −67.5 (3) C18---C19---C20---O32 169.06 (19) C68---C69---C70---O82 172.2 (2) O28---C19---C20---C21 172.1 (2) O78---C69---C70---C71 174.6 (2) C18---C19---C20---C21 53.1 (3) C68---C69---C70---C71 54.2 (3) O32---C20---C21---O23 −169.9 (2) O82---C70---C71---O73 −172.12 (19) C19---C20---C21---O23 −53.3 (3) C69---C70---C71---O73 −53.4 (3) O32---C20---C21---C22 72.6 (3) O82---C70---C71---C72 70.1 (3) C19---C20---C21---C22 −170.8 (2) C69---C70---C71---C72 −171.3 (2) O23---C21---C22---O36 57.8 (3) O73---C71---C72---O86 50.8 (3) C20---C21---C22---O36 177.5 (2) C70---C71---C72---O86 170.7 (2) O14---C17---O23---C21 56.5 (3) O64---C67---O73---C71 57.8 (3) C18---C17---O23---C21 −63.5 (3) C68---C67---O73---C71 −61.8 (3) C22---C21---O23---C17 −178.6 (2) C72---C71---O73---C67 180.0 (2) C20---C21---O23---C17 60.5 (3) C70---C71---O73---C67 59.1 (3) C19---C18---O24---C25 −160.4 (2) C69---C68---O74---C75 −161.9 (2) C17---C18---O24---C25 79.4 (3) C67---C68---O74---C75 77.3 (3) C18---O24---C25---O26 4.1 (4) C68---O74---C75---O76 1.4 (4) C18---O24---C25---C27 −176.4 (2) C68---O74---C75---C77 −179.6 (2) C18---C19---O28---C29 −112.1 (3) C68---C69---O78---C79 −105.6 (3) C20---C19---O28---C29 128.8 (2) C70---C69---O78---C79 134.9 (2) C19---O28---C29---O30 0.0 (4) C69---O78---C79---O80 −1.7 (4) C19---O28---C29---C31 178.9 (2) C69---O78---C79---C81 178.5 (2) C19---C20---O32---C33 103.3 (3) C69---C70---O82---C83 99.7 (3) C21---C20---O32---C33 −138.0 (2) C71---C70---O82---C83 −140.7 (2) C20---O32---C33---O35 6.1 (4) C70---O82---C83---O85 7.9 (4) C20---O32---C33---C34 −174.2 (3) C70---O82---C83---C84 −172.3 (2) C21---C22---O36---C37 79.0 (3) C71---C72---O86---C87 78.2 (3) C22---O36---C37---O39 2.3 (4) C72---O86---C87---O89 4.3 (4) C22---O36---C37---C38 −176.6 (2) C72---O86---C87---C88 −174.4 (3) --------------------------- ------------- --------------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.431553	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052099/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o718", "authors": [ { "first": "Krzysztof", "last": "Brzezinski" }, { "first": "Piotr", "last": "Wałejko" }, { "first": "Aneta", "last": "Baj" }, { "first": "Stanisław", "last": "Witkowski" }, { "first": "Zbigniew", "last": "Dauter" } ] }
PMC3052100	Related literature {#sec1} ================== For the isolation of β-himachalene, see: Joseph & Dev (1968[@bb10]); Plattier & Teisseire (1974[@bb12]). For the reactivity of this sesquiterpene, see: Lassaba et al. (1998[@bb11]); Chekroun et al. (2000[@bb2]); El Jamili et al. (2002[@bb6]); Sbai et al. (2002[@bb13]); Dakir et al. (2004[@bb4]). For its biological activity, see: Daoubi et al. (2004[@bb5]). For conformational analysis, see: Cremer & Pople (1975[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~24~Cl~2~OM ~r~ = 303.25Trigonal,a = 13.2323 (13) Åc = 7.9807 (8) ÅV = 1210.2 (2) Å^3^Z = 3Mo Kα radiationμ = 0.39 mm^−1^T = 298 K0.41 × 0.33 × 0.26 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometer8123 measured reflections3135 independent reflections2995 reflections with I \> 2σ(I)R ~int~ = 0.019 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.045wR(F ^2^) = 0.126S = 1.093135 reflections180 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.52 e Å^−3^Δρ~min~ = −0.33 e Å^−3^Absolute structure: Flack (1983[@bb9]), 1940 Friedel pairsFlack parameter: −0.11 (7) {#d5e437} Data collection: APEX2 (Bruker, 2009[@bb1]); cell refinement: SAINT (Bruker, 2009[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb14]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb14]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb7]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004788/tk2714sup1.cif](http://dx.doi.org/10.1107/S1600536811004788/tk2714sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004788/tk2714Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004788/tk2714Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?tk2714&file=tk2714sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?tk2714sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?tk2714&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [TK2714](http://scripts.iucr.org/cgi-bin/sendsup?tk2714)). We thank the National Center of Scientific and Technological Research (CNRST) which supports our scientific research. Comment ======= The bicyclic sesquiterpene β-himachalene is the main constituent of the essential oil of the Atlas cedar (Cedrus atlantica) (Joseph & Dev, 1968; Plattier & Teisseire, 1974). The reactivity of this sesquiterpene and its derivatives has been studied extensively by our team in order to prepare new products having biological proprieties (Lassaba et al., 1998; Chekroun et al., 2000; El Jamili et al., 2002; Sbai et al., 2002; Dakir et al., 2004). Indeed, these compounds were tested, using the food poisoning technique, for their potential antifungal activity against the phytopathogen Botrytis cinerea (Daoubi et al., 2004). The action of one equivalent of dichlorocarbene, generated in situ from chloroform in the presence of sodium hydroxide as base and n-benzyltriethylammonium chloride as catalyst, on β-himachalene produces only (1S,3R,8R)-2,2-dichloro-3,7,7,10- tetramethyltricyclo\[6.4.0.0^1,3^\]dodec-9-ene (El Jamili et al., 2002). Treatment of the latter compound with two equivalents of N-bromosuccinimide gives (1S, 3R, 8R, 11S)-2,2-dichloro -3,7,7,10-tetralethyltricyclo\[6.4.0.0^1,3^\]dodec-9-en-11-ol in a very low yield (5%), along with other products. The structure of this new product was determined by NMR (^1^H & ^13^C) spectral analysis and mass spectroscopy, and confirmed by a crystallographic study, reported herein. The molecule is built up from two fused six-membered and seven-membered rings (Fig. 1). The six-membered ring has a screw boat conformation, as indicated by the total puckering amplitude QT = 0.480 (3) Å and spherical polar angle θ = 130.6 (4) ° with φ = 151.5 (5) °, whereas the seven-membered ring displays a boat conformation with QT = 1.1449 (30) Å, θ~2~ = 88.29 (15) °, φ~2~ = -47.13 (14) ° and φ~3~ =-144.24 (5) ° (Cremer & Pople, 1975). In the crystal structure, molecules are linked into supramolecular chains (Fig. 2) running along the c axis by O---H···O hydrogen bonds (Table 1). Owing to the presence of Cl atoms, the absolute configuration could be fully confirmed, as C1(S), C3(R), C8(R) and C11(S). Experimental {#experimental} ============ In a reactor containing a solution of (1S, 3R, 8R)-2,2-dichloro-3,7,7,10 tetramethyltricyclo \[6.4.0.0^1,3^\] dodec-9-ene (1 g, 3.48 mmol) in 50 ml of tetrahydrofuran and water (THF/H~2~O) (4:1) cooled to 273 K and kept in the dark, was added in small portions 1.23 g (6.96 mmol) of N-bromosccinimide. The reaction mixture was left stirring for 1 h, after which 20 ml of a saturated solution of NaHCO~3~ was added. Subsequently, the extraction was performed three times with diethyl ether (3 x 20 ml). The organic extracts were dried over Na~2~SO~4~, filtered, concentrated, and chromatographed. The title compound, (1S, 3R, 8R, 11S,)-2,2-dichloro-3,7,7,10-tetralethyltricyclo \[6.4.0.0^1,3^\] dodec-9-by-11-ol was obtained with in a yield of 5% and was recrystallized its pentane solution. Refinement {#refinement} ========== All H atoms were fixed geometrically and treated as riding with O---H = 0.82 Å and C---H = 0.93 (ethylene), 0.96 Å (methyl), 0.97 Å (methylene) and 0.98Å (methine), and with U~iso~(H) = 1.2U~eq~ (ethylene, methylene, methine) or U~iso~(H) = 1.5U~eq~ (O, methyl). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o615-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing diagram showing the O---H···O interactions (dashed lines) and the formation of supramolecular chains parallel to the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o615-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e274 .table-wrap} ----------------------- --------------------------------------- C~16~H~24~Cl~2~O D~x~ = 1.244 Mg m^−3^ M~r~ = 303.25 Mo Kα radiation, λ = 0.71073 Å Trigonal, P3~2~ Cell parameters from 8123 reflections Hall symbol: P 32 θ = 4--26.4° a = 13.2323 (13) Å µ = 0.39 mm^−1^ c = 7.9807 (8) Å T = 298 K V = 1210.2 (2) Å^3^ Prism, colourless Z = 3 0.41 × 0.33 × 0.26 mm F(000) = 486 ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e390 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2995 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.019 graphite θ~max~ = 26.4°, θ~min~ = 4.0° ω and φ scans h = −15→16 8123 measured reflections k = −14→16 3135 independent reflections l = −9→9 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e488 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.045 H-atom parameters constrained wR(F^2^) = 0.126 w = 1/\[σ^2^(F~o~^2^) + (0.0761P)^2^ + 0.4405P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.09 (Δ/σ)~max~ \< 0.001 3135 reflections Δρ~max~ = 0.52 e Å^−3^ 180 parameters Δρ~min~ = −0.33 e Å^−3^ 1 restraint Absolute structure: Flack & Bernardinelli (2000), 1940 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.11 (7) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e653 .table-wrap} -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e673 .table-wrap} ------ -------------- ------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 1.0043 (2) 0.6432 (2) 0.5388 (3) 0.0304 (5) C2 0.9057 (2) 0.5880 (2) 0.4113 (4) 0.0370 (5) C3 0.8790 (2) 0.5564 (2) 0.5938 (4) 0.0392 (6) C4 0.8143 (3) 0.6069 (3) 0.6915 (4) 0.0464 (7) H4A 0.8228 0.6749 0.6329 0.056\ H4B 0.7319 0.5493 0.6955 0.056\* C5 0.8600 (3) 0.6411 (3) 0.8682 (5) 0.0541 (8) H5A 0.8234 0.5720 0.9384 0.065\* H5B 0.8370 0.6953 0.9106 0.065\* C6 0.9973 (3) 0.6991 (4) 0.8854 (5) 0.0591 (9) H6A 1.0178 0.7232 1.0010 0.071\* H6B 1.0175 0.6394 0.8633 0.071\* C7 1.0733 (2) 0.8032 (3) 0.7746 (4) 0.0426 (6) C8 1.0545 (2) 0.7728 (2) 0.5810 (3) 0.0308 (5) H8 0.9966 0.7933 0.5426 0.041 (8)\* C9 1.1625 (2) 0.8449 (2) 0.4781 (4) 0.0394 (6) H9 1.1895 0.9246 0.4721 0.039 (8)\* C10 1.2228 (2) 0.8058 (2) 0.3951 (4) 0.0367 (5) C11 1.1869 (2) 0.6778 (2) 0.3958 (3) 0.0333 (5) H11 1.1523 0.6443 0.2867 0.029 (7)\* C12 1.0980 (2) 0.6089 (2) 0.5320 (4) 0.0364 (5) H12A 1.0624 0.5260 0.5090 0.044\* H12B 1.1371 0.6242 0.6396 0.044\* C13 1.3285 (3) 0.8828 (3) 0.2905 (5) 0.0549 (8) H13A 1.3407 0.9607 0.2893 0.082\* H13B 1.3164 0.8532 0.1780 0.082\* H13C 1.3957 0.8837 0.3373 0.082\* C14 0.8465 (3) 0.4338 (3) 0.6503 (6) 0.0633 (10) H14A 0.7653 0.3913 0.6796 0.095\* H14B 0.8927 0.4386 0.7459 0.095\* H14C 0.8611 0.3943 0.5608 0.095\* C15 1.0481 (4) 0.9031 (4) 0.8042 (6) 0.0718 (11) H15A 0.9719 0.8811 0.7621 0.108\* H15B 1.1055 0.9718 0.7469 0.108\* H15C 1.0512 0.9188 0.9221 0.108\* C16 1.2019 (4) 0.8507 (4) 0.8255 (6) 0.0730 (11) H16A 1.2122 0.8740 0.9410 0.109\* H16B 1.2515 0.9168 0.7568 0.109\* H16C 1.2219 0.7909 0.8102 0.109\* O1 1.28683 (18) 0.6633 (2) 0.4212 (3) 0.0453 (5) H1 1.3211 0.6727 0.3319 0.068\* Cl1 0.85533 (6) 0.67322 (7) 0.30875 (9) 0.0497 (2) Cl2 0.90015 (7) 0.48357 (7) 0.26866 (11) 0.0605 (2) ------ -------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1228 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0314 (11) 0.0304 (11) 0.0315 (12) 0.0170 (10) 0.0015 (9) 0.0018 (9) C2 0.0353 (12) 0.0343 (12) 0.0391 (14) 0.0157 (10) −0.0032 (10) −0.0049 (10) C3 0.0350 (13) 0.0374 (13) 0.0431 (15) 0.0164 (11) 0.0042 (11) 0.0079 (11) C4 0.0365 (14) 0.0604 (18) 0.0436 (16) 0.0253 (13) 0.0107 (11) 0.0114 (13) C5 0.0556 (19) 0.069 (2) 0.0418 (16) 0.0344 (17) 0.0144 (14) 0.0117 (15) C6 0.065 (2) 0.079 (2) 0.0401 (17) 0.0407 (19) −0.0012 (14) 0.0047 (16) C7 0.0435 (14) 0.0539 (16) 0.0364 (14) 0.0289 (13) −0.0053 (11) −0.0123 (12) C8 0.0306 (11) 0.0319 (12) 0.0351 (12) 0.0197 (10) 0.0012 (9) −0.0015 (9) C9 0.0409 (14) 0.0287 (12) 0.0461 (16) 0.0155 (10) 0.0048 (11) 0.0006 (10) C10 0.0320 (12) 0.0339 (13) 0.0409 (14) 0.0141 (10) 0.0025 (10) −0.0003 (10) C11 0.0327 (12) 0.0367 (12) 0.0365 (14) 0.0218 (10) −0.0017 (9) −0.0045 (10) C12 0.0369 (12) 0.0343 (12) 0.0451 (14) 0.0230 (11) 0.0031 (10) 0.0023 (10) C13 0.0452 (16) 0.0493 (17) 0.064 (2) 0.0190 (14) 0.0200 (15) 0.0072 (14) C14 0.0562 (19) 0.0404 (16) 0.082 (3) 0.0158 (15) 0.0123 (17) 0.0191 (16) C15 0.078 (3) 0.071 (2) 0.078 (3) 0.046 (2) 0.002 (2) −0.023 (2) C16 0.058 (2) 0.087 (3) 0.069 (3) 0.033 (2) −0.0150 (19) −0.023 (2) O1 0.0410 (10) 0.0614 (13) 0.0479 (12) 0.0365 (10) 0.0009 (8) −0.0025 (9) Cl1 0.0471 (4) 0.0680 (5) 0.0384 (3) 0.0321 (4) −0.0065 (3) 0.0047 (3) Cl2 0.0541 (4) 0.0536 (4) 0.0643 (5) 0.0199 (4) −0.0071 (4) −0.0266 (4) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1591 .table-wrap} ---------------- ------------- ------------------- ----------- C1---C12 1.521 (3) C9---C10 1.326 (4) C1---C2 1.522 (3) C9---H9 0.9300 C1---C3 1.534 (3) C10---C13 1.506 (4) C1---C8 1.535 (3) C10---C11 1.513 (4) C2---C3 1.507 (4) C11---O1 1.442 (3) C2---Cl2 1.764 (3) C11---C12 1.524 (4) C2---Cl1 1.771 (3) C11---H11 0.9800 C3---C14 1.524 (4) C12---H12A 0.9700 C3---C4 1.535 (4) C12---H12B 0.9700 C4---C5 1.512 (5) C13---H13A 0.9600 C4---H4A 0.9700 C13---H13B 0.9600 C4---H4B 0.9700 C13---H13C 0.9600 C5---C6 1.584 (5) C14---H14A 0.9600 C5---H5A 0.9700 C14---H14B 0.9600 C5---H5B 0.9700 C14---H14C 0.9600 C6---C7 1.518 (5) C15---H15A 0.9600 C6---H6A 0.9700 C15---H15B 0.9600 C6---H6B 0.9700 C15---H15C 0.9600 C7---C15 1.534 (5) C16---H16A 0.9600 C7---C16 1.545 (5) C16---H16B 0.9600 C7---C8 1.585 (4) C16---H16C 0.9600 C8---C9 1.505 (3) O1---H1 0.8200 C8---H8 0.9800 C12---C1---C2 117.7 (2) C1---C8---H8 106.2 C12---C1---C3 121.6 (2) C7---C8---H8 106.2 C2---C1---C3 59.08 (17) C10---C9---C8 126.2 (2) C12---C1---C8 112.3 (2) C10---C9---H9 116.9 C2---C1---C8 118.1 (2) C8---C9---H9 116.9 C3---C1---C8 118.4 (2) C9---C10---C13 123.3 (3) C3---C2---C1 60.86 (17) C9---C10---C11 121.5 (2) C3---C2---Cl2 119.6 (2) C13---C10---C11 115.2 (2) C1---C2---Cl2 119.77 (19) O1---C11---C10 110.7 (2) C3---C2---Cl1 120.9 (2) O1---C11---C12 107.7 (2) C1---C2---Cl1 120.59 (18) C10---C11---C12 112.9 (2) Cl2---C2---Cl1 108.61 (15) O1---C11---H11 108.5 C2---C3---C14 118.9 (3) C10---C11---H11 108.5 C2---C3---C1 60.06 (16) C12---C11---H11 108.5 C14---C3---C1 120.3 (3) C1---C12---C11 110.3 (2) C2---C3---C4 118.3 (2) C1---C12---H12A 109.6 C14---C3---C4 113.0 (3) C11---C12---H12A 109.6 C1---C3---C4 116.7 (2) C1---C12---H12B 109.6 C5---C4---C3 112.2 (3) C11---C12---H12B 109.6 C5---C4---H4A 109.2 H12A---C12---H12B 108.1 C3---C4---H4A 109.2 C10---C13---H13A 109.5 C5---C4---H4B 109.2 C10---C13---H13B 109.5 C3---C4---H4B 109.2 H13A---C13---H13B 109.5 H4A---C4---H4B 107.9 C10---C13---H13C 109.5 C4---C5---C6 114.6 (3) H13A---C13---H13C 109.5 C4---C5---H5A 108.6 H13B---C13---H13C 109.5 C6---C5---H5A 108.6 C3---C14---H14A 109.5 C4---C5---H5B 108.6 C3---C14---H14B 109.5 C6---C5---H5B 108.6 H14A---C14---H14B 109.5 H5A---C5---H5B 107.6 C3---C14---H14C 109.5 C7---C6---C5 118.0 (3) H14A---C14---H14C 109.5 C7---C6---H6A 107.8 H14B---C14---H14C 109.5 C5---C6---H6A 107.8 C7---C15---H15A 109.5 C7---C6---H6B 107.8 C7---C15---H15B 109.5 C5---C6---H6B 107.8 H15A---C15---H15B 109.5 H6A---C6---H6B 107.2 C7---C15---H15C 109.5 C6---C7---C15 111.2 (3) H15A---C15---H15C 109.5 C6---C7---C16 108.2 (3) H15B---C15---H15C 109.5 C15---C7---C16 106.2 (3) C7---C16---H16A 109.5 C6---C7---C8 112.8 (2) C7---C16---H16B 109.5 C15---C7---C8 107.1 (3) H16A---C16---H16B 109.5 C16---C7---C8 111.1 (3) C7---C16---H16C 109.5 C9---C8---C1 109.4 (2) H16A---C16---H16C 109.5 C9---C8---C7 113.1 (2) H16B---C16---H16C 109.5 C1---C8---C7 115.0 (2) C11---O1---H1 109.5 C9---C8---H8 106.2 ---------------- ------------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2235 .table-wrap} ----------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1···O1^i^ 0.82 2.10 2.853 (4) 153 ----------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −y+2, x−y, z−1/3. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- --------- ------- ----------- ------------- O1---H1⋯O1^i^ 0.82 2.10 2.853 (4) 153 Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.449460	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052100/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o615", "authors": [ { "first": "Ahmed", "last": "Benharref" }, { "first": "Essêdiya", "last": "Lassaba" }, { "first": "Daniel", "last": "Avignant" }, { "first": "Abdelghani", "last": "Oudahmane" }, { "first": "Moha", "last": "Berraho" } ] }
PMC3052101	Related literature {#sec1} ================== For background to to the use of transition metal complexes with Schiff bases as potential enzyme inhibitors, see: You et al. (2008[@bb10]); Shi et al. (2007[@bb9]). For the use of transition metal complexes for the development of catalysis, magnetism and molecular architectures, see: Yu et al. (2007[@bb14]); You & Zhu (2004[@bb12]); You & Zhou (2007[@bb11]). For the use of transition metal complexes for optoelectronic and also for photo- and electroluminescence applications, see: Yu et al. (2008[@bb15]). For the potential use of transition metal complexes in the modeling of multisite metalloproteins and in nano-science, see: Chattopadhyay et al. (2006[@bb2]). For the importance of tri-nuclear cobalt Schiff base complexes as catalysts for organic molecules and as antiviral agents due to their ability to interact with proteins and nucleic acids, see: Chattopadhyay et al. (2006[@bb2], 2008[@bb3]); Babushkin & Talsi (1998)[@bb1]. For background to metallosalen complexes, see: Dong et al. (2008[@bb4]). For the magnetic properties of quadridentate metal complexes of Schiff bases, see: He et al. (2006[@bb6]); Gerli et al. (1991[@bb5]). For the antimicrobial activity of Schiff base ligands and their complexes, see: You et al. (2004[@bb13]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co~3~(C~2~H~3~O~2~)~4~(C~20~H~22~N~2~O~6~)~2~\]·2CH~2~Cl~2~M ~r~ = 1355.61Monoclinic,a = 13.9235 (9) Åb = 13.4407 (8) Åc = 16.0019 (11) Åβ = 112.724 (8)°V = 2762.2 (3) Å^3^Z = 2Cu Kα radiationμ = 9.45 mm^−1^T = 110 K0.42 × 0.25 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcalibur diffractometer with a Ruby detectorAbsorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009[@bb7]) T ~min~ = 0.320, T ~max~ = 1.00010708 measured reflections5306 independent reflections3777 reflections with I \> 2σ(I)R ~int~ = 0.043 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.083wR(F ^2^) = 0.251S = 1.035306 reflections373 parametersH-atom parameters constrainedΔρ~max~ = 1.11 e Å^−3^Δρ~min~ = −1.66 e Å^−3^ {#d5e710} Data collection: CrysAlis PRO (Oxford Diffraction, 2009[@bb7]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb8]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003783/jj2072sup1.cif](http://dx.doi.org/10.1107/S1600536811003783/jj2072sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003783/jj2072Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003783/jj2072Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jj2072&file=jj2072sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jj2072sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jj2072&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JJ2072](http://scripts.iucr.org/cgi-bin/sendsup?jj2072)). RJB wishes to acknowledge the NSF-MRI program (grant CHE-0619278) for funds to purchase the diffractometer. Comment ======= A number of transition metal complexes with Schiff base ligands have been studied as potential inhibitors for the xanthine oxidase (XO) enzyme (You et al., 2008) and also for the jack bean urease enzyme (jbU) (Shi et al., 2007). The enzyme XO catalyzes the hydroxylation of hypoxanthine and xanthine to yield uric acid and superoxide anions. Other areas where complexes of transition metals have played roles are in the development of catalysis, magnetism and molecular architecture (Yu et al., 2007, You & Zhu, 2004, You & Zhou, 2007). Complexes of transition metals with Schiff base ligands have also been shown to be useful materials for optoelectronics and also for photo and electro-luminance applications (Yu et al., 2008). Studies for antimicrobial activities of Schiff base ligands as well as those of their corresponding complexes have been investigated (You et al., 2004) where it was shown that Schiff base ligands as well as their complexes exhibited good antibacterial properties. Metallosalen complexes are of great importance due to their use in various catalytic chemical transformations that includes, epoxidation of olefins, symmetric ring opening, azirdination of olefins, olefine cyclopropanation and formation of linear and cyclic hydrocarbonation (Dong et al., 2008). The importance of tri-nuclear cobalt Schiff base complexes ranges from, catalysts for oxidation of organic molecules, antiviral agents due to their ability to interact with proteins and nucleic acids and they have also used to mimic the biological co-factor such as cobalamin (Chattopadhyay et al., 2008, Babushkin & Talsi, 1998). The quadridentate metal complexes of Schiff bases have been studied extensively as B12 models, their magnetic interaction between bridged paramagnetic metal ions and their applications (Gerli et al., 1991). Magnetic susceptibilities data for the trinuclear mixed valence compound \[Co^II^(OAc)~2~(hapt)~2~Co~2~(III)(py)~2~\](ClO~4~)~2~ \[where (hapt) is bis-(2-hydroxyacetophenone) trimethylenediimine\] were measured in the temperature range of 300--2 K and it was found that µ~eff~ values are almost constant ranging from 4.37 to 5.00 BM (He et al., 2006). The values obtained suggested that the oxidation states are Co^III^(S = 0)-Co^II^(S = 3/2)-Co^III^(S = 0). Cyclic tri-nuclear cobalt complexes have also shown some catalytic activities in epoxidation of olefins, autoxidation of hydrocarbons, utility in modeling multinuclear active sites of metalloproteins and their potential use in nanoscience (Chattopadhyay et al., 2006). The title compound C~50~H~60~Cl~4~Co~3~N~4~O~20~ is a trinuclear cobalt Schiff base complex containing a central high spin Co^II^ and two terminal low spin Co^III^ centers. The environment around Co(1) is hexacoordinated with two imine nitrogen atoms, N(1) and N(2), two phenolate oxygen atoms, O(1) and O(2), and two oxygen atoms, O(11 A) and O(21 A), from two acetate groups. The central Co(2) ion is coordinated by four phenolate oxygen atoms and two acetate oxygen atoms O(12 A), O(2)\#2, O(2), O(1), O(1), O(1)\#1 and O(12)\#1. The bond distances of the coordination atoms around Co(1) are Co(1)---N(2) = 1.861 (5) Å, Co(1)---N(1) = 1.871 (5) Å, Co(1)---O(2) = 1.887 (4) Å, Co(1)---O(1) = 1.89 (4) Å, Co(1)---O(21 A) = 1.891 (4) Å, Co(1)---O(11 A) = 1.929 (4) Å and the bond lengths between Co(2) and its coordinating atoms are Co(2)---O(12 A)\#1 = 2.043 (4) Å, Co(2)---O(12 A) = 2.043 (4) Å, Co(2)---O(2)\#1 = 2.117 (4) Å, Co(A)---O(2) = 2.117 (4) Å, Co(2)---O(1) = 2.160 (4) Å, Co(2)---O(1)\#1 = 2.160 (4) Å. The coordination around the central metal ion displays a slight distortion from octahedral geometry as shown by the cis angles are mostly close to 90°. The main deviations are caused by the small bite of the salen O donors \[72.15 (15)°\]. The basal planes of the complex are formed by the two bridging O atoms and two N atoms of the Schiff base ligand. The O atoms of the acetate group occupy apical positions. There are weak intermolecular C---H···O interactions involving the methoxy groups and acetate anions. In addition the dichoromethane solvate molecules are held in place by weak C---H···Cl interactions. Experimental {#experimental} ============ The synthesis of the ligand ethylene-bis(2,4-dimethoxy-salicylaldimine) was achieved by adding a solution of (2 g, 33.3 mmol) ethylenediamine in 25 ml s of methanol to the solution of (12.13 g, 66.6 mmol) 2,4-dimethoxysalicylaldehyde in 40 ml s of methanol. The mixture was refluxed overnight while stirring. The reaction mixture was then evaporated under reduced pressure to afford yellow solids. The synthesis of the complex C~50~H~60~Cl~4~Co~3~N~4~O~20~ was accomplished by adding a solution of (0.38 g, 1 mmol) of ethylene-bis(2,4-dimethoxy-salicylaldimine) in 20 ml dichloromethane to a solution of Co(CH~3~COO)~2~.H~2~O in 5 ml me thanol. The mixture was stirred for 3 h, filtered and layered with di-ethyl ether for crystallization. Crystals suitable for X-ray diffraction were obtained. Refinement {#refinement} ========== H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with a C---H distances of 0.95 and 0.99 Å U~iso~(H) = 1.2U~eq~(C) and 0.98 Å for CH~3~ \[U~iso~(H) = 1.5U~eq~(C)\]. In the final difference Fourier the maximum and minimum electron density of 1.11 and -1.66 e^-^/Å^3^ were located 0.93 Å and 0.44 Å from H0A and Cl1 respectively Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Diagram of trinuclear C48H56Co3N4O20 unit showing atom labeling. Thermal ellipsoids are at the 30% probability level. ::: ![](e-67-0m303-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular packing for C48H56Co3N4O20.2(CH2Cl2) viewed down the b axis. C---H···Cl and C---H···O interactions bonds are shown by dashed lines. ::: ![](e-67-0m303-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e297 .table-wrap} --------------------------------------------------------------- --------------------------------------- \[Co~3~(C~2~H~3~O~2~)~4~(C~20~H~22~N~2~O~6~)~2~\]·2CH~2~Cl~2~ F(000) = 1394 M~r~ = 1355.61 D~x~ = 1.630 Mg m^−3^ Monoclinic, P2~1~/n Cu Kα radiation, λ = 1.54178 Å Hall symbol: -P 2yn Cell parameters from 4463 reflections a = 13.9235 (9) Å θ = 4.4--73.9° b = 13.4407 (8) Å µ = 9.45 mm^−1^ c = 16.0019 (11) Å T = 110 K β = 112.724 (8)° Thick needle, red-brown V = 2762.2 (3) Å^3^ 0.42 × 0.25 × 0.18 mm Z = 2 --------------------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e453 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcalibur diffractometer with a Ruby (Gemini Cu) detector 5306 independent reflections Radiation source: Enhance (Cu) X-ray Source 3777 reflections with I \> 2σ(I) graphite R~int~ = 0.043 Detector resolution: 10.5081 pixels mm^-1^ θ~max~ = 74.2°, θ~min~ = 4.5° ω scans h = −17→13 Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009) k = −16→13 T~min~ = 0.320, T~max~ = 1.000 l = −19→18 10708 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e573 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.083 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.251 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.1718P)^2^ + 2.5393P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5306 reflections (Δ/σ)~max~ \< 0.001 373 parameters Δρ~max~ = 1.11 e Å^−3^ 0 restraints Δρ~min~ = −1.66 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e730 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e829 .table-wrap} ------ -------------- ------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ Co1 0.31088 (7) 0.37441 (7) 0.38337 (6) 0.0133 (3) Co2 0.5000 0.5000 0.5000 0.0138 (3) Cl1 −0.1730 (2) 0.4911 (2) 0.0248 (2) 0.0736 (8) Cl2 −0.2861 (3) 0.3805 (3) 0.1142 (2) 0.0826 (10) O1 0.4170 (3) 0.4463 (3) 0.3637 (3) 0.0142 (8) O2 0.3510 (3) 0.4519 (3) 0.4897 (3) 0.0176 (9) O3 0.5670 (4) 0.6103 (3) 0.1809 (3) 0.0229 (10) O4 0.3576 (4) 0.3258 (4) 0.0695 (3) 0.0239 (10) O5 0.0593 (4) 0.3797 (4) 0.5633 (3) 0.0276 (11) O6 0.2587 (4) 0.6707 (4) 0.6799 (3) 0.0279 (11) O11A 0.4076 (3) 0.2697 (3) 0.4437 (3) 0.0178 (9) O12A 0.5482 (3) 0.3568 (3) 0.5344 (3) 0.0182 (9) O21A 0.2186 (3) 0.4771 (3) 0.3178 (3) 0.0213 (10) O22A 0.0637 (4) 0.3991 (4) 0.2533 (3) 0.0296 (11) N1 0.2737 (4) 0.2957 (4) 0.2792 (3) 0.0154 (10) N2 0.2130 (4) 0.3016 (4) 0.4107 (3) 0.0179 (11) C −0.1698 (10) 0.3882 (8) 0.0942 (7) 0.062 (3) H0A −0.1096 0.3946 0.1527 0.075\ H0B −0.1608 0.3263 0.0644 0.075\* C1 0.4274 (4) 0.4539 (5) 0.2860 (4) 0.0146 (12) C2 0.4903 (4) 0.5312 (5) 0.2754 (4) 0.0129 (11) H2A 0.5195 0.5790 0.3222 0.015\* C3 0.5093 (5) 0.5373 (5) 0.1979 (4) 0.0190 (13) C4 0.6125 (5) 0.6836 (5) 0.2508 (4) 0.0265 (15) H4A 0.6550 0.7298 0.2323 0.040\* H4B 0.6563 0.6503 0.3072 0.040\* H4C 0.5570 0.7205 0.2607 0.040\* C5 0.4666 (5) 0.4690 (5) 0.1259 (4) 0.0188 (13) H5A 0.4817 0.4740 0.0731 0.023\* C6 0.4019 (5) 0.3940 (5) 0.1342 (4) 0.0170 (12) C7 0.3851 (7) 0.3271 (6) −0.0085 (5) 0.0353 (18) H7A 0.3580 0.2671 −0.0448 0.053\* H7B 0.4611 0.3288 0.0114 0.053\* H7C 0.3550 0.3861 −0.0452 0.053\* C8 0.3786 (5) 0.3854 (5) 0.2132 (4) 0.0179 (12) C9 0.3083 (4) 0.3071 (5) 0.2162 (4) 0.0150 (12) H9A 0.2861 0.2607 0.1678 0.018\* C10 0.1969 (5) 0.2181 (5) 0.2716 (4) 0.0210 (13) H10A 0.2179 0.1549 0.2518 0.025\* H10B 0.1280 0.2376 0.2261 0.025\* C11 0.1902 (6) 0.2044 (5) 0.3629 (5) 0.0267 (15) H11A 0.1197 0.1814 0.3551 0.032\* H11B 0.2413 0.1538 0.3987 0.032\* C12 0.1734 (4) 0.3272 (5) 0.4676 (4) 0.0176 (12) H12A 0.1235 0.2839 0.4752 0.021\* C13 0.1990 (5) 0.4164 (5) 0.5206 (4) 0.0181 (13) C14 0.1394 (5) 0.4440 (5) 0.5709 (4) 0.0238 (14) C15 −0.0028 (6) 0.4037 (6) 0.6139 (5) 0.0316 (17) H15A −0.0562 0.3525 0.6038 0.047\* H15B −0.0363 0.4684 0.5941 0.047\* H15C 0.0417 0.4067 0.6786 0.047\* C16 0.1603 (5) 0.5288 (5) 0.6242 (5) 0.0231 (14) H16A 0.1192 0.5456 0.6577 0.028\* C17 0.2433 (5) 0.5885 (5) 0.6274 (4) 0.0223 (14) C18 0.3486 (6) 0.7310 (6) 0.6947 (6) 0.041 (2) H18A 0.3498 0.7866 0.7347 0.061\* H18B 0.3458 0.7570 0.6366 0.061\* H18C 0.4116 0.6907 0.7229 0.061\* C19 0.3059 (5) 0.5648 (5) 0.5799 (4) 0.0185 (13) H19A 0.3616 0.6072 0.5825 0.022\* C20 0.2851 (4) 0.4775 (5) 0.5283 (4) 0.0178 (13) C11A 0.5005 (5) 0.2775 (5) 0.5022 (4) 0.0175 (12) C12A 0.5555 (5) 0.1810 (5) 0.5336 (5) 0.0272 (15) H12B 0.5189 0.1282 0.4910 0.041\* H12C 0.5569 0.1651 0.5938 0.041\* H12D 0.6270 0.1863 0.5367 0.041\* C21A 0.1218 (5) 0.4706 (5) 0.2639 (4) 0.0210 (13) C22A 0.0821 (6) 0.5634 (6) 0.2093 (5) 0.0308 (16) H22A 0.0067 0.5580 0.1758 0.046\* H22B 0.1163 0.5717 0.1665 0.046\* H22C 0.0974 0.6210 0.2500 0.046\* ------ -------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1745 .table-wrap} ------ ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Co1 0.0088 (5) 0.0168 (5) 0.0142 (5) −0.0035 (4) 0.0043 (3) −0.0026 (4) Co2 0.0088 (6) 0.0186 (7) 0.0142 (6) −0.0039 (5) 0.0046 (5) −0.0031 (5) Cl1 0.0671 (18) 0.0709 (19) 0.0748 (18) −0.0053 (15) 0.0184 (15) 0.0120 (15) Cl2 0.087 (2) 0.093 (2) 0.075 (2) −0.0023 (19) 0.0400 (18) 0.0040 (18) O1 0.0090 (19) 0.020 (2) 0.0145 (19) −0.0039 (17) 0.0058 (15) −0.0011 (17) O2 0.0118 (19) 0.024 (2) 0.019 (2) −0.0044 (18) 0.0085 (16) −0.0089 (18) O3 0.023 (2) 0.022 (2) 0.027 (2) −0.0050 (19) 0.0145 (19) 0.001 (2) O4 0.025 (2) 0.033 (3) 0.014 (2) −0.005 (2) 0.0088 (18) −0.004 (2) O5 0.017 (2) 0.035 (3) 0.037 (3) −0.004 (2) 0.017 (2) −0.005 (2) O6 0.023 (2) 0.031 (3) 0.034 (3) 0.004 (2) 0.016 (2) −0.010 (2) O11A 0.013 (2) 0.019 (2) 0.018 (2) −0.0029 (17) 0.0019 (16) −0.0023 (17) O12A 0.010 (2) 0.022 (2) 0.019 (2) −0.0030 (17) 0.0019 (16) −0.0040 (18) O21A 0.014 (2) 0.023 (2) 0.024 (2) 0.0015 (18) 0.0034 (17) −0.0020 (19) O22A 0.023 (2) 0.024 (3) 0.034 (3) −0.006 (2) 0.002 (2) 0.001 (2) N1 0.011 (2) 0.017 (2) 0.016 (2) −0.001 (2) 0.0028 (18) −0.004 (2) N2 0.012 (2) 0.020 (3) 0.021 (2) −0.007 (2) 0.005 (2) −0.001 (2) C 0.084 (8) 0.044 (5) 0.052 (6) −0.003 (6) 0.019 (6) 0.009 (5) C1 0.007 (2) 0.017 (3) 0.016 (3) 0.003 (2) 0.001 (2) 0.000 (2) C2 0.006 (2) 0.018 (3) 0.014 (3) 0.002 (2) 0.003 (2) 0.001 (2) C3 0.011 (3) 0.019 (3) 0.024 (3) 0.007 (2) 0.003 (2) 0.005 (3) C4 0.025 (3) 0.033 (4) 0.023 (3) −0.015 (3) 0.012 (3) −0.002 (3) C5 0.024 (3) 0.024 (3) 0.014 (3) 0.005 (3) 0.013 (2) 0.002 (3) C6 0.015 (3) 0.022 (3) 0.011 (3) 0.005 (2) 0.002 (2) 0.001 (2) C7 0.046 (5) 0.042 (5) 0.024 (3) −0.009 (4) 0.020 (3) −0.012 (3) C8 0.012 (3) 0.017 (3) 0.025 (3) 0.003 (2) 0.008 (2) 0.001 (3) C9 0.013 (3) 0.016 (3) 0.011 (2) 0.006 (2) 0.000 (2) −0.001 (2) C10 0.019 (3) 0.020 (3) 0.027 (3) −0.008 (3) 0.011 (3) −0.008 (3) C11 0.027 (4) 0.025 (4) 0.026 (3) −0.016 (3) 0.007 (3) −0.011 (3) C12 0.011 (3) 0.023 (3) 0.019 (3) −0.007 (2) 0.006 (2) −0.001 (3) C13 0.011 (3) 0.027 (3) 0.015 (3) 0.003 (2) 0.004 (2) 0.004 (3) C14 0.015 (3) 0.033 (4) 0.022 (3) 0.006 (3) 0.006 (3) 0.004 (3) C15 0.027 (4) 0.043 (4) 0.038 (4) 0.003 (3) 0.027 (3) 0.007 (3) C16 0.014 (3) 0.029 (4) 0.031 (3) 0.008 (3) 0.014 (3) 0.000 (3) C17 0.019 (3) 0.027 (3) 0.020 (3) 0.004 (3) 0.006 (2) 0.001 (3) C18 0.029 (4) 0.038 (4) 0.052 (5) 0.000 (4) 0.011 (4) −0.030 (4) C19 0.012 (3) 0.019 (3) 0.024 (3) 0.005 (2) 0.006 (2) −0.001 (3) C20 0.009 (3) 0.026 (3) 0.015 (3) 0.002 (2) 0.001 (2) 0.001 (3) C11A 0.012 (3) 0.026 (3) 0.017 (3) −0.001 (2) 0.008 (2) 0.004 (3) C12A 0.022 (3) 0.027 (4) 0.024 (3) −0.002 (3) −0.001 (3) −0.004 (3) C21A 0.017 (3) 0.028 (3) 0.019 (3) 0.006 (3) 0.008 (2) −0.003 (3) C22A 0.024 (3) 0.035 (4) 0.034 (4) −0.004 (3) 0.011 (3) 0.007 (3) ------ ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2500 .table-wrap} --------------------------- -------------- -------------------------- ------------ Co1---N2 1.861 (5) C4---H4B 0.9800 Co1---N1 1.871 (5) C4---H4C 0.9800 Co1---O2 1.887 (4) C5---C6 1.391 (9) Co1---O1 1.891 (4) C5---H5A 0.9500 Co1---O21A 1.902 (5) C6---C8 1.425 (9) Co1---O11A 1.929 (4) C7---H7A 0.9800 Co2---O12A^i^ 2.043 (4) C7---H7B 0.9800 Co2---O12A 2.043 (4) C7---H7C 0.9800 Co2---O2^i^ 2.117 (4) C8---C9 1.451 (8) Co2---O2 2.117 (4) C9---H9A 0.9500 Co2---O1 2.160 (4) C10---C11 1.511 (9) Co2---O1^i^ 2.160 (4) C10---H10A 0.9900 Cl1---C 1.763 (10) C10---H10B 0.9900 Cl2---C 1.771 (13) C11---H11A 0.9900 O1---C1 1.310 (7) C11---H11B 0.9900 O2---C20 1.334 (7) C12---C13 1.432 (9) O3---C3 1.361 (8) C12---H12A 0.9500 O3---C4 1.441 (8) C13---C14 1.411 (9) O4---C6 1.342 (7) C13---C20 1.418 (9) O4---C7 1.440 (8) C14---C16 1.385 (10) O5---C14 1.380 (8) C15---H15A 0.9800 O5---C15 1.431 (8) C15---H15B 0.9800 O6---C17 1.353 (8) C15---H15C 0.9800 O6---C18 1.432 (9) C16---C17 1.393 (9) O11A---C11A 1.275 (7) C16---H16A 0.9500 O12A---C11A 1.256 (8) C17---C19 1.397 (9) O21A---C21A 1.293 (8) C18---H18A 0.9800 O22A---C21A 1.226 (8) C18---H18B 0.9800 N1---C9 1.282 (8) C18---H18C 0.9800 N1---C10 1.465 (8) C19---C20 1.400 (9) N2---C12 1.281 (8) C19---H19A 0.9500 N2---C11 1.485 (8) C11A---C12A 1.491 (9) C---H0A 0.9900 C12A---H12B 0.9800 C---H0B 0.9900 C12A---H12C 0.9800 C1---C2 1.411 (8) C12A---H12D 0.9800 C1---C8 1.433 (8) C21A---C22A 1.500 (10) C2---C3 1.366 (9) C22A---H22A 0.9800 C2---H2A 0.9500 C22A---H22B 0.9800 C3---C5 1.412 (9) C22A---H22C 0.9800 C4---H4A 0.9800 N2---Co1---N1 86.4 (2) O4---C7---H7A 109.5 N2---Co1---O2 93.9 (2) O4---C7---H7B 109.5 N1---Co1---O2 178.7 (2) H7A---C7---H7B 109.5 N2---Co1---O1 176.1 (2) O4---C7---H7C 109.5 N1---Co1---O1 96.1 (2) H7A---C7---H7C 109.5 O2---Co1---O1 83.65 (18) H7B---C7---H7C 109.5 N2---Co1---O21A 96.4 (2) C6---C8---C1 118.0 (6) N1---Co1---O21A 91.4 (2) C6---C8---C9 118.4 (6) O2---Co1---O21A 89.90 (19) C1---C8---C9 123.5 (6) O1---Co1---O21A 86.66 (19) N1---C9---C8 125.2 (6) N2---Co1---O11A 86.1 (2) N1---C9---H9A 117.4 N1---Co1---O11A 86.2 (2) C8---C9---H9A 117.4 O2---Co1---O11A 92.57 (18) N1---C10---C11 108.8 (5) O1---Co1---O11A 90.98 (18) N1---C10---H10A 109.9 O21A---Co1---O11A 176.38 (19) C11---C10---H10A 109.9 O12A^i^---Co2---O12A 180.000 (1) N1---C10---H10B 109.9 O12A^i^---Co2---O2^i^ 86.78 (17) C11---C10---H10B 109.9 O12A---Co2---O2^i^ 93.22 (17) H10A---C10---H10B 108.3 O12A^i^---Co2---O2 93.22 (17) N2---C11---C10 108.0 (5) O12A---Co2---O2 86.78 (17) N2---C11---H11A 110.1 O2^i^---Co2---O2 180.0 C10---C11---H11A 110.1 O12A^i^---Co2---O1 92.92 (16) N2---C11---H11B 110.1 O12A---Co2---O1 87.08 (16) C10---C11---H11B 110.1 O2^i^---Co2---O1 107.85 (15) H11A---C11---H11B 108.4 O2---Co2---O1 72.15 (15) N2---C12---C13 124.7 (6) O12A^i^---Co2---O1^i^ 87.08 (16) N2---C12---H12A 117.7 O12A---Co2---O1^i^ 92.92 (16) C13---C12---H12A 117.7 O2^i^---Co2---O1^i^ 72.15 (15) C14---C13---C20 117.5 (6) O2---Co2---O1^i^ 107.85 (15) C14---C13---C12 119.5 (6) O1---Co2---O1^i^ 180.000 (1) C20---C13---C12 123.0 (5) C1---O1---Co1 125.3 (4) O5---C14---C16 122.7 (6) C1---O1---Co2 136.1 (4) O5---C14---C13 114.7 (6) Co1---O1---Co2 98.66 (17) C16---C14---C13 122.6 (6) C20---O2---Co1 122.9 (4) O5---C15---H15A 109.5 C20---O2---Co2 135.6 (4) O5---C15---H15B 109.5 Co1---O2---Co2 100.29 (18) H15A---C15---H15B 109.5 C3---O3---C4 117.0 (5) O5---C15---H15C 109.5 C6---O4---C7 117.7 (5) H15A---C15---H15C 109.5 C14---O5---C15 116.9 (6) H15B---C15---H15C 109.5 C17---O6---C18 118.9 (5) C14---C16---C17 118.1 (6) C11A---O11A---Co1 128.5 (4) C14---C16---H16A 121.0 C11A---O12A---Co2 128.5 (4) C17---C16---H16A 121.0 C21A---O21A---Co1 128.8 (4) O6---C17---C16 115.1 (6) C9---N1---C10 120.3 (5) O6---C17---C19 122.8 (6) C9---N1---Co1 125.0 (4) C16---C17---C19 122.2 (6) C10---N1---Co1 114.7 (4) O6---C18---H18A 109.5 C12---N2---C11 122.4 (5) O6---C18---H18B 109.5 C12---N2---Co1 125.5 (4) H18A---C18---H18B 109.5 C11---N2---Co1 111.9 (4) O6---C18---H18C 109.5 Cl1---C---Cl2 110.9 (7) H18A---C18---H18C 109.5 Cl1---C---H0A 109.5 H18B---C18---H18C 109.5 Cl2---C---H0A 109.5 C17---C19---C20 118.8 (6) Cl1---C---H0B 109.5 C17---C19---H19A 120.6 Cl2---C---H0B 109.5 C20---C19---H19A 120.6 H0A---C---H0B 108.0 O2---C20---C19 117.8 (5) O1---C1---C2 118.2 (5) O2---C20---C13 121.3 (6) O1---C1---C8 122.0 (5) C19---C20---C13 120.9 (6) C2---C1---C8 119.8 (5) O12A---C11A---O11A 126.6 (6) C3---C2---C1 119.9 (6) O12A---C11A---C12A 118.5 (5) C3---C2---H2A 120.0 O11A---C11A---C12A 114.9 (6) C1---C2---H2A 120.0 C11A---C12A---H12B 109.5 O3---C3---C2 124.1 (6) C11A---C12A---H12C 109.5 O3---C3---C5 113.6 (6) H12B---C12A---H12C 109.5 C2---C3---C5 122.3 (6) C11A---C12A---H12D 109.5 O3---C4---H4A 109.5 H12B---C12A---H12D 109.5 O3---C4---H4B 109.5 H12C---C12A---H12D 109.5 H4A---C4---H4B 109.5 O22A---C21A---O21A 127.5 (6) O3---C4---H4C 109.5 O22A---C21A---C22A 119.8 (6) H4A---C4---H4C 109.5 O21A---C21A---C22A 112.8 (6) H4B---C4---H4C 109.5 C21A---C22A---H22A 109.5 C6---C5---C3 118.5 (5) C21A---C22A---H22B 109.5 C6---C5---H5A 120.8 H22A---C22A---H22B 109.5 C3---C5---H5A 120.8 C21A---C22A---H22C 109.5 O4---C6---C5 122.9 (5) H22A---C22A---H22C 109.5 O4---C6---C8 115.8 (5) H22B---C22A---H22C 109.5 C5---C6---C8 121.4 (6) N1---Co1---O1---C1 18.7 (5) Co2---O1---C1---C8 160.4 (4) O2---Co1---O1---C1 −162.6 (5) O1---C1---C2---C3 175.2 (5) O21A---Co1---O1---C1 −72.3 (5) C8---C1---C2---C3 −3.6 (8) O11A---Co1---O1---C1 104.9 (5) C4---O3---C3---C2 1.8 (9) N1---Co1---O1---Co2 −160.9 (2) C4---O3---C3---C5 179.5 (5) O2---Co1---O1---Co2 17.86 (18) C1---C2---C3---O3 178.4 (5) O21A---Co1---O1---Co2 108.13 (19) C1---C2---C3---C5 0.9 (9) O11A---Co1---O1---Co2 −74.62 (18) O3---C3---C5---C6 −176.8 (5) O12A^i^---Co2---O1---C1 71.5 (5) C2---C3---C5---C6 1.0 (9) O12A---Co2---O1---C1 −108.5 (5) C7---O4---C6---C5 4.5 (9) O2^i^---Co2---O1---C1 −16.1 (6) C7---O4---C6---C8 −175.5 (6) O2---Co2---O1---C1 163.9 (6) C3---C5---C6---O4 180.0 (5) O12A^i^---Co2---O1---Co1 −109.03 (19) C3---C5---C6---C8 −0.1 (9) O12A---Co2---O1---Co1 70.97 (19) O4---C6---C8---C1 177.4 (5) O2^i^---Co2---O1---Co1 163.42 (17) C5---C6---C8---C1 −2.5 (9) O2---Co2---O1---Co1 −16.58 (17) O4---C6---C8---C9 −1.7 (8) N2---Co1---O2---C20 −32.5 (5) C5---C6---C8---C9 178.4 (6) O1---Co1---O2---C20 150.6 (5) O1---C1---C8---C6 −174.4 (5) O21A---Co1---O2---C20 63.9 (5) C2---C1---C8---C6 4.4 (8) O11A---Co1---O2---C20 −118.7 (5) O1---C1---C8---C9 4.6 (9) N2---Co1---O2---Co2 158.6 (2) C2---C1---C8---C9 −176.6 (5) O1---Co1---O2---Co2 −18.32 (19) C10---N1---C9---C8 175.5 (6) O21A---Co1---O2---Co2 −105.0 (2) Co1---N1---C9---C8 −2.7 (8) O11A---Co1---O2---Co2 72.4 (2) C6---C8---C9---N1 −173.9 (6) O12A^i^---Co2---O2---C20 −57.9 (6) C1---C8---C9---N1 7.1 (9) O12A---Co2---O2---C20 122.1 (6) C9---N1---C10---C11 166.1 (6) O1---Co2---O2---C20 −149.9 (6) Co1---N1---C10---C11 −15.5 (7) O1^i^---Co2---O2---C20 30.1 (6) C12---N2---C11---C10 149.8 (6) O12A^i^---Co2---O2---Co1 108.7 (2) Co1---N2---C11---C10 −34.2 (6) O12A---Co2---O2---Co1 −71.3 (2) N1---C10---C11---N2 30.8 (7) O1---Co2---O2---Co1 16.70 (17) C11---N2---C12---C13 174.9 (6) O1^i^---Co2---O2---Co1 −163.30 (17) Co1---N2---C12---C13 −0.6 (9) N2---Co1---O11A---C11A −133.8 (5) N2---C12---C13---C14 170.6 (6) N1---Co1---O11A---C11A 139.6 (5) N2---C12---C13---C20 −12.1 (10) O2---Co1---O11A---C11A −40.1 (5) C15---O5---C14---C16 −0.3 (9) O1---Co1---O11A---C11A 43.6 (5) C15---O5---C14---C13 179.3 (6) O2^i^---Co2---O12A---C11A −140.5 (5) C20---C13---C14---O5 −177.6 (5) O2---Co2---O12A---C11A 39.5 (5) C12---C13---C14---O5 −0.2 (9) O1---Co2---O12A---C11A −32.8 (5) C20---C13---C14---C16 2.0 (10) O1^i^---Co2---O12A---C11A 147.2 (5) C12---C13---C14---C16 179.4 (6) N2---Co1---O21A---C21A −37.0 (6) O5---C14---C16---C17 179.8 (6) N1---Co1---O21A---C21A 49.5 (5) C13---C14---C16---C17 0.2 (10) O2---Co1---O21A---C21A −130.8 (5) C18---O6---C17---C16 173.6 (6) O1---Co1---O21A---C21A 145.5 (5) C18---O6---C17---C19 −6.2 (10) N2---Co1---N1---C9 175.4 (5) C14---C16---C17---O6 179.2 (6) O1---Co1---N1---C9 −7.7 (5) C14---C16---C17---C19 −0.9 (10) O21A---Co1---N1---C9 79.1 (5) O6---C17---C19---C20 179.1 (6) O11A---Co1---N1---C9 −98.3 (5) C16---C17---C19---C20 −0.8 (10) N2---Co1---N1---C10 −2.9 (4) Co1---O2---C20---C19 −153.3 (4) O1---Co1---N1---C10 174.0 (4) Co2---O2---C20---C19 11.0 (9) O21A---Co1---N1---C10 −99.2 (4) Co1---O2---C20---C13 29.1 (8) O11A---Co1---N1---C10 83.4 (4) Co2---O2---C20---C13 −166.6 (4) N1---Co1---N2---C12 −162.8 (6) C17---C19---C20---O2 −174.5 (6) O2---Co1---N2---C12 18.5 (5) C17---C19---C20---C13 3.1 (9) O1---Co1---N2---C12 69 (3) C14---C13---C20---O2 173.8 (6) O21A---Co1---N2---C12 −71.9 (5) C12---C13---C20---O2 −3.5 (9) O11A---Co1---N2---C12 110.8 (5) C14---C13---C20---C19 −3.6 (9) N1---Co1---N2---C11 21.3 (4) C12---C13---C20---C19 179.0 (6) O2---Co1---N2---C11 −157.4 (4) Co2---O12A---C11A---O11A −4.4 (9) O21A---Co1---N2---C11 112.3 (4) Co2---O12A---C11A---C12A 175.4 (4) O11A---Co1---N2---C11 −65.1 (4) Co1---O11A---C11A---O12A 1.6 (9) Co1---O1---C1---C2 162.2 (4) Co1---O11A---C11A---C12A −178.2 (4) Co2---O1---C1---C2 −18.5 (8) Co1---O21A---C21A---O22A 11.6 (10) Co1---O1---C1---C8 −19.0 (8) Co1---O21A---C21A---C22A −167.3 (4) --------------------------- -------------- -------------------------- ------------ ::: Symmetry codes: (i) −x+1, −y+1, −z+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4365 .table-wrap} ------------------------ --------- --------- ------------ --------------- D---H···A D---H H···A D···A D---H···A C---H0A···O22A 0.99 2.33 3.269 (13) 158 C4---H4A···O6^ii^ 0.98 2.35 3.326 (8) 175 C7---H7A···O6^iii^ 0.98 2.51 3.421 (9) 156 C11---H11A···O3^iii^ 0.99 2.62 3.602 (8) 174 C11---H11B···Cl1^iv^ 0.99 2.73 3.664 (8) 158 C15---H15A···O4^v^ 0.98 2.64 3.568 (10) 158 C12A---H12B···Cl1^iii^ 0.98 2.91 3.354 (8) 108 ------------------------ --------- --------- ------------ --------------- ::: Symmetry codes: (ii) x+1/2, −y+3/2, z−1/2; (iii) −x+1/2, y−1/2, −z+1/2; (iv) x+1/2, −y+1/2, z+1/2; (v) x−1/2, −y+1/2, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------------- --------- ------- ------------ ------------- C---H0A⋯O22A 0.99 2.33 3.269 (13) 158 C4---H4A⋯O6^i^ 0.98 2.35 3.326 (8) 175 C7---H7A⋯O6^ii^ 0.98 2.51 3.421 (9) 156 C11---H11A⋯O3^ii^ 0.99 2.62 3.602 (8) 174 C11---H11B⋯Cl1^iii^ 0.99 2.73 3.664 (8) 158 C15---H15A⋯O4^iv^ 0.98 2.64 3.568 (10) 158 C12A---H12B⋯Cl1^ii^ 0.98 2.91 3.354 (8) 108 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::	PubMed Central	2024-06-05T04:04:18.455573	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052101/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):m303-m304", "authors": [ { "first": "Gervas E.", "last": "Assey" }, { "first": "Ray J.", "last": "Butcher" }, { "first": "Yilma", "last": "Gultneh" } ] }
PMC3052102	Related literature {#sec1} ================== For applications of long-chain n-alkylammonium halides, see: Aratono et al. (1998[@bb1]); Tornblom et al. (2000[@bb10]); Ringsdorf et al. (1988[@bb5]). For details of phase transitions in n-alkylammonium chlorides, see: Terreros et al. (2000[@bb9]). For related structures, see: Rademeyer et al. (2009[@bb4]); Lundén (1974[@bb3]); Clark & Hudgens (1950[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~30~N^+^·Cl^−^·H~2~OM ~r~ = 253.85Monoclinic,a = 4.7420 (5) Åb = 45.250 (3) Åc = 7.8191 (9) Åβ = 106.332 (2)°V = 1610.1 (3) Å^3^Z = 4Mo Kα radiationμ = 0.22 mm^−1^T = 298 K0.34 × 0.33 × 0.03 mm ### Data collection {#sec2.1.2} Siemens SMART CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb6]) T ~min~ = 0.928, T ~max~ = 0.9938230 measured reflections2845 independent reflections1379 reflections with I \> 2σ(I)R ~int~ = 0.077 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.067wR(F ^2^) = 0.124S = 1.032845 reflections147 parametersH-atom parameters constrainedΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e506} Data collection: SMART (Siemens, 1996[@bb8]); cell refinement: SAINT (Siemens, 1996[@bb8]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb7]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006246/lh5197sup1.cif](http://dx.doi.org/10.1107/S1600536811006246/lh5197sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006246/lh5197Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006246/lh5197Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5197&file=lh5197sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5197sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5197&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5197](http://scripts.iucr.org/cgi-bin/sendsup?lh5197)). We acknowledge the National Natural Science Foundation of China (20973089) for financial support. Comment ======= Long-chain n-alkylammonium halides are widely used as surfactants (Aratono et al., 1998; Tornblom et al., 2000) and as models for biological membranes (Ringsdorf et al., 1988). It has been shown that phase transitions occur in n-alkylammonium chlorides (Terreros et al., 2000). As a part of our studies on novel potential phase transition materials with thermochemical properties, we report herein the crystal structure of the title compound (Fig. 1). Atoms C2--C13 are essentially co-planar with a maximum deviation of 0.048 (3)Å for atom C2. The alkyl chain in related compounds is typically in the extended conformation e.g. in the isostructural n-tridecylamine bromide monohydrate compound (Rademeyer et al., 2009), n--dodecylammonium bromide (Lundén, 1974) and n--tridecylamine chloride (Clark & Hudgens, 1950). Although the methylene chain has the extended all--trans conformation, it is slightly bent in the vicinity of the ammonium group possibly to accommodate the hydrogen--bonding interactions. Only the C1--C2--C3--C4 torsion angle deviates significantly from 180 °, with a value of 169.84 (3)°. The crystal packing (Fig. 2) is stabilized by intermolecular N---H···Cl, N---H···O and O---H···Cl hydrogen bonds (Table 1 and Fig.2). Experimental {#experimental} ============ n--Tridecylamine chloride monohydrate was prepared by the addition of hydrochloric acid to an ethanolic solution of n--tridecylamine. The mixture was heated and stirred under reflux for 6 h. Single crystals suitable for X--ray diffraction were prepared by evaporation of the resulting solution at room temperature. Analysis, calculated for C~13~H~32~ClNO (Mr =253.85): C 61.51, H 12.71, N 5.52, Cl 13.96%; found: C 61.50, H 12.72, N 5.51, Cl 13.95%. Refinement {#refinement} ========== All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with methylene C---H = 0.97 Å, methyl C---H = 0.96 Å, N---H = 0.89 Å, O-H = 0.85 Å and refined as riding on their parent atoms. TheU~iso~(H) values were set at 1.2U~eq~(C~methylene~, O) at 1.5U~eq~(C~methyl~,N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o717-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds shown as dashed lines. ::: ![](e-67-0o717-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e167 .table-wrap} ---------------------------- -------------------------------------- C~13~H~30~N^+^·Cl^−^·H~2~O F(000) = 568 M~r~ = 253.85 D~x~ = 1.047 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 817 reflections a = 4.7420 (5) Å θ = 2.7--20.8° b = 45.250 (3) Å µ = 0.22 mm^−1^ c = 7.8191 (9) Å T = 298 K β = 106.332 (2)° Acicular, colourless V = 1610.1 (3) Å^3^ 0.34 × 0.33 × 0.03 mm Z = 4 ---------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e302 .table-wrap} --------------------------------------------------------------- -------------------------------------- Siemens SMART CCD area-detector diffractometer 2845 independent reflections Radiation source: fine-focus sealed tube 1379 reflections with I \> 2σ(I) graphite R~int~ = 0.077 Detector resolution: 10 pixels mm^-1^ θ~max~ = 25.0°, θ~min~ = 2.7° φ and ω scans h = −5→5 Absorption correction: multi-scan (SADABS; Sheldrick, 1996) k = −53→46 T~min~ = 0.928, T~max~ = 0.993 l = −7→9 8230 measured reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e425 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.067 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.124 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0256P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 2845 reflections (Δ/σ)~max~ = 0.001 147 parameters Δρ~max~ = 0.25 e Å^−3^ 0 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e579 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cl1 0.77004 (19) 0.727389 (19) 0.54882 (12) 0.0578 (3) N1 0.2908 (5) 0.72396 (5) 0.1504 (4) 0.0486 (8) H1A 0.4378 0.7281 0.2466 0.073\ H1B 0.1648 0.7390 0.1270 0.073\* H1C 0.3618 0.7210 0.0578 0.073\* O1 0.3848 (5) 0.70538 (5) 0.8156 (3) 0.0690 (8) H1H 0.5034 0.7102 0.7566 0.083\* H1I 0.2125 0.7103 0.7554 0.083\* C1 0.1369 (7) 0.69683 (6) 0.1834 (4) 0.0462 (9) H1D −0.0396 0.6941 0.0856 0.055\* H1E 0.0779 0.6994 0.2915 0.055\* C2 0.3263 (7) 0.66944 (6) 0.2017 (4) 0.0445 (9) H2A 0.5028 0.6722 0.2995 0.053\* H2B 0.3852 0.6668 0.0935 0.053\* C3 0.1677 (7) 0.64186 (6) 0.2355 (4) 0.0467 (9) H3A −0.0251 0.6412 0.1498 0.056\* H3B 0.1397 0.6431 0.3534 0.056\* C4 0.3305 (7) 0.61334 (6) 0.2221 (4) 0.0444 (9) H4A 0.5222 0.6140 0.3090 0.053\* H4B 0.3616 0.6123 0.1049 0.053\* C5 0.1730 (7) 0.58533 (6) 0.2526 (4) 0.0471 (9) H5A 0.1495 0.5860 0.3718 0.056\* H5B −0.0219 0.5851 0.1691 0.056\* C6 0.3292 (7) 0.55675 (6) 0.2317 (4) 0.0440 (9) H6A 0.3543 0.5562 0.1128 0.053\* H6B 0.5234 0.5569 0.3159 0.053\* C7 0.1722 (7) 0.52882 (6) 0.2603 (4) 0.0450 (9) H7A −0.0231 0.5288 0.1773 0.054\* H7B 0.1496 0.5292 0.3798 0.054\* C8 0.3260 (6) 0.50019 (6) 0.2369 (4) 0.0440 (9) H8A 0.3473 0.4997 0.1171 0.053\* H8B 0.5218 0.5003 0.3193 0.053\* C9 0.1705 (7) 0.47222 (6) 0.2666 (4) 0.0448 (9) H9A −0.0251 0.4721 0.1839 0.054\* H9B 0.1485 0.4727 0.3862 0.054\* C10 0.3245 (7) 0.44364 (6) 0.2439 (4) 0.0438 (9) H10A 0.3458 0.4431 0.1242 0.053\* H10B 0.5204 0.4438 0.3263 0.053\* C11 0.1702 (7) 0.41561 (6) 0.2745 (4) 0.0448 (9) H11A 0.1479 0.4162 0.3940 0.054\* H11B −0.0253 0.4154 0.1917 0.054\* C12 0.3236 (7) 0.38729 (6) 0.2530 (5) 0.0522 (10) H12A 0.5194 0.3876 0.3355 0.063\* H12B 0.3452 0.3867 0.1333 0.063\* C13 0.1688 (8) 0.35920 (7) 0.2844 (5) 0.0703 (12) H13A 0.1532 0.3591 0.4042 0.105\* H13B 0.2798 0.3423 0.2668 0.105\* H13C −0.0242 0.3584 0.2021 0.105\* ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1308 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cl1 0.0520 (5) 0.0590 (6) 0.0612 (6) −0.0052 (5) 0.0137 (4) −0.0036 (5) N1 0.0485 (16) 0.0358 (17) 0.061 (2) 0.0041 (15) 0.0145 (14) 0.0002 (14) O1 0.0659 (17) 0.0752 (17) 0.0683 (19) 0.0036 (15) 0.0230 (13) 0.0100 (14) C1 0.044 (2) 0.034 (2) 0.062 (3) 0.0005 (18) 0.0178 (17) 0.0039 (16) C2 0.046 (2) 0.035 (2) 0.053 (2) −0.0022 (18) 0.0152 (17) −0.0021 (16) C3 0.052 (2) 0.039 (2) 0.053 (2) −0.0043 (19) 0.0209 (18) 0.0011 (17) C4 0.050 (2) 0.036 (2) 0.050 (2) −0.0033 (18) 0.0191 (18) 0.0020 (16) C5 0.053 (2) 0.041 (2) 0.049 (2) −0.005 (2) 0.0189 (18) 0.0004 (17) C6 0.048 (2) 0.039 (2) 0.048 (2) −0.0014 (19) 0.0177 (17) 0.0012 (16) C7 0.048 (2) 0.039 (2) 0.050 (2) −0.0024 (19) 0.0178 (17) 0.0029 (17) C8 0.047 (2) 0.040 (2) 0.047 (2) −0.003 (2) 0.0170 (17) 0.0042 (16) C9 0.051 (2) 0.037 (2) 0.049 (2) −0.0035 (19) 0.0190 (18) −0.0009 (16) C10 0.048 (2) 0.040 (2) 0.047 (2) −0.0014 (19) 0.0194 (17) −0.0011 (16) C11 0.050 (2) 0.039 (2) 0.048 (2) −0.0033 (19) 0.0167 (17) 0.0026 (16) C12 0.062 (2) 0.041 (2) 0.054 (3) 0.004 (2) 0.0163 (19) 0.0000 (17) C13 0.094 (3) 0.043 (2) 0.076 (3) −0.005 (2) 0.026 (2) 0.001 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1626 .table-wrap} ------------------- ------------ ----------------------- ------------ N1---C1 1.487 (3) C6---H6B 0.9700 N1---H1A 0.8900 C7---C8 1.523 (4) N1---H1B 0.8900 C7---H7A 0.9700 N1---H1C 0.8900 C7---H7B 0.9700 O1---H1H 0.8499 C8---C9 1.515 (4) O1---H1I 0.8499 C8---H8A 0.9700 C1---C2 1.513 (4) C8---H8B 0.9700 C1---H1D 0.9700 C9---C10 1.520 (4) C1---H1E 0.9700 C9---H9A 0.9700 C2---C3 1.518 (4) C9---H9B 0.9700 C2---H2A 0.9700 C10---C11 1.517 (4) C2---H2B 0.9700 C10---H10A 0.9700 C3---C4 1.523 (4) C10---H10B 0.9700 C3---H3A 0.9700 C11---C12 1.506 (4) C3---H3B 0.9700 C11---H11A 0.9700 C4---C5 1.524 (4) C11---H11B 0.9700 C4---H4A 0.9700 C12---C13 1.522 (4) C4---H4B 0.9700 C12---H12A 0.9700 C5---C6 1.522 (4) C12---H12B 0.9700 C5---H5A 0.9700 C13---H13A 0.9600 C5---H5B 0.9700 C13---H13B 0.9600 C6---C7 1.515 (4) C13---H13C 0.9600 C6---H6A 0.9700 C1---N1---H1A 109.5 C6---C7---C8 114.8 (3) C1---N1---H1B 109.5 C6---C7---H7A 108.6 H1A---N1---H1B 109.5 C8---C7---H7A 108.6 C1---N1---H1C 109.5 C6---C7---H7B 108.6 H1A---N1---H1C 109.5 C8---C7---H7B 108.6 H1B---N1---H1C 109.5 H7A---C7---H7B 107.5 H1H---O1---H1I 108.1 C9---C8---C7 114.9 (2) N1---C1---C2 112.7 (3) C9---C8---H8A 108.5 N1---C1---H1D 109.1 C7---C8---H8A 108.5 C2---C1---H1D 109.1 C9---C8---H8B 108.5 N1---C1---H1E 109.1 C7---C8---H8B 108.5 C2---C1---H1E 109.1 H8A---C8---H8B 107.5 H1D---C1---H1E 107.8 C8---C9---C10 115.0 (3) C1---C2---C3 112.3 (3) C8---C9---H9A 108.5 C1---C2---H2A 109.1 C10---C9---H9A 108.5 C3---C2---H2A 109.1 C8---C9---H9B 108.5 C1---C2---H2B 109.1 C10---C9---H9B 108.5 C3---C2---H2B 109.1 H9A---C9---H9B 107.5 H2A---C2---H2B 107.9 C11---C10---C9 115.1 (3) C2---C3---C4 113.5 (3) C11---C10---H10A 108.5 C2---C3---H3A 108.9 C9---C10---H10A 108.5 C4---C3---H3A 108.9 C11---C10---H10B 108.5 C2---C3---H3B 108.9 C9---C10---H10B 108.5 C4---C3---H3B 108.9 H10A---C10---H10B 107.5 H3A---C3---H3B 107.7 C12---C11---C10 115.1 (3) C3---C4---C5 114.5 (3) C12---C11---H11A 108.5 C3---C4---H4A 108.6 C10---C11---H11A 108.5 C5---C4---H4A 108.6 C12---C11---H11B 108.5 C3---C4---H4B 108.6 C10---C11---H11B 108.5 C5---C4---H4B 108.6 H11A---C11---H11B 107.5 H4A---C4---H4B 107.6 C11---C12---C13 115.0 (3) C6---C5---C4 114.5 (3) C11---C12---H12A 108.5 C6---C5---H5A 108.6 C13---C12---H12A 108.5 C4---C5---H5A 108.6 C11---C12---H12B 108.5 C6---C5---H5B 108.6 C13---C12---H12B 108.5 C4---C5---H5B 108.6 H12A---C12---H12B 107.5 H5A---C5---H5B 107.6 C12---C13---H13A 109.5 C7---C6---C5 114.8 (3) C12---C13---H13B 109.5 C7---C6---H6A 108.6 H13A---C13---H13B 109.5 C5---C6---H6A 108.6 C12---C13---H13C 109.5 C7---C6---H6B 108.6 H13A---C13---H13C 109.5 C5---C6---H6B 108.6 H13B---C13---H13C 109.5 H6A---C6---H6B 107.6 N1---C1---C2---C3 180.0 (3) C6---C7---C8---C9 179.6 (3) C1---C2---C3---C4 169.9 (3) C7---C8---C9---C10 −179.8 (3) C2---C3---C4---C5 −179.1 (3) C8---C9---C10---C11 179.7 (3) C3---C4---C5---C6 177.6 (3) C9---C10---C11---C12 −179.7 (3) C4---C5---C6---C7 −179.5 (3) C10---C11---C12---C13 179.8 (3) C5---C6---C7---C8 179.2 (3) ------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2308 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···Cl1 0.89 2.44 3.303 (3) 162 N1---H1B···Cl1^i^ 0.89 2.36 3.236 (2) 170 N1---H1C···O1^ii^ 0.89 2.05 2.901 (4) 159 O1---H1H···Cl1 0.85 2.45 3.290 (3) 170 O1---H1I···Cl1^iii^ 0.85 2.39 3.228 (2) 170 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x−1, −y+3/2, z−1/2; (ii) x, y, z−1; (iii) x−1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- N1---H1A⋯Cl1 0.89 2.44 3.303 (3) 162 N1---H1B⋯Cl1^i^ 0.89 2.36 3.236 (2) 170 N1---H1C⋯O1^ii^ 0.89 2.05 2.901 (4) 159 O1---H1H⋯Cl1 0.85 2.45 3.290 (3) 170 O1---H1I⋯Cl1^iii^ 0.85 2.39 3.228 (2) 170 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.465859	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052102/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o717", "authors": [ { "first": "Lijun", "last": "Zhang" }, { "first": "Youying", "last": "Di" }, { "first": "Wenyan", "last": "Dan" } ] }
PMC3052103	Related literature {#sec1} ================== For pyrazole derivatives and their microbial activity, see: Ragavan et al. (2009[@bb4], 2010[@bb5]). For related structures, see: Shahani et al. (2009[@bb6], 2010a [@bb7],b [@bb8],c [@bb9]). For bond-length data, see: Allen et al. (1987[@bb1]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~11~H~12~N~2~OSM ~r~ = 220.30Orthorhombic,a = 10.9479 (2) Åb = 11.3470 (3) Åc = 17.7392 (4) ÅV = 2203.67 (9) Å^3^Z = 8Mo Kα radiationμ = 0.27 mm^−1^T = 100 K0.33 × 0.13 × 0.11 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2009[@bb2]) T ~min~ = 0.917, T ~max~ = 0.97112209 measured reflections3027 independent reflections2406 reflections with I \> 2σ(I)R ~int~ = 0.041 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.039wR(F ^2^) = 0.104S = 1.043027 reflections142 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.31 e Å^−3^ {#d5e452} Data collection: APEX2 (Bruker, 2009[@bb2]); cell refinement: SAINT (Bruker, 2009[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb10]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004922/is2676sup1.cif](http://dx.doi.org/10.1107/S1600536811004922/is2676sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004922/is2676Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004922/is2676Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2676&file=is2676sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2676sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2676&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2676](http://scripts.iucr.org/cgi-bin/sendsup?is2676)). HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSH also thanks USM for the award of a research fellowship. Comment ======= Antibacterial and antifungal activities of the azoles are most widely studied and some of them are in clinical practice as anti-microbial agents. However, the azole-resistant strain had led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have the broad spectrum of biological properties, such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling, and antiviral activities. Pyrazole derivatives also act as antiangiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity, and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan et al., 2009, 2010). The structure of the title compound is presented here. In the title compound, (Fig. 1), the 1H-pyrazol ring (C7--C9/N1/N2) \[maximum deviation of 0.00117 (14) Å\] makes a dihedral angle of 85.40 (8)° with the phenyl ring (C1--C6). The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to those closely related structures (Shahani et al., 2009, 2010a,b,c). In the crystal packing (Fig. 2), pairs of intermolecular N1---H1N1···O1 and C3---H3A···O1 hydrogen bonds (Table 1) link the molecules into two-dimensional networks parallel to the bc plane. Experimental {#experimental} ============ The compound has been synthesized using the method available in the literature (Ragavan et al., 2009) and recrystallized using the ethanol-chloroform 1:1 mixture (yield 60%, m.p. 444 K). Refinement {#refinement} ========== The H atoms bound to C atoms were positioned geometrically (C---H = 0.93--0.96 Å) with U~iso~(H) =1.2 or 1.5U~eq~(C). The H atoms attached to the N atom was located from the difference map and refined freely, \[N---H = 0.94 (2) Å\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom numbering scheme. ::: ![](e-67-0o633-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal structure of the title compound viewed approximately along the b axis. Intermolecular interactions are shown in dashed lines. Hydrogen bond not involved in intermolecular interactions are omitted for clarity. ::: ![](e-67-0o633-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------- --------------------------------------- C~11~H~12~N~2~OS F(000) = 928 M~r~ = 220.30 D~x~ = 1.328 Mg m^−3^ Orthorhombic, Pbca Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ac 2ab Cell parameters from 2873 reflections a = 10.9479 (2) Å θ = 2.8--29.1° b = 11.3470 (3) Å µ = 0.27 mm^−1^ c = 17.7392 (4) Å T = 100 K V = 2203.67 (9) Å^3^ Block, colourless Z = 8 0.33 × 0.13 × 0.11 mm ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e265 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 3027 independent reflections Radiation source: fine-focus sealed tube 2406 reflections with I \> 2σ(I) graphite R~int~ = 0.041 φ and ω scans θ~max~ = 29.4°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Bruker, 2009) h = −11→15 T~min~ = 0.917, T~max~ = 0.971 k = −15→15 12209 measured reflections l = −16→24 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e382 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.039 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.104 H atoms treated by a mixture of independent and constrained refinement S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0481P)^2^ + 0.8061P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3027 reflections (Δ/σ)~max~ \< 0.001 142 parameters Δρ~max~ = 0.33 e Å^−3^ 0 restraints Δρ~min~ = −0.31 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e539 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e644 .table-wrap} ------ -------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ S1 0.09449 (3) 0.31932 (3) 0.09298 (2) 0.01802 (11) O1 0.32686 (10) 0.34450 (8) −0.02532 (6) 0.0207 (2) N1 0.20240 (12) 0.61926 (10) 0.00845 (8) 0.0202 (3) N2 0.28173 (12) 0.54374 (10) −0.02791 (7) 0.0192 (3) C1 0.28747 (15) 0.36136 (13) 0.19278 (9) 0.0225 (3) H1A 0.3057 0.4285 0.1649 0.027\ C2 0.35663 (15) 0.33304 (13) 0.25590 (9) 0.0254 (3) H2A 0.4211 0.3816 0.2700 0.031\* C3 0.33066 (15) 0.23327 (14) 0.29808 (9) 0.0236 (3) H3A 0.3766 0.2154 0.3407 0.028\* C4 0.23531 (15) 0.16043 (13) 0.27606 (9) 0.0243 (3) H4A 0.2180 0.0929 0.3037 0.029\* C5 0.16551 (14) 0.18758 (13) 0.21304 (9) 0.0212 (3) H5A 0.1019 0.1382 0.1986 0.025\* C6 0.19092 (13) 0.28904 (12) 0.17148 (8) 0.0173 (3) C7 0.16428 (13) 0.43840 (11) 0.04922 (8) 0.0166 (3) C8 0.26321 (13) 0.43076 (11) −0.00304 (8) 0.0164 (3) C9 0.13144 (14) 0.55679 (12) 0.05474 (8) 0.0178 (3) C10 0.38173 (15) 0.58669 (13) −0.07387 (10) 0.0239 (3) H10A 0.4171 0.5222 −0.1013 0.036\* H10B 0.4427 0.6217 −0.0420 0.036\* H10C 0.3517 0.6446 −0.1087 0.036\* C11 0.03683 (15) 0.61354 (14) 0.10271 (9) 0.0248 (3) H11A 0.0198 0.6912 0.0839 0.037\* H11B 0.0661 0.6189 0.1536 0.037\* H11C −0.0365 0.5672 0.1016 0.037\* H1N1 0.1983 (19) 0.700 (2) −0.0036 (13) 0.047 (6)\* ------ -------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1024 .table-wrap} ----- -------------- -------------- ------------ --------------- --------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ S1 0.01876 (19) 0.01847 (18) 0.0168 (2) −0.00372 (13) −0.00109 (13) 0.00267 (13) O1 0.0267 (6) 0.0139 (4) 0.0215 (6) 0.0008 (4) 0.0046 (4) 0.0000 (4) N1 0.0264 (7) 0.0129 (5) 0.0212 (7) 0.0017 (5) −0.0005 (5) −0.0006 (5) N2 0.0240 (6) 0.0131 (5) 0.0206 (7) −0.0002 (5) 0.0034 (5) 0.0007 (5) C1 0.0273 (8) 0.0198 (7) 0.0204 (8) −0.0046 (6) −0.0027 (6) 0.0034 (6) C2 0.0285 (8) 0.0257 (7) 0.0221 (9) −0.0037 (6) −0.0065 (7) −0.0002 (6) C3 0.0255 (8) 0.0298 (8) 0.0155 (8) 0.0053 (6) −0.0012 (6) 0.0006 (6) C4 0.0247 (8) 0.0260 (7) 0.0222 (8) 0.0015 (6) 0.0032 (6) 0.0082 (6) C5 0.0197 (7) 0.0213 (7) 0.0225 (8) −0.0015 (6) 0.0013 (6) 0.0043 (6) C6 0.0196 (7) 0.0188 (6) 0.0134 (7) 0.0007 (5) 0.0019 (5) 0.0003 (5) C7 0.0193 (7) 0.0148 (6) 0.0156 (7) −0.0014 (5) −0.0003 (5) 0.0005 (5) C8 0.0224 (7) 0.0127 (6) 0.0141 (7) −0.0017 (5) −0.0018 (6) 0.0001 (5) C9 0.0207 (7) 0.0179 (6) 0.0149 (7) 0.0009 (5) −0.0035 (6) −0.0002 (5) C10 0.0283 (8) 0.0184 (7) 0.0250 (8) −0.0043 (6) 0.0050 (7) 0.0032 (6) C11 0.0248 (8) 0.0250 (7) 0.0245 (9) 0.0071 (6) −0.0008 (6) −0.0021 (6) ----- -------------- -------------- ------------ --------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1337 .table-wrap} -------------------- -------------- -------------------- -------------- S1---C7 1.7356 (14) C3---H3A 0.9300 S1---C6 1.7809 (15) C4---C5 1.389 (2) O1---C8 1.2648 (17) C4---H4A 0.9300 N1---C9 1.3343 (19) C5---C6 1.395 (2) N1---N2 1.3801 (17) C5---H5A 0.9300 N1---H1N1 0.94 (2) C7---C9 1.3942 (19) N2---C8 1.3708 (17) C7---C8 1.428 (2) N2---C10 1.4494 (19) C9---C11 1.487 (2) C1---C2 1.389 (2) C10---H10A 0.9600 C1---C6 1.391 (2) C10---H10B 0.9600 C1---H1A 0.9300 C10---H10C 0.9600 C2---C3 1.387 (2) C11---H11A 0.9600 C2---H2A 0.9300 C11---H11B 0.9600 C3---C4 1.388 (2) C11---H11C 0.9600 C7---S1---C6 103.83 (7) C1---C6---S1 123.32 (11) C9---N1---N2 108.92 (11) C5---C6---S1 117.02 (11) C9---N1---H1N1 129.0 (13) C9---C7---C8 107.44 (12) N2---N1---H1N1 121.9 (13) C9---C7---S1 127.24 (12) C8---N2---N1 109.70 (12) C8---C7---S1 125.24 (10) C8---N2---C10 127.39 (13) O1---C8---N2 122.79 (13) N1---N2---C10 121.97 (11) O1---C8---C7 131.88 (13) C2---C1---C6 119.79 (14) N2---C8---C7 105.33 (12) C2---C1---H1A 120.1 N1---C9---C7 108.57 (13) C6---C1---H1A 120.1 N1---C9---C11 121.85 (13) C3---C2---C1 120.80 (15) C7---C9---C11 129.57 (14) C3---C2---H2A 119.6 N2---C10---H10A 109.5 C1---C2---H2A 119.6 N2---C10---H10B 109.5 C2---C3---C4 119.26 (15) H10A---C10---H10B 109.5 C2---C3---H3A 120.4 N2---C10---H10C 109.5 C4---C3---H3A 120.4 H10A---C10---H10C 109.5 C3---C4---C5 120.56 (14) H10B---C10---H10C 109.5 C3---C4---H4A 119.7 C9---C11---H11A 109.5 C5---C4---H4A 119.7 C9---C11---H11B 109.5 C4---C5---C6 119.92 (14) H11A---C11---H11B 109.5 C4---C5---H5A 120.0 C9---C11---H11C 109.5 C6---C5---H5A 120.0 H11A---C11---H11C 109.5 C1---C6---C5 119.66 (14) H11B---C11---H11C 109.5 C9---N1---N2---C8 −1.48 (17) N1---N2---C8---O1 −177.46 (13) C9---N1---N2---C10 −171.15 (14) C10---N2---C8---O1 −8.5 (2) C6---C1---C2---C3 0.0 (2) N1---N2---C8---C7 2.10 (16) C1---C2---C3---C4 0.9 (2) C10---N2---C8---C7 171.06 (14) C2---C3---C4---C5 −0.8 (2) C9---C7---C8---O1 177.55 (16) C3---C4---C5---C6 −0.2 (2) S1---C7---C8---O1 −5.6 (2) C2---C1---C6---C5 −1.0 (2) C9---C7---C8---N2 −1.96 (16) C2---C1---C6---S1 178.43 (12) S1---C7---C8---N2 174.91 (11) C4---C5---C6---C1 1.1 (2) N2---N1---C9---C7 0.18 (17) C4---C5---C6---S1 −178.38 (12) N2---N1---C9---C11 179.36 (13) C7---S1---C6---C1 7.87 (15) C8---C7---C9---N1 1.12 (17) C7---S1---C6---C5 −172.70 (12) S1---C7---C9---N1 −175.67 (11) C6---S1---C7---C9 −100.38 (14) C8---C7---C9---C11 −177.97 (15) C6---S1---C7---C8 83.36 (14) S1---C7---C9---C11 5.2 (2) -------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1854 .table-wrap} ------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1N1···O1^i^ 0.94 (2) 1.71 (2) 2.6446 (16) 173 (2) C3---H3A···O1^ii^ 0.93 2.53 3.2549 (19) 135 ------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −x+1/2, y+1/2, z; (ii) x, −y+1/2, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- ---------- ---------- ------------- ------------- N1---H1N1⋯O1^i^ 0.94 (2) 1.71 (2) 2.6446 (16) 173 (2) C3---H3A⋯O1^ii^ 0.93 2.53 3.2549 (19) 135 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.	PubMed Central	2024-06-05T04:04:18.473048	2011-2-16	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052103/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o633", "authors": [ { "first": "Tara", "last": "Shahani" }, { "first": "Hoong-Kun", "last": "Fun" }, { "first": "R. Venkat", "last": "Ragavan" }, { "first": "V.", "last": "Vijayakumar" }, { "first": "S.", "last": "Sarveswari" } ] }
PMC3052104	Related literature {#sec1} ================== Kumagai et al. (2002[@bb7]) describe different coordinations for carboxylate groups. For background information about the title compound and its metal complexes, see: Viola-Villegas & Doyle (2009[@bb11]). For macrocycle configurations, see: Bosnich et al. (1965[@bb1]); Dale (1973[@bb4], 1976[@bb5], 1980[@bb6]); Meyer et al. (1998[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~28~N~4~O~8~·2H~2~OM ~r~ = 440.46Orthorhombic,a = 17.183 (2) Åb = 6.5826 (9) Åc = 17.983 (2) ÅV = 2034.0 (5) Å^3^Z = 4Mo Kα radiationμ = 0.12 mm^−1^T = 100 K0.43 × 0.27 × 0.27 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker 2003[@bb3]) T ~min~ = 0.810, T ~max~ = 1.00019408 measured reflections2520 independent reflections2236 reflections with I \> 2σ(I)R ~int~ = 0.037 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.042wR(F ^2^) = 0.112S = 1.082520 reflections144 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.70 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e478} Data collection: SMART (Bruker, 2001[@bb2]); cell refinement: SAINT-Plus (Bruker, 2001[@bb2]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb9]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb9]); software used to prepare material for publication: SHELXL97 and PLATON Spek (2009)[@bb10]. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004843/kp2290sup1.cif](http://dx.doi.org/10.1107/S1600536811004843/kp2290sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004843/kp2290Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004843/kp2290Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?kp2290&file=kp2290sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?kp2290sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?kp2290&checkcif=yes) Enhanced figure: [interactive version of Fig. 3](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=fignum&cnor=kp2290&fignum=3) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [KP2290](http://scripts.iucr.org/cgi-bin/sendsup?kp2290)). MZ was supported by NSF grant 0111511. The diffractometer was funded by NSF grant 0087210, by the Ohio Board of Regents grant CAP-491 and by Youngstown State University. Comment ======= In the course of our studies to prepare coordination polymer and metal-organic framework type compounds we investigated the title compound as a potentional building block. The molecule 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid DOTAH~4~ and its deprotonated analogs, \[DOTAH~2~\]^2-^ and \[DOTA\]^4-^ have several features desirable in coordination chemistry. The ligand offers a macrocycle with four neutral nitrogen donor sites as well as four dangling carboxylic acid groups. Carboxylate groups when deprotonated have been shown to exhibit nine different coordination modes with metal ions, seven of which coordinate two or more metal ions (Kumagai et al., 2002). Therefore, the potential for forming molecular species as well as coordination polymers or metal-organic framework type compounds exists for this organic building block. For numerous examples of metal containing DOTAH~4~ compounds and its charged analogues see Viola-Villegas & Doyle (2009). Only half of DOTAH~4~ molecule (Fig. 1) in the structure is an asymmetric unit. The other half of the macrocycle is generated by a twofold rotation axis parallel to the b axis. There is no significant ring strain based on an analysis of the bond angles withing the ring. The ring is composed of eight methylene carbons (C1---C4, C1^i^---C4^i^), two ammonium N atoms (N1, N1^i^) and two tertiary N atoms (N2, N2^i^) (symmetry operator (i): -x + 1, y, -z + 3/2). The bond angles between them range from 110--112°. The configuration has all four N atoms located above the eight methylene carbons along the direction of the twofold axis in the centre of the ring producing a basket-like shape that would be able to coordinate a metal without large changes of the overall structure of the molecule. According to the system outlined by Dale this arrangement would be described as (3,3,3,3)-B (Dale, 1973, 1976, 1980, Meyer et al., 1998). This system uses numbers to indicate the number of chemical bonds between the genuinie corners in the macrocycle. Genuine corners are the central atoms in an anti-gauche-gauche-anti bond sequence. In the title compound the atoms C1, C3, C1A, and C3A constitute genuine corners which are separated from each other along the macrocycle by three bonds. The \"B\" designation indicates that the four heteroatoms in this 12-membered macrocylce reside in a square planar arrangement above the methylene carbons (as described above). Using the terminology of Bosnich et al. (1965) the configuration of the macrocycle would be cis-I since all of the carboxylate containing groups project in the same direction. The weighted average ring bond distance is 1.503 Å (PLATON, Spek (2009)). The weighted average absolute torsion angle is 100.45°. The total puckering amplitude of the ring is 1.526 Å. The four carboxylic acid and carboxylate groups are bound to the N atoms and also all reside above the macrocycle. This arrangement leads to well separated hydrophobic and hydrophilic parts within the molecule. The H atoms bound to the N atoms within the macrocyle are engaged in two equivalent hydrogen bonds with the adjacent nitrogen atoms (N1---H1···N2, N1^i^---H1^i^···N2^i^, Table 1). The N1---H1 and H1···N2 distances are 0.93 Å and 2.44 Å respectively. The angle between the donor and acceptor is 110.1° in accord with the donor and acceptor both residing within the ring and being separated by two atoms. The crystal packing (Figs. 2 and 3) is dominated by hydrogen bonding between the crystal water molecules and the carboxylic acid and carboxylate groups. Each water molecule forms three hydrogen bonding interactions with the two hydrogen atoms oriented towards carboxylate groups (O5---H5D···O1^ii^, O5---H5C···O1^iii^, Table 1) and the oxygen directed towards a carboxylic acid group (O3---H3···O5, Table 1). Experimental {#experimental} ============ The title compound 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid was purchased from Strem Chemicals and used without further purification. The compound was crystallized from a saturated DMSO solution. A DMSO solution (2 mL) was saturated with DOTAH~4~ at 323 K. Upon cooling to room temperature and sitting for four days colourless block shaped crystals were formed. Refinement {#refinement} ========== The oxygen to hydrogen bond distances in the solvent water molecule were restrained to be 0.84 Å with a standard deviation of 0.02 Å. They were set to have an isotropic displacement parameter of 1.5 times that of the adjacent oxygen atom. The same displacement parameter was used for the hydrogen bound to the carboxylic acid, which were placed in calculated positions at a distance of 0.84 Å from the O atom but that were allowed to freely rotate at a fixed angle around the C---O bond to best fit the experimental electron density. All other hydrogen atoms in the structure were placed in calculated positions with X---H distances of 0.99 (methylene) or 0.93 Å (amine) with U~iso~(H) = 1.2 U~eq~(X). The highest residual electron density peak in the final Fourier map, with a heigth of 0.70 e^-^×Å^-3^, is located at the center of the macrocylce. An electron density difference Fourier map cutting through the protonated amine N atoms and the center of the residual electron density in the middle of the ring (with the protic amine H atoms removed prior to generation of the map) shows electron densities in the positions of the amine H atoms that are substantially larger than that of the residual electron density in the center of the ring, thus indicating that the amine H atoms are indeed fully protonated (which is supported by a refinement of the amine H atom occupancy, which yielded full occupancy). The residual density in the center of the ring refines to about 60% of one electron and it is located on a special position (site symmetry of 4c). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the title compound \[DOTAH4\] and water molecule (hydrogen atoms bound to carbon atoms are omitted for clarity). Dispalacement ellipsoids are shown at the 50% probability level. The two fold rotation axis that generates the symmetry related half of the molecule has a site symmetry of 4c. ::: ![](e-67-0o644-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A packing diagram of \[DOTAH4\] as viewed along the c axis. ::: ![](e-67-0o644-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Enhanced figure view of the packing of the title compound along the b axis. ::: ![](e-67-0o644-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e230 .table-wrap} --------------------------- ---------------------------------------- C~16~H~28~N~4~O~8~·2H~2~O D~x~ = 1.438 Mg m^−3^ M~r~ = 440.46 Mo Kα radiation, λ = 0.71073 Å Orthorhombic, Pbcn Cell parameters from 13988 reflections a = 17.183 (2) Å θ = 1.0--28.3° b = 6.5826 (9) Å µ = 0.12 mm^−1^ c = 17.983 (2) Å T = 100 K V = 2034.0 (5) Å^3^ Block, colourless Z = 4 0.43 × 0.27 × 0.27 mm F(000) = 944 --------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e357 .table-wrap} ----------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD diffractometer 2520 independent reflections Radiation source: fine-focus sealed tube 2236 reflections with I \> 2σ(I) graphite R~int~ = 0.037 ω scans θ~max~ = 28.3°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Bruker 2003) h = −22→22 T~min~ = 0.810, T~max~ = 1.000 k = −8→8 19408 measured reflections l = −23→23 ----------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e471 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.042 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.112 H atoms treated by a mixture of independent and constrained refinement S = 1.08 w = 1/\[σ^2^(F~o~^2^) + (0.0616P)^2^ + 0.8651P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2520 reflections (Δ/σ)~max~ = 0.003 144 parameters Δρ~max~ = 0.70 e Å^−3^ 2 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e628 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e727 .table-wrap} ----- ------------- -------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.52319 (7) 0.29809 (18) 0.59684 (7) 0.0172 (2) H1A 0.5484 0.1817 0.5716 0.021\ H1B 0.5118 0.4028 0.5588 0.021\* C2 0.44727 (7) 0.22770 (18) 0.63205 (7) 0.0169 (2) H2A 0.4101 0.1899 0.5923 0.020\* H2B 0.4573 0.1052 0.6625 0.020\* C3 0.35164 (7) 0.29561 (18) 0.72810 (7) 0.0161 (2) H3A 0.3257 0.1827 0.7015 0.019\* H3B 0.3118 0.3994 0.7398 0.019\* C4 0.61331 (7) 0.21651 (18) 0.70032 (7) 0.0165 (2) H4A 0.6542 0.1467 0.6711 0.020\* H4B 0.5724 0.1157 0.7123 0.020\* C5 0.64046 (7) 0.50850 (18) 0.61660 (7) 0.0175 (2) H5A 0.6619 0.4297 0.5744 0.021\* H5B 0.6833 0.5319 0.6524 0.021\* C6 0.61183 (7) 0.71385 (19) 0.58773 (7) 0.0190 (3) C7 0.37872 (7) 0.54695 (18) 0.63298 (7) 0.0167 (2) H7A 0.3332 0.4922 0.6058 0.020\* H7B 0.4178 0.5900 0.5957 0.020\* C8 0.35349 (7) 0.73022 (18) 0.67787 (7) 0.0187 (3) N1 0.57832 (6) 0.38475 (15) 0.65388 (5) 0.0147 (2) H1 0.5502 0.4699 0.6852 0.018\* N2 0.41201 (5) 0.38638 (15) 0.67930 (6) 0.0156 (2) O1 0.66535 (6) 0.81050 (15) 0.55408 (6) 0.0293 (2) O2 0.54404 (5) 0.76758 (14) 0.59796 (6) 0.0248 (2) O3 0.31304 (5) 0.86834 (13) 0.64068 (5) 0.0201 (2) H3 0.3110 0.8356 0.5956 0.030\* O4 0.36798 (7) 0.75428 (15) 0.74325 (5) 0.0286 (2) O5 0.29964 (6) 0.82984 (15) 0.50131 (5) 0.0218 (2) H5C 0.2571 (9) 0.800 (3) 0.4810 (9) 0.033\* H5D 0.3139 (11) 0.942 (2) 0.4806 (10) 0.033\* ----- ------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1137 .table-wrap} ---- ------------ ------------ ------------ ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0153 (5) 0.0185 (5) 0.0176 (5) −0.0004 (4) −0.0003 (4) −0.0007 (4) C2 0.0144 (5) 0.0160 (5) 0.0204 (6) −0.0006 (4) −0.0001 (4) −0.0015 (4) C3 0.0124 (5) 0.0153 (5) 0.0205 (6) −0.0014 (4) −0.0004 (4) −0.0014 (4) C4 0.0159 (5) 0.0127 (5) 0.0209 (6) 0.0024 (4) −0.0001 (4) 0.0018 (4) C5 0.0141 (5) 0.0164 (5) 0.0219 (6) −0.0006 (4) 0.0033 (4) 0.0026 (4) C6 0.0210 (6) 0.0160 (5) 0.0201 (6) −0.0001 (4) −0.0001 (4) 0.0014 (4) C7 0.0148 (5) 0.0157 (5) 0.0195 (5) 0.0005 (4) −0.0017 (4) 0.0005 (4) C8 0.0183 (6) 0.0143 (5) 0.0236 (6) −0.0037 (4) 0.0004 (4) 0.0004 (4) N1 0.0132 (4) 0.0137 (5) 0.0173 (5) 0.0007 (3) 0.0010 (3) 0.0008 (4) N2 0.0127 (4) 0.0142 (5) 0.0198 (5) 0.0004 (3) 0.0003 (4) 0.0010 (4) O1 0.0287 (5) 0.0212 (5) 0.0381 (6) 0.0002 (4) 0.0111 (4) 0.0102 (4) O2 0.0187 (5) 0.0196 (4) 0.0361 (5) 0.0025 (4) −0.0007 (4) 0.0035 (4) O3 0.0218 (4) 0.0158 (4) 0.0227 (4) 0.0021 (3) 0.0013 (3) −0.0007 (3) O4 0.0445 (6) 0.0186 (5) 0.0227 (5) −0.0021 (4) −0.0053 (4) −0.0026 (4) O5 0.0234 (5) 0.0173 (4) 0.0246 (5) 0.0009 (4) −0.0023 (4) 0.0023 (3) ---- ------------ ------------ ------------ ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1450 .table-wrap} ------------------- -------------- ---------------------- -------------- C1---N1 1.5082 (15) C5---C6 1.5294 (17) C1---C2 1.5223 (16) C5---H5A 0.9900 C1---H1A 0.9900 C5---H5B 0.9900 C1---H1B 0.9900 C6---O2 1.2312 (16) C2---N2 1.4765 (15) C6---O1 1.2715 (16) C2---H2A 0.9900 C7---N2 1.4622 (15) C2---H2B 0.9900 C7---C8 1.5149 (17) C3---N2 1.4844 (15) C7---H7A 0.9900 C3---C4^i^ 1.5136 (16) C7---H7B 0.9900 C3---H3A 0.9900 C8---O4 1.2122 (16) C3---H3B 0.9900 C8---O3 1.3255 (15) C4---N1 1.5117 (15) N1---H1 0.9300 C4---C3^i^ 1.5136 (17) O3---H3 0.8400 C4---H4A 0.9900 O5---H5C 0.840 (15) C4---H4B 0.9900 O5---H5D 0.865 (15) C5---N1 1.5011 (15) N1---C1---C2 111.75 (10) N1---C5---H5B 108.8 N1---C1---H1A 109.3 C6---C5---H5B 108.8 C2---C1---H1A 109.3 H5A---C5---H5B 107.7 N1---C1---H1B 109.3 O2---C6---O1 127.71 (12) C2---C1---H1B 109.3 O2---C6---C5 120.50 (11) H1A---C1---H1B 107.9 O1---C6---C5 111.78 (11) N2---C2---C1 112.06 (10) N2---C7---C8 112.59 (10) N2---C2---H2A 109.2 N2---C7---H7A 109.1 C1---C2---H2A 109.2 C8---C7---H7A 109.1 N2---C2---H2B 109.2 N2---C7---H7B 109.1 C1---C2---H2B 109.2 C8---C7---H7B 109.1 H2A---C2---H2B 107.9 H7A---C7---H7B 107.8 N2---C3---C4^i^ 111.30 (9) O4---C8---O3 120.49 (12) N2---C3---H3A 109.4 O4---C8---C7 124.21 (12) C4^i^---C3---H3A 109.4 O3---C8---C7 115.30 (11) N2---C3---H3B 109.4 C5---N1---C1 110.39 (9) C4^i^---C3---H3B 109.4 C5---N1---C4 111.18 (9) H3A---C3---H3B 108.0 C1---N1---C4 110.39 (9) N1---C4---C3^i^ 112.09 (9) C5---N1---H1 108.3 N1---C4---H4A 109.2 C1---N1---H1 108.3 C3^i^---C4---H4A 109.2 C4---N1---H1 108.3 N1---C4---H4B 109.2 C7---N2---C2 110.13 (9) C3^i^---C4---H4B 109.2 C7---N2---C3 110.75 (9) H4A---C4---H4B 107.9 C2---N2---C3 110.02 (9) N1---C5---C6 113.73 (10) C8---O3---H3 109.5 N1---C5---H5A 108.8 H5C---O5---H5D 105.1 (18) C6---C5---H5A 108.8 N1---C1---C2---N2 51.11 (13) C3^i^---C4---N1---C5 74.84 (12) N1---C5---C6---O2 2.30 (17) C3^i^---C4---N1---C1 −162.30 (9) N1---C5---C6---O1 −177.48 (11) C8---C7---N2---C2 −170.60 (9) N2---C7---C8---O4 8.99 (17) C8---C7---N2---C3 67.48 (12) N2---C7---C8---O3 −170.88 (10) C1---C2---N2---C7 73.24 (12) C6---C5---N1---C1 73.84 (12) C1---C2---N2---C3 −164.40 (10) C6---C5---N1---C4 −163.30 (10) C4^i^---C3---N2---C7 −150.74 (10) C2---C1---N1---C5 −162.75 (9) C4^i^---C3---N2---C2 87.27 (11) C2---C1---N1---C4 73.93 (12) ------------------- -------------- ---------------------- -------------- ::: Symmetry codes: (i) −x+1, y, −z+3/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2003 .table-wrap} -------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A O3---H3···O5 0.84 1.71 2.5295 (14) 166 N1---H1···N2 0.93 2.44 2.8940 (14) 110 O5---H5D···O1^ii^ 0.86 (1) 1.78 (2) 2.6380 (14) 173.(2) O5---H5C···O1^iii^ 0.84 (1) 1.85 (2) 2.6776 (14) 170.(2) -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (ii) −x+1, −y+2, −z+1; (iii) x−1/2, −y+3/2, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- ---------- ---------- ------------- ------------- O3---H3⋯O5 0.84 1.71 2.5295 (14) 166 N1---H1⋯N2 0.93 2.44 2.8940 (14) 110 O5---H5D⋯O1^i^ 0.86 (1) 1.78 (2) 2.6380 (14) 173 (2) O5---H5C⋯O1^ii^ 0.84 (1) 1.85 (2) 2.6776 (14) 170 (2) Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.476815	2011-2-16	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052104/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o644", "authors": [ { "first": "Paul S.", "last": "Szalay" }, { "first": "Matthias", "last": "Zeller" }, { "first": "Allen D.", "last": "Hunter" } ] }
PMC3052105	Related literature {#sec1} ================== For the preparation of 1,2-dihydroquinoline, see: Dauphinee & Forrest (1978[@bb3]); Katritzky et al. (1996[@bb8]); Elmore et al. (2001[@bb4]); Lu & Malinakova (2004[@bb10]); Wang et al. (2009[@bb16]); Rezgui et al. (1999[@bb11]). For related structures, see: Yadav et al. (2007[@bb17]); Kamakshi & Reddy (2007[@bb7]); Kim et al. (2001[@bb9]); Sundèn et al. (2007[@bb14]); Waldmann et al. (2008[@bb15]). For ring puckering analysis, see: Cremer & Pople (1975[@bb2]). For graph-set theory, see: Bernstein et al. (1995[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~17~NO~5~M ~r~ = 303.31Monoclinic,a = 8.0222 (3) Åb = 18.2466 (9) Åc = 10.3478 (4) Åβ = 101.042 (3)°V = 1486.65 (11) Å^3^Z = 4Mo Kα radiationμ = 0.10 mm^−1^T = 296 K0.74 × 0.43 × 0.23 mm ### Data collection {#sec2.1.2} Stoe IPDS 2 diffractometerAbsorption correction: integration (X-RED32; Stoe & Cie, 2002[@bb13]) T ~min~ = 0.823, T ~max~ = 0.96814613 measured reflections3068 independent reflections2221 reflections with I \> 2σ(I)R ~int~ = 0.055 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.059wR(F ^2^) = 0.169S = 1.0714613 reflections205 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.43 e Å^−3^Δρ~min~ = −0.36 e Å^−3^ {#d5e528} Data collection: X-AREA (Stoe & Cie, 2002[@bb13]); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002[@bb13]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb12]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb12]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb5]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003564/si2329sup1.cif](http://dx.doi.org/10.1107/S1600536811003564/si2329sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003564/si2329Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003564/si2329Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2329&file=si2329sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2329sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2329&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2329](http://scripts.iucr.org/cgi-bin/sendsup?si2329)). The title product was synthesized at RWTH Aachen University. The authors thank Professor Magnus Rueping of RWTH Aachen University, Germany, for helpful discussions and acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund). Comment ======= Dihydroquinoline moiety is found in a wide variety of natural products and they have attracted a lot of attention from synthetic organic chemists (Kamakshi & Reddy, 2007). 1,2-Dihydroquinolines have received substantial attention due to their potential biological activities arising from their antioxidative properties as well as their usefulness as precursors of some other biologically active compounds (Kim et al., 2001). 1,2-Dihydroquinoline derivatives are known to exhibit a wide spectrum of biological activities such as antimalarial, antibacterial and anti-inflammatory behavior (Yadav et al., 2007). Asymmetric synthesis of 1,2-dihydroquinolin have been attracted in recent years (Wang et al., 2009; Rezgui et al., 1999). Sundèn and co-worker has reported asymmetric synthesis of 1,2-dihydroquinolines using Domino reactions between 2-aminobenzaldehyde and α,β-unsaturated aldehydes to give pharmaceutically valuable 1,2-dihydroquinolines in high enantioselectivity (Sundèn et al., 2007). 1,2-dihydroquinolines was used for several applications, such as synthesis of quinolines: (Dauphinee & Forrest, 1978; Lu & Malinakova, 2004), 1,2,3,4- tetrahydroquinolines: (Katritzky et al., 1996) and natural products: (Elmore et al., 2001). The molecule of the title compound contains dihydroquinoline, two methoxycarbonyl (O=C---O---CH~3~) and acetyl group (O=C---CH~3~). The two --CO~2~Me groups are antisymmetric with respect to atom C10 (Fig. 1). The six-membered N containing ring of the quinoline system displays a half-boat conformation with the puckering parameters of Q~T~=0.261 (2) Å, Φ=146.7 (6)° and Θ=112.7 (4) ° (Cremer & Pople, 1975) and the spiro carbon atom deviates 0.34 (2) Å from the plane (r.m.s. deviation 0.051 Å) defined by the N1 and C1, C6, C9, C10 atoms. The intramolecular N---H..O hydrogen bond generate S(6) ring motif (Bernstein et al., 1995) (Fig. 1, Table 1). The dihedral angle between the S(6) ring mean plane and the half-boat plane of five atoms is 3.39 (2)°. The crystal packing is stabilized by C10---H10···O3^i^ intermolecular hydrogen bonds linking the molecules into chains in a zigzag mode along \[0 0 1\] due to c-glide symmetry, and there are also two C---H···π interactions C14---H14c···Cg1^i^ and C8---H8b···Cg1^ii^ \[(i): x,1/2 - y,-1/2 + z; (ii):1 - x,1 - y,1 - z\] extending along the b axis (Fig. 2., Table 1.). Experimental {#experimental} ============ The title compound was synthesized after a method described by Waldmann et al., (2008). 2\'-aminoacetophenone (100 mg, 1 eq) was dissolved in acetonitrile (1.5 ml) in a screw-capped test tube and Bi(OTf)~3~ (5 mol %, 0.05 eq) was added to the mixture. This mixture were stirred at room temperature for 4 days until the starting material was completely consumed as monitored by TLC. The resultant residue was directly purified by flash chromatography on silica (EtOAc: Cyclohexane 2:98) gave 27% yield as a yellow solid. Recrystallized over pentan and ethyl acetate gave yellow crystalline solid. R~f~ 0.5 (2:1 Cyclohexane/EtOAc); m.p: (374--375 K). Refinement {#refinement} ========== The H atom of the NH group was located in a difference Fourier map and refined with the constraint N---H = 0.86 (2) Å. All other H atoms were positioned with idealized geometry using a riding model, \[C---H = 0.93--0.96Å and U~iso~ = 1.2U~eq~(C)\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### An ORTEP view of (I), with the atom-numbering scheme and 30% probability displacement ellipsoids. Dashed lines indicate H-bonds. ::: ![](e-67-0o544-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A packing diagram for (I), showing the C---H···O hydrogen bonds and C---H···π interactions. H atoms not involved in hydrogen bonding (dashed lines) have been omitted for clarity. \[Symmetry code; (i): x,1/2 - y,-1/2 + z; (ii): 1 - x,1 - y,1 - z\]. (Cg1 is the centroid of the C1---C6 ring). ::: ![](e-67-0o544-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e248 .table-wrap} ------------------------- ---------------------------------------- C~16~H~17~NO~5~ F(000) = 640 M~r~ = 303.31 D~x~ = 1.355 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 14613 reflections a = 8.0222 (3) Å θ = 2.0--28.0° b = 18.2466 (9) Å µ = 0.10 mm^−1^ c = 10.3478 (4) Å T = 296 K β = 101.042 (3)° Prism, brown V = 1486.65 (11) Å^3^ 0.74 × 0.43 × 0.23 mm Z = 4 ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e375 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Stoe IPDS 2 diffractometer 3068 independent reflections Radiation source: fine-focus sealed tube 2221 reflections with I \> 2σ(I) graphite R~int~ = 0.055 rotation method scans θ~max~ = 26.5°, θ~min~ = 2.2° Absorption correction: integration (X-RED32; Stoe & Cie, 2002) h = −10→10 T~min~ = 0.823, T~max~ = 0.968 k = −22→22 14613 measured reflections l = −12→12 ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.059 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.169 H atoms treated by a mixture of independent and constrained refinement S = 1.07 w = 1/\[σ^2^(F~o~^2^) + (0.0846P)^2^ + 0.2827P\] where P = (F~o~^2^ + 2F~c~^2^)/3 14613 reflections (Δ/σ)~max~ \< 0.001 205 parameters Δρ~max~ = 0.43 e Å^−3^ 1 restraint Δρ~min~ = −0.36 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ------ ------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.4104 (2) 0.37012 (12) 0.3615 (2) 0.0427 (5) C2 0.5203 (3) 0.39441 (12) 0.4782 (2) 0.0458 (5) C3 0.4559 (3) 0.39964 (14) 0.5939 (2) 0.0537 (6) H3 0.5267 0.4161 0.6702 0.064\ C4 0.2911 (3) 0.38117 (16) 0.5987 (2) 0.0582 (6) H4 0.2512 0.3853 0.6771 0.070\* C5 0.1846 (3) 0.35628 (15) 0.4853 (2) 0.0529 (6) H5 0.0732 0.3436 0.4887 0.064\* C6 0.2403 (2) 0.34998 (13) 0.3675 (2) 0.0436 (5) C7 0.6980 (3) 0.41517 (14) 0.4779 (2) 0.0507 (6) C8 0.8065 (3) 0.44802 (16) 0.5984 (3) 0.0618 (7) H8A 0.8402 0.4104 0.6630 0.074\* H8B 0.7431 0.4850 0.6341 0.074\* H8C 0.9058 0.4697 0.5751 0.074\* C9 0.1341 (2) 0.32351 (13) 0.2442 (2) 0.0454 (5) C10 0.1863 (3) 0.32944 (14) 0.1302 (2) 0.0491 (5) H10 0.1169 0.3113 0.0547 0.059\* C11 0.3514 (3) 0.36395 (13) 0.1178 (2) 0.0462 (5) C12 −0.0356 (3) 0.28883 (15) 0.2385 (2) 0.0521 (6) C13 −0.2120 (3) 0.21400 (18) 0.3394 (3) 0.0732 (8) H13A −0.2844 0.2489 0.3708 0.088\* H13B −0.1979 0.1719 0.3960 0.088\* H13C −0.2625 0.1993 0.2515 0.088\* C14 0.4362 (3) 0.32316 (16) 0.0183 (2) 0.0572 (6) H14A 0.5410 0.3470 0.0119 0.069\* H14B 0.3620 0.3234 −0.0663 0.069\* H14C 0.4588 0.2735 0.0469 0.069\* C15 0.3165 (3) 0.44329 (14) 0.0688 (2) 0.0496 (6) C16 0.1661 (4) 0.51590 (18) −0.1039 (3) 0.0788 (9) H16A 0.1176 0.5463 −0.0450 0.095\* H16B 0.0861 0.5102 −0.1851 0.095\* H16C 0.2678 0.5384 −0.1211 0.095\* N1 0.4639 (2) 0.36371 (12) 0.24524 (18) 0.0508 (5) O1 0.7624 (2) 0.40668 (13) 0.38037 (19) 0.0708 (6) O2 −0.1528 (2) 0.29932 (15) 0.1485 (2) 0.0906 (8) O3 −0.0469 (2) 0.24724 (11) 0.33918 (18) 0.0657 (5) O4 0.3796 (3) 0.49676 (12) 0.1243 (2) 0.0794 (6) O5 0.2062 (2) 0.44499 (10) −0.04465 (18) 0.0641 (5) H1 0.566 (2) 0.3785 (15) 0.248 (3) 0.065 (8)\* ------ ------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1276 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0390 (10) 0.0448 (12) 0.0419 (11) 0.0046 (9) 0.0017 (8) 0.0007 (9) C2 0.0438 (11) 0.0449 (12) 0.0450 (12) 0.0039 (9) −0.0014 (9) 0.0003 (10) C3 0.0524 (12) 0.0619 (16) 0.0425 (12) −0.0001 (11) −0.0015 (10) −0.0073 (11) C4 0.0540 (13) 0.0755 (18) 0.0454 (13) 0.0000 (12) 0.0099 (10) −0.0068 (12) C5 0.0463 (11) 0.0635 (15) 0.0486 (13) 0.0016 (10) 0.0081 (10) −0.0037 (11) C6 0.0397 (10) 0.0455 (12) 0.0431 (12) 0.0025 (8) 0.0018 (8) −0.0009 (9) C7 0.0441 (11) 0.0536 (14) 0.0507 (14) 0.0021 (10) −0.0005 (10) −0.0018 (11) C8 0.0503 (12) 0.0684 (17) 0.0611 (16) −0.0086 (11) −0.0031 (11) −0.0069 (13) C9 0.0392 (10) 0.0497 (13) 0.0446 (12) 0.0008 (9) 0.0013 (9) 0.0021 (10) C10 0.0422 (10) 0.0575 (14) 0.0440 (12) −0.0040 (10) −0.0007 (9) −0.0034 (10) C11 0.0407 (10) 0.0574 (14) 0.0391 (11) −0.0018 (9) 0.0041 (8) −0.0030 (10) C12 0.0461 (12) 0.0657 (16) 0.0424 (12) −0.0063 (10) 0.0027 (10) −0.0011 (11) C13 0.0639 (15) 0.086 (2) 0.0689 (18) −0.0292 (15) 0.0113 (13) 0.0083 (16) C14 0.0509 (12) 0.0676 (17) 0.0534 (15) 0.0019 (11) 0.0108 (10) −0.0106 (12) C15 0.0463 (11) 0.0599 (15) 0.0428 (12) −0.0056 (10) 0.0095 (9) −0.0046 (11) C16 0.0801 (19) 0.077 (2) 0.074 (2) 0.0029 (16) 0.0012 (15) 0.0221 (17) N1 0.0375 (9) 0.0726 (14) 0.0405 (10) −0.0042 (9) 0.0032 (8) −0.0029 (9) O1 0.0446 (9) 0.1052 (16) 0.0605 (11) −0.0100 (9) 0.0051 (8) −0.0129 (11) O2 0.0528 (10) 0.149 (2) 0.0624 (12) −0.0263 (11) −0.0078 (9) 0.0270 (13) O3 0.0573 (9) 0.0731 (13) 0.0615 (11) −0.0174 (8) −0.0020 (8) 0.0178 (10) O4 0.1003 (15) 0.0624 (12) 0.0673 (13) −0.0137 (11) −0.0043 (11) −0.0087 (10) O5 0.0648 (10) 0.0631 (12) 0.0566 (11) −0.0039 (8) −0.0079 (8) 0.0080 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1725 .table-wrap} --------------------- ------------- ---------------------- -------------- C1---N1 1.358 (3) C10---H10 0.9300 C1---C2 1.423 (3) C11---N1 1.448 (3) C1---C6 1.426 (3) C11---C14 1.531 (3) C2---C3 1.395 (3) C11---C15 1.542 (3) C2---C7 1.475 (3) C12---O2 1.205 (3) C3---C4 1.374 (3) C12---O3 1.306 (3) C3---H3 0.9300 C13---O3 1.457 (3) C4---C5 1.389 (3) C13---H13A 0.9600 C4---H4 0.9300 C13---H13B 0.9600 C5---C6 1.381 (3) C13---H13C 0.9600 C5---H5 0.9300 C14---H14A 0.9600 C6---C9 1.474 (3) C14---H14B 0.9600 C7---O1 1.229 (3) C14---H14C 0.9600 C7---C8 1.502 (3) C15---O4 1.195 (3) C8---H8A 0.9600 C15---O5 1.328 (3) C8---H8B 0.9600 C16---O5 1.442 (3) C8---H8C 0.9600 C16---H16A 0.9600 C9---C10 1.330 (3) C16---H16B 0.9600 C9---C12 1.492 (3) C16---H16C 0.9600 C10---C11 1.494 (3) N1---H1 0.858 (17) N1---C1---C2 121.97 (18) N1---C11---C14 109.33 (18) N1---C1---C6 118.91 (19) C10---C11---C14 111.6 (2) C2---C1---C6 119.11 (19) N1---C11---C15 110.15 (19) C3---C2---C1 118.56 (19) C10---C11---C15 108.43 (18) C3---C2---C7 120.1 (2) C14---C11---C15 108.15 (19) C1---C2---C7 121.3 (2) O2---C12---O3 123.1 (2) C4---C3---C2 122.1 (2) O2---C12---C9 122.3 (2) C4---C3---H3 118.9 O3---C12---C9 114.68 (19) C2---C3---H3 118.9 O3---C13---H13A 109.5 C3---C4---C5 119.3 (2) O3---C13---H13B 109.5 C3---C4---H4 120.3 H13A---C13---H13B 109.5 C5---C4---H4 120.3 O3---C13---H13C 109.5 C6---C5---C4 121.5 (2) H13A---C13---H13C 109.5 C6---C5---H5 119.3 H13B---C13---H13C 109.5 C4---C5---H5 119.3 C11---C14---H14A 109.5 C5---C6---C1 119.4 (2) C11---C14---H14B 109.5 C5---C6---C9 124.05 (19) H14A---C14---H14B 109.5 C1---C6---C9 116.55 (19) C11---C14---H14C 109.5 O1---C7---C2 121.9 (2) H14A---C14---H14C 109.5 O1---C7---C8 117.6 (2) H14B---C14---H14C 109.5 C2---C7---C8 120.5 (2) O4---C15---O5 123.7 (2) C7---C8---H8A 109.5 O4---C15---C11 125.1 (2) C7---C8---H8B 109.5 O5---C15---C11 111.1 (2) H8A---C8---H8B 109.5 O5---C16---H16A 109.5 C7---C8---H8C 109.5 O5---C16---H16B 109.5 H8A---C8---H8C 109.5 H16A---C16---H16B 109.5 H8B---C8---H8C 109.5 O5---C16---H16C 109.5 C10---C9---C6 120.85 (19) H16A---C16---H16C 109.5 C10---C9---C12 116.1 (2) H16B---C16---H16C 109.5 C6---C9---C12 123.04 (19) C1---N1---C11 124.00 (17) C9---C10---C11 123.1 (2) C1---N1---H1 114.2 (19) C9---C10---H10 118.5 C11---N1---H1 116.7 (19) C11---C10---H10 118.5 C12---O3---C13 116.44 (19) N1---C11---C10 109.17 (18) C15---O5---C16 117.0 (2) N1---C1---C2---C3 179.9 (2) C12---C9---C10---C11 178.9 (2) C6---C1---C2---C3 −1.8 (3) C9---C10---C11---N1 20.8 (3) N1---C1---C2---C7 1.1 (3) C9---C10---C11---C14 141.8 (2) C6---C1---C2---C7 179.3 (2) C9---C10---C11---C15 −99.2 (3) C1---C2---C3---C4 0.9 (4) C10---C9---C12---O2 −37.6 (4) C7---C2---C3---C4 179.8 (2) C6---C9---C12---O2 142.5 (3) C2---C3---C4---C5 0.2 (4) C10---C9---C12---O3 143.2 (2) C3---C4---C5---C6 −0.3 (4) C6---C9---C12---O3 −36.7 (3) C4---C5---C6---C1 −0.6 (4) N1---C11---C15---O4 3.5 (3) C4---C5---C6---C9 179.6 (2) C10---C11---C15---O4 122.9 (3) N1---C1---C6---C5 180.0 (2) C14---C11---C15---O4 −115.9 (3) C2---C1---C6---C5 1.7 (3) N1---C11---C15---O5 −176.59 (17) N1---C1---C6---C9 −0.2 (3) C10---C11---C15---O5 −57.2 (2) C2---C1---C6---C9 −178.5 (2) C14---C11---C15---O5 64.0 (2) C3---C2---C7---O1 175.0 (3) C2---C1---N1---C11 −158.1 (2) C1---C2---C7---O1 −6.1 (4) C6---C1---N1---C11 23.6 (3) C3---C2---C7---C8 −5.2 (4) C10---C11---N1---C1 −32.7 (3) C1---C2---C7---C8 173.6 (2) C14---C11---N1---C1 −155.0 (2) C5---C6---C9---C10 169.4 (2) C15---C11---N1---C1 86.3 (3) C1---C6---C9---C10 −10.4 (3) O2---C12---O3---C13 −0.9 (4) C5---C6---C9---C12 −10.7 (4) C9---C12---O3---C13 178.3 (2) C1---C6---C9---C12 169.5 (2) O4---C15---O5---C16 1.8 (4) C6---C9---C10---C11 −1.3 (4) C11---C15---O5---C16 −178.1 (2) --------------------- ------------- ---------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2493 .table-wrap} ----------------------------------------- Cg1 is the centroid of the C1--C6 ring. ----------------------------------------- ::: ::: {#d1e2497 .table-wrap} --------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1···O1 0.86 (2) 1.95 (2) 2.650 (2) 138 (2) C10---H10···O3^i^ 0.93 2.59 3.517 (3) 174 C14---H14C···Cg1^i^ 0.96 2.89 3.692 (3) 142 C8---H8B···Cg1^ii^ 0.96 2.85 3.501 (3) 126 --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 is the centroid of the C1--C6 ring. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ----------------------- ---------- ---------- ----------- ------------- N1---H1⋯O1 0.86 (2) 1.95 (2) 2.650 (2) 138 (2) C10---H10⋯O3^i^ 0.93 2.59 3.517 (3) 174 C14---H14C⋯Cg1^i^ 0.96 2.89 3.692 (3) 142 C8---H8B⋯Cg1^ii^ 0.96 2.85 3.501 (3) 126 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.480567	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052105/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o544-o545", "authors": [ { "first": "Zeynep", "last": "Keleşoğlu" }, { "first": "Zeynep", "last": "Gültekin" }, { "first": "Orhan", "last": "Büyükgüngör" } ] }
PMC3052106	Related literature {#sec1} ================== For related structures, see: Mikuriya et al. (1992[@bb4]); Li et al. (1997[@bb1]); Lu et al. (2006[@bb2]); Wang et al. (2008[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Mn(C~16~H~12~Br~2~N~2~O~2~)(N~3~)\]M ~r~ = 1042.13Monoclinic,a = 8.7068 (17) Åb = 15.269 (3) Åc = 13.684 (3) Åβ = 107.47 (3)°V = 1735.4 (6) Å^3^Z = 2Mo Kα radiationμ = 5.39 mm^−1^T = 153 K0.20 × 0.17 × 0.10 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (SORTAV; Blessing, 1995[@bb7]) T ~min~ = 0.352, T ~max~ = 0.5837747 measured reflections3961 independent reflections3093 reflections with I \> 2σ(I)R ~int~ = 0.015 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.030wR(F ^2^) = 0.074S = 1.043961 reflections235 parametersH-atom parameters constrainedΔρ~max~ = 0.82 e Å^−3^Δρ~min~ = −0.90 e Å^−3^ {#d5e370} Data collection: COLLECT (Nonius, 1998[@bb5]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[@bb6]); data reduction: DENZO (Otwinowski & Minor, 1997[@bb6]) and maXus (Mackay et al., 1998[@bb3]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb8]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004594/pk2299sup1.cif](http://dx.doi.org/10.1107/S1600536811004594/pk2299sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004594/pk2299Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004594/pk2299Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?pk2299&file=pk2299sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?pk2299sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?pk2299&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [PK2299](http://scripts.iucr.org/cgi-bin/sendsup?pk2299)). Comment ======= In the past decade there has been much interest in the magneto-chemistry of manganese because of its special magnetic properties. As is well known, manganese (III) Schiff base complexes display interesting structural, magnetic properties and electronic effects which rank it among the most appealing candidates as a building paramagnetic motif for multidimensional expanded structures. The variation of in-plane chelating and axial sites often leads to a change in the spin state of the metal ions: high-spin, low-spin or spin-crossover state. The nature and the tuning of magnetic interactions between metal centers are crucial points in the conception of molecular-based magnetic materials. The molecular structure of the title compound is shown in Figure 1. The Mn^III^ ion is involved in a distorted square-pyramidal arrangement by a N3O2 unit, in which the four basal sites are occupied by two N atoms and two O atoms from the Schiff base ligand, and the apical position is occupied by the N atom of an azido ligand. The bond distances are comparable to those found in related structures (Lu, et al., 2006; Mikuriya, et al., 1992; Li, et al., 1997; Wang, et al., 2008). The Mn^III^ ion lies above the basal plane formed by N2O2 unit by 0.228 (1) Å. The short intermolecular distance of Mn···O~phenolate~ 2.667 (2) Å indicates that there exists weak interaction between the two complexes related by inversion centers in the crystal (Figure 2). The phenyl groups of the Schiff base are involved in an offset face-to-face π-π inter-complexes stacking interaction (ring centroid separation Cg···Cg^i^, 3.598 (2) Å) \[symmetry code: 2 - x,1 - y,1 - z\]. Experimental {#experimental} ============ This compound was synthesized by mixing a solution of Schiff base (2,2\'-((1E,1\'E)-(ethane-1,2-diylbis(azanylylidene)) bis(methanylylidene))bis(4-bromophenol)) (0.5 mmol) in methanol (5 ml) with a solution of MnCl~2~.4H~2~O (0.5 mmol) in methanol (5 ml), followed by the dropwise addition of an aqueous solution NaN~3~(0.6 mmol, 2 mL) without stirring. The black mixture was allowed to stand for several days until good quality black block crystals of the compound were obtained in a yield of 68.3%. Refinement {#refinement} ========== All the H atoms bonded to the C atoms were placed using the HFIX commands in SHELXL97 (Sheldrick, 2008) with C---H distances of 0.93 and 0.97 Å, respectively, and were allowed for as riding atoms with U~iso~(H) = 1.2Ueq(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure (30% thermal probability ellipsoids) of the compound showing the atom numbering. ::: ![](e-67-0m322-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A pair of inversion-related molecules, showing the intermolecular weak interactions between Mn and Ophenolate atoms. The \'A\' molecule is related to the \'B\' molecule by \[A: (x, y, z) ---\> B: (2-x, 1-y, -z)\]. ::: ![](e-67-0m322-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e170 .table-wrap} --------------------------------------- ---------------------------------------- \[Mn(C~16~H~12~Br~2~N~2~O~2~)(N~3~)\] F(000) = 1016 M~r~ = 1042.13 D~x~ = 1.994 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 19417 reflections a = 8.7068 (17) Å θ = 3.4--27.5° b = 15.269 (3) Å µ = 5.39 mm^−1^ c = 13.684 (3) Å T = 153 K β = 107.47 (3)° Block, black V = 1735.4 (6) Å^3^ 0.20 × 0.17 × 0.10 mm Z = 2 --------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e308 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 3961 independent reflections Radiation source: fine-focus sealed tube 3093 reflections with I \> 2σ(I) graphite R~int~ = 0.015 ω scans θ~max~ = 27.5°, θ~min~ = 3.5° Absorption correction: multi-scan (SORTAV; Blessing, 1995) h = −11→11 T~min~ = 0.352, T~max~ = 0.583 k = −19→19 7747 measured reflections l = −17→17 -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e422 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.074 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0376P)^2^ + 0.8161P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3961 reflections (Δ/σ)~max~ = 0.001 235 parameters Δρ~max~ = 0.82 e Å^−3^ 0 restraints Δρ~min~ = −0.90 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e579 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Mn1 0.85052 (5) 0.50918 (2) 0.38001 (3) 0.02912 (10) Br1 1.11255 (4) 0.95137 (2) 0.37896 (3) 0.05433 (11) Br2 0.43251 (4) 0.106181 (19) 0.44904 (2) 0.04785 (10) C1 0.9787 (3) 0.67065 (17) 0.46365 (19) 0.0282 (5) C2 0.9438 (3) 0.74469 (17) 0.5129 (2) 0.0323 (6) H2 0.8919 0.7381 0.5627 0.039\ C3 0.9851 (3) 0.82750 (18) 0.4890 (2) 0.0358 (6) H3 0.9580 0.8764 0.5208 0.043\* C4 1.0675 (3) 0.83713 (17) 0.4168 (2) 0.0336 (6) C5 1.1113 (3) 0.76578 (18) 0.3710 (2) 0.0321 (6) H5 1.1715 0.7732 0.3258 0.039\* C6 1.0655 (3) 0.68135 (17) 0.39187 (19) 0.0279 (5) C7 1.1100 (3) 0.60754 (17) 0.33963 (19) 0.0307 (5) H7 1.1928 0.6147 0.3104 0.037\* C8 1.0902 (4) 0.45714 (18) 0.2823 (2) 0.0403 (7) H8A 1.1603 0.4191 0.3333 0.048\* H8B 1.1476 0.4763 0.2354 0.048\* C9 0.9380 (4) 0.4093 (2) 0.2250 (2) 0.0446 (7) H9A 0.8813 0.4411 0.1634 0.054\* H9B 0.9636 0.3512 0.2056 0.054\* C10 0.7619 (3) 0.33187 (17) 0.30160 (19) 0.0314 (5) H10 0.7730 0.2845 0.2615 0.038\* C11 0.6617 (3) 0.32053 (16) 0.36746 (19) 0.0274 (5) C12 0.6028 (3) 0.23581 (17) 0.37468 (19) 0.0309 (5) H12 0.6289 0.1898 0.3380 0.037\* C13 0.5066 (3) 0.22139 (16) 0.4361 (2) 0.0316 (6) C14 0.4649 (3) 0.28895 (18) 0.4908 (2) 0.0348 (6) H14 0.3986 0.2780 0.5315 0.042\* C15 0.5215 (3) 0.37191 (18) 0.4848 (2) 0.0344 (6) H15 0.4912 0.4173 0.5204 0.041\* C16 0.6248 (3) 0.38931 (16) 0.4256 (2) 0.0285 (5) N1 1.0407 (3) 0.53307 (14) 0.33190 (16) 0.0304 (5) N2 0.8372 (3) 0.40293 (14) 0.29446 (16) 0.0314 (5) N3 0.7109 (3) 0.60055 (17) 0.2717 (2) 0.0449 (6) N4 0.5810 (3) 0.62722 (17) 0.26329 (18) 0.0412 (6) N5 0.4533 (4) 0.6552 (3) 0.2518 (3) 0.0747 (10) O1 0.9342 (2) 0.59151 (11) 0.48779 (14) 0.0333 (4) O2 0.6852 (2) 0.46910 (12) 0.42930 (15) 0.0362 (4) ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1173 .table-wrap} ----- ------------- -------------- -------------- --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Mn1 0.0366 (2) 0.02311 (19) 0.0337 (2) −0.00517 (16) 0.01976 (18) −0.00327 (16) Br1 0.0655 (2) 0.02778 (16) 0.0791 (3) −0.00838 (14) 0.03595 (19) 0.00547 (15) Br2 0.0672 (2) 0.02952 (16) 0.05173 (19) −0.01626 (14) 0.02536 (16) −0.00135 (13) C1 0.0296 (12) 0.0273 (13) 0.0273 (12) −0.0038 (10) 0.0079 (11) 0.0013 (10) C2 0.0329 (13) 0.0305 (13) 0.0362 (14) −0.0032 (11) 0.0147 (12) −0.0028 (11) C3 0.0336 (14) 0.0287 (14) 0.0472 (16) −0.0010 (11) 0.0154 (13) −0.0036 (12) C4 0.0332 (14) 0.0243 (12) 0.0417 (15) −0.0062 (11) 0.0090 (12) 0.0028 (11) C5 0.0304 (13) 0.0330 (14) 0.0331 (14) −0.0066 (11) 0.0096 (11) 0.0033 (11) C6 0.0284 (12) 0.0273 (13) 0.0285 (13) −0.0026 (10) 0.0092 (11) 0.0025 (10) C7 0.0322 (13) 0.0331 (14) 0.0293 (13) −0.0012 (11) 0.0129 (11) 0.0040 (11) C8 0.0549 (18) 0.0305 (14) 0.0490 (17) 0.0016 (13) 0.0359 (15) −0.0012 (12) C9 0.070 (2) 0.0367 (16) 0.0416 (16) −0.0095 (14) 0.0383 (16) −0.0092 (13) C10 0.0389 (14) 0.0269 (13) 0.0282 (13) 0.0003 (11) 0.0101 (11) −0.0034 (10) C11 0.0288 (12) 0.0250 (13) 0.0282 (13) −0.0032 (10) 0.0080 (11) −0.0008 (10) C12 0.0363 (14) 0.0244 (13) 0.0305 (13) −0.0038 (11) 0.0076 (11) −0.0027 (10) C13 0.0355 (14) 0.0239 (13) 0.0327 (13) −0.0065 (10) 0.0061 (12) 0.0009 (10) C14 0.0326 (14) 0.0335 (14) 0.0417 (15) −0.0060 (11) 0.0162 (13) −0.0004 (12) C15 0.0349 (14) 0.0295 (14) 0.0438 (16) −0.0020 (11) 0.0194 (13) −0.0047 (12) C16 0.0290 (12) 0.0219 (12) 0.0357 (14) −0.0037 (10) 0.0112 (11) −0.0011 (10) N1 0.0386 (12) 0.0272 (11) 0.0309 (11) −0.0008 (9) 0.0189 (10) 0.0017 (9) N2 0.0432 (12) 0.0282 (11) 0.0283 (11) −0.0045 (10) 0.0190 (10) −0.0033 (9) N3 0.0442 (15) 0.0419 (15) 0.0490 (15) −0.0026 (12) 0.0146 (12) 0.0109 (12) N4 0.0473 (15) 0.0413 (14) 0.0349 (13) −0.0036 (12) 0.0121 (12) 0.0038 (11) N5 0.061 (2) 0.105 (3) 0.060 (2) 0.028 (2) 0.0223 (17) 0.0147 (19) O1 0.0480 (11) 0.0255 (9) 0.0327 (9) −0.0090 (8) 0.0215 (9) −0.0016 (7) O2 0.0427 (11) 0.0239 (9) 0.0514 (12) −0.0061 (8) 0.0283 (10) −0.0083 (8) ----- ------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1686 .table-wrap} ----------------------- ------------- ---------------------- -------------- Mn1---O2 1.8669 (18) C8---C9 1.511 (4) Mn1---O1 1.9083 (19) C8---H8A 0.9700 Mn1---N2 1.984 (2) C8---H8B 0.9700 Mn1---N1 1.991 (2) C9---N2 1.478 (3) Mn1---N3 2.130 (3) C9---H9A 0.9700 Br1---C4 1.894 (3) C9---H9B 0.9700 Br2---C13 1.900 (2) C10---N2 1.286 (3) C1---O1 1.340 (3) C10---C11 1.441 (3) C1---C2 1.396 (4) C10---H10 0.9300 C1---C6 1.418 (3) C11---C12 1.406 (3) C2---C3 1.381 (4) C11---C16 1.411 (3) C2---H2 0.9300 C12---C13 1.371 (4) C3---C4 1.392 (4) C12---H12 0.9300 C3---H3 0.9300 C13---C14 1.385 (4) C4---C5 1.367 (4) C14---C15 1.371 (4) C5---C6 1.404 (4) C14---H14 0.9300 C5---H5 0.9300 C15---C16 1.405 (4) C6---C7 1.448 (4) C15---H15 0.9300 C7---N1 1.277 (3) C16---O2 1.322 (3) C7---H7 0.9300 N3---N4 1.175 (3) C8---N1 1.472 (3) N4---N5 1.157 (4) O2---Mn1---O1 95.38 (8) N2---C9---C8 107.2 (2) O2---Mn1---N2 91.73 (8) N2---C9---H9A 110.3 O1---Mn1---N2 159.40 (9) C8---C9---H9A 110.3 O2---Mn1---N1 171.04 (9) N2---C9---H9B 110.3 O1---Mn1---N1 88.41 (9) C8---C9---H9B 110.3 N2---Mn1---N1 82.06 (9) H9A---C9---H9B 108.5 O2---Mn1---N3 97.19 (10) N2---C10---C11 124.5 (2) O1---Mn1---N3 96.43 (10) N2---C10---H10 117.7 N2---Mn1---N3 101.83 (10) C11---C10---H10 117.7 N1---Mn1---N3 90.43 (9) C12---C11---C16 119.7 (2) O1---C1---C2 119.4 (2) C12---C11---C10 117.2 (2) O1---C1---C6 121.9 (2) C16---C11---C10 123.1 (2) C2---C1---C6 118.7 (2) C13---C12---C11 119.6 (2) C3---C2---C1 121.2 (2) C13---C12---H12 120.2 C3---C2---H2 119.4 C11---C12---H12 120.2 C1---C2---H2 119.4 C12---C13---C14 121.3 (2) C2---C3---C4 119.4 (3) C12---C13---Br2 119.5 (2) C2---C3---H3 120.3 C14---C13---Br2 119.22 (19) C4---C3---H3 120.3 C15---C14---C13 119.9 (2) C5---C4---C3 121.0 (2) C15---C14---H14 120.0 C5---C4---Br1 119.94 (19) C13---C14---H14 120.0 C3---C4---Br1 119.0 (2) C14---C15---C16 120.9 (2) C4---C5---C6 120.2 (2) C14---C15---H15 119.6 C4---C5---H5 119.9 C16---C15---H15 119.6 C6---C5---H5 119.9 O2---C16---C15 117.9 (2) C5---C6---C1 119.3 (2) O2---C16---C11 123.6 (2) C5---C6---C7 118.7 (2) C15---C16---C11 118.5 (2) C1---C6---C7 122.0 (2) C7---N1---C8 122.9 (2) N1---C7---C6 123.0 (2) C7---N1---Mn1 123.72 (18) N1---C7---H7 118.5 C8---N1---Mn1 113.33 (16) C6---C7---H7 118.5 C10---N2---C9 121.2 (2) N1---C8---C9 106.7 (2) C10---N2---Mn1 125.88 (17) N1---C8---H8A 110.4 C9---N2---Mn1 112.66 (17) C9---C8---H8A 110.4 N4---N3---Mn1 128.8 (2) N1---C8---H8B 110.4 N5---N4---N3 177.5 (3) C9---C8---H8B 110.4 C1---O1---Mn1 118.36 (16) H8A---C8---H8B 108.6 C16---O2---Mn1 128.97 (16) O1---C1---C2---C3 −178.9 (3) O1---Mn1---N1---C7 −33.1 (2) C6---C1---C2---C3 3.3 (4) N2---Mn1---N1---C7 165.2 (2) C1---C2---C3---C4 −2.1 (4) N3---Mn1---N1---C7 63.3 (2) C2---C3---C4---C5 −1.4 (4) O2---Mn1---N1---C8 34.1 (7) C2---C3---C4---Br1 176.4 (2) O1---Mn1---N1---C8 149.32 (19) C3---C4---C5---C6 3.6 (4) N2---Mn1---N1---C8 −12.37 (19) Br1---C4---C5---C6 −174.3 (2) N3---Mn1---N1---C8 −114.3 (2) C4---C5---C6---C1 −2.3 (4) C11---C10---N2---C9 179.9 (3) C4---C5---C6---C7 178.2 (2) C11---C10---N2---Mn1 6.0 (4) O1---C1---C6---C5 −178.9 (2) C8---C9---N2---C10 −137.6 (3) C2---C1---C6---C5 −1.2 (4) C8---C9---N2---Mn1 37.1 (3) O1---C1---C6---C7 0.6 (4) O2---Mn1---N2---C10 −13.6 (2) C2---C1---C6---C7 178.3 (2) O1---Mn1---N2---C10 96.7 (3) C5---C6---C7---N1 −161.0 (3) N1---Mn1---N2---C10 159.9 (2) C1---C6---C7---N1 19.5 (4) N3---Mn1---N2---C10 −111.3 (2) N1---C8---C9---N2 −45.4 (3) O2---Mn1---N2---C9 172.0 (2) N2---C10---C11---C12 −173.0 (3) O1---Mn1---N2---C9 −77.7 (3) N2---C10---C11---C16 5.3 (4) N1---Mn1---N2---C9 −14.4 (2) C16---C11---C12---C13 1.7 (4) N3---Mn1---N2---C9 74.3 (2) C10---C11---C12---C13 −179.9 (2) O2---Mn1---N3---N4 12.9 (3) C11---C12---C13---C14 0.5 (4) O1---Mn1---N3---N4 −83.4 (3) C11---C12---C13---Br2 −178.1 (2) N2---Mn1---N3---N4 106.2 (3) C12---C13---C14---C15 −0.7 (4) N1---Mn1---N3---N4 −171.8 (3) Br2---C13---C14---C15 178.0 (2) Mn1---N3---N4---N5 −177 (100) C13---C14---C15---C16 −1.5 (4) C2---C1---O1---Mn1 139.8 (2) C14---C15---C16---O2 −174.8 (3) C6---C1---O1---Mn1 −42.5 (3) C14---C15---C16---C11 3.7 (4) O2---Mn1---O1---C1 −138.02 (18) C12---C11---C16---O2 174.7 (2) N2---Mn1---O1---C1 112.3 (3) C10---C11---C16---O2 −3.6 (4) N1---Mn1---O1---C1 50.12 (18) C12---C11---C16---C15 −3.8 (4) N3---Mn1---O1---C1 −40.14 (19) C10---C11---C16---C15 177.9 (2) C15---C16---O2---Mn1 168.3 (2) C6---C7---N1---C8 −177.5 (2) C11---C16---O2---Mn1 −10.2 (4) C6---C7---N1---Mn1 5.1 (4) O1---Mn1---O2---C16 −144.9 (2) C9---C8---N1---C7 −142.4 (3) N2---Mn1---O2---C16 15.7 (2) C9---C8---N1---Mn1 35.2 (3) N1---Mn1---O2---C16 −30.2 (7) O2---Mn1---N1---C7 −148.3 (5) N3---Mn1---O2---C16 117.9 (2) ----------------------- ------------- ---------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.486759	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052106/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m322", "authors": [ { "first": "Yingxia", "last": "Liu" } ] }
PMC3052107	Related literature {#sec1} ================== For general background to the biological activity of salicylaldehydes and their derivatives, see: Jahnke et al. (1993[@bb4]); Pelttari et al. (2007[@bb6]); Fillebeen & Pantopoulos (2010[@bb3]); Fan et al. (2010[@bb2]). For related structures, see: Mori et al. (2010[@bb5]); Potapov et al. (2009[@bb7]); Purushothaman & Raghunathan (2009[@bb8]). For the preparation of the title compound, see: Purushothaman & Raghunathan (2009[@bb8]); Zhang et al. (2010[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~23~H~20~Br~2~O~4~M ~r~ = 520.19Monoclinic,a = 12.867 (7) Åb = 18.07 (1) Åc = 9.649 (5) Åβ = 108.955 (6)°V = 2122 (2) Å^3^Z = 4Mo Kα radiationμ = 3.85 mm^−1^T = 296 K0.34 × 0.32 × 0.28 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb9]) T ~min~ = 0.281, T ~max~ = 0.34115392 measured reflections3944 independent reflections1905 reflections with I \> 2σ(I)R ~int~ = 0.063 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.062wR(F ^2^) = 0.207S = 1.023944 reflections263 parametersH-atom parameters constrainedΔρ~max~ = 0.79 e Å^−3^Δρ~min~ = −0.75 e Å^−3^ {#d5e452} Data collection: APEX2 (Bruker, 2007[@bb1]); cell refinement: SAINT (Bruker, 2007[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb10]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb10]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb10]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100643X/rk2257sup1.cif](http://dx.doi.org/10.1107/S160053681100643X/rk2257sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100643X/rk2257Isup2.hkl](http://dx.doi.org/10.1107/S160053681100643X/rk2257Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rk2257&file=rk2257sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rk2257sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rk2257&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RK2257](http://scripts.iucr.org/cgi-bin/sendsup?rk2257)). The authors acknowledge the Fundamental Research Funds for the Central Universities (lzujbky-2010-43) and the Research Foundation for Young Teachers Possessing a Doctoral Degree of Lanzhou University for financial support. Comment ======= It is reported that salicylaldehydes and their derivatives have showed a wide variety of biological activities, such as antiseptic, labelling cell, antiproliferative and pesticidal (Jahnke et al., 1993; Pelttari et al., 2007; Fillebeen & Pantopoulos, 2010; Fan et al., 2010). As an important class of aldehydes, substituted aldehydes also exhibit potential biological activities. The related structures also have been reported (Mori et al., 2010; Potapov et al., 2009; Purushothaman & Raghunathan, 2009). On this base, the title compound was synthesized. In the title compound (Fig. 1), a dihedral angle 63.0 (2)° is observed between benzene rings on the both ends of molecule. The crystal structure is stabilized by weak intramolecular C---H···O bonds. The molecule of the title compound is linked by the C---H···Br bonding (Fig. 2) in to the Z formation. Furthermore, the weak intermolecular π--π stacking interactions - Cg1···Cg2^ii^= 3.698 (4)Å, Cg3···Cg3^iii^ = 4.193 (5)Å, where Cg1 is centroid of the ring C2--C7, Cg2 is centroid of the ring C9--C14 and Cg3 is centroid of the ring C17--C22. Symmetry codes: (ii) -x, 1-y, -z; (iii) 1-x, 1-y, 1-z. Experimental {#experimental} ============ All reagents and solvents were obtained from commercial sources and needed to be further purified. The title compound was synthesized according to the related literature (Purushothaman & Raghunathan, 2009). A solution of salicylaldehyde (2 mmol in 10 ml acetone) was slowly added dropwise to a suspension of 1,2-bis(2-(bromomethyl)phenoxy) ethane (1 mmol in 20 ml acetone) prepared according to the reported method (Zhang et al., 2010) and anhydrous potassium carbonate (2 mmol). The mixture was refluxed for 8 h. The reaction mixture was then cooled to room temperature and filtered. After this period, the residue was dissolved and extracted by ethyl acetate. The combined organical layer was washed with water and then dried with anhydrous sodium sulfate. After that the solvent was evaporated under vacuum to give the product. The obtained residue was purified by flash column chromatography on silica gel using petroleum ether/ethylacetate (5:2) mixtures as eluent. Refinement {#refinement} ========== All H atoms were found from difference Fourier maps and were subsequently refined in a riding-model approximation with C---H distances ranging from 0.93Å to 0.98Å and with U~iso~(H) = 1.2 U~eq~(C) of the carrier atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o714-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the C---H···Bri interactions in the crystal structure of the title compound. Symmetry code: (i) -x+1, y+1/2, -z+1/2). ::: ![](e-67-0o714-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e197 .table-wrap} ------------------------- --------------------------------------- C~23~H~20~Br~2~O~4~ F(000) = 1040 M~r~ = 520.19 D~x~ = 1.628 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 1808 reflections a = 12.867 (7) Å θ = 2.3--17.5° b = 18.07 (1) Å µ = 3.85 mm^−1^ c = 9.649 (5) Å T = 296 K β = 108.955 (6)° Block, colourless V = 2122 (2) Å^3^ 0.34 × 0.32 × 0.28 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e327 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 3944 independent reflections Radiation source: fine-focus sealed tube 1905 reflections with I \> 2σ(I) graphite R~int~ = 0.063 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −15→15 T~min~ = 0.281, T~max~ = 0.341 k = −21→21 15392 measured reflections l = −11→11 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e444 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.062 H-atom parameters constrained wR(F^2^) = 0.207 w = 1/\[σ^2^(F~o~^2^) + (0.1049P)^2^ + 0.4797P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.02 (Δ/σ)~max~ \< 0.001 3944 reflections Δρ~max~ = 0.79 e Å^−3^ 263 parameters Δρ~min~ = −0.75 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0020 (3) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e625 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e724 .table-wrap} ------ ------------- ------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.56817 (7) 0.30130 (6) 0.29797 (13) 0.1092 (5) Br2 0.37069 (9) 0.31794 (5) −0.00106 (10) 0.0986 (5) C1 −0.1269 (7) 0.7137 (4) −0.1294 (8) 0.069 (2) H1 −0.1621 0.6777 −0.0919 0.083\ C2 −0.0059 (6) 0.7075 (3) −0.0932 (6) 0.0509 (16) C3 0.0495 (7) 0.7556 (4) −0.1572 (7) 0.0658 (19) H3 0.0096 0.7922 −0.2199 0.079\* C4 0.1583 (7) 0.7514 (4) −0.1323 (8) 0.073 (2) H4 0.1932 0.7846 −0.1761 0.088\* C5 0.2176 (6) 0.6962 (4) −0.0397 (8) 0.070 (2) H5 0.2930 0.6929 −0.0213 0.084\* C6 0.1660 (6) 0.6458 (4) 0.0260 (7) 0.0551 (16) H6 0.2062 0.6085 0.0865 0.066\* C7 0.0548 (6) 0.6522 (3) −0.0001 (6) 0.0511 (16) C8 0.0522 (5) 0.5531 (3) 0.1655 (7) 0.0487 (15) H8A 0.1057 0.5775 0.2474 0.058\* H8B 0.0905 0.5182 0.1229 0.058\* C9 −0.0317 (5) 0.5130 (3) 0.2169 (6) 0.0470 (15) C10 −0.1419 (6) 0.5287 (4) 0.1643 (7) 0.0617 (18) H10 −0.1676 0.5664 0.0961 0.074\* C11 −0.2162 (6) 0.4878 (5) 0.2135 (8) 0.070 (2) H11 −0.2910 0.4979 0.1766 0.084\* C12 −0.1791 (7) 0.4340 (4) 0.3138 (8) 0.071 (2) H12 −0.2284 0.4073 0.3465 0.085\* C13 −0.0685 (6) 0.4184 (4) 0.3684 (7) 0.0602 (17) H13 −0.0436 0.3811 0.4378 0.072\* C14 0.0057 (5) 0.4576 (3) 0.3211 (7) 0.0487 (16) C15 0.1611 (5) 0.3890 (3) 0.4722 (6) 0.0536 (16) H15A 0.1381 0.3412 0.4268 0.064\* H15B 0.1347 0.3939 0.5552 0.064\* C16 0.2849 (6) 0.3950 (4) 0.5223 (7) 0.0670 (19) H16A 0.3066 0.4437 0.5639 0.080\* H16B 0.3163 0.3586 0.5984 0.080\* C17 0.3652 (5) 0.4407 (4) 0.3435 (7) 0.0556 (17) C18 0.3584 (6) 0.5154 (4) 0.3772 (8) 0.0675 (19) H18 0.3226 0.5295 0.4426 0.081\* C19 0.4055 (6) 0.5681 (4) 0.3121 (9) 0.077 (2) H19 0.4046 0.6176 0.3381 0.092\* C20 0.4531 (6) 0.5485 (5) 0.2106 (9) 0.076 (2) H20 0.4825 0.5846 0.1656 0.091\* C21 0.4579 (6) 0.4750 (5) 0.1743 (8) 0.071 (2) H21 0.4906 0.4622 0.1047 0.086\* C22 0.4145 (5) 0.4197 (4) 0.2401 (7) 0.0536 (16) C23 0.4210 (6) 0.3400 (4) 0.2060 (8) 0.0657 (19) H23 0.3725 0.3135 0.2490 0.079\* O1 −0.1819 (4) 0.7608 (3) −0.2023 (5) 0.0824 (16) O2 −0.0053 (3) 0.6067 (2) 0.0578 (4) 0.0549 (11) O3 0.1171 (4) 0.4474 (2) 0.3681 (4) 0.0560 (11) O4 0.3266 (4) 0.3834 (2) 0.4054 (5) 0.0737 (14) ------ ------------- ------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1404 .table-wrap} ----- ------------ ------------ ------------- ------------ ------------ ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0693 (7) 0.0994 (8) 0.1485 (10) 0.0213 (5) 0.0212 (6) 0.0112 (6) Br2 0.1243 (9) 0.0954 (7) 0.0791 (7) 0.0014 (5) 0.0372 (6) −0.0179 (5) C1 0.084 (6) 0.059 (4) 0.059 (5) 0.000 (4) 0.015 (4) 0.000 (4) C2 0.070 (5) 0.037 (3) 0.042 (4) −0.006 (3) 0.013 (3) −0.004 (3) C3 0.087 (6) 0.052 (4) 0.054 (4) −0.005 (4) 0.017 (4) −0.002 (3) C4 0.096 (6) 0.059 (5) 0.065 (5) −0.022 (4) 0.027 (5) 0.010 (4) C5 0.063 (5) 0.082 (5) 0.064 (5) −0.015 (4) 0.019 (4) −0.008 (4) C6 0.058 (5) 0.051 (4) 0.049 (4) −0.005 (3) 0.008 (3) −0.001 (3) C7 0.062 (5) 0.046 (4) 0.041 (4) −0.004 (3) 0.011 (3) −0.007 (3) C8 0.056 (4) 0.040 (3) 0.051 (4) 0.001 (3) 0.019 (3) 0.004 (3) C9 0.056 (4) 0.044 (4) 0.042 (4) 0.000 (3) 0.016 (3) −0.010 (3) C10 0.073 (5) 0.055 (4) 0.060 (4) 0.005 (4) 0.026 (4) −0.005 (3) C11 0.051 (4) 0.087 (5) 0.077 (5) −0.013 (4) 0.030 (4) −0.016 (5) C12 0.083 (6) 0.078 (5) 0.071 (5) −0.028 (4) 0.049 (5) −0.019 (4) C13 0.069 (5) 0.062 (4) 0.051 (4) −0.008 (4) 0.021 (4) 0.002 (3) C14 0.058 (5) 0.045 (4) 0.049 (4) −0.005 (3) 0.025 (3) −0.001 (3) C15 0.071 (5) 0.056 (4) 0.034 (3) 0.001 (3) 0.017 (3) 0.006 (3) C16 0.082 (5) 0.069 (5) 0.053 (4) 0.004 (4) 0.025 (4) 0.006 (4) C17 0.047 (4) 0.060 (4) 0.056 (4) 0.000 (3) 0.012 (3) 0.003 (3) C18 0.064 (5) 0.065 (5) 0.075 (5) 0.008 (4) 0.024 (4) 0.011 (4) C19 0.064 (5) 0.057 (4) 0.086 (6) 0.004 (4) −0.006 (5) 0.003 (4) C20 0.063 (5) 0.082 (6) 0.079 (6) −0.023 (4) 0.020 (4) 0.013 (4) C21 0.061 (5) 0.088 (6) 0.064 (5) −0.019 (4) 0.018 (4) −0.002 (4) C22 0.038 (4) 0.069 (4) 0.052 (4) −0.005 (3) 0.011 (3) −0.003 (3) C23 0.061 (5) 0.064 (4) 0.081 (5) 0.007 (3) 0.035 (4) 0.001 (4) O1 0.089 (4) 0.072 (3) 0.068 (3) 0.029 (3) 0.000 (3) 0.008 (3) O2 0.058 (3) 0.050 (3) 0.057 (3) 0.002 (2) 0.019 (2) 0.014 (2) O3 0.061 (3) 0.058 (3) 0.051 (3) −0.002 (2) 0.021 (2) 0.011 (2) O4 0.097 (4) 0.059 (3) 0.084 (3) 0.006 (3) 0.056 (3) 0.007 (3) ----- ------------ ------------ ------------- ------------ ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1942 .table-wrap} ----------------------- ------------ ----------------------- ------------ Br1---C23 1.941 (7) C12---C13 1.377 (10) Br2---C23 1.931 (7) C12---H12 0.9300 C1---O1 1.182 (8) C13---C14 1.380 (8) C1---C2 1.485 (10) C13---H13 0.9300 C1---H1 0.9300 C14---O3 1.368 (7) C2---C3 1.389 (9) C15---O3 1.441 (7) C2---C7 1.400 (8) C15---C16 1.510 (9) C3---C4 1.344 (10) C15---H15A 0.9700 C3---H3 0.9300 C15---H15B 0.9700 C4---C5 1.389 (10) C16---O4 1.414 (7) C4---H4 0.9300 C16---H16A 0.9700 C5---C6 1.395 (9) C16---H16B 0.9700 C5---H5 0.9300 C17---O4 1.367 (7) C6---C7 1.376 (9) C17---C18 1.397 (9) C6---H6 0.9300 C17---C22 1.397 (9) C7---O2 1.366 (7) C18---C19 1.385 (10) C8---O2 1.437 (7) C18---H18 0.9300 C8---C9 1.510 (8) C19---C20 1.361 (11) C8---H8A 0.9700 C19---H19 0.9300 C8---H8B 0.9700 C20---C21 1.379 (11) C9---C10 1.372 (9) C20---H20 0.9300 C9---C14 1.390 (8) C21---C22 1.394 (9) C10---C11 1.408 (9) C21---H21 0.9300 C10---H10 0.9300 C22---C23 1.486 (9) C11---C12 1.344 (10) C23---H23 0.9800 C11---H11 0.9300 O1---C1---C2 124.9 (7) O3---C14---C13 125.8 (6) O1---C1---H1 117.5 O3---C14---C9 114.6 (5) C2---C1---H1 117.5 C13---C14---C9 119.7 (6) C3---C2---C7 118.2 (7) O3---C15---C16 107.8 (5) C3---C2---C1 119.9 (6) O3---C15---H15A 110.1 C7---C2---C1 121.9 (6) C16---C15---H15A 110.1 C4---C3---C2 122.7 (7) O3---C15---H15B 110.1 C4---C3---H3 118.7 C16---C15---H15B 110.1 C2---C3---H3 118.7 H15A---C15---H15B 108.5 C3---C4---C5 118.6 (7) O4---C16---C15 111.6 (5) C3---C4---H4 120.7 O4---C16---H16A 109.3 C5---C4---H4 120.7 C15---C16---H16A 109.3 C4---C5---C6 121.2 (7) O4---C16---H16B 109.3 C4---C5---H5 119.4 C15---C16---H16B 109.3 C6---C5---H5 119.4 H16A---C16---H16B 108.0 C7---C6---C5 118.8 (6) O4---C17---C18 124.7 (6) C7---C6---H6 120.6 O4---C17---C22 114.9 (6) C5---C6---H6 120.6 C18---C17---C22 120.4 (6) O2---C7---C6 124.6 (6) C19---C18---C17 119.3 (7) O2---C7---C2 114.9 (6) C19---C18---H18 120.4 C6---C7---C2 120.5 (6) C17---C18---H18 120.4 O2---C8---C9 107.8 (5) C20---C19---C18 120.8 (7) O2---C8---H8A 110.1 C20---C19---H19 119.6 C9---C8---H8A 110.1 C18---C19---H19 119.6 O2---C8---H8B 110.1 C19---C20---C21 120.1 (7) C9---C8---H8B 110.1 C19---C20---H20 119.9 H8A---C8---H8B 108.5 C21---C20---H20 119.9 C10---C9---C14 119.3 (6) C20---C21---C22 121.1 (7) C10---C9---C8 122.8 (6) C20---C21---H21 119.5 C14---C9---C8 117.8 (5) C22---C21---H21 119.5 C9---C10---C11 120.0 (7) C17---C22---C21 118.2 (7) C9---C10---H10 120.0 C17---C22---C23 119.5 (6) C11---C10---H10 120.0 C21---C22---C23 122.3 (6) C12---C11---C10 120.1 (7) C22---C23---Br2 113.9 (5) C12---C11---H11 120.0 C22---C23---Br1 111.4 (5) C10---C11---H11 120.0 Br2---C23---Br1 110.4 (3) C11---C12---C13 120.3 (6) C22---C23---H23 106.9 C11---C12---H12 119.8 Br2---C23---H23 106.9 C13---C12---H12 119.8 Br1---C23---H23 106.9 C14---C13---C12 120.6 (7) C7---O2---C8 118.4 (5) C14---C13---H13 119.7 C14---O3---C15 117.5 (5) C12---C13---H13 119.7 C17---O4---C16 121.6 (5) O1---C1---C2---C3 −6.0 (10) O3---C15---C16---O4 −63.5 (7) O1---C1---C2---C7 176.8 (6) O4---C17---C18---C19 176.8 (6) C7---C2---C3---C4 −0.6 (10) C22---C17---C18---C19 −3.0 (10) C1---C2---C3---C4 −178.0 (6) C17---C18---C19---C20 3.4 (11) C2---C3---C4---C5 0.6 (10) C18---C19---C20---C21 −1.9 (11) C3---C4---C5---C6 0.3 (10) C19---C20---C21---C22 0.0 (11) C4---C5---C6---C7 −1.1 (10) O4---C17---C22---C21 −178.7 (6) C5---C6---C7---O2 −179.8 (5) C18---C17---C22---C21 1.1 (9) C5---C6---C7---C2 1.1 (9) O4---C17---C22---C23 0.1 (9) C3---C2---C7---O2 −179.5 (5) C18---C17---C22---C23 179.9 (6) C1---C2---C7---O2 −2.2 (8) C20---C21---C22---C17 0.4 (10) C3---C2---C7---C6 −0.3 (9) C20---C21---C22---C23 −178.3 (7) C1---C2---C7---C6 177.0 (6) C17---C22---C23---Br2 130.6 (5) O2---C8---C9---C10 0.0 (8) C21---C22---C23---Br2 −50.7 (8) O2---C8---C9---C14 179.3 (5) C17---C22---C23---Br1 −103.8 (6) C14---C9---C10---C11 −1.3 (9) C21---C22---C23---Br1 75.0 (7) C8---C9---C10---C11 178.0 (5) C6---C7---O2---C8 6.8 (8) C9---C10---C11---C12 1.0 (10) C2---C7---O2---C8 −174.1 (5) C10---C11---C12---C13 −0.4 (10) C9---C8---O2---C7 177.1 (4) C11---C12---C13---C14 0.0 (10) C13---C14---O3---C15 2.5 (8) C12---C13---C14---O3 179.5 (6) C9---C14---O3---C15 −177.8 (5) C12---C13---C14---C9 −0.3 (9) C16---C15---O3---C14 −172.6 (5) C10---C9---C14---O3 −178.8 (5) C18---C17---O4---C16 −6.4 (10) C8---C9---C14---O3 1.8 (7) C22---C17---O4---C16 173.5 (5) C10---C9---C14---C13 1.0 (9) C15---C16---O4---C17 105.9 (7) C8---C9---C14---C13 −178.4 (5) ----------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2866 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C1---H1···O2 0.93 2.42 2.753 (9) 101 C10---H10···O2 0.93 2.35 2.710 (8) 102 C23---H23···O4 0.98 2.19 2.700 (8) 111 C5---H5···Br1^i^ 0.93 3.03 3.529 (7) 116 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, y+1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- C5---H5⋯Br1^i^ 0.93 3.03 3.529 (7) 116 Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.493152	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052107/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o714", "authors": [ { "first": "Juan", "last": "Xia" }, { "first": "Xiang", "last": "Liu" }, { "first": "An-Qi", "last": "Wang" }, { "first": "Zhong-Xing", "last": "Su" } ] }
PMC3052108	Related literature {#sec1} ================== For the pharmacological activity of benzofuran compounds, see: Aslam et al. (2006[@bb2]); Galal et al. (2009[@bb8]); Khan et al. (2005[@bb9]). For natural products with benzofuran rings, see: Akgul & Anil (2003[@bb1]); Soekamto et al. (2003[@bb12]). For structural studies of related 3-arylsulfonyl-5-bromo-2-methyl-1-benzofuran derivatives, see: Choi et al. (2008[@bb5], 2010[@bb6]). For a review of halogen bonding, see: Politzer et al. (2007[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~15~H~17~BrO~3~SM ~r~ = 357.26Triclinic,a = 6.3452 (1) Åb = 8.2065 (1) Åc = 14.4866 (2) Åα = 98.842 (1)°β = 97.693 (1)°γ = 96.385 (1)°V = 731.95 (2) Å^3^Z = 2Mo Kα radiationμ = 2.95 mm^−1^T = 173 K0.33 × 0.26 × 0.23 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2009[@bb4]) T ~min~ = 0.585, T ~max~ = 0.74613107 measured reflections3377 independent reflections3109 reflections with I \> 2σ(I)R ~int~ = 0.034 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.028wR(F ^2^) = 0.073S = 1.073377 reflections182 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.70 e Å^−3^ {#d5e476} Data collection: APEX2 (Bruker, 2009[@bb4]); cell refinement: SAINT (Bruker, 2009[@bb4]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb11]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb11]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb7]) and DIAMOND (Brandenburg, 1998[@bb3]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003515/ld2001sup1.cif](http://dx.doi.org/10.1107/S1600536811003515/ld2001sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003515/ld2001Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003515/ld2001Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ld2001&file=ld2001sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ld2001sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ld2001&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LD2001](http://scripts.iucr.org/cgi-bin/sendsup?ld2001)). Comment ======= Many compounds containing a benzofuran ring show diverse pharmacological properties such as antifungal, antitumor and antiviral, and antimicrobial activities (Aslam et al., 2006, Galal et al., 2009, Khan et al., 2005). These compounds occur in a wide range of natural products (Akgul & Anil, 2003; Soekamto et al., 2003). As a part of our ongoing study of the substituent effect on the solid state structures of 3-arylsulfonyl-5-bromo-2-methyl-1-benzofuran analogues (Choi et al., 2008, 2010), we report herein the crystal structure of the title compound. In the title molecule (Fig. 1), the benzofuran unit is essentially planar, with a mean deviation of 0.006 (2) Å from the least-squares plane defined by the nine constituent atoms. The cyclohexyl ring is in the chair form and arylsulfonyl moiety is positioned equatorial relative to the cyclohexyl group. The molecular packing (Fig. 2) is stabilized by intermolecular C---H···O hydrogen bonds - between an arene H atom and the furan O atom (Table 1; C6---H6···O1^i^), and between a methyl H atom and a sulfonyl oxygen (Table 1; C9---H9B···O3^ii^). The crystal structure is further stabilized by Br···O halogen bonding between the bromine and an oxygen of the sulfonyl group \[Br1···O3^iii^ = 3.250 (2) Å, C4---Br1···O3^iii^ = 165.29 (6)°\] (Politzer et al., 2007). The crystal packing (Fig. 2) also exhibits π--π overlap between the benzene and furan rings of neighbouring molecules, with a Cg1···Cg2^iv^ distance of 3.633 (2) Å (Cg1 and Cg2 are the centroids of the C2-C7 benzene ring and the C1/C2/C7/O1/C8 furan ring, respectively), wherein the inter-planar distance between the benzene and furan rings is 3.391 (2) Å. Experimental {#experimental} ============ 77% 3-chloroperoxybenzoic acid (381 mg, 1.7 mmol) was added in small portions to a stirred solution of 5-bromo-3-cyclohexylsulfanyl-2-methyl-1-benzofuran (260 mg, 0.8 mmol) in dichloromethane (40 mL) at 273 K. After being stirred at room temperature for 5h, the mixture was washed with saturated sodium bicarbonate solution and the organic layer was separated, dried over magnesium sulfate, filtered and concentrated at reduced pressure. The residue was purified by column chromatography (hexane--ethyl acetate, 4:1 v/v) to afford the title compound as a colorless solid \[yield 76%, m.p. 446--447 K; R~f~ = 0.58 (hexane--ethyl acetate, 4:1 v/v)\]. Single crystals suitable for X-ray diffraction were prepared by slow evaporation of acetone solution of the title compound at room temperature. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding and rotating model, with C---H = 0.95 Å for aryl, 1.00 Å for methine, 0.99 Å for methylene and 0.98 Å for methyl H atoms, respectively. U~iso~(H) = 1.2U~eq~(C) for aryl, methine, methylene and 1.5U~eq~(C) for methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radius. ::: ![](e-67-0o542-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the C---H···O, Br···O and π--π interactions (dotted lines) in the crystal structure of the title compound. \[Symmetry codes: (i) - x + 2, - y + 2, - z + 1; (ii) x + 1, y, z; (iii) - x, - y + 1, - z + 1 ; (iv) - x + 1, - y + 2, - z + 1; (v) x - 1, y, z .\] ::: ![](e-67-0o542-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e198 .table-wrap} ----------------------- --------------------------------------- C~15~H~17~BrO~3~S Z = 2 M~r~ = 357.26 F(000) = 364 Triclinic, P1 D~x~ = 1.621 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 6.3452 (1) Å Cell parameters from 8112 reflections b = 8.2065 (1) Å θ = 2.7--27.5° c = 14.4866 (2) Å µ = 2.95 mm^−1^ α = 98.842 (1)° T = 173 K β = 97.693 (1)° Block, colourless γ = 96.385 (1)° 0.33 × 0.26 × 0.23 mm V = 731.95 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e332 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD diffractometer 3377 independent reflections Radiation source: rotating anode 3109 reflections with I \> 2σ(I) graphite multilayer R~int~ = 0.034 Detector resolution: 10.0 pixels mm^-1^ θ~max~ = 27.6°, θ~min~ = 1.4° φ and ω scans h = −8→8 Absorption correction: multi-scan (SADABS; Bruker, 2009) k = −10→10 T~min~ = 0.585, T~max~ = 0.746 l = −18→18 13107 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e455 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.028 Hydrogen site location: difference Fourier map wR(F^2^) = 0.073 H-atom parameters constrained S = 1.07 w = 1/\[σ^2^(F~o~^2^) + (0.0389P)^2^ + 0.2624P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3377 reflections (Δ/σ)~max~ = 0.001 182 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.70 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e612 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e657 .table-wrap} ------ ------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.24178 (3) 0.58796 (3) 0.634104 (12) 0.03547 (8) S1 0.21139 (7) 0.69361 (6) 0.22168 (3) 0.02801 (11) O1 0.7467 (2) 0.92120 (16) 0.38017 (9) 0.0310 (3) O2 0.2068 (3) 0.78049 (19) 0.14233 (10) 0.0400 (3) O3 0.0254 (2) 0.6830 (2) 0.26875 (10) 0.0396 (3) C1 0.4294 (3) 0.7824 (2) 0.30762 (12) 0.0267 (4) C2 0.4500 (3) 0.7619 (2) 0.40566 (12) 0.0261 (3) C3 0.3234 (3) 0.6829 (2) 0.46111 (12) 0.0284 (4) H3 0.1862 0.6225 0.4355 0.034\ C4 0.4078 (3) 0.6967 (2) 0.55581 (13) 0.0286 (4) C5 0.6076 (3) 0.7838 (3) 0.59542 (13) 0.0324 (4) H5 0.6582 0.7887 0.6607 0.039\* C6 0.7337 (3) 0.8635 (3) 0.54056 (14) 0.0330 (4) H6 0.8706 0.9243 0.5663 0.040\* C7 0.6495 (3) 0.8496 (2) 0.44644 (13) 0.0284 (4) C8 0.6100 (3) 0.8776 (2) 0.29616 (13) 0.0290 (4) C9 0.6862 (4) 0.9444 (3) 0.21558 (15) 0.0365 (4) H9A 0.5693 0.9244 0.1619 0.055\* H9B 0.8070 0.8887 0.1974 0.055\* H9C 0.7330 1.0643 0.2340 0.055\* C10 0.2636 (3) 0.4859 (2) 0.18543 (12) 0.0244 (3) H10 0.3071 0.4386 0.2436 0.029\* C11 0.4467 (3) 0.4811 (2) 0.12705 (13) 0.0288 (4) H11A 0.5802 0.5433 0.1657 0.035\* H11B 0.4124 0.5353 0.0714 0.035\* C12 0.4807 (3) 0.3011 (3) 0.09420 (14) 0.0328 (4) H12A 0.5919 0.2997 0.0523 0.039\* H12B 0.5334 0.2522 0.1498 0.039\* C13 0.2750 (3) 0.1955 (3) 0.04136 (16) 0.0419 (5) H13A 0.2310 0.2363 −0.0182 0.050\* H13B 0.3015 0.0787 0.0249 0.050\* C14 0.0960 (4) 0.2023 (3) 0.10074 (18) 0.0474 (6) H14A 0.1341 0.1512 0.1573 0.057\* H14B −0.0373 0.1371 0.0636 0.057\* C15 0.0563 (3) 0.3812 (3) 0.13187 (14) 0.0358 (4) H15A −0.0560 0.3825 0.1732 0.043\* H15B 0.0050 0.4294 0.0757 0.043\* ------ ------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1146 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.03585 (12) 0.04254 (13) 0.02647 (11) 0.00000 (9) 0.00393 (8) 0.00562 (8) S1 0.0262 (2) 0.0334 (2) 0.0240 (2) 0.00874 (18) 0.00065 (16) 0.00314 (18) O1 0.0298 (7) 0.0289 (7) 0.0321 (7) 0.0000 (6) 0.0053 (5) 0.0004 (5) O2 0.0471 (8) 0.0414 (8) 0.0332 (7) 0.0134 (7) −0.0016 (6) 0.0129 (6) O3 0.0277 (7) 0.0553 (10) 0.0352 (7) 0.0134 (7) 0.0045 (6) 0.0009 (7) C1 0.0294 (9) 0.0247 (9) 0.0243 (8) 0.0049 (7) 0.0024 (7) −0.0003 (7) C2 0.0272 (8) 0.0236 (8) 0.0248 (8) 0.0043 (7) 0.0017 (6) −0.0026 (7) C3 0.0280 (9) 0.0290 (9) 0.0251 (8) 0.0023 (7) 0.0012 (7) −0.0013 (7) C4 0.0308 (9) 0.0270 (9) 0.0266 (8) 0.0035 (7) 0.0038 (7) 0.0007 (7) C5 0.0348 (10) 0.0330 (10) 0.0255 (8) 0.0026 (8) −0.0020 (7) −0.0002 (7) C6 0.0278 (9) 0.0323 (10) 0.0327 (10) −0.0025 (8) −0.0031 (7) −0.0025 (8) C7 0.0282 (9) 0.0256 (9) 0.0296 (9) 0.0029 (7) 0.0045 (7) −0.0009 (7) C8 0.0337 (9) 0.0242 (9) 0.0287 (9) 0.0076 (7) 0.0051 (7) 0.0000 (7) C9 0.0413 (11) 0.0336 (10) 0.0379 (10) 0.0078 (9) 0.0114 (9) 0.0098 (8) C10 0.0228 (8) 0.0285 (9) 0.0197 (7) 0.0003 (7) 0.0004 (6) 0.0023 (6) C11 0.0243 (8) 0.0303 (9) 0.0312 (9) 0.0018 (7) 0.0057 (7) 0.0032 (7) C12 0.0284 (9) 0.0316 (10) 0.0353 (10) 0.0052 (8) 0.0019 (7) −0.0018 (8) C13 0.0363 (11) 0.0423 (12) 0.0377 (11) 0.0002 (9) −0.0012 (9) −0.0124 (9) C14 0.0374 (11) 0.0441 (13) 0.0496 (13) −0.0147 (10) 0.0052 (10) −0.0107 (10) C15 0.0213 (8) 0.0485 (12) 0.0313 (9) −0.0042 (8) 0.0018 (7) −0.0047 (9) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1526 .table-wrap} -------------------- -------------- ----------------------- -------------- Br1---O3^i^ 3.250 (2) C9---H9A 0.9800 Br1---C4 1.901 (2) C9---H9B 0.9800 S1---O3 1.4409 (15) C9---H9C 0.9800 S1---O2 1.4416 (15) C10---C11 1.526 (2) S1---C1 1.7408 (18) C10---C15 1.530 (2) S1---C10 1.7852 (18) C10---H10 1.0000 O1---C8 1.370 (2) C11---C12 1.529 (3) O1---C7 1.378 (2) C11---H11A 0.9900 C1---C8 1.357 (3) C11---H11B 0.9900 C1---C2 1.446 (2) C12---C13 1.523 (3) C2---C3 1.388 (3) C12---H12A 0.9900 C2---C7 1.392 (3) C12---H12B 0.9900 C3---C4 1.387 (2) C13---C14 1.515 (3) C3---H3 0.9500 C13---H13A 0.9900 C4---C5 1.387 (3) C13---H13B 0.9900 C5---C6 1.383 (3) C14---C15 1.527 (3) C5---H5 0.9500 C14---H14A 0.9900 C6---C7 1.379 (3) C14---H14B 0.9900 C6---H6 0.9500 C15---H15A 0.9900 C8---C9 1.479 (3) C15---H15B 0.9900 C4---Br1---O3^i^ 165.29 (6) H9B---C9---H9C 109.5 O3---S1---O2 118.38 (9) C11---C10---C15 112.06 (14) O3---S1---C1 106.84 (9) C11---C10---S1 111.82 (13) O2---S1---C1 109.77 (9) C15---C10---S1 108.98 (13) O3---S1---C10 107.26 (9) C11---C10---H10 107.9 O2---S1---C10 109.22 (9) C15---C10---H10 107.9 C1---S1---C10 104.45 (8) S1---C10---H10 107.9 C8---O1---C7 106.96 (14) C10---C11---C12 110.24 (15) C8---C1---C2 107.72 (16) C10---C11---H11A 109.6 C8---C1---S1 127.65 (14) C12---C11---H11A 109.6 C2---C1---S1 124.60 (14) C10---C11---H11B 109.6 C3---C2---C7 119.65 (16) C12---C11---H11B 109.6 C3---C2---C1 135.86 (17) H11A---C11---H11B 108.1 C7---C2---C1 104.48 (16) C13---C12---C11 111.97 (16) C4---C3---C2 116.54 (17) C13---C12---H12A 109.2 C4---C3---H3 121.7 C11---C12---H12A 109.2 C2---C3---H3 121.7 C13---C12---H12B 109.2 C3---C4---C5 123.20 (18) C11---C12---H12B 109.2 C3---C4---Br1 118.01 (14) H12A---C12---H12B 107.9 C5---C4---Br1 118.78 (14) C14---C13---C12 111.09 (17) C6---C5---C4 120.46 (17) C14---C13---H13A 109.4 C6---C5---H5 119.8 C12---C13---H13A 109.4 C4---C5---H5 119.8 C14---C13---H13B 109.4 C7---C6---C5 116.23 (17) C12---C13---H13B 109.4 C7---C6---H6 121.9 H13A---C13---H13B 108.0 C5---C6---H6 121.9 C13---C14---C15 111.34 (19) O1---C7---C6 125.59 (17) C13---C14---H14A 109.4 O1---C7---C2 110.49 (16) C15---C14---H14A 109.4 C6---C7---C2 123.91 (18) C13---C14---H14B 109.4 C1---C8---O1 110.33 (16) C15---C14---H14B 109.4 C1---C8---C9 134.57 (18) H14A---C14---H14B 108.0 O1---C8---C9 115.09 (17) C14---C15---C10 110.09 (16) C8---C9---H9A 109.5 C14---C15---H15A 109.6 C8---C9---H9B 109.5 C10---C15---H15A 109.6 H9A---C9---H9B 109.5 C14---C15---H15B 109.6 C8---C9---H9C 109.5 C10---C15---H15B 109.6 H9A---C9---H9C 109.5 H15A---C15---H15B 108.2 O3---S1---C1---C8 −150.39 (17) C3---C2---C7---C6 0.4 (3) O2---S1---C1---C8 −20.86 (19) C1---C2---C7---C6 179.62 (18) C10---S1---C1---C8 96.14 (18) C2---C1---C8---O1 −0.3 (2) O3---S1---C1---C2 31.47 (18) S1---C1---C8---O1 −178.67 (13) O2---S1---C1---C2 161.01 (15) C2---C1---C8---C9 −179.0 (2) C10---S1---C1---C2 −81.99 (16) S1---C1---C8---C9 2.6 (3) C8---C1---C2---C3 178.9 (2) C7---O1---C8---C1 0.59 (19) S1---C1---C2---C3 −2.7 (3) C7---O1---C8---C9 179.58 (15) C8---C1---C2---C7 −0.1 (2) O3---S1---C10---C11 175.09 (12) S1---C1---C2---C7 178.32 (13) O2---S1---C10---C11 45.64 (14) C7---C2---C3---C4 −0.3 (3) C1---S1---C10---C11 −71.74 (14) C1---C2---C3---C4 −179.25 (19) O3---S1---C10---C15 50.66 (14) C2---C3---C4---C5 −0.1 (3) O2---S1---C10---C15 −78.79 (14) C2---C3---C4---Br1 −179.16 (13) C1---S1---C10---C15 163.83 (13) C3---C4---C5---C6 0.4 (3) C15---C10---C11---C12 −55.1 (2) Br1---C4---C5---C6 179.53 (15) S1---C10---C11---C12 −177.82 (12) C4---C5---C6---C7 −0.4 (3) C10---C11---C12---C13 54.5 (2) C8---O1---C7---C6 −179.79 (18) C11---C12---C13---C14 −55.5 (3) C8---O1---C7---C2 −0.68 (19) C12---C13---C14---C15 56.4 (3) C5---C6---C7---O1 178.95 (17) C13---C14---C15---C10 −56.4 (2) C5---C6---C7---C2 0.0 (3) C11---C10---C15---C14 56.2 (2) C3---C2---C7---O1 −178.72 (15) S1---C10---C15---C14 −179.50 (15) C1---C2---C7---O1 0.5 (2) -------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) −x, −y+1, −z+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2340 .table-wrap} -------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C6---H6···O1^ii^ 0.95 2.57 3.518 (2) 174 C9---H9B···O3^iii^ 0.98 2.55 3.303 (2) 134 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −x+2, −y+2, −z+1; (iii) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- --------- ------- ----------- ------------- C6---H6⋯O1^i^ 0.95 2.57 3.518 (2) 174 C9---H9B⋯O3^ii^ 0.98 2.55 3.303 (2) 134 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.499799	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052108/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o542", "authors": [ { "first": "Hong Dae", "last": "Choi" }, { "first": "Pil Ja", "last": "Seo" }, { "first": "Byeng Wha", "last": "Son" }, { "first": "Uk", "last": "Lee" } ] }
PMC3052109	Related literature {#sec1} ================== For the isolation of β-himachalene, see: Joseph & Dev (1968[@bb10]); Plattier & Teisseire (1974[@bb12]). For the reactivity of β-himachalene, see: Lassaba et al. (1998[@bb11]); Chekroun et al. (2000[@bb2]); El Jamili et al. (2002[@bb6]); Dakir et al. (2004[@bb4]). For the biological activity of β-himachalene, see: Daoubi et al. (2004[@bb5]). For conformational analysis, see: Cremer & Pople (1975[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~23~Cl~2~NOM ~r~ = 316.25Monoclinic,a = 7.7570 (7) Åb = 9.7041 (9) Åc = 10.6901 (10) Åβ = 93.432 (3)°V = 803.25 (13) Å^3^Z = 2Mo Kα radiationμ = 0.40 mm^−1^T = 298 K0.41 × 0.33 × 0.26 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometer4954 measured reflections2355 independent reflections2297 reflections with I \> 2σ(I)R ~int~ = 0.015 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.028wR(F ^2^) = 0.080S = 1.082355 reflections193 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.22 e Å^−3^Absolute structure: Flack & Bernardinelli (2000[@bb9]), 614 Friedel pairsFlack parameter: −0.02 (5) {#d5e465} Data collection: APEX2 (Bruker, 2009[@bb1]); cell refinement: SAINT-Plus (Bruker, 2009[@bb1]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb13]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb13]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb7]) and PLATON (Spek, 2009[@bb14]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005307/fj2396sup1.cif](http://dx.doi.org/10.1107/S1600536811005307/fj2396sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005307/fj2396Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005307/fj2396Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?fj2396&file=fj2396sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?fj2396sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?fj2396&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [FJ2396](http://scripts.iucr.org/cgi-bin/sendsup?fj2396)). We thank the National Center of Scientific and Technological Research (CNRST) which supports our scientific research. Comment ======= The essential oil of the Alas cedar (Cedrus atlantica) consist mainly (50%) of a bicyclic hydrocarbon called β-himachalene (Joseph & Dev (1968); Plattier & Teisseire(1974)). The reactivity of this sesquiterpene and its derivatives has been studied extensively by our team in order to prepare new products having biological proprieties (Lassaba et al., 1998; Chekroun et al., 2000; El Jamili et al., 2002; Dakir et al., 2004). Indeed, these compounds were tested, using the food poisoning technique, for their potential antifungal activity against phytopathogen Botrytis cinerea (Daoubi et al., 2004). Thus the action of one equivalent of dichlorocarbene, generated in situ from chloroform in the presence of sodium hydroxide as base and n-benzyltriethylammonium chloride as catalyst, on β-himachalene produces only (1S,3R,8R)-2,2-dichloro-3,7,7,10- tetramethyltricyclo\[6.4.0.0^1,3^\] dodec-9-ene (El Jamili et al., 2002). Treatment of the latter by two equivalents of N-bromosccinimide (NBS) give (1S, 3R, 8R, 11R)-2,2-dichloro-3,7,7,10-tetralethyltricyclo\[6.4.0.0^1,3^\] dodec-9-en-11-one(Dakir et al., 2004). This enone was treated with the sodium azide in trifluoroacetic acide medium, give with a yield (60%) (1S, 3R, 8R) -9-(1-aminoethylidene)-2,2-dichloro-3,7,7- trimethyltricyclo\[6.3.0.0^1,3^\]undecan -10-one. The structure of this new product was determined by NMR spectral analysis of 1H, 13 C and mass spectroscopy and confirmed by its single-crystal X-ray structure. The molecule is built up from two fused five-membered and seven-membered rings (Fig. 1). The five-membered ring adopts a twisted conformation,as indicated by Cremer & Pople (1975) puckering parameters Q = 0.2822 (2) Å and φ = 199.2 (4)°. The seven-membered ring displays a chair conformation with QT = 0.7470 (2) Å, θ2 = 27.72 (2)°, φ2 = -51.85 (14)° and φ3 =-78.15 (2)°. In the crystal structure, molecules are linked into chains (Fig. 2) running along the b axis by intermolecular N---H···O hydrogen bonds (Table 1) involving the O1 and N atoms. Owing to the presence of Cl atoms, the absolute configuration could be fully confirmed, by refining the Flack parameter (Flack & Bernardinelli (2000)) as C1(S), C3(R)and C8(R). Experimental {#experimental} ============ To a solution of enone 1 g (3.32 mmol) in 20 ml of trifluoroacetic acid at 10 °C was added with stirring 1 g (15.38 mmol) of NaN3. After being stirred at room temperature for 24 h, the reaction mixture was neutralized with a solution of Na2CO3 (10%) and extracted three time with diethylether (3x20ml). The combined organic phases were dried on Na2SO4, filtred and concentrated at reduced pressure to give the crude product which was chromatographed on a silica gel column with hexane- ether as eluent (20/80) to give 630 mg(1.99 mmol) of (1S, 3R, 8R)-9-(1-aminoethylidene)-2,2-dichloro-3,7,7-trimethyltricyclo \[6.3.0.0^1,3^\]undecan -10-one.The title compound was recrystallized in diethylether. Refinement {#refinement} ========== except H1 and H2,all H atoms were fixed geometrically and treated as riding with C---H = 0.96 Å (methyl), 0.97 Å (methylene), 0.98Å (methine) with U~iso~(H) = 1.2U~eq~ (methylene, methine) or U~iso~(H) = 1.5U~eq~ (methyl). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### : Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability. level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o645-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### : Partial packing view showing the C---H···O interactions (dashed lines) and the formation of a chain parallel to the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity. \[Symmetry code:(i) 2 - y, x-y, z - 1/3\] ::: ![](e-67-0o645-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e238 .table-wrap} ------------------------ --------------------------------------- C~16~H~23~Cl~2~NO F(000) = 336 M~r~ = 316.25 D~x~ = 1.308 Mg m^−3^ Monoclinic, P2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2yb Cell parameters from 4954 reflections a = 7.7570 (7) Å θ = 3.4--26.4° b = 9.7041 (9) Å µ = 0.40 mm^−1^ c = 10.6901 (10) Å T = 298 K β = 93.432 (3)° Prism, colourless V = 803.25 (13) Å^3^ 0.41 × 0.33 × 0.26 mm Z = 2 ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e363 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2297 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.015 graphite θ~max~ = 26.4°, θ~min~ = 3.4° ω and φ scans h = −9→9 4954 measured reflections k = −12→6 2355 independent reflections l = −12→13 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e461 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.028 H atoms treated by a mixture of independent and constrained refinement wR(F^2^) = 0.080 w = 1/\[σ^2^(F~o~^2^) + (0.0528P)^2^ + 0.0821P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.08 (Δ/σ)~max~ = 0.001 2355 reflections Δρ~max~ = 0.24 e Å^−3^ 193 parameters Δρ~min~ = −0.22 e Å^−3^ 1 restraint Absolute structure: Flack & Bernardinelli (2000), 614 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.02 (5) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e629 .table-wrap} -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e649 .table-wrap} ------ ------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ H2 1.000 (3) −0.257 (3) 0.553 (2) 0.042 (6)\ H1 0.933 (3) −0.125 (4) 0.502 (3) 0.050 (7)\* Cl1 0.88492 (8) 0.36063 (7) 0.85606 (7) 0.06081 (18) Cl2 0.79425 (7) 0.12962 (6) 1.00496 (4) 0.05055 (16) C9 0.7491 (2) −0.0408 (2) 0.66044 (16) 0.0293 (4) O1 0.8629 (2) 0.07077 (17) 0.48287 (13) 0.0448 (4) C8 0.6205 (2) 0.0004 (2) 0.75543 (15) 0.0274 (4) H8 0.6565 −0.0383 0.8375 0.033\* C1 0.6443 (2) 0.15793 (19) 0.75843 (15) 0.0297 (4) C12 0.8402 (2) −0.16350 (19) 0.65295 (17) 0.0321 (4) C10 0.7797 (2) 0.0713 (2) 0.57971 (17) 0.0333 (4) N1 0.9341 (3) −0.1878 (2) 0.5548 (2) 0.0444 (4) C7 0.4310 (2) −0.0475 (2) 0.71640 (17) 0.0357 (4) C3 0.5434 (3) 0.2575 (2) 0.83808 (17) 0.0362 (4) C2 0.7312 (2) 0.2285 (2) 0.87178 (18) 0.0363 (4) C4 0.4090 (3) 0.2029 (3) 0.9238 (2) 0.0462 (5) H4A 0.4656 0.1417 0.9852 0.055\* H4B 0.3620 0.2797 0.9688 0.055\* C16 0.4318 (3) −0.2036 (3) 0.6976 (2) 0.0451 (5) H16A 0.5082 −0.2267 0.6333 0.068\* H16B 0.3171 −0.2344 0.6731 0.068\* H16C 0.4707 −0.2478 0.7745 0.068\* C11 0.7012 (3) 0.2010 (2) 0.62976 (17) 0.0386 (5) H11A 0.6033 0.2311 0.5759 0.046\* H11B 0.7855 0.2747 0.6371 0.046\* C14 0.4943 (4) 0.3966 (3) 0.7812 (2) 0.0543 (6) H14A 0.5823 0.4261 0.7276 0.082\* H14B 0.4834 0.4629 0.8469 0.082\* H14C 0.3863 0.3887 0.7330 0.082\* C5 0.2612 (3) 0.1259 (3) 0.8557 (2) 0.0551 (6) H5A 0.2260 0.1757 0.7798 0.066\* H5B 0.1637 0.1242 0.9084 0.066\* C6 0.3060 (3) −0.0212 (3) 0.8212 (2) 0.0491 (5) H6A 0.1986 −0.0681 0.7975 0.059\* H6B 0.3545 −0.0657 0.8966 0.059\* C15 0.3604 (3) 0.0199 (3) 0.5944 (2) 0.0512 (6) H15A 0.3540 0.1178 0.6058 0.077\* H15B 0.2472 −0.0157 0.5721 0.077\* H15C 0.4358 −0.0003 0.5287 0.077\* C13 0.8492 (3) −0.2716 (3) 0.7522 (2) 0.0488 (5) H13A 0.9673 −0.2981 0.7700 0.073\* H13B 0.7832 −0.3504 0.7236 0.073\* H13C 0.8028 −0.2358 0.8268 0.073\* ------ ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1244 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cl1 0.0562 (3) 0.0361 (3) 0.0907 (4) −0.0136 (3) 0.0093 (3) −0.0118 (3) Cl2 0.0568 (3) 0.0510 (3) 0.0424 (2) 0.0037 (3) −0.0094 (2) −0.0038 (2) C9 0.0310 (8) 0.0247 (9) 0.0331 (8) −0.0017 (7) 0.0087 (6) −0.0004 (7) O1 0.0579 (9) 0.0357 (8) 0.0439 (7) −0.0015 (7) 0.0276 (6) 0.0035 (6) C8 0.0315 (8) 0.0246 (9) 0.0266 (7) −0.0005 (7) 0.0060 (6) 0.0011 (6) C1 0.0335 (8) 0.0239 (10) 0.0326 (8) 0.0028 (7) 0.0085 (6) 0.0003 (7) C12 0.0317 (8) 0.0242 (11) 0.0406 (9) −0.0021 (7) 0.0043 (7) −0.0033 (7) C10 0.0380 (9) 0.0274 (10) 0.0354 (8) −0.0023 (8) 0.0103 (7) 0.0017 (7) N1 0.0467 (10) 0.0312 (10) 0.0571 (11) 0.0074 (9) 0.0187 (8) −0.0038 (10) C7 0.0328 (9) 0.0380 (11) 0.0365 (9) −0.0049 (8) 0.0048 (7) −0.0009 (8) C3 0.0429 (10) 0.0292 (10) 0.0372 (9) 0.0069 (8) 0.0097 (7) −0.0042 (8) C2 0.0410 (10) 0.0262 (10) 0.0419 (9) −0.0012 (8) 0.0055 (8) −0.0051 (8) C4 0.0469 (11) 0.0492 (14) 0.0444 (10) 0.0094 (10) 0.0175 (8) −0.0066 (10) C16 0.0449 (11) 0.0412 (13) 0.0493 (11) −0.0131 (10) 0.0039 (9) −0.0024 (10) C11 0.0546 (12) 0.0245 (10) 0.0382 (9) 0.0020 (8) 0.0159 (8) 0.0049 (8) C14 0.0698 (15) 0.0353 (13) 0.0589 (13) 0.0194 (11) 0.0119 (11) −0.0001 (11) C5 0.0365 (10) 0.0652 (17) 0.0656 (12) 0.0064 (12) 0.0196 (9) −0.0057 (14) C6 0.0361 (10) 0.0549 (15) 0.0579 (12) −0.0084 (10) 0.0156 (9) −0.0035 (11) C15 0.0459 (12) 0.0577 (16) 0.0484 (11) 0.0006 (11) −0.0093 (9) 0.0019 (11) C13 0.0531 (12) 0.0324 (12) 0.0613 (12) 0.0075 (10) 0.0052 (10) 0.0115 (10) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1640 .table-wrap} ---------------- ------------- ------------------- ------------- Cl1---C2 1.766 (2) C4---C5 1.517 (4) Cl2---C2 1.762 (2) C4---H4A 0.9700 C9---C12 1.389 (3) C4---H4B 0.9700 C9---C10 1.418 (3) C16---H16A 0.9600 C9---C8 1.519 (2) C16---H16B 0.9600 O1---C10 1.253 (2) C16---H16C 0.9600 C8---C1 1.539 (3) C11---H11A 0.9700 C8---C7 1.574 (2) C11---H11B 0.9700 C8---H8 0.9800 C14---H14A 0.9600 C1---C2 1.515 (3) C14---H14B 0.9600 C1---C11 1.528 (2) C14---H14C 0.9600 C1---C3 1.533 (2) C5---C6 1.519 (4) C12---N1 1.334 (3) C5---H5A 0.9700 C12---C13 1.490 (3) C5---H5B 0.9700 C10---C11 1.509 (3) C6---H6A 0.9700 N1---H2 0.84 (3) C6---H6B 0.9700 N1---H1 0.83 (3) C15---H15A 0.9600 C7---C16 1.528 (3) C15---H15B 0.9600 C7---C15 1.531 (3) C15---H15C 0.9600 C7---C6 1.546 (3) C13---H13A 0.9600 C3---C2 1.506 (3) C13---H13B 0.9600 C3---C14 1.520 (3) C13---H13C 0.9600 C3---C4 1.524 (3) C12---C9---C10 121.23 (16) C5---C4---H4B 108.7 C12---C9---C8 128.39 (17) C3---C4---H4B 108.7 C10---C9---C8 110.19 (16) H4A---C4---H4B 107.6 C9---C8---C1 101.12 (14) C7---C16---H16A 109.5 C9---C8---C7 112.64 (14) C7---C16---H16B 109.5 C1---C8---C7 114.08 (16) H16A---C16---H16B 109.5 C9---C8---H8 109.6 C7---C16---H16C 109.5 C1---C8---H8 109.6 H16A---C16---H16C 109.5 C7---C8---H8 109.6 H16B---C16---H16C 109.5 C2---C1---C11 117.28 (17) C10---C11---C1 103.64 (15) C2---C1---C3 59.21 (12) C10---C11---H11A 111.0 C11---C1---C3 120.82 (16) C1---C11---H11A 111.0 C2---C1---C8 120.85 (16) C10---C11---H11B 111.0 C11---C1---C8 107.05 (14) C1---C11---H11B 111.0 C3---C1---C8 124.93 (16) H11A---C11---H11B 109.0 N1---C12---C9 120.03 (19) C3---C14---H14A 109.5 N1---C12---C13 115.56 (19) C3---C14---H14B 109.5 C9---C12---C13 124.34 (17) H14A---C14---H14B 109.5 O1---C10---C9 127.82 (19) C3---C14---H14C 109.5 O1---C10---C11 122.38 (17) H14A---C14---H14C 109.5 C9---C10---C11 109.76 (15) H14B---C14---H14C 109.5 C12---N1---H2 120.9 (16) C4---C5---C6 113.71 (19) C12---N1---H1 115.2 (19) C4---C5---H5A 108.8 H2---N1---H1 123 (2) C6---C5---H5A 108.8 C16---C7---C15 108.37 (18) C4---C5---H5B 108.8 C16---C7---C6 105.49 (18) C6---C5---H5B 108.8 C15---C7---C6 109.80 (18) H5A---C5---H5B 107.7 C16---C7---C8 108.48 (17) C5---C6---C7 119.6 (2) C15---C7---C8 112.35 (17) C5---C6---H6A 107.4 C6---C7---C8 112.04 (16) C7---C6---H6A 107.4 C2---C3---C14 118.5 (2) C5---C6---H6B 107.4 C2---C3---C4 118.56 (17) C7---C6---H6B 107.4 C14---C3---C4 112.69 (18) H6A---C6---H6B 107.0 C2---C3---C1 59.77 (12) C7---C15---H15A 109.5 C14---C3---C1 117.47 (17) C7---C15---H15B 109.5 C4---C3---C1 120.35 (18) H15A---C15---H15B 109.5 C3---C2---C1 61.01 (12) C7---C15---H15C 109.5 C3---C2---Cl2 120.86 (14) H15A---C15---H15C 109.5 C1---C2---Cl2 119.26 (15) H15B---C15---H15C 109.5 C3---C2---Cl1 119.40 (16) C12---C13---H13A 109.5 C1---C2---Cl1 121.53 (14) C12---C13---H13B 109.5 Cl2---C2---Cl1 108.41 (11) H13A---C13---H13B 109.5 C5---C4---C3 114.04 (18) C12---C13---H13C 109.5 C5---C4---H4A 108.7 H13A---C13---H13C 109.5 C3---C4---H4A 108.7 H13B---C13---H13C 109.5 ---------------- ------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2277 .table-wrap} ----------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H2···O1^i^ 0.85 (3) 2.03 (3) 2.865 (3) 170 (2) N1---H1···O1 0.83 (4) 1.98 (4) 2.672 (3) 140 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+2, y−1/2, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- ---------- ---------- ----------- ------------- N1---H2⋯O1^i^ 0.85 (3) 2.03 (3) 2.865 (3) 170 (2) N1---H1⋯O1 0.83 (4) 1.98 (4) 2.672 (3) 140 (3) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.505082	2011-2-16	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052109/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o645-o646", "authors": [ { "first": "Ahmed", "last": "Benharref" }, { "first": "Essêdiya", "last": "Lassaba" }, { "first": "Daniel", "last": "Avignant" }, { "first": "Abdelghani", "last": "Oudahmane" }, { "first": "Moha", "last": "Berraho" } ] }
PMC3052110	Related literature {#sec1} ================== For related structures, see: Keypour et al. (2009[@bb3]). For background information on diimine complexes, see: Mahmoudi et al. (2009[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~29~H~25~N~3~O~3~M ~r~ = 463.52Monoclinic,a = 9.1097 (6) Åb = 18.1946 (11) Åc = 13.7769 (5) Åβ = 93.405 (4)°V = 2279.5 (2) Å^3^Z = 4Mo Kα radiationμ = 0.09 mm^−1^T = 150 K0.25 × 0.12 × 0.10 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (SORTAV; Blessing, 1995[@bb2]) T ~min~ = 0.866, T ~max~ = 0.99316359 measured reflections5135 independent reflections3083 reflections with I \> 2σ(I)R ~int~ = 0.054 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.055wR(F ^2^) = 0.137S = 1.065135 reflections318 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e439} Data collection: COLLECT (Nonius, 2002[@bb5]); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997[@bb6]); data reduction: DENZO-SMN; program(s) used to solve structure: SIR92 (Altomare et al., 1994[@bb1]); program(s) used to refine structure: SHELXTL (Sheldrick, 2008[@bb7]); molecular graphics: PLATON (Spek, 2009[@bb8]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005319/bh2338sup1.cif](http://dx.doi.org/10.1107/S1600536811005319/bh2338sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005319/bh2338Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005319/bh2338Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bh2338&file=bh2338sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bh2338sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bh2338&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BH2338](http://scripts.iucr.org/cgi-bin/sendsup?bh2338)). We are grateful to Bu-Ali Sina and Alzahra Universities for financial support. Comment ======= In our ongoing studies on the synthesis, structural and spectroscopic characterization of the products derived from N^1^-(3-(2-aminophenoxy)propyl)-benzene-1,2-diamine with aldehydes (Keypour et al., 2009; Mahmoudi et al., 2009) we report herein the crystal structure of the title compound, prepared by the reaction of N^1^-(3-(2-aminophenoxy)propyl)-benzene-1,2-diamine with salicyl aldehyde. The molecular structure of the title compound is shown in Fig. 1. The molecule adopts the E configuration with respect to the imine C═N bond. Two hydroxyl groups are located close to N atoms, and form strong intramolecular hydrogen bonds (Table 1). Experimental {#experimental} ============ N^1^-(3-(2-aminophenoxy)propyl)benzene-1,2-diamine (0.064 g, 0.25 mmol) in methanol (20 ml) was added dropwise with stirring to a solution of salicylaldehyde (0.061 g, 0.5 mmol) in methanol (30 ml). The mixture was refluxed for 12 h. Then, the solution volume was reduced to 10 ml by evaporation, and a precipitate was formed. This was filtered off, washed with ether, and dried in vacuo. Vapour diffusion of diethyl ether into a methanolic solution of the product afforded yellow crystals in 60% yield. Refinement {#refinement} ========== All C-bonded H atoms positions were calculated and refined with a riding model and U~iso~(H) parameters set to 1.2 times U~eq~(carrier C atom). Hydroxyl H atoms also ride on their O atoms, with O---H bond lengths fixed to 0.84 Å and U~iso~(H) = 1.5 U~eq~(carrier O atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the structure of the title complex, with displacement ellipsoids drawn at the 50% probability level. ::: ![](e-67-0o657-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e140 .table-wrap} ------------------------- ---------------------------------------- C~29~H~25~N~3~O~3~ F(000) = 976 M~r~ = 463.52 D~x~ = 1.351 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 16359 reflections a = 9.1097 (6) Å θ = 2.7--27.5° b = 18.1946 (11) Å µ = 0.09 mm^−1^ c = 13.7769 (5) Å T = 150 K β = 93.405 (4)° Needle, yellow V = 2279.5 (2) Å^3^ 0.25 × 0.12 × 0.10 mm Z = 4 ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 5135 independent reflections Radiation source: fine-focus sealed tube 3083 reflections with I \> 2σ(I) graphite R~int~ = 0.054 Detector resolution: 9 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.7° φ scans and ω scans with κ offsets h = −11→11 Absorption correction: multi-scan (SORTAV; Blessing, 1995) k = −22→23 T~min~ = 0.866, T~max~ = 0.993 l = −17→17 16359 measured reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e396 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.137 H-atom parameters constrained S = 1.06 w = 1/\[σ^2^(F~o~^2^) + (0.0536P)^2^ + 0.4485P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5135 reflections (Δ/σ)~max~ = 0.001 318 parameters Δρ~max~ = 0.23 e Å^−3^ 1 restraint Δρ~min~ = −0.20 e Å^−3^ 0 constraints ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e559 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.98262 (18) 0.22668 (8) 0.88875 (9) 0.0465 (4) H1O 0.9212 0.1922 0.8864 0.070\ O2 0.80830 (16) 0.02045 (7) 0.35975 (9) 0.0369 (4) O3 0.69646 (17) −0.13681 (8) 0.49252 (9) 0.0418 (4) H2O 0.7212 −0.1156 0.4418 0.063\* N1 0.82575 (18) 0.08636 (9) 0.66217 (11) 0.0352 (4) N2 0.80517 (19) 0.13040 (9) 0.81279 (11) 0.0378 (4) N3 0.70199 (18) −0.10938 (9) 0.31140 (11) 0.0323 (4) C1 0.8674 (2) 0.13987 (11) 0.72906 (13) 0.0348 (5) C2 0.7258 (2) 0.04118 (11) 0.70695 (14) 0.0355 (5) C3 0.6454 (2) −0.01894 (12) 0.67220 (16) 0.0424 (5) H3A 0.6527 −0.0369 0.6079 0.051\* C4 0.5538 (2) −0.05139 (12) 0.73642 (17) 0.0461 (6) H4A 0.4961 −0.0926 0.7155 0.055\* C5 0.5439 (2) −0.02520 (12) 0.83139 (17) 0.0462 (6) H5A 0.4805 −0.0492 0.8736 0.055\* C6 0.6241 (2) 0.03446 (12) 0.86451 (16) 0.0428 (5) H6A 0.6173 0.0520 0.9290 0.051\* C7 0.7156 (2) 0.06849 (11) 0.80071 (14) 0.0371 (5) C8 0.9683 (2) 0.20146 (11) 0.71522 (14) 0.0342 (5) C9 1.0249 (2) 0.24102 (12) 0.79778 (14) 0.0358 (5) C10 1.1272 (2) 0.29677 (12) 0.78825 (15) 0.0406 (5) H10A 1.1682 0.3211 0.8445 0.049\* C11 1.1694 (2) 0.31703 (12) 0.69784 (16) 0.0433 (5) H11A 1.2402 0.3549 0.6920 0.052\* C12 1.1092 (2) 0.28247 (12) 0.61553 (15) 0.0411 (5) H12A 1.1353 0.2979 0.5530 0.049\* C13 1.0116 (2) 0.22574 (11) 0.62434 (14) 0.0375 (5) H13A 0.9720 0.2021 0.5671 0.045\* C14 0.8752 (2) 0.07122 (11) 0.56509 (13) 0.0354 (5) H14A 0.8771 0.0174 0.5545 0.042\* H14B 0.9765 0.0900 0.5607 0.042\* C15 0.7747 (2) 0.10687 (12) 0.48571 (13) 0.0372 (5) H15A 0.6749 0.0856 0.4877 0.045\* H15B 0.7675 0.1602 0.4991 0.045\* C16 0.8287 (2) 0.09626 (11) 0.38527 (14) 0.0375 (5) H16A 0.7725 0.1280 0.3380 0.045\* H16B 0.9341 0.1095 0.3847 0.045\* C17 0.8190 (2) 0.00152 (11) 0.26392 (13) 0.0319 (5) C18 0.8766 (2) 0.04669 (12) 0.19473 (14) 0.0382 (5) H18A 0.9154 0.0936 0.2127 0.046\* C19 0.8774 (2) 0.02298 (12) 0.09868 (15) 0.0420 (5) H19A 0.9156 0.0542 0.0510 0.050\* C20 0.8233 (2) −0.04524 (12) 0.07220 (14) 0.0408 (5) H20A 0.8249 −0.0611 0.0066 0.049\* C21 0.7667 (2) −0.09051 (12) 0.14125 (14) 0.0367 (5) H21A 0.7311 −0.1379 0.1230 0.044\* C22 0.7614 (2) −0.06751 (11) 0.23715 (13) 0.0320 (5) C23 0.5987 (2) −0.15625 (11) 0.29380 (14) 0.0344 (5) H23A 0.5604 −0.1634 0.2288 0.041\* C24 0.5396 (2) −0.19841 (11) 0.37172 (14) 0.0339 (5) C25 0.4292 (2) −0.25061 (12) 0.35230 (16) 0.0403 (5) H25A 0.3930 −0.2584 0.2870 0.048\* C26 0.3717 (2) −0.29106 (12) 0.42569 (17) 0.0458 (6) H26A 0.2965 −0.3263 0.4114 0.055\* C27 0.4258 (2) −0.27940 (12) 0.52143 (16) 0.0444 (6) H27A 0.3875 −0.3073 0.5725 0.053\* C28 0.5338 (2) −0.22813 (12) 0.54275 (15) 0.0407 (5) H28A 0.5687 −0.2206 0.6083 0.049\* C29 0.5923 (2) −0.18717 (11) 0.46906 (14) 0.0340 (5) ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1372 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0556 (11) 0.0529 (11) 0.0310 (8) −0.0016 (8) 0.0015 (7) −0.0072 (7) O2 0.0491 (9) 0.0346 (8) 0.0271 (7) −0.0053 (7) 0.0029 (6) −0.0018 (6) O3 0.0502 (10) 0.0431 (9) 0.0320 (8) −0.0091 (7) 0.0014 (6) 0.0014 (6) N1 0.0373 (10) 0.0394 (10) 0.0289 (9) 0.0047 (8) 0.0017 (7) −0.0045 (7) N2 0.0435 (11) 0.0402 (11) 0.0298 (9) 0.0039 (9) 0.0032 (7) −0.0015 (7) N3 0.0351 (10) 0.0305 (10) 0.0314 (9) 0.0023 (8) 0.0033 (7) 0.0000 (7) C1 0.0339 (12) 0.0397 (13) 0.0307 (11) 0.0079 (9) −0.0001 (8) −0.0026 (9) C2 0.0312 (12) 0.0353 (12) 0.0401 (12) 0.0057 (9) 0.0023 (9) 0.0017 (9) C3 0.0427 (13) 0.0416 (14) 0.0423 (13) 0.0072 (11) −0.0021 (10) −0.0059 (10) C4 0.0393 (14) 0.0382 (13) 0.0604 (15) 0.0013 (11) −0.0010 (11) −0.0007 (11) C5 0.0420 (14) 0.0399 (14) 0.0577 (15) 0.0057 (11) 0.0120 (11) 0.0111 (11) C6 0.0461 (14) 0.0430 (14) 0.0398 (12) 0.0082 (11) 0.0076 (10) 0.0045 (10) C7 0.0366 (12) 0.0392 (13) 0.0354 (12) 0.0060 (10) 0.0017 (9) −0.0001 (9) C8 0.0298 (11) 0.0366 (12) 0.0358 (11) 0.0035 (9) −0.0005 (8) −0.0022 (9) C9 0.0358 (12) 0.0432 (13) 0.0283 (11) 0.0114 (10) 0.0000 (8) −0.0022 (9) C10 0.0368 (13) 0.0430 (13) 0.0410 (13) 0.0051 (11) −0.0046 (9) −0.0104 (10) C11 0.0356 (13) 0.0408 (13) 0.0533 (14) 0.0008 (10) 0.0021 (10) −0.0037 (10) C12 0.0413 (13) 0.0444 (14) 0.0380 (12) 0.0029 (11) 0.0062 (9) −0.0009 (10) C13 0.0387 (13) 0.0415 (13) 0.0321 (11) 0.0024 (10) 0.0001 (9) −0.0048 (9) C14 0.0390 (12) 0.0399 (12) 0.0275 (11) 0.0067 (10) 0.0041 (8) −0.0067 (9) C15 0.0392 (12) 0.0392 (13) 0.0327 (11) 0.0039 (10) −0.0007 (9) −0.0045 (9) C16 0.0437 (13) 0.0349 (12) 0.0335 (11) −0.0050 (10) −0.0003 (9) −0.0007 (9) C17 0.0323 (11) 0.0390 (12) 0.0244 (10) 0.0016 (9) 0.0011 (8) −0.0013 (8) C18 0.0417 (13) 0.0408 (13) 0.0325 (12) −0.0043 (10) 0.0051 (9) 0.0012 (9) C19 0.0448 (14) 0.0487 (14) 0.0334 (12) −0.0011 (11) 0.0102 (9) 0.0040 (10) C20 0.0458 (14) 0.0488 (14) 0.0286 (11) 0.0046 (11) 0.0080 (9) −0.0028 (9) C21 0.0398 (13) 0.0366 (13) 0.0336 (11) 0.0047 (10) 0.0024 (9) −0.0041 (9) C22 0.0308 (11) 0.0342 (12) 0.0310 (11) 0.0050 (9) 0.0027 (8) 0.0025 (8) C23 0.0376 (12) 0.0333 (12) 0.0322 (11) 0.0058 (10) 0.0019 (9) −0.0013 (9) C24 0.0346 (12) 0.0297 (11) 0.0377 (12) 0.0050 (9) 0.0040 (9) −0.0009 (9) C25 0.0384 (13) 0.0353 (12) 0.0471 (13) 0.0004 (10) 0.0025 (10) −0.0056 (10) C26 0.0382 (14) 0.0345 (13) 0.0649 (16) −0.0034 (10) 0.0058 (11) 0.0011 (11) C27 0.0413 (14) 0.0381 (13) 0.0549 (14) 0.0044 (11) 0.0116 (10) 0.0133 (10) C28 0.0406 (13) 0.0407 (13) 0.0414 (12) 0.0051 (11) 0.0061 (9) 0.0085 (10) C29 0.0330 (12) 0.0295 (12) 0.0397 (12) 0.0026 (9) 0.0043 (9) 0.0005 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2018 .table-wrap} ------------------ ------------- ------------------- ------------- O1---C9 1.358 (2) C12---H12A 0.9500 O1---H1O 0.8400 C13---H13A 0.9500 O2---C17 1.373 (2) C14---C15 1.528 (3) O2---C16 1.433 (2) C14---H14A 0.9900 O3---C29 1.344 (2) C14---H14B 0.9900 O3---H2O 0.8400 C15---C16 1.508 (3) N1---C1 1.378 (2) C15---H15A 0.9900 N1---C2 1.397 (3) C15---H15B 0.9900 N1---C14 1.462 (2) C16---H16A 0.9900 N2---C1 1.326 (2) C16---H16B 0.9900 N2---C7 1.395 (3) C17---C18 1.385 (3) N3---C23 1.282 (2) C17---C22 1.402 (3) N3---C22 1.409 (2) C18---C19 1.392 (3) C1---C8 1.469 (3) C18---H18A 0.9500 C2---C3 1.386 (3) C19---C20 1.377 (3) C2---C7 1.392 (3) C19---H19A 0.9500 C3---C4 1.384 (3) C20---C21 1.381 (3) C3---H3A 0.9500 C20---H20A 0.9500 C4---C5 1.400 (3) C21---C22 1.390 (3) C4---H4A 0.9500 C21---H21A 0.9500 C5---C6 1.371 (3) C23---C24 1.449 (3) C5---H5A 0.9500 C23---H23A 0.9500 C6---C7 1.392 (3) C24---C25 1.397 (3) C6---H6A 0.9500 C24---C29 1.412 (3) C8---C13 1.406 (3) C25---C26 1.379 (3) C8---C9 1.417 (3) C25---H25A 0.9500 C9---C10 1.388 (3) C26---C27 1.397 (3) C10---C11 1.376 (3) C26---H26A 0.9500 C10---H10A 0.9500 C27---C28 1.374 (3) C11---C12 1.381 (3) C27---H27A 0.9500 C11---H11A 0.9500 C28---C29 1.391 (3) C12---C13 1.372 (3) C28---H28A 0.9500 C9---O1---H1O 109.5 H14A---C14---H14B 107.9 C17---O2---C16 117.50 (14) C16---C15---C14 112.85 (17) C29---O3---H2O 109.5 C16---C15---H15A 109.0 C1---N1---C2 106.32 (16) C14---C15---H15A 109.0 C1---N1---C14 131.09 (17) C16---C15---H15B 109.0 C2---N1---C14 122.48 (16) C14---C15---H15B 109.0 C1---N2---C7 106.17 (16) H15A---C15---H15B 107.8 C23---N3---C22 122.11 (16) O2---C16---C15 107.68 (16) N2---C1---N1 112.02 (18) O2---C16---H16A 110.2 N2---C1---C8 121.00 (17) C15---C16---H16A 110.2 N1---C1---C8 126.98 (18) O2---C16---H16B 110.2 C3---C2---C7 122.6 (2) C15---C16---H16B 110.2 C3---C2---N1 131.05 (19) H16A---C16---H16B 108.5 C7---C2---N1 106.32 (18) O2---C17---C18 124.33 (18) C4---C3---C2 116.2 (2) O2---C17---C22 115.51 (17) C4---C3---H3A 121.9 C18---C17---C22 120.12 (17) C2---C3---H3A 121.9 C17---C18---C19 119.6 (2) C3---C4---C5 121.8 (2) C17---C18---H18A 120.2 C3---C4---H4A 119.1 C19---C18---H18A 120.2 C5---C4---H4A 119.1 C20---C19---C18 120.6 (2) C6---C5---C4 121.2 (2) C20---C19---H19A 119.7 C6---C5---H5A 119.4 C18---C19---H19A 119.7 C4---C5---H5A 119.4 C19---C20---C21 119.83 (19) C5---C6---C7 118.0 (2) C19---C20---H20A 120.1 C5---C6---H6A 121.0 C21---C20---H20A 120.1 C7---C6---H6A 121.0 C20---C21---C22 120.7 (2) C6---C7---C2 120.2 (2) C20---C21---H21A 119.6 C6---C7---N2 130.68 (19) C22---C21---H21A 119.6 C2---C7---N2 109.13 (17) C21---C22---C17 119.08 (18) C13---C8---C9 116.56 (19) C21---C22---N3 124.35 (18) C13---C8---C1 124.48 (18) C17---C22---N3 116.57 (16) C9---C8---C1 118.95 (18) N3---C23---C24 120.85 (18) O1---C9---C10 117.15 (18) N3---C23---H23A 119.6 O1---C9---C8 122.22 (19) C24---C23---H23A 119.6 C10---C9---C8 120.63 (18) C25---C24---C29 118.71 (18) C11---C10---C9 120.45 (19) C25---C24---C23 120.85 (18) C11---C10---H10A 119.8 C29---C24---C23 120.43 (18) C9---C10---H10A 119.8 C26---C25---C24 121.5 (2) C10---C11---C12 120.2 (2) C26---C25---H25A 119.2 C10---C11---H11A 119.9 C24---C25---H25A 119.2 C12---C11---H11A 119.9 C25---C26---C27 118.9 (2) C13---C12---C11 119.8 (2) C25---C26---H26A 120.6 C13---C12---H12A 120.1 C27---C26---H26A 120.6 C11---C12---H12A 120.1 C28---C27---C26 120.9 (2) C12---C13---C8 122.18 (18) C28---C27---H27A 119.6 C12---C13---H13A 118.9 C26---C27---H27A 119.6 C8---C13---H13A 118.9 C27---C28---C29 120.5 (2) N1---C14---C15 111.78 (16) C27---C28---H28A 119.7 N1---C14---H14A 109.3 C29---C28---H28A 119.7 C15---C14---H14A 109.3 O3---C29---C28 119.03 (18) N1---C14---H14B 109.3 O3---C29---C24 121.48 (18) C15---C14---H14B 109.3 C28---C29---C24 119.48 (19) ------------------ ------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2803 .table-wrap} --------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1O···N2 0.84 1.81 2.564 (2) 148 O3---H2O···N3 0.84 1.80 2.548 (2) 148 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- --------- ------- ----------- ------------- O1---H1O⋯N2 0.84 1.81 2.564 (2) 148 O3---H2O⋯N3 0.84 1.80 2.548 (2) 148 :::	PubMed Central	2024-06-05T04:04:18.510005	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052110/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o657-o658", "authors": [ { "first": "Hassan", "last": "Keypour" }, { "first": "Sareh", "last": "Tamizi" }, { "first": "Saeed", "last": "Dehghanpour" }, { "first": "Reza", "last": "Azadbakht" }, { "first": "Mehdi", "last": "Khalaj" } ] }
PMC3052111	Related literature {#sec1} ================== For other metal complexes based on the N,N-dimethylaminomethane-1,1- diphosphonate ligand, see: Du et al. (2009[@bb4], 2010a [@bb5],b [@bb6]). For bond-length data, see: Lutz & Muller (1995[@bb7]); Distler et al. (1999[@bb3]); Stock & Bein (2004[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Mg(C~3~H~10~NO~6~P~2~)~2~\]M ~r~ = 460.43Monoclinic,a = 5.4507 (3) Åb = 11.2166 (6) Åc = 12.5770 (7) Åβ = 94.984 (1)°V = 766.03 (7) Å^3^Z = 2Mo Kα radiationμ = 0.61 mm^−1^T = 296 K0.40 × 0.30 × 0.24 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2008[@bb2]) T ~min~ = 0.675, T ~max~ = 0.7464801 measured reflections1492 independent reflections1447 reflections with I \> 2σ(I)R ~int~ = 0.014 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.024wR(F ^2^) = 0.066S = 1.091492 reflections115 parametersH-atom parameters constrainedΔρ~max~ = 0.38 e Å^−3^Δρ~min~ = −0.33 e Å^−3^ {#d5e617} Data collection: SMART (Bruker, 2008[@bb2]); cell refinement: SAINT (Bruker, 2008[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb8]) and DIAMOND (Brandenburg, 1999[@bb1]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005976/sj5102sup1.cif](http://dx.doi.org/10.1107/S1600536811005976/sj5102sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005976/sj5102Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005976/sj5102Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5102&file=sj5102sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5102sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5102&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5102](http://scripts.iucr.org/cgi-bin/sendsup?sj5102)). This work was supported by the Natural Science Foundation of Jiangxi Province (grant 2008GQH0013) and the Natural Science Foundation of Jiangxi Provincial Education Department (grant GJJ09317). Comment ======= Among many of the phosphonate ligands studied so far, methylenediphosphonic acid and its derivatives are quite unique because they feature a close connection of two phosphonate moieties via one carbon atom, which facilitate their combined coordination ability to act as a \[CP~2~O~6~\] unit rather than two \[CPO~3~\] units. As a result, they show diversified coordination capabilities with metal ions and thus lead to the formation of new structural types. Recently, by using such ligand types, i.e. N,N-dimethylaminomethane-1,1-diphosphonate, we have isolated a series of diphosphonate complexes of metals such as Al^III^, Fe^III^, Cd^II^, Pb^II^ and Ba^II^, which exhibit variable structures such as zero-dimensional, one-dimensional, double-1-dimensional, double-2-dimensional, and three-dimensional structures (Du et al., 2009, 2010a,b). As an expansion of our previous work, we have also obtained a one-dimensional magnesium(II) diphosphonate, namely \[Mg(C~6~H~20~N~2~O~12~P~4~)\]~n~, which is isostructural with the previously reported cadmium(II) complex based on the same ligand and shows a one-dimensional chain structure. The asymmetric unit contains a half Mg^2+^ cation and one H~3~L^-^ anion. The unique Mg^2+^ cation lies on an inversion center and is octahedrally coordinated by the O atoms of six phosphonate groups from four H~3~L^-^ anions. The Mg---O \[2.0448 (11) -- 2.1879 (11) Å\] bond lengths are comparable to those reported for other Mg^II^ phosphonate complexes (Lutz & Muller, 1995; Distler et al., 1999; Stock & Bein, 2004). The unique H~3~L^-^ anion, with one protonated N atom and two phosphonate OH groups, serves as a tridentate ligand. By using three of its six phosphonate O atoms, it chelates in a bidentate fashion with one Mg^2+^ cation and also bridges to a second Mg^2+^ ion. The interconnection of Mg^2+^ cations by the H~3~L^-^ anions leads to the formation of a one-dimensional chain along the a-axis, in which the adjacent Mg^2+^ ions are doubly bridged by two equivalent H~3~L^-^ anions. These discrete one-dimensional chains are further assembled into a three-dimensional supramolecular network via O---H···O and N---H···O hydrogen bonds involving the non-coordinated phosphonate O atoms and the protonated N atoms. Experimental {#experimental} ============ For the preparation of (I), a mixture of Mg(NO~3~)~2~ (0.20 mmol) and H~4~L (0.50 mmol) and ethanol (3 ml) in 10 ml distilled water, was sealed into a Parr Teflon-lined autoclave (23 ml) and heated at 393 K for 3 d. Colorless block-shaped crystals were collected in ca 55% yield based on Mg. Analysis calculated for C~6~H~20~N~2~O~12~Mg~1~P~4~: C 15.65, H 4.38, N 6.08%; found: C 15.59, H 4.48, N 6.03%. Refinement {#refinement} ========== The N-bound and the tertiary C-bound H atoms were positioned geometrically and refined using a riding model: N---H = 0.91 and C---H = 0.98 Å, with Uiso(H) = 1.2U~eq~(N, C); while the O-bound and the primary C-bound H atoms were placed in idealized positions and constrained to ride on their parent atoms: O---H = 0.82 and C---H = 0.96 Å, with U~iso~(H) = 1.5 times U~eq~(O, C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the selected unit of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms have been omitted for clarity. \[Symmetry codes: (i) x - 1, y, z; (ii) -x + 1, -y + 1, -z + 1; (iii) -x, -y + 1, -z + 1; (iv) x + 1, y, z.\] ::: ![](e-67-0m362-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the chain structure of (I) along the a-axis. The CPO3 tetrahedra are shaded in purple. Mg, N and C atoms are drawn as cyan, blue and grey circles, respectively. Hydrogen atoms have been omitted for clarity. ::: ![](e-67-0m362-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view of the three-dimensional supramolecular structure of (I) down the a-axis. The MgO6 octahedra and CPO3 tetrahedra are shaded in cyan and purple, respectively. N, C and H atoms are drawn as blue, grey and green circles, respectively. Hydrogen bonds are represented by dashed lines. ::: ![](e-67-0m362-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e335 .table-wrap} ------------------------------- --------------------------------------- \[Mg(C~3~H~10~NO~6~P~2~)~2~\] F(000) = 476 M~r~ = 460.43 D~x~ = 1.996 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 4647 reflections a = 5.4507 (3) Å θ = 2.4--29.4° b = 11.2166 (6) Å µ = 0.61 mm^−1^ c = 12.5770 (7) Å T = 296 K β = 94.984 (1)° Block, colourless V = 766.03 (7) Å^3^ 0.40 × 0.30 × 0.24 mm Z = 2 ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e469 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEX CCD area-detector diffractometer 1492 independent reflections Radiation source: fine-focus sealed tube 1447 reflections with I \> 2σ(I) graphite R~int~ = 0.014 φ and ω scans θ~max~ = 26.0°, θ~min~ = 2.4° Absorption correction: multi-scan (SADABS; Bruker, 2008) h = −6→6 T~min~ = 0.675, T~max~ = 0.746 k = −13→13 4801 measured reflections l = −15→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e586 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.024 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.066 H-atom parameters constrained S = 1.09 w = 1/\[σ^2^(F~o~^2^) + (0.0347P)^2^ + 0.6187P\] where P = (F~o~^2^ + 2F~c~^2^)/3 1492 reflections (Δ/σ)~max~ = 0.001 115 parameters Δρ~max~ = 0.38 e Å^−3^ 0 restraints Δρ~min~ = −0.33 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e743 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. IR data (KBr, ν, cm^-1^): 3437 (m), 3137 (s), 3071 (m), 2986 (m), 2826 (m), 2280 (m), 1815 (m), 1473 (m), 1457 (m), 1421 (m), 1388 (m), 1256 (s), 1225 (s), 1200 (versus), 1155 (s), 1128 (s), 1088 (s), 1036 (s), 995 (s), 950 (s), 928 (s), 854 (m), 827 (m), 725 (m), 615 (m), 573 (s), 517 (m), 476 (m). Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e943 .table-wrap} ----- ------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Mg1 0.0000 0.5000 0.5000 0.01237 (17) P1 0.52519 (7) 0.34374 (3) 0.59421 (3) 0.01109 (12) P2 0.34788 (7) 0.55738 (3) 0.72234 (3) 0.01225 (13) N1 0.5807 (3) 0.35032 (12) 0.81729 (11) 0.0161 (3) H1B 0.6307 0.2757 0.8007 0.019\ C1 0.4187 (3) 0.39596 (14) 0.72149 (12) 0.0126 (3) H1A 0.2596 0.3565 0.7262 0.015\* C2 0.4447 (4) 0.33952 (16) 0.91574 (13) 0.0217 (4) H2A 0.5545 0.3102 0.9737 0.032\* H2B 0.3096 0.2851 0.9024 0.032\* H2C 0.3831 0.4163 0.9341 0.032\* C3 0.8076 (3) 0.42374 (19) 0.84083 (15) 0.0264 (4) H3A 0.9027 0.3918 0.9021 0.040\* H3B 0.7620 0.5045 0.8550 0.040\* H3C 0.9041 0.4221 0.7805 0.040\* O1 0.7774 (2) 0.38860 (10) 0.57970 (9) 0.0168 (3) O2 0.3180 (2) 0.38023 (10) 0.51279 (9) 0.0160 (2) O3 0.5417 (2) 0.20563 (10) 0.60652 (10) 0.0182 (3) H3D 0.4114 0.1800 0.6253 0.027\* O4 0.5780 (2) 0.62560 (11) 0.68532 (9) 0.0177 (3) H4A 0.5846 0.6161 0.6210 0.027\* O5 0.1277 (2) 0.57125 (10) 0.64393 (9) 0.0167 (3) O6 0.3209 (2) 0.59441 (11) 0.83501 (9) 0.0187 (3) ----- ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1257 .table-wrap} ----- ------------- ------------- ------------ --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Mg1 0.0099 (4) 0.0144 (4) 0.0127 (4) −0.0013 (3) 0.0006 (3) 0.0007 (3) P1 0.0111 (2) 0.0108 (2) 0.0117 (2) −0.00042 (14) 0.00234 (15) 0.00033 (14) P2 0.0116 (2) 0.0127 (2) 0.0124 (2) 0.00185 (14) 0.00060 (15) −0.00118 (14) N1 0.0179 (7) 0.0157 (7) 0.0144 (6) 0.0044 (5) −0.0008 (5) 0.0006 (5) C1 0.0116 (7) 0.0146 (7) 0.0114 (7) 0.0011 (6) 0.0004 (6) 0.0000 (6) C2 0.0286 (10) 0.0216 (9) 0.0150 (8) 0.0014 (7) 0.0029 (7) 0.0032 (6) C3 0.0153 (9) 0.0371 (10) 0.0257 (9) −0.0014 (8) −0.0047 (7) 0.0022 (8) O1 0.0137 (6) 0.0172 (6) 0.0200 (6) −0.0027 (4) 0.0041 (4) 0.0022 (5) O2 0.0142 (6) 0.0197 (6) 0.0141 (5) 0.0016 (4) 0.0008 (4) 0.0009 (4) O3 0.0178 (6) 0.0122 (6) 0.0253 (6) −0.0009 (4) 0.0067 (5) 0.0010 (5) O4 0.0171 (6) 0.0191 (6) 0.0171 (5) −0.0036 (5) 0.0022 (5) −0.0025 (5) O5 0.0147 (6) 0.0173 (6) 0.0174 (6) 0.0022 (4) −0.0018 (5) −0.0004 (4) O6 0.0196 (6) 0.0217 (6) 0.0148 (6) 0.0060 (5) 0.0015 (5) −0.0033 (5) ----- ------------- ------------- ------------ --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1524 .table-wrap} ------------------------ ------------- ------------------- ------------- Mg1---O5^i^ 2.0448 (11) N1---C3 1.494 (2) Mg1---O5 2.0448 (11) N1---C2 1.502 (2) Mg1---O1^ii^ 2.0615 (11) N1---C1 1.5196 (19) Mg1---O1^iii^ 2.0616 (11) N1---H1B 0.9100 Mg1---O2 2.1879 (11) C1---H1A 0.9800 Mg1---O2^i^ 2.1879 (11) C2---H2A 0.9600 P1---O1 1.4898 (12) C2---H2B 0.9600 P1---O2 1.5134 (12) C2---H2C 0.9600 P1---O3 1.5587 (12) C3---H3A 0.9600 P1---C1 1.8451 (15) C3---H3B 0.9600 P2---O5 1.4938 (12) C3---H3C 0.9600 P2---O6 1.4961 (12) O1---Mg1^iv^ 2.0615 (11) P2---O4 1.5737 (12) O3---H3D 0.8200 P2---C1 1.8515 (16) O4---H4A 0.8200 O5^i^---Mg1---O5 179.999 (1) C3---N1---C1 112.68 (13) O5^i^---Mg1---O1^ii^ 88.62 (5) C2---N1---C1 112.71 (13) O5---Mg1---O1^ii^ 91.38 (5) C3---N1---H1B 107.1 O5^i^---Mg1---O1^iii^ 91.38 (5) C2---N1---H1B 107.1 O5---Mg1---O1^iii^ 88.62 (5) C1---N1---H1B 107.1 O1^ii^---Mg1---O1^iii^ 180.0 N1---C1---P1 112.08 (10) O5^i^---Mg1---O2 91.82 (4) N1---C1---P2 115.59 (10) O5---Mg1---O2 88.18 (4) P1---C1---P2 113.39 (8) O1^ii^---Mg1---O2 84.94 (4) N1---C1---H1A 104.8 O1^iii^---Mg1---O2 95.06 (4) P1---C1---H1A 104.8 O5^i^---Mg1---O2^i^ 88.19 (4) P2---C1---H1A 104.8 O5---Mg1---O2^i^ 91.82 (4) N1---C2---H2A 109.5 O1^ii^---Mg1---O2^i^ 95.06 (4) N1---C2---H2B 109.5 O1^iii^---Mg1---O2^i^ 84.94 (4) H2A---C2---H2B 109.5 O2---Mg1---O2^i^ 180.00 (6) N1---C2---H2C 109.5 O1---P1---O2 117.90 (7) H2A---C2---H2C 109.5 O1---P1---O3 107.58 (7) H2B---C2---H2C 109.5 O2---P1---O3 111.67 (7) N1---C3---H3A 109.5 O1---P1---C1 111.24 (7) N1---C3---H3B 109.5 O2---P1---C1 103.22 (7) H3A---C3---H3B 109.5 O3---P1---C1 104.42 (7) N1---C3---H3C 109.5 O5---P2---O6 117.19 (7) H3A---C3---H3C 109.5 O5---P2---O4 111.67 (7) H3B---C3---H3C 109.5 O6---P2---O4 106.96 (7) P1---O1---Mg1^iv^ 148.50 (8) O5---P2---C1 104.71 (7) P1---O2---Mg1 139.08 (7) O6---P2---C1 108.34 (7) P1---O3---H3D 109.5 O4---P2---C1 107.57 (7) P2---O4---H4A 109.5 C3---N1---C2 109.91 (14) P2---O5---Mg1 137.38 (7) ------------------------ ------------- ------------------- ------------- ::: Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x+1, −y+1, −z+1; (iii) x−1, y, z; (iv) x+1, y, z. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2030 .table-wrap} ------------------- --------- --------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1B···O3 0.91 2.57 3.0997 (18) 118 N1---H1B···O4^v^ 0.91 2.31 3.1346 (18) 151 O3---H3D···O6^vi^ 0.82 1.70 2.5011 (16) 166 O4---H4A···O2^ii^ 0.82 1.81 2.6037 (16) 163 ------------------- --------- --------- ------------- --------------- ::: Symmetry codes: (v) −x+3/2, y−1/2, −z+3/2; (vi) −x+1/2, y−1/2, −z+3/2; (ii) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- --------- ------- ------------- ------------- N1---H1B⋯O3 0.91 2.57 3.0997 (18) 118 N1---H1B⋯O4^i^ 0.91 2.31 3.1346 (18) 151 O3---H3D⋯O6^ii^ 0.82 1.70 2.5011 (16) 166 O4---H4A⋯O2^iii^ 0.82 1.81 2.6037 (16) 163 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.515437	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052111/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m362-m363", "authors": [ { "first": "Qiao-Sheng", "last": "Hu" }, { "first": "Xiao-Yu", "last": "Deng" }, { "first": "Yu-Hui", "last": "Sun" }, { "first": "Zi-Yi", "last": "Du" } ] }
PMC3052112	Related literature {#sec1} ================== For tetrahydrocarbazole systems present in the framework of a number of indole-type alkaloids of biological interest, see: Saxton (1983[@bb10]). For related structures and background references, see: Patır et al. (1997[@bb7]); Hökelek & Patır (1999[@bb6]). For applications of carbazole derivatives, see: Cloutet et al. (1999[@bb3]); Wei et al. (2006[@bb15]); Tirapattur et al. (2003[@bb14]); Taoudi et al. (2001[@bb13]); Saraswathi et al. (1999[@bb9]); Sarac et al. (2000[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~17~H~14~Br~2~N~2~M ~r~ = 406.10Monoclinic,a = 10.5654 (2) Åb = 13.1471 (3) Åc = 11.6260 (2) Åβ = 105.257 (2)°V = 1557.99 (6) Å^3^Z = 4Mo Kα radiationμ = 5.20 mm^−1^T = 100 K0.34 × 0.27 × 0.24 mm ### Data collection {#sec2.1.2} Bruker Kappa APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2005[@bb1]) T ~min~ = 0.201, T ~max~ = 0.28615409 measured reflections3906 independent reflections3344 reflections with I \> 2σ(I)R ~int~ = 0.022 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.023wR(F ^2^) = 0.054S = 1.043906 reflections190 parametersH-atom parameters constrainedΔρ~max~ = 0.52 e Å^−3^Δρ~min~ = −0.36 e Å^−3^ {#d5e381} Data collection: APEX2 (Bruker, 2007[@bb2]); cell refinement: SAINT (Bruker, 2007[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb11]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb11]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb4]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb5]) and PLATON (Spek, 2009[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005162/xu5160sup1.cif](http://dx.doi.org/10.1107/S1600536811005162/xu5160sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005162/xu5160Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005162/xu5160Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5160&file=xu5160sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5160sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5160&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5160](http://scripts.iucr.org/cgi-bin/sendsup?xu5160)). The authors are indebted to Anadolu University and the Medicinal Plants and Medicine Research Centre of Anadolu University, Eskişehir, Turkey, for the use of X-ray diffractometer. This work was supported financially by the Turkish Scientific Research Council (grant No. TUBITAK-105 T516). Comment ======= Tetrahydrocarbazole systems are present in the framework of a number of indole-type alkaloids of biological interest (Saxton, 1983). The structures of tricyclic, tetracyclic and pentacyclic ring systems with dithiolane and other substituents of the tetrahydrocarbazole core, have been reported previously (Patır et al., 1997; Hökelek & Patır, 1999). Substituted carbazole based monomers exhibit good electroactive and photoactive properties which make them the most promising candidates for hole transporting mobility of charge carriers (Cloutet et al., 1999) and photoluminescence efficiencies (Wei et al., 2006). Carbazole based heterocyclic polymer systems can be chemically or electrochemically polymerized to yield materials with interesting properties with a number of applications, such as electroluminescent (Tirapattur et al., 2003), photoactive devices (Taoudi et al., 2001), sensors and rechargable batteries (Saraswathi et al., 1999) and electrochromic displays (Sarac et al., 2000). The title compound, (I), may be considered as a synthetic precursor of tetracyclic indole alkaloids of biological interests. The present study was undertaken to ascertain its crystal structure. The title compound consists of a carbazole skeleton with a pentanenitrile group (Fig. 1), where the bond lengths and angles are within normal ranges, and generally agree with those in the previously reported compounds. In all structures atom N9 is substituted. An examination of the deviations from the least-squares planes through individual rings shows that rings A (C1---C4/C4a/C9a), B (C4a/C5a/C8a/N9/C9a) and C (C5a/C5---C8/C8a) are planar. The carbazole skeleton, containing the rings A, B and C is also nearly coplanar \[with a maximum deviation of 0.055 (2) Å for atom C2\] with dihedral angles of A/B = 2.10 (6), A/C = 2.79 (5) and B/C = 0.69 (5) °. Atoms Br1, C10 and Br2 displaced by 0.0476 (2), 0.062 (2) and 0.0052 (2) Å from the corresponding planes of the carbazole skeleton. In the crystal structure, molecules are alongated along the b axis and stacked nearly parallel to (101) (Fig. 2). The π···π contacts between the pyrrole and benzene rings and the benzene rings, Cg2---Cg3^i^ and Cg3···Cg3^i^ \[symmetry code: (i) -x, 1 - y, -z, where Cg1, Cg2 and Cg3 are centroids of the rings A (C1---C4/C4a/C9a), B (C4a/C5a/C8a/N9/C9a) and C (C5a/C5---C8/C8a), respectively\] may stabilize the structure, with centroid-centroid distances of 3.548 (1) and 3.4769 (11) Å, respectively. Experimental {#experimental} ============ For the preparation of the title compound, (I), sodium hydride (1.16 g, 30.76 mmol) was added to a solution of 3,6-dibromocarbazole (5.00 g, 15.38 mmol) in dry tetrahydrofuran (200 ml) in several portions, and stirred at 353 K for 2 h under argon atmosphere. Then, chlorovaleronitrile (3.46 ml, 30.76 mmol) was added and stirred at 373 K for 6 d. The reaction mixture was cooled in an ice bath, and hydrochloric acid (10%, 200 ml) was added. After the extraction with chloroform (300 ml), the organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography using silica gel and chloroform, and the product was recrystallized from diethyl ether (yield 4.50 g, 80.12%; m.p. 327 K). Refinement {#refinement} ========== H atoms were positioned geometrically with C---H = 0.95 and 0.99 Å for aromatic and methylene H atoms, respectively, and constrained to ride on their parent atoms, with U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title molecule with the atom-numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o642-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A partial packing diagram. Hydrogen atoms have been omitted for clarity. ::: ![](e-67-0o642-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e180 .table-wrap} ------------------------- --------------------------------------- C~17~H~14~Br~2~N~2~ F(000) = 800 M~r~ = 406.10 D~x~ = 1.731 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 6957 reflections a = 10.5654 (2) Å θ = 2.3--28.3° b = 13.1471 (3) Å µ = 5.20 mm^−1^ c = 11.6260 (2) Å T = 100 K β = 105.257 (2)° Block, colorless V = 1557.99 (6) Å^3^ 0.34 × 0.27 × 0.24 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e310 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker Kappa APEXII CCD area-detector diffractometer 3906 independent reflections Radiation source: fine-focus sealed tube 3344 reflections with I \> 2σ(I) graphite R~int~ = 0.022 φ and ω scans θ~max~ = 28.4°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Bruker, 2005) h = −14→12 T~min~ = 0.201, T~max~ = 0.286 k = −17→16 15409 measured reflections l = −15→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e427 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.023 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.054 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0246P)^2^ + 0.8394P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3906 reflections (Δ/σ)~max~ = 0.001 190 parameters Δρ~max~ = 0.52 e Å^−3^ 0 restraints Δρ~min~ = −0.36 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e584 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e683 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 1.00971 (2) 0.746932 (15) 0.392293 (17) 0.02544 (6) Br2 0.636774 (19) 1.287581 (14) 0.589087 (17) 0.02193 (6) C1 0.6131 (2) 0.78706 (15) 0.22924 (16) 0.0211 (4) H1 0.5468 0.7526 0.1712 0.025\ C2 0.7401 (2) 0.75033 (15) 0.26348 (16) 0.0210 (4) H2 0.7622 0.6904 0.2274 0.025\* C3 0.83635 (18) 0.80073 (14) 0.35103 (16) 0.0190 (4) C4 0.81077 (18) 0.88872 (14) 0.40557 (15) 0.0172 (4) H4 0.8771 0.9213 0.4655 0.021\* C4A 0.68395 (18) 0.92805 (13) 0.36933 (15) 0.0157 (3) C5 0.66897 (18) 1.09921 (13) 0.47909 (15) 0.0160 (3) H5 0.7573 1.1017 0.5261 0.019\* C5A 0.62282 (17) 1.01868 (14) 0.40085 (14) 0.0152 (3) C6 0.58032 (18) 1.17500 (14) 0.48494 (15) 0.0177 (4) C7 0.44886 (19) 1.17234 (15) 0.41908 (16) 0.0196 (4) H7 0.3913 1.2259 0.4268 0.024\* C8 0.40232 (18) 1.09231 (15) 0.34294 (16) 0.0193 (4) H8 0.3130 1.0893 0.2984 0.023\* C8A 0.49060 (18) 1.01611 (14) 0.33353 (15) 0.0168 (4) C9A 0.58570 (18) 0.87634 (14) 0.28268 (15) 0.0175 (4) N9 0.46917 (15) 0.92922 (12) 0.26366 (13) 0.0185 (3) N10 −0.06092 (19) 0.97527 (16) −0.28226 (17) 0.0359 (4) C10 0.34532 (18) 0.90394 (15) 0.17760 (16) 0.0208 (4) H10A 0.2718 0.9203 0.2125 0.025\* H10B 0.3428 0.8299 0.1615 0.025\* C11 0.32683 (18) 0.96151 (14) 0.06050 (16) 0.0189 (4) H11A 0.3385 1.0353 0.0771 0.023\* H11B 0.3944 0.9395 0.0208 0.023\* C12 0.19112 (18) 0.94248 (15) −0.02221 (15) 0.0193 (4) H12A 0.1235 0.9614 0.0189 0.023\* H12B 0.1810 0.8692 −0.0421 0.023\* C13 0.17058 (19) 1.00466 (16) −0.13739 (16) 0.0234 (4) H13A 0.1815 1.0778 −0.1169 0.028\* H13B 0.2388 0.9857 −0.1778 0.028\* C14 0.0405 (2) 0.98855 (16) −0.21986 (17) 0.0247 (4) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1158 .table-wrap} ----- -------------- -------------- -------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.02541 (11) 0.02488 (11) 0.02659 (10) 0.00894 (8) 0.00780 (8) −0.00022 (8) Br2 0.02582 (11) 0.01562 (10) 0.02420 (10) −0.00012 (7) 0.00630 (8) −0.00316 (7) C1 0.0282 (10) 0.0212 (10) 0.0139 (8) −0.0040 (8) 0.0054 (7) −0.0019 (7) C2 0.0304 (11) 0.0171 (9) 0.0174 (9) 0.0008 (8) 0.0096 (8) −0.0014 (7) C3 0.0194 (9) 0.0205 (10) 0.0184 (9) 0.0034 (7) 0.0072 (7) 0.0033 (7) C4 0.0198 (9) 0.0190 (9) 0.0131 (8) −0.0001 (7) 0.0050 (7) 0.0014 (6) C4A 0.0202 (9) 0.0164 (9) 0.0111 (8) −0.0023 (7) 0.0051 (7) 0.0003 (6) C5 0.0169 (9) 0.0167 (9) 0.0145 (8) −0.0004 (7) 0.0046 (7) 0.0019 (6) C5A 0.0165 (9) 0.0177 (9) 0.0123 (8) −0.0001 (7) 0.0052 (7) 0.0034 (6) C6 0.0241 (10) 0.0140 (9) 0.0155 (8) −0.0021 (7) 0.0059 (7) −0.0002 (6) C7 0.0205 (9) 0.0193 (9) 0.0204 (9) 0.0054 (7) 0.0077 (7) 0.0052 (7) C8 0.0167 (9) 0.0233 (10) 0.0173 (9) 0.0010 (7) 0.0033 (7) 0.0037 (7) C8A 0.0195 (9) 0.0182 (9) 0.0124 (8) −0.0013 (7) 0.0036 (7) 0.0030 (6) C9A 0.0208 (9) 0.0195 (9) 0.0129 (8) −0.0009 (7) 0.0054 (7) 0.0019 (6) N9 0.0186 (8) 0.0212 (8) 0.0138 (7) −0.0016 (6) 0.0010 (6) −0.0002 (6) N10 0.0297 (11) 0.0438 (12) 0.0288 (10) −0.0051 (9) −0.0018 (8) 0.0102 (8) C10 0.0199 (10) 0.0229 (10) 0.0177 (9) −0.0049 (7) 0.0015 (7) 0.0004 (7) C11 0.0192 (9) 0.0196 (10) 0.0169 (8) −0.0014 (7) 0.0030 (7) 0.0022 (7) C12 0.0186 (9) 0.0216 (10) 0.0166 (8) −0.0030 (7) 0.0029 (7) 0.0005 (7) C13 0.0240 (10) 0.0257 (11) 0.0184 (9) −0.0050 (8) 0.0017 (7) 0.0035 (7) C14 0.0279 (11) 0.0258 (11) 0.0197 (9) −0.0012 (8) 0.0048 (8) 0.0053 (8) ----- -------------- -------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1565 .table-wrap} ----------------------- -------------- ----------------------- -------------- Br1---C3 1.9033 (19) C9A---C1 1.394 (3) Br2---C6 1.9059 (18) C9A---C4A 1.416 (2) C1---H1 0.9500 N9---C8A 1.385 (2) C2---C1 1.382 (3) N9---C9A 1.380 (2) C2---H2 0.9500 N9---C10 1.461 (2) C3---C2 1.402 (3) N10---C14 1.138 (3) C4---C3 1.380 (3) C10---H10A 0.9900 C4---H4 0.9500 C10---H10B 0.9900 C4A---C4 1.394 (3) C11---C10 1.525 (2) C4A---C5A 1.448 (2) C11---H11A 0.9900 C5---C5A 1.397 (2) C11---H11B 0.9900 C5---H5 0.9500 C12---C11 1.522 (3) C5A---C8A 1.411 (3) C12---H12A 0.9900 C6---C5 1.381 (3) C12---H12B 0.9900 C6---C7 1.399 (3) C13---C12 1.535 (2) C7---H7 0.9500 C13---H13A 0.9900 C8---C7 1.380 (3) C13---H13B 0.9900 C8---H8 0.9500 C14---C13 1.470 (3) C8A---C8 1.393 (3) C2---C1---C9A 117.75 (18) N9---C8A---C8 129.03 (17) C2---C1---H1 121.1 C1---C9A---C4A 121.49 (17) C9A---C1---H1 121.1 N9---C9A---C1 129.35 (18) C1---C2---C3 120.53 (17) N9---C9A---C4A 109.16 (16) C1---C2---H2 119.7 C8A---N9---C10 124.59 (16) C3---C2---H2 119.7 C9A---N9---C8A 108.68 (15) C2---C3---Br1 118.28 (14) C9A---N9---C10 126.55 (16) C4---C3---Br1 119.19 (15) N9---C10---C11 112.32 (15) C4---C3---C2 122.51 (18) N9---C10---H10A 109.1 C3---C4---C4A 117.46 (17) N9---C10---H10B 109.1 C3---C4---H4 121.3 C11---C10---H10A 109.1 C4A---C4---H4 121.3 C11---C10---H10B 109.1 C4---C4A---C5A 133.33 (17) H10A---C10---H10B 107.9 C4---C4A---C9A 120.22 (16) C10---C11---H11A 109.4 C9A---C4A---C5A 106.44 (16) C10---C11---H11B 109.4 C5A---C5---H5 121.5 C12---C11---C10 111.13 (15) C6---C5---C5A 116.97 (17) C12---C11---H11A 109.4 C6---C5---H5 121.5 C12---C11---H11B 109.4 C5---C5A---C4A 133.30 (17) H11A---C11---H11B 108.0 C5---C5A---C8A 120.28 (16) C11---C12---C13 110.92 (15) C8A---C5A---C4A 106.41 (16) C11---C12---H12A 109.5 C5---C6---Br2 119.25 (14) C11---C12---H12B 109.5 C5---C6---C7 122.91 (17) C13---C12---H12A 109.5 C7---C6---Br2 117.83 (14) C13---C12---H12B 109.5 C6---C7---H7 119.8 H12A---C12---H12B 108.0 C8---C7---C6 120.35 (17) C12---C13---H13A 109.1 C8---C7---H7 119.8 C12---C13---H13B 109.1 C7---C8---C8A 117.78 (17) C14---C13---C12 112.69 (16) C7---C8---H8 121.1 C14---C13---H13A 109.1 C8A---C8---H8 121.1 C14---C13---H13B 109.1 C8---C8A---C5A 121.68 (17) H13A---C13---H13B 107.8 C1---C9A---C4A 121.49 (17) N10---C14---C13 178.9 (2) N9---C8A---C5A 109.28 (16) C3---C2---C1---C9A 1.4 (3) N9---C8A---C8---C7 −179.45 (16) Br1---C3---C2---C1 −179.17 (14) C5A---C8A---C8---C7 1.3 (2) C4---C3---C2---C1 −0.9 (3) N9---C9A---C1---C2 179.02 (17) C4A---C4---C3---Br1 177.36 (12) C4A---C9A---C1---C2 −0.1 (3) C4A---C4---C3---C2 −0.9 (3) N9---C9A---C4A---C4 179.02 (15) C5A---C4A---C4---C3 −176.78 (17) N9---C9A---C4A---C5A −1.80 (18) C9A---C4A---C4---C3 2.1 (2) C1---C9A---C4A---C4 −1.7 (3) C4---C4A---C5A---C5 −0.1 (3) C1---C9A---C4A---C5A 177.48 (15) C4---C4A---C5A---C8A −179.90 (18) C9A---N9---C8A---C5A −1.15 (19) C9A---C4A---C5A---C5 −179.15 (17) C9A---N9---C8A---C8 179.49 (17) C9A---C4A---C5A---C8A 1.08 (18) C10---N9---C8A---C5A −176.60 (15) C6---C5---C5A---C4A 179.22 (17) C10---N9---C8A---C8 4.0 (3) C6---C5---C5A---C8A −1.0 (2) C8A---N9---C9A---C1 −177.36 (17) C4A---C5A---C8A---N9 0.02 (18) C8A---N9---C9A---C4A 1.85 (19) C4A---C5A---C8A---C8 179.44 (15) C10---N9---C9A---C1 −2.0 (3) C5---C5A---C8A---N9 −179.80 (14) C10---N9---C9A---C4A 177.18 (15) C5---C5A---C8A---C8 −0.4 (2) C8A---N9---C10---C11 79.5 (2) Br2---C6---C5---C5A −179.64 (12) C9A---N9---C10---C11 −95.1 (2) C7---C6---C5---C5A 1.6 (2) C12---C11---C10---N9 −173.89 (15) Br2---C6---C7---C8 −179.52 (13) C13---C12---C11---C10 177.23 (16) C5---C6---C7---C8 −0.7 (3) C14---C13---C12---C11 −179.95 (17) C8A---C8---C7---C6 −0.7 (3) ----------------------- -------------- ----------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.519020	2011-2-16	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052112/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o642", "authors": [ { "first": "Nesimi", "last": "Uludağ" }, { "first": "Murat", "last": "Ateş" }, { "first": "Barış", "last": "Tercan" }, { "first": "Tuncer", "last": "Hökelek" } ] }
PMC3052113	Related literature {#sec1} ================== For the sulfanilamide moiety in sulfonamide drugs, see; Maren (1976[@bb5]). For its ability to form hydrogen bonds in the solid state, see; Yang & Guillory (1972[@bb9]). For the hydrogen-bonding characteristics of sulfonamides, see; Adsmond & Grant (2001[@bb1]). For the effect of substituents on the crystal structures of sulfonoamides, see: Gowda et al. (2008[@bb4], 2009[@bb2], 2010[@bb3]) Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~12~ClNO~3~SM ~r~ = 261.72Triclinic,a = 8.365 (1) Åb = 8.719 (1) Åc = 9.143 (1) Åα = 92.74 (1)°β = 104.22 (1)°γ = 108.75 (1)°V = 606.24 (12) Å^3^Z = 2Mo Kα radiationμ = 0.48 mm^−1^T = 293 K0.45 × 0.35 × 0.35 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorAbsorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009[@bb6]) T ~min~ = 0.814, T ~max~ = 0.8514031 measured reflections2481 independent reflections2200 reflections with I \> 2σ(I)R ~int~ = 0.011 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.036wR(F ^2^) = 0.102S = 1.042481 reflections149 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.39 e Å^−3^Δρ~min~ = −0.27 e Å^−3^ {#d5e418} Data collection: CrysAlis CCD (Oxford Diffraction, 2009[@bb6]); cell refinement: CrysAlis RED (Oxford Diffraction, 2009[@bb6]); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: PLATON (Spek, 2009[@bb8]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004284/ds2091sup1.cif](http://dx.doi.org/10.1107/S1600536811004284/ds2091sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004284/ds2091Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004284/ds2091Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ds2091&file=ds2091sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ds2091sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ds2091&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DS2091](http://scripts.iucr.org/cgi-bin/sendsup?ds2091)). KS thanks the University Grants Commission, Government of India, New Delhi, for the award of a research fellowship under its faculty improvement program. Comment ======= The molecular structures of sulfonamide drugs contain the sulfanilamide moiety (Maren, 1976). The affinity for hydrogen bonding in the solid state due to the presence of various hydrogen bond donors and acceptors can give rise to polymorphism (Yang & Guillory, 1972). The hydrogen bonding preferences of sulfonamides has also been investigated (Adsmond & Grant, 2001). The nature and position of substituents play a significant role on the crystal structures of N-(aryl)sulfonoamides (Gowda et al., 2008, 2009, 2010). As a part of studying the substituent effects on the structures of this class of compounds, the structure of N-(2-chlorophenylsulfonyl)-2,2-dimethylacetamide (I) has been determined. The conformations of the N---H and C=O bonds of the SO~2~---NH---CO---C segment in the structure are anti to each other (Fig. 1), similar to that observed in N-(phenylsulfonyl)-acetamide (II) (Gowda et al., 2010), 2,2-dimethyl-N-(phenylsulfonyl)- acetamide (III)(Gowda et al., 2009) and 2,2-dichloro-N- (phenylsulfonyl)-acetamide (IV) (Gowda et al., 2008). The molecule in (I) is bent at the S-atom with a C1---S1---N1---C7 torsion angle of 64.4 (2)°, compared to the values of -58.8 (4)° in (II), 67.1 (3)° in (III) and -66.3 (3)° in (IV). Further, the dihedral angle between the benzene ring and the SO2---NH---CO---C group in (I) is 87.4 (1)°, compared to the values of 89.0 (2)° in (II), 87.4 (1)° in (III) and 79.8 (1)° in (IV), In the crystal structure, the intermolecular N--H···O hydrogen bonds (Table 1) link the molecules through inversion-related dimers into zigzag chains in the bc-plane. Part of the crystal structure is shown in Fig. 2. Experimental {#experimental} ============ The title compound was prepared by refluxing 2-chlorobenzenesulfonamide (0.10 mole) with an excess of 2,2-dimethylacetyl chloride (0.20 mole) for one hour on a water bath. The reaction mixture was cooled and poured into ice cold water. The resulting solid was separated, washed thoroughly with water and dissolved in warm dilute sodium hydrogen carbonate solution. The title compound was reprecipitated by acidifying the filtered solution with glacial acetic acid. It was filtered, dried and recrystallized from ethanol. The purity of the compound was checked by determining its melting point. It was further characterized by recording its infrared spectra. Prism like colorless single crystals of the title compound used in X-ray diffraction studies were obtained from a slow evaporation of an ethanolic solution of the compound. Refinement {#refinement} ========== The H atom of the NH group was located in a difference map and later restrained to the distance N---H = 0.86 (2) Å. The other H atoms were positioned with idealized geometry using a riding model with C---H = 0.93--0.98 Å. All H atoms were refined with isotropic displacement parameters (set to 1.2 times of the U~eq~ of the parent atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound, showing the atom- labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o595-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Molecular packing in the title compound. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o595-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------ --------------------------------------- C~10~H~12~ClNO~3~S Z = 2 M~r~ = 261.72 F(000) = 272 Triclinic, P1 D~x~ = 1.434 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.365 (1) Å Cell parameters from 2678 reflections b = 8.719 (1) Å θ = 3.0--27.7° c = 9.143 (1) Å µ = 0.48 mm^−1^ α = 92.74 (1)° T = 293 K β = 104.22 (1)° Prism, colourless γ = 108.75 (1)° 0.45 × 0.35 × 0.35 mm V = 606.24 (12) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e277 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector 2481 independent reflections Radiation source: fine-focus sealed tube 2200 reflections with I \> 2σ(I) graphite R~int~ = 0.011 Rotation method data acquisition using ω scans θ~max~ = 26.4°, θ~min~ = 3.0° Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009) h = −10→10 T~min~ = 0.814, T~max~ = 0.851 k = −10→9 4031 measured reflections l = −11→11 ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e392 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.036 H atoms treated by a mixture of independent and constrained refinement wR(F^2^) = 0.102 w = 1/\[σ^2^(F~o~^2^) + (0.0589P)^2^ + 0.1796P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.04 (Δ/σ)~max~ \< 0.001 2481 reflections Δρ~max~ = 0.39 e Å^−3^ 149 parameters Δρ~min~ = −0.27 e Å^−3^ 1 restraint Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.074 (7) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e573 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. CrysAlis RED (Oxford Diffraction, 2009) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.8887 (2) 0.33504 (18) 0.17180 (18) 0.0374 (3) C2 0.9618 (2) 0.2693 (2) 0.07502 (19) 0.0455 (4) C3 1.1391 (3) 0.3366 (3) 0.0881 (2) 0.0571 (5) H3 1.1882 0.2924 0.0234 0.069\ C4 1.2436 (3) 0.4688 (3) 0.1967 (3) 0.0581 (5) H4 1.3630 0.5137 0.2051 0.070\* C5 1.1725 (3) 0.5347 (2) 0.2926 (2) 0.0546 (5) H5 1.2436 0.6243 0.3656 0.065\* C6 0.9956 (2) 0.4682 (2) 0.2808 (2) 0.0441 (4) H6 0.9477 0.5128 0.3462 0.053\* C7 0.7107 (2) 0.0482 (2) 0.36475 (18) 0.0397 (4) C8 0.6623 (2) −0.1303 (2) 0.3835 (2) 0.0481 (4) H8 0.5375 −0.1848 0.3306 0.058\* C9 0.6889 (5) −0.1514 (4) 0.5501 (3) 0.0922 (9) H9A 0.6168 −0.1053 0.5915 0.111\* H9B 0.8101 −0.0965 0.6046 0.111\* H9C 0.6566 −0.2657 0.5599 0.111\* C10 0.7668 (3) −0.2058 (3) 0.3089 (3) 0.0720 (6) H10A 0.8900 −0.1503 0.3556 0.086\* H10B 0.7401 −0.1958 0.2023 0.086\* H10C 0.7368 −0.3194 0.3215 0.086\* Cl1 0.83725 (8) 0.10188 (7) −0.06290 (7) 0.0749 (2) N1 0.63339 (19) 0.07529 (16) 0.22009 (16) 0.0418 (3) H1N 0.578 (3) −0.005 (2) 0.150 (2) 0.050\* O1 0.55713 (17) 0.22202 (16) 0.00990 (15) 0.0571 (4) O2 0.63345 (17) 0.36011 (15) 0.27093 (17) 0.0567 (4) O3 0.8089 (2) 0.16099 (17) 0.46098 (15) 0.0609 (4) S1 0.66390 (5) 0.25610 (5) 0.16468 (5) 0.04147 (16) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1076 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0413 (8) 0.0280 (7) 0.0386 (8) 0.0104 (6) 0.0055 (6) 0.0046 (6) C2 0.0544 (10) 0.0359 (8) 0.0409 (8) 0.0119 (7) 0.0098 (7) −0.0009 (7) C3 0.0622 (12) 0.0528 (11) 0.0604 (11) 0.0176 (9) 0.0277 (10) 0.0037 (9) C4 0.0452 (10) 0.0501 (11) 0.0717 (13) 0.0050 (8) 0.0189 (9) 0.0054 (9) C5 0.0481 (10) 0.0384 (9) 0.0610 (11) 0.0013 (8) 0.0072 (8) −0.0068 (8) C6 0.0469 (9) 0.0341 (8) 0.0452 (9) 0.0108 (7) 0.0077 (7) −0.0024 (7) C7 0.0393 (8) 0.0378 (8) 0.0400 (8) 0.0126 (7) 0.0090 (7) 0.0020 (6) C8 0.0424 (9) 0.0400 (9) 0.0549 (10) 0.0088 (7) 0.0070 (8) 0.0130 (8) C9 0.118 (2) 0.0910 (19) 0.0757 (17) 0.0331 (18) 0.0383 (16) 0.0458 (15) C10 0.0806 (16) 0.0527 (12) 0.0824 (16) 0.0358 (12) 0.0069 (12) −0.0016 (11) Cl1 0.0767 (4) 0.0630 (4) 0.0670 (4) 0.0134 (3) 0.0098 (3) −0.0306 (3) N1 0.0444 (8) 0.0286 (7) 0.0412 (7) 0.0055 (6) 0.0017 (6) 0.0008 (5) O1 0.0500 (7) 0.0446 (7) 0.0586 (8) 0.0094 (6) −0.0090 (6) 0.0123 (6) O2 0.0506 (7) 0.0399 (7) 0.0824 (10) 0.0184 (6) 0.0210 (7) 0.0004 (6) O3 0.0738 (9) 0.0465 (7) 0.0459 (7) 0.0160 (7) −0.0040 (6) −0.0078 (6) S1 0.0381 (2) 0.0302 (2) 0.0493 (3) 0.01005 (16) 0.00256 (17) 0.00424 (17) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1378 .table-wrap} -------------------- -------------- ------------------- -------------- C1---C6 1.387 (2) C7---C8 1.507 (2) C1---C2 1.389 (2) C8---C10 1.511 (3) C1---S1 1.7659 (17) C8---C9 1.514 (3) C2---C3 1.380 (3) C8---H8 0.9800 C2---Cl1 1.7344 (18) C9---H9A 0.9600 C3---C4 1.377 (3) C9---H9B 0.9600 C3---H3 0.9300 C9---H9C 0.9600 C4---C5 1.371 (3) C10---H10A 0.9600 C4---H4 0.9300 C10---H10B 0.9600 C5---C6 1.379 (3) C10---H10C 0.9600 C5---H5 0.9300 N1---S1 1.6396 (14) C6---H6 0.9300 N1---H1N 0.843 (15) C7---O3 1.208 (2) O1---S1 1.4341 (13) C7---N1 1.390 (2) O2---S1 1.4202 (14) C6---C1---C2 119.32 (16) C7---C8---H8 108.1 C6---C1---S1 117.57 (13) C10---C8---H8 108.1 C2---C1---S1 123.11 (13) C9---C8---H8 108.1 C3---C2---C1 119.91 (16) C8---C9---H9A 109.5 C3---C2---Cl1 118.08 (14) C8---C9---H9B 109.5 C1---C2---Cl1 122.01 (14) H9A---C9---H9B 109.5 C4---C3---C2 120.17 (18) C8---C9---H9C 109.5 C4---C3---H3 119.9 H9A---C9---H9C 109.5 C2---C3---H3 119.9 H9B---C9---H9C 109.5 C5---C4---C3 120.34 (18) C8---C10---H10A 109.5 C5---C4---H4 119.8 C8---C10---H10B 109.5 C3---C4---H4 119.8 H10A---C10---H10B 109.5 C4---C5---C6 119.98 (17) C8---C10---H10C 109.5 C4---C5---H5 120.0 H10A---C10---H10C 109.5 C6---C5---H5 120.0 H10B---C10---H10C 109.5 C5---C6---C1 120.28 (17) C7---N1---S1 124.59 (11) C5---C6---H6 119.9 C7---N1---H1N 119.7 (15) C1---C6---H6 119.9 S1---N1---H1N 115.1 (14) O3---C7---N1 120.87 (16) O2---S1---O1 118.79 (9) O3---C7---C8 125.77 (16) O2---S1---N1 109.66 (8) N1---C7---C8 113.34 (14) O1---S1---N1 104.14 (8) C7---C8---C10 109.40 (16) O2---S1---C1 107.71 (8) C7---C8---C9 110.55 (18) O1---S1---C1 110.42 (8) C10---C8---C9 112.5 (2) N1---S1---C1 105.30 (8) C6---C1---C2---C3 0.1 (3) O3---C7---C8---C9 23.2 (3) S1---C1---C2---C3 −179.39 (15) N1---C7---C8---C9 −158.19 (19) C6---C1---C2---Cl1 179.41 (13) O3---C7---N1---S1 −0.2 (2) S1---C1---C2---Cl1 0.0 (2) C8---C7---N1---S1 −178.89 (12) C1---C2---C3---C4 −0.1 (3) C7---N1---S1---O2 −51.29 (16) Cl1---C2---C3---C4 −179.50 (16) C7---N1---S1---O1 −179.42 (14) C2---C3---C4---C5 0.0 (3) C7---N1---S1---C1 64.35 (16) C3---C4---C5---C6 0.2 (3) C6---C1---S1---O2 4.95 (16) C4---C5---C6---C1 −0.3 (3) C2---C1---S1---O2 −175.59 (14) C2---C1---C6---C5 0.1 (3) C6---C1---S1---O1 136.13 (13) S1---C1---C6---C5 179.61 (14) C2---C1---S1---O1 −44.41 (16) O3---C7---C8---C10 −101.1 (2) C6---C1---S1---N1 −112.02 (14) N1---C7---C8---C10 77.45 (19) C2---C1---S1---N1 67.44 (15) -------------------- -------------- ------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1893 .table-wrap} ------------------ ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1N···O1^i^ 0.84 (2) 2.14 (2) 2.976 (2) 174 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y, −z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ ---------- ---------- ----------- ------------- N1---H1N⋯O1^i^ 0.84 (2) 2.14 (2) 2.976 (2) 174 (2) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.524143	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052113/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o595", "authors": [ { "first": "K.", "last": "Shakuntala" }, { "first": "Sabine", "last": "Foro" }, { "first": "B. Thimme", "last": "Gowda" } ] }
PMC3052114	Related literature {#sec1} ================== For applications of N-heterocyclic carbenes, see: Tryg et al. (2005[@bb12]); Herrmann (2002[@bb4]); Tominaga et al. (2004[@bb11]); Magill et al. (2001[@bb7]); Arduengo et al. (1991[@bb1]); Herrmann & Kocher (1997[@bb6]); Herrmann et al. (1998[@bb5]); McGuinness et al. (1999[@bb8]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~38~N~4~ ^2+^·2PF~6~ ^−^M ~r~ = 684.53Monoclinic,a = 12.3851 (2) Åb = 19.6516 (3) Åc = 12.7586 (2) Åβ = 104.698 (1)°V = 3003.66 (8) Å^3^Z = 4Mo Kα radiationμ = 0.24 mm^−1^T = 100 K0.39 × 0.17 × 0.12 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2009[@bb2]) T ~min~ = 0.911, T ~max~ = 0.97134854 measured reflections8766 independent reflections5113 reflections with I \> 2σ(I)R ~int~ = 0.064 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.055wR(F ^2^) = 0.135S = 1.038766 reflections453 parameters177 restraintsH-atom parameters constrainedΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e591} Data collection: APEX2 (Bruker, 2009[@bb2]); cell refinement: SAINT (Bruker, 2009[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003916/sj5098sup1.cif](http://dx.doi.org/10.1107/S1600536811003916/sj5098sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003916/sj5098Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003916/sj5098Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5098&file=sj5098sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5098sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5098&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5098](http://scripts.iucr.org/cgi-bin/sendsup?sj5098)). RAH thanks Universiti Sains Malaysia for the FRGS fund (203/PKIMIA/671115), short-term grant (304/PKIMIA/639001) and RU grants (1001/PKIMIA/813023 and 1001/PKIMIA/811157). AWS thanks Universiti Sains Malaysia for the RU grant (1001/PKIMIA/843090). HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for the Research University grant No. 1001/PFIZIK/811160. MH also thanks Universiti Sains Malaysia for a post-doctoral research fellowship. Comment ======= N-heterocyclic carbenes (NHCs) are now ubiquitous in their usage as ligands for transition metals (Tryg et al., 2005; Herrmann, 2002). These complexes with different metals such as Pd and Ru have been used as catalysts for many reactions; for example C-C coupling reactions and reactions involving olefin metathesis (Tominaga et al., 2004; Magill et al., 2001). This has become an important area of research after the isolation of the first stable crystalline carbene (Arduengo et al., 1991). NHCs are neutral 2-electron donors, with an ability to bond to both hard and soft metals making them more versatile ligands than phosphines (Herrmann & Kocher, 1997). They are easier to synthesise and functionalise and form stronger bonds to metals leading to more stable metal complexes than metal phosphine complexes (Herrmann et al., 1998). The coordination chemistry of NHCs and their metal complexes continues to be actively studied, particularly for catalytic applications (McGuinness et al., 1999). The asymmetric unit of the title compound, (Fig. 1), consists of a 1,3-bis(3-butylimidazolium-1-ylmethyl)mesitylene cation and two hexafluorophosphate anions. One of the butyl groups and four F atoms in the basal plane of one of the PF~6~^-^ octahedra are disordered over two sets of sites, with occupancy ratios of 0.704 (5):0.296 (5) and 0.71 (3):0.29 (3) respectively. The central benzene (C9--C14) ring makes dihedral angles of 85.17 (12)° and 81.97 (12)° with the terminal imidazole (N1/N2/C5--C7)/(N3/N4/C16--C18) rings. In the crystal structure (Fig. 2), the cations and anions are linked together via intermolecular C2---H2A···F5, C5---H5A···F9A, C6---H6A···F6, C6---H6A···F12, C7---H7A···F4, C15---H15A···F10A, C15---H15A···F11 and C19---H19B···F6 (Table 1) hydrogen bonds forming a three-dimensional network. Experimental {#experimental} ============ A mixture of 1,3-bis(bromomethyl)mesitylene (0.9 g, 3.0 mmol) and 1-butylimidazole (0.75 g, 6.0 mmol) in 25 ml of 1,4-dioxane was refluxed at 373 K for 24 h. The resulting slurry was isolated by decantation and washed with fresh 1,4-dioxane (2 x 5 ml) and diethyl ether (2 x 3 ml). The bromide salt was converted directly to its corresponding hexafluorophosphate by a metathesis reaction with methanolic KPF~6~ (1.2 g, 6.5 mmol). The resulting yellowish solid was washed with distilled water and recrystallised from acetonitrile to give pale-yellow crystals. (yield 1.4 g, 88.26 %). Crystals suitable for X-ray diffraction studies were obtained by slow evaporation of the salt solution in acetonitrile at ambient temperature. Refinement {#refinement} ========== All the H atoms were positioned geometrically \[ C--H = 0.93--0.97 Å \] and were refined using a riding model, with U~iso~(H) = 1.2 or 1.5 U~eq~(C). One of the butyl groups and the F7, F8, F9 and F10 fluorine atoms in the one of the phosphate anions are disordered over two sets of sites, with occupancy ratios of 0.704 (5):0.296 (5) and 0.71 (3):0.29 (3) respectively. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. Open bonds represents the minor disorder components \[H atoms are omitted for clarity\]. ::: ![](e-67-0o562-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound, showing a hydrogen-bonded (dashed lines) network. Only atoms of the major disorder components are shown for clarity. ::: ![](e-67-0o562-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e141 .table-wrap} ------------------------------ --------------------------------------- C~25~H~38~N~4~^2+^·2PF~6~^−^ F(000) = 1416 M~r~ = 684.53 D~x~ = 1.514 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 5155 reflections a = 12.3851 (2) Å θ = 2.9--27.3° b = 19.6516 (3) Å µ = 0.24 mm^−1^ c = 12.7586 (2) Å T = 100 K β = 104.698 (1)° Block, pale yellow V = 3003.66 (8) Å^3^ 0.39 × 0.17 × 0.12 mm Z = 4 ------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e276 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 8766 independent reflections Radiation source: fine-focus sealed tube 5113 reflections with I \> 2σ(I) graphite R~int~ = 0.064 φ and ω scans θ~max~ = 30.1°, θ~min~ = 2.0° Absorption correction: multi-scan (SADABS; Bruker, 2009) h = −17→16 T~min~ = 0.911, T~max~ = 0.971 k = −25→27 34854 measured reflections l = −17→17 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e393 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.135 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.051P)^2^ + 0.7397P\] where P = (F~o~^2^ + 2F~c~^2^)/3 8766 reflections (Δ/σ)~max~ = 0.001 453 parameters Δρ~max~ = 0.33 e Å^−3^ 177 restraints Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e550 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e604 .table-wrap} ------ -------------- --------------- --------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) P1 0.20895 (5) 0.21416 (3) 0.70794 (5) 0.02528 (14) F1 0.27007 (13) 0.19236 (8) 0.82874 (11) 0.0516 (4) F2 0.15016 (13) 0.23475 (8) 0.58707 (12) 0.0539 (4) F3 0.12414 (12) 0.25961 (7) 0.75254 (13) 0.0506 (4) F4 0.29111 (12) 0.27811 (7) 0.71659 (12) 0.0457 (4) F5 0.12931 (11) 0.14951 (7) 0.69934 (12) 0.0440 (4) F6 0.29625 (11) 0.16855 (7) 0.66468 (12) 0.0411 (4) P2 0.10834 (6) 0.08585 (3) 0.25608 (5) 0.03360 (16) F7A 0.1954 (7) 0.1328 (5) 0.2220 (9) 0.086 (2) 0.71 (3) F8A 0.0192 (10) 0.1437 (7) 0.2271 (10) 0.095 (3) 0.71 (3) F9A 0.0210 (6) 0.0378 (6) 0.2895 (7) 0.067 (2) 0.71 (3) F10A 0.1988 (7) 0.0260 (4) 0.2873 (7) 0.0559 (15) 0.71 (3) F7B 0.172 (3) 0.1469 (16) 0.231 (3) 0.137 (11) 0.29 (3) F8B −0.0055 (14) 0.1272 (12) 0.227 (2) 0.063 (4) 0.29 (3) F9B 0.0389 (18) 0.0197 (8) 0.2790 (14) 0.060 (4) 0.29 (3) F10B 0.2128 (15) 0.0415 (15) 0.279 (2) 0.088 (7) 0.29 (3) F11 0.07227 (13) 0.05889 (8) 0.13307 (11) 0.0469 (4) F12 0.14197 (13) 0.11048 (8) 0.37886 (11) 0.0539 (4) N1 0.85438 (15) 0.08695 (9) 0.41927 (14) 0.0265 (4) N2 0.73557 (15) 0.01726 (9) 0.32089 (14) 0.0269 (4) N3 0.84666 (14) 0.11056 (9) −0.07330 (14) 0.0259 (4) N4 0.94852 (15) 0.19703 (9) −0.00729 (15) 0.0288 (4) C1 0.8135 (2) 0.22441 (12) 0.6905 (2) 0.0394 (6) H1A 0.7985 0.2044 0.7539 0.059\ H1B 0.7463 0.2443 0.6467 0.059\* H1C 0.8695 0.2590 0.7117 0.059\* C2 0.85494 (19) 0.16985 (12) 0.62574 (19) 0.0333 (5) H2A 0.9262 0.1527 0.6679 0.040\* H2B 0.8025 0.1323 0.6124 0.040\* C3 0.8684 (2) 0.19657 (12) 0.51876 (18) 0.0344 (6) H3A 0.7952 0.2088 0.4743 0.041\* H3B 0.9126 0.2379 0.5325 0.041\* C4 0.92215 (19) 0.14853 (12) 0.45473 (18) 0.0322 (5) H4A 0.9334 0.1721 0.3915 0.039\* H4B 0.9948 0.1351 0.4990 0.039\* C5 0.85966 (19) 0.02770 (11) 0.47726 (18) 0.0306 (5) H5A 0.9056 0.0193 0.5459 0.037\* C6 0.78581 (19) −0.01605 (11) 0.41627 (18) 0.0301 (5) H6A 0.7714 −0.0603 0.4349 0.036\* C7 0.77865 (18) 0.07964 (11) 0.32502 (17) 0.0272 (5) H7A 0.7591 0.1125 0.2711 0.033\* C8 0.64688 (19) −0.01183 (11) 0.23136 (18) 0.0307 (5) H8A 0.5788 −0.0166 0.2551 0.037\* H8B 0.6694 −0.0568 0.2139 0.037\* C9 0.62393 (17) 0.03175 (10) 0.13126 (17) 0.0253 (5) C10 0.69484 (17) 0.02784 (10) 0.06159 (17) 0.0247 (5) C11 0.67302 (17) 0.06873 (11) −0.03184 (17) 0.0255 (5) C12 0.58185 (18) 0.11365 (11) −0.05516 (18) 0.0293 (5) C13 0.51248 (18) 0.11498 (11) 0.0150 (2) 0.0320 (5) H13A 0.4505 0.1435 −0.0012 0.038\* C14 0.53172 (18) 0.07571 (11) 0.10792 (19) 0.0295 (5) C15 0.74935 (18) 0.06444 (12) −0.10679 (18) 0.0311 (5) H15A 0.7756 0.0180 −0.1079 0.037\* H15B 0.7077 0.0761 −0.1797 0.037\* C16 0.94168 (18) 0.10753 (12) −0.11101 (18) 0.0304 (5) H16A 0.9588 0.0743 −0.1562 0.036\* C17 1.0046 (2) 0.16150 (12) −0.07013 (19) 0.0328 (5) H17A 1.0735 0.1728 −0.0820 0.039\* C18 0.85343 (18) 0.16506 (11) −0.01042 (17) 0.0266 (5) H18A 0.8003 0.1786 0.0254 0.032\* C19 0.9808 (2) 0.26251 (12) 0.0467 (2) 0.0404 (6) H19A 1.0614 0.2662 0.0701 0.048\* 0.704 (5) H19B 0.9509 0.2666 0.1097 0.048\* 0.704 (5) H19C 1.0461 0.2548 0.1047 0.048\* 0.296 (5) H19D 0.9222 0.2762 0.0790 0.048\* 0.296 (5) C20A 0.9304 (4) 0.32135 (17) −0.0399 (3) 0.0387 (9) 0.704 (5) H20A 0.9613 0.3165 −0.1022 0.046\* 0.704 (5) H20B 0.8502 0.3157 −0.0646 0.046\* 0.704 (5) C21A 0.9560 (3) 0.39198 (18) 0.0069 (3) 0.0426 (10) 0.704 (5) H21A 0.9283 0.3962 0.0712 0.051\* 0.704 (5) H21B 0.9173 0.4252 −0.0455 0.051\* 0.704 (5) C22A 1.0797 (4) 0.4072 (3) 0.0360 (5) 0.0587 (13) 0.704 (5) H22A 1.0920 0.4533 0.0609 0.088\* 0.704 (5) H22B 1.1081 0.4010 −0.0267 0.088\* 0.704 (5) H22C 1.1176 0.3768 0.0924 0.088\* 0.704 (5) C20B 1.0049 (9) 0.3150 (4) −0.0097 (8) 0.040 (2) 0.296 (5) H20C 0.9405 0.3245 −0.0693 0.048\* 0.296 (5) H20D 1.0657 0.3019 −0.0407 0.048\* 0.296 (5) C21B 1.0374 (10) 0.3794 (5) 0.0545 (8) 0.047 (3) 0.296 (5) H21C 1.0987 0.3702 0.1171 0.057\* 0.296 (5) H21D 0.9747 0.3957 0.0801 0.057\* 0.296 (5) C22B 1.0725 (10) 0.4342 (6) −0.0164 (11) 0.0587 (13) 0.296 (5) H22D 1.1108 0.4703 0.0289 0.088\* 0.296 (5) H22E 1.0074 0.4522 −0.0665 0.088\* 0.296 (5) H22F 1.1212 0.4144 −0.0558 0.088\* 0.296 (5) C23 0.79482 (18) −0.01942 (11) 0.08577 (19) 0.0327 (5) H23A 0.8134 −0.0317 0.1611 0.049\* H23B 0.8572 0.0032 0.0693 0.049\* H23C 0.7772 −0.0597 0.0423 0.049\* C24 0.4549 (2) 0.08292 (13) 0.1822 (2) 0.0422 (6) H24A 0.3953 0.1137 0.1504 0.063\* H24B 0.4961 0.1004 0.2510 0.063\* H24C 0.4243 0.0392 0.1923 0.063\* C25 0.5587 (2) 0.16090 (13) −0.1517 (2) 0.0424 (6) H25A 0.4941 0.1881 −0.1522 0.064\* H25B 0.5451 0.1346 −0.2172 0.064\* H25C 0.6219 0.1900 −0.1471 0.064\* ------ -------------- --------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1919 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ P1 0.0270 (3) 0.0194 (3) 0.0286 (3) −0.0011 (2) 0.0055 (2) −0.0012 (2) F1 0.0674 (10) 0.0463 (9) 0.0311 (8) 0.0023 (8) −0.0061 (7) −0.0005 (7) F2 0.0686 (10) 0.0479 (9) 0.0357 (8) 0.0083 (8) −0.0042 (7) 0.0101 (7) F3 0.0523 (9) 0.0371 (8) 0.0731 (11) 0.0098 (7) 0.0355 (8) −0.0018 (8) F4 0.0525 (9) 0.0246 (7) 0.0672 (11) −0.0149 (6) 0.0281 (8) −0.0157 (7) F5 0.0394 (8) 0.0342 (8) 0.0592 (10) −0.0139 (6) 0.0142 (7) −0.0038 (7) F6 0.0426 (8) 0.0257 (7) 0.0603 (10) −0.0008 (6) 0.0226 (7) −0.0104 (7) P2 0.0460 (4) 0.0291 (3) 0.0283 (3) 0.0019 (3) 0.0144 (3) 0.0021 (3) F7A 0.105 (4) 0.094 (5) 0.069 (3) −0.063 (3) 0.041 (3) −0.002 (3) F8A 0.166 (8) 0.081 (4) 0.038 (3) 0.087 (5) 0.023 (6) 0.014 (3) F9A 0.047 (2) 0.114 (6) 0.041 (2) −0.032 (3) 0.0124 (16) 0.014 (3) F10A 0.081 (4) 0.054 (3) 0.031 (2) 0.0346 (19) 0.009 (2) −0.0015 (14) F7B 0.26 (3) 0.079 (10) 0.073 (9) −0.093 (14) 0.052 (14) 0.008 (8) F8B 0.047 (6) 0.107 (13) 0.033 (5) 0.040 (6) 0.010 (3) 0.001 (8) F9B 0.103 (10) 0.036 (6) 0.025 (5) −0.021 (5) −0.014 (6) 0.015 (3) F10B 0.030 (5) 0.171 (18) 0.057 (9) 0.036 (8) 0.004 (5) −0.022 (10) F11 0.0660 (10) 0.0470 (9) 0.0271 (8) 0.0099 (8) 0.0105 (7) 0.0005 (6) F12 0.0779 (11) 0.0462 (9) 0.0348 (8) 0.0090 (8) 0.0092 (8) −0.0085 (7) N1 0.0313 (10) 0.0241 (10) 0.0227 (9) −0.0024 (7) 0.0045 (7) 0.0013 (7) N2 0.0347 (10) 0.0199 (9) 0.0258 (9) −0.0025 (8) 0.0074 (8) 0.0018 (7) N3 0.0299 (10) 0.0260 (10) 0.0221 (9) 0.0002 (8) 0.0069 (7) 0.0023 (8) N4 0.0306 (10) 0.0254 (10) 0.0315 (10) −0.0016 (8) 0.0094 (8) 0.0000 (8) C1 0.0413 (14) 0.0328 (14) 0.0431 (15) 0.0032 (11) 0.0090 (11) −0.0040 (11) C2 0.0339 (13) 0.0310 (13) 0.0361 (13) 0.0022 (10) 0.0110 (10) 0.0014 (10) C3 0.0428 (14) 0.0264 (12) 0.0294 (12) −0.0080 (10) 0.0009 (10) 0.0010 (10) C4 0.0363 (13) 0.0351 (13) 0.0236 (11) −0.0125 (10) 0.0045 (9) −0.0017 (10) C5 0.0367 (12) 0.0273 (12) 0.0269 (12) 0.0054 (10) 0.0065 (9) 0.0063 (9) C6 0.0430 (13) 0.0198 (11) 0.0293 (12) 0.0030 (9) 0.0125 (10) 0.0061 (9) C7 0.0339 (12) 0.0236 (11) 0.0231 (11) −0.0044 (9) 0.0053 (9) 0.0034 (9) C8 0.0378 (13) 0.0233 (11) 0.0305 (12) −0.0077 (9) 0.0079 (10) −0.0031 (9) C9 0.0294 (11) 0.0184 (10) 0.0267 (11) −0.0054 (8) 0.0045 (9) −0.0040 (9) C10 0.0257 (11) 0.0172 (10) 0.0275 (11) −0.0017 (8) −0.0001 (8) −0.0030 (8) C11 0.0264 (11) 0.0230 (11) 0.0239 (11) −0.0038 (8) 0.0006 (8) −0.0026 (9) C12 0.0285 (11) 0.0214 (11) 0.0324 (12) −0.0038 (9) −0.0026 (9) −0.0017 (9) C13 0.0246 (11) 0.0203 (11) 0.0459 (14) 0.0006 (9) −0.0008 (10) −0.0069 (10) C14 0.0269 (11) 0.0219 (11) 0.0390 (13) −0.0053 (9) 0.0072 (10) −0.0117 (10) C15 0.0355 (12) 0.0308 (12) 0.0252 (12) −0.0059 (10) 0.0044 (9) −0.0045 (9) C16 0.0361 (13) 0.0296 (12) 0.0296 (12) 0.0058 (10) 0.0157 (10) 0.0035 (10) C17 0.0358 (13) 0.0295 (13) 0.0367 (13) 0.0026 (10) 0.0158 (10) 0.0038 (10) C18 0.0285 (11) 0.0268 (11) 0.0256 (11) −0.0010 (9) 0.0089 (9) 0.0026 (9) C19 0.0357 (13) 0.0321 (13) 0.0552 (17) −0.0076 (11) 0.0152 (12) −0.0116 (12) C20A 0.048 (2) 0.033 (2) 0.034 (2) 0.0015 (17) 0.0102 (18) 0.0030 (16) C21A 0.044 (2) 0.036 (2) 0.049 (2) 0.0031 (17) 0.0127 (19) 0.0075 (17) C22A 0.059 (3) 0.040 (3) 0.078 (4) −0.010 (2) 0.020 (3) 0.008 (2) C20B 0.045 (6) 0.029 (4) 0.045 (5) −0.009 (4) 0.010 (4) −0.006 (4) C21B 0.046 (6) 0.043 (6) 0.053 (6) −0.015 (5) 0.011 (5) −0.005 (4) C22B 0.059 (3) 0.040 (3) 0.078 (4) −0.010 (2) 0.020 (3) 0.008 (2) C23 0.0332 (12) 0.0266 (12) 0.0359 (13) 0.0053 (9) 0.0042 (10) 0.0014 (10) C24 0.0405 (14) 0.0383 (15) 0.0515 (16) −0.0043 (11) 0.0184 (12) −0.0166 (12) C25 0.0394 (14) 0.0377 (14) 0.0423 (15) −0.0002 (11) −0.0042 (11) 0.0103 (12) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2838 .table-wrap} ----------------------- -------------- -------------------------- -------------- P1---F2 1.5819 (15) C10---C11 1.406 (3) P1---F3 1.5901 (14) C10---C23 1.516 (3) P1---F1 1.5937 (14) C11---C12 1.404 (3) P1---F5 1.5950 (14) C11---C15 1.508 (3) P1---F4 1.6032 (13) C12---C13 1.389 (3) P1---F6 1.6063 (14) C12---C25 1.511 (3) P2---F7B 1.515 (18) C13---C14 1.384 (3) P2---F10B 1.525 (16) C13---H13A 0.9300 P2---F8A 1.562 (7) C14---C24 1.510 (3) P2---F7A 1.562 (6) C15---H15A 0.9700 P2---F9A 1.575 (6) C15---H15B 0.9700 P2---F8B 1.587 (15) C16---C17 1.341 (3) P2---F12 1.5907 (15) C16---H16A 0.9300 P2---F10A 1.604 (6) C17---H17A 0.9300 P2---F11 1.6087 (15) C18---H18A 0.9300 P2---F9B 1.626 (14) C19---C20B 1.335 (9) N1---C7 1.332 (3) C19---C20A 1.611 (4) N1---C5 1.372 (3) C19---H19A 0.9700 N1---C4 1.477 (3) C19---H19B 0.9700 N2---C7 1.333 (3) C19---H19C 0.9600 N2---C6 1.383 (3) C19---H19D 0.9601 N2---C8 1.484 (3) C20A---C21A 1.512 (5) N3---C18 1.328 (3) C20A---H20A 0.9700 N3---C16 1.381 (3) C20A---H20B 0.9700 N3---C15 1.482 (3) C21A---C22A 1.512 (5) N4---C18 1.326 (3) C21A---H21A 0.9700 N4---C17 1.377 (3) C21A---H21B 0.9700 N4---C19 1.466 (3) C22A---H22A 0.9600 C1---C2 1.520 (3) C22A---H22B 0.9600 C1---H1A 0.9600 C22A---H22C 0.9600 C1---H1B 0.9600 C20B---C21B 1.505 (11) C1---H1C 0.9600 C20B---H20C 0.9700 C2---C3 1.511 (3) C20B---H20D 0.9700 C2---H2A 0.9700 C21B---C22B 1.538 (12) C2---H2B 0.9700 C21B---H21C 0.9700 C3---C4 1.510 (3) C21B---H21D 0.9700 C3---H3A 0.9700 C22B---H22D 0.9600 C3---H3B 0.9700 C22B---H22E 0.9600 C4---H4A 0.9700 C22B---H22F 0.9600 C4---H4B 0.9700 C23---H23A 0.9600 C5---C6 1.349 (3) C23---H23B 0.9600 C5---H5A 0.9300 C23---H23C 0.9600 C6---H6A 0.9300 C24---H24A 0.9600 C7---H7A 0.9300 C24---H24B 0.9600 C8---C9 1.504 (3) C24---H24C 0.9600 C8---H8A 0.9700 C25---H25A 0.9600 C8---H8B 0.9700 C25---H25B 0.9600 C9---C10 1.401 (3) C25---H25C 0.9600 C9---C14 1.402 (3) F2---P1---F3 91.31 (9) C9---C8---H8A 109.2 F2---P1---F1 178.71 (9) N2---C8---H8B 109.2 F3---P1---F1 89.98 (9) C9---C8---H8B 109.2 F2---P1---F5 90.75 (8) H8A---C8---H8B 107.9 F3---P1---F5 91.09 (8) C10---C9---C14 120.5 (2) F1---P1---F5 89.20 (8) C10---C9---C8 119.58 (19) F2---P1---F4 89.64 (8) C14---C9---C8 120.0 (2) F3---P1---F4 90.02 (8) C9---C10---C11 119.33 (19) F1---P1---F4 90.38 (8) C9---C10---C23 121.0 (2) F5---P1---F4 178.81 (8) C11---C10---C23 119.6 (2) F2---P1---F6 89.49 (8) C12---C11---C10 120.7 (2) F3---P1---F6 179.03 (9) C12---C11---C15 120.0 (2) F1---P1---F6 89.22 (8) C10---C11---C15 119.28 (19) F5---P1---F6 89.44 (7) C13---C12---C11 118.1 (2) F4---P1---F6 89.44 (7) C13---C12---C25 119.5 (2) F7B---P2---F10B 91.8 (11) C11---C12---C25 122.4 (2) F7B---P2---F8A 75.5 (12) C14---C13---C12 122.8 (2) F10B---P2---F8A 167.3 (10) C14---C13---H13A 118.6 F10B---P2---F7A 77.3 (12) C12---C13---H13A 118.6 F8A---P2---F7A 90.0 (5) C13---C14---C9 118.6 (2) F7B---P2---F9A 164.5 (13) C13---C14---C24 119.1 (2) F10B---P2---F9A 102.2 (10) C9---C14---C24 122.2 (2) F8A---P2---F9A 90.5 (4) N3---C15---C11 112.20 (17) F7A---P2---F9A 179.3 (6) N3---C15---H15A 109.2 F7B---P2---F8B 91.5 (12) C11---C15---H15A 109.2 F10B---P2---F8B 175.6 (12) N3---C15---H15B 109.2 F7A---P2---F8B 105.5 (9) C11---C15---H15B 109.2 F9A---P2---F8B 74.9 (9) H15A---C15---H15B 107.9 F7B---P2---F12 86.9 (13) C17---C16---N3 107.0 (2) F10B---P2---F12 89.2 (9) C17---C16---H16A 126.5 F8A---P2---F12 90.2 (5) N3---C16---H16A 126.5 F7A---P2---F12 93.9 (4) C16---C17---N4 107.3 (2) F9A---P2---F12 86.7 (4) C16---C17---H17A 126.3 F8B---P2---F12 94.0 (10) N4---C17---H17A 126.3 F7B---P2---F10A 105.3 (14) N4---C18---N3 108.6 (2) F8A---P2---F10A 179.0 (5) N4---C18---H18A 125.7 F7A---P2---F10A 90.9 (4) N3---C18---H18A 125.7 F9A---P2---F10A 88.7 (4) C20B---C19---N4 119.8 (4) F8B---P2---F10A 163.1 (9) N4---C19---C20A 107.2 (2) F12---P2---F10A 89.2 (3) C20B---C19---H19A 75.8 F7B---P2---F11 95.0 (13) N4---C19---H19A 110.3 F10B---P2---F11 90.8 (9) C20A---C19---H19A 110.3 F8A---P2---F11 90.2 (5) C20B---C19---H19B 124.6 F7A---P2---F11 87.9 (4) N4---C19---H19B 110.3 F9A---P2---F11 91.5 (4) C20A---C19---H19B 110.3 F8B---P2---F11 86.0 (10) H19A---C19---H19B 108.5 F12---P2---F11 178.15 (9) C20B---C19---H19C 106.1 F10A---P2---F11 90.3 (3) N4---C19---H19C 107.4 F7B---P2---F9B 178.3 (14) C20A---C19---H19C 138.2 F10B---P2---F9B 88.2 (10) H19B---C19---H19C 78.4 F8A---P2---F9B 104.5 (7) C20B---C19---H19D 108.2 F7A---P2---F9B 163.0 (9) N4---C19---H19D 107.7 F8B---P2---F9B 88.4 (9) C20A---C19---H19D 83.7 F12---P2---F9B 94.9 (7) H19A---C19---H19D 132.7 F10A---P2---F9B 74.7 (8) H19C---C19---H19D 107.1 F11---P2---F9B 83.3 (7) C21A---C20A---C19 112.5 (3) C7---N1---C5 108.76 (18) C21A---C20A---H20A 109.1 C7---N1---C4 125.47 (18) C19---C20A---H20A 109.1 C5---N1---C4 125.77 (18) C21A---C20A---H20B 109.1 C7---N2---C6 108.33 (18) C19---C20A---H20B 109.1 C7---N2---C8 126.56 (18) H20A---C20A---H20B 107.8 C6---N2---C8 125.10 (17) C20A---C21A---C22A 112.1 (4) C18---N3---C16 108.45 (19) C20A---C21A---H21A 109.2 C18---N3---C15 126.12 (19) C22A---C21A---H21A 109.2 C16---N3---C15 125.17 (19) C20A---C21A---H21B 109.2 C18---N4---C17 108.53 (19) C22A---C21A---H21B 109.2 C18---N4---C19 124.3 (2) H21A---C21A---H21B 107.9 C17---N4---C19 126.94 (19) C19---C20B---C21B 114.9 (8) C2---C1---H1A 109.5 C19---C20B---H20C 108.5 C2---C1---H1B 109.5 C21B---C20B---H20C 108.5 H1A---C1---H1B 109.5 C19---C20B---H20D 108.5 C2---C1---H1C 109.5 C21B---C20B---H20D 108.5 H1A---C1---H1C 109.5 H20C---C20B---H20D 107.5 H1B---C1---H1C 109.5 C20B---C21B---C22B 110.2 (9) C3---C2---C1 112.05 (19) C20B---C21B---H21C 109.6 C3---C2---H2A 109.2 C22B---C21B---H21C 109.6 C1---C2---H2A 109.2 C20B---C21B---H21D 109.6 C3---C2---H2B 109.2 C22B---C21B---H21D 109.6 C1---C2---H2B 109.2 H21C---C21B---H21D 108.1 H2A---C2---H2B 107.9 C21B---C22B---H22D 109.5 C4---C3---C2 115.88 (19) C21B---C22B---H22E 109.5 C4---C3---H3A 108.3 H22D---C22B---H22E 109.5 C2---C3---H3A 108.3 C21B---C22B---H22F 109.5 C4---C3---H3B 108.3 H22D---C22B---H22F 109.5 C2---C3---H3B 108.3 H22E---C22B---H22F 109.5 H3A---C3---H3B 107.4 C10---C23---H23A 109.5 N1---C4---C3 112.56 (18) C10---C23---H23B 109.5 N1---C4---H4A 109.1 H23A---C23---H23B 109.5 C3---C4---H4A 109.1 C10---C23---H23C 109.5 N1---C4---H4B 109.1 H23A---C23---H23C 109.5 C3---C4---H4B 109.1 H23B---C23---H23C 109.5 H4A---C4---H4B 107.8 C14---C24---H24A 109.5 C6---C5---N1 107.29 (19) C14---C24---H24B 109.5 C6---C5---H5A 126.4 H24A---C24---H24B 109.5 N1---C5---H5A 126.4 C14---C24---H24C 109.5 C5---C6---N2 107.08 (19) H24A---C24---H24C 109.5 C5---C6---H6A 126.5 H24B---C24---H24C 109.5 N2---C6---H6A 126.5 C12---C25---H25A 109.5 N1---C7---N2 108.55 (19) C12---C25---H25B 109.5 N1---C7---H7A 125.7 H25A---C25---H25B 109.5 N2---C7---H7A 125.7 C12---C25---H25C 109.5 N2---C8---C9 112.20 (17) H25A---C25---H25C 109.5 N2---C8---H8A 109.2 H25B---C25---H25C 109.5 C1---C2---C3---C4 172.95 (19) C25---C12---C13---C14 −176.7 (2) C7---N1---C4---C3 92.1 (3) C12---C13---C14---C9 −1.3 (3) C5---N1---C4---C3 −88.6 (3) C12---C13---C14---C24 177.1 (2) C2---C3---C4---N1 64.3 (3) C10---C9---C14---C13 0.0 (3) C7---N1---C5---C6 0.2 (3) C8---C9---C14---C13 −179.73 (18) C4---N1---C5---C6 −179.2 (2) C10---C9---C14---C24 −178.4 (2) N1---C5---C6---N2 −0.1 (3) C8---C9---C14---C24 1.9 (3) C7---N2---C6---C5 0.0 (2) C18---N3---C15---C11 −21.2 (3) C8---N2---C6---C5 −178.6 (2) C16---N3---C15---C11 165.40 (19) C5---N1---C7---N2 −0.2 (3) C12---C11---C15---N3 92.8 (2) C4---N1---C7---N2 179.2 (2) C10---C11---C15---N3 −86.7 (2) C6---N2---C7---N1 0.1 (2) C18---N3---C16---C17 −0.5 (2) C8---N2---C7---N1 178.71 (19) C15---N3---C16---C17 173.93 (19) C7---N2---C8---C9 11.8 (3) N3---C16---C17---N4 0.3 (2) C6---N2---C8---C9 −169.8 (2) C18---N4---C17---C16 −0.1 (2) N2---C8---C9---C10 80.2 (2) C19---N4---C17---C16 −174.8 (2) N2---C8---C9---C14 −100.1 (2) C17---N4---C18---N3 −0.2 (2) C14---C9---C10---C11 0.3 (3) C19---N4---C18---N3 174.7 (2) C8---C9---C10---C11 −179.96 (18) C16---N3---C18---N4 0.4 (2) C14---C9---C10---C23 179.98 (18) C15---N3---C18---N4 −173.91 (18) C8---C9---C10---C23 −0.3 (3) C18---N4---C19---C20B −122.8 (6) C9---C10---C11---C12 0.6 (3) C17---N4---C19---C20B 51.1 (7) C23---C10---C11---C12 −179.06 (19) C18---N4---C19---C20A −87.6 (3) C9---C10---C11---C15 −179.96 (18) C17---N4---C19---C20A 86.3 (3) C23---C10---C11---C15 0.4 (3) C20B---C19---C20A---C21A −63.4 (7) C10---C11---C12---C13 −1.8 (3) N4---C19---C20A---C21A 178.8 (3) C15---C11---C12---C13 178.77 (19) C19---C20A---C21A---C22A 65.0 (5) C10---C11---C12---C25 177.0 (2) N4---C19---C20B---C21B −179.7 (7) C15---C11---C12---C25 −2.4 (3) C20A---C19---C20B---C21B 103.6 (12) C11---C12---C13---C14 2.2 (3) C19---C20B---C21B---C22B 175.3 (9) ----------------------- -------------- -------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4572 .table-wrap} ----------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C2---H2A···F5^i^ 0.97 2.45 3.312 (3) 149 C5---H5A···F9A^ii^ 0.93 2.35 3.235 (9) 159 C6---H6A···F6^ii^ 0.93 2.51 3.248 (3) 136 C6---H6A···F12^ii^ 0.93 2.54 3.145 (3) 123 C7---H7A···F4^iii^ 0.93 2.32 3.140 (3) 146. C15---H15A···F10A^iv^ 0.97 2.54 3.103 (9) 117 C15---H15A···F11^iv^ 0.97 2.50 3.353 (3) 147 C19---H19B···F6^iii^ 0.97 2.54 3.327 (3) 138 ----------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y, −z+1; (iii) x+1/2, −y+1/2, z−1/2; (iv) −x+1, −y, −z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------------- --------- ------- ----------- ------------- C2---H2A⋯F5^i^ 0.97 2.45 3.312 (3) 149 C5---H5A⋯F9A^ii^ 0.93 2.35 3.235 (9) 159 C6---H6A⋯F6^ii^ 0.93 2.51 3.248 (3) 136 C6---H6A⋯F12^ii^ 0.93 2.54 3.145 (3) 123 C7---H7A⋯F4^iii^ 0.93 2.32 3.140 (3) 146 C15---H15A⋯F10A^iv^ 0.97 2.54 3.103 (9) 117 C15---H15A⋯F11^iv^ 0.97 2.50 3.353 (3) 147 C19---H19B⋯F6^iii^ 0.97 2.54 3.327 (3) 138 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.	PubMed Central	2024-06-05T04:04:18.528372	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052114/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o562-o563", "authors": [ { "first": "Rosenani A.", "last": "Haque" }, { "first": "Abbas Washeel", "last": "Salman" }, { "first": "Madhukar", "last": "Hemamalini" }, { "first": "Hoong-Kun", "last": "Fun" } ] }
PMC3052115	Related literature {#sec1} ================== For the structures of similar crown ether clathrates, see: Akutagawa et al. (2002[@bb1]); Ge & Zhao (2010a [@bb3],b [@bb4];); Guo & Zhao (2010[@bb5]); Zhao (2010[@bb10]); Zhao & Qu (2010a [@bb11],b [@bb12]). The title compound was prepared as part of a study of ferroelectric materials. For their properties, see: Fu et al. (2007[@bb2]); Zhang et al. (2009[@bb9]); Ye et al. (2009[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~7~H~9~BrN^+^·ClO~4~ ^−^·C~12~H~24~O~6~M ~r~ = 550.81Monoclinic,a = 11.967 (2) Åb = 13.446 (3) Åc = 15.677 (3) Åβ = 94.05 (3)°V = 2516.3 (9) Å^3^Z = 4Mo Kα radiationμ = 1.79 mm^−1^T = 296 K0.40 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Rigaku SCXmini diffractometerAbsorption correction: multi-scan (CrystalClear; Rigaku, 2005[@bb6]) T ~min~ = 0.530, T ~max~ = 0.69925007 measured reflections5665 independent reflections4005 reflections with I \> 2σ(I)R ~int~ = 0.066 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.060wR(F ^2^) = 0.157S = 1.095665 reflections289 parametersH-atom parameters constrainedΔρ~max~ = 0.41 e Å^−3^Δρ~min~ = −0.98 e Å^−3^ {#d5e529} Data collection: CrystalClear (Rigaku, 2005[@bb6]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb7]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003540/jh2260sup1.cif](http://dx.doi.org/10.1107/S1600536811003540/jh2260sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003540/jh2260Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003540/jh2260Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2260&file=jh2260sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2260sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2260&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2260](http://scripts.iucr.org/cgi-bin/sendsup?jh2260)). The authors are grateful to the starter fund of Southeast University for financial support to purchase the X-ray diffractometer. Comment ======= There is currently a great deal of interest in crown ethers because of their ability to form non-covalent, H-bonding complexes with ammonium cations both in solid and in solution (Akutagawa et al., 2002; Ge et al., 2010a,b; Guo et al., 2010; Zhao et al., 2010a,b). Not only the size of the crown ether, but also the nature of the ammonium cation (--NH~4~^+^, RNH~3~^+^, R~2~NH~2~^+^, etc) can influence on the stoichiometry and stability of these host--guest complexes. The host molecules combine with the guest species by intermolecular interaction, and if the host molecule possess some specific sites, it is easy to realise high selectivity in ion or molecular recognitions. 18-Crown-6 have the highest affinity for ammonium cation RNH~3~^+^, while most studies of 18-crown-6 and its derivatives invariably showed a 1:1 stoichiometry with RNH~3~^+^ cations. Dielectric permittivity of the title compound is tested to systematically investigate the ferroelectric phase transitions materials (Ye et al., 2009; Zhang et al., 2009). The title compound has no dielectric anomaly with the value of 5 and 8 under 1M Hz in the temperature from 80 to 433 K (the compound m.p.\> 453 K), suggesting that the compound should be no distinct phase transition occurred within the measured temperature range. The title compound is composed of cationic \[C~7~H~9~NBr(18-Crown-6)\]^+^ and one single anionic \[ClO~4~\]^-^ anions (Fig. 1). Supramolecular rotators was assembled between protonated 4-bromo-3-methylanilinium \[C~7~H~6~Br---NH~3~\]^+^ and 18-crown-6 by hydrogen-bonding. The ammonium moieties of (--NH~3~^+^) cations were interacted with the oxygen atom of crown ethers through six simple N---H···O hydrogen bonding, forming 1:1 supramolecular rotator-stator structures. The macrocycle adopts a conformation with approximate D~3\ d~ symmetry, with all O---C---C---O torsion angles being gauche and alternating in sign, and all C---O---C---C torsion angles being trans. The C---N bonds of \[C~7~H~6~Br---NH~3~\]^+^ were almost perpendicular to the mean oxygen planes of crown ethers. Supramolecular cation structure, \[C~7~H~9~NBr(18-Crown-6)\]^+^, were introduced as counter cations to \[ClO~4~\]^-^ anions. Cl has a flattened tetrahedral coordination by four O^2-^ ions \[range of cis-bond angles = 108.4 (2)--110.3 (2) °; dav(Cl---O) = 1.426 (3)--1.457 (3) Å\]. The title compound was stabilized by intramolecular N---H···O hydrogen bonds, but no intermolecular hydrogen bond was observed. The intramolecular N---H···O hydrogen bonding length are within the usual range: 2.893 (4) and 2.970 (4) Å. Experimental {#experimental} ============ C~7~H~8~NBr. HClO~4~ (2 mmol, 0.57 g) and 18-crown-6 (2 mmol, 0.528 g) were dissolved in 40 ml me thanol solution. The precipitate was filtered out. Two days later, single crystals suitable for X-ray diffraction analysis were obtained from slow evaporation of methanol solution at 0°C. Refinement {#refinement} ========== All the C---H hydrogen atoms were calculated geometrically, with C---H = 0.93, 0.97 and 0.96 Å for aromatic, methylene and methyl H respectively, and constrained to ride on their parent atoms with U~iso~(H) = xU~eq~(C), where x = 1.5 for methyl H and x = 1.2 for all other H atoms. All the N---H hydrogen atoms were calculated geometrically. The positions of the H atoms of the nitrogen atoms were refined using a riding model with N---H = 0.89 Å and U~iso~(H) = 1.5U~eq~(N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The title molecules with the atomic numbering scheme. The displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0o579-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e281 .table-wrap} ----------------------------------------- ---------------------------------------- C~7~H~9~BrN^+^·ClO~4~^−^·C~12~H~24~O~6~ F(000) = 1144 M~r~ = 550.81 D~x~ = 1.454 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 20001 reflections a = 11.967 (2) Å θ = 3.0--27.3° b = 13.446 (3) Å µ = 1.79 mm^−1^ c = 15.677 (3) Å T = 296 K β = 94.05 (3)° Prism, colorless V = 2516.3 (9) Å^3^ 0.40 × 0.30 × 0.20 mm Z = 4 ----------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e424 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Rigaku SCXmini diffractometer 5665 independent reflections Radiation source: fine-focus sealed tube 4005 reflections with I \> 2σ(I) graphite R~int~ = 0.066 Detector resolution: 28.5714 pixels mm^-1^ θ~max~ = 27.3°, θ~min~ = 3.0° CCD\_Profile\_fitting scans h = −15→15 Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) k = −17→17 T~min~ = 0.530, T~max~ = 0.699 l = −20→20 25007 measured reflections ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e542 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.060 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.157 H-atom parameters constrained S = 1.09 w = 1/\[σ^2^(F~o~^2^) + (0.0769P)^2^ + 0.8528P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5665 reflections (Δ/σ)~max~ = 0.001 289 parameters Δρ~max~ = 0.41 e Å^−3^ 0 restraints Δρ~min~ = −0.98 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e699 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e798 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.19928 (4) 1.01458 (3) −0.00712 (3) 0.06334 (18) O8 0.0452 (2) 0.60635 (19) 0.30049 (15) 0.0495 (6) N1 0.2459 (2) 0.72782 (19) 0.29922 (16) 0.0367 (6) H1A 0.1796 0.7195 0.3206 0.055\ H1B 0.2937 0.7545 0.3389 0.055\* H1E 0.2719 0.6692 0.2833 0.055\* O9 0.0542 (2) 0.78578 (18) 0.39854 (15) 0.0499 (6) C15 0.3203 (3) 0.8828 (2) 0.1107 (2) 0.0370 (7) C16 0.2147 (3) 0.9217 (2) 0.08602 (19) 0.0398 (7) O6 0.4462 (2) 0.59829 (19) 0.29366 (17) 0.0551 (7) O5 0.4715 (2) 0.78411 (19) 0.37212 (16) 0.0518 (6) O7 0.2319 (2) 0.53548 (19) 0.21645 (17) 0.0554 (7) O10 0.2751 (2) 0.84908 (18) 0.45312 (16) 0.0506 (6) C13 0.2336 (3) 0.7946 (2) 0.22444 (19) 0.0332 (7) C17 0.1196 (3) 0.8976 (3) 0.1282 (2) 0.0453 (8) H17A 0.0503 0.9242 0.1098 0.054\* C18 0.1292 (3) 0.8336 (2) 0.1982 (2) 0.0415 (8) H18A 0.0664 0.8171 0.2270 0.050\* C14 0.3275 (3) 0.8187 (2) 0.1809 (2) 0.0398 (7) H14A 0.3966 0.7914 0.1990 0.048\* C11 0.5624 (3) 0.7135 (3) 0.3751 (3) 0.0545 (10) H11A 0.5601 0.6721 0.4256 0.065\* H11B 0.6335 0.7484 0.3781 0.065\* C6 −0.0296 (3) 0.7105 (3) 0.4065 (2) 0.0537 (9) H6A −0.0976 0.7405 0.4250 0.064\* H6B −0.0033 0.6619 0.4490 0.064\* C10 0.4740 (3) 0.8459 (3) 0.4471 (3) 0.0600 (10) H10A 0.5406 0.8872 0.4499 0.072\* H10B 0.4766 0.8045 0.4979 0.072\* C7 0.0804 (3) 0.8360 (3) 0.4778 (2) 0.0562 (10) H7A 0.1013 0.7881 0.5224 0.067\* H7B 0.0155 0.8726 0.4944 0.067\* C19 0.4241 (3) 0.9087 (3) 0.0644 (3) 0.0580 (10) H19A 0.4878 0.8747 0.0911 0.087\* H19B 0.4366 0.9792 0.0673 0.087\* H19C 0.4132 0.8887 0.0056 0.087\* C8 0.1762 (3) 0.9065 (3) 0.4666 (3) 0.0579 (10) H8A 0.1585 0.9496 0.4180 0.070\* H8B 0.1891 0.9476 0.5172 0.070\* C3 0.1271 (4) 0.4814 (3) 0.2176 (3) 0.0600 (10) H3A 0.1286 0.4386 0.2675 0.072\* H3B 0.1164 0.4401 0.1670 0.072\* C5 −0.0538 (3) 0.6604 (3) 0.3215 (2) 0.0517 (9) H5A −0.1164 0.6149 0.3244 0.062\* H5B −0.0733 0.7096 0.2778 0.062\* C4 0.0330 (3) 0.5545 (3) 0.2200 (2) 0.0539 (9) H4A 0.0356 0.6014 0.1731 0.065\* H4B −0.0383 0.5201 0.2144 0.065\* C9 0.3713 (3) 0.9105 (3) 0.4438 (3) 0.0583 (10) H9A 0.3780 0.9592 0.4895 0.070\* H9B 0.3633 0.9457 0.3897 0.070\* C12 0.5517 (3) 0.6502 (3) 0.2967 (3) 0.0573 (10) H12A 0.5554 0.6914 0.2462 0.069\* H12B 0.6128 0.6027 0.2978 0.069\* C1 0.4329 (4) 0.5300 (4) 0.2234 (4) 0.0794 (15) H1C 0.4969 0.4856 0.2243 0.095\* H1D 0.4290 0.5664 0.1698 0.095\* C2 0.3278 (4) 0.4705 (3) 0.2295 (4) 0.0794 (15) H2A 0.3239 0.4185 0.1866 0.095\* H2B 0.3280 0.4395 0.2854 0.095\* Cl2 0.75937 (7) 0.70425 (7) 0.09959 (6) 0.0485 (2) O2 0.7570 (3) 0.6235 (2) 0.15986 (19) 0.0709 (8) O1 0.6613 (3) 0.7637 (3) 0.1044 (3) 0.0979 (12) O4 0.7607 (3) 0.6624 (3) 0.01394 (19) 0.0784 (9) O3 0.8582 (3) 0.7636 (3) 0.1177 (2) 0.0849 (10) ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1635 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0687 (3) 0.0700 (3) 0.0526 (3) 0.0157 (2) 0.0132 (2) 0.02676 (19) O8 0.0416 (13) 0.0607 (16) 0.0458 (13) −0.0055 (11) −0.0003 (11) −0.0053 (11) N1 0.0388 (14) 0.0358 (14) 0.0359 (14) −0.0015 (11) 0.0058 (11) 0.0020 (11) O9 0.0502 (14) 0.0543 (15) 0.0469 (14) −0.0092 (11) 0.0152 (11) −0.0020 (11) C15 0.0384 (17) 0.0343 (16) 0.0393 (17) 0.0015 (13) 0.0110 (14) −0.0005 (13) C16 0.052 (2) 0.0352 (17) 0.0332 (16) 0.0051 (14) 0.0053 (14) 0.0025 (13) O6 0.0451 (14) 0.0589 (16) 0.0627 (16) 0.0068 (12) 0.0125 (12) −0.0091 (13) O5 0.0417 (14) 0.0535 (15) 0.0588 (16) 0.0012 (11) −0.0066 (12) 0.0054 (12) O7 0.0568 (16) 0.0443 (14) 0.0657 (17) 0.0002 (12) 0.0081 (13) −0.0090 (12) O10 0.0548 (15) 0.0390 (13) 0.0585 (16) −0.0048 (11) 0.0074 (12) −0.0054 (11) C13 0.0372 (16) 0.0302 (15) 0.0326 (15) −0.0003 (12) 0.0049 (13) 0.0004 (12) C17 0.0337 (17) 0.053 (2) 0.050 (2) 0.0103 (15) 0.0032 (15) 0.0062 (16) C18 0.0326 (17) 0.0468 (19) 0.0459 (18) 0.0020 (14) 0.0089 (14) 0.0067 (15) C14 0.0338 (17) 0.0399 (18) 0.0461 (18) 0.0050 (14) 0.0054 (14) 0.0034 (14) C11 0.0356 (19) 0.056 (2) 0.072 (3) −0.0006 (16) 0.0029 (18) 0.019 (2) C6 0.044 (2) 0.064 (2) 0.056 (2) −0.0041 (17) 0.0191 (17) 0.0041 (18) C10 0.053 (2) 0.050 (2) 0.073 (3) −0.0102 (18) −0.016 (2) −0.007 (2) C7 0.065 (3) 0.059 (2) 0.047 (2) −0.0005 (19) 0.0175 (18) −0.0075 (17) C19 0.047 (2) 0.061 (2) 0.068 (3) 0.0070 (18) 0.0247 (19) 0.015 (2) C8 0.066 (3) 0.051 (2) 0.058 (2) 0.0028 (19) 0.0092 (19) −0.0115 (18) C3 0.072 (3) 0.046 (2) 0.062 (3) −0.0129 (19) 0.003 (2) −0.0103 (18) C5 0.0389 (19) 0.057 (2) 0.059 (2) −0.0073 (17) 0.0030 (17) 0.0075 (18) C4 0.059 (2) 0.058 (2) 0.045 (2) −0.0166 (19) −0.0031 (17) −0.0041 (17) C9 0.056 (2) 0.045 (2) 0.073 (3) −0.0110 (18) −0.004 (2) −0.0066 (18) C12 0.0360 (19) 0.073 (3) 0.064 (2) 0.0088 (18) 0.0142 (17) 0.013 (2) C1 0.065 (3) 0.084 (3) 0.091 (4) 0.021 (2) 0.015 (3) −0.035 (3) C2 0.080 (3) 0.051 (3) 0.107 (4) 0.008 (2) 0.003 (3) −0.032 (3) Cl2 0.0381 (4) 0.0543 (5) 0.0526 (5) 0.0011 (4) −0.0005 (4) 0.0077 (4) O2 0.075 (2) 0.0661 (19) 0.0713 (19) −0.0057 (15) 0.0047 (15) 0.0206 (15) O1 0.074 (2) 0.105 (3) 0.114 (3) 0.043 (2) 0.002 (2) −0.002 (2) O4 0.080 (2) 0.101 (3) 0.0551 (18) −0.0078 (19) 0.0068 (15) −0.0074 (16) O3 0.074 (2) 0.097 (2) 0.081 (2) −0.0366 (19) −0.0162 (17) 0.0177 (18) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2240 .table-wrap} ----------------------- ------------ --------------------- ------------- Br1---C16 1.921 (3) C6---H6B 0.9700 O8---C4 1.440 (4) C10---C9 1.503 (5) O8---C5 1.448 (4) C10---H10A 0.9700 N1---C13 1.476 (4) C10---H10B 0.9700 N1---H1A 0.8900 C7---C8 1.507 (5) N1---H1B 0.8900 C7---H7A 0.9700 N1---H1E 0.8900 C7---H7B 0.9700 O9---C7 1.430 (4) C19---H19A 0.9600 O9---C6 1.437 (4) C19---H19B 0.9600 C15---C14 1.396 (4) C19---H19C 0.9600 C15---C16 1.397 (4) C8---H8A 0.9700 C15---C19 1.523 (4) C8---H8B 0.9700 C16---C17 1.393 (5) C3---C4 1.497 (6) O6---C1 1.435 (5) C3---H3A 0.9700 O6---C12 1.440 (4) C3---H3B 0.9700 O5---C10 1.437 (5) C5---H5A 0.9700 O5---C11 1.442 (4) C5---H5B 0.9700 O7---C2 1.445 (5) C4---H4A 0.9700 O7---C3 1.451 (5) C4---H4B 0.9700 O10---C9 1.432 (4) C9---H9A 0.9700 O10---C8 1.440 (4) C9---H9B 0.9700 C13---C18 1.390 (4) C12---H12A 0.9700 C13---C14 1.394 (4) C12---H12B 0.9700 C17---C18 1.393 (4) C1---C2 1.498 (7) C17---H17A 0.9300 C1---H1C 0.9700 C18---H18A 0.9300 C1---H1D 0.9700 C14---H14A 0.9300 C2---H2A 0.9700 C11---C12 1.493 (6) C2---H2B 0.9700 C11---H11A 0.9700 Cl2---O1 1.426 (3) C11---H11B 0.9700 Cl2---O3 1.439 (3) C6---C5 1.503 (5) Cl2---O2 1.441 (3) C6---H6A 0.9700 Cl2---O4 1.457 (3) C4---O8---C5 114.1 (3) C15---C19---H19C 109.5 C13---N1---H1A 109.5 H19A---C19---H19C 109.5 C13---N1---H1B 109.5 H19B---C19---H19C 109.5 H1A---N1---H1B 109.5 O10---C8---C7 108.7 (3) C13---N1---H1E 109.5 O10---C8---H8A 110.0 H1A---N1---H1E 109.5 C7---C8---H8A 110.0 H1B---N1---H1E 109.5 O10---C8---H8B 110.0 C7---O9---C6 111.6 (3) C7---C8---H8B 110.0 C14---C15---C16 117.0 (3) H8A---C8---H8B 108.3 C14---C15---C19 120.6 (3) O7---C3---C4 108.9 (3) C16---C15---C19 122.3 (3) O7---C3---H3A 109.9 C17---C16---C15 122.3 (3) C4---C3---H3A 109.9 C17---C16---Br1 118.3 (2) O7---C3---H3B 109.9 C15---C16---Br1 119.4 (2) C4---C3---H3B 109.9 C1---O6---C12 112.7 (3) H3A---C3---H3B 108.3 C10---O5---C11 112.5 (3) O8---C5---C6 108.5 (3) C2---O7---C3 112.0 (3) O8---C5---H5A 110.0 C9---O10---C8 112.4 (3) C6---C5---H5A 110.0 C18---C13---C14 120.5 (3) O8---C5---H5B 110.0 C18---C13---N1 120.1 (3) C6---C5---H5B 110.0 C14---C13---N1 119.4 (3) H5A---C5---H5B 108.4 C18---C17---C16 119.5 (3) O8---C4---C3 108.0 (3) C18---C17---H17A 120.2 O8---C4---H4A 110.1 C16---C17---H17A 120.2 C3---C4---H4A 110.1 C13---C18---C17 119.2 (3) O8---C4---H4B 110.1 C13---C18---H18A 120.4 C3---C4---H4B 110.1 C17---C18---H18A 120.4 H4A---C4---H4B 108.4 C13---C14---C15 121.4 (3) O10---C9---C10 108.9 (3) C13---C14---H14A 119.3 O10---C9---H9A 109.9 C15---C14---H14A 119.3 C10---C9---H9A 109.9 O5---C11---C12 109.2 (3) O10---C9---H9B 109.9 O5---C11---H11A 109.8 C10---C9---H9B 109.9 C12---C11---H11A 109.8 H9A---C9---H9B 108.3 O5---C11---H11B 109.8 O6---C12---C11 109.1 (3) C12---C11---H11B 109.8 O6---C12---H12A 109.9 H11A---C11---H11B 108.3 C11---C12---H12A 109.9 O9---C6---C5 109.3 (3) O6---C12---H12B 109.9 O9---C6---H6A 109.8 C11---C12---H12B 109.9 C5---C6---H6A 109.8 H12A---C12---H12B 108.3 O9---C6---H6B 109.8 O6---C1---C2 109.9 (4) C5---C6---H6B 109.8 O6---C1---H1C 109.7 H6A---C6---H6B 108.3 C2---C1---H1C 109.7 O5---C10---C9 109.7 (3) O6---C1---H1D 109.7 O5---C10---H10A 109.7 C2---C1---H1D 109.7 C9---C10---H10A 109.7 H1C---C1---H1D 108.2 O5---C10---H10B 109.7 O7---C2---C1 109.3 (4) C9---C10---H10B 109.7 O7---C2---H2A 109.8 H10A---C10---H10B 108.2 C1---C2---H2A 109.8 O9---C7---C8 108.5 (3) O7---C2---H2B 109.8 O9---C7---H7A 110.0 C1---C2---H2B 109.8 C8---C7---H7A 110.0 H2A---C2---H2B 108.3 O9---C7---H7B 110.0 O1---Cl2---O3 110.3 (2) C8---C7---H7B 110.0 O1---Cl2---O2 109.5 (2) H7A---C7---H7B 108.4 O3---Cl2---O2 110.04 (19) C15---C19---H19A 109.5 O1---Cl2---O4 109.1 (2) C15---C19---H19B 109.5 O3---Cl2---O4 109.5 (2) H19A---C19---H19B 109.5 O2---Cl2---O4 108.4 (2) C14---C15---C16---C17 −0.6 (5) C6---O9---C7---C8 174.6 (3) C19---C15---C16---C17 179.8 (3) C9---O10---C8---C7 −178.6 (3) C14---C15---C16---Br1 177.5 (2) O9---C7---C8---O10 −67.0 (4) C19---C15---C16---Br1 −2.1 (4) C2---O7---C3---C4 169.7 (4) C15---C16---C17---C18 0.7 (5) C4---O8---C5---C6 180.0 (3) Br1---C16---C17---C18 −177.4 (3) O9---C6---C5---O8 66.3 (4) C14---C13---C18---C17 −0.5 (5) C5---O8---C4---C3 −164.9 (3) N1---C13---C18---C17 179.1 (3) O7---C3---C4---O8 −66.0 (4) C16---C17---C18---C13 −0.2 (5) C8---O10---C9---C10 169.2 (3) C18---C13---C14---C15 0.6 (5) O5---C10---C9---O10 68.3 (4) N1---C13---C14---C15 −178.9 (3) C1---O6---C12---C11 −175.7 (4) C16---C15---C14---C13 −0.1 (5) O5---C11---C12---O6 −60.0 (4) C19---C15---C14---C13 179.6 (3) C12---O6---C1---C2 173.7 (4) C10---O5---C11---C12 178.1 (3) C3---O7---C2---C1 177.2 (4) C7---O9---C6---C5 180.0 (3) O6---C1---C2---O7 67.1 (5) C11---O5---C10---C9 −174.4 (3) ----------------------- ------------ --------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3246 .table-wrap} ---------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1B···O5 0.89 2.19 2.955 (4) 144 N1---H1E···O6 0.89 2.29 2.970 (4) 133 N1---H1E···O7 0.89 2.12 2.893 (4) 145 N1---H1A···O8 0.89 2.22 2.905 (4) 134 N1---H1A···O9 0.89 2.19 2.966 (4) 145 N1---H1B···O10 0.89 2.22 2.912 (4) 134 ---------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- N1---H1A⋯O8 0.89 2.22 2.905 (4) 134 N1---H1A⋯O9 0.89 2.19 2.966 (4) 145 N1---H1B⋯O5 0.89 2.19 2.955 (4) 144 N1---H1B⋯O10 0.89 2.22 2.912 (4) 134 N1---H1E⋯O6 0.89 2.29 2.970 (4) 133 N1---H1E⋯O7 0.89 2.12 2.893 (4) 145 :::	PubMed Central	2024-06-05T04:04:18.539368	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052115/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o579", "authors": [ { "first": "Qian", "last": "Xu" }, { "first": "Min Min", "last": "Zhao" } ] }
PMC3052116	Related literature {#sec1} ================== For the coordinating ability of N,N-dialkyl-N′-benzoylthioureas; see: Binzet et al. (2009[@bb3]); Gunasekaran et al. (2010[@bb7]); Sacht et al. (2000[@bb10]). For the utility of Cd derivatives to serve as synthetic precursors for CdS nanoparticles, see: Bruce et al. (2007[@bb5]). For their biological activity, see: Arslan et al. (2006[@bb2]). For related structures, see: Gunasekaran et al. (2010a [@bb8],b [@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~24~N~2~OSM ~r~ = 292.43Triclinic,a = 8.9331 (10) Åb = 10.1023 (9) Åc = 11.0725 (12) Åα = 105.776 (9)°β = 112.734 (10)°γ = 100.782 (9)°V = 837.47 (19) Å^3^Z = 2Mo Kα radiationμ = 0.19 mm^−1^T = 295 K0.35 × 0.30 × 0.25 mm ### Data collection {#sec2.1.2} Agilent Supernova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb1]) T ~min~ = 0.936, T ~max~ = 0.9546265 measured reflections3693 independent reflections2232 reflections with I \> 2σ(I)R ~int~ = 0.025 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.074wR(F ^2^) = 0.219S = 1.043693 reflections181 parameters12 restraintsH-atom parameters constrainedΔρ~max~ = 0.86 e Å^−3^Δρ~min~ = −0.58 e Å^−3^ {#d5e466} Data collection: CrysAlis PRO (Agilent, 2010[@bb1]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb11]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb11]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb6]) and DIAMOND (Brandenburg, 2006[@bb4]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004557/ez2230sup1.cif](http://dx.doi.org/10.1107/S1600536811004557/ez2230sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004557/ez2230Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004557/ez2230Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2230&file=ez2230sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2230sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2230&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2230](http://scripts.iucr.org/cgi-bin/sendsup?ez2230)). NS thanks the NITT for a Fellowship. The authors thank the University of Malaya for supporting this study. Comment ======= N,N-Dialkyl-N\'-benzoylthioureas are versatile ligands which can coordinate to transition metal centres either as neutral species or in an anionic form. The complexation capacity of thiourea derivatives has been reported in several studies (Binzet et al., 2009; Gunasekaran et al., 2010). Chiral and achiral platinum(II) complexes of these ligands have been used as chemotherapeutic agents (Sacht et al., 2000) while cadmium(II) complexes of N,N-diethyl-N\'-benzoylthiourea have been used as single-source precursors for the preparation of CdS nanoparticles (Bruce et al., 2007). In addition, thioureas have been shown to possess anti-tubercular, anti-helmintic, anti-bacterial, insecticidal and rodenticidal properties (Arslan et al., 2006). In continuation of structural studies of these derivatives (Gunasekaran et al., 2010a; Gunasekaran et al., 2010b), the title compound, (I), was investigated. In (I), Fig. 1, the molecule exhibits a significant twist about the central N(H)--C bond as seen in the value of the C7--N1--C8--S1 torsion angle of 119.6 (3) °. This arrangement causes the carbonyl-O and thione-S atoms to lie on opposite sides of the molecule. Similarly, the carbonyl and N--H groups are directed away from each other. This conformation allows for the formation of N--H···S hydrogen bonds, Table 1, via an eight-membered {···HNCS}~2~ ring which has the shape of an elongated chair. These are connected into supramolecular chains along \[1 1 1\] via C--H···O contacts that close 14-membered {···HCNCNCO}~2~ synthons, also adopting the shape of an elongated chair, Table 1 and Fig. 2. Chains are arranged into layers via weak π···π interactions \[Cg(C1--C6)···Cg(C1--C6)^i^ = 3.806 (3) Å for i: 2 - x, 1 - y, 2 - z\] and these stack as shown in Fig. 3. Experimental {#experimental} ============ A solution of benzoyl chloride (0.7029 g, 5 mmol) in acetone (50 ml) was added drop wise to a suspension of potassium thiocyanate (0.4859 g, 5 mmol) in anhydrous acetone (50 ml). The reaction mixture was heated under reflux for 45 min. and then cooled to room temperature. A solution of diisobutyl amine (0.6462 g, 5 mmol) in acetone (30 ml) was added and the resulting mixture was stirred for 2 h. Hydrochloric acid (0.1 N, 300 ml) was added and the resulting white solid was filtered, washed with water and dried in vacuo. Single crystals for X-ray diffraction were grown at room temperature from an acetonitrile solution of the compound. Yield 72%; M.Pt. 415 K. FT---IR (KBr) ν(N---H) 3268, ν(C═O) 1688, ν(C=S) 1264 cm^-1^. Refinement {#refinement} ========== The H-atoms were placed in calculated positions (N---H = 0.88; C---H 0.93 to 0.98 Å) and were included in the refinement in the riding model approximation, with U~iso~(H) set to 1.2 to 1.5U~equiv~(N, C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o602-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Supramolecular chain in (I) mediated by N--H···S hydrogen bonds and C--H···O contacts, shown as orange and blue dashed lines, respectively. ::: ![](e-67-0o602-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### View in projection down the b axis of the unit cell contents of (I). The N--H···S hydrogen bonds and C--H···O contacts are shown as orange and blue dashed lines, respectively. ::: ![](e-67-0o602-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e226 .table-wrap} ------------------------ --------------------------------------- C~16~H~24~N~2~OS Z = 2 M~r~ = 292.43 F(000) = 316 Triclinic, P1 D~x~ = 1.160 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.9331 (10) Å Cell parameters from 1845 reflections b = 10.1023 (9) Å θ = 2.2--29.2° c = 11.0725 (12) Å µ = 0.19 mm^−1^ α = 105.776 (9)° T = 295 K β = 112.734 (10)° Block, colourless γ = 100.782 (9)° 0.35 × 0.30 × 0.25 mm V = 837.47 (19) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e360 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent Supernova Dual diffractometer with an Atlas detector 3693 independent reflections Radiation source: SuperNova (Mo) X-ray Source 2232 reflections with I \> 2σ(I) Mirror R~int~ = 0.025 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.2° ω scans h = −10→11 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −13→12 T~min~ = 0.936, T~max~ = 0.954 l = −14→12 6265 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e480 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.074 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.219 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.078P)^2^ + 0.7593P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3693 reflections (Δ/σ)~max~ = 0.001 181 parameters Δρ~max~ = 0.86 e Å^−3^ 12 restraints Δρ~min~ = −0.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e637 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e736 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ S1 0.74828 (14) 0.92803 (11) 0.99096 (12) 0.0711 (4) O1 0.6998 (3) 0.5295 (2) 0.7153 (3) 0.0585 (7) N1 0.8690 (3) 0.7638 (3) 0.8494 (3) 0.0512 (7) H1 0.9753 0.8236 0.8909 0.061\ N2 0.6172 (3) 0.7981 (3) 0.7098 (3) 0.0515 (7) C1 0.9961 (4) 0.5699 (3) 0.8524 (3) 0.0431 (7) C2 0.9697 (5) 0.4222 (4) 0.8112 (4) 0.0535 (9) H2 0.8597 0.3566 0.7487 0.064\* C3 1.1045 (5) 0.3706 (4) 0.8615 (5) 0.0653 (11) H3 1.0847 0.2708 0.8335 0.078\* C4 1.2664 (5) 0.4656 (5) 0.9522 (5) 0.0669 (11) H4 1.3568 0.4306 0.9866 0.080\* C5 1.2961 (5) 0.6133 (5) 0.9929 (5) 0.0661 (11) H5 1.4069 0.6780 1.0542 0.079\* C6 1.1618 (4) 0.6657 (4) 0.9431 (4) 0.0538 (9) H6 1.1826 0.7656 0.9705 0.065\* C7 0.8421 (4) 0.6165 (3) 0.7986 (3) 0.0426 (7) C8 0.7372 (4) 0.8250 (3) 0.8392 (4) 0.0513 (9) C9 0.6351 (4) 0.7432 (3) 0.5811 (4) 0.0526 (9) H9A 0.5352 0.6588 0.5122 0.063\* H9B 0.7353 0.7118 0.6035 0.063\* C10 0.6535 (5) 0.8564 (4) 0.5150 (4) 0.0654 (11) H10 0.5463 0.8792 0.4831 0.079\* C11 0.6790 (7) 0.7906 (5) 0.3856 (4) 0.0892 (15) H11A 0.5849 0.7025 0.3204 0.134\* H11B 0.7847 0.7691 0.4149 0.134\* H11C 0.6835 0.8587 0.3403 0.134\* C12 0.7998 (6) 0.9970 (4) 0.6237 (5) 0.0877 (15) H12A 0.8091 1.0661 0.5801 0.132\* H12B 0.9057 0.9765 0.6583 0.132\* H12C 0.7765 1.0367 0.7012 0.132\* C13 0.4659 (4) 0.8426 (4) 0.6909 (5) 0.0662 (11) H13A 0.4206 0.8536 0.6005 0.079\* H13B 0.5025 0.9377 0.7640 0.079\* C14 0.3240 (5) 0.7441 (4) 0.6949 (7) 0.106 (2) H14 0.3640 0.7625 0.7957 0.127\* C15 0.1645 (5) 0.7914 (5) 0.6518 (6) 0.0888 (15) H15A 0.1979 0.8950 0.6987 0.133\* H15B 0.0863 0.7435 0.6785 0.133\* H15C 0.1094 0.7655 0.5512 0.133\* C16 0.2816 (6) 0.5830 (4) 0.6261 (6) 0.0816 (13) H16A 0.3853 0.5586 0.6554 0.122\* H16B 0.2264 0.5542 0.5251 0.122\* H16C 0.2058 0.5330 0.6536 0.122\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1304 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ S1 0.0676 (7) 0.0507 (6) 0.0765 (7) 0.0191 (5) 0.0294 (6) 0.0036 (5) O1 0.0434 (13) 0.0383 (13) 0.0653 (16) 0.0071 (11) 0.0031 (12) 0.0157 (12) N1 0.0344 (14) 0.0355 (15) 0.0622 (18) 0.0091 (12) 0.0100 (13) 0.0078 (13) N2 0.0364 (14) 0.0400 (15) 0.0659 (19) 0.0137 (12) 0.0144 (14) 0.0156 (14) C1 0.0428 (17) 0.0444 (18) 0.0423 (17) 0.0167 (15) 0.0181 (14) 0.0176 (14) C2 0.054 (2) 0.0427 (19) 0.059 (2) 0.0190 (16) 0.0215 (17) 0.0169 (17) C3 0.069 (3) 0.054 (2) 0.088 (3) 0.034 (2) 0.040 (2) 0.034 (2) C4 0.055 (2) 0.077 (3) 0.089 (3) 0.039 (2) 0.035 (2) 0.046 (3) C5 0.0419 (19) 0.071 (3) 0.077 (3) 0.0192 (19) 0.0186 (18) 0.029 (2) C6 0.0451 (19) 0.050 (2) 0.060 (2) 0.0171 (16) 0.0180 (16) 0.0193 (17) C7 0.0417 (17) 0.0384 (17) 0.0383 (16) 0.0125 (14) 0.0111 (14) 0.0128 (14) C8 0.0403 (17) 0.0325 (17) 0.067 (2) 0.0098 (14) 0.0173 (16) 0.0118 (16) C9 0.0438 (18) 0.0412 (19) 0.060 (2) 0.0136 (15) 0.0125 (16) 0.0183 (17) C10 0.055 (2) 0.052 (2) 0.075 (3) 0.0160 (18) 0.0104 (19) 0.032 (2) C11 0.113 (4) 0.077 (3) 0.071 (3) 0.025 (3) 0.033 (3) 0.038 (3) C12 0.092 (3) 0.052 (3) 0.089 (3) 0.000 (2) 0.021 (3) 0.030 (2) C13 0.046 (2) 0.057 (2) 0.089 (3) 0.0247 (18) 0.022 (2) 0.027 (2) C14 0.065 (3) 0.072 (3) 0.203 (7) 0.033 (3) 0.070 (4) 0.065 (4) C15 0.060 (3) 0.097 (4) 0.139 (5) 0.039 (3) 0.057 (3) 0.060 (4) C16 0.071 (3) 0.057 (3) 0.113 (4) 0.012 (2) 0.047 (3) 0.027 (3) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1650 .table-wrap} ------------------- ------------ ---------------------- ------------ S1---C8 1.673 (4) C9---H9B 0.9700 O1---C7 1.214 (4) C10---C12 1.528 (4) N1---C7 1.377 (4) C10---C11 1.529 (4) N1---C8 1.410 (4) C10---H10 0.9800 N1---H1 0.8800 C11---H11A 0.9600 N2---C8 1.330 (4) C11---H11B 0.9600 N2---C13 1.461 (4) C11---H11C 0.9600 N2---C9 1.464 (5) C12---H12A 0.9600 C1---C2 1.380 (5) C12---H12B 0.9600 C1---C6 1.386 (5) C12---H12C 0.9600 C1---C7 1.493 (4) C13---C14 1.482 (4) C2---C3 1.381 (5) C13---H13A 0.9700 C2---H2 0.9300 C13---H13B 0.9700 C3---C4 1.362 (6) C14---C16 1.498 (4) C3---H3 0.9300 C14---C15 1.530 (4) C4---C5 1.376 (6) C14---H14 0.9800 C4---H4 0.9300 C15---H15A 0.9600 C5---C6 1.382 (5) C15---H15B 0.9600 C5---H5 0.9300 C15---H15C 0.9600 C6---H6 0.9300 C16---H16A 0.9600 C9---C10 1.533 (4) C16---H16B 0.9600 C9---H9A 0.9700 C16---H16C 0.9600 C7---N1---C8 124.2 (3) C12---C10---H10 108.2 C7---N1---H1 117.9 C11---C10---H10 108.2 C8---N1---H1 117.9 C9---C10---H10 108.2 C8---N2---C13 120.0 (3) C10---C11---H11A 109.5 C8---N2---C9 124.2 (3) C10---C11---H11B 109.5 C13---N2---C9 115.2 (3) H11A---C11---H11B 109.5 C2---C1---C6 118.6 (3) C10---C11---H11C 109.5 C2---C1---C7 117.4 (3) H11A---C11---H11C 109.5 C6---C1---C7 124.0 (3) H11B---C11---H11C 109.5 C1---C2---C3 120.9 (4) C10---C12---H12A 109.5 C1---C2---H2 119.6 C10---C12---H12B 109.5 C3---C2---H2 119.6 H12A---C12---H12B 109.5 C4---C3---C2 120.1 (4) C10---C12---H12C 109.5 C4---C3---H3 119.9 H12A---C12---H12C 109.5 C2---C3---H3 119.9 H12B---C12---H12C 109.5 C3---C4---C5 120.0 (3) N2---C13---C14 116.6 (3) C3---C4---H4 120.0 N2---C13---H13A 108.1 C5---C4---H4 120.0 C14---C13---H13A 108.1 C4---C5---C6 120.2 (4) N2---C13---H13B 108.1 C4---C5---H5 119.9 C14---C13---H13B 108.1 C6---C5---H5 119.9 H13A---C13---H13B 107.3 C5---C6---C1 120.2 (3) C13---C14---C16 118.4 (4) C5---C6---H6 119.9 C13---C14---C15 111.0 (3) C1---C6---H6 119.9 C16---C14---C15 112.5 (4) O1---C7---N1 121.4 (3) C13---C14---H14 104.5 O1---C7---C1 122.1 (3) C16---C14---H14 104.5 N1---C7---C1 116.6 (3) C15---C14---H14 104.5 N2---C8---N1 117.1 (3) C14---C15---H15A 109.5 N2---C8---S1 125.9 (3) C14---C15---H15B 109.5 N1---C8---S1 117.1 (3) H15A---C15---H15B 109.5 N2---C9---C10 113.3 (3) C14---C15---H15C 109.5 N2---C9---H9A 108.9 H15A---C15---H15C 109.5 C10---C9---H9A 108.9 H15B---C15---H15C 109.5 N2---C9---H9B 108.9 C14---C16---H16A 109.5 C10---C9---H9B 108.9 C14---C16---H16B 109.5 H9A---C9---H9B 107.7 H16A---C16---H16B 109.5 C12---C10---C11 112.2 (3) C14---C16---H16C 109.5 C12---C10---C9 110.9 (3) H16A---C16---H16C 109.5 C11---C10---C9 109.1 (3) H16B---C16---H16C 109.5 C6---C1---C2---C3 1.4 (5) C13---N2---C8---N1 172.5 (3) C7---C1---C2---C3 −177.1 (3) C9---N2---C8---N1 −16.3 (5) C1---C2---C3---C4 −0.5 (6) C13---N2---C8---S1 −9.0 (5) C2---C3---C4---C5 −0.5 (6) C9---N2---C8---S1 162.2 (3) C3---C4---C5---C6 0.6 (7) C7---N1---C8---N2 −61.8 (5) C4---C5---C6---C1 0.4 (6) C7---N1---C8---S1 119.6 (3) C2---C1---C6---C5 −1.4 (5) C8---N2---C9---C10 −109.9 (4) C7---C1---C6---C5 177.1 (3) C13---N2---C9---C10 61.7 (4) C8---N1---C7---O1 15.7 (5) N2---C9---C10---C12 53.6 (4) C8---N1---C7---C1 −163.6 (3) N2---C9---C10---C11 177.6 (3) C2---C1---C7---O1 −4.2 (5) C8---N2---C13---C14 −82.1 (5) C6---C1---C7---O1 177.4 (3) C9---N2---C13---C14 105.9 (4) C2---C1---C7---N1 175.2 (3) N2---C13---C14---C16 −39.2 (7) C6---C1---C7---N1 −3.3 (5) N2---C13---C14---C15 −171.4 (4) ------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2386 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1···S1^i^ 0.88 2.74 3.586 (3) 162 C9---H9a···O1^ii^ 0.97 2.49 3.424 (5) 162 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+2, −y+2, −z+2; (ii) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ----------------- --------- ------- ----------- ------------- N1---H1⋯S1^i^ 0.88 2.74 3.586 (3) 162 C9---H9a⋯O1^ii^ 0.97 2.49 3.424 (5) 162 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Additional correspondence author, e-mail: kar@nitt.edu.	PubMed Central	2024-06-05T04:04:18.547641	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052116/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o602", "authors": [ { "first": "N.", "last": "Selvakumaran" }, { "first": "R.", "last": "Karvembu" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }
PMC3052117	Related literature {#sec1} ================== For background to chalcone chemistry, see: Roman (2004[@bb6]). For related structures, see: Prasath et al. (2010[@bb4]); Reddy et al. (2010[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~17~Cl~2~NOM ~r~ = 418.30Triclinic,a = 11.1704 (3) Åb = 12.8497 (5) Åc = 16.0591 (6) Åα = 74.914 (3)°β = 80.603 (3)°γ = 70.789 (3)°V = 2094.05 (13) Å^3^Z = 4Cu Kα radiationμ = 2.91 mm^−1^T = 295 K0.30 × 0.30 × 0.10 mm ### Data collection {#sec2.1.2} Agilent Supernova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb1]) T ~min~ = 0.574, T ~max~ = 1.00014958 measured reflections8252 independent reflections7088 reflections with I \> 2σ(I)R ~int~ = 0.026 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.052wR(F ^2^) = 0.158S = 1.038252 reflections525 parametersH-atom parameters constrainedΔρ~max~ = 0.43 e Å^−3^Δρ~min~ = −0.41 e Å^−3^ {#d5e448} Data collection: CrysAlis PRO (Agilent, 2010[@bb1]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb3]) and DIAMOND (Brandenburg, 2006[@bb2]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004740/hg2798sup1.cif](http://dx.doi.org/10.1107/S1600536811004740/hg2798sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004740/hg2798Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004740/hg2798Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg2798&file=hg2798sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg2798sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg2798&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG2798](http://scripts.iucr.org/cgi-bin/sendsup?hg2798)). VV is grateful to the DST, India, for funding through the Young Scientist Scheme (Fast Track Proposal). The authors are also grateful to the University of Malaya for support of the crystallographic facility. Comment ======= Chalcones and its analogs are valuable intermediates in organic synthesis and exhibit a multitude of biological activities. From a chemical point of view, an important feature of chalcones and their heteroanalogs is the ability to act as activated unsaturated systems in conjugated addition reactions of carbanions in the presence of basic catalysts (Roman, 2004). The title compound, (I), was examined in continuation of our interest in the structural chemistry of chalcones (Prasath et al., 2010; Reddy et al., 2010). Two independent molecules comprise the asymmetric unit of (I), one with an anti relationship between the carbonyl and ethylene double bonds, Fig. 1, and one with a syn relationship, Fig. 2. In each, the conformation about the ethylene bond \[C18═C19 = 1.319 (3) Å and C43═C44 = 1.328 (3) Å\] is E. For both molecules, the benzene ring is twisted out of the plane of the quinoline residue to which it is connected; the C6---C7---C11---C12 and C31---C32---C36---C37 torsion angles are -69.0 (2) and -107.1 (2) °, respectively. The prop-2-en-1-one substituents are also twisted out of the plane of the respective quinoline residues as seen in the values of the C7---C8---C17---O1 and C32---C33---C42---O2 torsion angles of 91.2 (2) and -119.1 (3) °, respectively. Within the prop-2-en-1-one substituents themselves, the terminal benzene rings are not co-planar with the C18---C19---C20---C21 and C43---C44---C45---C46 torsion angles being -159.6 (2) and -170.8 (2) °, respectively. The molecules are stabilized in the crystal packing by a combination of C---H···π, π--π, and C---Cl···π interactions. The C---H···π contacts, Table 1, occur between the two molecules comprising the asymmetric unit. The π--π interactions occur between centrosymmetrically related quinoline rings belonging to like molecules \[Cg(N1,C1,C6---C9)···Cg(C1---C6)^ii^ = 3.8446 (11) ° for ii: 1 - x, 1 - y, -z; and Cg(N2,C26,C31---C34)···Cg(C26---C31)^iii^ = 3.7809 (12) ° for iii: 1 - x, 1 - y, 1 - z\]. The C---H···Cl contacts \[C4---Cl1···Cg(C20---C25)^iv^ = 3.6082 (13) Å and angle at Cl1 = 116.34 (7) ° for iv: -1 + x, y, z\] also occur between like molecules. A view of the crystal packing is shown in Fig. 3. Experimental {#experimental} ============ A mixture of 3-acetyl-6-chloro-2-methyl-4-phenylquinoline (3.1 g, 0.01 M) and 4-chlorobenzaldehyde (1.4 g, 0.01 M) and a catalytic amount of KOH in distilled ethanol (40 ml) was stirred for about 12 h. The resulting mixture was concentrated to remove ethanol, poured onto ice and neutralized with dilute acetic acid. The resultant solid was filtered, dried and purified by column chromatography using a 1:1 mixture of ethyl acetate and petroleum ether. Recrystallization was from acetone; Yield: 64% and m.pt: 397--399 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.93 to 0.96 Å) and were included in the refinement in the riding model approximation, with U~iso~(H) set to 1.2 to 1.5U~equiv~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the first independent molecule of (I), i.e. the anti form, showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o624-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular structure of the second independent molecule of (I), i.e. the syn form, showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o624-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view in projection down the c axis of the unit-cell contents of (I). The C---H···π, π--π, and C---Cl···π interactions are shown as purple, orange and green dashed lines, respectively. ::: ![](e-67-0o624-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e255 .table-wrap} ------------------------- --------------------------------------- C~25~H~17~Cl~2~NO Z = 4 M~r~ = 418.30 F(000) = 864 Triclinic, P1 D~x~ = 1.327 Mg m^−3^ Hall symbol: -P 1 Cu Kα radiation, λ = 1.54184 Å a = 11.1704 (3) Å Cell parameters from 8901 reflections b = 12.8497 (5) Å θ = 2.9--74.1° c = 16.0591 (6) Å µ = 2.91 mm^−1^ α = 74.914 (3)° T = 295 K β = 80.603 (3)° Prism, colourless γ = 70.789 (3)° 0.30 × 0.30 × 0.10 mm V = 2094.05 (13) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e389 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent Supernova Dual diffractometer with an Atlas detector 8252 independent reflections Radiation source: SuperNova (Cu) X-ray Source 7088 reflections with I \> 2σ(I) Mirror R~int~ = 0.026 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 74.3°, θ~min~ = 2.9° ω scans h = −11→13 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −16→15 T~min~ = 0.574, T~max~ = 1.000 l = −20→19 14958 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e509 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.052 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.158 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0899P)^2^ + 0.4585P\] where P = (F~o~^2^ + 2F~c~^2^)/3 8252 reflections (Δ/σ)~max~ = 0.001 525 parameters Δρ~max~ = 0.43 e Å^−3^ 0 restraints Δρ~min~ = −0.41 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e666 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e765 .table-wrap} ------ -------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Cl1 0.16358 (5) 0.49560 (5) 0.26030 (4) 0.06920 (17) Cl2 1.33991 (8) 0.11218 (7) 0.45986 (5) 0.0924 (2) O1 0.86575 (14) 0.22234 (15) 0.02125 (11) 0.0691 (4) N1 0.61911 (15) 0.56418 (13) 0.04091 (10) 0.0501 (4) C1 0.51604 (16) 0.54394 (15) 0.09308 (11) 0.0443 (4) C2 0.40157 (18) 0.63350 (16) 0.09149 (13) 0.0512 (4) H2 0.3986 0.7037 0.0554 0.061\ C3 0.29485 (18) 0.61886 (17) 0.14218 (14) 0.0541 (4) H3 0.2196 0.6783 0.1404 0.065\* C4 0.30038 (17) 0.51310 (16) 0.19691 (13) 0.0501 (4) C5 0.40840 (17) 0.42366 (16) 0.20038 (12) 0.0486 (4) H5 0.4092 0.3542 0.2370 0.058\* C6 0.51918 (16) 0.43729 (14) 0.14790 (11) 0.0433 (4) C7 0.63491 (17) 0.34658 (15) 0.14543 (12) 0.0463 (4) C8 0.73523 (17) 0.36816 (16) 0.08963 (12) 0.0486 (4) C9 0.72457 (17) 0.47965 (17) 0.03906 (13) 0.0503 (4) C10 0.8367 (2) 0.5062 (2) −0.01747 (17) 0.0686 (6) H10A 0.8075 0.5746 −0.0603 0.103\* H10B 0.8815 0.4452 −0.0456 0.103\* H10C 0.8926 0.5159 0.0174 0.103\* C11 0.64371 (16) 0.23274 (15) 0.20244 (13) 0.0485 (4) C12 0.6432 (2) 0.21729 (18) 0.29087 (14) 0.0595 (5) H12 0.6381 0.2775 0.3146 0.071\* C13 0.6502 (2) 0.11177 (19) 0.34435 (16) 0.0692 (6) H13 0.6508 0.1012 0.4038 0.083\* C14 0.6564 (2) 0.02285 (19) 0.30963 (16) 0.0675 (6) H14 0.6597 −0.0474 0.3458 0.081\* C15 0.6575 (2) 0.03717 (19) 0.22225 (17) 0.0665 (6) H15 0.6624 −0.0234 0.1990 0.080\* C16 0.6514 (2) 0.14203 (18) 0.16806 (15) 0.0584 (5) H16 0.6524 0.1515 0.1086 0.070\* C17 0.85560 (18) 0.27261 (18) 0.07789 (13) 0.0542 (4) C18 0.95710 (19) 0.2412 (2) 0.13521 (15) 0.0622 (5) H18 1.0323 0.1867 0.1230 0.075\* C19 0.95068 (19) 0.28387 (19) 0.20273 (14) 0.0601 (5) H19 0.8771 0.3412 0.2127 0.072\* C20 1.0485 (2) 0.24950 (19) 0.26344 (14) 0.0597 (5) C21 1.0179 (2) 0.2730 (2) 0.34513 (15) 0.0667 (6) H21 0.9357 0.3158 0.3598 0.080\* C22 1.1072 (3) 0.2339 (2) 0.40532 (16) 0.0718 (6) H22 1.0853 0.2496 0.4601 0.086\* C23 1.2288 (2) 0.1717 (2) 0.38295 (15) 0.0657 (5) C24 1.2642 (2) 0.1516 (3) 0.30134 (17) 0.0769 (7) H24 1.3477 0.1123 0.2862 0.092\* C25 1.1743 (2) 0.1906 (2) 0.24211 (16) 0.0747 (7) H25 1.1981 0.1772 0.1867 0.090\* Cl3 0.90535 (6) 0.58126 (7) 0.40484 (4) 0.0849 (2) Cl4 0.90415 (7) −0.25246 (7) 1.15298 (5) 0.0979 (3) O2 0.4659 (2) 0.17598 (16) 0.71587 (14) 0.0901 (6) N2 0.45355 (15) 0.52142 (13) 0.63374 (11) 0.0513 (4) C26 0.56090 (18) 0.53029 (15) 0.58190 (12) 0.0473 (4) C27 0.5587 (2) 0.63632 (17) 0.52686 (14) 0.0595 (5) H27 0.4852 0.6972 0.5274 0.071\* C28 0.6626 (2) 0.65091 (18) 0.47297 (14) 0.0641 (5) H28 0.6597 0.7208 0.4365 0.077\* C29 0.7733 (2) 0.55961 (19) 0.47328 (13) 0.0578 (5) C30 0.78037 (19) 0.45574 (18) 0.52438 (13) 0.0530 (4) H30 0.8551 0.3963 0.5228 0.064\* C31 0.67341 (17) 0.43863 (15) 0.57993 (11) 0.0452 (4) C32 0.67093 (17) 0.33154 (15) 0.63337 (12) 0.0474 (4) C33 0.55979 (18) 0.32275 (16) 0.68166 (12) 0.0488 (4) C34 0.45213 (18) 0.42134 (17) 0.68166 (12) 0.0500 (4) C35 0.3321 (2) 0.4172 (2) 0.73827 (16) 0.0666 (6) H35A 0.2747 0.4924 0.7340 0.100\* H35B 0.3519 0.3848 0.7972 0.100\* H35C 0.2929 0.3717 0.7198 0.100\* C36 0.78570 (19) 0.23100 (16) 0.63245 (14) 0.0545 (4) C37 0.7881 (2) 0.1469 (2) 0.5930 (2) 0.0778 (7) H37 0.7175 0.1524 0.5665 0.093\* C38 0.8959 (3) 0.0539 (2) 0.5930 (3) 0.1036 (11) H38 0.8976 −0.0022 0.5657 0.124\* C39 0.9992 (3) 0.0443 (2) 0.6328 (3) 0.1048 (11) H39 1.0704 −0.0188 0.6334 0.126\* C40 0.9983 (3) 0.1272 (3) 0.6717 (2) 0.0936 (9) H40 1.0689 0.1204 0.6987 0.112\* C41 0.8928 (2) 0.2212 (2) 0.67094 (18) 0.0717 (6) H41 0.8934 0.2783 0.6964 0.086\* C42 0.5465 (2) 0.21028 (17) 0.73280 (14) 0.0578 (5) C43 0.6285 (2) 0.14702 (17) 0.80398 (13) 0.0555 (4) H43 0.6941 0.1725 0.8115 0.067\* C44 0.6106 (2) 0.05441 (17) 0.85759 (14) 0.0565 (5) H44 0.5444 0.0319 0.8470 0.068\* C45 0.68219 (19) −0.01640 (16) 0.93118 (13) 0.0534 (4) C46 0.6598 (2) −0.11931 (18) 0.97154 (15) 0.0632 (5) H46 0.5982 −0.1395 0.9523 0.076\* C47 0.7274 (2) −0.19163 (19) 1.03947 (15) 0.0676 (6) H47 0.7122 −0.2603 1.0655 0.081\* C48 0.8172 (2) −0.1612 (2) 1.06821 (14) 0.0655 (6) C49 0.8405 (2) −0.0588 (2) 1.03070 (16) 0.0661 (5) H49 0.9008 −0.0384 1.0513 0.079\* C50 0.7730 (2) 0.01233 (17) 0.96251 (14) 0.0599 (5) H50 0.7886 0.0809 0.9370 0.072\* ------ -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1945 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cl1 0.0485 (3) 0.0690 (3) 0.0810 (4) −0.0169 (2) 0.0158 (2) −0.0153 (3) Cl2 0.1064 (5) 0.0972 (5) 0.0794 (4) −0.0360 (4) −0.0375 (4) −0.0041 (4) O1 0.0567 (8) 0.0792 (10) 0.0693 (9) −0.0061 (7) −0.0043 (7) −0.0323 (8) N1 0.0507 (8) 0.0490 (8) 0.0522 (8) −0.0209 (7) −0.0003 (7) −0.0091 (7) C1 0.0447 (9) 0.0438 (9) 0.0456 (9) −0.0159 (7) −0.0037 (7) −0.0088 (7) C2 0.0532 (10) 0.0413 (9) 0.0542 (10) −0.0113 (8) −0.0039 (8) −0.0065 (8) C3 0.0474 (10) 0.0469 (10) 0.0610 (11) −0.0053 (8) −0.0037 (8) −0.0122 (8) C4 0.0434 (9) 0.0515 (10) 0.0537 (10) −0.0143 (8) 0.0019 (7) −0.0124 (8) C5 0.0472 (9) 0.0439 (9) 0.0513 (10) −0.0137 (7) 0.0007 (7) −0.0075 (7) C6 0.0413 (8) 0.0424 (9) 0.0455 (9) −0.0121 (7) −0.0030 (7) −0.0097 (7) C7 0.0437 (9) 0.0446 (9) 0.0475 (9) −0.0103 (7) −0.0028 (7) −0.0094 (7) C8 0.0404 (9) 0.0526 (10) 0.0519 (10) −0.0116 (7) −0.0016 (7) −0.0144 (8) C9 0.0452 (9) 0.0573 (11) 0.0525 (10) −0.0219 (8) 0.0014 (7) −0.0142 (8) C10 0.0540 (12) 0.0765 (14) 0.0781 (15) −0.0321 (11) 0.0114 (10) −0.0162 (12) C11 0.0383 (8) 0.0429 (9) 0.0567 (10) −0.0065 (7) −0.0001 (7) −0.0078 (8) C12 0.0637 (12) 0.0496 (10) 0.0579 (11) −0.0110 (9) 0.0003 (9) −0.0107 (9) C13 0.0793 (15) 0.0576 (12) 0.0578 (12) −0.0157 (11) −0.0012 (10) 0.0000 (10) C14 0.0659 (13) 0.0482 (11) 0.0749 (14) −0.0127 (9) 0.0006 (11) −0.0002 (10) C15 0.0656 (13) 0.0491 (11) 0.0833 (16) −0.0167 (9) 0.0014 (11) −0.0177 (10) C16 0.0586 (11) 0.0534 (11) 0.0616 (12) −0.0156 (9) −0.0024 (9) −0.0131 (9) C17 0.0436 (9) 0.0602 (11) 0.0550 (11) −0.0124 (8) 0.0025 (8) −0.0146 (9) C18 0.0435 (10) 0.0694 (13) 0.0672 (13) −0.0024 (9) −0.0036 (9) −0.0237 (10) C19 0.0473 (10) 0.0616 (12) 0.0645 (12) −0.0061 (9) −0.0003 (9) −0.0182 (10) C20 0.0565 (11) 0.0612 (12) 0.0596 (12) −0.0132 (9) −0.0025 (9) −0.0176 (10) C21 0.0698 (13) 0.0630 (13) 0.0652 (13) −0.0134 (10) 0.0016 (10) −0.0238 (11) C22 0.0950 (17) 0.0696 (14) 0.0553 (12) −0.0279 (13) −0.0025 (11) −0.0198 (11) C23 0.0756 (14) 0.0624 (13) 0.0633 (13) −0.0268 (11) −0.0144 (11) −0.0079 (10) C24 0.0577 (13) 0.0975 (19) 0.0731 (15) −0.0140 (12) −0.0089 (11) −0.0251 (14) C25 0.0580 (12) 0.1000 (19) 0.0616 (13) −0.0094 (12) −0.0046 (10) −0.0290 (13) Cl3 0.0766 (4) 0.1135 (5) 0.0664 (3) −0.0543 (4) 0.0053 (3) 0.0031 (3) Cl4 0.0807 (4) 0.1019 (5) 0.0778 (4) −0.0143 (4) −0.0140 (3) 0.0241 (4) O2 0.1015 (13) 0.0784 (11) 0.1015 (14) −0.0568 (11) −0.0422 (11) 0.0203 (10) N2 0.0514 (8) 0.0475 (8) 0.0523 (8) −0.0102 (7) −0.0031 (7) −0.0133 (7) C26 0.0530 (10) 0.0436 (9) 0.0450 (9) −0.0144 (7) −0.0042 (7) −0.0094 (7) C27 0.0722 (13) 0.0430 (10) 0.0570 (11) −0.0127 (9) −0.0058 (9) −0.0063 (8) C28 0.0881 (15) 0.0506 (11) 0.0527 (11) −0.0293 (11) −0.0055 (10) 0.0007 (9) C29 0.0638 (12) 0.0673 (12) 0.0469 (10) −0.0331 (10) −0.0024 (8) −0.0049 (9) C30 0.0489 (10) 0.0575 (11) 0.0525 (10) −0.0187 (8) −0.0034 (8) −0.0090 (8) C31 0.0475 (9) 0.0437 (9) 0.0455 (9) −0.0164 (7) −0.0043 (7) −0.0080 (7) C32 0.0471 (9) 0.0430 (9) 0.0516 (9) −0.0144 (7) −0.0070 (7) −0.0068 (7) C33 0.0512 (10) 0.0461 (9) 0.0491 (9) −0.0185 (8) −0.0069 (7) −0.0039 (7) C34 0.0487 (9) 0.0544 (10) 0.0476 (9) −0.0170 (8) −0.0034 (7) −0.0110 (8) C35 0.0556 (12) 0.0802 (15) 0.0641 (13) −0.0249 (11) 0.0053 (10) −0.0167 (11) C36 0.0510 (10) 0.0442 (9) 0.0626 (11) −0.0136 (8) −0.0022 (8) −0.0049 (8) C37 0.0637 (13) 0.0593 (13) 0.114 (2) −0.0181 (11) −0.0014 (13) −0.0297 (14) C38 0.0825 (19) 0.0600 (15) 0.170 (3) −0.0183 (14) 0.015 (2) −0.0479 (19) C39 0.0656 (17) 0.0584 (15) 0.164 (3) 0.0017 (12) 0.0044 (18) −0.0139 (18) C40 0.0580 (14) 0.0813 (18) 0.121 (3) 0.0008 (12) −0.0186 (15) −0.0100 (17) C41 0.0559 (12) 0.0682 (14) 0.0839 (16) −0.0075 (10) −0.0137 (11) −0.0146 (12) C42 0.0596 (11) 0.0514 (10) 0.0620 (12) −0.0247 (9) −0.0069 (9) −0.0008 (9) C43 0.0590 (11) 0.0495 (10) 0.0567 (11) −0.0203 (9) −0.0040 (9) −0.0048 (8) C44 0.0571 (11) 0.0497 (10) 0.0600 (11) −0.0191 (8) −0.0023 (9) −0.0055 (9) C45 0.0554 (10) 0.0450 (9) 0.0525 (10) −0.0126 (8) 0.0050 (8) −0.0074 (8) C46 0.0676 (13) 0.0562 (11) 0.0635 (12) −0.0262 (10) 0.0025 (10) −0.0044 (10) C47 0.0739 (14) 0.0528 (11) 0.0627 (13) −0.0189 (10) 0.0073 (10) 0.0020 (10) C48 0.0588 (12) 0.0623 (12) 0.0542 (11) −0.0054 (10) 0.0054 (9) 0.0002 (9) C49 0.0602 (12) 0.0679 (13) 0.0653 (13) −0.0170 (10) −0.0036 (10) −0.0104 (11) C50 0.0640 (12) 0.0478 (10) 0.0628 (12) −0.0167 (9) −0.0024 (9) −0.0055 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3159 .table-wrap} ----------------------- -------------- ----------------------- -------------- Cl1---C4 1.7382 (19) Cl3---C29 1.744 (2) Cl2---C23 1.742 (2) Cl4---C48 1.739 (2) O1---C17 1.217 (2) O2---C42 1.218 (3) N1---C9 1.316 (3) N2---C34 1.319 (3) N1---C1 1.365 (2) N2---C26 1.363 (3) C1---C2 1.410 (3) C26---C27 1.413 (3) C1---C6 1.416 (2) C26---C31 1.414 (3) C2---C3 1.368 (3) C27---C28 1.364 (3) C2---H2 0.9300 C27---H27 0.9300 C3---C4 1.401 (3) C28---C29 1.397 (3) C3---H3 0.9300 C28---H28 0.9300 C4---C5 1.362 (3) C29---C30 1.358 (3) C5---C6 1.413 (2) C30---C31 1.412 (3) C5---H5 0.9300 C30---H30 0.9300 C6---C7 1.431 (2) C31---C32 1.426 (2) C7---C8 1.372 (3) C32---C33 1.374 (3) C7---C11 1.492 (3) C32---C36 1.492 (3) C8---C9 1.428 (3) C33---C34 1.431 (3) C8---C17 1.517 (3) C33---C42 1.506 (3) C9---C10 1.503 (3) C34---C35 1.501 (3) C10---H10A 0.9600 C35---H35A 0.9600 C10---H10B 0.9600 C35---H35B 0.9600 C10---H10C 0.9600 C35---H35C 0.9600 C11---C12 1.381 (3) C36---C37 1.379 (3) C11---C16 1.387 (3) C36---C41 1.390 (3) C12---C13 1.388 (3) C37---C38 1.390 (4) C12---H12 0.9300 C37---H37 0.9300 C13---C14 1.374 (3) C38---C39 1.364 (5) C13---H13 0.9300 C38---H38 0.9300 C14---C15 1.365 (4) C39---C40 1.364 (5) C14---H14 0.9300 C39---H39 0.9300 C15---C16 1.388 (3) C40---C41 1.382 (3) C15---H15 0.9300 C40---H40 0.9300 C16---H16 0.9300 C41---H41 0.9300 C17---C18 1.464 (3) C42---C43 1.474 (3) C18---C19 1.319 (3) C43---C44 1.328 (3) C18---H18 0.9300 C43---H43 0.9300 C19---C20 1.465 (3) C44---C45 1.461 (3) C19---H19 0.9300 C44---H44 0.9300 C20---C21 1.386 (3) C45---C50 1.389 (3) C20---C25 1.394 (3) C45---C46 1.396 (3) C21---C22 1.384 (4) C46---C47 1.380 (3) C21---H21 0.9300 C46---H46 0.9300 C22---C23 1.375 (4) C47---C48 1.369 (4) C22---H22 0.9300 C47---H47 0.9300 C23---C24 1.371 (4) C48---C49 1.387 (3) C24---C25 1.377 (3) C49---C50 1.378 (3) C24---H24 0.9300 C49---H49 0.9300 C25---H25 0.9300 C50---H50 0.9300 C9---N1---C1 118.46 (16) C34---N2---C26 118.56 (16) N1---C1---C2 118.14 (16) N2---C26---C27 118.09 (17) N1---C1---C6 122.92 (16) N2---C26---C31 123.31 (17) C2---C1---C6 118.93 (16) C27---C26---C31 118.60 (18) C3---C2---C1 121.07 (17) C28---C27---C26 121.1 (2) C3---C2---H2 119.5 C28---C27---H27 119.4 C1---C2---H2 119.5 C26---C27---H27 119.4 C2---C3---C4 119.13 (17) C27---C28---C29 119.23 (19) C2---C3---H3 120.4 C27---C28---H28 120.4 C4---C3---H3 120.4 C29---C28---H28 120.4 C5---C4---C3 122.07 (17) C30---C29---C28 122.08 (19) C5---C4---Cl1 119.37 (15) C30---C29---Cl3 119.69 (17) C3---C4---Cl1 118.55 (14) C28---C29---Cl3 118.22 (16) C4---C5---C6 119.44 (17) C29---C30---C31 119.53 (19) C4---C5---H5 120.3 C29---C30---H30 120.2 C6---C5---H5 120.3 C31---C30---H30 120.2 C5---C6---C1 119.35 (16) C30---C31---C26 119.43 (17) C5---C6---C7 122.85 (16) C30---C31---C32 123.25 (17) C1---C6---C7 117.78 (15) C26---C31---C32 117.30 (16) C8---C7---C6 118.00 (16) C33---C32---C31 118.61 (16) C8---C7---C11 122.04 (16) C33---C32---C36 121.53 (16) C6---C7---C11 119.96 (15) C31---C32---C36 119.79 (16) C7---C8---C9 120.17 (16) C32---C33---C34 119.91 (17) C7---C8---C17 120.18 (17) C32---C33---C42 121.42 (17) C9---C8---C17 119.57 (16) C34---C33---C42 118.64 (17) N1---C9---C8 122.56 (16) N2---C34---C33 122.17 (17) N1---C9---C10 116.73 (18) N2---C34---C35 116.12 (18) C8---C9---C10 120.69 (18) C33---C34---C35 121.69 (18) C9---C10---H10A 109.5 C34---C35---H35A 109.5 C9---C10---H10B 109.5 C34---C35---H35B 109.5 H10A---C10---H10B 109.5 H35A---C35---H35B 109.5 C9---C10---H10C 109.5 C34---C35---H35C 109.5 H10A---C10---H10C 109.5 H35A---C35---H35C 109.5 H10B---C10---H10C 109.5 H35B---C35---H35C 109.5 C12---C11---C16 119.32 (19) C37---C36---C41 118.8 (2) C12---C11---C7 119.69 (17) C37---C36---C32 120.9 (2) C16---C11---C7 120.99 (18) C41---C36---C32 120.26 (19) C11---C12---C13 120.0 (2) C36---C37---C38 120.0 (3) C11---C12---H12 120.0 C36---C37---H37 120.0 C13---C12---H12 120.0 C38---C37---H37 120.0 C14---C13---C12 120.2 (2) C39---C38---C37 120.4 (3) C14---C13---H13 119.9 C39---C38---H38 119.8 C12---C13---H13 119.9 C37---C38---H38 119.8 C15---C14---C13 120.3 (2) C40---C39---C38 120.2 (3) C15---C14---H14 119.9 C40---C39---H39 119.9 C13---C14---H14 119.9 C38---C39---H39 119.9 C14---C15---C16 120.1 (2) C39---C40---C41 120.1 (3) C14---C15---H15 120.0 C39---C40---H40 119.9 C16---C15---H15 120.0 C41---C40---H40 119.9 C11---C16---C15 120.2 (2) C40---C41---C36 120.4 (3) C11---C16---H16 119.9 C40---C41---H41 119.8 C15---C16---H16 119.9 C36---C41---H41 119.8 O1---C17---C18 120.89 (18) O2---C42---C43 122.00 (19) O1---C17---C8 119.33 (18) O2---C42---C33 119.04 (19) C18---C17---C8 119.78 (17) C43---C42---C33 118.92 (17) C19---C18---C17 125.35 (19) C44---C43---C42 121.33 (19) C19---C18---H18 117.3 C44---C43---H43 119.3 C17---C18---H18 117.3 C42---C43---H43 119.3 C18---C19---C20 126.18 (19) C43---C44---C45 127.8 (2) C18---C19---H19 116.9 C43---C44---H44 116.1 C20---C19---H19 116.9 C45---C44---H44 116.1 C21---C20---C25 117.8 (2) C50---C45---C46 118.0 (2) C21---C20---C19 120.6 (2) C50---C45---C44 123.49 (18) C25---C20---C19 121.6 (2) C46---C45---C44 118.5 (2) C22---C21---C20 121.2 (2) C47---C46---C45 121.2 (2) C22---C21---H21 119.4 C47---C46---H46 119.4 C20---C21---H21 119.4 C45---C46---H46 119.4 C23---C22---C21 119.1 (2) C48---C47---C46 119.3 (2) C23---C22---H22 120.5 C48---C47---H47 120.4 C21---C22---H22 120.5 C46---C47---H47 120.4 C24---C23---C22 121.2 (2) C47---C48---C49 121.2 (2) C24---C23---Cl2 118.6 (2) C47---C48---Cl4 119.60 (18) C22---C23---Cl2 120.08 (19) C49---C48---Cl4 119.2 (2) C23---C24---C25 119.1 (2) C50---C49---C48 119.0 (2) C23---C24---H24 120.4 C50---C49---H49 120.5 C25---C24---H24 120.4 C48---C49---H49 120.5 C24---C25---C20 121.4 (2) C49---C50---C45 121.3 (2) C24---C25---H25 119.3 C49---C50---H50 119.4 C20---C25---H25 119.3 C45---C50---H50 119.4 C9---N1---C1---C2 −176.90 (17) C34---N2---C26---C27 176.12 (18) C9---N1---C1---C6 2.7 (3) C34---N2---C26---C31 −3.2 (3) N1---C1---C2---C3 −179.97 (18) N2---C26---C27---C28 −179.62 (19) C6---C1---C2---C3 0.4 (3) C31---C26---C27---C28 −0.2 (3) C1---C2---C3---C4 0.5 (3) C26---C27---C28---C29 −0.9 (3) C2---C3---C4---C5 −1.0 (3) C27---C28---C29---C30 1.3 (3) C2---C3---C4---Cl1 −179.51 (16) C27---C28---C29---Cl3 −179.09 (17) C3---C4---C5---C6 0.5 (3) C28---C29---C30---C31 −0.7 (3) Cl1---C4---C5---C6 179.04 (14) Cl3---C29---C30---C31 179.77 (15) C4---C5---C6---C1 0.4 (3) C29---C30---C31---C26 −0.5 (3) C4---C5---C6---C7 −177.66 (17) C29---C30---C31---C32 177.63 (18) N1---C1---C6---C5 179.54 (17) N2---C26---C31---C30 −179.74 (17) C2---C1---C6---C5 −0.9 (3) C27---C26---C31---C30 0.9 (3) N1---C1---C6---C7 −2.3 (3) N2---C26---C31---C32 2.0 (3) C2---C1---C6---C7 177.31 (16) C27---C26---C31---C32 −177.30 (17) C5---C6---C7---C8 177.51 (17) C30---C31---C32---C33 −176.60 (17) C1---C6---C7---C8 −0.6 (3) C26---C31---C32---C33 1.5 (3) C5---C6---C7---C11 −2.4 (3) C30---C31---C32---C36 0.4 (3) C1---C6---C7---C11 179.46 (16) C26---C31---C32---C36 178.50 (17) C6---C7---C8---C9 2.9 (3) C31---C32---C33---C34 −3.8 (3) C11---C7---C8---C9 −177.17 (17) C36---C32---C33---C34 179.30 (17) C6---C7---C8---C17 −173.98 (16) C31---C32---C33---C42 174.06 (17) C11---C7---C8---C17 6.0 (3) C36---C32---C33---C42 −2.8 (3) C1---N1---C9---C8 −0.2 (3) C26---N2---C34---C33 0.8 (3) C1---N1---C9---C10 −178.50 (17) C26---N2---C34---C35 179.19 (17) C7---C8---C9---N1 −2.6 (3) C32---C33---C34---N2 2.7 (3) C17---C8---C9---N1 174.28 (18) C42---C33---C34---N2 −175.19 (18) C7---C8---C9---C10 175.59 (19) C32---C33---C34---C35 −175.55 (18) C17---C8---C9---C10 −7.5 (3) C42---C33---C34---C35 6.5 (3) C8---C7---C11---C12 111.0 (2) C33---C32---C36---C37 69.7 (3) C6---C7---C11---C12 −69.0 (2) C31---C32---C36---C37 −107.1 (2) C8---C7---C11---C16 −69.5 (3) C33---C32---C36---C41 −110.8 (2) C6---C7---C11---C16 110.4 (2) C31---C32---C36---C41 72.3 (3) C16---C11---C12---C13 0.0 (3) C41---C36---C37---C38 0.6 (4) C7---C11---C12---C13 179.45 (19) C32---C36---C37---C38 −179.9 (3) C11---C12---C13---C14 −0.7 (4) C36---C37---C38---C39 0.9 (5) C12---C13---C14---C15 1.0 (4) C37---C38---C39---C40 −1.2 (6) C13---C14---C15---C16 −0.5 (4) C38---C39---C40---C41 0.0 (6) C12---C11---C16---C15 0.5 (3) C39---C40---C41---C36 1.5 (5) C7---C11---C16---C15 −178.98 (18) C37---C36---C41---C40 −1.8 (4) C14---C15---C16---C11 −0.2 (3) C32---C36---C41---C40 178.7 (2) C7---C8---C17---O1 91.2 (2) C32---C33---C42---O2 −119.1 (3) C9---C8---C17---O1 −85.7 (2) C34---C33---C42---O2 58.8 (3) C7---C8---C17---C18 −88.1 (2) C32---C33---C42---C43 63.1 (3) C9---C8---C17---C18 95.0 (2) C34---C33---C42---C43 −119.0 (2) O1---C17---C18---C19 −174.0 (2) O2---C42---C43---C44 −5.8 (4) C8---C17---C18---C19 5.3 (4) C33---C42---C43---C44 171.9 (2) C17---C18---C19---C20 176.6 (2) C42---C43---C44---C45 −179.3 (2) C18---C19---C20---C21 −159.6 (2) C43---C44---C45---C50 8.2 (3) C18---C19---C20---C25 19.1 (4) C43---C44---C45---C46 −170.8 (2) C25---C20---C21---C22 −3.5 (4) C50---C45---C46---C47 −1.2 (3) C19---C20---C21---C22 175.3 (2) C44---C45---C46---C47 177.8 (2) C20---C21---C22---C23 0.6 (4) C45---C46---C47---C48 0.6 (3) C21---C22---C23---C24 2.7 (4) C46---C47---C48---C49 0.5 (3) C21---C22---C23---Cl2 −175.03 (19) C46---C47---C48---Cl4 −179.29 (17) C22---C23---C24---C25 −2.9 (4) C47---C48---C49---C50 −1.0 (3) Cl2---C23---C24---C25 174.8 (2) Cl4---C48---C49---C50 178.82 (17) C23---C24---C25---C20 −0.2 (5) C48---C49---C50---C45 0.3 (3) C21---C20---C25---C24 3.3 (4) C46---C45---C50---C49 0.8 (3) C19---C20---C25---C24 −175.5 (3) C44---C45---C50---C49 −178.2 (2) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5010 .table-wrap} ------------------------------------------- Cg1 is the centroid of the C20--C25 ring. ------------------------------------------- ::: ::: {#d1e5014 .table-wrap} -------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C38---H38···Cg1^i^ 0.93 2.93 3.458 (3) 117 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+2, −y, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 is the centroid of the C20--C25 ring. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- --------- ------- ----------- ------------- C38---H38⋯Cg1^i^ 0.93 2.93 3.458 (3) 117 Symmetry code: (i) . ::: [^1]: ‡ Additional correspondence author, e-mail: kvpsvijayakumar@gmail.com.	PubMed Central	2024-06-05T04:04:18.553560	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052117/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o624", "authors": [ { "first": "S.", "last": "Sarveswari" }, { "first": "V.", "last": "Vijayakumar" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }
PMC3052118	Related literature {#sec1} ================== For background to metal salicylaldiminato complexes as optoelectronic materials, see: Liuzzo et al. (2010[@bb6]); Shirai et al., (2000[@bb10]). For background to zinc complexes as organic light-emitting diodes, see: Chen et al. (2009[@bb4]). For related structures, see: MacLachlan et al. (1996[@bb7]). For geometrical analysis, see: Addison et al. (1984[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(C~34~H~42~N~4~O~2~)(C~2~H~6~OS)\]·C~2~H~3~NM ~r~ = 723.27Monoclinic,a = 12.3288 (7) Åb = 17.7043 (9) Åc = 17.3932 (9) Åβ = 92.4391 (8)°V = 3793.0 (3) Å^3^Z = 4Mo Kα radiationμ = 0.74 mm^−1^T = 100 K0.45 × 0.30 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb8]) T ~min~ = 0.603, T ~max~ = 0.74635700 measured reflections8699 independent reflections7157 reflections with I \> 2σ(I)R ~int~ = 0.041 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.032wR(F ^2^) = 0.080S = 1.028699 reflections448 parametersH-atom parameters constrainedΔρ~max~ = 0.56 e Å^−3^Δρ~min~ = −0.29 e Å^−3^ {#d5e465} Data collection: APEX2 (Bruker, 2008[@bb3]); cell refinement: SAINT (Bruker, 2008[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb9]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb5]), DIAMOND (Brandenburg, 2006[@bb2]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb12]) and PLATON (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100359X/hb5794sup1.cif](http://dx.doi.org/10.1107/S160053681100359X/hb5794sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100359X/hb5794Isup2.hkl](http://dx.doi.org/10.1107/S160053681100359X/hb5794Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5794&file=hb5794sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5794sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5794&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5794](http://scripts.iucr.org/cgi-bin/sendsup?hb5794)). The authors acknowledge King Abdulaziz University for financial support (grant No. 17--013/430). The authors also thank the University of Malaya for support of the crystallographic facility. Comment ======= Metal complexes with salicylaldiminato ligands are promising materials for optoelectronic applications due to their outstanding photo- and electro-luminescent properties (Liuzzo et al., 2010; Shirai et al., 2000). One of the main appeals of this class of coordination complexes is that molecular engineering permits systematically the optimizing of spectroscopic and chemical properties. This chemical flexibility allows for the design of systems that respond to specific environmental variables. Recently, zinc complexes have been introduced to OLED\'s (organic light-emitting diodes) and recognized as useful electron transport materials (Chen et al., 2009). The above motivated the synthesis and structural characterization of the title complex, (I). The Zn atom in (I), Fig. 1, is tetracoordinated by the N~2~O~2~ donor atoms of the tetradentate Schiff-base ligand and the O atom derived from the dimethyl sulfoxide ligand, Table 1; the asymmetric unit is completed by a non-coordinating acetonitrile molecule. The resulting N~2~O~3~ donor set is based on a square pyramidal arrangement with the dimethyl sulfoxide-O3 atom occupying an axial site. The value of τ = 0.16 compares with τ = 0 and 1.0 for ideal square pyramidal and trigonal bipyramidal geometries, respectively (Addison et al., 1984). The r.m.s. deviation of the O1, O2, N1 and N2 atoms from their least-squares plane is 0.0836 Å and the Zn atom lies 0.3976 (7) Å out of the plane towards the O3 atom. The tetradentate mode of coordination of the Schiff-base leads to the formation of a five- and two six-membered rings. The former has a conformation based on an envelope on Zn (Spek, 2009). While the chelate ring involving the O1 atom is approximately planar (r.m.s. = 0.054 Å), there is significantly more distortion in the O2-containing chelate ring (r.m.s. = 0.203 Å). Schiff-base ligands derived from diaminomaleonitrile have been documented and shown to adopt comparable coordination modes towards transition metals (MacLachlan et al., 1996). Experimental {#experimental} ============ A mixture of diaminemaleonitrile (0.1 g, 0.93 mmol), 3,5-di-tert-butyl-2-hydroxybenzaldehyde (0.1 g, 1.86 mmol), zinc(II) acetate dihydrate (0.2 g, 0.93 mmol) and ethanol (5 ml) were placed in a glass Petri dish and capped with a glass cover. The dish was placed in a microwave oven (700 W) and irradiated for 1 min. The reaction mixture was cooled and washed with 15 ml of ethanol. The purple solid was filtered off and washed with ethanol. Re-crystallization was by slow evaporation of an acetonitrile/dimethyl sulfoxide (90/10 v/v) solution which yielded purple blocks of (I). Yield: 70%. M.pt. \> 623 K (dec.). ^1^H NMR (DMSO-d6, 500 MHz): δ = 1.25 (s, 18H, C(CH~3~)~3~), 1.47 (s, 18H, C(CH~3~)~3~), 2.06 (MeCN), 2.50 (DMSO), 7.24 (s, 2H, Ar---H), 7.43 (s, 2H, Ar---H), 8.58 (s, 2H, N═CH) p.p.m.. ^13^C NMR (DMSO-d6, 500 MHz): δ = 28.19, 29.80 (C(CH~3~)~3~), 32.61, 34.13 (C(CH~3~)~3~), 110.48, 116.85, 120.31, 128.10, 130.17, 134.20, 141.11, 161.68 and 172.33 p.p.m. IR: 2952, 2212 (C≡N), 1616 (C═N), 1569, 1519, 1433, 1372, 1170, 1154, 1119, 1032, 795, 656 cm^-1^. λ~max~ (DMSO, 10 ^-5^ mol L^-1^): 574, 501, 380, 375, 318, 245 nm. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C--H = 0.95 to 0.98 Å) and were included in the refinement in the riding model approximation, with U~iso~(H) set to 1.2--1.5U~equiv~(C). In the final refinement three low angle reflections evidently effected by the beam stop were omitted, i.e. (011), (101) and (110). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing displacement ellipsoids at the 50% probability level. ::: ![](e-67-0m314-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e217 .table-wrap} -------------------------------------------------- --------------------------------------- \[Zn(C~34~H~42~N~4~O~2~)(C~2~H~6~OS)\]·C~2~H~3~N F(000) = 1536 M~r~ = 723.27 D~x~ = 1.267 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 9906 reflections a = 12.3288 (7) Å θ = 2.3--28.3° b = 17.7043 (9) Å µ = 0.74 mm^−1^ c = 17.3932 (9) Å T = 100 K β = 92.4391 (8)° Block, purple V = 3793.0 (3) Å^3^ 0.45 × 0.30 × 0.10 mm Z = 4 -------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e361 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD diffractometer 8699 independent reflections Radiation source: fine-focus sealed tube 7157 reflections with I \> 2σ(I) graphite R~int~ = 0.041 ω scans θ~max~ = 27.5°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −16→16 T~min~ = 0.603, T~max~ = 0.746 k = −23→23 35700 measured reflections l = −22→22 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e475 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.032 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.080 H-atom parameters constrained S = 1.02 w = 1/\[σ^2^(F~o~^2^) + (0.036P)^2^ + 1.6768P\] where P = (F~o~^2^ + 2F~c~^2^)/3 8699 reflections (Δ/σ)~max~ = 0.002 448 parameters Δρ~max~ = 0.56 e Å^−3^ 0 restraints Δρ~min~ = −0.29 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e632 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e731 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Zn 0.516854 (14) 0.654898 (11) 0.558637 (10) 0.01242 (6) S1 0.41362 (3) 0.82176 (2) 0.50384 (2) 0.01635 (9) O1 0.63893 (9) 0.70123 (7) 0.61554 (7) 0.0184 (3) O2 0.44436 (9) 0.61428 (7) 0.64636 (6) 0.0167 (2) O3 0.41323 (9) 0.73722 (7) 0.51757 (7) 0.0198 (3) N1 0.61797 (11) 0.64054 (7) 0.46602 (8) 0.0129 (3) N2 0.42744 (10) 0.57668 (7) 0.49091 (7) 0.0121 (3) N3 0.64563 (12) 0.60956 (9) 0.27021 (9) 0.0224 (3) N4 0.34261 (12) 0.51244 (9) 0.30973 (9) 0.0221 (3) N5 0.63439 (16) 1.00678 (11) 0.54854 (14) 0.0500 (6) C1 0.73798 (13) 0.71491 (9) 0.59846 (9) 0.0133 (3) C2 0.81352 (12) 0.74304 (9) 0.65753 (9) 0.0127 (3) C3 0.91590 (13) 0.76392 (9) 0.63645 (9) 0.0136 (3) H3 0.9635 0.7851 0.6751 0.016\ C4 0.95562 (12) 0.75609 (9) 0.56135 (9) 0.0128 (3) C5 0.88612 (12) 0.72505 (9) 0.50676 (9) 0.0129 (3) H5 0.9107 0.7177 0.4563 0.015\* C6 0.77787 (12) 0.70320 (9) 0.52280 (9) 0.0130 (3) C7 0.78027 (12) 0.74618 (9) 0.74153 (9) 0.0138 (3) C8 0.87537 (14) 0.77112 (11) 0.79528 (10) 0.0212 (4) H8A 0.9355 0.7353 0.7914 0.032\* H8B 0.8520 0.7724 0.8484 0.032\* H8C 0.8994 0.8216 0.7804 0.032\* C9 0.68745 (14) 0.80283 (10) 0.75108 (10) 0.0206 (4) H9A 0.6683 0.8044 0.8052 0.031\* H9B 0.6240 0.7871 0.7191 0.031\* H9C 0.7108 0.8531 0.7350 0.031\* C10 0.74430 (15) 0.66745 (10) 0.76792 (10) 0.0211 (4) H10A 0.8033 0.6312 0.7613 0.032\* H10B 0.6801 0.6515 0.7370 0.032\* H10C 0.7266 0.6695 0.8223 0.032\* C11 1.07286 (13) 0.77942 (9) 0.54726 (9) 0.0148 (3) C12 1.08302 (14) 0.86593 (10) 0.55278 (11) 0.0221 (4) H12A 1.0340 0.8894 0.5140 0.033\* H12B 1.1580 0.8809 0.5437 0.033\* H12C 1.0636 0.8826 0.6042 0.033\* C13 1.10819 (14) 0.75406 (11) 0.46817 (10) 0.0226 (4) H13A 1.0609 0.7773 0.4281 0.034\* H13B 1.1029 0.6989 0.4643 0.034\* H13C 1.1834 0.7697 0.4614 0.034\* C14 1.15020 (13) 0.74290 (10) 0.60857 (10) 0.0186 (4) H14A 1.1375 0.6883 0.6098 0.028\* H14B 1.1367 0.7645 0.6591 0.028\* H14C 1.2256 0.7527 0.5958 0.028\* C15 0.71711 (12) 0.66741 (9) 0.46187 (9) 0.0131 (3) H15 0.7509 0.6624 0.4141 0.016\* C16 0.56431 (13) 0.60475 (9) 0.40459 (9) 0.0122 (3) C17 0.60834 (13) 0.60514 (9) 0.32927 (9) 0.0140 (3) C18 0.46527 (12) 0.57224 (9) 0.41737 (9) 0.0119 (3) C19 0.40078 (13) 0.53784 (9) 0.35600 (9) 0.0141 (3) C20 0.33269 (12) 0.55019 (9) 0.50908 (9) 0.0130 (3) H20 0.2899 0.5258 0.4697 0.016\* C21 0.28904 (12) 0.55523 (9) 0.58319 (9) 0.0122 (3) C22 0.18261 (13) 0.52592 (9) 0.59065 (9) 0.0144 (3) H22 0.1463 0.5038 0.5469 0.017\* C23 0.13077 (13) 0.52844 (9) 0.65864 (9) 0.0139 (3) C24 0.18870 (13) 0.56085 (9) 0.72222 (10) 0.0153 (3) H24 0.1538 0.5625 0.7699 0.018\* C25 0.29211 (13) 0.59022 (9) 0.72021 (9) 0.0143 (3) C26 0.34663 (13) 0.58787 (9) 0.64890 (9) 0.0137 (3) C27 0.01364 (13) 0.50025 (10) 0.66406 (10) 0.0170 (3) C28 0.00085 (18) 0.42155 (12) 0.63012 (14) 0.0377 (5) H28A 0.0470 0.3861 0.6599 0.056\* H28B 0.0225 0.4220 0.5766 0.056\* H28C −0.0752 0.4057 0.6320 0.056\* C29 −0.02449 (15) 0.49953 (13) 0.74654 (11) 0.0312 (5) H29A 0.0230 0.4666 0.7783 0.047\* H29B −0.0992 0.4806 0.7468 0.047\* H29C −0.0217 0.5509 0.7675 0.047\* C30 −0.06285 (15) 0.55409 (12) 0.61742 (12) 0.0287 (4) H30A −0.1381 0.5372 0.6214 0.043\* H30B −0.0437 0.5538 0.5633 0.043\* H30C −0.0552 0.6054 0.6380 0.043\* C31 0.34962 (14) 0.62514 (10) 0.79195 (10) 0.0175 (3) C32 0.27723 (16) 0.62444 (13) 0.86125 (11) 0.0293 (4) H32A 0.2104 0.6527 0.8487 0.044\* H32B 0.3159 0.6480 0.9054 0.044\* H32C 0.2590 0.5722 0.8740 0.044\* C33 0.45222 (14) 0.57956 (10) 0.81404 (10) 0.0213 (4) H33A 0.4881 0.6017 0.8601 0.032\* H33B 0.5018 0.5808 0.7715 0.032\* H33C 0.4322 0.5271 0.8246 0.032\* C34 0.37892 (15) 0.70810 (10) 0.77625 (11) 0.0227 (4) H34A 0.3126 0.7366 0.7629 0.034\* H34B 0.4280 0.7105 0.7335 0.034\* H34C 0.4147 0.7300 0.8224 0.034\* C35 0.44163 (17) 0.86449 (11) 0.59519 (11) 0.0272 (4) H35A 0.3795 0.8573 0.6277 0.041\* H35B 0.4546 0.9186 0.5883 0.041\* H35C 0.5062 0.8411 0.6198 0.041\* C36 0.53942 (15) 0.84257 (11) 0.46161 (12) 0.0260 (4) H36A 0.5411 0.8186 0.4109 0.039\* H36B 0.5994 0.8232 0.4947 0.039\* H36C 0.5469 0.8974 0.4560 0.039\* C37 0.71611 (16) 0.99001 (11) 0.57521 (12) 0.0284 (4) C38 0.82087 (17) 0.96856 (14) 0.60957 (14) 0.0398 (5) H38A 0.8254 0.9844 0.6636 0.060\* H38B 0.8786 0.9932 0.5818 0.060\* H38C 0.8294 0.9136 0.6066 0.060\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1980 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Zn 0.01068 (9) 0.01551 (10) 0.01115 (10) −0.00142 (7) 0.00141 (7) −0.00244 (7) S1 0.01486 (19) 0.0156 (2) 0.0185 (2) −0.00009 (15) −0.00009 (15) −0.00080 (16) O1 0.0123 (6) 0.0290 (7) 0.0141 (6) −0.0051 (5) 0.0029 (4) −0.0070 (5) O2 0.0122 (5) 0.0260 (7) 0.0120 (6) −0.0043 (5) 0.0008 (4) 0.0004 (5) O3 0.0160 (6) 0.0143 (6) 0.0291 (7) 0.0003 (5) −0.0007 (5) −0.0002 (5) N1 0.0125 (6) 0.0148 (7) 0.0112 (7) 0.0002 (5) −0.0010 (5) −0.0006 (5) N2 0.0133 (6) 0.0126 (7) 0.0105 (7) 0.0012 (5) 0.0014 (5) 0.0003 (5) N3 0.0248 (8) 0.0260 (8) 0.0167 (8) −0.0025 (6) 0.0036 (6) −0.0005 (6) N4 0.0203 (8) 0.0251 (8) 0.0207 (8) −0.0033 (6) −0.0005 (6) −0.0046 (6) N5 0.0405 (11) 0.0296 (11) 0.0778 (16) −0.0031 (9) −0.0226 (11) 0.0054 (10) C1 0.0124 (7) 0.0145 (8) 0.0130 (8) 0.0003 (6) 0.0007 (6) −0.0011 (6) C2 0.0135 (7) 0.0121 (8) 0.0125 (8) 0.0012 (6) 0.0002 (6) −0.0018 (6) C3 0.0139 (7) 0.0134 (8) 0.0132 (8) −0.0004 (6) −0.0015 (6) −0.0020 (6) C4 0.0120 (7) 0.0132 (8) 0.0131 (8) 0.0007 (6) 0.0014 (6) 0.0019 (6) C5 0.0129 (7) 0.0150 (8) 0.0109 (8) 0.0023 (6) 0.0018 (6) 0.0013 (6) C6 0.0126 (7) 0.0141 (8) 0.0122 (8) 0.0004 (6) 0.0002 (6) 0.0006 (6) C7 0.0135 (8) 0.0169 (8) 0.0113 (8) 0.0004 (6) 0.0013 (6) −0.0024 (6) C8 0.0187 (9) 0.0323 (10) 0.0125 (8) −0.0032 (7) −0.0005 (7) −0.0052 (7) C9 0.0215 (9) 0.0236 (10) 0.0169 (9) 0.0038 (7) 0.0037 (7) −0.0046 (7) C10 0.0271 (9) 0.0213 (9) 0.0154 (9) −0.0026 (7) 0.0060 (7) 0.0006 (7) C11 0.0118 (7) 0.0191 (8) 0.0135 (8) −0.0022 (6) 0.0020 (6) 0.0004 (7) C12 0.0181 (8) 0.0208 (9) 0.0274 (10) −0.0044 (7) 0.0011 (7) 0.0040 (8) C13 0.0136 (8) 0.0375 (11) 0.0171 (9) −0.0064 (7) 0.0040 (7) −0.0040 (8) C14 0.0124 (8) 0.0231 (9) 0.0203 (9) 0.0004 (7) 0.0017 (7) 0.0024 (7) C15 0.0135 (7) 0.0147 (8) 0.0112 (8) 0.0020 (6) 0.0017 (6) 0.0010 (6) C16 0.0144 (7) 0.0121 (8) 0.0100 (8) 0.0020 (6) 0.0001 (6) −0.0003 (6) C17 0.0127 (7) 0.0145 (8) 0.0146 (8) −0.0008 (6) −0.0014 (6) −0.0007 (6) C18 0.0138 (7) 0.0110 (8) 0.0108 (7) 0.0013 (6) 0.0000 (6) 0.0005 (6) C19 0.0139 (7) 0.0149 (8) 0.0138 (8) 0.0007 (6) 0.0033 (6) 0.0002 (6) C20 0.0144 (7) 0.0108 (8) 0.0138 (8) 0.0004 (6) −0.0010 (6) −0.0010 (6) C21 0.0125 (7) 0.0118 (8) 0.0125 (8) 0.0010 (6) 0.0009 (6) 0.0011 (6) C22 0.0150 (8) 0.0135 (8) 0.0145 (8) −0.0008 (6) −0.0003 (6) 0.0001 (6) C23 0.0131 (7) 0.0126 (8) 0.0162 (8) 0.0002 (6) 0.0018 (6) 0.0029 (6) C24 0.0167 (8) 0.0166 (8) 0.0129 (8) 0.0007 (6) 0.0038 (6) −0.0003 (6) C25 0.0160 (8) 0.0149 (8) 0.0118 (8) 0.0017 (6) 0.0005 (6) 0.0001 (6) C26 0.0136 (7) 0.0134 (8) 0.0140 (8) 0.0013 (6) −0.0006 (6) 0.0022 (6) C27 0.0166 (8) 0.0175 (9) 0.0172 (8) −0.0054 (6) 0.0055 (6) −0.0020 (7) C28 0.0358 (12) 0.0261 (11) 0.0527 (14) −0.0109 (9) 0.0218 (10) −0.0110 (10) C29 0.0212 (9) 0.0500 (13) 0.0228 (10) −0.0085 (9) 0.0055 (8) 0.0026 (9) C30 0.0181 (9) 0.0363 (12) 0.0316 (11) −0.0033 (8) −0.0012 (8) 0.0057 (9) C31 0.0181 (8) 0.0221 (9) 0.0125 (8) −0.0027 (7) 0.0018 (6) −0.0027 (7) C32 0.0260 (10) 0.0454 (12) 0.0168 (9) −0.0096 (9) 0.0045 (8) −0.0105 (9) C33 0.0236 (9) 0.0263 (10) 0.0136 (8) −0.0007 (7) −0.0037 (7) 0.0002 (7) C34 0.0257 (9) 0.0225 (9) 0.0196 (9) −0.0002 (7) −0.0022 (7) −0.0049 (7) C35 0.0344 (11) 0.0256 (10) 0.0215 (10) −0.0044 (8) 0.0019 (8) −0.0061 (8) C36 0.0213 (9) 0.0274 (10) 0.0300 (10) −0.0052 (8) 0.0092 (8) −0.0012 (8) C37 0.0312 (11) 0.0192 (10) 0.0345 (11) −0.0027 (8) −0.0034 (9) 0.0023 (8) C38 0.0298 (11) 0.0479 (14) 0.0412 (13) 0.0011 (10) −0.0056 (10) 0.0119 (11) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2883 .table-wrap} --------------------- -------------- ----------------------- -------------- Zn---O1 1.9470 (11) C14---H14C 0.9800 Zn---O2 1.9390 (11) C15---H15 0.9500 Zn---O3 2.0467 (12) C16---C18 1.377 (2) Zn---N1 2.0939 (14) C16---C17 1.439 (2) Zn---N2 2.1001 (13) C18---C19 1.439 (2) S1---O3 1.5155 (12) C20---C21 1.421 (2) S1---C35 1.7803 (19) C20---H20 0.9500 S1---C36 1.7826 (18) C21---C22 1.422 (2) O1---C1 1.2919 (19) C21---C26 1.440 (2) O2---C26 1.2950 (19) C22---C23 1.369 (2) N1---C15 1.317 (2) C22---H22 0.9500 N1---C16 1.386 (2) C23---C24 1.412 (2) N2---C20 1.310 (2) C23---C27 1.535 (2) N2---C18 1.382 (2) C24---C25 1.379 (2) N3---C17 1.146 (2) C24---H24 0.9500 N4---C19 1.147 (2) C25---C26 1.436 (2) N5---C37 1.131 (3) C25---C31 1.538 (2) C1---C6 1.439 (2) C27---C28 1.519 (3) C1---C2 1.446 (2) C27---C29 1.529 (2) C2---C3 1.380 (2) C27---C30 1.546 (3) C2---C7 1.535 (2) C28---H28A 0.9800 C3---C4 1.421 (2) C28---H28B 0.9800 C3---H3 0.9500 C28---H28C 0.9800 C4---C5 1.367 (2) C29---H29A 0.9800 C4---C11 1.533 (2) C29---H29B 0.9800 C5---C6 1.428 (2) C29---H29C 0.9800 C5---H5 0.9500 C30---H30A 0.9800 C6---C15 1.421 (2) C30---H30B 0.9800 C7---C8 1.533 (2) C30---H30C 0.9800 C7---C9 1.536 (2) C31---C32 1.530 (2) C7---C10 1.539 (2) C31---C33 1.535 (2) C8---H8A 0.9800 C31---C34 1.540 (3) C8---H8B 0.9800 C32---H32A 0.9800 C8---H8C 0.9800 C32---H32B 0.9800 C9---H9A 0.9800 C32---H32C 0.9800 C9---H9B 0.9800 C33---H33A 0.9800 C9---H9C 0.9800 C33---H33B 0.9800 C10---H10A 0.9800 C33---H33C 0.9800 C10---H10B 0.9800 C34---H34A 0.9800 C10---H10C 0.9800 C34---H34B 0.9800 C11---C13 1.528 (2) C34---H34C 0.9800 C11---C12 1.540 (2) C35---H35A 0.9800 C11---C14 1.542 (2) C35---H35B 0.9800 C12---H12A 0.9800 C35---H35C 0.9800 C12---H12B 0.9800 C36---H36A 0.9800 C12---H12C 0.9800 C36---H36B 0.9800 C13---H13A 0.9800 C36---H36C 0.9800 C13---H13B 0.9800 C37---C38 1.450 (3) C13---H13C 0.9800 C38---H38A 0.9800 C14---H14A 0.9800 C38---H38B 0.9800 C14---H14B 0.9800 C38---H38C 0.9800 O2---Zn---O1 97.38 (5) N3---C17---C16 176.04 (18) O2---Zn---O3 103.71 (5) C16---C18---N2 117.53 (14) O1---Zn---O3 109.57 (5) C16---C18---C19 121.55 (14) O2---Zn---N1 150.43 (5) N2---C18---C19 120.86 (14) O1---Zn---N1 88.26 (5) N4---C19---C18 174.84 (17) O3---Zn---N1 101.60 (5) N2---C20---C21 124.94 (14) O2---Zn---N2 87.04 (5) N2---C20---H20 117.5 O1---Zn---N2 159.88 (5) C21---C20---H20 117.5 O3---Zn---N2 88.21 (5) C20---C21---C22 116.52 (14) N1---Zn---N2 78.69 (5) C20---C21---C26 123.51 (14) O3---S1---C35 106.31 (8) C22---C21---C26 119.97 (14) O3---S1---C36 106.12 (8) C23---C22---C21 122.24 (15) C35---S1---C36 98.09 (9) C23---C22---H22 118.9 C1---O1---Zn 132.84 (10) C21---C22---H22 118.9 C26---O2---Zn 128.42 (10) C22---C23---C24 116.77 (15) S1---O3---Zn 138.77 (7) C22---C23---C27 121.18 (15) C15---N1---C16 122.47 (14) C24---C23---C27 122.00 (14) C15---N1---Zn 125.65 (11) C25---C24---C23 124.81 (15) C16---N1---Zn 111.62 (10) C25---C24---H24 117.6 C20---N2---C18 122.86 (14) C23---C24---H24 117.6 C20---N2---Zn 123.57 (11) C24---C25---C26 118.56 (15) C18---N2---Zn 111.52 (10) C24---C25---C31 121.73 (14) O1---C1---C6 123.11 (14) C26---C25---C31 119.71 (14) O1---C1---C2 119.20 (14) O2---C26---C25 119.29 (14) C6---C1---C2 117.68 (14) O2---C26---C21 123.08 (14) C3---C2---C1 118.19 (14) C25---C26---C21 117.63 (14) C3---C2---C7 121.84 (14) C28---C27---C29 109.03 (16) C1---C2---C7 119.93 (14) C28---C27---C23 110.91 (15) C2---C3---C4 124.96 (15) C29---C27---C23 112.83 (14) C2---C3---H3 117.5 C28---C27---C30 108.11 (16) C4---C3---H3 117.5 C29---C27---C30 107.01 (15) C5---C4---C3 116.58 (14) C23---C27---C30 108.77 (14) C5---C4---C11 124.38 (14) C27---C28---H28A 109.5 C3---C4---C11 119.00 (14) C27---C28---H28B 109.5 C4---C5---C6 122.44 (15) H28A---C28---H28B 109.5 C4---C5---H5 118.8 C27---C28---H28C 109.5 C6---C5---H5 118.8 H28A---C28---H28C 109.5 C15---C6---C5 116.26 (14) H28B---C28---H28C 109.5 C15---C6---C1 123.81 (14) C27---C29---H29A 109.5 C5---C6---C1 119.87 (14) C27---C29---H29B 109.5 C8---C7---C2 111.26 (13) H29A---C29---H29B 109.5 C8---C7---C9 107.46 (14) C27---C29---H29C 109.5 C2---C7---C9 110.91 (13) H29A---C29---H29C 109.5 C8---C7---C10 107.55 (14) H29B---C29---H29C 109.5 C2---C7---C10 110.07 (13) C27---C30---H30A 109.5 C9---C7---C10 109.50 (14) C27---C30---H30B 109.5 C7---C8---H8A 109.5 H30A---C30---H30B 109.5 C7---C8---H8B 109.5 C27---C30---H30C 109.5 H8A---C8---H8B 109.5 H30A---C30---H30C 109.5 C7---C8---H8C 109.5 H30B---C30---H30C 109.5 H8A---C8---H8C 109.5 C32---C31---C33 107.50 (15) H8B---C8---H8C 109.5 C32---C31---C25 111.81 (14) C7---C9---H9A 109.5 C33---C31---C25 109.75 (14) C7---C9---H9B 109.5 C32---C31---C34 107.25 (15) H9A---C9---H9B 109.5 C33---C31---C34 110.41 (14) C7---C9---H9C 109.5 C25---C31---C34 110.06 (14) H9A---C9---H9C 109.5 C31---C32---H32A 109.5 H9B---C9---H9C 109.5 C31---C32---H32B 109.5 C7---C10---H10A 109.5 H32A---C32---H32B 109.5 C7---C10---H10B 109.5 C31---C32---H32C 109.5 H10A---C10---H10B 109.5 H32A---C32---H32C 109.5 C7---C10---H10C 109.5 H32B---C32---H32C 109.5 H10A---C10---H10C 109.5 C31---C33---H33A 109.5 H10B---C10---H10C 109.5 C31---C33---H33B 109.5 C13---C11---C4 111.82 (13) H33A---C33---H33B 109.5 C13---C11---C12 108.83 (14) C31---C33---H33C 109.5 C4---C11---C12 109.44 (13) H33A---C33---H33C 109.5 C13---C11---C14 107.92 (14) H33B---C33---H33C 109.5 C4---C11---C14 109.64 (13) C31---C34---H34A 109.5 C12---C11---C14 109.13 (14) C31---C34---H34B 109.5 C11---C12---H12A 109.5 H34A---C34---H34B 109.5 C11---C12---H12B 109.5 C31---C34---H34C 109.5 H12A---C12---H12B 109.5 H34A---C34---H34C 109.5 C11---C12---H12C 109.5 H34B---C34---H34C 109.5 H12A---C12---H12C 109.5 S1---C35---H35A 109.5 H12B---C12---H12C 109.5 S1---C35---H35B 109.5 C11---C13---H13A 109.5 H35A---C35---H35B 109.5 C11---C13---H13B 109.5 S1---C35---H35C 109.5 H13A---C13---H13B 109.5 H35A---C35---H35C 109.5 C11---C13---H13C 109.5 H35B---C35---H35C 109.5 H13A---C13---H13C 109.5 S1---C36---H36A 109.5 H13B---C13---H13C 109.5 S1---C36---H36B 109.5 C11---C14---H14A 109.5 H36A---C36---H36B 109.5 C11---C14---H14B 109.5 S1---C36---H36C 109.5 H14A---C14---H14B 109.5 H36A---C36---H36C 109.5 C11---C14---H14C 109.5 H36B---C36---H36C 109.5 H14A---C14---H14C 109.5 N5---C37---C38 179.9 (3) H14B---C14---H14C 109.5 C37---C38---H38A 109.5 N1---C15---C6 125.57 (15) C37---C38---H38B 109.5 N1---C15---H15 117.2 H38A---C38---H38B 109.5 C6---C15---H15 117.2 C37---C38---H38C 109.5 C18---C16---N1 117.67 (14) H38A---C38---H38C 109.5 C18---C16---C17 121.36 (14) H38B---C38---H38C 109.5 N1---C16---C17 120.90 (14) O2---Zn---O1---C1 150.82 (15) C3---C4---C11---C12 −69.76 (19) O3---Zn---O1---C1 −101.74 (15) C5---C4---C11---C14 −127.48 (17) N1---Zn---O1---C1 −0.04 (15) C3---C4---C11---C14 49.91 (19) N2---Zn---O1---C1 49.2 (2) C16---N1---C15---C6 −178.57 (15) O1---Zn---O2---C26 166.41 (14) Zn---N1---C15---C6 7.9 (2) O3---Zn---O2---C26 54.13 (14) C5---C6---C15---N1 177.20 (15) N1---Zn---O2---C26 −94.02 (16) C1---C6---C15---N1 0.0 (3) N2---Zn---O2---C26 −33.31 (14) C15---N1---C16---C18 173.74 (15) C35---S1---O3---Zn −60.18 (14) Zn---N1---C16---C18 −11.89 (17) C36---S1---O3---Zn 43.54 (14) C15---N1---C16---C17 −9.4 (2) O2---Zn---O3---S1 119.64 (12) Zn---N1---C16---C17 164.96 (12) O1---Zn---O3---S1 16.51 (13) C18---C16---C17---N3 142 (2) N1---Zn---O3---S1 −75.78 (12) N1---C16---C17---N3 −34 (3) N2---Zn---O3---S1 −153.85 (12) N1---C16---C18---N2 −1.0 (2) O2---Zn---N1---C15 −108.97 (15) C17---C16---C18---N2 −177.83 (14) O1---Zn---N1---C15 −7.03 (13) N1---C16---C18---C19 176.23 (14) O3---Zn---N1---C15 102.59 (13) C17---C16---C18---C19 −0.6 (2) N2---Zn---N1---C15 −171.63 (14) C20---N2---C18---C16 177.49 (14) O2---Zn---N1---C16 76.88 (14) Zn---N2---C18---C16 13.30 (17) O1---Zn---N1---C16 178.82 (11) C20---N2---C18---C19 0.2 (2) O3---Zn---N1---C16 −71.56 (11) Zn---N2---C18---C19 −163.95 (12) N2---Zn---N1---C16 14.22 (10) C16---C18---C19---N4 −144 (2) O2---Zn---N2---C20 27.25 (13) N2---C18---C19---N4 33 (2) O1---Zn---N2---C20 130.72 (15) C18---N2---C20---C21 −178.19 (15) O3---Zn---N2---C20 −76.57 (13) Zn---N2---C20---C21 −15.9 (2) N1---Zn---N2---C20 −178.78 (13) N2---C20---C21---C22 177.32 (15) O2---Zn---N2---C18 −168.69 (11) N2---C20---C21---C26 −2.7 (3) O1---Zn---N2---C18 −65.23 (19) C20---C21---C22---C23 −178.94 (15) O3---Zn---N2---C18 87.48 (11) C26---C21---C22---C23 1.0 (2) N1---Zn---N2---C18 −14.73 (10) C21---C22---C23---C24 −0.9 (2) Zn---O1---C1---C6 6.6 (2) C21---C22---C23---C27 176.69 (15) Zn---O1---C1---C2 −173.09 (11) C22---C23---C24---C25 0.5 (2) O1---C1---C2---C3 −174.06 (15) C27---C23---C24---C25 −176.99 (16) C6---C1---C2---C3 6.2 (2) C23---C24---C25---C26 −0.4 (3) O1---C1---C2---C7 8.2 (2) C23---C24---C25---C31 179.57 (15) C6---C1---C2---C7 −171.50 (14) Zn---O2---C26---C25 −153.79 (12) C1---C2---C3---C4 −3.7 (2) Zn---O2---C26---C21 26.7 (2) C7---C2---C3---C4 173.99 (15) C24---C25---C26---O2 −179.06 (15) C2---C3---C4---C5 −0.4 (2) C31---C25---C26---O2 1.0 (2) C2---C3---C4---C11 −177.95 (15) C24---C25---C26---C21 0.5 (2) C3---C4---C5---C6 1.7 (2) C31---C25---C26---C21 −179.45 (14) C11---C4---C5---C6 179.12 (15) C20---C21---C26---O2 −1.3 (2) C4---C5---C6---C15 −176.22 (15) C22---C21---C26---O2 178.71 (15) C4---C5---C6---C1 1.1 (2) C20---C21---C26---C25 179.17 (15) O1---C1---C6---C15 −7.7 (3) C22---C21---C26---C25 −0.8 (2) C2---C1---C6---C15 172.05 (15) C22---C23---C27---C28 50.7 (2) O1---C1---C6---C5 175.20 (15) C24---C23---C27---C28 −131.85 (18) C2---C1---C6---C5 −5.1 (2) C22---C23---C27---C29 173.39 (16) C3---C2---C7---C8 −2.6 (2) C24---C23---C27---C29 −9.2 (2) C1---C2---C7---C8 175.02 (15) C22---C23---C27---C30 −68.0 (2) C3---C2---C7---C9 116.96 (17) C24---C23---C27---C30 109.38 (18) C1---C2---C7---C9 −65.43 (19) C24---C25---C31---C32 −1.6 (2) C3---C2---C7---C10 −121.71 (17) C26---C25---C31---C32 178.31 (16) C1---C2---C7---C10 55.90 (19) C24---C25---C31---C33 117.58 (17) C5---C4---C11---C13 −7.8 (2) C26---C25---C31---C33 −62.5 (2) C3---C4---C11---C13 169.57 (15) C24---C25---C31---C34 −120.71 (17) C5---C4---C11---C12 112.85 (18) C26---C25---C31---C34 59.2 (2) --------------------- -------------- ----------------------- -------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: --------- ------------- Zn---O1 1.9470 (11) Zn---O2 1.9390 (11) Zn---O3 2.0467 (12) Zn---N1 2.0939 (14) Zn---N2 2.1001 (13) --------- ------------- ::: [^1]: ‡ Additional correspondence author, e-mail: wayfield8@yahoo.com.	PubMed Central	2024-06-05T04:04:18.565285	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052118/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m314-m315", "authors": [ { "first": "E. S.", "last": "Aazam" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }
PMC3052119	In the paper by Castillo, Luque, De la Pinta & Román (2001[@bb1]), the ligand reported as nitrate should be carbonate and the oxidation state of the cobalt metal atom should be Co^III^ rather than Co^II^, thus making the correct chemical composition \[Co(CO~3~)(C~10~H~9~N~3~)~2~\]NO~3~ and the correct chemical name '\[Bis(2-pyridyl)amine-κ^2^ N,N′\](carbonato-κ^2^ O,O′)cobalt(III) nitrate'. Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co(CO~3~)(C~10~H~9~N~3~)~2~\]NO~3~M ~r~ = 523.35Monoclinic,a = 17.191 (3) Åb = 7.3080 (10) Åc = 17.843 (5) Åβ = 104.94 (3)°V = 2165.9 (8) Å^3^Z = 4Mo Kα radiationμ = 0.85 mm^−1^T = 293 K0.42 × 0.20 × 0.08 mm ### Data collection {#sec2.1.2} Stoe IPDS diffractometerAbsorption correction: numerical (Stoe & Cie, 1998[@bb4]) T ~min~ = 0.815, T ~max~ = 0.93414084 measured reflections4037 independent reflections2598 reflections with I \> 2σ(I)R ~int~ = 0.048 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.031wR(F ^2^) = 0.076S = 0.824037 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.31 e Å^−3^ {#d5e405} Data collection, cell refinement and data reduction: IPDS Software (Stoe & Cie, 1998[@bb4]); program(s) used to solve structure: SIR92 (Altomare et al., 1993[@bb2]); program(s) used to refine structure: SHELXL93 (Sheldrick, 1993[@bb3]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536810050798/bt9068sup1.cif](http://dx.doi.org/10.1107/S1600536810050798/bt9068sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536810050798/bt9068Isup2.hkl](http://dx.doi.org/10.1107/S1600536810050798/bt9068Isup2.hkl) . DOI: [10.1107/S1600536810050798/bt9068fig1.tif](http://dx.doi.org/10.1107/S1600536810050798/bt9068fig1.tif) ? Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt9068&file=bt9068sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt9068sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt9068&checkcif=yes)	PubMed Central	2024-06-05T04:04:18.577654	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052119/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):e15", "authors": [ { "first": "Oscar", "last": "Castillo" }, { "first": "Antonio", "last": "Luque" }, { "first": "Noelia", "last": "De la Pinta" }, { "first": "Pascual", "last": "Román" } ] }
PMC3052120	Related literature {#sec1} ================== For our previous reports of the pharmacological properties of benzofurans, see: Abdel-Aziz & Mekawey (2009[@bb1]); Abdel-Aziz et al. (2009[@bb2]). For a related structure, see: Kossakowski et al. (2005[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~11~H~9~BrO~3~M ~r~ = 269.09Monoclinic,a = 3.8869 (3) Åb = 23.780 (2) Åc = 11.0820 (7) Åβ = 96.905 (8)°V = 1016.89 (13) Å^3^Z = 4Mo Kα radiationμ = 4.02 mm^−1^T = 100 K0.30 × 0.20 × 0.10 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb3]) T ~min~ = 0.378, T ~max~ = 0.6896060 measured reflections2250 independent reflections1843 reflections with I \> 2σ(I)R ~int~ = 0.045 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.055wR(F ^2^) = 0.109S = 1.182250 reflections136 parametersH-atom parameters constrainedΔρ~max~ = 0.97 e Å^−3^Δρ~min~ = −0.71 e Å^−3^ {#d5e418} Data collection: CrysAlis PRO (Agilent, 2010[@bb3]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: X-SEED (Barbour, 2001[@bb4]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb7]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005897/xu5164sup1.cif](http://dx.doi.org/10.1107/S1600536811005897/xu5164sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005897/xu5164Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005897/xu5164Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5164&file=xu5164sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5164sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5164&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5164](http://scripts.iucr.org/cgi-bin/sendsup?xu5164)). We thank King Saud University and the University of Malaya for supporting this study. Comment ======= Ethyl 5-bromobenzofuran-2-carboxylate (Scheme I) is a commercially available chemical that has been evaluated for its pharmacological properties. We have reported the pharmacological properties of related compounds (Abdel-Aziz & Mekawey, 2009; Abdel-Aziz et al., 2009). The title compound is an approximately planar molecule; the carboxyl --CO~2~ fragment is aligned at 4.8 (7)° with respect to the benzofuran fused-ring (Fig. 1). Bond dimensions are similar to those found in methyl 7-methoxybenzofuran-2-carboxylate (Kossakowski et al., 2005). Experimental {#experimental} ============ 5-Bromosalicyladehyde (2.01 g, 10 mm l), diethyl bromomalonate (2.63 g 11 mmol) and potassium carbonate (2.28 g, 20 mmol) were heated in 2-butanone (20 ml) for 14 h. The solvent was evaporated and water was added to the residue. The organic compound was extracted by ether. The ether phase was washed with 5% sodium hydroxide. The ether was then evaporated and the product recrystallized from ethanol to give the title ester, m.p. 333--335 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.98 Å, U~iso~(H) 1.2 to 1.5U~eq~(C)\] and were included in the refinement in the riding model approximation. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C11H9BrO3 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o696-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e116 .table-wrap} ------------------------- --------------------------------------- C~11~H~9~BrO~3~ F(000) = 536 M~r~ = 269.09 D~x~ = 1.758 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2599 reflections a = 3.8869 (3) Å θ = 2.5--29.3° b = 23.780 (2) Å µ = 4.02 mm^−1^ c = 11.0820 (7) Å T = 100 K β = 96.905 (8)° Prism, colorless V = 1016.89 (13) Å^3^ 0.30 × 0.20 × 0.10 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e243 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 2250 independent reflections Radiation source: SuperNova (Mo) X-ray Source 1843 reflections with I \> 2σ(I) Mirror R~int~ = 0.045 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.5° ω scans h = −3→5 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −30→30 T~min~ = 0.378, T~max~ = 0.689 l = −13→14 6060 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e363 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.109 H-atom parameters constrained S = 1.18 w = 1/\[σ^2^(F~o~^2^) + (0.0086P)^2^ + 5.1797P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2250 reflections (Δ/σ)~max~ = 0.001 136 parameters Δρ~max~ = 0.97 e Å^−3^ 0 restraints Δρ~min~ = −0.71 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e522 .table-wrap} ------ -------------- -------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.84947 (14) 0.52531 (2) 0.18162 (5) 0.02119 (16) O1 0.2581 (9) 0.32380 (14) 0.4040 (3) 0.0157 (7) O2 0.0007 (10) 0.25870 (14) 0.5783 (3) 0.0228 (9) O3 0.1752 (9) 0.32488 (14) 0.7194 (3) 0.0165 (8) C1 0.3994 (13) 0.3662 (2) 0.3427 (4) 0.0146 (10) C2 0.4194 (14) 0.3670 (2) 0.2183 (4) 0.0189 (11) H2 0.3416 0.3363 0.1672 0.023\ C3 0.5588 (15) 0.4150 (2) 0.1733 (4) 0.0216 (12) H3 0.5746 0.4181 0.0886 0.026\* C4 0.6767 (13) 0.4590 (2) 0.2510 (4) 0.0163 (11) C5 0.6666 (13) 0.4576 (2) 0.3740 (4) 0.0151 (10) H5 0.7541 0.4878 0.4248 0.018\* C6 0.5205 (12) 0.4095 (2) 0.4220 (4) 0.0135 (10) C7 0.4517 (13) 0.3916 (2) 0.5397 (4) 0.0153 (10) H7 0.5060 0.4113 0.6141 0.018\* C8 0.2932 (14) 0.3408 (2) 0.5243 (4) 0.0161 (11) C9 0.1403 (13) 0.3029 (2) 0.6073 (4) 0.0157 (10) C10 0.0273 (14) 0.2924 (2) 0.8131 (4) 0.0202 (11) H10A 0.1957 0.2639 0.8488 0.024\* H10B −0.1857 0.2728 0.7775 0.024\* C11 −0.0555 (14) 0.3333 (2) 0.9091 (4) 0.0202 (11) H11A −0.1540 0.3130 0.9738 0.030\* H11B −0.2234 0.3611 0.8728 0.030\* H11C 0.1571 0.3526 0.9433 0.030\* ------ -------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e856 .table-wrap} ----- ------------ ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0225 (3) 0.0210 (3) 0.0205 (3) −0.0006 (2) 0.0046 (2) 0.0051 (2) O1 0.020 (2) 0.0151 (17) 0.0107 (15) −0.0015 (15) −0.0019 (14) −0.0010 (14) O2 0.032 (2) 0.0169 (19) 0.0191 (18) −0.0038 (17) 0.0022 (17) −0.0014 (15) O3 0.019 (2) 0.0196 (18) 0.0108 (15) −0.0032 (15) 0.0007 (14) 0.0015 (14) C1 0.015 (3) 0.016 (2) 0.013 (2) 0.003 (2) −0.0009 (19) 0.0018 (19) C2 0.021 (3) 0.022 (3) 0.013 (2) 0.002 (2) −0.001 (2) −0.002 (2) C3 0.032 (3) 0.021 (3) 0.013 (2) 0.004 (2) 0.006 (2) 0.002 (2) C4 0.013 (3) 0.018 (2) 0.019 (2) 0.002 (2) 0.005 (2) 0.007 (2) C5 0.013 (3) 0.014 (2) 0.018 (2) 0.000 (2) 0.001 (2) −0.003 (2) C6 0.008 (2) 0.018 (2) 0.012 (2) 0.001 (2) −0.0063 (19) −0.0007 (19) C7 0.016 (3) 0.016 (2) 0.013 (2) 0.004 (2) −0.001 (2) −0.0006 (19) C8 0.021 (3) 0.016 (2) 0.010 (2) 0.007 (2) 0.000 (2) 0.0000 (19) C9 0.014 (3) 0.019 (3) 0.013 (2) 0.005 (2) −0.003 (2) 0.001 (2) C10 0.023 (3) 0.022 (3) 0.016 (2) −0.003 (2) 0.004 (2) 0.006 (2) C11 0.020 (3) 0.027 (3) 0.014 (2) −0.007 (2) 0.001 (2) 0.003 (2) ----- ------------ ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1162 .table-wrap} -------------------- ------------ --------------------- ------------ Br1---C4 1.912 (5) C5---C6 1.410 (7) O1---C1 1.367 (6) C5---H5 0.9500 O1---C8 1.384 (5) C6---C7 1.428 (6) O2---C9 1.208 (6) C7---C8 1.357 (7) O3---C9 1.340 (5) C7---H7 0.9500 O3---C10 1.465 (6) C8---C9 1.464 (7) C1---C2 1.390 (6) C10---C11 1.505 (7) C1---C6 1.398 (7) C10---H10A 0.9900 C2---C3 1.382 (7) C10---H10B 0.9900 C2---H2 0.9500 C11---H11A 0.9800 C3---C4 1.397 (7) C11---H11B 0.9800 C3---H3 0.9500 C11---H11C 0.9800 C4---C5 1.369 (6) C1---O1---C8 105.3 (4) C8---C7---H7 126.8 C9---O3---C10 116.5 (4) C6---C7---H7 126.8 O1---C1---C2 125.2 (4) C7---C8---O1 111.9 (4) O1---C1---C6 110.8 (4) C7---C8---C9 133.0 (4) C2---C1---C6 124.0 (5) O1---C8---C9 115.1 (4) C3---C2---C1 116.1 (5) O2---C9---O3 125.3 (5) C3---C2---H2 121.9 O2---C9---C8 124.9 (4) C1---C2---H2 121.9 O3---C9---C8 109.8 (4) C2---C3---C4 120.6 (4) O3---C10---C11 107.2 (4) C2---C3---H3 119.7 O3---C10---H10A 110.3 C4---C3---H3 119.7 C11---C10---H10A 110.3 C5---C4---C3 123.4 (5) O3---C10---H10B 110.3 C5---C4---Br1 118.2 (4) C11---C10---H10B 110.3 C3---C4---Br1 118.4 (4) H10A---C10---H10B 108.5 C4---C5---C6 117.1 (4) C10---C11---H11A 109.5 C4---C5---H5 121.5 C10---C11---H11B 109.5 C6---C5---H5 121.5 H11A---C11---H11B 109.5 C1---C6---C5 118.8 (4) C10---C11---H11C 109.5 C1---C6---C7 105.6 (4) H11A---C11---H11C 109.5 C5---C6---C7 135.6 (5) H11B---C11---H11C 109.5 C8---C7---C6 106.4 (4) C8---O1---C1---C2 −179.8 (5) C4---C5---C6---C7 −178.1 (5) C8---O1---C1---C6 −0.3 (5) C1---C6---C7---C8 −1.0 (6) O1---C1---C2---C3 177.3 (5) C5---C6---C7---C8 177.8 (6) C6---C1---C2---C3 −2.1 (8) C6---C7---C8---O1 0.9 (6) C1---C2---C3---C4 1.2 (8) C6---C7---C8---C9 −175.5 (5) C2---C3---C4---C5 0.7 (8) C1---O1---C8---C7 −0.4 (6) C2---C3---C4---Br1 −177.6 (4) C1---O1---C8---C9 176.7 (4) C3---C4---C5---C6 −1.6 (7) C10---O3---C9---O2 −0.7 (7) Br1---C4---C5---C6 176.6 (4) C10---O3---C9---C8 178.6 (4) O1---C1---C6---C5 −178.3 (4) C7---C8---C9---O2 178.6 (6) C2---C1---C6---C5 1.2 (8) O1---C8---C9---O2 2.3 (7) O1---C1---C6---C7 0.8 (5) C7---C8---C9---O3 −0.7 (8) C2---C1---C6---C7 −179.7 (5) O1---C8---C9---O3 −177.1 (4) C4---C5---C6---C1 0.7 (7) C9---O3---C10---C11 −154.2 (4) -------------------- ------------ --------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1651 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C2---H2···O2^i^ 0.95 2.57 3.400 (6) 146 C11---H11A···O2^ii^ 0.98 2.53 3.472 (6) 160 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x+1/2, −y+1/2, z−1/2; (ii) x−1/2, −y+1/2, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- C2---H2⋯O2^i^ 0.95 2.57 3.400 (6) 146 C11---H11A⋯O2^ii^ 0.98 2.53 3.472 (6) 160 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.578028	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052120/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o696", "authors": [ { "first": "Hatem A.", "last": "Abdel-Aziz" }, { "first": "Ahmed", "last": "Bari" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052121	Related literature {#sec1} ================== For the structure of 9-aminoacridine hydrochloride monohydrate, see: Talacki et al. (1974[@bb8]). For positive-charge-assisted hydrogen bonds, see: Gilli et al. (1994[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~11~N~2~ ^+^·NO~3~ ^−^·H~2~OM ~r~ = 275.26Triclinic,a = 6.8556 (2) Åb = 10.0532 (2) Åc = 10.5912 (3) Åα = 117.016 (1)°β = 94.138 (1)°γ = 97.995 (1)°V = 636.36 (3) Å^3^Z = 2Mo Kα radiationμ = 0.11 mm^−1^T = 293 K0.75 × 0.75 × 0.45 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (Blessing, 1995[@bb9]) T ~min~ = 0.923, T ~max~ = 0.9538945 measured reflections2822 independent reflections2054 reflections with I \> 2σ(I)R ~int~ = 0.028 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.045wR(F ^2^) = 0.132S = 1.042822 reflections201 parameters5 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.26 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e541} Data collection: COLLECT (Nonius, 2001[@bb5]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[@bb6]); data reduction: DENZO (Otwinowski & Minor, 1997[@bb6]) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: Mercury (Macrae et al., 2006[@bb4]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb2]) and enCIFer (Allen et al., 2004[@bb1]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003953/ng5102sup1.cif](http://dx.doi.org/10.1107/S1600536811003953/ng5102sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003953/ng5102Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003953/ng5102Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5102&file=ng5102sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5102sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5102&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5102](http://scripts.iucr.org/cgi-bin/sendsup?ng5102)). Support of this investigation by Ferdowsi University of Mashhad and the Islamic Azad University Shahr-e-Rey Branch is gratefully acknowledged. Comment ======= In a previous work, the crystal structure of 9-aminoacridine hydrochloride monohydrate (Talacki et al., 1974) has been investigated. Here, we report on the crystal structure of title hydrated salt, C~13~H~11~N~2~^+^.NO~3~^-^.H~2~O (Fig. 1). In 9-amino-acridinium cation, the heteroatom N1 and the nitrogen atom of NH~2~ unit (N2) have a sp^2^ character. The C1---N1---C13 angle is 122.68 (11)°; the fused tricyclic system is essentially planar. The protonated pyridine nitrogen atom is involving in a positive charge assisted (Gilli et al., 1994) N---H···O hydrogen bond with a neighboring H~2~O molecule (N1···O4 = 2.7867 (15) Å). Moreover, the water molecule forms two O---H···O hydrogen bonds (O···O = 2.9058 (18) & 2.9147 (18) Å) with two adjacent NO~3~^-^ anions; also, the weak hydrogen bond O4---H4B···O2 (O4···O2 = 3.2039 (19) Å) may be considered which has not influence on the pattern of crystal packing. The NH~2~ unit of cation cooperates in three N---H···O hydrogen bonds (N···O = 2.9123 (15), 3.0619 (17) and 3.0662 (16) Å), with two neighboring nitrate anions. Cations, anions and water molecules are hydrogen bonded in a 2-D arrangement (Fig. 2). Experimental {#experimental} ============ The title hydrated salt was obtained fortuitously from the reaction between 9-aminoacridine and Fe(NO~3~)~3~.9H~2~O in CH~3~OH as follows: To a solution of 9-aminoacridine (0.194 g, 1 mmol) in CH~3~OH (5 ml), a solution of Fe(NO~3~)~3~.9H~2~O (0.202 g, 0.5 mmol) in CH~3~OH (5 ml) was added at 343 K. After 1 h stirring, the solid was filtered; the crystals were obtained from methanolic solution after a slow evaporation at room temperature. Refinement {#refinement} ========== The hydrogen atom of NH group and those of water molecule were found in difference Fourier synthesis.The NH H atoms were restrained to 0.90 A and the refinement give good values. The H atoms in the water molecule were refined with a restraint of 1.00 A for a ideal distance OH and obtained acceptable values. The H(C) atom positions were calculated. All hydrogen atoms were refined in isotropic approximation in riding model with the U~iso~(H) parameters equal to 1.2 U~eq~(Ci), for methyl groups equal to 1.5 U~eq~(Cii), where U(Ci) and U(Cii) are respectively the equivalent thermal parameters of the carbon atoms to which corresponding H atoms are bonded. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular view with the atom labeling scheme, displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o565-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing of cations, anions and water molecules in the title hydrated salt. H bonds are shown as dashed lines. ::: ![](e-67-0o565-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e187 .table-wrap} ---------------------------------- -------------------------------------- C~13~H~11~N~2~^+^·NO~3~^−^·H~2~O Z = 2 M~r~ = 275.26 F(000) = 288 Triclinic, P1 D~x~ = 1.437 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 6.8556 (2) Å Cell parameters from 600 reflections b = 10.0532 (2) Å θ = 1--14° c = 10.5912 (3) Å µ = 0.11 mm^−1^ α = 117.016 (1)° T = 293 K β = 94.138 (1)° Block, colourless γ = 97.995 (1)° 0.75 × 0.75 × 0.45 mm V = 636.36 (3) Å^3^ ---------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e333 .table-wrap} ---------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 2822 independent reflections Radiation source: fine-focus sealed tube 2054 reflections with I \> 2σ(I) graphite R~int~ = 0.028 CCD rotation images, thick slices scans θ~max~ = 27.6°, θ~min~ = 3.0° Absorption correction: multi-scan (Blessing, 1995) h = −8→8 T~min~ = 0.923, T~max~ = 0.953 k = −12→13 8945 measured reflections l = −13→13 ---------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e442 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.132 H atoms treated by a mixture of independent and constrained refinement S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0799P)^2^ + 0.0299P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2822 reflections (Δ/σ)~max~ \< 0.001 201 parameters Δρ~max~ = 0.26 e Å^−3^ 5 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e599 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e698 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.28645 (17) 0.69390 (14) 0.48088 (14) 0.0392 (3) C2 0.3072 (2) 0.82982 (15) 0.46976 (16) 0.0491 (3) H2 0.3418 0.9237 0.5518 0.059\ C3 0.2764 (2) 0.82263 (16) 0.33871 (17) 0.0548 (4) H3 0.2900 0.9123 0.3317 0.066\* C4 0.2245 (2) 0.68227 (17) 0.21357 (17) 0.0545 (4) H4 0.2054 0.6794 0.1245 0.065\* C5 0.20191 (19) 0.54989 (15) 0.22257 (14) 0.0456 (3) H5 0.1663 0.4572 0.1393 0.055\* C6 0.23215 (17) 0.55232 (13) 0.35736 (13) 0.0377 (3) C7 0.20689 (17) 0.41608 (13) 0.37264 (13) 0.0368 (3) C8 0.23830 (16) 0.43023 (13) 0.51410 (13) 0.0369 (3) C9 0.21635 (19) 0.30332 (15) 0.54077 (15) 0.0438 (3) H9 0.1779 0.2057 0.4642 0.053\* C10 0.2506 (2) 0.32195 (17) 0.67683 (16) 0.0513 (4) H10 0.2353 0.2375 0.6924 0.062\* C11 0.3088 (2) 0.46790 (18) 0.79260 (16) 0.0554 (4) H11 0.3326 0.4797 0.8850 0.066\* C12 0.3312 (2) 0.59339 (17) 0.77252 (14) 0.0512 (4) H12 0.3695 0.6900 0.8507 0.061\* C13 0.29601 (17) 0.57631 (14) 0.63302 (13) 0.0393 (3) N1 0.31813 (16) 0.70224 (12) 0.61313 (12) 0.0437 (3) N2 0.15562 (19) 0.28113 (13) 0.25875 (12) 0.0507 (3) N3 0.0612 (2) 1.10579 (12) 0.88933 (12) 0.0521 (3) O1 0.22383 (17) 1.19337 (12) 0.95048 (12) 0.0721 (4) O2 0.04483 (18) 1.00530 (11) 0.76309 (11) 0.0674 (3) O3 −0.08334 (18) 1.12104 (15) 0.95548 (12) 0.0739 (4) O4 0.4979 (2) 0.98619 (13) 0.83821 (14) 0.0775 (4) H1 0.361 (2) 0.7928 (17) 0.6889 (16) 0.062 (5)\* H2A 0.133 (2) 0.2695 (19) 0.1668 (16) 0.061 (4)\* H2B 0.126 (2) 0.1971 (17) 0.2686 (18) 0.067 (5)\* H4A 0.626 (2) 1.017 (2) 0.883 (2) 0.094 (7)\* H4B 0.422 (3) 1.057 (2) 0.875 (2) 0.098 (7)\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1135 .table-wrap} ----- ------------ ------------- ------------- ------------- ------------- ------------ U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0320 (6) 0.0385 (6) 0.0459 (7) 0.0080 (5) 0.0077 (5) 0.0183 (6) C2 0.0462 (7) 0.0360 (6) 0.0613 (9) 0.0068 (5) 0.0078 (6) 0.0200 (6) C3 0.0529 (8) 0.0489 (8) 0.0750 (10) 0.0128 (6) 0.0108 (7) 0.0386 (8) C4 0.0580 (8) 0.0612 (9) 0.0577 (9) 0.0190 (7) 0.0121 (6) 0.0369 (8) C5 0.0480 (7) 0.0453 (7) 0.0441 (7) 0.0138 (6) 0.0073 (5) 0.0202 (6) C6 0.0321 (6) 0.0383 (6) 0.0432 (7) 0.0097 (5) 0.0083 (5) 0.0183 (6) C7 0.0315 (6) 0.0356 (6) 0.0398 (7) 0.0079 (5) 0.0061 (5) 0.0142 (5) C8 0.0288 (6) 0.0407 (7) 0.0418 (7) 0.0092 (5) 0.0076 (5) 0.0189 (6) C9 0.0407 (7) 0.0435 (7) 0.0495 (7) 0.0097 (5) 0.0093 (5) 0.0229 (6) C10 0.0475 (7) 0.0610 (9) 0.0605 (9) 0.0167 (6) 0.0154 (6) 0.0387 (8) C11 0.0543 (8) 0.0750 (10) 0.0448 (8) 0.0185 (7) 0.0128 (6) 0.0325 (8) C12 0.0494 (8) 0.0565 (8) 0.0390 (7) 0.0103 (6) 0.0078 (6) 0.0148 (6) C13 0.0326 (6) 0.0428 (7) 0.0399 (7) 0.0084 (5) 0.0077 (5) 0.0166 (6) N1 0.0450 (6) 0.0353 (6) 0.0412 (6) 0.0056 (5) 0.0052 (5) 0.0107 (5) N2 0.0694 (8) 0.0356 (6) 0.0397 (6) 0.0073 (5) 0.0013 (5) 0.0133 (5) N3 0.0707 (8) 0.0388 (6) 0.0428 (6) 0.0083 (6) −0.0041 (6) 0.0182 (5) O1 0.0757 (8) 0.0523 (6) 0.0587 (7) −0.0043 (6) −0.0034 (6) 0.0076 (5) O2 0.0965 (8) 0.0445 (6) 0.0431 (6) 0.0017 (5) −0.0006 (5) 0.0100 (5) O3 0.0681 (7) 0.0950 (9) 0.0604 (7) 0.0244 (6) 0.0096 (6) 0.0358 (7) O4 0.0701 (8) 0.0541 (7) 0.0758 (8) 0.0067 (6) −0.0002 (6) 0.0060 (6) ----- ------------ ------------- ------------- ------------- ------------- ------------ ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1491 .table-wrap} -------------------- -------------- ----------------------- -------------- C1---N1 1.3641 (18) C9---H9 0.9300 C1---C6 1.4024 (18) C10---C11 1.396 (2) C1---C2 1.4127 (18) C10---H10 0.9300 C2---C3 1.356 (2) C11---C12 1.362 (2) C2---H2 0.9300 C11---H11 0.9300 C3---C4 1.403 (2) C12---C13 1.4061 (19) C3---H3 0.9300 C12---H12 0.9300 C4---C5 1.3654 (19) C13---N1 1.3650 (17) C4---H4 0.9300 N1---H1 0.887 (14) C5---C6 1.4163 (18) N2---H2A 0.925 (14) C5---H5 0.9300 N2---H2B 0.895 (14) C6---C7 1.4393 (17) N3---O2 1.2411 (15) C7---N2 1.3186 (16) N3---O1 1.2417 (16) C7---C8 1.4361 (17) N3---O3 1.2417 (17) C8---C13 1.4091 (18) O4---H4A 0.909 (16) C8---C9 1.4178 (17) O4---H4B 0.901 (16) C9---C10 1.364 (2) N1---C1---C6 120.53 (11) C10---C9---H9 119.4 N1---C1---C2 119.19 (12) C8---C9---H9 119.4 C6---C1---C2 120.28 (12) C9---C10---C11 119.94 (13) C3---C2---C1 119.60 (13) C9---C10---H10 120.0 C3---C2---H2 120.2 C11---C10---H10 120.0 C1---C2---H2 120.2 C12---C11---C10 121.11 (13) C2---C3---C4 121.12 (13) C12---C11---H11 119.4 C2---C3---H3 119.4 C10---C11---H11 119.4 C4---C3---H3 119.4 C11---C12---C13 119.71 (13) C5---C4---C3 120.01 (13) C11---C12---H12 120.1 C5---C4---H4 120.0 C13---C12---H12 120.1 C3---C4---H4 120.0 N1---C13---C12 119.63 (12) C4---C5---C6 120.69 (13) N1---C13---C8 120.00 (11) C4---C5---H5 119.7 C12---C13---C8 120.37 (12) C6---C5---H5 119.7 C1---N1---C13 122.68 (11) C1---C6---C5 118.30 (11) C1---N1---H1 118.7 (11) C1---C6---C7 118.91 (11) C13---N1---H1 118.6 (11) C5---C6---C7 122.78 (11) C7---N2---H2A 122.2 (10) N2---C7---C8 120.83 (11) C7---N2---H2B 120.4 (11) N2---C7---C6 120.48 (11) H2A---N2---H2B 116.9 (16) C8---C7---C6 118.70 (11) O2---N3---O1 119.79 (14) C13---C8---C9 117.72 (11) O2---N3---O3 120.94 (13) C13---C8---C7 119.16 (11) O1---N3---O3 119.27 (12) C9---C8---C7 123.11 (11) H4A---O4---H4B 114 (2) C10---C9---C8 121.15 (13) N1---C1---C2---C3 179.86 (12) N2---C7---C8---C9 −0.21 (19) C6---C1---C2---C3 −0.71 (19) C6---C7---C8---C9 179.70 (10) C1---C2---C3---C4 −0.1 (2) C13---C8---C9---C10 −0.24 (18) C2---C3---C4---C5 0.7 (2) C7---C8---C9---C10 179.00 (11) C3---C4---C5---C6 −0.6 (2) C8---C9---C10---C11 −0.1 (2) N1---C1---C6---C5 −179.71 (11) C9---C10---C11---C12 0.4 (2) C2---C1---C6---C5 0.87 (17) C10---C11---C12---C13 −0.2 (2) N1---C1---C6---C7 1.12 (17) C11---C12---C13---N1 179.87 (12) C2---C1---C6---C7 −178.31 (10) C11---C12---C13---C8 −0.1 (2) C4---C5---C6---C1 −0.23 (19) C9---C8---C13---N1 −179.64 (10) C4---C5---C6---C7 178.91 (11) C7---C8---C13---N1 1.09 (17) C1---C6---C7---N2 179.90 (11) C9---C8---C13---C12 0.38 (17) C5---C6---C7---N2 0.77 (19) C7---C8---C13---C12 −178.89 (11) C1---C6---C7---C8 −0.01 (16) C6---C1---N1---C13 −1.16 (18) C5---C6---C7---C8 −179.14 (11) C2---C1---N1---C13 178.27 (10) N2---C7---C8---C13 179.02 (11) C12---C13---N1---C1 −179.99 (11) C6---C7---C8---C13 −1.08 (16) C8---C13---N1---C1 0.03 (18) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2085 .table-wrap} -------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N2---H2A···O1^i^ 0.93 (1) 2.23 (2) 3.0619 (17) 149.(1) N2---H2A···O3^i^ 0.93 (1) 2.30 (2) 3.0662 (16) 140.(1) N2---H2B···O2^ii^ 0.90 (1) 2.07 (1) 2.9123 (15) 157.(2) O4---H4A···O3^iii^ 0.91 (2) 2.03 (2) 2.9147 (18) 164.(2) N1---H1···O4 0.89 (1) 1.91 (1) 2.7867 (15) 170.(2) O4---H4B···O1 0.90 (2) 2.01 (2) 2.9058 (18) 173 (2) O4---H4B···O2 0.90 (2) 2.64 (2) 3.2039 (19) 122.(2) -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) x, y−1, z−1; (ii) −x, −y+1, −z+1; (iii) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- ---------- ---------- ------------- ------------- N2---H2A⋯O1^i^ 0.93 (1) 2.23 (2) 3.0619 (17) 149 (1) N2---H2A⋯O3^i^ 0.93 (1) 2.30 (2) 3.0662 (16) 140 (1) N2---H2B⋯O2^ii^ 0.90 (1) 2.07 (1) 2.9123 (15) 157 (2) O4---H4A⋯O3^iii^ 0.91 (2) 2.03 (2) 2.9147 (18) 164 (2) N1---H1⋯O4 0.89 (1) 1.91 (1) 2.7867 (15) 170 (2) O4---H4B⋯O1 0.90 (2) 2.01 (2) 2.9058 (18) 173 (2) O4---H4B⋯O2 0.90 (2) 2.64 (2) 3.2039 (19) 122 (2) Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.582755	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052121/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o565", "authors": [ { "first": "Mehrdad", "last": "Pourayoubi" }, { "first": "Hossein", "last": "Eshtiagh-Hosseini" }, { "first": "Somayyeh", "last": "Sanaei Ataabadi" }, { "first": "Teresa", "last": "Mancilla Percino" }, { "first": "Marco", "last": "A. Leyva Ramírez" } ] }
PMC3052122	Related literature {#sec1} ================== For the biological activity of pyrazole oxime ether derivatives, see: Drabek (1992[@bb3]); Motoba et al. (2000[@bb6]); Park et al. (2005[@bb7]); Watanabe et al. (2001[@bb10]). For the bioactivity of compounds containing a thiazole ring, see: Araki (2004[@bb1]); Fahmy & Bekhit (2002[@bb4]); Manabe et al. (2003[@bb5]); Zhang et al. (2000[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~22~H~19~ClN~4~O~2~SM ~r~ = 438.92Triclinic,a = 8.114 (3) Åb = 11.452 (4) Åc = 12.494 (4) Åα = 102.700 (6)°β = 107.885 (6)°γ = 93.634 (7)°V = 1067.1 (6) Å^3^Z = 2Mo Kα radiationμ = 0.30 mm^−1^T = 294 K0.20 × 0.18 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb8]) T ~min~ = 0.938, T ~max~ = 0.9685562 measured reflections3755 independent reflections2030 reflections with I \> 2σ(I)R ~int~ = 0.029 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.049wR(F ^2^) = 0.124S = 1.003755 reflections273 parametersH-atom parameters constrainedΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e381} Data collection: SMART (Bruker, 2000[@bb2]); cell refinement: SAINT (Bruker, 2000[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb9]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb9]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006702/ds2094sup1.cif](http://dx.doi.org/10.1107/S1600536811006702/ds2094sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006702/ds2094Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006702/ds2094Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ds2094&file=ds2094sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ds2094sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ds2094&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DS2094](http://scripts.iucr.org/cgi-bin/sendsup?ds2094)). This work was supported by the Science and Technology Projects Fund of Nantong City (grant Nos. K2010016, AS2010005), the Science Foundation of Nantong University (grant Nos. 09Z010, 09 C001) and the Scientific Research Foundation for Talent Introduction of Nantong University. Comment ======= In the past few years, pyrazole oxime ethers have been found to exhibit a wide range of bioactivities, such as fungicidal, insecticidal, acaricidal and anticancer activities (Drabek, 1992; Motoba et al., 2000; Watanabe et al., 2001;Park et al., 2005). In addition, the biological activity of thiazole derivatives has been the subject of intense interest for past decades. They are widely used as fungicide, insecticide, herbicide and antitumor agents (Zhang et al., 2000; Fahmy & Bekhit, 2002; Manabe et al., 2003; Araki,2004). Having the above facts in mind and in continuation of our efforts to explore more biologically active moleculars, we synthesized a series of pyrazole oxime ether compounds containing a thiazole moiety. Herein we report the crystal structure of the title compound. The molecule of the title compound (Fig.1)contains four planar rings, the benzene ring (p1: C1/C2/C3/C4/C5/C6), the substituted phenyl ring (p2: C11/C12/C13/C14/C15/C16),the thiazole ring(p3: C20/C21/N4/C22/S1) and the pyrazole ring(p4: N1/N2/C8/C9/C10).The planes of p1, p2 and p3 make dihedral angles of 18.4 (3)°, 88.9 (2) ° and 63.0 (3) °,respectively, with p4. Experimental {#experimental} ============ To a well stirred solution of 1-phenyl-3-methyl-5-(4-methylphenoxy)-1H- pyrazole-4-carbaldehyde oxime (3 mmol),and powdered potassium carbonate (6 mmol) in 20 ml of anhydrous acetone, was added 2-chloro-5-chloromethyl thiazole (3.3 mmol) at room temperature. The mixture was heated to reflux for 10 h. The solvent was evaporated under reduced pressure, and then 80 ml of dichloromethane was added to the residue. The organic layer was washed with saturated brine(3 \* 20 ml),and dried over anhydrous magnesium sulfate. After removal of the solvent, the residue was separated by column chromatography on silica gel with petroleum ether/ethyl acetate(6:1 v/v) as eluent, and recrystallized from ethyl acetate to give a colourless crystal. Refinement {#refinement} ========== All H atoms were placed in calculated positions, with C--H = 0.93, 0.96 and 0.97 Å, and included in the final cycles of refinement using a riding model, with U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title compound, with displacement ellipsoids drawn at the 30% probability level. ::: ![](e-67-0o727-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e122 .table-wrap} ----------------------- --------------------------------------- C~22~H~19~ClN~4~O~2~S Z = 2 M~r~ = 438.92 F(000) = 456 Triclinic, P1 D~x~ = 1.366 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.114 (3) Å Cell parameters from 1218 reflections b = 11.452 (4) Å θ = 2.7--22.3° c = 12.494 (4) Å µ = 0.30 mm^−1^ α = 102.700 (6)° T = 294 K β = 107.885 (6)° Triclinic, colourless γ = 93.634 (7)° 0.20 × 0.18 × 0.10 mm V = 1067.1 (6) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e259 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3755 independent reflections Radiation source: fine-focus sealed tube 2030 reflections with I \> 2σ(I) graphite R~int~ = 0.029 φ and ω scans θ~max~ = 25.0°, θ~min~ = 1.8° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −9→9 T~min~ = 0.938, T~max~ = 0.968 k = −10→13 5562 measured reflections l = −14→14 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.049 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.124 H-atom parameters constrained S = 1.00 w = 1/\[σ^2^(F~o~^2^) + (0.049P)^2^ + 0.1132P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3755 reflections (Δ/σ)~max~ = 0.001 273 parameters Δρ~max~ = 0.17 e Å^−3^ 0 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e533 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e632 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ S1 0.45270 (11) 0.85178 (9) 0.33662 (8) 0.0647 (3) Cl1 0.61728 (16) 0.68418 (11) 0.47383 (9) 0.0975 (4) O1 −0.0621 (2) 0.84964 (18) 0.10876 (17) 0.0450 (5) O2 0.4577 (3) 1.0355 (2) 0.16837 (17) 0.0530 (6) N1 −0.2014 (3) 0.7626 (2) −0.0923 (2) 0.0434 (7) N2 −0.1696 (3) 0.7554 (2) −0.1953 (2) 0.0510 (7) N3 0.2917 (3) 0.9627 (2) 0.1279 (2) 0.0479 (7) N4 0.7640 (4) 0.8986 (3) 0.4813 (2) 0.0660 (9) C1 −0.3633 (4) 0.7038 (3) −0.0939 (3) 0.0471 (8) C2 −0.4206 (4) 0.7326 (3) 0.0001 (3) 0.0636 (10) H2 −0.3572 0.7937 0.0653 0.076\ C3 −0.5742 (5) 0.6692 (4) −0.0040 (4) 0.0768 (12) H3 −0.6126 0.6870 0.0599 0.092\* C4 −0.6702 (5) 0.5811 (4) −0.0999 (5) 0.0914 (14) H4 −0.7723 0.5384 −0.1009 0.110\* C5 −0.6157 (5) 0.5561 (4) −0.1939 (4) 0.0941 (14) H5 −0.6828 0.4975 −0.2602 0.113\* C6 −0.4610 (5) 0.6171 (4) −0.1921 (3) 0.0719 (11) H6 −0.4240 0.5994 −0.2566 0.086\* C7 0.0690 (4) 0.8267 (4) −0.2568 (3) 0.0676 (11) H7A 0.1699 0.7855 −0.2474 0.101\* H7B 0.1031 0.9108 −0.2490 0.101\* H7C −0.0152 0.7919 −0.3324 0.101\* C8 −0.0104 (4) 0.8142 (3) −0.1657 (3) 0.0465 (8) C9 0.0656 (4) 0.8599 (3) −0.0440 (2) 0.0400 (8) C10 −0.0610 (4) 0.8238 (3) −0.0019 (3) 0.0395 (8) C11 −0.0066 (4) 0.7658 (3) 0.1735 (2) 0.0408 (8) C12 −0.0280 (4) 0.7901 (3) 0.2804 (3) 0.0541 (9) H12 −0.0762 0.8582 0.3055 0.065\* C13 0.0232 (4) 0.7116 (3) 0.3504 (3) 0.0591 (10) H13 0.0085 0.7278 0.4230 0.071\* C14 0.0945 (4) 0.6111 (3) 0.3161 (3) 0.0531 (9) C15 0.1125 (4) 0.5889 (3) 0.2072 (3) 0.0550 (9) H15 0.1606 0.5209 0.1819 0.066\* C16 0.0612 (4) 0.6647 (3) 0.1352 (3) 0.0449 (8) H16 0.0725 0.6474 0.0617 0.054\* C17 0.1474 (5) 0.5256 (4) 0.3933 (3) 0.0871 (13) H17A 0.2202 0.5707 0.4695 0.131\* H17B 0.2110 0.4678 0.3609 0.131\* H17C 0.0447 0.4841 0.3984 0.131\* C18 0.2345 (4) 0.9303 (3) 0.0182 (3) 0.0437 (8) H18 0.3035 0.9525 −0.0233 0.052\* C19 0.5031 (4) 1.0792 (3) 0.2911 (3) 0.0565 (9) H19A 0.4004 1.1029 0.3096 0.068\* H19B 0.5904 1.1505 0.3175 0.068\* C20 0.5727 (4) 0.9879 (3) 0.3541 (3) 0.0468 (8) C21 0.7309 (4) 0.9944 (4) 0.4334 (3) 0.0606 (10) H21 0.8149 1.0620 0.4548 0.073\* C22 0.6282 (5) 0.8196 (4) 0.4373 (3) 0.0581 (10) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1336 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ S1 0.0518 (6) 0.0703 (7) 0.0665 (6) −0.0003 (5) 0.0059 (5) 0.0280 (5) Cl1 0.1287 (10) 0.0848 (9) 0.0856 (8) 0.0232 (7) 0.0255 (7) 0.0467 (7) O1 0.0519 (13) 0.0432 (14) 0.0441 (13) 0.0105 (11) 0.0182 (11) 0.0148 (11) O2 0.0445 (13) 0.0612 (16) 0.0491 (14) −0.0041 (11) 0.0079 (11) 0.0191 (12) N1 0.0359 (15) 0.0482 (18) 0.0457 (16) 0.0056 (13) 0.0095 (13) 0.0168 (14) N2 0.0474 (17) 0.062 (2) 0.0428 (16) 0.0036 (15) 0.0121 (14) 0.0170 (14) N3 0.0375 (15) 0.0513 (18) 0.0510 (18) −0.0010 (13) 0.0074 (13) 0.0170 (14) N4 0.062 (2) 0.077 (2) 0.0519 (19) 0.0171 (19) 0.0049 (16) 0.0184 (18) C1 0.0368 (18) 0.041 (2) 0.065 (2) 0.0078 (16) 0.0136 (18) 0.0205 (18) C2 0.049 (2) 0.073 (3) 0.073 (3) 0.005 (2) 0.026 (2) 0.019 (2) C3 0.059 (3) 0.084 (3) 0.099 (3) 0.009 (2) 0.042 (2) 0.025 (3) C4 0.058 (3) 0.072 (3) 0.150 (5) −0.003 (2) 0.051 (3) 0.020 (3) C5 0.057 (3) 0.080 (3) 0.118 (4) −0.016 (2) 0.025 (3) −0.017 (3) C6 0.049 (2) 0.070 (3) 0.084 (3) −0.002 (2) 0.022 (2) −0.002 (2) C7 0.069 (2) 0.089 (3) 0.050 (2) −0.001 (2) 0.0227 (19) 0.027 (2) C8 0.0408 (19) 0.053 (2) 0.048 (2) 0.0056 (17) 0.0118 (16) 0.0210 (17) C9 0.0383 (18) 0.043 (2) 0.0402 (19) 0.0085 (15) 0.0097 (15) 0.0171 (16) C10 0.0390 (18) 0.039 (2) 0.0418 (19) 0.0092 (15) 0.0118 (16) 0.0146 (16) C11 0.0399 (17) 0.045 (2) 0.0403 (19) 0.0021 (16) 0.0149 (15) 0.0149 (16) C12 0.067 (2) 0.053 (2) 0.050 (2) 0.0139 (19) 0.0300 (18) 0.0120 (18) C13 0.072 (2) 0.064 (3) 0.047 (2) 0.004 (2) 0.0266 (19) 0.016 (2) C14 0.060 (2) 0.049 (2) 0.058 (2) 0.0042 (19) 0.0227 (19) 0.0241 (19) C15 0.059 (2) 0.049 (2) 0.064 (2) 0.0136 (18) 0.0257 (18) 0.0194 (19) C16 0.0498 (19) 0.044 (2) 0.0461 (19) 0.0081 (17) 0.0217 (16) 0.0128 (17) C17 0.116 (3) 0.080 (3) 0.084 (3) 0.021 (3) 0.038 (3) 0.050 (3) C18 0.0398 (18) 0.050 (2) 0.049 (2) 0.0083 (16) 0.0161 (17) 0.0251 (17) C19 0.053 (2) 0.057 (2) 0.050 (2) 0.0042 (18) 0.0068 (17) 0.0090 (19) C20 0.0438 (19) 0.054 (2) 0.0397 (18) 0.0060 (17) 0.0121 (16) 0.0077 (17) C21 0.054 (2) 0.065 (3) 0.051 (2) 0.0035 (19) 0.0053 (18) 0.011 (2) C22 0.069 (2) 0.064 (3) 0.047 (2) 0.018 (2) 0.0207 (19) 0.020 (2) ----- ------------- ------------- ------------- -------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1851 .table-wrap} --------------------- ------------ ----------------------- ------------ S1---C22 1.708 (4) C7---H7A 0.9600 S1---C20 1.718 (3) C7---H7B 0.9600 Cl1---C22 1.714 (4) C7---H7C 0.9600 O1---C10 1.352 (3) C8---C9 1.414 (4) O1---C11 1.397 (3) C9---C10 1.370 (4) O2---N3 1.421 (3) C9---C18 1.436 (4) O2---C19 1.424 (3) C11---C16 1.368 (4) N1---C10 1.351 (3) C11---C12 1.370 (4) N1---N2 1.375 (3) C12---C13 1.384 (4) N1---C1 1.430 (4) C12---H12 0.9300 N2---C8 1.321 (4) C13---C14 1.365 (5) N3---C18 1.264 (4) C13---H13 0.9300 N4---C22 1.272 (4) C14---C15 1.383 (4) N4---C21 1.365 (4) C14---C17 1.512 (4) C1---C2 1.374 (4) C15---C16 1.377 (4) C1---C6 1.374 (5) C15---H15 0.9300 C2---C3 1.383 (5) C16---H16 0.9300 C2---H2 0.9300 C17---H17A 0.9600 C3---C4 1.362 (6) C17---H17B 0.9600 C3---H3 0.9300 C17---H17C 0.9600 C4---C5 1.358 (6) C18---H18 0.9300 C4---H4 0.9300 C19---C20 1.482 (4) C5---C6 1.388 (5) C19---H19A 0.9700 C5---H5 0.9300 C19---H19B 0.9700 C6---H6 0.9300 C20---C21 1.345 (4) C7---C8 1.497 (4) C21---H21 0.9300 C22---S1---C20 88.36 (18) C16---C11---C12 120.9 (3) C10---O1---C11 117.5 (2) C16---C11---O1 124.2 (3) N3---O2---C19 107.2 (2) C12---C11---O1 114.9 (3) C10---N1---N2 110.3 (2) C11---C12---C13 118.9 (3) C10---N1---C1 130.4 (3) C11---C12---H12 120.6 N2---N1---C1 119.3 (3) C13---C12---H12 120.6 C8---N2---N1 105.2 (2) C14---C13---C12 121.9 (3) C18---N3---O2 110.9 (2) C14---C13---H13 119.0 C22---N4---C21 108.2 (3) C12---C13---H13 119.0 C2---C1---C6 120.4 (3) C13---C14---C15 117.6 (3) C2---C1---N1 121.3 (3) C13---C14---C17 121.1 (3) C6---C1---N1 118.3 (3) C15---C14---C17 121.3 (3) C1---C2---C3 118.9 (4) C16---C15---C14 121.8 (3) C1---C2---H2 120.6 C16---C15---H15 119.1 C3---C2---H2 120.6 C14---C15---H15 119.1 C4---C3---C2 121.2 (4) C11---C16---C15 118.9 (3) C4---C3---H3 119.4 C11---C16---H16 120.5 C2---C3---H3 119.4 C15---C16---H16 120.5 C5---C4---C3 119.5 (4) C14---C17---H17A 109.5 C5---C4---H4 120.3 C14---C17---H17B 109.5 C3---C4---H4 120.3 H17A---C17---H17B 109.5 C4---C5---C6 120.7 (4) C14---C17---H17C 109.5 C4---C5---H5 119.6 H17A---C17---H17C 109.5 C6---C5---H5 119.6 H17B---C17---H17C 109.5 C1---C6---C5 119.2 (4) N3---C18---C9 121.6 (3) C1---C6---H6 120.4 N3---C18---H18 119.2 C5---C6---H6 120.4 C9---C18---H18 119.2 C8---C7---H7A 109.5 O2---C19---C20 112.5 (3) C8---C7---H7B 109.5 O2---C19---H19A 109.1 H7A---C7---H7B 109.5 C20---C19---H19A 109.1 C8---C7---H7C 109.5 O2---C19---H19B 109.1 H7A---C7---H7C 109.5 C20---C19---H19B 109.1 H7B---C7---H7C 109.5 H19A---C19---H19B 107.8 N2---C8---C9 112.1 (3) C21---C20---C19 128.5 (3) N2---C8---C7 120.5 (3) C21---C20---S1 108.3 (3) C9---C8---C7 127.4 (3) C19---C20---S1 123.1 (2) C10---C9---C8 103.7 (3) C20---C21---N4 117.8 (3) C10---C9---C18 129.1 (3) C20---C21---H21 121.1 C8---C9---C18 127.2 (3) N4---C21---H21 121.1 N1---C10---O1 122.1 (3) N4---C22---S1 117.4 (3) N1---C10---C9 108.8 (3) N4---C22---Cl1 122.8 (3) O1---C10---C9 128.9 (3) S1---C22---Cl1 119.9 (2) C10---N1---N2---C8 −0.8 (3) C8---C9---C10---O1 −175.4 (3) C1---N1---N2---C8 −178.1 (2) C18---C9---C10---O1 3.0 (5) C19---O2---N3---C18 173.5 (3) C10---O1---C11---C16 5.4 (4) C10---N1---C1---C2 20.1 (5) C10---O1---C11---C12 −173.3 (3) N2---N1---C1---C2 −163.2 (3) C16---C11---C12---C13 1.2 (5) C10---N1---C1---C6 −159.8 (3) O1---C11---C12---C13 179.9 (3) N2---N1---C1---C6 16.9 (4) C11---C12---C13---C14 0.1 (5) C6---C1---C2---C3 2.8 (5) C12---C13---C14---C15 −0.8 (5) N1---C1---C2---C3 −177.1 (3) C12---C13---C14---C17 −179.2 (3) C1---C2---C3---C4 −1.3 (6) C13---C14---C15---C16 0.1 (5) C2---C3---C4---C5 −1.0 (7) C17---C14---C15---C16 178.6 (3) C3---C4---C5---C6 1.8 (7) C12---C11---C16---C15 −1.8 (4) C2---C1---C6---C5 −2.0 (5) O1---C11---C16---C15 179.6 (3) N1---C1---C6---C5 177.9 (3) C14---C15---C16---C11 1.1 (5) C4---C5---C6---C1 −0.3 (6) O2---N3---C18---C9 −177.5 (2) N1---N2---C8---C9 0.4 (3) C10---C9---C18---N3 4.6 (5) N1---N2---C8---C7 −179.3 (3) C8---C9---C18---N3 −177.4 (3) N2---C8---C9---C10 0.0 (3) N3---O2---C19---C20 79.6 (3) C7---C8---C9---C10 179.7 (3) O2---C19---C20---C21 119.4 (3) N2---C8---C9---C18 −178.4 (3) O2---C19---C20---S1 −62.1 (3) C7---C8---C9---C18 1.3 (5) C22---S1---C20---C21 0.0 (2) N2---N1---C10---O1 176.1 (3) C22---S1---C20---C19 −178.9 (3) C1---N1---C10---O1 −7.0 (5) C19---C20---C21---N4 178.9 (3) N2---N1---C10---C9 0.8 (3) S1---C20---C21---N4 0.1 (4) C1---N1---C10---C9 177.8 (3) C22---N4---C21---C20 −0.2 (4) C11---O1---C10---N1 90.5 (3) C21---N4---C22---S1 0.1 (4) C11---O1---C10---C9 −95.2 (4) C21---N4---C22---Cl1 179.3 (2) C8---C9---C10---N1 −0.5 (3) C20---S1---C22---N4 −0.1 (3) C18---C9---C10---N1 177.9 (3) C20---S1---C22---Cl1 −179.3 (2) --------------------- ------------ ----------------------- ------------ :::	PubMed Central	2024-06-05T04:04:18.587187	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052122/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o727", "authors": [ { "first": "Hong", "last": "Dai" }, { "first": "Yu-Ting", "last": "Zhang" }, { "first": "Yu-Jun", "last": "Shi" }, { "first": "Wen-Wen", "last": "Zhang" }, { "first": "Yong-Jun", "last": "Shen" } ] }
PMC3052123	Related literature {#sec1} ================== For related structures of β-amino alcohols, see: Lohray et al. (2002[@bb11]); Bodkin et al. (2008[@bb2]). For the structures of tosylamino compounds, see: Coote et al. (2008[@bb5]); Liu et al. (2005[@bb10]); Fadlalla et al. (2010[@bb6]). For the synthesis of the title compound, see: Naicker et al. (2008[@bb12]); Govender et al. (2003[@bb9]). For hydrogen-bond motifs, see: Bernstein et al. (1995[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~15~H~23~NO~5~SM ~r~ = 329.4Triclinic,a = 9.6038 (8) Åb = 9.9059 (8) Åc = 10.1064 (11) Åα = 119.342 (2)°β = 92.307 (2)°γ = 93.422 (2)°V = 833.95 (13) Å^3^Z = 2Mo Kα radiationμ = 0.22 mm^−1^T = 100 K0.22 × 0.18 × 0.14 mm ### Data collection {#sec2.1.2} Bruker X8 APEXII 4K Kappa CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2007[@bb4]) T ~min~ = 0.954, T ~max~ = 0.97024635 measured reflections4192 independent reflections3712 reflections with I \> 2σ(I)R ~int~ = 0.031 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.030wR(F ^2^) = 0.083S = 1.054192 reflections209 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.45 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e503} Data collection: APEX2 (Bruker, 2007[@bb4]); cell refinement: SAINT-Plus (Bruker, 2007[@bb4]); data reduction: SAINT-Plus and XPREP (Bruker, 2007[@bb4]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb13]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb13]); molecular graphics: DIAMOND (Brandenburg & Putz, 2005[@bb3]) and ORTEP-3 (Farrugia, 1997[@bb7]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004934/hg2795sup1.cif](http://dx.doi.org/10.1107/S1600536811004934/hg2795sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004934/hg2795Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004934/hg2795Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg2795&file=hg2795sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg2795sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg2795&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG2795](http://scripts.iucr.org/cgi-bin/sendsup?hg2795)). Financial assistance from Mintek and THRIP is gratefully acknowledged. Comment ======= The aminohydroxylation reaction of alkenes is the most simple, single step reaction in the production of β-amino alcohols. The product (β-amino alcohol) is present in many natural products and biologically active compounds (such as Acranil which is an antiprotozoal drug) (Bodkin et al., 2008, Lohray et al., 2002). Furthermore, β-amino alcohols are utilized in asymmetric catalysis in the synthesis of chiral ligands. As part of investigating new heterogeneous route to the aminohydroxylation reaction to produce β-amino alcohols, we report the crystal structure of the title compound (I). The molecular structure of (I) is related to that of (2,3)-Methyl 2-hydroxy-3-(4-methylbenzenesulfonamido)-3-phenylpropanoate (Fadlalla et al., (2010). Other related structures have been reported by Coote et al. (2008) and Liu et al., (2005). Fig. I shows the asymetric unit of (I). The compound is chiral and has an S chirality at C6 and an R chirality at C7. In the crystal, adjacent molecules are connected by a pair of N---H···O and O---H···O hydrogen bonds (Fig. 2) that result in centrosymmetric dimers that can be described by R~2~^2^(12) and R~2~^2^(14) graph set notations (Bernstein et al. 1995) respectively. In addition, weak C---H···O intermolecular interactions (Table 1) contribute to the stability of the crystal lattice. Experimental {#experimental} ============ The title compound (I) was obtained through a modified literature method (Naicker et al., 2008, Govender et al., 2003).To a nitrogen saturated Schlenk tube 6 ml of a mixture of acetonitrile and water (1:1 v/v), tert-butylcrotonate (76 µL, 0.478 mmol), chloramine-T (0.956 g, 0.956 mmol), hydrotalcite-like catalyst (0.03 g) were added in that order. The catalyst was gravity filtered off after 15 h. The reaction mixture was then washed with sodium sulfite (1 g in 20 ml of de-ionized water) followed by 15 ml of ethyl acetate. The aqueous layer was separated from the organic layer and further washed by 3x 15 ml of ethyl acetate. The solvent of the combined organic mixture was removed in vacuo. The resulting crude product was purified by preparative high preasure liquid chromatography to yield the title compound as a white solid. Crystals of I were obtained by slow evaporation of a hexane layered solution of the compound in dichloro methane at room temperature (m.p. 142--145 K). Spectroscopic data: ^1^H NMR (400 MHz, CDCl~3~, δ. p.p.m.): = 0.9 (d, 3H), 1.5 (s, 9H), 2.4 (s, 3H), 3.2 (d, 1H), 3.8 (m, 2H), 4.7 (d, 1H), 7.3 (d, 2H), 7.7 (d, 2H). ^13^C NMR (100 MHz, CDCl~3~, δ. p.p.m.): = 17.9 (s,1 C), 21.5 (s, 1 C), 27.9 (s, 3 C), 51.5 (s, 1 C), 73.6 (s, 1 C), 84.1 (s, 1 C), 126.9 (s, 2 C), 138.6 (s, 1 C), 143.3 (s, 1 C), 171.6 (s, 1 C). IR (cm^-1^): = 3446 (m), (OH), 3260 (m), (NH), 2985 (w), 2919 (w), 1598 (w), (ar), 1716 (m), (C=O), 1048 (m), (S=O). Mass calculated = 329, MS = 351 m/z (M + Na). Refinement {#refinement} ========== The methyl, methine and aromatic H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C---H = 0.95 Å and U~iso~(H) = 1.2U~eq~(C) for aromatic, C---H = 0.98 Å and U~iso~(H) = 1.2U~eq~(C) for CH~3~, C---H = 1.00 Å and U~iso~(H) = 1.2U~eq~(C) for CH. N---H = 0.84 Å and U~iso~(H) = 1.2U~eq~(N) for N---H and O---H = 0.84 Å and U~iso~(H) = 1.5U~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of (I) (50% probability displacement ellipsoids). H atoms have been omited for clarity. ::: ![](e-67-0o648-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### N---H···O and O---H···O hydrogen bond interactions in the crystal structure of (I). \[Symmetry operators: (i) = 1 - x, 1 - y, 1 - z; (ii) = 1 - x, 2 - y, 2 - z\] ::: ![](e-67-0o648-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e285 .table-wrap} ------------------------ ---------------------------------------- C~15~H~23~NO~5~S Z = 2 M~r~ = 329.4 F(000) = 352 Triclinic, P1 D~x~ = 1.312 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 9.6038 (8) Å Cell parameters from 24635 reflections b = 9.9059 (8) Å θ = 2.1--28.5° c = 10.1064 (11) Å µ = 0.22 mm^−1^ α = 119.342 (2)° T = 100 K β = 92.307 (2)° Block, colourless γ = 93.422 (2)° 0.22 × 0.18 × 0.14 mm V = 833.95 (13) Å^3^ ------------------------ ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e419 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker X8 APEXII 4K Kappa CCD diffractometer 3712 reflections with I \> 2σ(I) graphite R~int~ = 0.031 φ and ω scans θ~max~ = 28.5°, θ~min~ = 2.1° Absorption correction: multi-scan (SADABS; Bruker, 2007) h = −12→12 T~min~ = 0.954, T~max~ = 0.970 k = −13→13 24635 measured reflections l = −13→13 4192 independent reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e535 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.083 H atoms treated by a mixture of independent and constrained refinement S = 1.05 w = 1/\[σ^2^(F~o~^2^) + (0.0395P)^2^ + 0.3237P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4192 reflections (Δ/σ)~max~ = 0.005 209 parameters Δρ~max~ = 0.45 e Å^−3^ 0 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e692 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The intensity data was collected on a Bruker X8 Apex 4 K CCD diffractometer using an exposure time of 15 sec/per frame. A total of 3328 frames were collected with a frame width of 0.5° covering upto θ = 28.45° with 99.8% completeness accomplished. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e800 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.74584 (13) 1.08296 (13) 0.93414 (13) 0.0208 (2) H1A 0.6562 1.118 0.9193 0.031\ H1B 0.8195 1.1223 0.8942 0.031\* H1C 0.7685 1.1225 1.0431 0.031\* C2 0.87462 (12) 0.84588 (14) 0.86348 (14) 0.0241 (2) H2A 0.9444 0.8772 0.8132 0.036\* H2B 0.8629 0.7322 0.8145 0.036\* H2C 0.9061 0.8896 0.9712 0.036\* C3 0.61532 (13) 0.83957 (14) 0.90149 (13) 0.0222 (2) H3A 0.6156 0.7262 0.8517 0.033\* H3B 0.5263 0.8661 0.8736 0.033\* H3C 0.627 0.8836 1.0122 0.033\* C4 0.73538 (11) 0.90605 (13) 0.85019 (12) 0.0165 (2) C5 0.68030 (10) 0.71782 (12) 0.58068 (12) 0.0145 (2) C6 0.63194 (11) 0.69956 (12) 0.42678 (12) 0.0151 (2) H6 0.7064 0.7491 0.3939 0.018\* C7 0.49600 (11) 0.77696 (12) 0.43670 (12) 0.0152 (2) H7 0.5149 0.891 0.5094 0.018\* C8 0.44465 (12) 0.75423 (15) 0.28179 (13) 0.0223 (2) H8A 0.3603 0.8085 0.2919 0.033\* H8B 0.4228 0.643 0.2101 0.033\* H8C 0.5178 0.7965 0.2438 0.033\* C9 0.12195 (11) 0.73713 (13) 0.43575 (12) 0.0166 (2) C10 0.05152 (11) 0.58888 (13) 0.37062 (13) 0.0177 (2) H10 0.0739 0.5198 0.4067 0.021\* C11 −0.05154 (11) 0.54303 (14) 0.25272 (13) 0.0197 (2) H11 −0.0984 0.4414 0.2071 0.024\* C12 −0.08741 (11) 0.64442 (15) 0.19995 (13) 0.0209 (2) C13 −0.01768 (12) 0.79315 (15) 0.26927 (14) 0.0233 (2) H13 −0.0425 0.8639 0.2362 0.028\* C14 0.08753 (12) 0.84021 (14) 0.38584 (14) 0.0215 (2) H14 0.1352 0.9413 0.4308 0.026\* C15 −0.19933 (13) 0.59239 (18) 0.07100 (15) 0.0296 (3) H15A −0.1592 0.5302 −0.0263 0.044\* H15B −0.2358 0.6838 0.0733 0.044\* H15C −0.2756 0.5295 0.0824 0.044\* N1 0.39695 (9) 0.71013 (11) 0.50168 (10) 0.01484 (18) O1 0.70108 (8) 0.86607 (8) 0.68847 (8) 0.01528 (15) O2 0.69788 (8) 0.60683 (9) 0.59739 (9) 0.01913 (17) O3 0.60741 (8) 0.53975 (9) 0.31707 (9) 0.01922 (17) H3 0.6564 0.4879 0.3431 0.029\* O4 0.21687 (9) 0.71817 (10) 0.66814 (9) 0.02355 (18) O5 0.29082 (9) 0.95624 (10) 0.65376 (10) 0.02641 (19) S1 0.25877 (3) 0.79036 (3) 0.58022 (3) 0.01691 (8) H1D 0.3859 (16) 0.6124 (18) 0.4581 (17) 0.025 (4)\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1400 .table-wrap} ----- -------------- -------------- -------------- ------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0283 (6) 0.0164 (5) 0.0150 (5) −0.0004 (4) −0.0005 (4) 0.0059 (4) C2 0.0216 (5) 0.0238 (6) 0.0233 (6) 0.0015 (4) −0.0067 (4) 0.0095 (5) C3 0.0261 (6) 0.0222 (5) 0.0196 (5) 0.0003 (4) 0.0039 (4) 0.0114 (5) C4 0.0196 (5) 0.0169 (5) 0.0124 (5) 0.0001 (4) −0.0021 (4) 0.0072 (4) C5 0.0108 (4) 0.0148 (5) 0.0162 (5) 0.0007 (4) 0.0006 (4) 0.0065 (4) C6 0.0152 (5) 0.0141 (5) 0.0140 (5) 0.0003 (4) 0.0008 (4) 0.0055 (4) C7 0.0159 (5) 0.0144 (5) 0.0160 (5) 0.0000 (4) −0.0002 (4) 0.0083 (4) C8 0.0221 (5) 0.0290 (6) 0.0201 (5) 0.0010 (4) −0.0021 (4) 0.0159 (5) C9 0.0138 (5) 0.0186 (5) 0.0178 (5) 0.0042 (4) 0.0029 (4) 0.0088 (4) C10 0.0153 (5) 0.0201 (5) 0.0206 (5) 0.0044 (4) 0.0031 (4) 0.0119 (4) C11 0.0152 (5) 0.0230 (5) 0.0211 (5) 0.0016 (4) 0.0018 (4) 0.0112 (5) C12 0.0135 (5) 0.0337 (6) 0.0211 (5) 0.0060 (4) 0.0051 (4) 0.0171 (5) C13 0.0196 (5) 0.0310 (6) 0.0306 (6) 0.0089 (5) 0.0064 (5) 0.0229 (5) C14 0.0192 (5) 0.0197 (5) 0.0287 (6) 0.0046 (4) 0.0042 (4) 0.0140 (5) C15 0.0204 (6) 0.0507 (8) 0.0263 (6) 0.0044 (5) 0.0003 (5) 0.0256 (6) N1 0.0145 (4) 0.0121 (4) 0.0174 (4) 0.0014 (3) 0.0016 (3) 0.0068 (4) O1 0.0187 (4) 0.0130 (3) 0.0129 (3) 0.0001 (3) −0.0015 (3) 0.0058 (3) O2 0.0199 (4) 0.0148 (4) 0.0221 (4) 0.0016 (3) −0.0027 (3) 0.0090 (3) O3 0.0220 (4) 0.0143 (4) 0.0157 (4) 0.0026 (3) −0.0009 (3) 0.0031 (3) O4 0.0227 (4) 0.0316 (5) 0.0163 (4) 0.0011 (3) 0.0028 (3) 0.0118 (4) O5 0.0257 (4) 0.0159 (4) 0.0268 (4) 0.0034 (3) 0.0006 (3) 0.0022 (3) S1 0.01644 (13) 0.01627 (13) 0.01483 (13) 0.00257 (9) 0.00163 (9) 0.00506 (10) ----- -------------- -------------- -------------- ------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1795 .table-wrap} ----------------------- -------------- --------------------- -------------- C1---C4 1.5218 (15) C8---H8B 0.98 C1---H1A 0.98 C8---H8C 0.98 C1---H1B 0.98 C9---C14 1.3921 (15) C1---H1C 0.98 C9---C10 1.3949 (15) C2---C4 1.5235 (15) C9---S1 1.7733 (11) C2---H2A 0.98 C10---C11 1.3881 (15) C2---H2B 0.98 C10---H10 0.95 C2---H2C 0.98 C11---C12 1.4012 (16) C3---C4 1.5245 (16) C11---H11 0.95 C3---H3A 0.98 C12---C13 1.3938 (18) C3---H3B 0.98 C12---C15 1.5106 (16) C3---H3C 0.98 C13---C14 1.3914 (17) C4---O1 1.4978 (12) C13---H13 0.95 C5---O2 1.2115 (13) C14---H14 0.95 C5---O1 1.3277 (12) C15---H15A 0.98 C5---C6 1.5244 (14) C15---H15B 0.98 C6---O3 1.4161 (12) C15---H15C 0.98 C6---C7 1.5353 (14) N1---S1 1.6172 (9) C6---H6 1 N1---H1D 0.842 (16) C7---N1 1.4750 (13) O3---H3 0.84 C7---C8 1.5245 (15) O4---S1 1.4422 (9) C7---H7 1 O5---S1 1.4393 (9) C8---H8A 0.98 C4---C1---H1A 109.5 C7---C8---H8B 109.5 C4---C1---H1B 109.5 H8A---C8---H8B 109.5 H1A---C1---H1B 109.5 C7---C8---H8C 109.5 C4---C1---H1C 109.5 H8A---C8---H8C 109.5 H1A---C1---H1C 109.5 H8B---C8---H8C 109.5 H1B---C1---H1C 109.5 C14---C9---C10 120.57 (10) C4---C2---H2A 109.5 C14---C9---S1 120.59 (9) C4---C2---H2B 109.5 C10---C9---S1 118.82 (8) H2A---C2---H2B 109.5 C11---C10---C9 119.49 (10) C4---C2---H2C 109.5 C11---C10---H10 120.3 H2A---C2---H2C 109.5 C9---C10---H10 120.3 H2B---C2---H2C 109.5 C10---C11---C12 120.95 (11) C4---C3---H3A 109.5 C10---C11---H11 119.5 C4---C3---H3B 109.5 C12---C11---H11 119.5 H3A---C3---H3B 109.5 C13---C12---C11 118.43 (10) C4---C3---H3C 109.5 C13---C12---C15 121.30 (11) H3A---C3---H3C 109.5 C11---C12---C15 120.27 (11) H3B---C3---H3C 109.5 C14---C13---C12 121.41 (10) O1---C4---C1 102.44 (8) C14---C13---H13 119.3 O1---C4---C2 109.60 (9) C12---C13---H13 119.3 C1---C4---C2 111.41 (9) C13---C14---C9 119.13 (11) O1---C4---C3 108.99 (9) C13---C14---H14 120.4 C1---C4---C3 111.22 (9) C9---C14---H14 120.4 C2---C4---C3 112.66 (10) C12---C15---H15A 109.5 O2---C5---O1 125.85 (10) C12---C15---H15B 109.5 O2---C5---C6 122.05 (9) H15A---C15---H15B 109.5 O1---C5---C6 112.09 (9) C12---C15---H15C 109.5 O3---C6---C5 109.87 (8) H15A---C15---H15C 109.5 O3---C6---C7 108.58 (8) H15B---C15---H15C 109.5 C5---C6---C7 110.83 (8) C7---N1---S1 123.52 (7) O3---C6---H6 109.2 C7---N1---H1D 116.2 (10) C5---C6---H6 109.2 S1---N1---H1D 112.5 (10) C7---C6---H6 109.2 C5---O1---C4 119.50 (8) N1---C7---C8 114.28 (9) C6---O3---H3 109.5 N1---C7---C6 105.79 (8) O5---S1---O4 120.06 (5) C8---C7---C6 110.98 (9) O5---S1---N1 107.61 (5) N1---C7---H7 108.5 O4---S1---N1 105.57 (5) C8---C7---H7 108.5 O5---S1---C9 108.09 (5) C6---C7---H7 108.5 O4---S1---C9 106.33 (5) C7---C8---H8A 109.5 N1---S1---C9 108.80 (5) O2---C5---C6---O3 2.43 (14) S1---C9---C14---C13 178.17 (9) O1---C5---C6---O3 −178.31 (8) C8---C7---N1---S1 −76.81 (11) O2---C5---C6---C7 122.43 (11) C6---C7---N1---S1 160.79 (7) O1---C5---C6---C7 −58.31 (11) O2---C5---O1---C4 −6.69 (15) O3---C6---C7---N1 67.16 (10) C6---C5---O1---C4 174.08 (8) C5---C6---C7---N1 −53.61 (11) C1---C4---O1---C5 −178.29 (9) O3---C6---C7---C8 −57.32 (11) C2---C4---O1---C5 63.33 (12) C5---C6---C7---C8 −178.09 (9) C3---C4---O1---C5 −60.39 (12) C14---C9---C10---C11 1.46 (16) C7---N1---S1---O5 −33.34 (10) S1---C9---C10---C11 −177.12 (8) C7---N1---S1---O4 −162.69 (8) C9---C10---C11---C12 −1.07 (17) C7---N1---S1---C9 83.54 (9) C10---C11---C12---C13 −0.37 (17) C14---C9---S1---O5 15.26 (11) C10---C11---C12---C15 179.70 (10) C10---C9---S1---O5 −166.16 (9) C11---C12---C13---C14 1.47 (17) C14---C9---S1---O4 145.40 (9) C15---C12---C13---C14 −178.60 (11) C10---C9---S1---O4 −36.01 (10) C12---C13---C14---C9 −1.10 (18) C14---C9---S1---N1 −101.32 (10) C10---C9---C14---C13 −0.39 (17) C10---C9---S1---N1 77.26 (9) ----------------------- -------------- --------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2586 .table-wrap} ------------------- ------------ ------------ ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1D···O2^i^ 0.842 (16) 2.059 (16) 2.8625 (12) 159.5 (14) O3---H3···O4^i^ 0.84 2.40 3.2041 (12) 162 C1---H1C···O4^ii^ 0.98 2.54 3.4936 (14) 164 ------------------- ------------ ------------ ------------- --------------- ::: Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, −y+2, −z+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- ------------ ------------ ------------- ------------- N1---H1D⋯O2^i^ 0.842 (16) 2.059 (16) 2.8625 (12) 159.5 (14) O3---H3⋯O4^i^ 0.84 2.40 3.2041 (12) 162 C1---H1C⋯O4^ii^ 0.98 2.54 3.4936 (14) 164 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.593258	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052123/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o648", "authors": [ { "first": "Mohamed I.", "last": "Fadlalla" }, { "first": "Holger B.", "last": "Friedrich" }, { "first": "Glenn E. M.", "last": "Maguire" }, { "first": "Bernard", "last": "Omondi" } ] }
PMC3052124	Related literature {#sec1} ================== For background to the coordination chemistry of 1,10-phenanthroline derivatives, see: Wang et al. (2010[@bb7]). For the synthetic procedure, see: Steck & Day (1943[@bb6]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~23~H~14~N~4~OM ~r~ = 362.38Tetragonal,a = 22.5800 (4) Åc = 13.7196 (5) ÅV = 6995.0 (3) Å^3^Z = 16Mo Kα radiationμ = 0.09 mm^−1^T = 293 K0.30 × 0.21 × 0.18 mm ### Data collection {#sec2.1.2} Bruker APEX diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb4]) T ~min~ = 0.41, T ~max~ = 0.7218374 measured reflections3433 independent reflections3153 reflections with I \> 2σ(I)R ~int~ = 0.022 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.031wR(F ^2^) = 0.081S = 1.063433 reflections253 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.14 e Å^−3^Absolute structure: Flack (1983[@bb3]), 1629 Friedel pairsFlack parameter: 0.0 (13) {#d5e416} Data collection: SMART (Bruker, 1997[@bb1]); cell refinement: SAINT (Bruker, 1999[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb5]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005861/lh5209sup1.cif](http://dx.doi.org/10.1107/S1600536811005861/lh5209sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005861/lh5209Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005861/lh5209Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5209&file=lh5209sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5209sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5209&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5209](http://scripts.iucr.org/cgi-bin/sendsup?lh5209)). The authors thank the Key Laboratory of Preparation and Applications of Environmentally Friendly Materials and the Institute Foundation of Siping City (No. 2009011) for supporting this work. Comment ======= 1,10-Phenanthroline and its derivatives, are potentially important chelating ligands with excellent coordinating abilities and have been extensively used to build supramolecular architectures (Wang et al., 2010). We report herein the synthesis and crystal structure of the title compound The molecular structure of the title compound is shown in Fig. 1. The dihedral angle between the pyridine rings of the phenanthroline unit \[N2/C4-C8 and N1/C1/C2/C3/C11/C23\] is 4.43 (8)Å and the dihedral angle formed by the nine essentially planar non-hydrogen atoms of the benzimidazole unit \[C3/C4/C8-C12; maximum deviation 0.0389 (16)Å for C4\] and the naphthalene ring system is 74.22 (5)°. In the crystal, molecules are linked by intermolecular N---H···N and O---H···N hydrogen bonds to form a three-dimensional network. Experimental {#experimental} ============ The title compound was synthesized according to the literature method of Steck & Day (1943). We carried out the following reaction but the unreacted title compound was found in the reaction vessel. A mixture of Bi(NO~3~)~3~^.^5H~2~O (0.5 mmol) and L (0.5 mmol) in 10 mL distilled water was heated at 463 K in a Teflon-lined stainless steel autoclave for three days. The reaction system was then slowly cooled to room temperature. Pale yellow crystals suitable for single crystal X-ray diffraction analysis were collected from the final reaction system. Refinement {#refinement} ========== All H atoms were positioned geometrically (N---H = 0.86, C---H = 0.93 and O---H = 0.82 Å ) and refined as riding, with U~iso~(H) = 1.2U~eq~(C,N) or U~iso~(H) = 1.5U~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of of the title compound showing displacement ellipsoids drawn at the 30% probability. ::: ![](e-67-0o725-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e116 .table-wrap} ------------------------- --------------------------------------- C~23~H~14~N~4~O D~x~ = 1.376 Mg m^−3^ M~r~ = 362.38 Mo Kα radiation, λ = 0.71073 Å Tetragonal, I4~1~cd Cell parameters from 3433 reflections Hall symbol: I 4bw -2c θ = 1.8--26.0° a = 22.5800 (4) Å µ = 0.09 mm^−1^ c = 13.7196 (5) Å T = 293 K V = 6995.0 (3) Å^3^ Block, pale yellow Z = 16 0.30 × 0.21 × 0.18 mm F(000) = 3008 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e236 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEX diffractometer 3433 independent reflections Radiation source: fine-focus sealed tube 3153 reflections with I \> 2σ(I) graphite R~int~ = 0.022 φ and ω scans θ~max~ = 26.0°, θ~min~ = 1.8° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −27→27 T~min~ = 0.41, T~max~ = 0.72 k = −27→20 18374 measured reflections l = −16→16 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e353 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.031 H-atom parameters constrained wR(F^2^) = 0.081 w = 1/\[σ^2^(F~o~^2^) + (0.0457P)^2^ + 1.1603P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.06 (Δ/σ)~max~ = 0.001 3433 reflections Δρ~max~ = 0.12 e Å^−3^ 253 parameters Δρ~min~ = −0.14 e Å^−3^ 1 restraint Absolute structure: Flack (1983), 1629 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.0 (13) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e515 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e560 .table-wrap} ----- -------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ N4 0.15231 (6) 0.04557 (6) 0.26423 (9) 0.0422 (3) H4 0.1345 0.0224 0.3045 0.051\ O1 0.15580 (7) 0.17926 (6) 0.40232 (9) 0.0690 (4) H1 0.1466 0.2049 0.4418 0.104\* N1 0.14620 (7) 0.08057 (7) −0.13144 (9) 0.0534 (4) C14 0.19348 (7) 0.14069 (7) 0.44439 (12) 0.0468 (4) N2 0.08332 (6) −0.01202 (7) −0.06297 (11) 0.0569 (4) C4 0.11269 (7) 0.02173 (7) 0.00293 (11) 0.0442 (4) C12 0.19309 (6) 0.08738 (6) 0.28685 (10) 0.0389 (3) N3 0.21230 (5) 0.11616 (5) 0.20892 (9) 0.0398 (3) C11 0.18392 (7) 0.10501 (6) 0.02914 (10) 0.0386 (3) C3 0.14849 (6) 0.07058 (7) −0.03403 (10) 0.0421 (3) C18 0.25212 (6) 0.05078 (7) 0.42951 (11) 0.0437 (3) C13 0.21381 (7) 0.09461 (7) 0.38867 (11) 0.0410 (3) C20 0.31013 (8) −0.03905 (8) 0.41619 (17) 0.0641 (5) H20 0.3238 −0.0707 0.3791 0.077\* C9 0.14476 (6) 0.04705 (6) 0.16521 (10) 0.0390 (3) C1 0.21610 (9) 0.15939 (8) −0.11023 (13) 0.0585 (5) H1A 0.2389 0.1889 −0.1391 0.070\* C19 0.27385 (7) 0.00224 (8) 0.37510 (13) 0.0516 (4) H19 0.2632 −0.0016 0.3099 0.062\* C21 0.30698 (8) 0.01212 (10) 0.56875 (15) 0.0677 (6) H21 0.3185 0.0151 0.6337 0.081\* C15 0.21017 (8) 0.14513 (9) 0.54344 (13) 0.0576 (4) H15 0.1961 0.1762 0.5815 0.069\* C8 0.10968 (7) 0.01000 (7) 0.10380 (11) 0.0422 (3) C10 0.18153 (6) 0.09101 (6) 0.13142 (10) 0.0373 (3) C7 0.07478 (8) −0.03699 (8) 0.13643 (14) 0.0582 (4) H7 0.0721 −0.0458 0.2025 0.070\* C17 0.26900 (7) 0.05588 (8) 0.52860 (13) 0.0516 (4) C2 0.17893 (9) 0.12442 (9) −0.16609 (13) 0.0613 (5) H2 0.1768 0.1323 −0.2325 0.074\* C16 0.24695 (8) 0.10373 (10) 0.58300 (13) 0.0601 (5) H16 0.2578 0.1073 0.6481 0.072\* C5 0.05054 (10) −0.05570 (10) −0.02947 (17) 0.0720 (6) H5 0.0300 −0.0787 −0.0744 0.086\* C6 0.04461 (9) −0.06976 (9) 0.06877 (17) 0.0729 (6) H6 0.0205 −0.1010 0.0882 0.087\* C23 0.21879 (8) 0.14991 (7) −0.01156 (12) 0.0473 (4) H23 0.2433 0.1729 0.0276 0.057\* C22 0.32682 (9) −0.03397 (10) 0.51413 (19) 0.0726 (6) H22 0.3516 −0.0623 0.5419 0.087\* ----- -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1147 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ N4 0.0482 (7) 0.0475 (7) 0.0308 (6) −0.0029 (6) 0.0025 (5) 0.0074 (5) O1 0.0956 (10) 0.0655 (8) 0.0461 (7) 0.0325 (7) −0.0183 (7) −0.0127 (6) N1 0.0634 (9) 0.0683 (9) 0.0286 (6) 0.0102 (7) 0.0019 (6) −0.0026 (6) C14 0.0506 (8) 0.0539 (9) 0.0358 (8) 0.0075 (7) −0.0057 (7) 0.0015 (7) N2 0.0590 (8) 0.0651 (9) 0.0467 (8) −0.0034 (7) 0.0024 (7) −0.0196 (7) C4 0.0427 (8) 0.0511 (9) 0.0387 (8) 0.0058 (7) 0.0031 (6) −0.0095 (7) C12 0.0418 (7) 0.0431 (7) 0.0318 (7) 0.0050 (6) −0.0003 (6) 0.0024 (6) N3 0.0430 (6) 0.0443 (6) 0.0321 (6) 0.0014 (5) 0.0008 (5) 0.0029 (5) C11 0.0424 (7) 0.0433 (8) 0.0303 (7) 0.0072 (6) 0.0043 (6) 0.0024 (6) C3 0.0438 (8) 0.0503 (8) 0.0321 (8) 0.0092 (6) 0.0043 (6) −0.0041 (6) C18 0.0381 (7) 0.0521 (8) 0.0409 (8) −0.0018 (6) −0.0005 (6) 0.0117 (7) C13 0.0442 (8) 0.0489 (8) 0.0299 (7) 0.0002 (6) −0.0014 (6) 0.0058 (6) C20 0.0497 (9) 0.0542 (10) 0.0883 (15) 0.0043 (7) 0.0029 (10) 0.0120 (10) C9 0.0421 (7) 0.0444 (8) 0.0304 (7) 0.0022 (6) 0.0033 (6) 0.0036 (6) C1 0.0691 (11) 0.0645 (11) 0.0417 (9) 0.0023 (8) 0.0123 (8) 0.0152 (8) C19 0.0458 (8) 0.0523 (9) 0.0566 (10) 0.0011 (7) 0.0016 (7) 0.0069 (8) C21 0.0561 (10) 0.0880 (15) 0.0590 (11) −0.0003 (10) −0.0157 (9) 0.0290 (10) C15 0.0649 (10) 0.0704 (11) 0.0375 (9) 0.0043 (8) −0.0026 (8) −0.0084 (8) C8 0.0417 (8) 0.0443 (8) 0.0405 (8) 0.0017 (6) 0.0039 (6) −0.0036 (6) C10 0.0398 (7) 0.0424 (8) 0.0297 (7) 0.0029 (6) 0.0016 (6) 0.0008 (6) C7 0.0633 (11) 0.0557 (10) 0.0557 (11) −0.0100 (8) 0.0084 (8) 0.0002 (8) C17 0.0441 (8) 0.0673 (10) 0.0433 (9) −0.0035 (7) −0.0061 (7) 0.0154 (8) C2 0.0767 (12) 0.0770 (12) 0.0302 (8) 0.0113 (10) 0.0063 (8) 0.0087 (8) C16 0.0627 (10) 0.0864 (13) 0.0314 (7) −0.0018 (10) −0.0115 (8) 0.0070 (8) C5 0.0764 (13) 0.0718 (12) 0.0679 (13) −0.0183 (10) 0.0033 (11) −0.0268 (11) C6 0.0809 (13) 0.0620 (12) 0.0756 (15) −0.0267 (10) 0.0108 (11) −0.0115 (10) C23 0.0529 (9) 0.0505 (9) 0.0387 (8) 0.0023 (7) 0.0061 (7) 0.0043 (7) C22 0.0569 (11) 0.0678 (13) 0.0932 (16) 0.0089 (9) −0.0099 (11) 0.0312 (12) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1670 .table-wrap} ----------------- ------------- ----------------- ------------- N4---C12 1.3548 (19) C20---H20 0.9300 N4---C9 1.3697 (19) C9---C10 1.375 (2) N4---H4 0.8600 C9---C8 1.427 (2) O1---C14 1.3476 (18) C1---C23 1.372 (2) O1---H1 0.8200 C1---C2 1.384 (3) N1---C2 1.324 (2) C1---H1A 0.9300 N1---C3 1.3563 (19) C19---H19 0.9300 C14---C13 1.370 (2) C21---C22 1.358 (3) C14---C15 1.414 (2) C21---C17 1.420 (2) N2---C5 1.316 (3) C21---H21 0.9300 N2---C4 1.356 (2) C15---C16 1.363 (3) C4---C8 1.411 (2) C15---H15 0.9300 C4---C3 1.459 (2) C8---C7 1.395 (2) C12---N3 1.3241 (18) C7---C6 1.369 (3) C12---C13 1.482 (2) C7---H7 0.9300 N3---C10 1.3912 (19) C17---C16 1.404 (3) C11---C23 1.400 (2) C2---H2 0.9300 C11---C3 1.413 (2) C16---H16 0.9300 C11---C10 1.4394 (19) C5---C6 1.391 (3) C18---C19 1.414 (2) C5---H5 0.9300 C18---C17 1.417 (2) C6---H6 0.9300 C18---C13 1.429 (2) C23---H23 0.9300 C20---C19 1.363 (3) C22---H22 0.9300 C20---C22 1.400 (3) C12---N4---C9 107.15 (12) C20---C19---H19 119.3 C12---N4---H4 126.4 C18---C19---H19 119.3 C9---N4---H4 126.4 C22---C21---C17 121.23 (19) C14---O1---H1 109.5 C22---C21---H21 119.4 C2---N1---C3 117.19 (16) C17---C21---H21 119.4 O1---C14---C13 117.60 (14) C16---C15---C14 119.76 (17) O1---C14---C15 122.28 (14) C16---C15---H15 120.1 C13---C14---C15 120.07 (14) C14---C15---H15 120.1 C5---N2---C4 117.62 (16) C7---C8---C4 118.98 (16) N2---C4---C8 121.68 (15) C7---C8---C9 124.73 (15) N2---C4---C3 117.67 (14) C4---C8---C9 116.26 (14) C8---C4---C3 120.64 (14) C9---C10---N3 109.79 (12) N3---C12---N4 112.31 (13) C9---C10---C11 120.66 (13) N3---C12---C13 127.13 (13) N3---C10---C11 129.55 (13) N4---C12---C13 120.47 (13) C6---C7---C8 118.34 (18) C12---N3---C10 104.67 (11) C6---C7---H7 120.8 C23---C11---C3 118.18 (14) C8---C7---H7 120.8 C23---C11---C10 124.68 (14) C16---C17---C18 118.50 (15) C3---C11---C10 117.14 (13) C16---C17---C21 122.93 (18) N1---C3---C11 122.32 (15) C18---C17---C21 118.57 (18) N1---C3---C4 116.56 (14) N1---C2---C1 124.50 (16) C11---C3---C4 121.11 (13) N1---C2---H2 117.8 C19---C18---C17 118.45 (15) C1---C2---H2 117.8 C19---C18---C13 122.67 (14) C15---C16---C17 122.14 (16) C17---C18---C13 118.88 (15) C15---C16---H16 118.9 C14---C13---C18 120.65 (14) C17---C16---H16 118.9 C14---C13---C12 120.25 (13) N2---C5---C6 124.30 (18) C18---C13---C12 118.97 (14) N2---C5---H5 117.9 C19---C20---C22 120.18 (19) C6---C5---H5 117.9 C19---C20---H20 119.9 C7---C6---C5 119.06 (18) C22---C20---H20 119.9 C7---C6---H6 120.5 N4---C9---C10 106.07 (13) C5---C6---H6 120.5 N4---C9---C8 129.82 (13) C1---C23---C11 118.80 (17) C10---C9---C8 124.02 (13) C1---C23---H23 120.6 C23---C1---C2 118.97 (17) C11---C23---H23 120.6 C23---C1---H1A 120.5 C21---C22---C20 120.22 (17) C2---C1---H1A 120.5 C21---C22---H22 119.9 C20---C19---C18 121.35 (17) C20---C22---H22 119.9 ----------------- ------------- ----------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2252 .table-wrap} ------------------ --------- --------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N4---H4···N2^i^ 0.86 2.17 2.9361 (19) 149 N4---H4···N1^i^ 0.86 2.50 3.191 (2) 138 O1---H1···N3^ii^ 0.82 2.01 2.7203 (17) 145 ------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (i) x, −y, z+1/2; (ii) y, −x+1/2, z+1/4. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ------------- ------------- N4---H4⋯N2^i^ 0.86 2.17 2.9361 (19) 149 N4---H4⋯N1^i^ 0.86 2.50 3.191 (2) 138 O1---H1⋯N3^ii^ 0.82 2.01 2.7203 (17) 145 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.598998	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052124/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o725", "authors": [ { "first": "Xiu-Yan", "last": "Wang" }, { "first": "Shuai", "last": "Ma" }, { "first": "Yu", "last": "He" } ] }
PMC3052125	Related literature {#sec1} ================== For the synthesis and pharmacological activity of compounds containing indole and tetrazole groups, see: Itoh et al. (1995[@bb3]); Semenov (2002[@bb5]). For the synthesis of 6-cyanoindole, a starting material for the title compound, see: Frederick (1949[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~9~H~7~N~5~·H~2~OM ~r~ = 203.21Monoclinic,a = 17.175 (3) Åb = 4.0653 (8) Åc = 14.421 (3) Åβ = 107.59 (3)°V = 959.8 (3) Å^3^Z = 4Mo Kα radiationμ = 0.10 mm^−1^T = 293 K0.20 × 0.05 × 0.05 mm ### Data collection {#sec2.1.2} Rigaku Mercury2 diffractometerAbsorption correction: multi-scan (CrystalClear; Rigaku, 2005[@bb4]) T ~min~ = 0.737, T ~max~ = 1.0007430 measured reflections1683 independent reflections945 reflections with I \> 2σ(I)R ~int~ = 0.120 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.066wR(F ^2^) = 0.131S = 1.011683 reflections144 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.15 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e466} Data collection: CrystalClear (Rigaku, 2005[@bb4]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb6]) and DIAMOND (Brandenburg, 2006[@bb1]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003990/lh5195sup1.cif](http://dx.doi.org/10.1107/S1600536811003990/lh5195sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003990/lh5195Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003990/lh5195Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5195&file=lh5195sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5195sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5195&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5195](http://scripts.iucr.org/cgi-bin/sendsup?lh5195)). Comment ======= In recent decades, there have been some reports on the compounds which are synthesized by the combination of the tetrazole and indole rings (Itoh et al.,1995) and property studies reveals that these compounds always perform unique pharmacological activities (Semenov et al., 2002). In order to obtain such compounds, we have attempted to synthesize the indole compounds with tetrazole as a substituent. Herein, we report the crystal structure of the title compound (I). The molecular structure of (1) is shown in Fig. 1. The indole unit is essentially planar, with a mean deviation of 0.007 (8)Å from the least-squares plane defined by the nine constituent atoms. The dihedral angle formed by the indole plane and the tetrazole ring is 1.82 (1)°. The crystal packing (Fig. 2) is stabilized by intermolecular O-H···N, N---H···O and N---H···N hydrogen bonds (Table 1). Further stabilization is provided by aromatic π--π interactions with a Cg1···Cg2(x, 1+y, z) distance of 3.698 (2) Å (Cg1 and Cg2 are the centroids of the N5/C4-C7 and C2-C4/C7-C9 rings, respectively). Experimental {#experimental} ============ All chemicals used (reagent grade) were commercially available. 6-Cyanoindole was synthesized following the methods described by Frederick (1949). To the stirring DMF solution of NaN~3~ and triethylamine, 6-cyanoindole was added. Then the mixture was heated to 120, about 1 h later, the solution was cooled to room temperature, and DMF was distilled in a vacuum. With some follow-up treatment, the crude product was recrystallized in methanol solution and seven days later, yellow prism crystal was obtained. Refinement {#refinement} ========== H atoms bound to C and N atoms were placed in calculated positions and refined using a riding model, with C---H = 0.94Å and U~iso~(H) =1.2U~eq~(C) or N---H = 0.86Å and U~iso~(H) =1.5U~eq~(N) . The H atoms of the water molecule were located in a difference map and refined freely. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o692-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds and π--π interactions shown as dashed lines. Only H atoms involed in hydrogen bonds are shown. CP denotes a ring centroid. \[Symmetry codes: (i) x, y-1,z; (ii) -x+1, y+1/2, -z+1/2; (iii)x, -y+1/2, z-1/2; (iv) x, -y+3/2, z-1/2\] ::: ![](e-67-0o692-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e139 .table-wrap} ------------------------- --------------------------------------- C~9~H~7~N~5~·H~2~O F(000) = 424 M~r~ = 203.21 D~x~ = 1.406 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 2795 reflections a = 17.175 (3) Å θ = 3.1--27.5° b = 4.0653 (8) Å µ = 0.10 mm^−1^ c = 14.421 (3) Å T = 293 K β = 107.59 (3)° Needle, colorless V = 959.8 (3) Å^3^ 0.20 × 0.05 × 0.05 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} ------------------------------------------------------------------ ------------------------------------- Rigaku Mercury2 diffractometer 1683 independent reflections Radiation source: fine-focus sealed tube 945 reflections with I \> 2σ(I) graphite R~int~ = 0.120 Detector resolution: 13.6612 pixels mm^-1^ θ~max~ = 25.0°, θ~min~ = 3.2° CCD\_Profile\_fitting scans h = −20→20 Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) k = −4→4 T~min~ = 0.737, T~max~ = 1.000 l = −17→17 7430 measured reflections ------------------------------------------------------------------ ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.066 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.131 H atoms treated by a mixture of independent and constrained refinement S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.0398P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 1683 reflections (Δ/σ)~max~ \< 0.001 144 parameters Δρ~max~ = 0.15 e Å^−3^ 0 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e542 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e587 .table-wrap} ----- -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.0699 (2) −0.0517 (10) 0.1761 (2) 0.0720 (10) H1A 0.088 (2) −0.161 (10) 0.132 (3) 0.095 (17)\ H1B 0.033 (3) 0.048 (11) 0.147 (3) 0.10 (2)\* N1 0.19161 (16) −0.0016 (7) 0.5257 (2) 0.0453 (8) N2 0.12138 (17) −0.1708 (7) 0.5143 (2) 0.0518 (9) N3 0.08061 (16) −0.1971 (7) 0.4227 (2) 0.0509 (9) N4 0.12440 (15) −0.0389 (7) 0.37351 (19) 0.0415 (8) H4N 0.1108 −0.0189 0.3113 0.062\* N5 0.32387 (16) 0.6304 (7) 0.21458 (19) 0.0442 (8) H5N 0.2898 0.6026 0.1576 0.066\* C1 0.19266 (19) 0.0829 (8) 0.4367 (2) 0.0349 (8) C2 0.25600 (18) 0.2697 (8) 0.4122 (2) 0.0325 (8) C3 0.25007 (18) 0.3476 (8) 0.3176 (2) 0.0349 (8) H3 0.2048 0.2852 0.2666 0.042\* C4 0.31364 (19) 0.5219 (8) 0.3008 (2) 0.0346 (8) C5 0.3976 (2) 0.7902 (8) 0.2348 (2) 0.0436 (9) H5 0.4185 0.8834 0.1884 0.052\* C6 0.4357 (2) 0.7929 (8) 0.3320 (2) 0.0394 (9) H6 0.4862 0.8864 0.3636 0.047\* C7 0.38315 (18) 0.6239 (8) 0.3762 (2) 0.0339 (8) C8 0.38770 (19) 0.5422 (8) 0.4718 (2) 0.0403 (9) H8 0.4327 0.6052 0.5231 0.048\* C9 0.32503 (18) 0.3679 (8) 0.4894 (2) 0.0382 (9) H9 0.3280 0.3136 0.5530 0.046\* ----- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e927 .table-wrap} ---- ------------- ----------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.057 (2) 0.112 (3) 0.0391 (17) 0.0266 (19) 0.0019 (15) −0.0135 (18) N1 0.0348 (18) 0.058 (2) 0.0385 (18) −0.0073 (16) 0.0049 (14) 0.0043 (16) N2 0.0431 (19) 0.069 (2) 0.040 (2) −0.0068 (17) 0.0080 (16) 0.0037 (17) N3 0.0424 (19) 0.064 (2) 0.045 (2) −0.0102 (16) 0.0113 (16) 0.0047 (17) N4 0.0327 (16) 0.056 (2) 0.0329 (16) −0.0036 (15) 0.0047 (14) 0.0050 (15) N5 0.0454 (18) 0.057 (2) 0.0279 (16) 0.0038 (16) 0.0071 (13) 0.0024 (14) C1 0.032 (2) 0.037 (2) 0.032 (2) 0.0057 (16) 0.0037 (16) −0.0009 (16) C2 0.0322 (19) 0.034 (2) 0.0292 (19) 0.0031 (16) 0.0062 (15) −0.0008 (15) C3 0.0297 (18) 0.043 (2) 0.030 (2) 0.0060 (17) 0.0047 (15) −0.0045 (16) C4 0.038 (2) 0.040 (2) 0.0256 (19) 0.0101 (18) 0.0093 (16) 0.0014 (16) C5 0.038 (2) 0.046 (2) 0.048 (2) 0.0017 (19) 0.0154 (18) 0.0049 (19) C6 0.0371 (19) 0.045 (2) 0.034 (2) −0.0005 (18) 0.0075 (17) 0.0021 (17) C7 0.034 (2) 0.037 (2) 0.0288 (19) 0.0045 (16) 0.0072 (16) −0.0011 (16) C8 0.035 (2) 0.051 (2) 0.029 (2) −0.0065 (17) 0.0010 (16) −0.0045 (17) C9 0.041 (2) 0.047 (2) 0.0240 (19) −0.0011 (18) 0.0052 (16) −0.0010 (16) ---- ------------- ----------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1226 .table-wrap} ------------------- ------------ ------------------- ------------ O1---H1A 0.90 (4) C2---C9 1.417 (4) O1---H1B 0.77 (4) C3---C4 1.383 (4) N1---C1 1.333 (4) C3---H3 0.9300 N1---N2 1.355 (3) C4---C7 1.413 (4) N2---N3 1.298 (3) C5---C6 1.355 (4) N3---N4 1.344 (3) C5---H5 0.9300 N4---C1 1.344 (4) C6---C7 1.429 (4) N4---H4N 0.8600 C6---H6 0.9300 N5---C5 1.374 (4) C7---C8 1.397 (4) N5---C4 1.380 (4) C8---C9 1.375 (4) N5---H5N 0.8600 C8---H8 0.9300 C1---C2 1.456 (4) C9---H9 0.9300 C2---C3 1.373 (4) H1A---O1---H1B 106 (4) N5---C4---C3 130.1 (3) C1---N1---N2 106.5 (3) N5---C4---C7 107.0 (3) N3---N2---N1 110.6 (3) C3---C4---C7 122.9 (3) N2---N3---N4 106.4 (2) C6---C5---N5 110.5 (3) C1---N4---N3 109.3 (3) C6---C5---H5 124.8 C1---N4---H4N 125.3 N5---C5---H5 124.8 N3---N4---H4N 125.3 C5---C6---C7 106.6 (3) C5---N5---C4 108.7 (3) C5---C6---H6 126.7 C5---N5---H5N 125.7 C7---C6---H6 126.7 C4---N5---H5N 125.7 C8---C7---C4 118.2 (3) N1---C1---N4 107.2 (3) C8---C7---C6 134.5 (3) N1---C1---C2 126.7 (3) C4---C7---C6 107.3 (3) N4---C1---C2 126.2 (3) C9---C8---C7 119.4 (3) C3---C2---C9 120.6 (3) C9---C8---H8 120.3 C3---C2---C1 121.7 (3) C7---C8---H8 120.3 C9---C2---C1 117.7 (3) C8---C9---C2 121.0 (3) C2---C3---C4 117.8 (3) C8---C9---H9 119.5 C2---C3---H3 121.1 C2---C9---H9 119.5 C4---C3---H3 121.1 C1---N1---N2---N3 1.0 (4) C2---C3---C4---N5 179.7 (3) N1---N2---N3---N4 −0.8 (4) C2---C3---C4---C7 −0.6 (4) N2---N3---N4---C1 0.2 (4) C4---N5---C5---C6 −0.7 (4) N2---N1---C1---N4 −0.9 (4) N5---C5---C6---C7 0.1 (4) N2---N1---C1---C2 179.6 (3) N5---C4---C7---C8 −179.8 (3) N3---N4---C1---N1 0.4 (4) C3---C4---C7---C8 0.5 (5) N3---N4---C1---C2 179.9 (3) N5---C4---C7---C6 −0.8 (3) N1---C1---C2---C3 −178.9 (3) C3---C4---C7---C6 179.4 (3) N4---C1---C2---C3 1.6 (5) C5---C6---C7---C8 179.2 (3) N1---C1---C2---C9 1.5 (5) C5---C6---C7---C4 0.4 (3) N4---C1---C2---C9 −177.9 (3) C4---C7---C8---C9 −0.2 (5) C9---C2---C3---C4 0.4 (5) C6---C7---C8---C9 −178.8 (3) C1---C2---C3---C4 −179.1 (3) C7---C8---C9---C2 0.1 (5) C5---N5---C4---C3 −179.4 (3) C3---C2---C9---C8 −0.2 (5) C5---N5---C4---C7 0.9 (3) C1---C2---C9---C8 179.4 (3) ------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1701 .table-wrap} -------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1A···N2^i^ 0.90 (4) 2.07 (4) 2.957 (4) 169 (4) O1---H1B···N3^ii^ 0.76 (5) 2.17 (5) 2.927 (5) 172 (5) N4---H4N···O1 0.86 1.87 2.715 (4) 169 N5---H5N···N1^iii^ 0.86 2.17 3.019 (4) 171 -------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) x, −y−1/2, z−1/2; (ii) −x, y+1/2, −z+1/2; (iii) x, −y+1/2, z−1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- ---------- ---------- ----------- ------------- O1---H1A⋯N2^i^ 0.90 (4) 2.07 (4) 2.957 (4) 169 (4) O1---H1B⋯N3^ii^ 0.76 (5) 2.17 (5) 2.927 (5) 172 (5) N4---H4N⋯O1 0.86 1.87 2.715 (4) 169 N5---H5N⋯N1^iii^ 0.86 2.17 3.019 (4) 171 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.603536	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052125/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o692", "authors": [ { "first": "Yu-Hua", "last": "Ge" }, { "first": "Pei", "last": "Han" }, { "first": "Ping", "last": "Wei" }, { "first": "Ping-Kai", "last": "Ou-yang" } ] }
PMC3052126	Related literature {#sec1} ================== For a similar compound, see: Ali et al. (2011[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~47~H~58~N~6~O~6~M ~r~ = 802.99Triclinic,a = 19.4751 (6) Åb = 19.7067 (6) Åc = 20.6938 (7) Åα = 113.881 (3)°β = 113.983 (3)°γ = 95.343 (2)°V = 6311.7 (3) Å^3^Z = 6Mo Kα radiationμ = 0.09 mm^−1^T = 100 K0.30 × 0.20 × 0.10 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb1]) T ~min~ = 0.975, T ~max~ = 0.99255060 measured reflections27973 independent reflections17926 reflections with I \> 2σ(I)R ~int~ = 0.044 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.070wR(F ^2^) = 0.185S = 1.0727973 reflections1642 parameters43 restraintsH-atom parameters constrainedΔρ~max~ = 1.01 e Å^−3^Δρ~min~ = −1.30 e Å^−3^ {#d5e402} Data collection: CrysAlis PRO (Agilent, 2010[@bb1]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: X-SEED (Barbour, 2001[@bb3]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb5]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006362/zs2091sup1.cif](http://dx.doi.org/10.1107/S1600536811006362/zs2091sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006362/zs2091Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006362/zs2091Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?zs2091&file=zs2091sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?zs2091sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?zs2091&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [ZS2091](http://scripts.iucr.org/cgi-bin/sendsup?zs2091)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= Some background on di(aryl)methane compounds having oxyacetate substituents was presented in an earlier report (Ali et al., 2011). The title compound also has an N-heterocyclic substituent in the rings (Scheme I). The asymmetric unit of C~47~H~58~N~6~O~6~ consists of three molecules (Figs. 1 to 3), one of which is disordered in one tert-butyl group in a 1:1 ratio. For the molecule having the disordered tert-butyl group, the aryl rings make an angle of 115.3 (2) ° at the methylene carbon with one aryl ring aligned at 42.0 (1) ° with respect to the N-heterocyclic substituent and the other at 48.7 (1) ° with respect to its substituent. The two ordered molecules are disposed about a false center-of-inversion with the pairs of twist angles in the other two molecules different \[52.7 (1) and 61.7 (1)°; 29.1 (1) and 58.5 (1) °\]. Experimental {#experimental} ============ 6,6\'-Methylenebis(2-(2H-benzo\[d\]\[1,2,3\]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol) (0.10 g) and potassium carbonate (0.05 g) were dissolved in acetone (20 ml) at 323 K. Chloromethyl acetate (0.04 ml) was added and the reaction was stirred for 20 h. The progress of the reaction was monitored by thin layer chromatography (hexane:dichloromethane 60:40). The reaction was quenched by adding 1 M hydrochloric acid (10 ml). The aqueous phase was extracted with dichloromethane, the solvent evaporated and the crude product was recrystallized from dichloromethane (yield 80%). Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.98 Å, U~iso~(H) = 1.2 to 1.5U~eq~(C)\] and were included in the refinement in the riding model approximation. One of the tert-butyl groups of one of the three independent molecules is disordered over two positions; the disorder could not be refined, and was assumed to be a 1:1 type of disorder. The C--C~methyl~ bond distance was restrained to 1.50±0.01 and the C···C~methyl~ distance to 2.35±0.01 Å. The displacement parameters of the primed atoms were set to those of the unprimed ones, and the anisotropic displacement parameters were restrained to be nearly isotropic. The anisotropic displacement parameters of the O12 atom were similarly restrained as the ellipsoid was too elongated. The final difference Fourier map had a large peak 0.34 Å from H21F and a hole 0.23 Å from C23\'. One of the H-atoms of C23\' (i.e., H23E) is close to an ordered H18B atom at a distance of 1.78 Å; the interaction is probably an artifact of the disorder. The \'huge\' version of SHELXL97 was used for refining the structure. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of one of the three independent molecules of C47H58N6O6 at the 70% probability level, with hydrogen atoms drawn as spheres of arbitrary radius. The disorder in the tert-butyl group is not shown. ::: ![](e-67-0o722-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the second independent C47H58N6O6 molecule. The molecule is ordered. ::: ![](e-67-0o722-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the third independent C47H58N6O6 molecule. The molecule is ordered. ::: ![](e-67-0o722-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e201 .table-wrap} ----------------------- ---------------------------------------- C~47~H~58~N~6~O~6~ Z = 6 M~r~ = 802.99 F(000) = 2580 Triclinic, P1 D~x~ = 1.268 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 19.4751 (6) Å Cell parameters from 12624 reflections b = 19.7067 (6) Å θ = 2.2--29.3° c = 20.6938 (7) Å µ = 0.09 mm^−1^ α = 113.881 (3)° T = 100 K β = 113.983 (3)° Block, colorless γ = 95.343 (2)° 0.30 × 0.20 × 0.10 mm V = 6311.7 (3) Å^3^ ----------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e337 .table-wrap} ------------------------------------------------------------------- --------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 27973 independent reflections Radiation source: SuperNova (Mo) X-ray Source 17926 reflections with I \> 2σ(I) Mirror R~int~ = 0.044 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.2° ω scans h = −21→24 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −24→24 T~min~ = 0.975, T~max~ = 0.992 l = −26→26 55060 measured reflections ------------------------------------------------------------------- --------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e457 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.070 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.185 H-atom parameters constrained S = 1.07 w = 1/\[σ^2^(F~o~^2^) + (0.0603P)^2^ + 2.8599P\] where P = (F~o~^2^ + 2F~c~^2^)/3 27973 reflections (Δ/σ)~max~ = 0.001 1642 parameters Δρ~max~ = 1.01 e Å^−3^ 43 restraints Δρ~min~ = −1.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e616 .table-wrap} ------- -------------- -------------- --------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) O1 0.73152 (10) 0.56720 (9) 0.77982 (10) 0.0207 (4) O2 0.85523 (11) 0.45200 (10) 0.82251 (11) 0.0260 (4) O3 0.81080 (14) 0.47752 (13) 0.71920 (13) 0.0428 (6) O4 0.90742 (10) 0.73822 (10) 0.70957 (10) 0.0220 (4) O5 1.05002 (10) 0.64625 (11) 0.68355 (11) 0.0276 (4) O6 1.00785 (14) 0.66968 (15) 0.77371 (14) 0.0510 (6) O7 0.39861 (9) 0.90251 (9) 0.28506 (10) 0.0199 (4) O8 0.28531 (11) 1.03092 (10) 0.32003 (11) 0.0292 (4) O9 0.30210 (12) 0.97055 (12) 0.21200 (12) 0.0371 (5) O10 0.57413 (10) 1.07394 (9) 0.21479 (10) 0.0216 (4) O11 0.48334 (11) 1.21343 (10) 0.18105 (11) 0.0278 (4) O12 0.48700 (18) 1.16101 (16) 0.25872 (17) 0.0727 (9) O13 0.75124 (10) 0.58181 (10) 0.28035 (10) 0.0217 (4) O14 0.61810 (10) 0.68267 (10) 0.31868 (11) 0.0267 (4) O15 0.67145 (16) 0.67580 (18) 0.24041 (17) 0.0712 (9) O16 0.92310 (10) 0.75874 (9) 0.21179 (10) 0.0210 (4) O17 0.80837 (11) 0.88388 (11) 0.18169 (11) 0.0305 (4) O18 0.86067 (14) 0.86029 (13) 0.28557 (12) 0.0450 (6) N1 0.62974 (12) 0.57433 (12) 0.85424 (13) 0.0223 (5) N2 0.69904 (11) 0.62930 (11) 0.91052 (12) 0.0183 (4) N3 0.72977 (12) 0.63815 (12) 0.98517 (12) 0.0212 (5) N4 0.91394 (12) 0.84301 (12) 0.63749 (12) 0.0222 (5) N5 0.85063 (11) 0.78069 (11) 0.58118 (12) 0.0183 (4) N6 0.82883 (12) 0.75881 (12) 0.50399 (12) 0.0204 (4) N7 0.40599 (12) 0.80571 (12) 0.36251 (13) 0.0227 (5) N8 0.46353 (11) 0.87336 (11) 0.41788 (12) 0.0183 (4) N9 0.47710 (12) 0.90290 (12) 0.49412 (12) 0.0211 (5) N10 0.59904 (12) 1.00301 (12) 0.01474 (12) 0.0217 (5) N11 0.62368 (12) 1.02063 (11) 0.09157 (12) 0.0193 (4) N12 0.68861 (12) 1.08076 (11) 0.14875 (13) 0.0233 (5) N13 0.74878 (12) 0.46790 (12) 0.34612 (12) 0.0211 (5) N14 0.80490 (11) 0.53557 (11) 0.40402 (12) 0.0180 (4) N15 0.81346 (12) 0.56327 (12) 0.47805 (12) 0.0204 (4) N16 1.01935 (12) 0.75529 (12) 0.13324 (13) 0.0230 (5) N17 0.95471 (12) 0.69412 (11) 0.07873 (12) 0.0184 (4) N18 0.92752 (12) 0.67388 (12) 0.00071 (12) 0.0226 (5) C1 0.61365 (15) 0.54357 (14) 0.89600 (16) 0.0216 (5) C2 0.54644 (16) 0.48354 (15) 0.86945 (18) 0.0274 (6) H2 0.5051 0.4564 0.8148 0.033\ C3 0.54465 (16) 0.46709 (15) 0.92705 (18) 0.0300 (6) H3 0.5008 0.4272 0.9118 0.036\* C4 0.60611 (16) 0.50762 (16) 1.00875 (18) 0.0294 (6) H4 0.6017 0.4943 1.0465 0.035\* C5 0.67123 (16) 0.56490 (16) 1.03508 (18) 0.0276 (6) H5 0.7121 0.5913 1.0899 0.033\* C6 0.67516 (14) 0.58322 (14) 0.97698 (15) 0.0204 (5) C7 0.73651 (14) 0.67915 (14) 0.89162 (15) 0.0178 (5) C8 0.75003 (14) 0.64661 (13) 0.82607 (15) 0.0181 (5) C9 0.78143 (14) 0.69602 (14) 0.80547 (14) 0.0185 (5) C10 0.79896 (14) 0.77637 (14) 0.85179 (15) 0.0204 (5) H10 0.8196 0.8098 0.8371 0.025\* C11 0.78746 (14) 0.80968 (14) 0.91889 (15) 0.0202 (5) C12 0.75618 (14) 0.75877 (14) 0.93844 (15) 0.0197 (5) H12 0.7484 0.7792 0.9843 0.024\* C13 0.77144 (15) 0.52843 (14) 0.82148 (15) 0.0206 (5) H13A 0.7328 0.4917 0.8211 0.025\* H13B 0.8097 0.5671 0.8785 0.025\* C14 0.81423 (15) 0.48462 (14) 0.78077 (15) 0.0217 (5) C15 0.89703 (17) 0.40463 (16) 0.78880 (18) 0.0319 (6) H15A 0.9193 0.3782 0.8199 0.048\* H15B 0.9398 0.4380 0.7914 0.048\* H15C 0.8603 0.3657 0.7322 0.048\* C16 0.81088 (16) 0.89799 (15) 0.97262 (16) 0.0260 (6) C17 0.74943 (16) 0.91726 (16) 1.00037 (17) 0.0307 (6) H17A 0.6963 0.8921 0.9532 0.046\* H17B 0.7596 0.9739 1.0273 0.046\* H17C 0.7533 0.8981 1.0382 0.046\* C18 0.8124 (3) 0.93979 (18) 0.9253 (2) 0.0612 (11) H18A 0.8562 0.9347 0.9136 0.092\* H18B 0.8195 0.9951 0.9574 0.092\* H18C 0.7624 0.9165 0.8743 0.092\* C19 0.89453 (14) 0.92226 (13) 1.04831 (15) 0.0367 (7) H19A 0.8865 0.8910 1.0734 0.044\* H19B 0.9283 0.9013 1.0251 0.044\* C20 0.94440 (15) 1.00016 (14) 1.11614 (16) 0.0381 (7) C21 0.9996 (3) 0.9840 (3) 1.1841 (2) 0.0383 (11) 0.50 H21A 1.0400 1.0329 1.2300 0.057\* 0.50 H21B 1.0252 0.9469 1.1630 0.057\* 0.50 H21C 0.9684 0.9621 1.2020 0.057\* 0.50 C22 0.9083 (3) 1.0520 (3) 1.1501 (3) 0.0340 (13) 0.50 H22A 0.9490 1.0967 1.2015 0.051\* 0.50 H22B 0.8718 1.0250 1.1598 0.051\* 0.50 H22C 0.8792 1.0703 1.1127 0.051\* 0.50 C23 1.0004 (3) 1.0347 (3) 1.0991 (3) 0.0436 (11) 0.50 H23A 1.0412 1.0808 1.1489 0.065\* 0.50 H23B 0.9724 1.0500 1.0584 0.065\* 0.50 H23C 1.0253 0.9964 1.0784 0.065\* 0.50 C21\' 1.0229 (2) 1.0038 (3) 1.1594 (3) 0.0383 (11) 0.50 H21D 1.0555 1.0585 1.1964 0.057\* 0.50 H21E 1.0422 0.9790 1.1215 0.057\* 0.50 H21F 1.0259 0.9766 1.1905 0.057\* 0.50 C22\' 0.9078 (3) 1.0294 (3) 1.1683 (3) 0.0340 (13) 0.50 H22D 0.9442 1.0788 1.2169 0.051\* 0.50 H22E 0.8963 0.9910 1.1842 0.051\* 0.50 H22F 0.8585 1.0378 1.1383 0.051\* 0.50 C23\' 0.9438 (3) 1.0593 (3) 1.0860 (3) 0.0436 (11) 0.50 H23D 0.9754 1.1115 1.1323 0.065\* 0.50 H23E 0.8894 1.0586 1.0568 0.065\* 0.50 H23F 0.9664 1.0456 1.0496 0.065\* 0.50 C24 0.80119 (15) 0.66235 (15) 0.73768 (15) 0.0232 (6) H24A 0.7768 0.6050 0.7074 0.028\* H24B 0.8592 0.6731 0.7619 0.028\* C25 0.77457 (14) 0.69317 (13) 0.67822 (14) 0.0183 (5) C26 0.82864 (14) 0.72557 (14) 0.66195 (15) 0.0188 (5) C27 0.79985 (14) 0.74635 (13) 0.60139 (14) 0.0178 (5) C28 0.72023 (14) 0.73713 (14) 0.55893 (15) 0.0196 (5) H28 0.7025 0.7510 0.5173 0.024\* C29 0.66579 (14) 0.70813 (14) 0.57598 (15) 0.0198 (5) C30 0.69503 (14) 0.68525 (14) 0.63524 (15) 0.0192 (5) H30 0.6588 0.6632 0.6467 0.023\* C31 0.95160 (14) 0.70682 (15) 0.67052 (15) 0.0219 (5) H31A 0.9835 0.7484 0.6698 0.026\* H31B 0.9153 0.6657 0.6139 0.026\* C32 1.00501 (15) 0.67286 (15) 0.71661 (15) 0.0223 (5) C33 1.10627 (16) 0.61398 (16) 0.72295 (17) 0.0292 (6) H33A 1.1392 0.6007 0.6972 0.044\* H33B 1.0779 0.5669 0.7181 0.044\* H33C 1.1399 0.6525 0.7803 0.044\* C34 0.57944 (14) 0.70691 (15) 0.53766 (15) 0.0215 (5) C35 0.56255 (16) 0.75144 (17) 0.60751 (17) 0.0317 (6) H35A 0.6016 0.8035 0.6443 0.048\* H35B 0.5659 0.7227 0.6372 0.048\* H35C 0.5094 0.7565 0.5854 0.048\* C36 0.56638 (15) 0.75121 (15) 0.49003 (16) 0.0239 (6) H36A 0.6004 0.8055 0.5264 0.036\* H36B 0.5110 0.7499 0.4665 0.036\* H36C 0.5794 0.7267 0.4466 0.036\* C37 0.52027 (15) 0.62313 (15) 0.48710 (15) 0.0245 (6) H37A 0.5399 0.5963 0.5191 0.029\* H37B 0.4697 0.6289 0.4855 0.029\* C38 0.49961 (15) 0.56603 (14) 0.39984 (16) 0.0221 (5) C39 0.45560 (16) 0.48536 (16) 0.37917 (18) 0.0327 (7) H39A 0.4910 0.4680 0.4144 0.049\* H39B 0.4380 0.4482 0.3225 0.049\* H39C 0.4096 0.4882 0.3874 0.049\* C40 0.57346 (16) 0.55975 (16) 0.39092 (17) 0.0297 (6) H40A 0.6006 0.6095 0.3995 0.045\* H40B 0.5580 0.5184 0.3364 0.045\* H40C 0.6090 0.5473 0.4311 0.045\* C41 0.44393 (16) 0.58696 (16) 0.33847 (16) 0.0296 (6) H41A 0.4725 0.6350 0.3450 0.044\* H41B 0.3991 0.5949 0.3477 0.044\* H41C 0.4246 0.5444 0.2835 0.044\* C42 0.93656 (14) 0.86362 (14) 0.59234 (16) 0.0215 (5) C43 0.99901 (16) 0.92642 (15) 0.61611 (17) 0.0272 (6) H43 1.0353 0.9616 0.6716 0.033\* C44 1.00488 (16) 0.93427 (16) 0.55597 (17) 0.0278 (6) H44 1.0463 0.9759 0.5700 0.033\* C45 0.95081 (15) 0.88207 (15) 0.47293 (17) 0.0261 (6) H45 0.9570 0.8903 0.4332 0.031\* C46 0.89053 (16) 0.82077 (15) 0.44817 (16) 0.0247 (6) H46 0.8547 0.7860 0.3925 0.030\* C47 0.88406 (14) 0.81159 (14) 0.51006 (15) 0.0191 (5) C48 0.37877 (14) 0.78967 (15) 0.40707 (15) 0.0211 (5) C49 0.31958 (15) 0.72354 (16) 0.38296 (17) 0.0256 (6) H49 0.2899 0.6832 0.3282 0.031\* C50 0.30716 (15) 0.72051 (16) 0.44238 (17) 0.0277 (6) H50 0.2682 0.6769 0.4287 0.033\* C51 0.35113 (16) 0.78092 (16) 0.52372 (18) 0.0284 (6) H51 0.3405 0.7764 0.5630 0.034\* C52 0.40800 (16) 0.84524 (16) 0.54826 (17) 0.0270 (6) H52 0.4368 0.8853 0.6032 0.032\* C53 0.42230 (15) 0.84974 (14) 0.48800 (16) 0.0213 (5) C54 0.51288 (14) 0.90783 (13) 0.39646 (15) 0.0174 (5) C55 0.47908 (14) 0.92018 (13) 0.33010 (14) 0.0176 (5) C56 0.52797 (14) 0.94924 (13) 0.30702 (14) 0.0177 (5) C57 0.60935 (14) 0.96519 (13) 0.35216 (15) 0.0190 (5) H57 0.6427 0.9839 0.3359 0.023\* C58 0.64420 (14) 0.95503 (13) 0.41988 (14) 0.0177 (5) C59 0.59371 (14) 0.92622 (13) 0.44160 (14) 0.0181 (5) H59 0.6152 0.9192 0.4879 0.022\* C60 0.36237 (15) 0.94849 (15) 0.32643 (15) 0.0227 (6) H60A 0.4035 0.9906 0.3807 0.027\* H60B 0.3276 0.9155 0.3336 0.027\* C61 0.31459 (14) 0.98341 (14) 0.27784 (15) 0.0218 (5) C62 0.23258 (16) 1.06462 (16) 0.27908 (18) 0.0327 (7) H62A 0.2064 1.0894 0.3098 0.049\* H62B 0.1927 1.0235 0.2247 0.049\* H62C 0.2629 1.1038 0.2750 0.049\* C63 0.73427 (14) 0.97618 (14) 0.47100 (15) 0.0200 (5) C64 0.77201 (15) 0.96583 (15) 0.41638 (16) 0.0246 (6) H64A 0.7442 0.9143 0.3680 0.037\* H64B 0.8277 0.9703 0.4461 0.037\* H64C 0.7681 1.0064 0.4003 0.037\* C65 0.75389 (15) 0.92045 (14) 0.50543 (16) 0.0241 (6) H65A 0.7271 0.8664 0.4614 0.036\* H65B 0.7360 0.9297 0.5453 0.036\* H65C 0.8111 0.9297 0.5316 0.036\* C66 0.76084 (14) 1.06264 (14) 0.53770 (15) 0.0214 (5) H66A 0.7497 1.0936 0.5092 0.026\* H66B 0.7245 1.0655 0.5603 0.026\* C67 0.84515 (15) 1.10735 (15) 0.61117 (16) 0.0236 (6) C68 0.86502 (17) 1.07819 (17) 0.67249 (17) 0.0359 (7) H68A 0.9133 1.1154 0.7226 0.054\* H68B 0.8731 1.0272 0.6502 0.054\* H68C 0.8214 1.0732 0.6841 0.054\* C69 0.84695 (17) 1.19215 (16) 0.65328 (18) 0.0368 (7) H69A 0.8339 1.2123 0.6150 0.055\* H69B 0.8999 1.2237 0.6994 0.055\* H69C 0.8083 1.1949 0.6724 0.055\* C70 0.91048 (16) 1.10661 (17) 0.58821 (18) 0.0341 (7) H70A 0.8980 1.1234 0.5473 0.051\* H70B 0.9144 1.0537 0.5663 0.051\* H70C 0.9609 1.1423 0.6364 0.051\* C71 0.49259 (15) 0.96613 (14) 0.23754 (14) 0.0198 (5) H71A 0.4999 1.0228 0.2599 0.024\* H71B 0.4350 0.9388 0.2057 0.024\* C72 0.52706 (14) 0.94218 (14) 0.18089 (14) 0.0174 (5) C73 0.56231 (14) 0.99634 (13) 0.16717 (14) 0.0180 (5) C74 0.58637 (14) 0.96950 (13) 0.10944 (14) 0.0176 (5) C75 0.57821 (14) 0.89075 (13) 0.06679 (14) 0.0182 (5) H75 0.5948 0.8741 0.0272 0.022\* C76 0.54607 (14) 0.83626 (14) 0.08144 (14) 0.0186 (5) C77 0.52043 (14) 0.86404 (14) 0.13834 (14) 0.0186 (5) H77 0.4972 0.8277 0.1486 0.022\* C78 0.54868 (15) 1.11972 (14) 0.17648 (15) 0.0208 (5) H78A 0.5147 1.0854 0.1174 0.025\* H78B 0.5950 1.1556 0.1858 0.025\* C79 0.50314 (16) 1.16571 (15) 0.21116 (16) 0.0250 (6) C80 0.43948 (16) 1.26189 (16) 0.20948 (17) 0.0290 (6) H80A 0.4242 1.2910 0.1799 0.044\* H80B 0.4726 1.2986 0.2675 0.044\* H80C 0.3920 1.2289 0.2003 0.044\* C81 0.54547 (15) 0.75078 (14) 0.04287 (15) 0.0200 (5) C82 0.58856 (15) 0.73806 (14) −0.00630 (16) 0.0231 (5) H82A 0.5636 0.7526 −0.0484 0.035\* H82B 0.5858 0.6830 −0.0316 0.035\* H82C 0.6440 0.7704 0.0295 0.035\* C83 0.59283 (16) 0.73531 (15) 0.11333 (16) 0.0268 (6) H83A 0.6455 0.7739 0.1487 0.040\* H83B 0.5979 0.6828 0.0915 0.040\* H83C 0.5651 0.7394 0.1444 0.040\* C84 0.46125 (15) 0.69253 (14) −0.00552 (15) 0.0228 (5) H84A 0.4676 0.6423 −0.0084 0.027\* H84B 0.4355 0.7113 0.0280 0.027\* C85 0.40164 (15) 0.67374 (15) −0.09188 (16) 0.0234 (6) C86 0.39489 (16) 0.74684 (16) −0.09990 (17) 0.0300 (6) H86A 0.4455 0.7747 −0.0901 0.045\* H86B 0.3812 0.7808 −0.0602 0.045\* H86C 0.3536 0.7319 −0.1546 0.045\* C87 0.42033 (16) 0.61839 (16) −0.15518 (16) 0.0289 (6) H87A 0.4678 0.6464 −0.1507 0.043\* H87B 0.3757 0.5991 −0.2095 0.043\* H87C 0.4295 0.5743 −0.1459 0.043\* C88 0.32046 (16) 0.63051 (16) −0.11078 (18) 0.0323 (7) H88A 0.3041 0.6655 −0.0743 0.049\* H88B 0.3238 0.5848 −0.1031 0.049\* H88C 0.2817 0.6137 −0.1670 0.049\* C89 0.65312 (15) 1.05808 (14) 0.02252 (16) 0.0222 (5) C90 0.66150 (16) 1.06765 (17) −0.03827 (18) 0.0292 (6) H90 0.6250 1.0344 −0.0941 0.035\* C91 0.72441 (17) 1.12683 (17) −0.01283 (19) 0.0330 (7) H91 0.7321 1.1346 −0.0521 0.040\* C92 0.77882 (17) 1.17726 (16) 0.07037 (19) 0.0324 (7) H92 0.8209 1.2187 0.0850 0.039\* C93 0.77294 (16) 1.16841 (15) 0.13056 (18) 0.0289 (6) H93 0.8101 1.2019 0.1862 0.035\* C94 0.70838 (15) 1.10661 (14) 0.10492 (16) 0.0230 (6) C95 0.71648 (14) 0.44991 (14) 0.38654 (15) 0.0202 (5) C96 0.65517 (15) 0.38359 (15) 0.35888 (17) 0.0262 (6) H96 0.6273 0.3438 0.3038 0.031\* C97 0.63829 (16) 0.37978 (16) 0.41544 (18) 0.0292 (6) H97 0.5974 0.3363 0.3991 0.035\* C98 0.67970 (16) 0.43859 (16) 0.49754 (18) 0.0300 (6) H98 0.6662 0.4329 0.5347 0.036\* C99 0.73827 (16) 0.50319 (15) 0.52530 (17) 0.0270 (6) H99 0.7653 0.5425 0.5806 0.032\* C100 0.75691 (15) 0.50890 (14) 0.46785 (16) 0.0213 (5) C101 0.85790 (14) 0.57377 (13) 0.38853 (14) 0.0173 (5) C102 0.83023 (14) 0.59678 (13) 0.32965 (14) 0.0179 (5) C103 0.88495 (14) 0.63311 (13) 0.31684 (14) 0.0180 (5) C104 0.96456 (14) 0.64260 (14) 0.36162 (15) 0.0196 (5) H10B 1.0013 0.6667 0.3521 0.024\* C105 0.99330 (14) 0.61855 (14) 0.41971 (15) 0.0198 (5) C106 0.93774 (14) 0.58513 (14) 0.43318 (15) 0.0202 (5) H10C 0.9549 0.5699 0.4737 0.024\* C107 0.70480 (14) 0.60898 (14) 0.31805 (15) 0.0205 (5) H10D 0.7390 0.6396 0.3775 0.025\* H10E 0.6648 0.5641 0.3056 0.025\* C108 0.66457 (15) 0.65916 (15) 0.28687 (16) 0.0240 (6) C109 0.57343 (16) 0.72991 (16) 0.29222 (17) 0.0283 (6) H10F 0.5436 0.7459 0.3212 0.042\* H10G 0.5367 0.6995 0.2339 0.042\* H10H 0.6098 0.7763 0.3037 0.042\* C110 1.08055 (14) 0.62109 (15) 0.45923 (16) 0.0232 (6) C111 1.09692 (16) 0.57357 (16) 0.38952 (17) 0.0310 (6) H11A 1.1503 0.5693 0.4122 0.047\* H11B 1.0925 0.6001 0.3575 0.047\* H11C 1.0583 0.5213 0.3547 0.047\* C112 1.09561 (15) 0.58104 (15) 0.51050 (16) 0.0250 (6) H11D 1.1517 0.5852 0.5361 0.038\* H11E 1.0639 0.5259 0.4761 0.038\* H11F 1.0809 0.6062 0.5525 0.038\* C113 1.13838 (15) 0.70448 (15) 0.50574 (16) 0.0257 (6) H11G 1.1183 0.7287 0.4711 0.031\* H11H 1.1894 0.6987 0.5087 0.031\* C114 1.15775 (16) 0.76523 (15) 0.59237 (17) 0.0269 (6) C115 1.08274 (16) 0.76919 (17) 0.59879 (18) 0.0340 (7) H11I 1.0963 0.8116 0.6521 0.051\* H11J 1.0573 0.7196 0.5918 0.051\* H11K 1.0465 0.7790 0.5565 0.051\* C116 1.19896 (17) 0.84487 (16) 0.60803 (18) 0.0326 (7) H11L 1.2170 0.8842 0.6641 0.049\* H11M 1.1618 0.8595 0.5711 0.049\* H11N 1.2444 0.8418 0.5989 0.049\* C117 1.21601 (17) 0.74909 (16) 0.65698 (17) 0.0319 (6) H11O 1.2350 0.7936 0.7108 0.048\* H11P 1.2609 0.7412 0.6478 0.048\* H11Q 1.1894 0.7021 0.6536 0.048\* C118 0.86001 (16) 0.66527 (15) 0.25868 (15) 0.0229 (6) H11R 0.8859 0.7224 0.2896 0.027\* H11S 0.8022 0.6561 0.2348 0.027\* C119 0.87942 (14) 0.63072 (14) 0.19051 (14) 0.0188 (5) C120 0.90770 (14) 0.67926 (13) 0.16729 (14) 0.0185 (5) C121 0.92115 (14) 0.64627 (14) 0.10172 (15) 0.0181 (5) C122 0.90568 (14) 0.56650 (13) 0.05851 (15) 0.0183 (5) H122 0.9137 0.5455 0.0129 0.022\* C123 0.87852 (14) 0.51687 (14) 0.08116 (15) 0.0185 (5) C124 0.86603 (14) 0.55079 (14) 0.14746 (15) 0.0199 (5) H124 0.8476 0.5179 0.1640 0.024\* C125 0.87848 (16) 0.79448 (14) 0.16965 (15) 0.0231 (6) H12D 0.8330 0.7541 0.1174 0.028\* H12E 0.9118 0.8240 0.1582 0.028\* C126 0.84944 (15) 0.84879 (14) 0.22054 (16) 0.0228 (5) C127 0.77839 (17) 0.93978 (16) 0.22430 (18) 0.0320 (7) H12F 0.7571 0.9680 0.1951 0.048\* H12G 0.8213 0.9768 0.2790 0.048\* H12H 0.7365 0.9124 0.2278 0.048\* C128 0.85950 (15) 0.42822 (14) 0.03149 (15) 0.0224 (5) C129 0.91741 (15) 0.41108 (14) −0.00175 (16) 0.0251 (6) H12I 0.9718 0.4395 0.0427 0.038\* H12J 0.9070 0.4279 −0.0425 0.038\* H12K 0.9104 0.3550 −0.0266 0.038\* C130 0.87054 (17) 0.39182 (15) 0.08632 (16) 0.0288 (6) H13C 0.9227 0.4198 0.1348 0.043\* H13D 0.8666 0.3369 0.0571 0.043\* H13E 0.8295 0.3954 0.1023 0.043\* C131 0.77218 (15) 0.40095 (14) −0.03718 (16) 0.0246 (6) H13F 0.7399 0.4126 −0.0098 0.030\* H13G 0.7700 0.4361 −0.0607 0.030\* C132 0.72797 (15) 0.31810 (15) −0.10902 (16) 0.0238 (6) C133 0.72679 (18) 0.25482 (16) −0.08463 (17) 0.0337 (7) H13H 0.7800 0.2500 −0.0620 0.051\* H13I 0.6901 0.2050 −0.1323 0.051\* H13J 0.7095 0.2688 −0.0439 0.051\* C134 0.64202 (16) 0.31588 (17) −0.15380 (18) 0.0361 (7) H13K 0.6110 0.2637 −0.2004 0.054\* H13L 0.6403 0.3544 −0.1725 0.054\* H13M 0.6199 0.3281 −0.1170 0.054\* C135 0.75888 (17) 0.29649 (16) −0.16929 (16) 0.0322 (7) H13N 0.8105 0.2890 −0.1454 0.048\* H13O 0.7643 0.3385 −0.1824 0.048\* H13P 0.7217 0.2481 −0.2188 0.048\* C136 1.03623 (15) 0.77844 (14) 0.08674 (15) 0.0210 (5) C137 1.09976 (16) 0.83920 (15) 0.10892 (18) 0.0277 (6) H137 1.1384 0.8731 0.1639 0.033\* C138 1.10304 (17) 0.84698 (16) 0.04738 (18) 0.0304 (6) H138 1.1445 0.8878 0.0600 0.036\* C139 1.04599 (17) 0.79553 (18) −0.03502 (18) 0.0339 (7) H139 1.0510 0.8028 −0.0758 0.041\* C140 0.98468 (16) 0.73641 (18) −0.05786 (18) 0.0324 (7) H140 0.9471 0.7023 −0.1132 0.039\* C141 0.97961 (15) 0.72811 (15) 0.00499 (15) 0.0221 (5) ------- -------------- -------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e5156 .table-wrap} ------- ------------- ------------- ------------- -------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0247 (9) 0.0205 (9) 0.0153 (9) 0.0093 (7) 0.0087 (8) 0.0078 (8) O2 0.0320 (10) 0.0294 (10) 0.0244 (10) 0.0183 (8) 0.0162 (9) 0.0155 (9) O3 0.0683 (16) 0.0575 (14) 0.0406 (13) 0.0451 (12) 0.0422 (13) 0.0352 (12) O4 0.0176 (9) 0.0315 (10) 0.0157 (9) 0.0107 (7) 0.0077 (8) 0.0103 (8) O5 0.0283 (10) 0.0399 (11) 0.0280 (11) 0.0207 (9) 0.0182 (9) 0.0214 (9) O6 0.0688 (16) 0.0883 (18) 0.0504 (15) 0.0602 (14) 0.0473 (14) 0.0545 (14) O7 0.0174 (9) 0.0257 (9) 0.0160 (9) 0.0088 (7) 0.0087 (8) 0.0084 (8) O8 0.0295 (10) 0.0328 (11) 0.0263 (11) 0.0179 (8) 0.0150 (9) 0.0123 (9) O9 0.0473 (13) 0.0524 (13) 0.0265 (11) 0.0323 (11) 0.0212 (10) 0.0251 (10) O10 0.0330 (10) 0.0176 (9) 0.0155 (9) 0.0111 (7) 0.0123 (8) 0.0080 (7) O11 0.0395 (11) 0.0307 (10) 0.0317 (11) 0.0222 (9) 0.0251 (10) 0.0209 (9) O12 0.137 (3) 0.096 (2) 0.094 (2) 0.0952 (19) 0.102 (2) 0.0811 (18) O13 0.0184 (9) 0.0306 (10) 0.0155 (9) 0.0113 (7) 0.0083 (8) 0.0096 (8) O14 0.0317 (10) 0.0347 (11) 0.0305 (11) 0.0217 (9) 0.0206 (9) 0.0225 (9) O15 0.094 (2) 0.133 (2) 0.103 (2) 0.096 (2) 0.0862 (19) 0.107 (2) O16 0.0269 (10) 0.0183 (9) 0.0150 (9) 0.0091 (7) 0.0080 (8) 0.0075 (7) O17 0.0409 (12) 0.0316 (11) 0.0276 (11) 0.0228 (9) 0.0182 (10) 0.0178 (9) O18 0.0670 (16) 0.0585 (14) 0.0292 (12) 0.0445 (12) 0.0306 (12) 0.0256 (11) N1 0.0236 (11) 0.0204 (11) 0.0210 (12) 0.0052 (9) 0.0131 (10) 0.0067 (9) N2 0.0188 (11) 0.0200 (11) 0.0161 (11) 0.0063 (8) 0.0097 (9) 0.0075 (9) N3 0.0223 (11) 0.0255 (11) 0.0190 (12) 0.0098 (9) 0.0112 (10) 0.0120 (10) N4 0.0182 (11) 0.0257 (12) 0.0173 (11) 0.0020 (9) 0.0063 (10) 0.0093 (10) N5 0.0164 (10) 0.0215 (11) 0.0143 (11) 0.0045 (8) 0.0058 (9) 0.0084 (9) N6 0.0246 (11) 0.0235 (11) 0.0176 (11) 0.0103 (9) 0.0128 (10) 0.0109 (9) N7 0.0208 (11) 0.0267 (12) 0.0193 (12) 0.0043 (9) 0.0095 (10) 0.0112 (10) N8 0.0188 (11) 0.0220 (11) 0.0163 (11) 0.0062 (8) 0.0091 (9) 0.0106 (9) N9 0.0274 (12) 0.0228 (11) 0.0187 (11) 0.0098 (9) 0.0147 (10) 0.0111 (9) N10 0.0247 (12) 0.0283 (12) 0.0183 (11) 0.0113 (9) 0.0121 (10) 0.0145 (10) N11 0.0240 (11) 0.0187 (11) 0.0198 (11) 0.0072 (9) 0.0130 (10) 0.0109 (9) N12 0.0285 (12) 0.0176 (11) 0.0233 (12) 0.0039 (9) 0.0148 (11) 0.0080 (10) N13 0.0182 (11) 0.0227 (11) 0.0195 (11) 0.0036 (9) 0.0072 (10) 0.0103 (9) N14 0.0200 (11) 0.0178 (10) 0.0158 (11) 0.0057 (8) 0.0085 (9) 0.0081 (9) N15 0.0233 (11) 0.0227 (11) 0.0183 (11) 0.0091 (9) 0.0128 (10) 0.0097 (9) N16 0.0258 (12) 0.0199 (11) 0.0192 (12) 0.0024 (9) 0.0111 (10) 0.0069 (9) N17 0.0199 (11) 0.0204 (11) 0.0146 (11) 0.0060 (8) 0.0078 (9) 0.0089 (9) N18 0.0225 (11) 0.0307 (12) 0.0167 (11) 0.0095 (9) 0.0102 (10) 0.0124 (10) C1 0.0237 (13) 0.0196 (13) 0.0269 (15) 0.0100 (10) 0.0164 (12) 0.0110 (11) C2 0.0268 (14) 0.0236 (14) 0.0327 (16) 0.0068 (11) 0.0180 (13) 0.0112 (12) C3 0.0332 (16) 0.0244 (14) 0.0466 (19) 0.0115 (12) 0.0284 (15) 0.0199 (14) C4 0.0368 (16) 0.0327 (15) 0.0424 (18) 0.0200 (13) 0.0291 (15) 0.0268 (14) C5 0.0299 (15) 0.0319 (15) 0.0350 (17) 0.0161 (12) 0.0197 (14) 0.0229 (13) C6 0.0204 (13) 0.0224 (13) 0.0242 (14) 0.0122 (10) 0.0123 (12) 0.0135 (11) C7 0.0163 (12) 0.0200 (12) 0.0195 (13) 0.0076 (10) 0.0090 (11) 0.0110 (11) C8 0.0172 (12) 0.0188 (12) 0.0167 (13) 0.0076 (10) 0.0075 (11) 0.0078 (10) C9 0.0172 (12) 0.0249 (13) 0.0133 (12) 0.0085 (10) 0.0065 (11) 0.0097 (11) C10 0.0205 (13) 0.0248 (13) 0.0211 (14) 0.0089 (10) 0.0109 (12) 0.0144 (11) C11 0.0193 (13) 0.0222 (13) 0.0171 (13) 0.0083 (10) 0.0069 (11) 0.0095 (11) C12 0.0214 (13) 0.0260 (13) 0.0157 (13) 0.0101 (10) 0.0117 (11) 0.0102 (11) C13 0.0271 (14) 0.0194 (13) 0.0183 (13) 0.0093 (10) 0.0118 (12) 0.0105 (11) C14 0.0231 (13) 0.0208 (13) 0.0172 (13) 0.0047 (10) 0.0088 (12) 0.0075 (11) C15 0.0319 (16) 0.0355 (16) 0.0344 (17) 0.0195 (13) 0.0188 (14) 0.0177 (14) C16 0.0336 (15) 0.0209 (13) 0.0229 (15) 0.0052 (11) 0.0159 (13) 0.0087 (12) C17 0.0257 (15) 0.0268 (15) 0.0293 (16) 0.0136 (12) 0.0084 (13) 0.0088 (13) C18 0.131 (4) 0.0254 (17) 0.053 (2) 0.028 (2) 0.061 (3) 0.0236 (17) C19 0.0235 (15) 0.0345 (16) 0.0385 (18) 0.0084 (12) 0.0163 (15) 0.0052 (14) C20 0.0406 (18) 0.0256 (15) 0.0368 (18) −0.0011 (13) 0.0236 (16) 0.0030 (13) C21 0.027 (2) 0.034 (2) 0.038 (3) 0.0084 (17) 0.0177 (19) 0.0016 (18) C22 0.0313 (18) 0.035 (3) 0.020 (2) 0.0114 (19) 0.0057 (18) 0.0071 (16) C23 0.040 (2) 0.045 (2) 0.038 (2) 0.0011 (18) 0.017 (2) 0.017 (2) C21\' 0.027 (2) 0.034 (2) 0.038 (3) 0.0084 (17) 0.0177 (19) 0.0016 (18) C22\' 0.0313 (18) 0.035 (3) 0.020 (2) 0.0114 (19) 0.0057 (18) 0.0071 (16) C23\' 0.040 (2) 0.045 (2) 0.038 (2) 0.0011 (18) 0.017 (2) 0.017 (2) C24 0.0272 (14) 0.0305 (14) 0.0214 (14) 0.0163 (11) 0.0150 (12) 0.0161 (12) C25 0.0232 (13) 0.0169 (12) 0.0160 (13) 0.0091 (10) 0.0114 (11) 0.0065 (10) C26 0.0194 (13) 0.0191 (12) 0.0152 (13) 0.0075 (10) 0.0078 (11) 0.0063 (10) C27 0.0203 (13) 0.0175 (12) 0.0166 (13) 0.0063 (10) 0.0108 (11) 0.0072 (10) C28 0.0221 (13) 0.0207 (13) 0.0157 (13) 0.0066 (10) 0.0092 (11) 0.0085 (11) C29 0.0205 (13) 0.0229 (13) 0.0167 (13) 0.0085 (10) 0.0107 (11) 0.0082 (11) C30 0.0209 (13) 0.0218 (13) 0.0198 (13) 0.0078 (10) 0.0132 (11) 0.0108 (11) C31 0.0194 (13) 0.0320 (14) 0.0186 (14) 0.0124 (11) 0.0114 (12) 0.0130 (12) C32 0.0220 (13) 0.0261 (14) 0.0190 (14) 0.0097 (11) 0.0100 (12) 0.0107 (11) C33 0.0291 (15) 0.0311 (15) 0.0329 (16) 0.0180 (12) 0.0154 (14) 0.0183 (13) C34 0.0190 (13) 0.0293 (14) 0.0197 (14) 0.0091 (11) 0.0103 (12) 0.0137 (12) C35 0.0261 (15) 0.0461 (18) 0.0264 (16) 0.0161 (13) 0.0162 (14) 0.0163 (14) C36 0.0216 (13) 0.0278 (14) 0.0240 (14) 0.0117 (11) 0.0107 (12) 0.0136 (12) C37 0.0197 (13) 0.0324 (15) 0.0240 (15) 0.0058 (11) 0.0113 (12) 0.0157 (12) C38 0.0232 (13) 0.0237 (13) 0.0230 (14) 0.0087 (11) 0.0130 (12) 0.0126 (11) C39 0.0289 (15) 0.0346 (16) 0.0366 (17) 0.0075 (12) 0.0160 (14) 0.0195 (14) C40 0.0291 (15) 0.0312 (15) 0.0334 (17) 0.0100 (12) 0.0184 (14) 0.0164 (13) C41 0.0313 (15) 0.0275 (15) 0.0224 (15) 0.0109 (12) 0.0085 (13) 0.0098 (12) C42 0.0201 (13) 0.0247 (13) 0.0241 (14) 0.0091 (10) 0.0130 (12) 0.0129 (12) C43 0.0246 (14) 0.0276 (14) 0.0256 (15) 0.0058 (11) 0.0105 (13) 0.0118 (12) C44 0.0261 (14) 0.0298 (15) 0.0358 (17) 0.0098 (12) 0.0184 (14) 0.0198 (13) C45 0.0302 (15) 0.0319 (15) 0.0326 (16) 0.0158 (12) 0.0216 (14) 0.0220 (13) C46 0.0304 (15) 0.0266 (14) 0.0236 (15) 0.0122 (11) 0.0169 (13) 0.0131 (12) C47 0.0200 (13) 0.0211 (13) 0.0232 (14) 0.0110 (10) 0.0140 (12) 0.0124 (11) C48 0.0179 (13) 0.0295 (14) 0.0226 (14) 0.0106 (11) 0.0104 (12) 0.0170 (12) C49 0.0196 (13) 0.0305 (15) 0.0313 (16) 0.0091 (11) 0.0123 (13) 0.0189 (13) C50 0.0239 (14) 0.0335 (15) 0.0413 (18) 0.0133 (12) 0.0210 (14) 0.0256 (14) C51 0.0345 (16) 0.0352 (16) 0.0379 (17) 0.0202 (13) 0.0267 (15) 0.0260 (14) C52 0.0353 (16) 0.0305 (15) 0.0299 (16) 0.0162 (12) 0.0240 (14) 0.0180 (13) C53 0.0238 (13) 0.0249 (13) 0.0242 (14) 0.0133 (11) 0.0159 (12) 0.0143 (12) C54 0.0214 (13) 0.0165 (12) 0.0190 (13) 0.0070 (10) 0.0131 (11) 0.0090 (10) C55 0.0169 (12) 0.0174 (12) 0.0164 (13) 0.0070 (9) 0.0072 (11) 0.0070 (10) C56 0.0243 (13) 0.0158 (12) 0.0146 (13) 0.0092 (10) 0.0109 (11) 0.0068 (10) C57 0.0217 (13) 0.0195 (13) 0.0189 (13) 0.0075 (10) 0.0120 (11) 0.0098 (11) C58 0.0215 (13) 0.0168 (12) 0.0157 (13) 0.0088 (10) 0.0095 (11) 0.0077 (10) C59 0.0221 (13) 0.0187 (12) 0.0150 (13) 0.0085 (10) 0.0102 (11) 0.0081 (10) C60 0.0212 (13) 0.0322 (14) 0.0192 (14) 0.0121 (11) 0.0129 (12) 0.0123 (12) C61 0.0192 (13) 0.0245 (14) 0.0176 (14) 0.0056 (10) 0.0085 (11) 0.0077 (11) C62 0.0299 (16) 0.0292 (15) 0.0354 (17) 0.0148 (12) 0.0132 (14) 0.0143 (14) C63 0.0185 (13) 0.0249 (13) 0.0185 (13) 0.0095 (10) 0.0095 (11) 0.0113 (11) C64 0.0199 (13) 0.0317 (15) 0.0234 (14) 0.0091 (11) 0.0127 (12) 0.0120 (12) C65 0.0227 (14) 0.0232 (13) 0.0261 (15) 0.0092 (11) 0.0100 (12) 0.0132 (12) C66 0.0209 (13) 0.0207 (13) 0.0188 (13) 0.0074 (10) 0.0081 (11) 0.0079 (11) C67 0.0213 (13) 0.0251 (14) 0.0198 (14) 0.0058 (11) 0.0074 (12) 0.0100 (11) C68 0.0342 (17) 0.0361 (17) 0.0224 (16) 0.0016 (13) 0.0037 (14) 0.0135 (14) C69 0.0335 (17) 0.0295 (16) 0.0305 (17) 0.0099 (13) 0.0086 (14) 0.0071 (13) C70 0.0234 (15) 0.0407 (17) 0.0293 (17) 0.0033 (12) 0.0102 (13) 0.0133 (14) C71 0.0235 (13) 0.0241 (13) 0.0158 (13) 0.0102 (10) 0.0113 (11) 0.0106 (11) C72 0.0169 (12) 0.0241 (13) 0.0131 (12) 0.0074 (10) 0.0075 (11) 0.0102 (11) C73 0.0199 (12) 0.0192 (12) 0.0141 (12) 0.0078 (10) 0.0071 (11) 0.0083 (10) C74 0.0217 (13) 0.0173 (12) 0.0186 (13) 0.0076 (10) 0.0110 (11) 0.0113 (11) C75 0.0198 (12) 0.0207 (13) 0.0140 (12) 0.0064 (10) 0.0089 (11) 0.0077 (10) C76 0.0196 (13) 0.0209 (13) 0.0147 (13) 0.0067 (10) 0.0075 (11) 0.0089 (11) C77 0.0196 (12) 0.0213 (13) 0.0177 (13) 0.0043 (10) 0.0089 (11) 0.0124 (11) C78 0.0270 (14) 0.0198 (13) 0.0197 (14) 0.0091 (10) 0.0121 (12) 0.0121 (11) C79 0.0349 (15) 0.0258 (14) 0.0199 (14) 0.0135 (12) 0.0166 (13) 0.0118 (12) C80 0.0322 (15) 0.0341 (15) 0.0317 (16) 0.0208 (12) 0.0197 (14) 0.0189 (13) C81 0.0261 (13) 0.0193 (13) 0.0165 (13) 0.0075 (10) 0.0104 (12) 0.0103 (11) C82 0.0267 (14) 0.0201 (13) 0.0233 (14) 0.0109 (11) 0.0128 (12) 0.0099 (11) C83 0.0339 (15) 0.0233 (14) 0.0250 (15) 0.0108 (12) 0.0121 (13) 0.0151 (12) C84 0.0293 (14) 0.0196 (13) 0.0227 (14) 0.0081 (11) 0.0144 (12) 0.0113 (11) C85 0.0233 (14) 0.0270 (14) 0.0203 (14) 0.0094 (11) 0.0109 (12) 0.0111 (12) C86 0.0305 (15) 0.0325 (15) 0.0309 (16) 0.0139 (12) 0.0126 (14) 0.0202 (13) C87 0.0290 (15) 0.0321 (15) 0.0194 (14) 0.0106 (12) 0.0100 (13) 0.0087 (12) C88 0.0280 (15) 0.0335 (16) 0.0345 (17) 0.0072 (12) 0.0153 (14) 0.0161 (14) C89 0.0240 (13) 0.0251 (14) 0.0303 (15) 0.0150 (11) 0.0172 (13) 0.0188 (12) C90 0.0319 (15) 0.0404 (16) 0.0337 (17) 0.0190 (13) 0.0202 (14) 0.0280 (14) C91 0.0382 (17) 0.0417 (17) 0.050 (2) 0.0229 (14) 0.0324 (16) 0.0357 (16) C92 0.0360 (16) 0.0286 (15) 0.053 (2) 0.0139 (13) 0.0324 (16) 0.0254 (15) C93 0.0311 (15) 0.0231 (14) 0.0384 (17) 0.0089 (11) 0.0216 (14) 0.0151 (13) C94 0.0287 (14) 0.0229 (13) 0.0301 (15) 0.0136 (11) 0.0211 (13) 0.0157 (12) C95 0.0170 (12) 0.0252 (13) 0.0218 (14) 0.0096 (10) 0.0097 (11) 0.0135 (11) C96 0.0205 (13) 0.0270 (14) 0.0312 (16) 0.0061 (11) 0.0100 (13) 0.0173 (13) C97 0.0260 (14) 0.0323 (15) 0.0428 (18) 0.0112 (12) 0.0202 (14) 0.0260 (14) C98 0.0353 (16) 0.0379 (16) 0.0404 (18) 0.0209 (13) 0.0279 (15) 0.0278 (15) C99 0.0370 (16) 0.0280 (14) 0.0289 (15) 0.0147 (12) 0.0237 (14) 0.0164 (13) C100 0.0231 (13) 0.0221 (13) 0.0275 (15) 0.0119 (10) 0.0151 (12) 0.0157 (12) C101 0.0184 (12) 0.0176 (12) 0.0155 (13) 0.0050 (10) 0.0091 (11) 0.0070 (10) C102 0.0190 (12) 0.0183 (12) 0.0147 (12) 0.0083 (10) 0.0083 (11) 0.0058 (10) C103 0.0250 (13) 0.0162 (12) 0.0153 (13) 0.0093 (10) 0.0124 (11) 0.0066 (10) C104 0.0215 (13) 0.0205 (13) 0.0182 (13) 0.0067 (10) 0.0111 (11) 0.0092 (11) C105 0.0204 (13) 0.0200 (13) 0.0153 (13) 0.0049 (10) 0.0089 (11) 0.0056 (10) C106 0.0239 (13) 0.0205 (13) 0.0163 (13) 0.0072 (10) 0.0098 (11) 0.0092 (11) C107 0.0208 (13) 0.0238 (13) 0.0181 (13) 0.0079 (10) 0.0109 (11) 0.0096 (11) C108 0.0230 (14) 0.0321 (15) 0.0227 (14) 0.0113 (11) 0.0128 (12) 0.0160 (12) C109 0.0339 (16) 0.0319 (15) 0.0308 (16) 0.0205 (12) 0.0187 (14) 0.0202 (13) C110 0.0186 (13) 0.0300 (14) 0.0219 (14) 0.0073 (11) 0.0106 (12) 0.0129 (12) C111 0.0258 (15) 0.0386 (16) 0.0274 (16) 0.0111 (12) 0.0153 (13) 0.0124 (13) C112 0.0221 (14) 0.0263 (14) 0.0270 (15) 0.0092 (11) 0.0115 (12) 0.0132 (12) C113 0.0194 (13) 0.0337 (15) 0.0272 (15) 0.0083 (11) 0.0118 (12) 0.0172 (13) C114 0.0281 (15) 0.0283 (14) 0.0287 (16) 0.0115 (12) 0.0163 (13) 0.0146 (13) C115 0.0328 (16) 0.0335 (16) 0.0362 (18) 0.0110 (13) 0.0209 (15) 0.0132 (14) C116 0.0336 (16) 0.0283 (15) 0.0325 (17) 0.0075 (12) 0.0154 (14) 0.0130 (13) C117 0.0343 (16) 0.0306 (15) 0.0226 (15) 0.0098 (12) 0.0101 (14) 0.0097 (13) C118 0.0304 (14) 0.0272 (14) 0.0227 (14) 0.0153 (11) 0.0185 (13) 0.0151 (12) C119 0.0169 (12) 0.0250 (13) 0.0159 (13) 0.0083 (10) 0.0079 (11) 0.0109 (11) C120 0.0193 (12) 0.0192 (13) 0.0149 (13) 0.0078 (10) 0.0072 (11) 0.0073 (10) C121 0.0163 (12) 0.0220 (13) 0.0167 (13) 0.0065 (10) 0.0061 (11) 0.0118 (11) C122 0.0190 (12) 0.0207 (13) 0.0145 (13) 0.0072 (10) 0.0086 (11) 0.0072 (10) C123 0.0160 (12) 0.0197 (12) 0.0161 (13) 0.0057 (10) 0.0051 (11) 0.0084 (10) C124 0.0193 (13) 0.0243 (13) 0.0213 (14) 0.0078 (10) 0.0100 (11) 0.0152 (11) C125 0.0321 (15) 0.0221 (13) 0.0176 (13) 0.0114 (11) 0.0117 (12) 0.0116 (11) C126 0.0243 (14) 0.0224 (13) 0.0193 (14) 0.0069 (11) 0.0091 (12) 0.0098 (11) C127 0.0327 (16) 0.0299 (15) 0.0340 (17) 0.0179 (13) 0.0167 (14) 0.0140 (13) C128 0.0266 (14) 0.0200 (13) 0.0204 (14) 0.0063 (10) 0.0129 (12) 0.0083 (11) C129 0.0249 (14) 0.0216 (13) 0.0256 (15) 0.0089 (11) 0.0119 (13) 0.0087 (12) C130 0.0374 (16) 0.0245 (14) 0.0254 (15) 0.0107 (12) 0.0148 (14) 0.0133 (12) C131 0.0247 (14) 0.0246 (14) 0.0247 (15) 0.0089 (11) 0.0119 (12) 0.0118 (12) C132 0.0235 (14) 0.0247 (14) 0.0220 (14) 0.0089 (11) 0.0114 (12) 0.0098 (12) C133 0.0415 (17) 0.0249 (15) 0.0269 (16) 0.0056 (13) 0.0136 (14) 0.0099 (13) C134 0.0290 (16) 0.0323 (16) 0.0311 (17) 0.0079 (12) 0.0096 (14) 0.0072 (14) C135 0.0294 (15) 0.0341 (16) 0.0214 (15) 0.0041 (12) 0.0108 (13) 0.0063 (13) C136 0.0259 (14) 0.0217 (13) 0.0234 (14) 0.0119 (11) 0.0165 (12) 0.0123 (11) C137 0.0305 (15) 0.0240 (14) 0.0325 (16) 0.0081 (11) 0.0199 (14) 0.0126 (12) C138 0.0322 (16) 0.0317 (15) 0.0440 (19) 0.0153 (12) 0.0278 (15) 0.0224 (14) C139 0.0342 (16) 0.0529 (19) 0.0401 (19) 0.0209 (14) 0.0264 (15) 0.0346 (16) C140 0.0288 (15) 0.0521 (19) 0.0257 (16) 0.0155 (13) 0.0162 (14) 0.0235 (15) C141 0.0224 (13) 0.0305 (14) 0.0227 (14) 0.0134 (11) 0.0141 (12) 0.0167 (12) ------- ------------- ------------- ------------- -------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e7918 .table-wrap} ------------------------- -------------- --------------------------- ------------- O1---C8 1.377 (3) C57---C58 1.394 (3) O1---C13 1.425 (3) C57---H57 0.9500 O2---C14 1.335 (3) C58---C59 1.398 (3) O2---C15 1.448 (3) C58---C63 1.539 (3) O3---C14 1.197 (3) C59---H59 0.9500 O4---C26 1.374 (3) C60---C61 1.506 (3) O4---C31 1.427 (3) C60---H60A 0.9900 O5---C32 1.339 (3) C60---H60B 0.9900 O5---C33 1.447 (3) C62---H62A 0.9800 O6---C32 1.188 (3) C62---H62B 0.9800 O7---C55 1.376 (3) C62---H62C 0.9800 O7---C60 1.426 (3) C63---C65 1.533 (3) O8---C61 1.344 (3) C63---C64 1.541 (3) O8---C62 1.445 (3) C63---C66 1.558 (3) O9---C61 1.192 (3) C64---H64A 0.9800 O10---C73 1.376 (3) C64---H64B 0.9800 O10---C78 1.425 (3) C64---H64C 0.9800 O11---C79 1.330 (3) C65---H65A 0.9800 O11---C80 1.447 (3) C65---H65B 0.9800 O12---C79 1.181 (3) C65---H65C 0.9800 O13---C102 1.375 (3) C66---C67 1.549 (3) O13---C107 1.428 (3) C66---H66A 0.9900 O14---C108 1.335 (3) C66---H66B 0.9900 O14---C109 1.449 (3) C67---C68 1.524 (4) O15---C108 1.184 (3) C67---C70 1.528 (4) O16---C120 1.383 (3) C67---C69 1.529 (4) O16---C125 1.417 (3) C68---H68A 0.9800 O17---C126 1.340 (3) C68---H68B 0.9800 O17---C127 1.443 (3) C68---H68C 0.9800 O18---C126 1.189 (3) C69---H69A 0.9800 N1---N2 1.334 (3) C69---H69B 0.9800 N1---C1 1.350 (3) C69---H69C 0.9800 N2---N3 1.336 (3) C70---H70A 0.9800 N2---C7 1.435 (3) C70---H70B 0.9800 N3---C6 1.350 (3) C70---H70C 0.9800 N4---N5 1.333 (3) C71---C72 1.516 (3) N4---C42 1.357 (3) C71---H71A 0.9900 N5---N6 1.332 (3) C71---H71B 0.9900 N5---C27 1.432 (3) C72---C77 1.391 (3) N6---C47 1.353 (3) C72---C73 1.400 (3) N7---N8 1.337 (3) C73---C74 1.384 (3) N7---C48 1.354 (3) C74---C75 1.394 (3) N8---N9 1.337 (3) C75---C76 1.389 (3) N8---C54 1.432 (3) C75---H75 0.9500 N9---C53 1.352 (3) C76---C77 1.394 (3) N10---N11 1.334 (3) C76---C81 1.541 (3) N10---C89 1.349 (3) C77---H77 0.9500 N11---N12 1.331 (3) C78---C79 1.505 (3) N11---C74 1.437 (3) C78---H78A 0.9900 N12---C94 1.361 (3) C78---H78B 0.9900 N13---N14 1.334 (3) C80---H80A 0.9800 N13---C95 1.359 (3) C80---H80B 0.9800 N14---N15 1.331 (3) C80---H80C 0.9800 N14---C101 1.433 (3) C81---C82 1.526 (3) N15---C100 1.347 (3) C81---C83 1.545 (3) N16---N17 1.331 (3) C81---C84 1.547 (3) N16---C136 1.352 (3) C82---H82A 0.9800 N17---N18 1.338 (3) C82---H82B 0.9800 N17---C121 1.430 (3) C82---H82C 0.9800 N18---C141 1.352 (3) C83---H83A 0.9800 C1---C6 1.410 (4) C83---H83B 0.9800 C1---C2 1.420 (3) C83---H83C 0.9800 C2---C3 1.368 (4) C84---C85 1.541 (4) C2---H2 0.9500 C84---H84A 0.9900 C3---C4 1.419 (4) C84---H84B 0.9900 C3---H3 0.9500 C85---C86 1.527 (4) C4---C5 1.361 (4) C85---C87 1.531 (3) C4---H4 0.9500 C85---C88 1.534 (3) C5---C6 1.415 (3) C86---H86A 0.9800 C5---H5 0.9500 C86---H86B 0.9800 C7---C12 1.379 (3) C86---H86C 0.9800 C7---C8 1.392 (3) C87---H87A 0.9800 C8---C9 1.393 (3) C87---H87B 0.9800 C9---C10 1.395 (3) C87---H87C 0.9800 C9---C24 1.513 (3) C88---H88A 0.9800 C10---C11 1.397 (3) C88---H88B 0.9800 C10---H10 0.9500 C88---H88C 0.9800 C11---C12 1.399 (3) C89---C94 1.406 (4) C11---C16 1.532 (3) C89---C90 1.413 (3) C12---H12 0.9500 C90---C91 1.360 (4) C13---C14 1.505 (3) C90---H90 0.9500 C13---H13A 0.9900 C91---C92 1.418 (4) C13---H13B 0.9900 C91---H91 0.9500 C15---H15A 0.9800 C92---C93 1.372 (4) C15---H15B 0.9800 C92---H92 0.9500 C15---H15C 0.9800 C93---C94 1.412 (3) C16---C18 1.520 (4) C93---H93 0.9500 C16---C17 1.540 (4) C95---C100 1.404 (3) C16---C19 1.584 (4) C95---C96 1.417 (3) C17---H17A 0.9800 C96---C97 1.365 (4) C17---H17B 0.9800 C96---H96 0.9500 C17---H17C 0.9800 C97---C98 1.413 (4) C18---H18A 0.9800 C97---H97 0.9500 C18---H18B 0.9800 C98---C99 1.363 (4) C18---H18C 0.9800 C98---H98 0.9500 C19---C20 1.463 (3) C99---C100 1.417 (3) C19---H19A 0.9900 C99---H99 0.9500 C19---H19B 0.9900 C101---C106 1.386 (3) C20---C21\' 1.399 (3) C101---C102 1.393 (3) C20---C22 1.408 (3) C102---C103 1.400 (3) C20---C23 1.466 (3) C103---C104 1.391 (3) C20---C22\' 1.485 (3) C103---C118 1.512 (3) C20---C23\' 1.527 (4) C104---C105 1.395 (3) C20---C21 1.560 (4) C104---H10B 0.9500 C21---H21A 0.9800 C105---C106 1.394 (3) C21---H21B 0.9800 C105---C110 1.543 (3) C21---H21C 0.9800 C106---H10C 0.9500 C22---H22A 0.9800 C107---C108 1.503 (3) C22---H22B 0.9800 C107---H10D 0.9900 C22---H22C 0.9800 C107---H10E 0.9900 C23---H23A 0.9800 C109---H10F 0.9800 C23---H23B 0.9800 C109---H10G 0.9800 C23---H23C 0.9800 C109---H10H 0.9800 C21\'---H21D 0.9800 C110---C112 1.518 (3) C21\'---H21E 0.9800 C110---C113 1.546 (3) C21\'---H21F 0.9800 C110---C111 1.548 (3) C22\'---H22D 0.9800 C111---H11A 0.9800 C22\'---H22E 0.9800 C111---H11B 0.9800 C22\'---H22F 0.9800 C111---H11C 0.9800 C23\'---H23D 0.9800 C112---H11D 0.9800 C23\'---H23E 0.9800 C112---H11E 0.9800 C23\'---H23F 0.9800 C112---H11F 0.9800 C24---C25 1.516 (3) C113---C114 1.555 (4) C24---H24A 0.9900 C113---H11G 0.9900 C24---H24B 0.9900 C113---H11H 0.9900 C25---C30 1.392 (3) C114---C115 1.526 (4) C25---C26 1.402 (3) C114---C117 1.534 (4) C26---C27 1.393 (3) C114---C116 1.535 (4) C27---C28 1.386 (3) C115---H11I 0.9800 C28---C29 1.389 (3) C115---H11J 0.9800 C28---H28 0.9500 C115---H11K 0.9800 C29---C30 1.400 (3) C116---H11L 0.9800 C29---C34 1.533 (3) C116---H11M 0.9800 C30---H30 0.9500 C116---H11N 0.9800 C31---C32 1.510 (3) C117---H11O 0.9800 C31---H31A 0.9900 C117---H11P 0.9800 C31---H31B 0.9900 C117---H11Q 0.9800 C33---H33A 0.9800 C118---C119 1.517 (3) C33---H33B 0.9800 C118---H11R 0.9900 C33---H33C 0.9800 C118---H11S 0.9900 C34---C36 1.527 (3) C119---C120 1.392 (3) C34---C35 1.543 (3) C119---C124 1.393 (3) C34---C37 1.554 (3) C120---C121 1.393 (3) C35---H35A 0.9800 C121---C122 1.384 (3) C35---H35B 0.9800 C122---C123 1.390 (3) C35---H35C 0.9800 C122---H122 0.9500 C36---H36A 0.9800 C123---C124 1.395 (3) C36---H36B 0.9800 C123---C128 1.537 (3) C36---H36C 0.9800 C124---H124 0.9500 C37---C38 1.539 (4) C125---C126 1.503 (3) C37---H37A 0.9900 C125---H12D 0.9900 C37---H37B 0.9900 C125---H12E 0.9900 C38---C39 1.531 (3) C127---H12F 0.9800 C38---C41 1.532 (4) C127---H12G 0.9800 C38---C40 1.532 (3) C127---H12H 0.9800 C39---H39A 0.9800 C128---C130 1.529 (3) C39---H39B 0.9800 C128---C129 1.540 (3) C39---H39C 0.9800 C128---C131 1.564 (4) C40---H40A 0.9800 C129---H12I 0.9800 C40---H40B 0.9800 C129---H12J 0.9800 C40---H40C 0.9800 C129---H12K 0.9800 C41---H41A 0.9800 C130---H13C 0.9800 C41---H41B 0.9800 C130---H13D 0.9800 C41---H41C 0.9800 C130---H13E 0.9800 C42---C47 1.404 (4) C131---C132 1.533 (3) C42---C43 1.412 (3) C131---H13F 0.9900 C43---C44 1.362 (4) C131---H13G 0.9900 C43---H43 0.9500 C132---C133 1.525 (4) C44---C45 1.420 (4) C132---C135 1.526 (3) C44---H44 0.9500 C132---C134 1.535 (4) C45---C46 1.359 (3) C133---H13H 0.9800 C45---H45 0.9500 C133---H13I 0.9800 C46---C47 1.415 (3) C133---H13J 0.9800 C46---H46 0.9500 C134---H13K 0.9800 C48---C53 1.407 (4) C134---H13L 0.9800 C48---C49 1.415 (3) C134---H13M 0.9800 C49---C50 1.368 (4) C135---H13N 0.9800 C49---H49 0.9500 C135---H13O 0.9800 C50---C51 1.414 (4) C135---H13P 0.9800 C50---H50 0.9500 C136---C141 1.408 (4) C51---C52 1.361 (4) C136---C137 1.412 (3) C51---H51 0.9500 C137---C138 1.368 (4) C52---C53 1.417 (3) C137---H137 0.9500 C52---H52 0.9500 C138---C139 1.421 (4) C54---C59 1.381 (3) C138---H138 0.9500 C54---C55 1.394 (3) C139---C140 1.358 (4) C55---C56 1.397 (3) C139---H139 0.9500 C56---C57 1.396 (3) C140---C141 1.415 (3) C56---C71 1.509 (3) C140---H140 0.9500 C8---O1---C13 115.89 (19) H66A---C66---H66B 106.4 C14---O2---C15 116.1 (2) C68---C67---C70 108.0 (2) C26---O4---C31 118.18 (18) C68---C67---C69 107.7 (2) C32---O5---C33 116.10 (19) C70---C67---C69 107.7 (2) C55---O7---C60 115.42 (18) C68---C67---C66 113.2 (2) C61---O8---C62 115.8 (2) C70---C67---C66 114.0 (2) C73---O10---C78 118.62 (18) C69---C67---C66 106.0 (2) C79---O11---C80 116.64 (19) C67---C68---H68A 109.5 C102---O13---C107 117.83 (18) C67---C68---H68B 109.5 C108---O14---C109 116.40 (19) H68A---C68---H68B 109.5 C120---O16---C125 116.33 (18) C67---C68---H68C 109.5 C126---O17---C127 116.0 (2) H68A---C68---H68C 109.5 N2---N1---C1 102.3 (2) H68B---C68---H68C 109.5 N1---N2---N3 117.50 (19) C67---C69---H69A 109.5 N1---N2---C7 120.6 (2) C67---C69---H69B 109.5 N3---N2---C7 121.9 (2) H69A---C69---H69B 109.5 N2---N3---C6 102.4 (2) C67---C69---H69C 109.5 N5---N4---C42 102.41 (19) H69A---C69---H69C 109.5 N6---N5---N4 117.38 (19) H69B---C69---H69C 109.5 N6---N5---C27 120.12 (19) C67---C70---H70A 109.5 N4---N5---C27 121.66 (19) C67---C70---H70B 109.5 N5---N6---C47 102.60 (19) H70A---C70---H70B 109.5 N8---N7---C48 102.3 (2) C67---C70---H70C 109.5 N9---N8---N7 117.42 (19) H70A---C70---H70C 109.5 N9---N8---C54 122.1 (2) H70B---C70---H70C 109.5 N7---N8---C54 120.21 (19) C56---C71---C72 114.9 (2) N8---N9---C53 102.43 (19) C56---C71---H71A 108.6 N11---N10---C89 102.1 (2) C72---C71---H71A 108.6 N12---N11---N10 117.80 (19) C56---C71---H71B 108.6 N12---N11---C74 121.9 (2) C72---C71---H71B 108.6 N10---N11---C74 119.8 (2) H71A---C71---H71B 107.5 N11---N12---C94 102.3 (2) C77---C72---C73 118.7 (2) N14---N13---C95 102.39 (19) C77---C72---C71 119.6 (2) N15---N14---N13 117.36 (19) C73---C72---C71 121.6 (2) N15---N14---C101 121.24 (19) O10---C73---C74 123.8 (2) N13---N14---C101 121.22 (19) O10---C73---C72 117.6 (2) N14---N15---C100 102.6 (2) C74---C73---C72 118.6 (2) N17---N16---C136 102.5 (2) C73---C74---C75 121.6 (2) N16---N17---N18 117.54 (19) C73---C74---N11 122.6 (2) N16---N17---C121 121.1 (2) C75---C74---N11 115.7 (2) N18---N17---C121 120.91 (19) C76---C75---C74 120.9 (2) N17---N18---C141 102.2 (2) C76---C75---H75 119.6 N1---C1---C6 109.0 (2) C74---C75---H75 119.6 N1---C1---C2 129.3 (3) C75---C76---C77 116.7 (2) C6---C1---C2 121.7 (2) C75---C76---C81 122.0 (2) C3---C2---C1 116.2 (3) C77---C76---C81 121.1 (2) C3---C2---H2 121.9 C72---C77---C76 123.4 (2) C1---C2---H2 121.9 C72---C77---H77 118.3 C2---C3---C4 122.2 (2) C76---C77---H77 118.3 C2---C3---H3 118.9 O10---C78---C79 108.83 (19) C4---C3---H3 118.9 O10---C78---H78A 109.9 C5---C4---C3 122.4 (2) C79---C78---H78A 109.9 C5---C4---H4 118.8 O10---C78---H78B 109.9 C3---C4---H4 118.8 C79---C78---H78B 109.9 C4---C5---C6 116.9 (3) H78A---C78---H78B 108.3 C4---C5---H5 121.6 O12---C79---O11 124.0 (2) C6---C5---H5 121.6 O12---C79---C78 125.5 (2) N3---C6---C1 108.7 (2) O11---C79---C78 110.5 (2) N3---C6---C5 130.5 (2) O11---C80---H80A 109.5 C1---C6---C5 120.7 (2) O11---C80---H80B 109.5 C12---C7---C8 121.9 (2) H80A---C80---H80B 109.5 C12---C7---N2 118.2 (2) O11---C80---H80C 109.5 C8---C7---N2 119.8 (2) H80A---C80---H80C 109.5 O1---C8---C7 122.1 (2) H80B---C80---H80C 109.5 O1---C8---C9 119.1 (2) C82---C81---C76 111.15 (19) C7---C8---C9 118.8 (2) C82---C81---C83 106.8 (2) C8---C9---C10 118.8 (2) C76---C81---C83 106.7 (2) C8---C9---C24 119.7 (2) C82---C81---C84 113.2 (2) C10---C9---C24 121.3 (2) C76---C81---C84 112.3 (2) C9---C10---C11 122.8 (2) C83---C81---C84 106.26 (19) C9---C10---H10 118.6 C81---C82---H82A 109.5 C11---C10---H10 118.6 C81---C82---H82B 109.5 C10---C11---C12 117.2 (2) H82A---C82---H82B 109.5 C10---C11---C16 122.9 (2) C81---C82---H82C 109.5 C12---C11---C16 119.8 (2) H82A---C82---H82C 109.5 C7---C12---C11 120.4 (2) H82B---C82---H82C 109.5 C7---C12---H12 119.8 C81---C83---H83A 109.5 C11---C12---H12 119.8 C81---C83---H83B 109.5 O1---C13---C14 109.56 (19) H83A---C83---H83B 109.5 O1---C13---H13A 109.8 C81---C83---H83C 109.5 C14---C13---H13A 109.8 H83A---C83---H83C 109.5 O1---C13---H13B 109.8 H83B---C83---H83C 109.5 C14---C13---H13B 109.8 C85---C84---C81 122.9 (2) H13A---C13---H13B 108.2 C85---C84---H84A 106.6 O3---C14---O2 124.4 (2) C81---C84---H84A 106.6 O3---C14---C13 126.0 (2) C85---C84---H84B 106.6 O2---C14---C13 109.5 (2) C81---C84---H84B 106.6 O2---C15---H15A 109.5 H84A---C84---H84B 106.6 O2---C15---H15B 109.5 C86---C85---C87 110.5 (2) H15A---C15---H15B 109.5 C86---C85---C88 107.6 (2) O2---C15---H15C 109.5 C87---C85---C88 106.7 (2) H15A---C15---H15C 109.5 C86---C85---C84 112.8 (2) H15B---C15---H15C 109.5 C87---C85---C84 111.8 (2) C18---C16---C11 110.3 (2) C88---C85---C84 107.1 (2) C18---C16---C17 107.8 (3) C85---C86---H86A 109.5 C11---C16---C17 109.6 (2) C85---C86---H86B 109.5 C18---C16---C19 112.5 (3) H86A---C86---H86B 109.5 C11---C16---C19 106.4 (2) C85---C86---H86C 109.5 C17---C16---C19 110.2 (2) H86A---C86---H86C 109.5 C16---C17---H17A 109.5 H86B---C86---H86C 109.5 C16---C17---H17B 109.5 C85---C87---H87A 109.5 H17A---C17---H17B 109.5 C85---C87---H87B 109.5 C16---C17---H17C 109.5 H87A---C87---H87B 109.5 H17A---C17---H17C 109.5 C85---C87---H87C 109.5 H17B---C17---H17C 109.5 H87A---C87---H87C 109.5 C16---C18---H18A 109.5 H87B---C87---H87C 109.5 C16---C18---H18B 109.5 C85---C88---H88A 109.5 H18A---C18---H18B 109.5 C85---C88---H88B 109.5 C16---C18---H18C 109.5 H88A---C88---H88B 109.5 H18A---C18---H18C 109.5 C85---C88---H88C 109.5 H18B---C18---H18C 109.5 H88A---C88---H88C 109.5 C20---C19---C16 128.6 (2) H88B---C88---H88C 109.5 C20---C19---H19A 105.1 N10---C89---C94 109.4 (2) C16---C19---H19A 105.1 N10---C89---C90 129.3 (3) C20---C19---H19B 105.1 C94---C89---C90 121.2 (2) C16---C19---H19B 105.1 C91---C90---C89 116.7 (3) H19A---C19---H19B 105.9 C91---C90---H90 121.7 C22---C20---C19 118.6 (3) C89---C90---H90 121.7 C22---C20---C23 114.0 (3) C90---C91---C92 122.2 (3) C19---C20---C23 110.2 (3) C90---C91---H91 118.9 C21\'---C20---C22\' 113.0 (3) C92---C91---H91 118.9 C19---C20---C22\' 109.9 (3) C93---C92---C91 122.4 (2) C21\'---C20---C23\' 108.2 (3) C93---C92---H92 118.8 C19---C20---C23\' 110.3 (3) C91---C92---H92 118.8 C22\'---C20---C23\' 101.6 (3) C92---C93---C94 116.0 (3) C22---C20---C21 106.2 (3) C92---C93---H93 122.0 C19---C20---C21 103.8 (2) C94---C93---H93 122.0 C23---C20---C21 102.1 (3) N12---C94---C89 108.3 (2) C20---C21---H21A 109.5 N12---C94---C93 130.1 (3) C20---C21---H21B 109.5 C89---C94---C93 121.5 (2) C20---C21---H21C 109.5 N13---C95---C100 108.5 (2) C20---C22---H22A 109.5 N13---C95---C96 130.0 (2) C20---C22---H22B 109.5 C100---C95---C96 121.4 (2) C20---C22---H22C 109.5 C97---C96---C95 116.6 (3) C20---C23---H23A 109.5 C97---C96---H96 121.7 C20---C23---H23B 109.5 C95---C96---H96 121.7 C20---C23---H23C 109.5 C96---C97---C98 122.0 (2) C20---C21\'---H21D 109.5 C96---C97---H97 119.0 C20---C21\'---H21E 109.5 C98---C97---H97 119.0 H21D---C21\'---H21E 109.5 C99---C98---C97 122.4 (2) C20---C21\'---H21F 109.5 C99---C98---H98 118.8 H21D---C21\'---H21F 109.5 C97---C98---H98 118.8 H21E---C21\'---H21F 109.5 C98---C99---C100 116.9 (3) C20---C22\'---H22D 109.5 C98---C99---H99 121.6 C20---C22\'---H22E 109.5 C100---C99---H99 121.6 H22D---C22\'---H22E 109.5 N15---C100---C95 109.1 (2) C20---C22\'---H22F 109.5 N15---C100---C99 130.1 (2) H22D---C22\'---H22F 109.5 C95---C100---C99 120.7 (2) H22E---C22\'---H22F 109.5 C106---C101---C102 121.3 (2) C20---C23\'---H23D 109.5 C106---C101---N14 117.2 (2) C20---C23\'---H23E 109.5 C102---C101---N14 121.4 (2) H23D---C23\'---H23E 109.5 O13---C102---C101 123.1 (2) C20---C23\'---H23F 109.5 O13---C102---C103 118.2 (2) H23D---C23\'---H23F 109.5 C101---C102---C103 118.7 (2) H23E---C23\'---H23F 109.5 C104---C103---C102 118.7 (2) C9---C24---C25 115.3 (2) C104---C103---C118 119.6 (2) C9---C24---H24A 108.4 C102---C103---C118 121.7 (2) C25---C24---H24A 108.4 C103---C104---C105 123.5 (2) C9---C24---H24B 108.4 C103---C104---H10B 118.3 C25---C24---H24B 108.4 C105---C104---H10B 118.3 H24A---C24---H24B 107.5 C106---C105---C104 116.5 (2) C30---C25---C26 119.0 (2) C106---C105---C110 122.5 (2) C30---C25---C24 120.2 (2) C104---C105---C110 120.7 (2) C26---C25---C24 120.7 (2) C101---C106---C105 121.3 (2) O4---C26---C27 124.0 (2) C101---C106---H10C 119.4 O4---C26---C25 117.7 (2) C105---C106---H10C 119.4 C27---C26---C25 118.3 (2) O13---C107---C108 108.92 (19) C28---C27---C26 121.5 (2) O13---C107---H10D 109.9 C28---C27---N5 116.2 (2) C108---C107---H10D 109.9 C26---C27---N5 122.3 (2) O13---C107---H10E 109.9 C27---C28---C29 121.4 (2) C108---C107---H10E 109.9 C27---C28---H28 119.3 H10D---C107---H10E 108.3 C29---C28---H28 119.3 O15---C108---O14 123.7 (2) C28---C29---C30 116.5 (2) O15---C108---C107 126.2 (2) C28---C29---C34 122.5 (2) O14---C108---C107 110.1 (2) C30---C29---C34 120.8 (2) O14---C109---H10F 109.5 C25---C30---C29 123.2 (2) O14---C109---H10G 109.5 C25---C30---H30 118.4 H10F---C109---H10G 109.5 C29---C30---H30 118.4 O14---C109---H10H 109.5 O4---C31---C32 108.40 (19) H10F---C109---H10H 109.5 O4---C31---H31A 110.0 H10G---C109---H10H 109.5 C32---C31---H31A 110.0 C112---C110---C105 111.5 (2) O4---C31---H31B 110.0 C112---C110---C113 112.7 (2) C32---C31---H31B 110.0 C105---C110---C113 112.6 (2) H31A---C31---H31B 108.4 C112---C110---C111 106.7 (2) O6---C32---O5 124.1 (2) C105---C110---C111 106.8 (2) O6---C32---C31 126.2 (2) C113---C110---C111 106.0 (2) O5---C32---C31 109.7 (2) C110---C111---H11A 109.5 O5---C33---H33A 109.5 C110---C111---H11B 109.5 O5---C33---H33B 109.5 H11A---C111---H11B 109.5 H33A---C33---H33B 109.5 C110---C111---H11C 109.5 O5---C33---H33C 109.5 H11A---C111---H11C 109.5 H33A---C33---H33C 109.5 H11B---C111---H11C 109.5 H33B---C33---H33C 109.5 C110---C112---H11D 109.5 C36---C34---C29 111.0 (2) C110---C112---H11E 109.5 C36---C34---C35 106.5 (2) H11D---C112---H11E 109.5 C29---C34---C35 107.2 (2) C110---C112---H11F 109.5 C36---C34---C37 112.8 (2) H11D---C112---H11F 109.5 C29---C34---C37 112.7 (2) H11E---C112---H11F 109.5 C35---C34---C37 106.1 (2) C110---C113---C114 122.9 (2) C34---C35---H35A 109.5 C110---C113---H11G 106.6 C34---C35---H35B 109.5 C114---C113---H11G 106.6 H35A---C35---H35B 109.5 C110---C113---H11H 106.6 C34---C35---H35C 109.5 C114---C113---H11H 106.6 H35A---C35---H35C 109.5 H11G---C113---H11H 106.6 H35B---C35---H35C 109.5 C115---C114---C117 111.3 (2) C34---C36---H36A 109.5 C115---C114---C116 108.5 (2) C34---C36---H36B 109.5 C117---C114---C116 107.1 (2) H36A---C36---H36B 109.5 C115---C114---C113 111.3 (2) C34---C36---H36C 109.5 C117---C114---C113 111.6 (2) H36A---C36---H36C 109.5 C116---C114---C113 106.7 (2) H36B---C36---H36C 109.5 C114---C115---H11I 109.5 C38---C37---C34 123.7 (2) C114---C115---H11J 109.5 C38---C37---H37A 106.4 H11I---C115---H11J 109.5 C34---C37---H37A 106.4 C114---C115---H11K 109.5 C38---C37---H37B 106.4 H11I---C115---H11K 109.5 C34---C37---H37B 106.4 H11J---C115---H11K 109.5 H37A---C37---H37B 106.5 C114---C116---H11L 109.5 C39---C38---C41 107.1 (2) C114---C116---H11M 109.5 C39---C38---C40 107.6 (2) H11L---C116---H11M 109.5 C41---C38---C40 110.3 (2) C114---C116---H11N 109.5 C39---C38---C37 107.3 (2) H11L---C116---H11N 109.5 C41---C38---C37 112.1 (2) H11M---C116---H11N 109.5 C40---C38---C37 112.2 (2) C114---C117---H11O 109.5 C38---C39---H39A 109.5 C114---C117---H11P 109.5 C38---C39---H39B 109.5 H11O---C117---H11P 109.5 H39A---C39---H39B 109.5 C114---C117---H11Q 109.5 C38---C39---H39C 109.5 H11O---C117---H11Q 109.5 H39A---C39---H39C 109.5 H11P---C117---H11Q 109.5 H39B---C39---H39C 109.5 C103---C118---C119 114.9 (2) C38---C40---H40A 109.5 C103---C118---H11R 108.5 C38---C40---H40B 109.5 C119---C118---H11R 108.5 H40A---C40---H40B 109.5 C103---C118---H11S 108.5 C38---C40---H40C 109.5 C119---C118---H11S 108.5 H40A---C40---H40C 109.5 H11R---C118---H11S 107.5 H40B---C40---H40C 109.5 C120---C119---C124 118.7 (2) C38---C41---H41A 109.5 C120---C119---C118 119.5 (2) C38---C41---H41B 109.5 C124---C119---C118 121.7 (2) H41A---C41---H41B 109.5 O16---C120---C119 118.4 (2) C38---C41---H41C 109.5 O16---C120---C121 122.7 (2) H41A---C41---H41C 109.5 C119---C120---C121 118.9 (2) H41B---C41---H41C 109.5 C122---C121---C120 121.5 (2) N4---C42---C47 108.8 (2) C122---C121---N17 117.5 (2) N4---C42---C43 130.5 (2) C120---C121---N17 121.0 (2) C47---C42---C43 120.7 (2) C121---C122---C123 120.7 (2) C44---C43---C42 117.0 (3) C121---C122---H122 119.6 C44---C43---H43 121.5 C123---C122---H122 119.6 C42---C43---H43 121.5 C122---C123---C124 117.2 (2) C43---C44---C45 121.9 (2) C122---C123---C128 120.3 (2) C43---C44---H44 119.1 C124---C123---C128 122.5 (2) C45---C44---H44 119.1 C119---C124---C123 123.0 (2) C46---C45---C44 122.5 (2) C119---C124---H124 118.5 C46---C45---H45 118.8 C123---C124---H124 118.5 C44---C45---H45 118.8 O16---C125---C126 109.18 (19) C45---C46---C47 116.2 (2) O16---C125---H12D 109.8 C45---C46---H46 121.9 C126---C125---H12D 109.8 C47---C46---H46 121.9 O16---C125---H12E 109.8 N6---C47---C42 108.8 (2) C126---C125---H12E 109.8 N6---C47---C46 129.4 (2) H12D---C125---H12E 108.3 C42---C47---C46 121.7 (2) O18---C126---O17 124.0 (2) N7---C48---C53 109.0 (2) O18---C126---C125 126.5 (2) N7---C48---C49 129.2 (2) O17---C126---C125 109.5 (2) C53---C48---C49 121.7 (2) O17---C127---H12F 109.5 C50---C49---C48 116.7 (3) O17---C127---H12G 109.5 C50---C49---H49 121.6 H12F---C127---H12G 109.5 C48---C49---H49 121.6 O17---C127---H12H 109.5 C49---C50---C51 121.4 (2) H12F---C127---H12H 109.5 C49---C50---H50 119.3 H12G---C127---H12H 109.5 C51---C50---H50 119.3 C130---C128---C123 109.4 (2) C52---C51---C50 122.9 (2) C130---C128---C129 107.8 (2) C52---C51---H51 118.5 C123---C128---C129 109.54 (19) C50---C51---H51 118.5 C130---C128---C131 113.5 (2) C51---C52---C53 116.9 (3) C123---C128---C131 104.0 (2) C51---C52---H52 121.6 C129---C128---C131 112.5 (2) C53---C52---H52 121.6 C128---C129---H12I 109.5 N9---C53---C48 108.9 (2) C128---C129---H12J 109.5 N9---C53---C52 130.6 (2) H12I---C129---H12J 109.5 C48---C53---C52 120.4 (2) C128---C129---H12K 109.5 C59---C54---C55 121.5 (2) H12I---C129---H12K 109.5 C59---C54---N8 118.4 (2) H12J---C129---H12K 109.5 C55---C54---N8 120.1 (2) C128---C130---H13C 109.5 O7---C55---C54 121.9 (2) C128---C130---H13D 109.5 O7---C55---C56 118.8 (2) H13C---C130---H13D 109.5 C54---C55---C56 119.2 (2) C128---C130---H13E 109.5 C57---C56---C55 118.2 (2) H13C---C130---H13E 109.5 C57---C56---C71 121.9 (2) H13D---C130---H13E 109.5 C55---C56---C71 119.8 (2) C132---C131---C128 124.7 (2) C58---C57---C56 123.3 (2) C132---C131---H13F 106.2 C58---C57---H57 118.4 C128---C131---H13F 106.2 C56---C57---H57 118.4 C132---C131---H13G 106.2 C57---C58---C59 117.1 (2) C128---C131---H13G 106.2 C57---C58---C63 122.5 (2) H13F---C131---H13G 106.3 C59---C58---C63 120.3 (2) C133---C132---C135 108.1 (2) C54---C59---C58 120.6 (2) C133---C132---C131 113.9 (2) C54---C59---H59 119.7 C135---C132---C131 113.6 (2) C58---C59---H59 119.7 C133---C132---C134 107.2 (2) O7---C60---C61 109.27 (19) C135---C132---C134 107.4 (2) O7---C60---H60A 109.8 C131---C132---C134 106.2 (2) C61---C60---H60A 109.8 C132---C133---H13H 109.5 O7---C60---H60B 109.8 C132---C133---H13I 109.5 C61---C60---H60B 109.8 H13H---C133---H13I 109.5 H60A---C60---H60B 108.3 C132---C133---H13J 109.5 O9---C61---O8 124.4 (2) H13H---C133---H13J 109.5 O9---C61---C60 126.9 (2) H13I---C133---H13J 109.5 O8---C61---C60 108.7 (2) C132---C134---H13K 109.5 O8---C62---H62A 109.5 C132---C134---H13L 109.5 O8---C62---H62B 109.5 H13K---C134---H13L 109.5 H62A---C62---H62B 109.5 C132---C134---H13M 109.5 O8---C62---H62C 109.5 H13K---C134---H13M 109.5 H62A---C62---H62C 109.5 H13L---C134---H13M 109.5 H62B---C62---H62C 109.5 C132---C135---H13N 109.5 C65---C63---C58 110.04 (19) C132---C135---H13O 109.5 C65---C63---C64 107.2 (2) H13N---C135---H13O 109.5 C58---C63---C64 109.2 (2) C132---C135---H13P 109.5 C65---C63---C66 113.2 (2) H13N---C135---H13P 109.5 C58---C63---C66 104.76 (18) H13O---C135---H13P 109.5 C64---C63---C66 112.4 (2) N16---C136---C141 108.7 (2) C63---C64---H64A 109.5 N16---C136---C137 130.0 (2) C63---C64---H64B 109.5 C141---C136---C137 121.2 (2) H64A---C64---H64B 109.5 C138---C137---C136 116.8 (3) C63---C64---H64C 109.5 C138---C137---H137 121.6 H64A---C64---H64C 109.5 C136---C137---H137 121.6 H64B---C64---H64C 109.5 C137---C138---C139 121.6 (2) C63---C65---H65A 109.5 C137---C138---H138 119.2 C63---C65---H65B 109.5 C139---C138---H138 119.2 H65A---C65---H65B 109.5 C140---C139---C138 122.7 (3) C63---C65---H65C 109.5 C140---C139---H139 118.7 H65A---C65---H65C 109.5 C138---C139---H139 118.7 H65B---C65---H65C 109.5 C139---C140---C141 116.6 (3) C67---C66---C63 124.4 (2) C139---C140---H140 121.7 C67---C66---H66A 106.2 C141---C140---H140 121.7 C63---C66---H66A 106.2 N18---C141---C136 109.0 (2) C67---C66---H66B 106.2 N18---C141---C140 129.8 (2) C63---C66---H66B 106.2 C136---C141---C140 121.1 (2) C1---N1---N2---N3 −0.5 (3) C59---C58---C63---C65 34.2 (3) C1---N1---N2---C7 −177.5 (2) C57---C58---C63---C64 −30.0 (3) N1---N2---N3---C6 0.2 (3) C59---C58---C63---C64 151.7 (2) C7---N2---N3---C6 177.1 (2) C57---C58---C63---C66 90.6 (3) C42---N4---N5---N6 −0.8 (3) C59---C58---C63---C66 −87.7 (3) C42---N4---N5---C27 −170.2 (2) C65---C63---C66---C67 51.6 (3) N4---N5---N6---C47 0.8 (3) C58---C63---C66---C67 171.5 (2) C27---N5---N6---C47 170.5 (2) C64---C63---C66---C67 −70.0 (3) C48---N7---N8---N9 0.5 (3) C63---C66---C67---C68 −69.6 (3) C48---N7---N8---C54 174.6 (2) C63---C66---C67---C70 54.3 (3) N7---N8---N9---C53 −0.8 (3) C63---C66---C67---C69 172.5 (2) C54---N8---N9---C53 −174.8 (2) C57---C56---C71---C72 44.2 (3) C89---N10---N11---N12 −0.8 (3) C55---C56---C71---C72 −138.9 (2) C89---N10---N11---C74 −173.0 (2) C56---C71---C72---C77 61.6 (3) N10---N11---N12---C94 1.1 (3) C56---C71---C72---C73 −121.5 (2) C74---N11---N12---C94 173.1 (2) C78---O10---C73---C74 52.5 (3) C95---N13---N14---N15 0.8 (3) C78---O10---C73---C72 −130.5 (2) C95---N13---N14---C101 176.0 (2) C77---C72---C73---O10 −174.7 (2) N13---N14---N15---C100 −0.6 (3) C71---C72---C73---O10 8.4 (3) C101---N14---N15---C100 −175.8 (2) C77---C72---C73---C74 2.5 (3) C136---N16---N17---N18 0.7 (3) C71---C72---C73---C74 −174.4 (2) C136---N16---N17---C121 173.4 (2) O10---C73---C74---C75 175.2 (2) N16---N17---N18---C141 −0.6 (3) C72---C73---C74---C75 −1.8 (4) C121---N17---N18---C141 −173.3 (2) O10---C73---C74---N11 −2.5 (4) N2---N1---C1---C6 0.6 (2) C72---C73---C74---N11 −179.5 (2) N2---N1---C1---C2 178.2 (2) N12---N11---C74---C73 55.4 (3) N1---C1---C2---C3 −176.8 (2) N10---N11---C74---C73 −132.7 (2) C6---C1---C2---C3 0.6 (4) N12---N11---C74---C75 −122.5 (2) C1---C2---C3---C4 0.2 (4) N10---N11---C74---C75 49.4 (3) C2---C3---C4---C5 −0.7 (4) C73---C74---C75---C76 −0.6 (4) C3---C4---C5---C6 0.4 (4) N11---C74---C75---C76 177.3 (2) N2---N3---C6---C1 0.2 (2) C74---C75---C76---C77 2.1 (4) N2---N3---C6---C5 −177.0 (3) C74---C75---C76---C81 −172.5 (2) N1---C1---C6---N3 −0.6 (3) C73---C72---C77---C76 −1.0 (4) C2---C1---C6---N3 −178.4 (2) C71---C72---C77---C76 176.0 (2) N1---C1---C6---C5 177.0 (2) C75---C76---C77---C72 −1.3 (4) C2---C1---C6---C5 −0.8 (4) C81---C76---C77---C72 173.3 (2) C4---C5---C6---N3 177.3 (2) C73---O10---C78---C79 132.3 (2) C4---C5---C6---C1 0.3 (4) C80---O11---C79---O12 0.1 (4) N1---N2---C7---C12 124.4 (2) C80---O11---C79---C78 −179.7 (2) N3---N2---C7---C12 −52.4 (3) O10---C78---C79---O12 −4.2 (4) N1---N2---C7---C8 −53.8 (3) O10---C78---C79---O11 175.5 (2) N3---N2---C7---C8 129.3 (2) C75---C76---C81---C82 3.8 (3) C13---O1---C8---C7 −61.1 (3) C77---C76---C81---C82 −170.6 (2) C13---O1---C8---C9 120.5 (2) C75---C76---C81---C83 119.8 (2) C12---C7---C8---O1 179.1 (2) C77---C76---C81---C83 −54.5 (3) N2---C7---C8---O1 −2.8 (3) C75---C76---C81---C84 −124.1 (2) C12---C7---C8---C9 −2.6 (4) C77---C76---C81---C84 61.5 (3) N2---C7---C8---C9 175.6 (2) C82---C81---C84---C85 −47.1 (3) O1---C8---C9---C10 179.0 (2) C76---C81---C84---C85 79.7 (3) C7---C8---C9---C10 0.7 (3) C83---C81---C84---C85 −164.0 (2) O1---C8---C9---C24 −5.3 (3) C81---C84---C85---C86 −48.2 (3) C7---C8---C9---C24 176.3 (2) C81---C84---C85---C87 77.0 (3) C8---C9---C10---C11 1.0 (4) C81---C84---C85---C88 −166.4 (2) C24---C9---C10---C11 −174.6 (2) N11---N10---C89---C94 0.1 (2) C9---C10---C11---C12 −0.7 (4) N11---N10---C89---C90 176.1 (3) C9---C10---C11---C16 176.5 (2) N10---C89---C90---C91 −176.9 (2) C8---C7---C12---C11 2.9 (4) C94---C89---C90---C91 −1.3 (4) N2---C7---C12---C11 −175.3 (2) C89---C90---C91---C92 −0.6 (4) C10---C11---C12---C7 −1.2 (4) C90---C91---C92---C93 1.9 (4) C16---C11---C12---C7 −178.5 (2) C91---C92---C93---C94 −1.1 (4) C8---O1---C13---C14 −123.9 (2) N11---N12---C94---C89 −0.9 (3) C15---O2---C14---O3 −0.6 (4) N11---N12---C94---C93 −178.6 (2) C15---O2---C14---C13 177.3 (2) N10---C89---C94---N12 0.6 (3) O1---C13---C14---O3 −5.6 (4) C90---C89---C94---N12 −175.8 (2) O1---C13---C14---O2 176.50 (19) N10---C89---C94---C93 178.5 (2) C10---C11---C16---C18 24.8 (4) C90---C89---C94---C93 2.1 (4) C12---C11---C16---C18 −158.0 (3) C92---C93---C94---N12 176.6 (3) C10---C11---C16---C17 143.4 (2) C92---C93---C94---C89 −0.9 (4) C12---C11---C16---C17 −39.5 (3) N14---N13---C95---C100 −0.6 (2) C10---C11---C16---C19 −97.5 (3) N14---N13---C95---C96 −178.1 (2) C12---C11---C16---C19 79.7 (3) N13---C95---C96---C97 176.4 (2) C18---C16---C19---C20 56.7 (4) C100---C95---C96---C97 −0.7 (4) C11---C16---C19---C20 177.6 (2) C95---C96---C97---C98 −0.2 (4) C17---C16---C19---C20 −63.7 (3) C96---C97---C98---C99 0.9 (4) C16---C19---C20---C21\' −162.5 (3) C97---C98---C99---C100 −0.6 (4) C16---C19---C20---C22 41.5 (4) N14---N15---C100---C95 0.1 (3) C16---C19---C20---C23 −92.5 (4) N14---N15---C100---C99 176.8 (3) C16---C19---C20---C22\' 70.2 (4) N13---C95---C100---N15 0.3 (3) C16---C19---C20---C23\' −41.0 (4) C96---C95---C100---N15 178.0 (2) C16---C19---C20---C21 158.9 (3) N13---C95---C100---C99 −176.7 (2) C8---C9---C24---C25 134.9 (2) C96---C95---C100---C99 1.0 (4) C10---C9---C24---C25 −49.6 (3) C98---C99---C100---N15 −176.6 (2) C9---C24---C25---C30 −58.5 (3) C98---C99---C100---C95 −0.3 (4) C9---C24---C25---C26 125.5 (2) N15---N14---C101---C106 56.3 (3) C31---O4---C26---C27 −56.1 (3) N13---N14---C101---C106 −118.7 (2) C31---O4---C26---C25 127.1 (2) N15---N14---C101---C102 −125.3 (2) C30---C25---C26---O4 175.1 (2) N13---N14---C101---C102 59.7 (3) C24---C25---C26---O4 −8.9 (3) C107---O13---C102---C101 56.3 (3) C30---C25---C26---C27 −1.9 (3) C107---O13---C102---C103 −127.3 (2) C24---C25---C26---C27 174.1 (2) C106---C101---C102---O13 175.4 (2) O4---C26---C27---C28 −175.5 (2) N14---C101---C102---O13 −2.9 (3) C25---C26---C27---C28 1.3 (3) C106---C101---C102---C103 −1.0 (3) O4---C26---C27---N5 2.4 (4) N14---C101---C102---C103 −179.3 (2) C25---C26---C27---N5 179.2 (2) O13---C102---C103---C104 −174.6 (2) N6---N5---C27---C28 −42.9 (3) C101---C102---C103---C104 2.0 (3) N4---N5---C27---C28 126.3 (2) O13---C102---C103---C118 8.2 (3) N6---N5---C27---C26 139.1 (2) C101---C102---C103---C118 −175.2 (2) N4---N5---C27---C26 −51.7 (3) C102---C103---C104---C105 −0.8 (4) C26---C27---C28---C29 1.3 (4) C118---C103---C104---C105 176.5 (2) N5---C27---C28---C29 −176.8 (2) C103---C104---C105---C106 −1.5 (4) C27---C28---C29---C30 −3.1 (3) C103---C104---C105---C110 172.0 (2) C27---C28---C29---C34 172.1 (2) C102---C101---C106---C105 −1.4 (4) C26---C25---C30---C29 0.0 (4) N14---C101---C106---C105 177.1 (2) C24---C25---C30---C29 −176.1 (2) C104---C105---C106---C101 2.5 (3) C28---C29---C30---C25 2.5 (4) C110---C105---C106---C101 −170.9 (2) C34---C29---C30---C25 −172.8 (2) C102---O13---C107---C108 124.6 (2) C26---O4---C31---C32 −138.1 (2) C109---O14---C108---O15 1.2 (4) C33---O5---C32---O6 −1.7 (4) C109---O14---C108---C107 −178.2 (2) C33---O5---C32---C31 178.2 (2) O13---C107---C108---O15 −2.0 (4) O4---C31---C32---O6 2.8 (4) O13---C107---C108---O14 177.4 (2) O4---C31---C32---O5 −177.1 (2) C106---C105---C110---C112 1.9 (3) C28---C29---C34---C36 −8.0 (3) C104---C105---C110---C112 −171.3 (2) C30---C29---C34---C36 167.0 (2) C106---C105---C110---C113 −126.0 (2) C28---C29---C34---C35 −124.0 (3) C104---C105---C110---C113 60.8 (3) C30---C29---C34---C35 51.0 (3) C106---C105---C110---C111 118.0 (3) C28---C29---C34---C37 119.7 (2) C104---C105---C110---C111 −55.1 (3) C30---C29---C34---C37 −65.3 (3) C112---C110---C113---C114 −47.2 (3) C36---C34---C37---C38 45.9 (3) C105---C110---C113---C114 80.1 (3) C29---C34---C37---C38 −80.8 (3) C111---C110---C113---C114 −163.5 (2) C35---C34---C37---C38 162.2 (2) C110---C113---C114---C115 −47.4 (3) C34---C37---C38---C39 167.0 (2) C110---C113---C114---C117 77.7 (3) C34---C37---C38---C41 −75.7 (3) C110---C113---C114---C116 −165.7 (2) C34---C37---C38---C40 49.1 (3) C104---C103---C118---C119 61.6 (3) N5---N4---C42---C47 0.4 (3) C102---C103---C118---C119 −121.2 (2) N5---N4---C42---C43 178.3 (3) C103---C118---C119---C120 −139.1 (2) N4---C42---C43---C44 −177.0 (3) C103---C118---C119---C124 44.2 (3) C47---C42---C43---C44 0.8 (4) C125---O16---C120---C119 −118.4 (2) C42---C43---C44---C45 0.1 (4) C125---O16---C120---C121 63.2 (3) C43---C44---C45---C46 −0.7 (4) C124---C119---C120---O16 −178.1 (2) C44---C45---C46---C47 0.2 (4) C118---C119---C120---O16 5.1 (3) N5---N6---C47---C42 −0.5 (2) C124---C119---C120---C121 0.4 (4) N5---N6---C47---C46 −177.0 (2) C118---C119---C120---C121 −176.5 (2) N4---C42---C47---N6 0.1 (3) O16---C120---C121---C122 179.6 (2) C43---C42---C47---N6 −178.1 (2) C119---C120---C121---C122 1.2 (4) N4---C42---C47---C46 176.9 (2) O16---C120---C121---N17 2.3 (4) C43---C42---C47---C46 −1.3 (4) C119---C120---C121---N17 −176.1 (2) C45---C46---C47---N6 176.8 (2) N16---N17---C121---C122 −128.7 (2) C45---C46---C47---C42 0.7 (4) N18---N17---C121---C122 43.7 (3) N8---N7---C48---C53 0.1 (3) N16---N17---C121---C120 48.7 (3) N8---N7---C48---C49 −177.0 (2) N18---N17---C121---C120 −138.9 (2) N7---C48---C49---C50 176.2 (2) C120---C121---C122---C123 −2.2 (4) C53---C48---C49---C50 −0.5 (4) N17---C121---C122---C123 175.3 (2) C48---C49---C50---C51 0.4 (4) C121---C122---C123---C124 1.5 (4) C49---C50---C51---C52 −0.1 (4) C121---C122---C123---C128 178.4 (2) C50---C51---C52---C53 −0.2 (4) C120---C119---C124---C123 −1.0 (4) N8---N9---C53---C48 0.7 (3) C118---C119---C124---C123 175.7 (2) N8---N9---C53---C52 176.7 (3) C122---C123---C124---C119 0.1 (4) N7---C48---C53---N9 −0.5 (3) C128---C123---C124---C119 −176.8 (2) C49---C48---C53---N9 176.8 (2) C120---O16---C125---C126 135.0 (2) N7---C48---C53---C52 −177.0 (2) C127---O17---C126---O18 1.3 (4) C49---C48---C53---C52 0.3 (4) C127---O17---C126---C125 −178.3 (2) C51---C52---C53---N9 −175.6 (3) O16---C125---C126---O18 −0.7 (4) C51---C52---C53---C48 0.1 (4) O16---C125---C126---O17 178.9 (2) N9---N8---C54---C59 48.5 (3) C122---C123---C128---C130 152.5 (2) N7---N8---C54---C59 −125.3 (2) C124---C123---C128---C130 −30.7 (3) N9---N8---C54---C55 −133.2 (2) C122---C123---C128---C129 34.6 (3) N7---N8---C54---C55 53.0 (3) C124---C123---C128---C129 −148.6 (2) C60---O7---C55---C54 66.2 (3) C122---C123---C128---C131 −85.9 (3) C60---O7---C55---C56 −115.7 (2) C124---C123---C128---C131 90.9 (3) C59---C54---C55---O7 −179.6 (2) C130---C128---C131---C132 −68.4 (3) N8---C54---C55---O7 2.2 (3) C123---C128---C131---C132 172.8 (2) C59---C54---C55---C56 2.3 (3) C129---C128---C131---C132 54.3 (3) N8---C54---C55---C56 −175.9 (2) C128---C131---C132---C133 55.0 (3) O7---C55---C56---C57 −178.5 (2) C128---C131---C132---C135 −69.4 (3) C54---C55---C56---C57 −0.3 (3) C128---C131---C132---C134 172.8 (2) O7---C55---C56---C71 4.4 (3) N17---N16---C136---C141 −0.5 (3) C54---C55---C56---C71 −177.4 (2) N17---N16---C136---C137 −177.7 (2) C55---C56---C57---C58 −1.3 (4) N16---C136---C137---C138 177.5 (3) C71---C56---C57---C58 175.7 (2) C141---C136---C137---C138 0.5 (4) C56---C57---C58---C59 1.0 (3) C136---C137---C138---C139 −1.0 (4) C56---C57---C58---C63 −177.4 (2) C137---C138---C139---C140 0.7 (4) C55---C54---C59---C58 −2.6 (4) C138---C139---C140---C141 0.2 (4) N8---C54---C59---C58 175.6 (2) N17---N18---C141---C136 0.3 (3) C57---C58---C59---C54 1.0 (3) N17---N18---C141---C140 177.2 (3) C63---C58---C59---C54 179.4 (2) N16---C136---C141---N18 0.1 (3) C55---O7---C60---C61 126.7 (2) C137---C136---C141---N18 177.7 (2) C62---O8---C61---O9 2.9 (4) N16---C136---C141---C140 −177.2 (2) C62---O8---C61---C60 −175.3 (2) C137---C136---C141---C140 0.4 (4) O7---C60---C61---O9 6.1 (4) C139---C140---C141---N18 −177.4 (3) O7---C60---C61---O8 −175.72 (19) C139---C140---C141---C136 −0.8 (4) C57---C58---C63---C65 −147.5 (2) ------------------------- -------------- --------------------------- ------------- :::	PubMed Central	2024-06-05T04:04:18.607328	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052126/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o722", "authors": [ { "first": "Tahir", "last": "Qadri" }, { "first": "Itrat", "last": "Anis" }, { "first": "M. R.", "last": "Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052127	Related literature {#sec1} ================== For general background to anthraquinones, see: Arai et al. (1985[@bb1]); Dalliya et al. (2007[@bb2]); Gatto et al. (1996[@bb4]); Kowalczyk et al. (2010[@bb6]); Mori et al. (1990[@bb7]); Ossowski et al. (2005[@bb8]); Zoń et al. (2003[@bb14]). For a related structure, see: Yatsenko et al. (2000[@bb13]). For molecular interactions, see: Hunter et al. (2001[@bb5]); Spek (2009[@bb11]); Takahashi et al. (2001[@bb12]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~13~NO~2~M ~r~ = 251.27Orthorhombic,a = 7.2823 (3) Åb = 11.1519 (7) Åc = 14.9834 (7) ÅV = 1216.82 (11) Å^3^Z = 4Mo Kα radiationμ = 0.09 mm^−1^T = 295 K0.45 × 0.20 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini R ULTRA Ruby CCD diffractometer4683 measured reflections1258 independent reflections918 reflections with I \> 2σ(I)R ~int~ = 0.033 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.037wR(F ^2^) = 0.079S = 0.961258 reflections174 parametersH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e498} Data collection: CrysAlis CCD (Oxford Diffraction, 2008[@bb9]); cell refinement: CrysAlis RED (Oxford Diffraction, 2008[@bb9]); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb10]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb10]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb3]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006829/ng5119sup1.cif](http://dx.doi.org/10.1107/S1600536811006829/ng5119sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006829/ng5119Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006829/ng5119Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5119&file=ng5119sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5119sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5119&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5119](http://scripts.iucr.org/cgi-bin/sendsup?ng5119)). This study was financed by the State Funds for Scientific Research (grant DS/8210-4-0177-11). Comment ======= Anthraquinones, the largest group of naturally occurring quinones, present in bacteria, fungi and many higher plant families contain π-electrons, reducible p-quinone system and are redoxactive (Zoń et al., 2003). That is the reason why those found many practical applications (Kowalczyk et al., 2010; Ossowski et al., 2005). Both natural and synthetic derivatives have been used as colourants in food, cosmetics, textiles and hair dyes (Mori et al., 1990). In medicine they are known as antitumor drugs and antibacterial or anti-inflammatory agents (Gatto et al., 1996). Among anthraquinones, the amino-derivatives, due to the possibility of their chemical modification, reveal greatest potential of application. Here, we present the crystal structure of the 1-(dimethylamino)-9,10-anthraquinone -- compound with interesting photophysical properties (Arai et al., 1985; Dalliya et al., 2007). In the molecule of the title compound (Fig. 1), likewise in the 1-(methyl(phenyl)amino)anthraquinone (Yatsenko et al., 2000), relatively strong deviation of planarity of the anthraquinone skeleton is observed. In case of the title compound, such distortion (0.1274 (3) Å) is directly caused by the steric effect of the bulky --N(CH~3~)~2~ group (Dalliya et al., 2007). The dimethylamino group is twisted at an angle of 38.4 (1)° relative to the anthracene fragment. The neighboring anthracene moieties are inclined at an angle of 59.3 (1)°, 75.7 (1)° and 76.0 (1)° in the crystal lattice. In the crystal structure, the adjacent molecules are linked by C--H···π (Table 2, Fig. 2) and π-π \[centroid-centroid distances = 3.844 (2) Å\] (Table 3, Fig. 3) contacts. All interactions demonstrated were found by PLATON (Spek, 2009). The C--H···π interactions should be of an attractive nature (Takahashi et al., 2001), like the π-π (Hunter et al., 2001) interactions. Experimental {#experimental} ============ 1-(Dimethylamino)-9,10-anthraquinone was synthesized according to the procedure described below. The solution of 40% dimethylamine in water (2,21 ml, 12.36 mmol) was added to 1-chloro-9,10-anthraquinone (1 g, 4.12 mmol) in 15 ml toluene. The mixture was stirred at 130° for 4 h. The progress of the reaction was monitored by TLC (SiO~2~, dichloromethane) until the completion of reaction. The resulting mixture was concentrated to remove the solvent and dissolved in 100 ml of dichloromethane. The solution was washed with water (100 ml), the organic phase was dried over MgSO~4~ and concentrated. The resultant solid was purified by column chromatography using dichloromethane as a solvent obtaining the title compound as a red solid (921 mg, 89%). The product was recrystallized by slow evaporation from methanol to give red crystals suitable for X-ray diffraction (m.p. 137.5--137.9°C). Spectral data: IR (KBr): 3584, 2916, 2806, 1662, 1637, 1551, 1499, 1374, 1311,1270, 1180, 1024, 935, 793, 731,704 cm^-1^; ^1^H NMR (CDCl~3~, 400 MHz): 3.03 (6H, s, CH~3~), 7.34--7.36 (1H, d, J~1~ = 8.8 Hz, H-2-Ar), 7.54--7.58 (1H, t, J~1~ = J~2~ = 8.0 Hz, H-3-Ar), 7.69--7.72 (1H, t, J~1~ = 7.6 Hz, J~1~ = 6.8 Hz, J~2~ = 7.2 Hz, H-6-Ar), 7.74--7.76 (1H, d, J~1~ = 7.6 Hz, H-4-Ar), 7.78--7.82 (1H, t, J~1~ = 7.6 Hz, J~1~ = 8.4 Hz, J~2~ = 8.0 Hz, H-7-Ar), 8.22--8.24 (1H, t, J~1~ = 7.2 Hz, H-8-Ar). Elemental analysis: calculated for C~16~H~13~NO~2~: C 76.48, H 5.21, N 5.57; found: C 76.52, H 5.28, N 5.51. Refinement {#refinement} ========== 1063 Friedel pairs were merged. H atoms were positioned geometrically, with C---H = 0.93 Å and 0.96 Å for the aromatic and methyl H atoms, respectively, and constrained to ride on their parent atoms with U~iso~(H) = xU~eq~(C), where x = 1.2 for the aromatic and x = 1.5 for the methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 25% probability level, and H atoms are shown as small spheres of arbitrary radius. Cg1 and Cg2 are the centroids of the C1---C4/C11/C12 and C5---C8/C13/C14 rings respectively. ::: ![](e-67-0o723-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The arrangement of the molecules in the crystal structure viewed approximately along a direction. The C--H···π interactions are represented by dotted lines. H atoms not involved in interactions have been omitted. \[Symmetry codes: (i) --x, y + 3/2, --z + 3/2; (ii) x + 3/2, --y + 1/2, --z + 1.\] ::: ![](e-67-0o723-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The arrangement of the molecules in the crystal structure viewed approximately along b direction. The π-π interactions are represented by dotted lines. H atoms have been omitted for clarity. \[Symmetry codes: (iii) x + 1, y, z; (iv) x -- 1, y + 1, z + 1.\] ::: ![](e-67-0o723-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e334 .table-wrap} ------------------------------- --------------------------------------- C~16~H~13~NO~2~ F(000) = 528 M~r~ = 251.27 D~x~ = 1.372 Mg m^−3^ Orthorhombic, P2~1~2~1~2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 1944 reflections a = 7.2823 (3) Å θ = 3.1--29.0° b = 11.1519 (7) Å µ = 0.09 mm^−1^ c = 14.9834 (7) Å T = 295 K V = 1216.82 (11) Å^3^ Prism, red Z = 4 0.45 × 0.20 × 0.18 mm ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e458 .table-wrap} ----------------------------------------------------------- ------------------------------------- Oxford Diffraction Gemini R ULTRA Ruby CCD diffractometer 918 reflections with I \> 2σ(I) Radiation source: Enhance (Mo) X-ray Source R~int~ = 0.033 graphite θ~max~ = 25.1°, θ~min~ = 3.1° Detector resolution: 10.4002 pixels mm^-1^ h = −8→6 ω scans k = −12→13 4683 measured reflections l = −17→13 1258 independent reflections ----------------------------------------------------------- ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e559 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.037 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.079 H-atom parameters constrained S = 0.96 w = 1/\[σ^2^(F~o~^2^) + (0.0492P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 1258 reflections (Δ/σ)~max~ \< 0.001 174 parameters Δρ~max~ = 0.12 e Å^−3^ 0 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e713 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e733 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.7457 (3) 0.5675 (2) 0.53415 (14) 0.0349 (6) C2 0.8768 (3) 0.6609 (3) 0.53396 (17) 0.0437 (7) H2 0.9738 0.6578 0.4937 0.052\ C3 0.8647 (4) 0.7554 (3) 0.59116 (18) 0.0486 (7) H3 0.9530 0.8155 0.5892 0.058\* C4 0.7235 (3) 0.7630 (2) 0.65179 (17) 0.0422 (6) H4 0.7206 0.8255 0.6928 0.051\* C5 0.1522 (4) 0.6067 (3) 0.78267 (16) 0.0459 (7) H5 0.1608 0.6622 0.8288 0.055\* C6 0.0081 (4) 0.5277 (3) 0.78088 (18) 0.0487 (7) H6 −0.0795 0.5290 0.8260 0.058\* C7 −0.0067 (3) 0.4466 (3) 0.71212 (17) 0.0465 (7) H7 −0.1065 0.3946 0.7099 0.056\* C8 0.1262 (3) 0.4422 (2) 0.64640 (17) 0.0409 (6) H8 0.1164 0.3863 0.6006 0.049\* C9 0.4157 (3) 0.5148 (2) 0.57716 (15) 0.0334 (6) C10 0.4341 (4) 0.6937 (2) 0.71603 (16) 0.0394 (7) C11 0.5878 (3) 0.5814 (2) 0.58994 (14) 0.0325 (6) C12 0.5869 (3) 0.6781 (2) 0.65160 (16) 0.0335 (6) C13 0.2744 (3) 0.5206 (2) 0.64829 (15) 0.0335 (6) C14 0.2856 (3) 0.6048 (2) 0.71661 (14) 0.0354 (6) N15 0.7757 (3) 0.4671 (2) 0.48311 (13) 0.0421 (6) C16 0.7173 (4) 0.3491 (2) 0.51109 (19) 0.0528 (8) H16A 0.6745 0.3525 0.5716 0.079\* H16B 0.8189 0.2945 0.5072 0.079\* H16C 0.6198 0.3219 0.4730 0.079\* C17 0.9195 (3) 0.4667 (3) 0.41526 (17) 0.0552 (8) H17A 0.9068 0.5362 0.3780 0.083\* H17B 0.9086 0.3957 0.3794 0.083\* H17C 1.0376 0.4679 0.4437 0.083\* O18 0.3823 (2) 0.45881 (18) 0.50827 (11) 0.0484 (5) O19 0.4317 (3) 0.77920 (19) 0.76763 (15) 0.0644 (6) ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1161 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0328 (13) 0.0405 (16) 0.0315 (12) 0.0014 (14) −0.0002 (12) 0.0029 (12) C2 0.0356 (14) 0.0555 (19) 0.0400 (14) −0.0071 (15) 0.0045 (12) 0.0082 (14) C3 0.0453 (14) 0.0471 (17) 0.0532 (16) −0.0149 (15) −0.0037 (15) 0.0040 (17) C4 0.0427 (14) 0.0392 (16) 0.0448 (14) −0.0052 (14) −0.0053 (13) −0.0071 (14) C5 0.0478 (15) 0.0464 (18) 0.0435 (14) 0.0079 (15) 0.0064 (13) −0.0049 (14) C6 0.0377 (14) 0.057 (2) 0.0512 (15) 0.0046 (16) 0.0143 (12) 0.0078 (17) C7 0.0345 (14) 0.0513 (19) 0.0538 (16) −0.0061 (14) −0.0005 (13) 0.0095 (17) C8 0.0348 (13) 0.0461 (16) 0.0416 (13) −0.0012 (13) −0.0033 (12) 0.0038 (14) C9 0.0339 (12) 0.0348 (15) 0.0314 (12) 0.0014 (12) −0.0027 (11) 0.0011 (12) C10 0.0434 (15) 0.0391 (16) 0.0358 (14) 0.0024 (13) −0.0017 (13) −0.0039 (13) C11 0.0296 (12) 0.0372 (15) 0.0306 (12) 0.0010 (12) −0.0026 (11) 0.0048 (12) C12 0.0317 (12) 0.0346 (14) 0.0342 (12) 0.0011 (13) −0.0051 (12) 0.0036 (12) C13 0.0284 (12) 0.0364 (15) 0.0358 (12) 0.0050 (12) −0.0062 (11) 0.0035 (12) C14 0.0319 (13) 0.0378 (15) 0.0364 (12) 0.0035 (12) −0.0001 (12) 0.0014 (13) N15 0.0347 (11) 0.0497 (14) 0.0418 (11) −0.0001 (12) 0.0084 (10) −0.0042 (12) C16 0.0510 (16) 0.0460 (18) 0.0614 (17) 0.0072 (16) 0.0043 (15) −0.0056 (16) C17 0.0407 (14) 0.076 (2) 0.0489 (15) 0.0057 (17) 0.0081 (13) −0.0116 (16) O18 0.0404 (10) 0.0629 (12) 0.0418 (10) −0.0084 (10) 0.0001 (8) −0.0145 (10) O19 0.0661 (13) 0.0604 (14) 0.0665 (13) −0.0108 (11) 0.0160 (11) −0.0280 (13) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1546 .table-wrap} ---------------------- ------------ ----------------------- ------------- C1---N15 1.373 (3) C8---H8 0.9300 C1---C2 1.413 (4) C9---O18 1.230 (3) C1---C11 1.430 (3) C9---C11 1.469 (3) C2---C3 1.360 (4) C9---C13 1.483 (3) C2---H2 0.9300 C10---O19 1.227 (3) C3---C4 1.374 (4) C10---C14 1.467 (4) C3---H3 0.9300 C10---C12 1.483 (3) C4---C12 1.374 (3) C11---C12 1.420 (3) C4---H4 0.9300 C13---C14 1.392 (3) C5---C6 1.370 (4) N15---C16 1.446 (3) C5---C14 1.387 (3) N15---C17 1.459 (3) C5---H5 0.9300 C16---H16A 0.9600 C6---C7 1.375 (4) C16---H16B 0.9600 C6---H6 0.9300 C16---H16C 0.9600 C7---C8 1.382 (3) C17---H17A 0.9600 C7---H7 0.9300 C17---H17B 0.9600 C8---C13 1.389 (3) C17---H17C 0.9600 N15---C1---C2 119.5 (2) C14---C10---C12 118.5 (2) N15---C1---C11 122.8 (2) C12---C11---C1 117.8 (2) C2---C1---C11 117.7 (2) C12---C11---C9 117.7 (2) C3---C2---C1 121.7 (2) C1---C11---C9 123.7 (2) C3---C2---H2 119.1 C4---C12---C11 121.4 (2) C1---C2---H2 119.1 C4---C12---C10 117.5 (2) C2---C3---C4 120.8 (3) C11---C12---C10 121.1 (2) C2---C3---H3 119.6 C8---C13---C14 119.0 (2) C4---C3---H3 119.6 C8---C13---C9 119.8 (2) C12---C4---C3 119.9 (2) C14---C13---C9 121.1 (2) C12---C4---H4 120.1 C5---C14---C13 119.6 (2) C3---C4---H4 120.1 C5---C14---C10 120.7 (2) C6---C5---C14 120.9 (2) C13---C14---C10 119.7 (2) C6---C5---H5 119.6 C1---N15---C16 122.26 (19) C14---C5---H5 119.6 C1---N15---C17 120.3 (2) C5---C6---C7 119.8 (2) C16---N15---C17 114.2 (2) C5---C6---H6 120.1 N15---C16---H16A 109.5 C7---C6---H6 120.1 N15---C16---H16B 109.5 C6---C7---C8 120.2 (2) H16A---C16---H16B 109.5 C6---C7---H7 119.9 N15---C16---H16C 109.5 C8---C7---H7 119.9 H16A---C16---H16C 109.5 C7---C8---C13 120.5 (2) H16B---C16---H16C 109.5 C7---C8---H8 119.8 N15---C17---H17A 109.5 C13---C8---H8 119.8 N15---C17---H17B 109.5 O18---C9---C11 122.3 (2) H17A---C17---H17B 109.5 O18---C9---C13 119.2 (2) N15---C17---H17C 109.5 C11---C9---C13 118.4 (2) H17A---C17---H17C 109.5 O19---C10---C14 120.7 (2) H17B---C17---H17C 109.5 O19---C10---C12 120.8 (2) N15---C1---C2---C3 −172.0 (2) O19---C10---C12---C11 −178.1 (2) C11---C1---C2---C3 6.6 (3) C14---C10---C12---C11 1.8 (3) C1---C2---C3---C4 0.2 (4) C7---C8---C13---C14 −0.9 (3) C2---C3---C4---C12 −3.7 (4) C7---C8---C13---C9 −179.9 (2) C14---C5---C6---C7 −1.0 (4) O18---C9---C13---C8 14.8 (3) C5---C6---C7---C8 1.9 (4) C11---C9---C13---C8 −168.1 (2) C6---C7---C8---C13 −1.0 (4) O18---C9---C13---C14 −164.1 (2) N15---C1---C11---C12 168.8 (2) C11---C9---C13---C14 12.9 (3) C2---C1---C11---C12 −9.8 (3) C6---C5---C14---C13 −0.9 (4) N15---C1---C11---C9 −21.7 (3) C6---C5---C14---C10 176.6 (2) C2---C1---C11---C9 159.7 (2) C8---C13---C14---C5 1.9 (3) O18---C9---C11---C12 155.6 (2) C9---C13---C14---C5 −179.2 (2) C13---C9---C11---C12 −21.3 (3) C8---C13---C14---C10 −175.7 (2) O18---C9---C11---C1 −13.8 (4) C9---C13---C14---C10 3.3 (3) C13---C9---C11---C1 169.2 (2) O19---C10---C14---C5 −8.3 (4) C3---C4---C12---C11 0.2 (4) C12---C10---C14---C5 171.8 (2) C3---C4---C12---C10 −177.5 (2) O19---C10---C14---C13 169.2 (2) C1---C11---C12---C4 6.6 (3) C12---C10---C14---C13 −10.7 (3) C9---C11---C12---C4 −163.5 (2) C2---C1---N15---C16 145.7 (2) C1---C11---C12---C10 −175.8 (2) C11---C1---N15---C16 −32.9 (3) C9---C11---C12---C10 14.1 (3) C2---C1---N15---C17 −12.9 (3) O19---C10---C12---C4 −0.4 (4) C11---C1---N15---C17 168.5 (2) C14---C10---C12---C4 179.5 (2) ---------------------- ------------ ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2243 .table-wrap} ------------------------------------------------------------------------------------------------ Cg1 and Cg2 are the centroids of the C1--C4/C11/C12 and C5--C8/C13/C14 rings respectively. ------------------------------------------------------------------------------------------------ ::: ::: {#d1e2252 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C2---H2···Cg1^i^ 0.93 2.99 3.724 (3) 137 C4---H4···Cg2^ii^ 0.93 2.81 3.678 (3) 156 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x, y+3/2, −z+3/2; (ii) x+3/2, −y+1/2, −z+1. Table 2 π--π interactions (Å,°). {#d1e2343} ================================ ::: {#d1e2360 .table-wrap} ----- -------- --------------- ---------------- ------------- --------------- I J CgI···CgJ Dihedral angle CgI\_Perp CgI\_Offset 1 2^iii^ 3.844 (2) 11.13 (12) 3.606 (10) 1.334 (10) 2 1^iv^ 3.844 (2) 11.13 (12) 3.606 (10) 1.334 (10) ----- -------- --------------- ---------------- ------------- --------------- ::: Symmetry codes: (iii) x + 1, y, z; (iv) x -- 1, y + 1, z + 1.Notes: Cg1 and Cg2 are the centroids of the C1-C4/C11/C12 and C5-C8/C13/C14 rings respectively. CgI···CgJ is the distance between ring centroids. The dihedral angle is that between the planes of the rings I and J. CgI\_Perp is the perpendicular distance of CgI from ring J. CgI\_Offset is the distance between CgI and perpendicular projection of CgJ on ring I. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 and Cg2 are the centroids of the C1--C4/C11/C12 and C5--C8/C13/C14 rings respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- --------- ------- ----------- ------------- C2---H2⋯Cg1^i^ 0.93 2.99 3.724 (3) 137 C4---H4⋯Cg2^ii^ 0.93 2.81 3.678 (3) 156 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.644415	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052127/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o723", "authors": [ { "first": "Paweł", "last": "Niedziałkowski" }, { "first": "Joanna", "last": "Narloch" }, { "first": "Damian", "last": "Trzybiński" }, { "first": "Tadeusz", "last": "Ossowski" } ] }
PMC3052128	Related literature {#sec1} ================== For related structures and background, see: Lanfredi et al. (1975[@bb8]); Ahmad et al. (2010[@bb1]). For graph-set notation, see: Bernstein et al. (1995[@bb2]). For puckering parameters, see: Cremer & Pople (1975[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~30~H~46~O~3~M ~r~ = 454.67Tetragonal,a = 13.3167 (6) Åc = 31.1595 (14) ÅV = 5525.7 (4) Å^3^Z = 8Mo Kα radiationμ = 0.07 mm^−1^T = 296 K0.28 × 0.15 × 0.10 mm ### Data collection {#sec2.1.2} Bruker Kappa APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2005[@bb3]) T ~min~ = 0.935, T ~max~ = 0.96580888 measured reflections3012 independent reflections1936 reflections with I \> 2σ(I)R ~int~ = 0.103 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.061wR(F ^2^) = 0.186S = 1.033012 reflections306 parametersH-atom parameters constrainedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e447} Data collection: APEX2 (Bruker, 2009[@bb4]); cell refinement: SAINT (Bruker, 2009[@bb4]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb9]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb6]) and PLATON (Spek, 2009[@bb10]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb7]) and PLATON. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006283/bq2281sup1.cif](http://dx.doi.org/10.1107/S1600536811006283/bq2281sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006283/bq2281Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006283/bq2281Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bq2281&file=bq2281sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bq2281sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bq2281&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BQ2281](http://scripts.iucr.org/cgi-bin/sendsup?bq2281)). The authors acknowledge the provision of funds for the purchase of the diffractometer and encouragement by Dr Muhammad Akram Chaudhary, Vice Chancellor, University of Sargodha, Pakistan. Comment ======= The crystal structure of Methyl (13α,14β,20S,24Z)-3-oxo-lanosta-8,24-dien-26-oate (Lanfredi et al., 1975) has been previously published which is closely related to the title compound (I. Fig. 1). This compound has been derived from the berries of Schinus molle. The title compound is isolated from the galls of Pistacia integerima Stewart which were collected from Razagran, District Dir, KPK, Pakistan. The isolated compound from the galls of Pistacia integerima Stewart by Ahmad et al., 2010 and reported as Pisticialanstenoic acid, seems the same as (I). However their spectral studies differ a litle bit from our X-ray analysis. In (I), three six membered rings A (C1---C6), B (C5---C10) and C (C9---C14) are confirmed by different puckering parameters (Cremer & Pople, 1975). The puckering amplitude Q for the rings A, B and C have values of 0.490 (5) Å, 0.503 (4) Å and 0.540 (4) Å, θ for the rings A, B and C have values of 20.4 (6)°, 131.6 (6)° and 119.3 (4)°, φ for the rings A, B and C have values of 217.0 (17)°, 244.0 (7)° and 69.7 (5)°, respectively. The five membered ring D (C13---C17) has approximately envelop confirmation. The linear chain E (C20/C21/C22/C24) is planar with r. m. s. deviation of 0.0175 Å. The groups F (C18/C19/C25) and G (C23/O2/O3) are of course planar. The dihedral angle between E/F, E/G and F/G is 46.67 (5)°, 8.64 (1)° and 49.61 (5)°, respectively. There exist a strong intramolecular C---H···O and intermolecular O---H···O type H-bonding (Table 1, Fig. 2). Due to the inramolecular H-bonding S(6) ring motif is formed (Bernstein et al., 1995). The molecules are stabilized in the form of conventional carboxylate dimers with R~2~^2^(8) ring motifs (Fig. 2). Experimental {#experimental} ============ The dried and crushed galls of Pistacia chinensis var integerima (5 kg) were subjected to cold extraction with methanol (MeOH). The MeOH extract (400 g) was suspended in water and successively partitioned with n-hexane, CHCl~3~, EtOAc and butanol (BuOH). The CHCl~3~ fraction (10 g) was subjected to column chromatography on silica gel. The column was first eluted with n-hexane:EtOAc (100:0 → 0:100) as solvent system. A total of 13 fractions, RF-1 to RF-13 were obtained based on TLC profiles. White crude product of fraction RF-4 was separated from the solution by decantation. This crude material was washed with acetone for several times. White crystals were obtained by re-crystallization from a mixture of n-hexane:acetone (80:20). Yield: 90 mg. Refinement {#refinement} ========== In the absence of anomalous scattering factor all of the Friedel pairs were merged. Initially all H-atoms were taken from the difference Fourier map and at the last stage these H-atoms were geometrically treated. The H-atoms were positioned geometrically (O---H = 0.82, C--H = 0.93--0.97 Å) and refined as riding with U~iso~(H) = xU~eq~(C, O), where x = 1.5 for methyl and x = 1.2 for all other H-atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title compound with the atom numbering scheme. The displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0o711-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The partial packing (PLATON; Spek, 2009) which shows that molecules form carboxylate dimers with R22(8) ring motif. ::: ![](e-67-0o711-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e172 .table-wrap} -------------------------- --------------------------------------- C~30~H~46~O~3~ D~x~ = 1.093 Mg m^−3^ M~r~ = 454.67 Mo Kα radiation, λ = 0.71073 Å Tetragonal, P4~3~2~1~2 Cell parameters from 1936 reflections Hall symbol: P 4nw 2abw θ = 2.0--25.5° a = 13.3167 (6) Å µ = 0.07 mm^−1^ c = 31.1595 (14) Å T = 296 K V = 5525.7 (4) Å^3^ Needle, brown Z = 8 0.28 × 0.15 × 0.10 mm F(000) = 2000 -------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e291 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker Kappa APEXII CCD diffractometer 3012 independent reflections Radiation source: fine-focus sealed tube 1936 reflections with I \> 2σ(I) graphite R~int~ = 0.103 Detector resolution: 7.50 pixels mm^-1^ θ~max~ = 25.5°, θ~min~ = 2.0° ω scans h = −15→15 Absorption correction: multi-scan (SADABS; Bruker, 2005) k = −15→15 T~min~ = 0.935, T~max~ = 0.965 l = −36→37 80888 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e411 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.061 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.186 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.086P)^2^ + 1.2062P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3012 reflections (Δ/σ)~max~ \< 0.001 306 parameters Δρ~max~ = 0.20 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e568 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e670 .table-wrap} ------ ------------- ------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.0467 (3) 0.2309 (4) 0.45862 (16) 0.153 (3) O2 0.4258 (4) 0.3086 (4) 0.04257 (10) 0.126 (2) O3 0.4457 (3) 0.2870 (3) −0.02665 (10) 0.0945 (15) C1 0.0545 (3) 0.1086 (4) 0.40354 (12) 0.0697 (16) C2 0.0997 (4) 0.1819 (4) 0.43511 (15) 0.0853 (19) C3 0.2098 (4) 0.1923 (6) 0.43906 (16) 0.113 (3) C4 0.2651 (3) 0.1886 (4) 0.39648 (13) 0.0790 (19) C5 0.2386 (3) 0.0961 (3) 0.36929 (11) 0.0543 (11) C6 0.1235 (3) 0.0989 (3) 0.36259 (11) 0.0531 (13) C7 0.0906 (4) 0.0152 (4) 0.33306 (13) 0.090 (2) C8 0.1410 (3) 0.0268 (4) 0.28990 (12) 0.0683 (16) C9 0.2428 (3) 0.0658 (3) 0.28939 (10) 0.0519 (11) C10 0.2894 (3) 0.1031 (4) 0.32563 (11) 0.0623 (14) C11 0.4001 (3) 0.1270 (4) 0.32455 (11) 0.0750 (18) C12 0.4550 (3) 0.1281 (4) 0.28202 (11) 0.0690 (18) C13 0.3835 (3) 0.1393 (3) 0.24358 (11) 0.0512 (11) C14 0.3017 (3) 0.0559 (3) 0.24792 (11) 0.0545 (14) C15 0.2439 (3) 0.0683 (4) 0.20556 (11) 0.0664 (15) C16 0.3252 (4) 0.0930 (4) 0.17256 (12) 0.0714 (15) C17 0.4235 (3) 0.1184 (3) 0.19773 (11) 0.0587 (14) C18 0.4879 (3) 0.1963 (3) 0.17434 (12) 0.0647 (16) C19 0.5185 (4) 0.1526 (3) 0.13015 (12) 0.0750 (16) C20 0.5711 (4) 0.2247 (4) 0.10054 (12) 0.0767 (18) C21 0.5919 (3) 0.1785 (3) 0.05758 (13) 0.0670 (17) C22 0.5515 (3) 0.1957 (3) 0.01936 (12) 0.0597 (14) C23 0.4697 (3) 0.2684 (3) 0.01166 (14) 0.0667 (17) C24 0.5897 (3) 0.1425 (3) −0.02023 (13) 0.0737 (17) C25 0.5801 (4) 0.2295 (4) 0.19933 (15) 0.094 (2) C26 0.3361 (3) 0.2445 (3) 0.24457 (13) 0.0650 (16) C27 0.3455 (4) −0.0514 (3) 0.24816 (14) 0.0810 (19) C28 0.2784 (5) 0.0019 (5) 0.39218 (17) 0.112 (3) C29 0.0378 (6) 0.0107 (5) 0.42829 (18) 0.130 (3) C30 −0.0470 (4) 0.1500 (6) 0.38967 (15) 0.111 (3) H2 0.37831 0.34194 0.03369 0.1506\ H3A 0.23489 0.13882 0.45730 0.1358\* H3B 0.22476 0.25557 0.45307 0.1358\* H4A 0.33683 0.18870 0.40194 0.0946\* H4B 0.24930 0.24873 0.38024 0.0946\* H6 0.11127 0.16060 0.34627 0.0637\* H7A 0.01822 0.01725 0.32950 0.1080\* H7B 0.10831 −0.04913 0.34551 0.1080\* H8A 0.14170 −0.03851 0.27608 0.0820\* H8B 0.09968 0.07064 0.27243 0.0820\* H11A 0.43374 0.07888 0.34294 0.0902\* H11B 0.40888 0.19258 0.33758 0.0902\* H12A 0.49270 0.06612 0.27900 0.0831\* H12B 0.50259 0.18325 0.28186 0.0831\* H15A 0.20905 0.00683 0.19801 0.0794\* H15B 0.19532 0.12242 0.20762 0.0794\* H16A 0.30481 0.14991 0.15518 0.0854\* H16B 0.33623 0.03599 0.15377 0.0854\* H17 0.46301 0.05644 0.19923 0.0702\* H18 0.44620 0.25568 0.16920 0.0777\* H19A 0.56223 0.09537 0.13492 0.0898\* H19B 0.45857 0.12811 0.11589 0.0898\* H20A 0.52964 0.28396 0.09671 0.0920\* H20B 0.63392 0.24570 0.11349 0.0920\* H21 0.64161 0.12939 0.05775 0.0805\* H24A 0.63824 0.09279 −0.01204 0.1105\* H24B 0.62052 0.19041 −0.03912 0.1105\* H24C 0.53461 0.11059 −0.03468 0.1105\* H25A 0.62046 0.27268 0.18170 0.1404\* H25B 0.61863 0.17158 0.20747 0.1404\* H25C 0.55949 0.26512 0.22462 0.1404\* H26A 0.29602 0.25408 0.21928 0.0973\* H26B 0.38814 0.29424 0.24548 0.0973\* H26C 0.29438 0.25074 0.26957 0.0973\* H27A 0.38542 −0.06134 0.22286 0.1215\* H27B 0.29170 −0.09931 0.24862 0.1215\* H27C 0.38672 −0.06017 0.27316 0.1215\* H28A 0.25466 −0.05697 0.37756 0.1687\* H28B 0.25480 0.00123 0.42129 0.1687\* H28C 0.35044 0.00259 0.39196 0.1687\* H29A 0.01134 −0.03938 0.40925 0.1956\* H29B −0.00884 0.02219 0.45125 0.1956\* H29C 0.10060 −0.01211 0.43991 0.1956\* H30A −0.07966 0.10242 0.37124 0.1662\* H30B −0.03736 0.21201 0.37448 0.1662\* H30C −0.08784 0.16178 0.41454 0.1662\* ------ ------------- ------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1699 .table-wrap} ----- ----------- ----------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.090 (3) 0.218 (6) 0.152 (4) −0.011 (3) 0.022 (3) −0.121 (4) O2 0.133 (4) 0.169 (4) 0.075 (2) 0.079 (3) 0.009 (2) −0.017 (3) O3 0.122 (3) 0.100 (3) 0.0614 (18) 0.021 (2) 0.0003 (19) −0.0075 (18) C1 0.066 (3) 0.098 (3) 0.045 (2) −0.016 (3) 0.010 (2) −0.017 (2) C2 0.068 (3) 0.123 (4) 0.065 (3) −0.005 (3) 0.007 (2) −0.037 (3) C3 0.067 (3) 0.191 (7) 0.082 (3) −0.007 (4) 0.001 (3) −0.073 (4) C4 0.059 (3) 0.109 (4) 0.069 (3) −0.007 (3) −0.003 (2) −0.036 (3) C5 0.063 (2) 0.061 (2) 0.0389 (17) 0.006 (2) −0.0009 (18) −0.0028 (18) C6 0.052 (2) 0.070 (3) 0.0373 (17) −0.009 (2) 0.0011 (16) −0.0099 (18) C7 0.094 (4) 0.116 (4) 0.061 (2) −0.042 (3) 0.019 (3) −0.036 (3) C8 0.075 (3) 0.080 (3) 0.050 (2) −0.013 (2) 0.004 (2) −0.022 (2) C9 0.064 (2) 0.053 (2) 0.0388 (18) −0.0026 (19) 0.0047 (18) −0.0079 (17) C10 0.053 (2) 0.093 (3) 0.0408 (19) −0.002 (2) −0.0015 (18) −0.004 (2) C11 0.051 (3) 0.129 (4) 0.045 (2) 0.007 (3) −0.0021 (19) 0.000 (2) C12 0.057 (3) 0.101 (4) 0.049 (2) 0.006 (2) 0.002 (2) 0.001 (2) C13 0.053 (2) 0.058 (2) 0.0425 (19) 0.0116 (18) 0.0040 (17) 0.0011 (17) C14 0.068 (3) 0.051 (2) 0.0445 (19) 0.0072 (19) 0.0025 (19) −0.0040 (18) C15 0.076 (3) 0.080 (3) 0.0431 (19) −0.006 (2) 0.001 (2) −0.012 (2) C16 0.092 (3) 0.080 (3) 0.0421 (19) 0.000 (3) −0.003 (2) −0.008 (2) C17 0.067 (3) 0.058 (2) 0.051 (2) 0.018 (2) 0.011 (2) 0.0031 (18) C18 0.075 (3) 0.058 (3) 0.061 (2) 0.011 (2) 0.011 (2) 0.007 (2) C19 0.090 (3) 0.073 (3) 0.062 (2) 0.005 (3) 0.027 (2) 0.006 (2) C20 0.095 (4) 0.078 (3) 0.057 (2) −0.001 (3) 0.012 (2) 0.004 (2) C21 0.074 (3) 0.056 (3) 0.071 (3) 0.000 (2) 0.023 (2) 0.008 (2) C22 0.064 (3) 0.055 (2) 0.060 (2) −0.008 (2) 0.018 (2) −0.002 (2) C23 0.073 (3) 0.064 (3) 0.063 (3) −0.006 (2) 0.019 (2) −0.010 (2) C24 0.075 (3) 0.069 (3) 0.077 (3) −0.008 (2) 0.024 (2) −0.014 (2) C25 0.088 (4) 0.112 (4) 0.081 (3) −0.016 (3) 0.011 (3) 0.005 (3) C26 0.069 (3) 0.059 (3) 0.067 (2) 0.005 (2) 0.015 (2) −0.008 (2) C27 0.114 (4) 0.060 (3) 0.069 (3) 0.018 (3) 0.023 (3) 0.001 (2) C28 0.120 (5) 0.110 (5) 0.107 (4) 0.045 (4) 0.025 (4) 0.042 (4) C29 0.171 (7) 0.131 (5) 0.089 (4) −0.039 (5) 0.066 (4) 0.004 (4) C30 0.053 (3) 0.203 (7) 0.077 (3) −0.010 (4) 0.009 (2) −0.029 (4) ----- ----------- ----------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2330 .table-wrap} ---------------------- ------------ ----------------------- ------------ O1---C2 1.209 (7) C6---H6 0.9800 O2---C23 1.247 (6) C7---H7A 0.9700 O3---C23 1.260 (5) C7---H7B 0.9700 O2---H2 0.8200 C8---H8A 0.9700 C1---C2 1.511 (7) C8---H8B 0.9700 C1---C6 1.578 (5) C11---H11A 0.9700 C1---C30 1.522 (7) C11---H11B 0.9700 C1---C29 1.531 (8) C12---H12A 0.9700 C2---C3 1.478 (8) C12---H12B 0.9700 C3---C4 1.518 (6) C15---H15A 0.9700 C4---C5 1.536 (6) C15---H15B 0.9700 C5---C6 1.547 (6) C16---H16A 0.9700 C5---C28 1.537 (7) C16---H16B 0.9700 C5---C10 1.522 (5) C17---H17 0.9800 C6---C7 1.510 (6) C18---H18 0.9800 C7---C8 1.511 (6) C19---H19A 0.9700 C8---C9 1.452 (6) C19---H19B 0.9700 C9---C10 1.381 (5) C20---H20A 0.9700 C9---C14 1.517 (5) C20---H20B 0.9700 C10---C11 1.509 (6) C21---H21 0.9300 C11---C12 1.514 (5) C24---H24A 0.9600 C12---C13 1.537 (5) C24---H24B 0.9600 C13---C17 1.550 (5) C24---H24C 0.9600 C13---C26 1.537 (6) C25---H25A 0.9600 C13---C14 1.562 (6) C25---H25B 0.9600 C14---C15 1.537 (5) C25---H25C 0.9600 C14---C27 1.543 (6) C26---H26A 0.9600 C15---C16 1.529 (6) C26---H26B 0.9600 C16---C17 1.563 (6) C26---H26C 0.9600 C17---C18 1.531 (6) C27---H27A 0.9600 C18---C25 1.520 (6) C27---H27B 0.9600 C18---C19 1.549 (5) C27---H27C 0.9600 C19---C20 1.505 (6) C28---H28A 0.9600 C20---C21 1.499 (6) C28---H28B 0.9600 C21---C22 1.327 (6) C28---H28C 0.9600 C22---C23 1.477 (6) C29---H29A 0.9600 C22---C24 1.511 (6) C29---H29B 0.9600 C3---H3A 0.9700 C29---H29C 0.9600 C3---H3B 0.9700 C30---H30A 0.9600 C4---H4A 0.9700 C30---H30B 0.9600 C4---H4B 0.9700 C30---H30C 0.9600 O2···O3^i^ 2.645 (7) H11B···C4 2.6500 O2···C20 2.873 (7) H11B···H4A 2.2200 O3···O2^i^ 2.645 (7) H12A···C27 2.6900 O1···H30C 2.4400 H12A···H17 2.5200 O1···H30B 2.8600 H12A···H27C 2.2000 O1···H3A^ii^ 2.8900 H12B···C25 2.8400 O1···H29B 2.8900 H12B···H25C 2.2200 O2···H20A 2.2100 H12B···H26B 2.4100 O2···H2^i^ 2.7800 H15A···C8 3.0100 O2···H30A^iii^ 2.8900 H15A···H27B 2.3900 O3···H24B 2.6900 H15B···C8 2.9500 O3···H25B^iv^ 2.7800 H15B···C26 2.7400 O3···H8B^v^ 2.8000 H15B···H8B 2.4900 O3···H24C 2.6400 H15B···H26A 2.2400 O3···H2^i^ 1.8500 H15B···C21^x^ 3.0200 C10···C26 3.211 (6) H16A···C19 2.9500 C11···C27 3.441 (6) H16A···C26 3.0900 C12···C25 3.352 (6) H16A···H18 2.3900 C20···O2 2.873 (7) H16A···H19B 2.4000 C25···C26 3.548 (7) H16A···H26A 2.4300 C25···C12 3.352 (6) H16B···C19 2.9700 C26···C25 3.548 (7) H16B···H19B 2.3600 C26···C10 3.211 (6) H16B···H27A 2.6000 C27···C11 3.441 (6) H16B···C11^iv^ 3.1000 C28···C29 3.398 (10) H16B···H11A^iv^ 2.5900 C29···C28 3.398 (10) H17···C27 2.6100 C1···H28B 3.0800 H17···H12A 2.5200 C3···H29C 3.0900 H17···H19A 2.4600 C3···H28B 2.6700 H17···H25B 2.5900 C4···H11B 2.6500 H17···H27A 2.0200 C7···H29A 2.7000 H17···H24C^vi^ 2.3600 C7···H28A 2.7600 H18···C26 2.7700 C7···H30A 2.8100 H18···H16A 2.3900 C8···H27B 2.9200 H18···H20A 2.5500 C8···H15B 2.9500 H18···H26A 2.5400 C8···H15A 3.0100 H18···H26B 2.5500 C9···H6 2.7900 H18···C30^iii^ 3.0600 C9···H26C 2.6300 H18···H30C^iii^ 2.5400 C10···H26C 2.6300 H19A···H17 2.4600 C10···H27C 3.0100 H19A···H25B 2.5900 C11···H26C 2.7600 H19B···C16 2.5500 C11···H16B^vi^ 3.1000 H19B···H16A 2.4000 C11···H27C 2.9700 H19B···H16B 2.3600 C11···H4A 2.6800 H20A···O2 2.2100 C11···H28C 2.7600 H20A···C23 2.7800 C12···H27C 2.6800 H20A···H18 2.5500 C12···H25C 2.9100 H20B···C25 2.7800 C13···H25C 2.9400 H20B···H25A 2.1600 C15···H26A 2.6000 H21···H24A 2.2300 C15···H8A 2.9500 H24A···H21 2.2300 C15···H8B 2.8300 H24B···O3 2.6900 C16···H19B 2.5500 H24B···H26C^v^ 2.5200 C16···H27A 2.7100 H24C···O3 2.6400 C16···H26A 2.6200 H24C···H17^iv^ 2.3600 C17···H27A 2.5700 H25A···C20 2.6900 C18···H26A 3.0100 H25A···H20B 2.1600 C18···H26B 2.8900 H25B···H17 2.5900 C19···H16A 2.9500 H25B···H19A 2.5900 C19···H16B 2.9700 H25B···O3^vi^ 2.7800 C20···H25A 2.6900 H25C···C12 2.9100 C21···H26A^v^ 2.9800 H25C···C13 2.9400 C21···H15B^v^ 3.0200 H25C···C26 3.0500 C23···H8B^v^ 2.9500 H25C···H12B 2.2200 C23···H20A 2.7800 H25C···H26B 2.4000 C23···H2^i^ 2.6500 H26A···C15 2.6000 C24···H26C^v^ 3.0700 H26A···C16 2.6200 C25···H20B 2.7800 H26A···C18 3.0100 C25···H12B 2.8400 H26A···H15B 2.2400 C25···H26B 3.0600 H26A···H16A 2.4300 C26···H18 2.7700 H26A···H18 2.5400 C26···H15B 2.7400 H26A···C21^x^ 2.9800 C26···H16A 3.0900 H26B···C18 2.8900 C26···H25C 3.0500 H26B···C25 3.0600 C27···H17 2.6100 H26B···H12B 2.4100 C27···H8A 2.8600 H26B···H18 2.5500 C27···H12A 2.6900 H26B···H25C 2.4000 C28···H3A 2.7900 H26C···C9 2.6300 C28···H11A 2.7700 H26C···C10 2.6300 C28···H29C 2.8000 H26C···C11 2.7600 C28···H7B 2.7800 H26C···C24^x^ 3.0700 C29···H7A 3.0900 H26C···H24B^x^ 2.5200 C29···H7B 2.8600 H27A···C16 2.7100 C29···H28B 2.9000 H27A···C17 2.5700 C30···H7A 2.7200 H27A···H16B 2.6000 C30···H18^vii^ 3.0600 H27A···H17 2.0200 H2···O2^i^ 2.7800 H27B···C8 2.9200 H2···O3^i^ 1.8500 H27B···H8A 2.3200 H2···C23^i^ 2.6500 H27B···H15A 2.3900 H2···H2^i^ 2.2100 H27B···H3B^xi^ 2.4600 H3A···C28 2.7900 H27C···C10 3.0100 H3A···H28B 2.1600 H27C···C11 2.9700 H3A···O1^ii^ 2.8900 H27C···C12 2.6800 H3B···H27B^viii^ 2.4600 H27C···H12A 2.2000 H4A···C11 2.6800 H28A···C7 2.7600 H4A···H11B 2.2200 H28A···H7B 2.1900 H4A···H28C 2.5000 H28A···H4B^xi^ 2.6000 H4B···H6 2.4200 H28B···C1 3.0800 H4B···H28A^viii^ 2.6000 H28B···C3 2.6700 H6···C9 2.7900 H28B···C29 2.9000 H6···H4B 2.4200 H28B···H3A 2.1600 H6···H8B 2.6000 H28B···H29C 2.1400 H6···H30B 2.2700 H28C···C11 2.7600 H7A···C29 3.0900 H28C···H4A 2.5000 H7A···C30 2.7200 H28C···H11A 2.1400 H7A···H29A 2.6000 H29A···C7 2.7000 H7A···H30A 2.1600 H29A···H7A 2.6000 H7B···C28 2.7800 H29A···H7B 2.3700 H7B···C29 2.8600 H29A···H30A 2.5400 H7B···H28A 2.1900 H29B···O1 2.8900 H7B···H29A 2.3700 H29B···H30C 2.4200 H8A···C15 2.9500 H29C···C3 3.0900 H8A···C27 2.8600 H29C···C28 2.8000 H8A···H27B 2.3200 H29C···H28B 2.1400 H8A···H8A^ix^ 2.5300 H30A···C7 2.8100 H8B···C15 2.8300 H30A···H7A 2.1600 H8B···H6 2.6000 H30A···H29A 2.5400 H8B···H15B 2.4900 H30A···O2^vii^ 2.8900 H8B···O3^x^ 2.8000 H30B···O1 2.8600 H8B···C23^x^ 2.9500 H30B···H6 2.2700 H11A···C28 2.7700 H30C···O1 2.4400 H11A···H28C 2.1400 H30C···H29B 2.4200 H11A···H16B^vi^ 2.5900 H30C···H18^vii^ 2.5400 C23---O2---H2 109.00 H8A---C8---H8B 107.00 C2---C1---C29 106.3 (4) C10---C11---H11A 107.00 C2---C1---C30 107.7 (4) C10---C11---H11B 107.00 C2---C1---C6 110.3 (4) C12---C11---H11A 108.00 C6---C1---C30 108.5 (3) C12---C11---H11B 107.00 C29---C1---C30 108.8 (5) H11A---C11---H11B 107.00 C6---C1---C29 115.0 (4) C11---C12---H12A 109.00 O1---C2---C3 118.6 (5) C11---C12---H12B 109.00 C1---C2---C3 120.7 (5) C13---C12---H12A 109.00 O1---C2---C1 120.7 (5) C13---C12---H12B 109.00 C2---C3---C4 113.9 (4) H12A---C12---H12B 108.00 C3---C4---C5 113.4 (4) C14---C15---H15A 111.00 C4---C5---C6 106.4 (3) C14---C15---H15B 111.00 C4---C5---C10 110.0 (3) C16---C15---H15A 111.00 C6---C5---C10 108.6 (3) C16---C15---H15B 111.00 C6---C5---C28 115.1 (4) H15A---C15---H15B 109.00 C10---C5---C28 108.1 (4) C15---C16---H16A 110.00 C4---C5---C28 108.6 (4) C15---C16---H16B 110.00 C1---C6---C5 118.0 (3) C17---C16---H16A 110.00 C5---C6---C7 110.6 (3) C17---C16---H16B 110.00 C1---C6---C7 112.6 (4) H16A---C16---H16B 108.00 C6---C7---C8 109.8 (4) C13---C17---H17 107.00 C7---C8---C9 117.5 (3) C16---C17---H17 107.00 C8---C9---C14 117.5 (3) C18---C17---H17 107.00 C10---C9---C14 119.7 (3) C17---C18---H18 108.00 C8---C9---C10 122.6 (3) C19---C18---H18 108.00 C5---C10---C11 117.9 (3) C25---C18---H18 108.00 C9---C10---C11 119.8 (3) C18---C19---H19A 108.00 C5---C10---C9 120.6 (4) C18---C19---H19B 108.00 C10---C11---C12 119.6 (3) C20---C19---H19A 108.00 C11---C12---C13 112.6 (3) C20---C19---H19B 108.00 C12---C13---C17 119.2 (3) H19A---C19---H19B 107.00 C12---C13---C26 109.1 (3) C19---C20---H20A 109.00 C14---C13---C17 101.1 (3) C19---C20---H20B 109.00 C14---C13---C26 111.1 (3) C21---C20---H20A 109.00 C17---C13---C26 108.9 (3) C21---C20---H20B 109.00 C12---C13---C14 107.2 (3) H20A---C20---H20B 108.00 C9---C14---C13 111.9 (3) C20---C21---H21 115.00 C9---C14---C27 105.8 (3) C22---C21---H21 115.00 C13---C14---C15 101.5 (3) C22---C24---H24A 109.00 C13---C14---C27 113.3 (3) C22---C24---H24B 109.00 C15---C14---C27 107.0 (3) C22---C24---H24C 109.00 C9---C14---C15 117.6 (3) H24A---C24---H24B 109.00 C14---C15---C16 104.3 (3) H24A---C24---H24C 110.00 C15---C16---C17 107.6 (3) H24B---C24---H24C 109.00 C13---C17---C18 120.7 (3) C18---C25---H25A 109.00 C16---C17---C18 112.2 (3) C18---C25---H25B 109.00 C13---C17---C16 102.3 (3) C18---C25---H25C 109.00 C17---C18---C19 108.4 (3) H25A---C25---H25B 109.00 C17---C18---C25 114.0 (3) H25A---C25---H25C 110.00 C19---C18---C25 110.6 (4) H25B---C25---H25C 109.00 C18---C19---C20 115.3 (3) C13---C26---H26A 109.00 C19---C20---C21 111.8 (4) C13---C26---H26B 109.00 C20---C21---C22 131.0 (4) C13---C26---H26C 109.00 C21---C22---C24 121.0 (4) H26A---C26---H26B 110.00 C23---C22---C24 115.0 (3) H26A---C26---H26C 109.00 C21---C22---C23 123.9 (4) H26B---C26---H26C 110.00 O2---C23---C22 120.1 (4) C14---C27---H27A 109.00 O3---C23---C22 118.0 (4) C14---C27---H27B 109.00 O2---C23---O3 121.9 (4) C14---C27---H27C 109.00 C2---C3---H3A 109.00 H27A---C27---H27B 110.00 C2---C3---H3B 109.00 H27A---C27---H27C 109.00 C4---C3---H3A 109.00 H27B---C27---H27C 110.00 C4---C3---H3B 109.00 C5---C28---H28A 109.00 H3A---C3---H3B 108.00 C5---C28---H28B 109.00 C3---C4---H4A 109.00 C5---C28---H28C 109.00 C3---C4---H4B 109.00 H28A---C28---H28B 109.00 C5---C4---H4A 109.00 H28A---C28---H28C 109.00 C5---C4---H4B 109.00 H28B---C28---H28C 110.00 H4A---C4---H4B 108.00 C1---C29---H29A 109.00 C1---C6---H6 105.00 C1---C29---H29B 109.00 C5---C6---H6 105.00 C1---C29---H29C 109.00 C7---C6---H6 105.00 H29A---C29---H29B 110.00 C6---C7---H7A 110.00 H29A---C29---H29C 109.00 C6---C7---H7B 110.00 H29B---C29---H29C 109.00 C8---C7---H7A 110.00 C1---C30---H30A 109.00 C8---C7---H7B 110.00 C1---C30---H30B 109.00 H7A---C7---H7B 108.00 C1---C30---H30C 109.00 C7---C8---H8A 108.00 H30A---C30---H30B 109.00 C7---C8---H8B 108.00 H30A---C30---H30C 110.00 C9---C8---H8A 108.00 H30B---C30---H30C 109.00 C9---C8---H8B 108.00 C6---C1---C2---O1 149.9 (5) C10---C9---C14---C15 −148.9 (4) C6---C1---C2---C3 −32.5 (6) C10---C9---C14---C27 91.7 (5) C29---C1---C2---O1 −84.9 (6) C5---C10---C11---C12 176.1 (4) C29---C1---C2---C3 92.7 (6) C9---C10---C11---C12 11.1 (7) C30---C1---C2---O1 31.6 (7) C10---C11---C12---C13 19.5 (7) C30---C1---C2---C3 −150.8 (5) C11---C12---C13---C14 −52.8 (5) C2---C1---C6---C5 40.4 (5) C11---C12---C13---C17 −166.6 (4) C2---C1---C6---C7 171.2 (4) C11---C12---C13---C26 67.6 (5) C29---C1---C6---C5 −79.7 (5) C12---C13---C14---C9 59.9 (4) C29---C1---C6---C7 51.1 (5) C12---C13---C14---C15 −173.9 (3) C30---C1---C6---C5 158.2 (4) C12---C13---C14---C27 −59.6 (4) C30---C1---C6---C7 −71.0 (5) C17---C13---C14---C9 −174.6 (3) O1---C2---C3---C4 −142.5 (6) C17---C13---C14---C15 −48.4 (4) C1---C2---C3---C4 39.9 (8) C17---C13---C14---C27 65.9 (4) C2---C3---C4---C5 −52.6 (7) C26---C13---C14---C9 −59.2 (4) C3---C4---C5---C6 57.3 (5) C26---C13---C14---C15 67.0 (4) C3---C4---C5---C10 174.7 (4) C26---C13---C14---C27 −178.7 (3) C3---C4---C5---C28 −67.1 (5) C12---C13---C17---C16 156.9 (4) C4---C5---C6---C1 −52.9 (5) C12---C13---C17---C18 −77.8 (5) C4---C5---C6---C7 175.4 (3) C14---C13---C17---C16 39.9 (4) C10---C5---C6---C1 −171.3 (4) C14---C13---C17---C18 165.2 (3) C10---C5---C6---C7 57.1 (4) C26---C13---C17---C16 −77.1 (4) C28---C5---C6---C1 67.4 (5) C26---C13---C17---C18 48.2 (5) C28---C5---C6---C7 −64.2 (4) C9---C14---C15---C16 159.8 (4) C4---C5---C10---C9 −145.8 (4) C13---C14---C15---C16 37.5 (4) C4---C5---C10---C11 49.4 (5) C27---C14---C15---C16 −81.5 (4) C6---C5---C10---C9 −29.7 (6) C14---C15---C16---C17 −12.7 (5) C6---C5---C10---C11 165.4 (4) C15---C16---C17---C13 −17.3 (5) C28---C5---C10---C9 95.8 (5) C15---C16---C17---C18 −148.0 (4) C28---C5---C10---C11 −69.1 (6) C13---C17---C18---C19 178.4 (3) C1---C6---C7---C8 165.3 (4) C13---C17---C18---C25 54.8 (5) C5---C6---C7---C8 −60.3 (5) C16---C17---C18---C19 −61.0 (4) C6---C7---C8---C9 35.0 (6) C16---C17---C18---C25 175.4 (4) C7---C8---C9---C10 −7.9 (7) C17---C18---C19---C20 172.5 (4) C7---C8---C9---C14 166.7 (4) C25---C18---C19---C20 −61.9 (5) C8---C9---C10---C5 5.7 (7) C18---C19---C20---C21 −176.2 (4) C8---C9---C10---C11 170.3 (4) C19---C20---C21---C22 109.0 (5) C14---C9---C10---C5 −168.8 (4) C20---C21---C22---C23 −1.6 (7) C14---C9---C10---C11 −4.2 (7) C20---C21---C22---C24 176.6 (4) C8---C9---C14---C13 153.2 (4) C21---C22---C23---O2 −9.1 (7) C8---C9---C14---C15 36.4 (5) C21---C22---C23---O3 171.7 (4) C8---C9---C14---C27 −83.0 (4) C24---C22---C23---O2 172.6 (4) C10---C9---C14---C13 −32.1 (5) C24---C22---C23---O3 −6.7 (6) ---------------------- ------------ ----------------------- ------------ ::: Symmetry codes: (i) y, x, −z; (ii) y, x, −z+1; (iii) −y+1/2, x+1/2, z−1/4; (iv) −y+1/2, x−1/2, z−1/4; (v) x+1/2, −y+1/2, −z+1/4; (vi) y+1/2, −x+1/2, z+1/4; (vii) y−1/2, −x+1/2, z+1/4; (viii) −x+1/2, y+1/2, −z+3/4; (ix) −y, −x, −z+1/2; (x) x−1/2, −y+1/2, −z+1/4; (xi) −x+1/2, y−1/2, −z+3/4. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5251 .table-wrap} ----------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O2---H2···O3^i^ 0.82 1.85 2.645 (7) 162 C20---H20A···O2 0.97 2.21 2.873 (7) 125 ----------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) y, x, −z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ----------------- --------- ------- ----------- ------------- O2---H2⋯O3^i^ 0.82 1.85 2.645 (7) 162 C20---H20A⋯O2 0.97 2.21 2.873 (7) 125 Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.650680	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052128/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o711", "authors": [ { "first": "Mohammad", "last": "Arfan" }, { "first": "Abdur", "last": "Rauf" }, { "first": "M. Nawaz", "last": "Tahir" }, { "first": "Mumtaz", "last": "Ali" }, { "first": "Ghias", "last": "Uddin" } ] }
PMC3052129	Related literature {#sec1} ================== For background to supramolecular polymers of zinc-triad 1,1-dithiolates, including dithiocarbamates, see: Chen et al. (2006[@bb3]); Benson et al. (2007[@bb1]). For a closely related 2,2′-bipyridyl adduct, see: Song & Tiekink (2009[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cd(C~6~H~12~NS~2~)~2~(C~10~H~8~N~2~)\]M ~r~ = 593.16Triclinic,a = 10.3215 (4) Åb = 10.6465 (4) Åc = 12.4546 (5) Åα = 81.566 (3)°β = 74.790 (3)°γ = 83.641 (3)°V = 1302.64 (9) Å^3^Z = 2Mo Kα radiationμ = 1.18 mm^−1^T = 150 K0.27 × 0.16 × 0.01 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcaliber Eos Gemini diffractometerAbsorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[@bb5]) T ~min~ = 0.829, T ~max~ = 0.99015837 measured reflections5393 independent reflections4623 reflections with I \> 2σ(I)R ~int~ = 0.042 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.029wR(F ^2^) = 0.066S = 1.065393 reflections284 parametersH-atom parameters constrainedΔρ~max~ = 0.90 e Å^−3^Δρ~min~ = −0.51 e Å^−3^ {#d5e554} Data collection: CrysAlis PRO (Oxford Diffraction, 2010[@bb5]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb4]) and DIAMOND (Brandenburg, 2006[@bb2]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006878/pk2304sup1.cif](http://dx.doi.org/10.1107/S1600536811006878/pk2304sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006878/pk2304Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006878/pk2304Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?pk2304&file=pk2304sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?pk2304sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?pk2304&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [PK2304](http://scripts.iucr.org/cgi-bin/sendsup?pk2304)). We thank UKM (UKM-GUP-NBT-08--27-111 and UKM-ST-06-FRGS0092--2010), UPM and the University of Malaya for supporting this study. Comment ======= Adducts related to the title compound, (I), attract attention in crystal engineering studies (Chen et al., 2006; Benson et al., 2007). The Cd^II^ atom in (I) is six-coordinated, being chelated by two almost symmetrically coordinating dithiocarbamate ligands, and the N donor atoms of 2,2\'-bipyridyl ligand, Fig. 1 and Table 1. The coordination geometry is intermediate between trigonal prismatic and octahedral with a leaning towards the former. The angle between the triangular faces defined by the S1,S3,N4 and S2,S4,N3 atoms is 5.36 (9) °, and these are twisted by approximately 13 ° about the axis through them, compared to 0 ° for an an ideal trigonal prism and 60 ° for an ideal octahedron. The symmetric mode of coordination of the dithiocarbamate ligands is reflected in the associated C≐S bond distances which lie in the narrow range of 1.721 (2) to 1.733 (3) Å. The mode of coordination of the dithiocarbamate ligand, the disposition of the ligand donor set, and the intermediate coordination geometry observed for (I) matches a literature precedent (Song & Tiekink, 2009). Linear supramolecular chains along the a axis are formed in the crystal structure via C---H···S interactions, Table 2 and Fig. 2. These are consolidated into layers in the ab plane by π--π interactions formed between the pyridyl rings \[Cg(N3,C14--C18)···Cg(N4,C19--C23)^i^ = 3.6587 (13) Å with angle between rings = 5.35 (11) ° for i: 2 - x, 1 - y, 1 - z\]. Supramolecular layers stack along the c axis, Fig. 3. Experimental {#experimental} ============ The title compound was prepared using an in situ method. The first step was the addition of carbon disulfide (0.03 mol) to an ethanolic solution (20 ml) of butylmethylamine (0.03 mol) in ethanol (20 ml). The mixture was stirred for 1 h at 277 K. The resulting solution was added drop wise to a solution of cadmium(II) dichloride (0.015 mol) in ethanol (20 ml) followed by stirring for 4 h. A white precipitate was formed, filtered and washed with cold ethanol. The precipitate, Cd(C~6~H~12~NS~2~)~2~ (0.01 mol), and 2,2\'-bipyridyl (0.01 mol) were dissolved together in chloroform (20 ml) and stirred for 1 h. A yellowish precipitate was formed, filtered and dried in a desiccator. Crystallization was from its ethanol:chloroform (1:2) solution. Yield 86%; M.pt. 424--426 K. Elemental analysis. Found (calculated) for C~22~H~32~CdN~4~S~4~: C, 44.21 (44.156); H 5.32 (5.40); Cd 18.54 (18.96); N 9.23 (9.40); S 21.45 (21.63) %. UV (CHCl~3~) λ~max~ 284 (L(π) →L(π\)). IR (KBr): ν(C---H) 2929m; ν(C≐N) 1485m; ν(N---C) 1158 s; ν(C≐S) 974 s; ν(Cd---S) 354 s cm^-1^. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.95 to 0.99 Å) and were included in the refinement in the riding model approximation, with U~iso~(H) set to 1.2 to 1.5U~equiv~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level. ::: ![](e-67-0m384-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the linear supramolecular chain along the a axis in (I) showing C---H···S contacts shown as orange dashed lines. ::: ![](e-67-0m384-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view in projection down the b axis of the unit-cell contents for (I) showing supramolecular layers stacking along the c axis. The intermolecular C--H···S and π--π contacts are shown as orange and purple dashed lines, respectively. ::: ![](e-67-0m384-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e271 .table-wrap} ------------------------------------------ --------------------------------------- \[Cd(C~6~H~12~NS~2~)~2~(C~10~H~8~N~2~)\] Z* = 2 M~r~ = 593.16 F(000) = 608 Triclinic, P1 D~x~ = 1.512 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.3215 (4) Å Cell parameters from 8976 reflections b = 10.6465 (4) Å θ = 2.0--29.0° c = 12.4546 (5) Å µ = 1.18 mm^−1^ α = 81.566 (3)° T = 150 K β = 74.790 (3)° Plate, colourless γ = 83.641 (3)° 0.27 × 0.16 × 0.01 mm V = 1302.64 (9) Å^3^ ------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e418 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcaliber Eos Gemini diffractometer 5393 independent reflections Radiation source: fine-focus sealed tube 4623 reflections with I \> 2σ(I) graphite R~int~ = 0.042 Detector resolution: 16.1952 pixels mm^-1^ θ~max~ = 26.5°, θ~min~ = 2.3° ω scans h = −12→12 Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) k = −13→13 T~min~ = 0.829, T~max~ = 0.990 l = −15→15 15837 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e538 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.029 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.066 H-atom parameters constrained S = 1.06 w = 1/\[σ^2^(F~o~^2^) + (0.0248P)^2^ + 0.0565P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5393 reflections (Δ/σ)~max~ = 0.001 284 parameters Δρ~max~ = 0.90 e Å^−3^ 0 restraints Δρ~min~ = −0.51 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e695 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e794 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Cd 0.669262 (17) 0.668974 (17) 0.664886 (14) 0.02060 (7) S1 0.60096 (7) 0.69901 (6) 0.47470 (5) 0.02501 (15) S2 0.73388 (7) 0.90040 (6) 0.53865 (5) 0.02474 (15) S3 0.47202 (7) 0.54259 (7) 0.80306 (6) 0.02816 (16) S4 0.56208 (7) 0.77897 (6) 0.85175 (5) 0.02633 (15) N1 0.6294 (2) 0.93184 (19) 0.36194 (16) 0.0217 (5) N2 0.3637 (2) 0.6493 (2) 0.98885 (17) 0.0274 (5) N3 0.8838 (2) 0.62383 (19) 0.70520 (15) 0.0188 (4) N4 0.7756 (2) 0.46118 (19) 0.61699 (16) 0.0220 (5) C1 0.6525 (2) 0.8525 (2) 0.44916 (19) 0.0208 (5) C2 0.6688 (3) 1.0633 (2) 0.3422 (2) 0.0274 (6) H2A 0.6156 1.1102 0.4032 0.041\ H2B 0.6525 1.1048 0.2708 0.041\* H2C 0.7647 1.0626 0.3393 0.041\* C3 0.5565 (3) 0.9003 (2) 0.2837 (2) 0.0261 (6) H3A 0.4858 0.9693 0.2754 0.031\* H3B 0.5114 0.8209 0.3156 0.031\* C4 0.6490 (3) 0.8829 (3) 0.1684 (2) 0.0286 (6) H4A 0.5930 0.8765 0.1162 0.034\* H4B 0.7002 0.9593 0.1401 0.034\* C5 0.7477 (3) 0.7662 (3) 0.1679 (2) 0.0300 (6) H5A 0.6968 0.6893 0.1940 0.036\* H5B 0.8026 0.7713 0.2212 0.036\* C6 0.8409 (3) 0.7531 (3) 0.0524 (2) 0.0453 (8) H6A 0.7872 0.7466 −0.0006 0.068\* H6B 0.9021 0.6764 0.0565 0.068\* H6C 0.8933 0.8280 0.0269 0.068\* C7 0.4562 (2) 0.6567 (2) 0.8919 (2) 0.0232 (6) C8 0.2758 (3) 0.5432 (3) 1.0244 (2) 0.0350 (7) H8A 0.2020 0.5592 0.9870 0.053\* H8B 0.2387 0.5358 1.1058 0.053\* H8C 0.3281 0.4638 1.0041 0.053\* C9 0.3423 (3) 0.7429 (3) 1.0687 (2) 0.0329 (7) H9A 0.4118 0.8051 1.0410 0.039\* H9B 0.3536 0.6986 1.1417 0.039\* C11 0.2043 (3) 0.8137 (3) 1.0860 (2) 0.0350 (7) H11A 0.1347 0.7521 1.1166 0.042\* H11B 0.1916 0.8560 1.0128 0.042\* C12 0.1862 (3) 0.9133 (3) 1.1660 (2) 0.0400 (7) H12A 0.2177 0.8748 1.2328 0.048\* H12B 0.2427 0.9843 1.1285 0.048\* C13 0.0408 (3) 0.9657 (3) 1.2032 (3) 0.0484 (9) H13A 0.0119 1.0120 1.1383 0.073\* H13B 0.0329 1.0237 1.2592 0.073\* H13C −0.0165 0.8953 1.2361 0.073\* C14 0.9307 (3) 0.7054 (2) 0.7554 (2) 0.0249 (6) H14 0.8736 0.7775 0.7797 0.030\* C15 1.0578 (3) 0.6896 (3) 0.7734 (2) 0.0299 (6) H15 1.0872 0.7486 0.8106 0.036\* C16 1.1413 (3) 0.5869 (3) 0.7364 (2) 0.0327 (7) H16 1.2303 0.5749 0.7459 0.039\* C17 1.0942 (3) 0.5005 (2) 0.6848 (2) 0.0257 (6) H17 1.1504 0.4285 0.6590 0.031\* C18 0.9638 (2) 0.5211 (2) 0.67166 (18) 0.0185 (5) C19 0.9038 (2) 0.4298 (2) 0.62209 (19) 0.0190 (5) C20 0.9733 (3) 0.3185 (2) 0.5849 (2) 0.0243 (6) H20 1.0649 0.2995 0.5867 0.029\* C21 0.9076 (3) 0.2359 (2) 0.5453 (2) 0.0299 (6) H21 0.9535 0.1592 0.5200 0.036\* C22 0.7746 (3) 0.2662 (3) 0.5428 (2) 0.0304 (6) H22 0.7265 0.2101 0.5177 0.037\* C23 0.7136 (3) 0.3805 (3) 0.5781 (2) 0.0287 (6) H23 0.6231 0.4030 0.5744 0.034\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1595 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cd 0.01478 (10) 0.02502 (11) 0.02106 (10) 0.00349 (7) −0.00428 (8) −0.00391 (7) S1 0.0271 (4) 0.0231 (3) 0.0261 (3) −0.0007 (3) −0.0104 (3) −0.0012 (3) S2 0.0229 (3) 0.0269 (4) 0.0250 (3) 0.0008 (3) −0.0077 (3) −0.0042 (3) S3 0.0179 (3) 0.0379 (4) 0.0285 (4) −0.0019 (3) −0.0040 (3) −0.0068 (3) S4 0.0222 (3) 0.0264 (4) 0.0254 (3) 0.0025 (3) 0.0001 (3) −0.0016 (3) N1 0.0219 (12) 0.0217 (11) 0.0210 (11) 0.0041 (9) −0.0064 (9) −0.0031 (9) N2 0.0221 (12) 0.0335 (13) 0.0215 (11) −0.0001 (10) −0.0003 (10) 0.0018 (9) N3 0.0158 (11) 0.0228 (11) 0.0161 (10) −0.0001 (9) −0.0010 (9) −0.0037 (8) N4 0.0172 (11) 0.0250 (12) 0.0240 (11) −0.0005 (9) −0.0045 (9) −0.0050 (9) C1 0.0137 (12) 0.0230 (13) 0.0221 (13) 0.0065 (10) 0.0000 (10) −0.0050 (10) C2 0.0314 (15) 0.0216 (14) 0.0284 (14) 0.0027 (11) −0.0085 (12) −0.0022 (11) C3 0.0248 (14) 0.0284 (15) 0.0270 (14) 0.0011 (12) −0.0123 (12) −0.0009 (11) C4 0.0344 (16) 0.0305 (15) 0.0232 (13) −0.0031 (12) −0.0128 (13) 0.0002 (11) C5 0.0317 (16) 0.0310 (15) 0.0271 (14) −0.0011 (12) −0.0055 (13) −0.0069 (12) C6 0.048 (2) 0.054 (2) 0.0311 (16) 0.0015 (16) −0.0035 (15) −0.0122 (14) C7 0.0152 (13) 0.0302 (14) 0.0215 (13) 0.0075 (11) −0.0060 (11) 0.0014 (11) C8 0.0290 (16) 0.0405 (17) 0.0288 (15) −0.0032 (13) −0.0003 (13) 0.0053 (12) C9 0.0273 (15) 0.0460 (18) 0.0215 (13) 0.0018 (13) −0.0010 (12) −0.0041 (12) C11 0.0304 (16) 0.0350 (16) 0.0338 (16) 0.0017 (13) −0.0018 (13) −0.0003 (13) C12 0.0358 (18) 0.0343 (17) 0.0392 (17) −0.0016 (14) 0.0066 (15) −0.0009 (13) C13 0.0395 (19) 0.0323 (18) 0.061 (2) 0.0016 (15) 0.0080 (17) −0.0069 (15) C14 0.0211 (14) 0.0278 (14) 0.0253 (13) 0.0004 (11) −0.0039 (11) −0.0073 (11) C15 0.0240 (15) 0.0383 (17) 0.0312 (15) −0.0058 (13) −0.0098 (13) −0.0086 (12) C16 0.0184 (14) 0.0440 (18) 0.0383 (16) −0.0010 (13) −0.0133 (13) −0.0032 (13) C17 0.0200 (14) 0.0277 (14) 0.0282 (14) 0.0059 (11) −0.0071 (12) −0.0036 (11) C18 0.0153 (12) 0.0236 (13) 0.0136 (11) −0.0004 (10) −0.0012 (10) 0.0022 (10) C19 0.0173 (13) 0.0191 (13) 0.0172 (12) 0.0008 (10) −0.0007 (10) 0.0005 (9) C20 0.0189 (13) 0.0248 (14) 0.0242 (13) 0.0002 (11) 0.0009 (11) 0.0003 (11) C21 0.0354 (16) 0.0219 (14) 0.0283 (14) −0.0002 (12) −0.0004 (13) −0.0054 (11) C22 0.0337 (16) 0.0295 (15) 0.0290 (14) −0.0090 (13) −0.0048 (13) −0.0064 (12) C23 0.0217 (14) 0.0325 (16) 0.0325 (15) −0.0020 (12) −0.0057 (12) −0.0075 (12) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2237 .table-wrap} -------------------- -------------- ----------------------- -------------- Cd---S1 2.6104 (7) C6---H6C 0.9800 Cd---S2 2.7685 (7) C8---H8A 0.9800 Cd---S3 2.6468 (7) C8---H8B 0.9800 Cd---S4 2.6783 (7) C8---H8C 0.9800 Cd---N3 2.379 (2) C9---C11 1.514 (4) Cd---N4 2.441 (2) C9---H9A 0.9900 S1---C1 1.733 (3) C9---H9B 0.9900 S2---C1 1.721 (2) C11---C12 1.522 (4) S3---C7 1.727 (3) C11---H11A 0.9900 S4---C7 1.725 (3) C11---H11B 0.9900 N1---C1 1.332 (3) C12---C13 1.518 (4) N1---C2 1.469 (3) C12---H12A 0.9900 N1---C3 1.471 (3) C12---H12B 0.9900 N2---C7 1.327 (3) C13---H13A 0.9800 N2---C9 1.469 (3) C13---H13B 0.9800 N2---C8 1.472 (3) C13---H13C 0.9800 N3---C14 1.338 (3) C14---C15 1.377 (4) N3---C18 1.344 (3) C14---H14 0.9500 N4---C23 1.337 (3) C15---C16 1.372 (4) N4---C19 1.344 (3) C15---H15 0.9500 C2---H2A 0.9800 C16---C17 1.389 (4) C2---H2B 0.9800 C16---H16 0.9500 C2---H2C 0.9800 C17---C18 1.388 (3) C3---C4 1.526 (3) C17---H17 0.9500 C3---H3A 0.9900 C18---C19 1.489 (3) C3---H3B 0.9900 C19---C20 1.390 (3) C4---C5 1.516 (4) C20---C21 1.382 (4) C4---H4A 0.9900 C20---H20 0.9500 C4---H4B 0.9900 C21---C22 1.383 (4) C5---C6 1.522 (4) C21---H21 0.9500 C5---H5A 0.9900 C22---C23 1.383 (4) C5---H5B 0.9900 C22---H22 0.9500 C6---H6A 0.9800 C23---H23 0.9500 C6---H6B 0.9800 N3---Cd---N4 67.00 (7) N2---C7---S4 121.3 (2) N3---Cd---S1 130.89 (5) N2---C7---S3 119.9 (2) N4---Cd---S1 87.19 (5) S4---C7---S3 118.79 (14) N3---Cd---S3 115.46 (5) N2---C8---H8A 109.5 N4---Cd---S3 86.24 (5) N2---C8---H8B 109.5 S1---Cd---S3 102.91 (2) H8A---C8---H8B 109.5 N3---Cd---S4 93.32 (5) N2---C8---H8C 109.5 N4---Cd---S4 137.16 (5) H8A---C8---H8C 109.5 S1---Cd---S4 130.38 (2) H8B---C8---H8C 109.5 S3---Cd---S4 67.82 (2) N2---C9---C11 112.8 (2) N3---Cd---S2 94.02 (5) N2---C9---H9A 109.0 N4---Cd---S2 125.32 (5) C11---C9---H9A 109.0 S1---Cd---S2 67.03 (2) N2---C9---H9B 109.0 S3---Cd---S2 144.43 (2) C11---C9---H9B 109.0 S4---Cd---S2 92.26 (2) H9A---C9---H9B 107.8 C1---S1---Cd 89.21 (8) C9---C11---C12 111.9 (3) C1---S2---Cd 84.39 (8) C9---C11---H11A 109.2 C7---S3---Cd 87.18 (9) C12---C11---H11A 109.2 C7---S4---Cd 86.21 (9) C9---C11---H11B 109.2 C1---N1---C2 120.7 (2) C12---C11---H11B 109.2 C1---N1---C3 124.2 (2) H11A---C11---H11B 107.9 C2---N1---C3 114.95 (19) C13---C12---C11 112.5 (3) C7---N2---C9 123.5 (2) C13---C12---H12A 109.1 C7---N2---C8 121.3 (2) C11---C12---H12A 109.1 C9---N2---C8 115.2 (2) C13---C12---H12B 109.1 C14---N3---C18 118.6 (2) C11---C12---H12B 109.1 C14---N3---Cd 120.22 (16) H12A---C12---H12B 107.8 C18---N3---Cd 121.00 (15) C12---C13---H13A 109.5 C23---N4---C19 118.4 (2) C12---C13---H13B 109.5 C23---N4---Cd 122.04 (16) H13A---C13---H13B 109.5 C19---N4---Cd 119.35 (15) C12---C13---H13C 109.5 N1---C1---S2 120.62 (19) H13A---C13---H13C 109.5 N1---C1---S1 120.58 (19) H13B---C13---H13C 109.5 S2---C1---S1 118.80 (14) N3---C14---C15 123.0 (2) N1---C2---H2A 109.5 N3---C14---H14 118.5 N1---C2---H2B 109.5 C15---C14---H14 118.5 H2A---C2---H2B 109.5 C16---C15---C14 118.6 (2) N1---C2---H2C 109.5 C16---C15---H15 120.7 H2A---C2---H2C 109.5 C14---C15---H15 120.7 H2B---C2---H2C 109.5 C15---C16---C17 119.3 (2) N1---C3---C4 112.5 (2) C15---C16---H16 120.3 N1---C3---H3A 109.1 C17---C16---H16 120.3 C4---C3---H3A 109.1 C18---C17---C16 118.9 (2) N1---C3---H3B 109.1 C18---C17---H17 120.6 C4---C3---H3B 109.1 C16---C17---H17 120.6 H3A---C3---H3B 107.8 N3---C18---C17 121.5 (2) C5---C4---C3 113.9 (2) N3---C18---C19 116.3 (2) C5---C4---H4A 108.8 C17---C18---C19 122.1 (2) C3---C4---H4A 108.8 N4---C19---C20 121.6 (2) C5---C4---H4B 108.8 N4---C19---C18 115.3 (2) C3---C4---H4B 108.8 C20---C19---C18 123.1 (2) H4A---C4---H4B 107.7 C21---C20---C19 119.2 (2) C4---C5---C6 112.7 (2) C21---C20---H20 120.4 C4---C5---H5A 109.1 C19---C20---H20 120.4 C6---C5---H5A 109.1 C20---C21---C22 119.3 (2) C4---C5---H5B 109.1 C20---C21---H21 120.3 C6---C5---H5B 109.1 C22---C21---H21 120.3 H5A---C5---H5B 107.8 C21---C22---C23 118.0 (2) C5---C6---H6A 109.5 C21---C22---H22 121.0 C5---C6---H6B 109.5 C23---C22---H22 121.0 H6A---C6---H6B 109.5 N4---C23---C22 123.4 (2) C5---C6---H6C 109.5 N4---C23---H23 118.3 H6A---C6---H6C 109.5 C22---C23---H23 118.3 H6B---C6---H6C 109.5 N3---Cd---S1---C1 −78.98 (10) Cd---S2---C1---S1 −7.09 (13) N4---Cd---S1---C1 −134.92 (9) Cd---S1---C1---N1 −172.43 (19) S3---Cd---S1---C1 139.60 (8) Cd---S1---C1---S2 7.49 (13) S4---Cd---S1---C1 67.87 (8) C1---N1---C3---C4 −108.9 (3) S2---Cd---S1---C1 −4.42 (8) C2---N1---C3---C4 75.2 (3) N3---Cd---S2---C1 137.55 (9) N1---C3---C4---C5 68.0 (3) N4---Cd---S2---C1 73.04 (10) C3---C4---C5---C6 −178.6 (2) S1---Cd---S2---C1 4.47 (8) C9---N2---C7---S4 0.6 (3) S3---Cd---S2---C1 −75.42 (9) C8---N2---C7---S4 −178.37 (19) S4---Cd---S2---C1 −128.96 (8) C9---N2---C7---S3 −179.28 (19) N3---Cd---S3---C7 82.82 (10) C8---N2---C7---S3 1.8 (3) N4---Cd---S3---C7 145.11 (9) Cd---S4---C7---N2 −179.9 (2) S1---Cd---S3---C7 −128.65 (8) Cd---S4---C7---S3 −0.02 (13) S4---Cd---S3---C7 −0.01 (8) Cd---S3---C7---N2 179.86 (19) S2---Cd---S3---C7 −60.22 (9) Cd---S3---C7---S4 0.02 (13) N3---Cd---S4---C7 −116.17 (9) C7---N2---C9---C11 116.6 (3) N4---Cd---S4---C7 −57.04 (11) C8---N2---C9---C11 −64.4 (3) S1---Cd---S4---C7 88.29 (8) N2---C9---C11---C12 −178.0 (2) S3---Cd---S4---C7 0.01 (8) C9---C11---C12---C13 −168.1 (3) S2---Cd---S4---C7 149.67 (8) C18---N3---C14---C15 0.6 (4) N4---Cd---N3---C14 −176.21 (19) Cd---N3---C14---C15 −174.99 (19) S1---Cd---N3---C14 119.77 (16) N3---C14---C15---C16 1.2 (4) S3---Cd---N3---C14 −102.54 (17) C14---C15---C16---C17 −1.7 (4) S4---Cd---N3---C14 −35.56 (17) C15---C16---C17---C18 0.3 (4) S2---Cd---N3---C14 56.94 (17) C14---N3---C18---C17 −2.1 (3) N4---Cd---N3---C18 8.28 (16) Cd---N3---C18---C17 173.52 (17) S1---Cd---N3---C18 −55.74 (19) C14---N3---C18---C19 176.7 (2) S3---Cd---N3---C18 81.95 (17) Cd---N3---C18---C19 −7.7 (3) S4---Cd---N3---C18 148.92 (16) C16---C17---C18---N3 1.6 (4) S2---Cd---N3---C18 −118.57 (16) C16---C17---C18---C19 −177.1 (2) N3---Cd---N4---C23 176.6 (2) C23---N4---C19---C20 2.0 (3) S1---Cd---N4---C23 −46.31 (18) Cd---N4---C19---C20 −173.34 (17) S3---Cd---N4---C23 56.83 (18) C23---N4---C19---C18 −177.0 (2) S4---Cd---N4---C23 107.98 (18) Cd---N4---C19---C18 7.6 (3) S2---Cd---N4---C23 −105.41 (18) N3---C18---C19---N4 −0.2 (3) N3---Cd---N4---C19 −8.27 (16) C17---C18---C19---N4 178.6 (2) S1---Cd---N4---C19 128.86 (17) N3---C18---C19---C20 −179.2 (2) S3---Cd---N4---C19 −128.00 (17) C17---C18---C19---C20 −0.4 (4) S4---Cd---N4---C19 −76.85 (19) N4---C19---C20---C21 −2.3 (4) S2---Cd---N4---C19 69.76 (18) C18---C19---C20---C21 176.7 (2) C2---N1---C1---S2 −2.0 (3) C19---C20---C21---C22 0.4 (4) C3---N1---C1---S2 −177.74 (18) C20---C21---C22---C23 1.5 (4) C2---N1---C1---S1 177.93 (18) C19---N4---C23---C22 0.1 (4) C3---N1---C1---S1 2.2 (3) Cd---N4---C23---C22 175.32 (19) Cd---S2---C1---N1 172.83 (19) C21---C22---C23---N4 −1.9 (4) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3649 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C16---H16···S3^i^ 0.95 2.74 3.685 (3) 172 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: --------- ------------ Cd---S1 2.6104 (7) Cd---S2 2.7685 (7) Cd---S3 2.6468 (7) Cd---S4 2.6783 (7) Cd---N3 2.379 (2) Cd---N4 2.441 (2) --------- ------------ ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ----------------- --------- ------- ----------- ------------- C16---H16⋯S3^i^ 0.95 2.74 3.685 (3) 172 Symmetry code: (i) . ::: [^1]: ‡ Additional correspondence author, e-mail: aibi@ukm.my.	PubMed Central	2024-06-05T04:04:18.661222	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052129/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m384-m385", "authors": [ { "first": "Nur Amirah", "last": "Jamaluddin" }, { "first": "Ibrahim", "last": "Baba" }, { "first": "Mohamed Ibrahim", "last": "Mohamed Tahir" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }
PMC3052130	Related literature {#sec1} ================== For standard bond lengths, see: Allen et al. (1987[@bb1]). For hydrogen-bond motifs, see: Bernstein et al. (1995[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~9~BrFNOM ~r~ = 294.12Monoclinic,a = 4.4820 (2) Åb = 20.8088 (9) Åc = 12.2189 (5) Åβ = 94.570 (2)°V = 1135.97 (8) Å^3^Z = 4Mo Kα radiationμ = 3.61 mm^−1^T = 296 K0.35 × 0.17 × 0.11 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2005[@bb3]) T ~min~ = 0.365, T ~max~ = 0.69210561 measured reflections2792 independent reflections1958 reflections with I \> 2σ(I)R ~int~ = 0.034 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.032wR(F ^2^) = 0.083S = 1.022792 reflections154 parametersH-atom parameters constrainedΔρ~max~ = 0.44 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e396} Data collection: APEX2 (Bruker, 2005[@bb3]); cell refinement: SAINT (Bruker, 2005[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[@bb5]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004429/jh2266sup1.cif](http://dx.doi.org/10.1107/S1600536811004429/jh2266sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004429/jh2266Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004429/jh2266Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2266&file=jh2266sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2266sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2266&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2266](http://scripts.iucr.org/cgi-bin/sendsup?jh2266)). AAA thanks the Islamic Azad University, Ardakan Branch for the research facilities (this paper was extracted from a research project supported by IAU). RK thanks the Science and Research Branch, Islamic Azad University, Tehran. HK thanks the PNU for financial support. MNT thanks Sargodha University for the research facilities. Comment ======= Schiff base ligands are one of the most prevalent systems in coordination chemistry. As part of a general study of Schiff bases, we have determined the crystal structure of the title compound. The asymmetric unit of the title compound, Fig. 1, comprises a potentially bidenate Schiff base ligand. The bond lengths (Allen et al., 1987) and angles are within the normal ranges. The dihedral angle between the substituted benzene rings is 9.00 (11)Å. Strong intramolecular O---H···N hydrogen bonds generate S(6) ring motifs (Bernstein et al., 1995). Experimental {#experimental} ============ The title compound was synthesized by adding 5-bromo-salicylaldehyde (2 mmol) to a solution of p-fluoroaniline (2 mmol) in ethanol (20 ml). The mixture was refluxed with stirring for half an hour. The resulting light-yellow solution was filtered. Pale-yellow single crystals suitable for X-ray diffraction were recrystallized from ethanol by slow evaporation of the solvents at room temperature over several days. Refinement {#refinement} ========== H atoms of the hydroxy groups were located by a rotating model and constrained to refine with the parent atoms with U~iso~(H) = 1.5 U~eq~(O), see Table 1. The remaining H atoms were positioned geometrically with C---H = 0.93 Å and included in a riding model approximation with U~iso~ (H) = 1.2 U~eq~ (C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound, showing 40% probability displacement ellipsoids and the atomic numbering. Intramolecular hydrogen bond is drawn as dashed lines. ::: ![](e-67-0o598-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram of the title compound, viewed down the c-axis. ::: ![](e-67-0o598-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e127 .table-wrap} ------------------------- --------------------------------------- C~13~H~9~BrFNO F(000) = 584 M~r~ = 294.12 D~x~ = 1.720 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2520 reflections a = 4.4820 (2) Å θ = 2.5--28.5° b = 20.8088 (9) Å µ = 3.61 mm^−1^ c = 12.2189 (5) Å T = 296 K β = 94.570 (2)° Prism, pale-yellow V = 1135.97 (8) Å^3^ 0.35 × 0.17 × 0.11 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e252 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 2792 independent reflections Radiation source: fine-focus sealed tube 1958 reflections with I \> 2σ(I) graphite R~int~ = 0.034 φ and ω scans θ~max~ = 28.3°, θ~min~ = 1.9° Absorption correction: multi-scan (SADABS; Bruker, 2005) h = −5→5 T~min~ = 0.365, T~max~ = 0.692 k = −27→27 10561 measured reflections l = −16→16 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e369 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.032 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.083 H-atom parameters constrained S = 1.02 w = 1/\[σ^2^(F~o~^2^) + (0.0413P)^2^ + 0.1115P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2792 reflections (Δ/σ)~max~ = 0.001 154 parameters Δρ~max~ = 0.44 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e526 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e571 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 1.14491 (6) 0.420695 (13) 0.55664 (2) 0.06007 (13) F1 −0.3896 (4) −0.01392 (7) 0.62967 (14) 0.0714 (5) O1 0.7822 (4) 0.23124 (8) 0.89264 (12) 0.0502 (4) H1 0.6582 0.2057 0.8661 0.075\ N1 0.4202 (4) 0.17993 (8) 0.73875 (14) 0.0357 (4) C1 0.7310 (5) 0.26970 (10) 0.70681 (16) 0.0322 (5) C2 0.8605 (5) 0.27266 (11) 0.81485 (16) 0.0356 (5) C3 1.0742 (5) 0.31885 (11) 0.84342 (17) 0.0415 (5) H3 1.1617 0.3204 0.9150 0.050\* C4 1.1590 (5) 0.36250 (11) 0.76728 (18) 0.0418 (5) H4 1.3019 0.3936 0.7873 0.050\* C5 1.0300 (5) 0.35970 (10) 0.66087 (18) 0.0377 (5) C6 0.8198 (5) 0.31402 (10) 0.63019 (17) 0.0369 (5) H6 0.7360 0.3126 0.5581 0.044\* C7 0.5052 (4) 0.22206 (10) 0.67230 (17) 0.0343 (5) H7 0.4212 0.2224 0.6002 0.041\* C8 0.2060 (4) 0.13210 (10) 0.70442 (17) 0.0332 (5) C9 0.1021 (5) 0.12019 (11) 0.59655 (18) 0.0418 (5) H9 0.1690 0.1454 0.5406 0.050\* C10 −0.0999 (5) 0.07125 (11) 0.57144 (19) 0.0460 (6) H10 −0.1702 0.0633 0.4990 0.055\* C11 −0.1946 (5) 0.03478 (11) 0.6549 (2) 0.0445 (6) C12 −0.0996 (5) 0.04499 (12) 0.7619 (2) 0.0483 (6) H12 −0.1684 0.0195 0.8171 0.058\* C13 0.1021 (5) 0.09426 (12) 0.78670 (19) 0.0443 (6) H13 0.1687 0.1021 0.8595 0.053\* ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e935 .table-wrap} ----- ------------- -------------- -------------- --------------- --------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0733 (2) 0.05159 (18) 0.05448 (18) −0.01654 (13) −0.00037 (13) 0.01097 (12) F1 0.0782 (11) 0.0552 (10) 0.0788 (11) −0.0331 (9) −0.0069 (9) 0.0023 (8) O1 0.0592 (10) 0.0587 (11) 0.0313 (8) −0.0167 (8) −0.0051 (7) 0.0033 (8) N1 0.0310 (10) 0.0401 (11) 0.0354 (9) 0.0009 (8) −0.0014 (7) −0.0038 (8) C1 0.0303 (11) 0.0348 (11) 0.0312 (10) 0.0019 (9) 0.0005 (8) −0.0036 (9) C2 0.0348 (12) 0.0405 (12) 0.0315 (11) 0.0018 (9) 0.0023 (9) −0.0039 (9) C3 0.0422 (13) 0.0505 (14) 0.0305 (11) −0.0031 (11) −0.0043 (9) −0.0084 (10) C4 0.0393 (13) 0.0388 (13) 0.0467 (13) −0.0048 (10) −0.0005 (10) −0.0125 (10) C5 0.0418 (13) 0.0314 (11) 0.0402 (12) 0.0017 (10) 0.0045 (10) 0.0001 (9) C6 0.0382 (12) 0.0387 (12) 0.0327 (11) 0.0021 (10) −0.0036 (9) −0.0026 (9) C7 0.0326 (11) 0.0372 (12) 0.0322 (10) 0.0025 (9) −0.0028 (9) −0.0055 (9) C8 0.0275 (11) 0.0361 (12) 0.0357 (11) 0.0019 (9) −0.0004 (9) −0.0001 (9) C9 0.0495 (14) 0.0409 (13) 0.0344 (11) −0.0059 (11) −0.0005 (10) 0.0009 (10) C10 0.0517 (15) 0.0451 (14) 0.0397 (12) −0.0089 (11) −0.0066 (11) −0.0024 (10) C11 0.0407 (13) 0.0364 (13) 0.0554 (14) −0.0050 (10) −0.0027 (11) 0.0008 (11) C12 0.0501 (15) 0.0462 (15) 0.0492 (14) −0.0058 (12) 0.0068 (11) 0.0128 (11) C13 0.0425 (13) 0.0523 (15) 0.0370 (12) −0.0029 (11) −0.0035 (10) 0.0038 (10) ----- ------------- -------------- -------------- --------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1300 .table-wrap} -------------------- -------------- ----------------------- ------------- Br1---C5 1.898 (2) C5---C6 1.370 (3) F1---C11 1.358 (3) C6---H6 0.9300 O1---C2 1.350 (2) C7---H7 0.9300 O1---H1 0.8176 C8---C9 1.385 (3) N1---C7 1.274 (3) C8---C13 1.387 (3) N1---C8 1.423 (3) C9---C10 1.381 (3) C1---C6 1.395 (3) C9---H9 0.9300 C1---C2 1.400 (3) C10---C11 1.366 (3) C1---C7 1.455 (3) C10---H10 0.9300 C2---C3 1.382 (3) C11---C12 1.359 (3) C3---C4 1.375 (3) C12---C13 1.384 (3) C3---H3 0.9300 C12---H12 0.9300 C4---C5 1.381 (3) C13---H13 0.9300 C4---H4 0.9300 C2---O1---H1 110.1 N1---C7---H7 119.3 C7---N1---C8 121.51 (18) C1---C7---H7 119.3 C6---C1---C2 118.99 (19) C9---C8---C13 118.8 (2) C6---C1---C7 119.02 (19) C9---C8---N1 125.01 (19) C2---C1---C7 121.99 (19) C13---C8---N1 116.18 (18) O1---C2---C3 118.68 (18) C10---C9---C8 120.5 (2) O1---C2---C1 121.60 (19) C10---C9---H9 119.7 C3---C2---C1 119.7 (2) C8---C9---H9 119.7 C4---C3---C2 120.78 (19) C11---C10---C9 118.8 (2) C4---C3---H3 119.6 C11---C10---H10 120.6 C2---C3---H3 119.6 C9---C10---H10 120.6 C3---C4---C5 119.4 (2) F1---C11---C12 118.8 (2) C3---C4---H4 120.3 F1---C11---C10 118.5 (2) C5---C4---H4 120.3 C12---C11---C10 122.7 (2) C6---C5---C4 120.9 (2) C11---C12---C13 118.4 (2) C6---C5---Br1 119.87 (16) C11---C12---H12 120.8 C4---C5---Br1 119.20 (17) C13---C12---H12 120.8 C5---C6---C1 120.14 (19) C12---C13---C8 120.9 (2) C5---C6---H6 119.9 C12---C13---H13 119.6 C1---C6---H6 119.9 C8---C13---H13 119.6 N1---C7---C1 121.38 (19) C6---C1---C2---O1 179.65 (18) C6---C1---C7---N1 178.87 (18) C7---C1---C2---O1 0.1 (3) C2---C1---C7---N1 −1.6 (3) C6---C1---C2---C3 −0.4 (3) C7---N1---C8---C9 9.7 (3) C7---C1---C2---C3 180.0 (2) C7---N1---C8---C13 −171.9 (2) O1---C2---C3---C4 −179.3 (2) C13---C8---C9---C10 −0.4 (3) C1---C2---C3---C4 0.8 (3) N1---C8---C9---C10 178.1 (2) C2---C3---C4---C5 −0.5 (3) C8---C9---C10---C11 −0.2 (4) C3---C4---C5---C6 −0.2 (3) C9---C10---C11---F1 −179.0 (2) C3---C4---C5---Br1 179.31 (17) C9---C10---C11---C12 0.5 (4) C4---C5---C6---C1 0.5 (3) F1---C11---C12---C13 179.2 (2) Br1---C5---C6---C1 −179.00 (15) C10---C11---C12---C13 −0.2 (4) C2---C1---C6---C5 −0.2 (3) C11---C12---C13---C8 −0.3 (4) C7---C1---C6---C5 179.4 (2) C9---C8---C13---C12 0.6 (4) C8---N1---C7---C1 −178.11 (18) N1---C8---C13---C12 −177.9 (2) -------------------- -------------- ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1797 .table-wrap} --------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1···N1 0.82 1.89 2.612 (2) 146 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------- --------- ------- ----------- ------------- O1---H1⋯N1 0.82 1.89 2.612 (2) 146 :::	PubMed Central	2024-06-05T04:04:18.670011	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052130/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o598", "authors": [ { "first": "Amir Adabi", "last": "Ardakani" }, { "first": "Reza", "last": "Kia" }, { "first": "Hadi", "last": "Kargar" }, { "first": "Muhammad Nawaz", "last": "Tahir" } ] }
PMC3052131	Related literature {#sec1} ================== For the isotypic Ce analogue, see: Gao et al. (2011[@bb3]). For the structures and properties of lanthanide coordination compounds, see: Xiao et al. (2008[@bb8]); Lv et al. (2010[@bb4]). For bond lengths and angles in other complexes with nine-coordinate Nd^III^, see: Xiao et al. (2008[@bb8]); Wang et al. (2009[@bb6]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Nd~2~(C~10~H~8~O~4~)~3~(H~2~O)~2~\]M ~r~ = 901.00Triclinic,a = 10.4846 (13) Åb = 11.9660 (16) Åc = 12.3514 (16) Åα = 105.619 (5)°β = 97.202 (5)°γ = 92.625 (6)°V = 1475.5 (3) Å^3^Z = 2Mo Kα radiationμ = 3.55 mm^−1^T = 296 K0.24 × 0.22 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 1997[@bb2]) T ~min~ = 0.516, T ~max~ = 0.5807865 measured reflections5315 independent reflections4806 reflections with I \> 2σ(I)R ~int~ = 0.013 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.021wR(F ^2^) = 0.054S = 1.035315 reflections415 parameters3 restraintsH-atom parameters constrainedΔρ~max~ = 0.64 e Å^−3^Δρ~min~ = −0.76 e Å^−3^ {#d5e579} Data collection: SMART (Bruker, 1997[@bb2]); cell refinement: SAINT (Bruker, 1997[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: XP in SHELXTL (Sheldrick, 2008[@bb5]) and DIAMOND (Brandenburg, 2006[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb7]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006817/wm2461sup1.cif](http://dx.doi.org/10.1107/S1600536811006817/wm2461sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006817/wm2461Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006817/wm2461Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2461&file=wm2461sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2461sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2461&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2461](http://scripts.iucr.org/cgi-bin/sendsup?wm2461)). Comment ======= Lanthanide coordination polymers have shown versatile structural architectures, accompanied with desirable properties, like luminescence, magnetism, catalysis, gas adsorption and separation (Xiao et al., 2008; Lv et al., 2010). In order to extend our investigations in this field, we chose 1,3-phenylendiacetic acid (pda) as a functional ligand and synthesized the lanthanide coordination polymer \[Nd~2~(pda)~3~(H~2~O)~2~\]~n~, the structure of which is reported here. The title compound is isotypic with its Ce analogue (Gao et al., 2011). The asymmetric unit of the title complex (Fig. 1) contains two crystallographically unique Nd^III^ ions, three pda ligands, and two coordinated water molecules. Both Nd1 and Nd2 are nine-coordinated within a distorted tricapped trigonal-prismatic geometry. The nine coordination sites are occupied by one O atom from a water molecule and eight O atoms from six different pda anions. The Nd---O bond lengths in the title complex are in the range 2.377 (2)--2.749 (2) Å, which is comparable to those reported for other Nd complexes with oxygen environment around the central metal (Xiao et al., 2008; Wang et al., 2009). The pda ligands adopt two coordination modes, viz. µ~4~-hexadentate and µ~4~-pentadentate. Eight Nd^III^ ions and twelve pda ligands form a large \[Nd~8~(pda)~12~\] ring, whereas four Nd^III^ ions and six pda ligands form a small \[Nd~4~(pda)~6~\] ring (Fig. 2). These rings are further connected by the coordination interactions of pda ligands and Nd^III^ to generate a three-dimensional supramolecular framework (Fig. 2). Experimental {#experimental} ============ To a solution of neodymium nitrate hexahydrate (0.088 g, 0.2 mmol) in water (5 ml) was added an aqueous solution (5 ml) of the ligand (0.058 g, 0.3 mmol) and a drop of triethylamine. The reactants were sealed in a 25-ml Teflon-lined stainless-steel Parr bomb. The bomb was heated at 433 K for 3 d. Upon cooling, the solution yielded single crystals of the title complex in ca 75% yield. Anal./calc. for C~30~H~28~Nd~2~O~14~: C, 39.99; H, 3.13; found: C, 40.43; H, 3.47. Refinement {#refinement} ========== The H atoms of the water molecules were located in a difference Fourier map and were refined with distance constraints of O--H = 0.83 (5) Å. The C-bound H atoms were placed in geometrically idealized positions, with C--H = 0.93 and 0.97 Å for aryl and methylene H-atoms, respectively, and constrained to ride on their respective parent atoms, with U~iso~(H) = 1.2 U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A drawing of the asymmetric unit in the structure of the title complex, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0m387-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Unit cell packing of the title complex showing the three-dimensional framework formed by a large \[Nd8(pda)12\] ring and a small \[Nd4(pda)6\] ring. ::: ![](e-67-0m387-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e205 .table-wrap} --------------------------------------- --------------------------------------- \[Nd~2~(C~10~H~8~O~4~)~3~(H~2~O)~2~\] Z = 2 M~r~ = 901.00 F(000) = 880 Triclinic, P1 D~x~ = 2.028 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.4846 (13) Å Cell parameters from 5315 reflections b = 11.9660 (16) Å θ = 1.7--25.3° c = 12.3514 (16) Å µ = 3.55 mm^−1^ α = 105.619 (5)° T = 296 K β = 97.202 (5)° Block, colorless γ = 92.625 (6)° 0.24 × 0.22 × 0.20 mm V = 1475.5 (3) Å^3^ --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART CCD diffractometer 5315 independent reflections Radiation source: fine-focus sealed tube 4806 reflections with I \> 2σ(I) graphite R~int~ = 0.013 Detector resolution: 0 pixels mm^-1^ θ~max~ = 25.3°, θ~min~ = 1.7° φ and ω scans h = −12→12 Absorption correction: multi-scan (SADABS; Bruker, 1997) k = −12→14 T~min~ = 0.516, T~max~ = 0.580 l = −14→14 7865 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e475 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.021 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.054 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0265P)^2^ + 1.487P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5315 reflections (Δ/σ)~max~ = 0.001 415 parameters Δρ~max~ = 0.64 e Å^−3^ 3 restraints Δρ~min~ = −0.76 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e632 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e731 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Nd1 0.029517 (16) 0.026539 (14) 0.183517 (13) 0.01602 (6) Nd2 0.306439 (16) 0.036922 (15) 0.455279 (14) 0.01818 (6) C1 0.0706 (3) 0.8190 (3) 0.2608 (3) 0.0194 (7) C2 0.1023 (4) 0.7042 (3) 0.2819 (3) 0.0314 (9) H2A 0.1766 0.6787 0.2453 0.038\ H2B 0.1270 0.7169 0.3629 0.038\* C3 −0.0041 (4) 0.6073 (3) 0.2411 (3) 0.0244 (8) C4 −0.1173 (4) 0.6146 (3) 0.2887 (3) 0.0340 (9) H4 −0.1275 0.6802 0.3468 0.041\* C5 −0.2149 (4) 0.5267 (3) 0.2516 (4) 0.0368 (9) H5 −0.2897 0.5324 0.2853 0.044\* C6 −0.2021 (4) 0.4299 (3) 0.1643 (3) 0.0330 (9) H6 −0.2691 0.3714 0.1383 0.040\* C7 −0.0910 (4) 0.4192 (3) 0.1154 (3) 0.0265 (8) C8 0.0082 (4) 0.5078 (3) 0.1549 (3) 0.0252 (8) H8 0.0843 0.5002 0.1230 0.030\* C9 −0.0755 (4) 0.3102 (3) 0.0240 (3) 0.0326 (9) H9A −0.1557 0.2884 −0.0279 0.039\* H9B −0.0092 0.3272 −0.0188 0.039\* C10 −0.0404 (3) 0.2088 (3) 0.0679 (3) 0.0220 (7) C11 −0.2153 (3) 0.7492 (3) 0.5878 (3) 0.0243 (7) C12 −0.1546 (4) 0.6428 (3) 0.6052 (4) 0.0475 (12) H12A −0.0771 0.6353 0.5692 0.057\* H12B −0.1280 0.6558 0.6860 0.057\* C13 −0.2359 (4) 0.5289 (3) 0.5614 (3) 0.0322 (9) C14 −0.3482 (4) 0.5093 (3) 0.6035 (3) 0.0393 (10) H14 −0.3755 0.5681 0.6597 0.047\* C15 −0.4198 (4) 0.4044 (3) 0.5636 (3) 0.0334 (9) H15 −0.4955 0.3927 0.5924 0.040\* C16 −0.3801 (3) 0.3155 (3) 0.4805 (3) 0.0280 (8) H16 −0.4301 0.2449 0.4526 0.034\* C17 −0.2661 (3) 0.3315 (3) 0.4388 (3) 0.0232 (7) C18 −0.1952 (3) 0.4387 (3) 0.4794 (3) 0.0258 (8) H18 −0.1190 0.4506 0.4512 0.031\* C19 −0.2165 (3) 0.2365 (3) 0.3508 (3) 0.0257 (8) H19A −0.1419 0.2690 0.3271 0.031\* H19B −0.2825 0.2110 0.2848 0.031\* C20 −0.1792 (3) 0.1314 (3) 0.3893 (3) 0.0194 (7) C21 0.4696 (3) 0.1360 (3) −0.3232 (3) 0.0249 (8) C22 0.5520 (3) 0.2052 (3) −0.2133 (3) 0.0289 (8) H22A 0.6237 0.1609 −0.1973 0.035\* H22B 0.5873 0.2772 −0.2238 0.035\* C23 0.4804 (3) 0.2339 (3) −0.1121 (3) 0.0272 (8) C24 0.3884 (5) 0.3138 (4) −0.1054 (4) 0.0496 (12) H24 0.3733 0.3507 −0.1626 0.060\* H1W −0.2406 0.0218 0.0635 0.060\* H2W −0.2406 −0.0802 0.1125 0.060\* H4W 0.1094 0.0990 0.6110 0.060\* H3W 0.0294 0.0896 0.5035 0.060\* C25 0.3193 (5) 0.3397 (4) −0.0164 (4) 0.0574 (14) H25 0.2561 0.3919 −0.0146 0.069\* C26 0.3432 (4) 0.2885 (4) 0.0707 (3) 0.0409 (10) H26 0.2972 0.3075 0.1319 0.049\* C27 0.4349 (3) 0.2093 (3) 0.0676 (3) 0.0270 (8) C28 0.5025 (3) 0.1825 (3) −0.0248 (3) 0.0261 (8) H28 0.5641 0.1286 −0.0278 0.031\* C29 0.4652 (4) 0.1561 (4) 0.1644 (3) 0.0348 (9) H29A 0.5015 0.2183 0.2310 0.042\* H29B 0.5324 0.1040 0.1459 0.042\* C30 0.3579 (3) 0.0892 (3) 0.1978 (3) 0.0242 (7) O1 0.1566 (2) 0.9053 (2) 0.2968 (2) 0.0274 (5) O2 −0.0342 (2) 0.8302 (2) 0.2080 (2) 0.0284 (6) O3 −0.0371 (3) 0.10987 (19) −0.0009 (2) 0.0300 (6) O4 −0.0146 (3) 0.2218 (2) 0.1716 (2) 0.0346 (6) O5 −0.1595 (2) 0.84733 (19) 0.64899 (19) 0.0252 (5) O6 −0.3093 (2) 0.7452 (2) 0.5148 (2) 0.0312 (6) O7 −0.0998 (2) 0.0686 (2) 0.3388 (2) 0.0274 (5) O8 −0.2271 (3) 0.1114 (2) 0.4695 (2) 0.0365 (6) O9 0.5273 (2) 0.1006 (2) −0.41110 (18) 0.0243 (5) O10 0.3524 (3) 0.1179 (3) −0.3299 (2) 0.0445 (7) O11 0.3881 (2) 0.0619 (2) 0.2879 (2) 0.0300 (6) O12 0.2492 (2) 0.0633 (2) 0.1359 (2) 0.0308 (6) O13 −0.2057 (2) −0.0221 (2) 0.1036 (2) 0.0355 (6) O14 0.1067 (2) 0.1022 (2) 0.5416 (2) 0.0334 (6) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1777 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Nd1 0.02272 (10) 0.01120 (9) 0.01384 (9) 0.00192 (7) 0.00258 (7) 0.00292 (7) Nd2 0.02183 (10) 0.01863 (10) 0.01494 (10) 0.00167 (7) 0.00283 (7) 0.00602 (7) C1 0.0306 (18) 0.0139 (16) 0.0136 (15) 0.0028 (14) 0.0065 (14) 0.0017 (13) C2 0.043 (2) 0.0156 (18) 0.037 (2) 0.0046 (15) −0.0013 (17) 0.0105 (16) C3 0.038 (2) 0.0119 (16) 0.0242 (18) 0.0036 (14) 0.0010 (15) 0.0084 (14) C4 0.060 (3) 0.0161 (18) 0.029 (2) 0.0100 (17) 0.0159 (19) 0.0066 (15) C5 0.044 (2) 0.030 (2) 0.046 (2) 0.0107 (18) 0.0183 (19) 0.0189 (19) C6 0.041 (2) 0.0188 (19) 0.040 (2) −0.0011 (16) −0.0013 (18) 0.0131 (17) C7 0.045 (2) 0.0113 (17) 0.0229 (18) 0.0071 (15) −0.0007 (16) 0.0063 (14) C8 0.037 (2) 0.0177 (17) 0.0242 (17) 0.0095 (15) 0.0074 (15) 0.0093 (14) C9 0.057 (3) 0.0178 (18) 0.0218 (18) 0.0051 (17) 0.0011 (17) 0.0055 (15) C10 0.0297 (18) 0.0129 (17) 0.0227 (18) 0.0016 (13) 0.0054 (14) 0.0032 (14) C11 0.0265 (18) 0.0175 (18) 0.0254 (18) −0.0028 (14) 0.0044 (15) 0.0005 (14) C12 0.039 (2) 0.016 (2) 0.073 (3) 0.0030 (17) −0.018 (2) −0.0002 (19) C13 0.034 (2) 0.0155 (18) 0.041 (2) 0.0040 (15) −0.0102 (17) 0.0048 (16) C14 0.048 (3) 0.029 (2) 0.036 (2) 0.0154 (19) 0.0028 (19) −0.0006 (17) C15 0.032 (2) 0.030 (2) 0.039 (2) 0.0066 (16) 0.0131 (17) 0.0079 (17) C16 0.0314 (19) 0.0191 (18) 0.033 (2) 0.0000 (15) 0.0033 (16) 0.0077 (15) C17 0.0307 (19) 0.0192 (17) 0.0210 (17) 0.0042 (14) 0.0007 (14) 0.0087 (14) C18 0.0224 (17) 0.0199 (18) 0.035 (2) 0.0017 (14) −0.0010 (15) 0.0103 (15) C19 0.0315 (19) 0.0219 (18) 0.0252 (18) 0.0034 (15) 0.0049 (15) 0.0082 (15) C20 0.0236 (17) 0.0151 (16) 0.0167 (16) −0.0015 (13) 0.0018 (13) 0.0007 (13) C21 0.0294 (19) 0.030 (2) 0.0158 (17) 0.0037 (15) 0.0031 (14) 0.0064 (15) C22 0.0305 (19) 0.035 (2) 0.0192 (18) 0.0000 (16) 0.0027 (15) 0.0038 (16) C23 0.033 (2) 0.030 (2) 0.0161 (17) −0.0001 (15) 0.0021 (15) 0.0036 (15) C24 0.069 (3) 0.055 (3) 0.039 (2) 0.029 (2) 0.026 (2) 0.026 (2) C25 0.077 (3) 0.063 (3) 0.050 (3) 0.043 (3) 0.037 (3) 0.027 (2) C26 0.056 (3) 0.040 (2) 0.030 (2) 0.010 (2) 0.0212 (19) 0.0081 (18) C27 0.0319 (19) 0.0269 (19) 0.0227 (18) −0.0050 (15) 0.0032 (15) 0.0094 (15) C28 0.0246 (18) 0.0267 (19) 0.0253 (18) −0.0011 (14) 0.0007 (15) 0.0060 (15) C29 0.030 (2) 0.047 (2) 0.030 (2) −0.0072 (17) 0.0004 (16) 0.0188 (18) C30 0.0282 (19) 0.0257 (19) 0.0193 (17) 0.0035 (15) 0.0082 (15) 0.0046 (15) O1 0.0361 (14) 0.0165 (12) 0.0282 (13) −0.0012 (10) −0.0038 (11) 0.0079 (10) O2 0.0297 (13) 0.0205 (13) 0.0363 (14) 0.0001 (10) −0.0006 (11) 0.0126 (11) O3 0.0495 (16) 0.0138 (12) 0.0258 (13) 0.0040 (11) 0.0117 (12) 0.0010 (10) O4 0.0642 (19) 0.0190 (13) 0.0199 (13) 0.0106 (12) −0.0007 (12) 0.0060 (10) O5 0.0326 (13) 0.0158 (12) 0.0228 (12) 0.0005 (10) −0.0011 (10) 0.0001 (10) O6 0.0322 (14) 0.0198 (13) 0.0356 (14) −0.0023 (10) −0.0064 (12) 0.0035 (11) O7 0.0340 (14) 0.0250 (13) 0.0264 (13) 0.0103 (11) 0.0121 (11) 0.0080 (11) O8 0.0593 (18) 0.0261 (14) 0.0353 (15) 0.0142 (13) 0.0287 (14) 0.0160 (12) O9 0.0316 (13) 0.0260 (13) 0.0162 (11) 0.0074 (10) 0.0064 (10) 0.0050 (10) O10 0.0263 (15) 0.073 (2) 0.0265 (14) −0.0010 (14) 0.0021 (12) 0.0016 (14) O11 0.0310 (14) 0.0403 (15) 0.0247 (13) 0.0063 (11) 0.0083 (11) 0.0165 (12) O12 0.0262 (13) 0.0424 (16) 0.0236 (13) −0.0044 (11) 0.0031 (11) 0.0100 (12) O13 0.0298 (14) 0.0386 (16) 0.0362 (15) −0.0043 (12) −0.0032 (12) 0.0119 (12) O14 0.0334 (14) 0.0384 (16) 0.0316 (14) 0.0090 (12) 0.0078 (11) 0.0129 (12) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2568 .table-wrap} -------------------------- ------------- ----------------------------- -------------- Nd1---O3^i^ 2.415 (2) C15---C16 1.384 (5) Nd1---O5^ii^ 2.416 (2) C15---H15 0.9300 Nd1---O4 2.441 (2) C16---C17 1.384 (5) Nd1---O7 2.442 (2) C16---H16 0.9300 Nd1---O12 2.496 (2) C17---C18 1.387 (5) Nd1---O13 2.519 (2) C17---C19 1.508 (5) Nd1---O2^iii^ 2.520 (2) C18---H18 0.9300 Nd1---O1^iii^ 2.576 (2) C19---C20 1.510 (5) Nd1---O3 2.749 (2) C19---H19A 0.9700 Nd2---O8^iv^ 2.377 (2) C19---H19B 0.9700 Nd2---O11 2.418 (2) C20---O8 1.239 (4) Nd2---O9^v^ 2.462 (2) C20---O7 1.257 (4) Nd2---O1^iii^ 2.475 (2) C21---O10 1.227 (4) Nd2---O14 2.529 (3) C21---O9 1.290 (4) Nd2---O6^ii^ 2.531 (2) C21---C22 1.519 (5) Nd2---O10^vi^ 2.542 (3) C21---Nd2^vii^ 2.952 (3) Nd2---O5^ii^ 2.571 (2) C22---C23 1.506 (5) Nd2---O9^vi^ 2.621 (2) C22---H22A 0.9700 C1---O2 1.237 (4) C22---H22B 0.9700 C1---O1 1.282 (4) C23---C28 1.380 (5) C1---C2 1.510 (4) C23---C24 1.383 (5) C2---C3 1.506 (5) C24---C25 1.366 (6) C2---H2A 0.9700 C24---H24 0.9300 C2---H2B 0.9700 C25---C26 1.377 (6) C3---C4 1.385 (5) C25---H25 0.9300 C3---C8 1.392 (5) C26---C27 1.377 (5) C4---C5 1.374 (6) C26---H26 0.9300 C4---H4 0.9300 C27---C28 1.391 (5) C5---C6 1.378 (5) C27---C29 1.507 (5) C5---H5 0.9300 C28---H28 0.9300 C6---C7 1.373 (5) C29---C30 1.512 (5) C6---H6 0.9300 C29---H29A 0.9700 C7---C8 1.392 (5) C29---H29B 0.9700 C7---C9 1.508 (5) C30---O11 1.251 (4) C8---H8 0.9300 C30---O12 1.266 (4) C9---C10 1.499 (5) O1---Nd2^viii^ 2.475 (2) C9---H9A 0.9700 O1---Nd1^viii^ 2.576 (2) C9---H9B 0.9700 O2---Nd1^viii^ 2.520 (2) C10---O4 1.241 (4) O3---Nd1^i^ 2.415 (2) C10---O3 1.263 (4) O5---Nd1^ii^ 2.416 (2) C11---O6 1.239 (4) O5---Nd2^ii^ 2.571 (2) C11---O5 1.281 (4) O6---Nd2^ii^ 2.531 (2) C11---C12 1.503 (5) O8---Nd2^iv^ 2.377 (2) C12---C13 1.502 (5) O9---Nd2^v^ 2.462 (2) C12---H12A 0.9700 O9---Nd2^vii^ 2.621 (2) C12---H12B 0.9700 O10---Nd2^vii^ 2.542 (3) C13---C14 1.381 (6) O13---H1W 0.8758 C13---C18 1.391 (5) O13---H2W 0.8110 C14---C15 1.367 (6) O14---H4W 0.8644 C14---H14 0.9300 O14---H3W 0.8693 O3^i^---Nd1---O5^ii^ 144.23 (9) C7---C9---H9B 108.7 O3^i^---Nd1---O4 113.33 (8) H9A---C9---H9B 107.6 O5^ii^---Nd1---O4 76.46 (8) O4---C10---O3 119.9 (3) O3^i^---Nd1---O7 141.44 (8) O4---C10---C9 120.3 (3) O5^ii^---Nd1---O7 71.16 (8) O3---C10---C9 119.9 (3) O4---Nd1---O7 84.45 (8) O6---C11---O5 120.5 (3) O3^i^---Nd1---O12 74.32 (8) O6---C11---C12 123.3 (3) O5^ii^---Nd1---O12 71.68 (8) O5---C11---C12 116.0 (3) O4---Nd1---O12 88.05 (9) C13---C12---C11 117.0 (3) O7---Nd1---O12 142.83 (8) C13---C12---H12A 108.0 O3^i^---Nd1---O13 77.43 (9) C11---C12---H12A 108.0 O5^ii^---Nd1---O13 138.26 (8) C13---C12---H12B 108.0 O4---Nd1---O13 83.71 (9) C11---C12---H12B 108.0 O7---Nd1---O13 70.65 (8) H12A---C12---H12B 107.3 O12---Nd1---O13 144.46 (8) C14---C13---C18 118.6 (3) O3^i^---Nd1---O2^iii^ 75.03 (8) C14---C13---C12 121.8 (4) O5^ii^---Nd1---O2^iii^ 112.51 (8) C18---C13---C12 119.6 (4) O4---Nd1---O2^iii^ 153.02 (9) C15---C14---C13 120.8 (4) O7---Nd1---O2^iii^ 75.35 (8) C15---C14---H14 119.6 O12---Nd1---O2^iii^ 118.83 (8) C13---C14---H14 119.6 O13---Nd1---O2^iii^ 72.90 (8) C14---C15---C16 120.4 (4) O3^i^---Nd1---O1^iii^ 94.43 (8) C14---C15---H15 119.8 O5^ii^---Nd1---O1^iii^ 69.57 (8) C16---C15---H15 119.8 O4---Nd1---O1^iii^ 146.02 (8) C15---C16---C17 120.1 (3) O7---Nd1---O1^iii^ 85.44 (8) C15---C16---H16 119.9 O12---Nd1---O1^iii^ 80.76 (8) C17---C16---H16 119.9 O13---Nd1---O1^iii^ 122.85 (8) C16---C17---C18 118.8 (3) O2^iii^---Nd1---O1^iii^ 50.71 (7) C16---C17---C19 122.3 (3) O3^i^---Nd1---O3 64.78 (9) C18---C17---C19 118.9 (3) O5^ii^---Nd1---O3 119.11 (7) C17---C18---C13 121.2 (3) O4---Nd1---O3 48.91 (7) C17---C18---H18 119.4 O7---Nd1---O3 119.10 (8) C13---C18---H18 119.4 O12---Nd1---O3 80.67 (8) C17---C19---C20 115.1 (3) O13---Nd1---O3 67.92 (8) C17---C19---H19A 108.5 O2^iii^---Nd1---O3 128.34 (7) C20---C19---H19A 108.5 O1^iii^---Nd1---O3 155.25 (8) C17---C19---H19B 108.5 O8^iv^---Nd2---O11 140.87 (9) C20---C19---H19B 108.5 O8^iv^---Nd2---O9^v^ 80.82 (8) H19A---C19---H19B 107.5 O11---Nd2---O9^v^ 72.33 (8) O8---C20---O7 123.0 (3) O8^iv^---Nd2---O1^iii^ 74.90 (9) O8---C20---C19 118.7 (3) O11---Nd2---O1^iii^ 76.48 (8) O7---C20---C19 118.3 (3) O9^v^---Nd2---O1^iii^ 88.60 (8) O10---C21---O9 120.9 (3) O8^iv^---Nd2---O14 71.83 (9) O10---C21---C22 121.8 (3) O11---Nd2---O14 131.77 (8) O9---C21---C22 117.3 (3) O9^v^---Nd2---O14 152.59 (8) C23---C22---C21 114.1 (3) O1^iii^---Nd2---O14 85.98 (8) C23---C22---H22A 108.7 O8^iv^---Nd2---O6^ii^ 140.58 (9) C21---C22---H22A 108.7 O11---Nd2---O6^ii^ 77.47 (9) C23---C22---H22B 108.7 O9^v^---Nd2---O6^ii^ 132.09 (8) C21---C22---H22B 108.7 O1^iii^---Nd2---O6^ii^ 119.41 (8) H22A---C22---H22B 107.6 O14---Nd2---O6^ii^ 72.89 (9) C28---C23---C24 118.0 (3) O8^iv^---Nd2---O10^vi^ 73.99 (10) C28---C23---C22 122.3 (3) O11---Nd2---O10^vi^ 139.31 (9) C24---C23---C22 119.7 (3) O9^v^---Nd2---O10^vi^ 103.61 (8) C25---C24---C23 121.3 (4) O1^iii^---Nd2---O10^vi^ 144.10 (9) C25---C24---H24 119.4 O14---Nd2---O10^vi^ 67.60 (8) C23---C24---H24 119.4 O6^ii^---Nd2---O10^vi^ 76.78 (9) C24---C25---C26 120.1 (4) O8^iv^---Nd2---O5^ii^ 123.39 (9) C24---C25---H25 120.0 O11---Nd2---O5^ii^ 67.91 (8) C26---C25---H25 120.0 O9^v^---Nd2---O5^ii^ 137.67 (7) C25---C26---C27 120.4 (4) O1^iii^---Nd2---O5^ii^ 68.79 (7) C25---C26---H26 119.8 O14---Nd2---O5^ii^ 63.87 (8) C27---C26---H26 119.8 O6^ii^---Nd2---O5^ii^ 50.79 (7) C26---C27---C28 118.7 (3) O10^vi^---Nd2---O5^ii^ 115.78 (9) C26---C27---C29 120.8 (3) O8^iv^---Nd2---O9^vi^ 99.49 (9) C28---C27---C29 120.5 (3) O11---Nd2---O9^vi^ 94.98 (8) C23---C28---C27 121.6 (3) O9^v^---Nd2---O9^vi^ 65.88 (9) C23---C28---H28 119.2 O1^iii^---Nd2---O9^vi^ 154.47 (8) C27---C28---H28 119.2 O14---Nd2---O9^vi^ 116.39 (8) C27---C29---C30 119.0 (3) O6^ii^---Nd2---O9^vi^ 80.98 (7) C27---C29---H29A 107.6 O10^vi^---Nd2---O9^vi^ 50.17 (8) C30---C29---H29A 107.6 O5^ii^---Nd2---O9^vi^ 130.65 (7) C27---C29---H29B 107.6 O2---C1---O1 120.1 (3) C30---C29---H29B 107.6 O2---C1---C2 121.6 (3) H29A---C29---H29B 107.0 O1---C1---C2 118.3 (3) O11---C30---O12 125.0 (3) C3---C2---C1 115.8 (3) O11---C30---C29 114.2 (3) C3---C2---H2A 108.3 O12---C30---C29 120.8 (3) C1---C2---H2A 108.3 C1---O1---Nd2^viii^ 149.4 (2) C3---C2---H2B 108.3 C1---O1---Nd1^viii^ 92.21 (19) C1---C2---H2B 108.3 Nd2^viii^---O1---Nd1^viii^ 109.46 (8) H2A---C2---H2B 107.4 C1---O2---Nd1^viii^ 96.0 (2) C4---C3---C8 118.0 (3) C10---O3---Nd1^i^ 155.9 (2) C4---C3---C2 120.9 (3) C10---O3---Nd1 87.89 (19) C8---C3---C2 121.1 (3) Nd1^i^---O3---Nd1 115.22 (9) C5---C4---C3 121.1 (4) C10---O4---Nd1 103.32 (19) C5---C4---H4 119.4 C11---O5---Nd1^ii^ 153.8 (2) C3---C4---H4 119.4 C11---O5---Nd2^ii^ 92.8 (2) C4---C5---C6 120.1 (4) Nd1^ii^---O5---Nd2^ii^ 111.55 (9) C4---C5---H5 120.0 C11---O6---Nd2^ii^ 95.8 (2) C6---C5---H5 120.0 C20---O7---Nd1 147.9 (2) C7---C6---C5 120.5 (4) C20---O8---Nd2^iv^ 144.9 (2) C7---C6---H6 119.7 C21---O9---Nd2^v^ 132.8 (2) C5---C6---H6 119.7 C21---O9---Nd2^vii^ 91.54 (19) C6---C7---C8 119.0 (3) Nd2^v^---O9---Nd2^vii^ 114.12 (8) C6---C7---C9 120.0 (3) C21---O10---Nd2^vii^ 96.9 (2) C8---C7---C9 120.9 (3) C30---O11---Nd2 143.5 (2) C7---C8---C3 121.3 (3) C30---O12---Nd1 131.1 (2) C7---C8---H8 119.4 Nd1---O13---H1W 116.9 C3---C8---H8 119.4 Nd1---O13---H2W 117.1 C10---C9---C7 114.1 (3) H1W---O13---H2W 125.7 C10---C9---H9A 108.7 Nd2---O14---H4W 113.5 C7---C9---H9A 108.7 Nd2---O14---H3W 123.7 C10---C9---H9B 108.7 H4W---O14---H3W 113.8 O2---C1---C2---C3 −3.6 (5) O1^iii^---Nd1---O3---C10 −137.8 (2) O1---C1---C2---C3 178.0 (3) C1^iii^---Nd1---O3---C10 171.40 (19) C1---C2---C3---C4 −65.1 (5) O3^i^---Nd1---O3---Nd1^i^ 0.0 C1---C2---C3---C8 115.0 (4) O5^ii^---Nd1---O3---Nd1^i^ 139.84 (10) C8---C3---C4---C5 −0.4 (5) O4---Nd1---O3---Nd1^i^ 172.57 (17) C2---C3---C4---C5 179.8 (3) O7---Nd1---O3---Nd1^i^ −136.64 (10) C3---C4---C5---C6 −1.1 (6) O12---Nd1---O3---Nd1^i^ 76.98 (11) C4---C5---C6---C7 1.4 (6) O13---Nd1---O3---Nd1^i^ −86.07 (11) C5---C6---C7---C8 −0.2 (5) O2^iii^---Nd1---O3---Nd1^i^ −42.57 (15) C5---C6---C7---C9 176.9 (3) O1^iii^---Nd1---O3---Nd1^i^ 35.2 (2) C6---C7---C8---C3 −1.3 (5) C1^iii^---Nd1---O3---Nd1^i^ −15.6 (2) C9---C7---C8---C3 −178.4 (3) O3---C10---O4---Nd1 −0.8 (4) C4---C3---C8---C7 1.6 (5) C9---C10---O4---Nd1 179.2 (3) C2---C3---C8---C7 −178.6 (3) O3^i^---Nd1---O4---C10 7.8 (3) C6---C7---C9---C10 −78.4 (4) O5^ii^---Nd1---O4---C10 151.4 (2) C8---C7---C9---C10 98.7 (4) O7---Nd1---O4---C10 −136.7 (2) C7---C9---C10---O4 −6.9 (5) O12---Nd1---O4---C10 79.8 (2) C7---C9---C10---O3 173.1 (3) O13---Nd1---O4---C10 −65.6 (2) O6---C11---C12---C13 −21.0 (6) O2^iii^---Nd1---O4---C10 −95.4 (3) O5---C11---C12---C13 162.9 (4) O1^iii^---Nd1---O4---C10 150.0 (2) C11---C12---C13---C14 −62.9 (6) O3---Nd1---O4---C10 0.4 (2) C11---C12---C13---C18 119.6 (4) C1^iii^---Nd1---O4---C10 −162.0 (3) C18---C13---C14---C15 −1.6 (6) O6---C11---O5---Nd1^ii^ 156.4 (4) C12---C13---C14---C15 −179.1 (4) C12---C11---O5---Nd1^ii^ −27.5 (7) C13---C14---C15---C16 0.5 (6) O6---C11---O5---Nd2^ii^ −2.8 (3) C14---C15---C16---C17 1.3 (6) C12---C11---O5---Nd2^ii^ 173.3 (3) C15---C16---C17---C18 −1.9 (5) O5---C11---O6---Nd2^ii^ 2.9 (4) C15---C16---C17---C19 178.2 (3) C12---C11---O6---Nd2^ii^ −173.0 (4) C16---C17---C18---C13 0.8 (5) O8---C20---O7---Nd1 175.1 (3) C19---C17---C18---C13 −179.3 (3) C19---C20---O7---Nd1 −5.4 (6) C14---C13---C18---C17 0.9 (5) O3^i^---Nd1---O7---C20 −105.2 (4) C12---C13---C18---C17 178.5 (3) O5^ii^---Nd1---O7---C20 93.5 (4) C16---C17---C19---C20 −65.2 (4) O4---Nd1---O7---C20 15.9 (4) C18---C17---C19---C20 114.9 (4) O12---Nd1---O7---C20 95.2 (4) C17---C19---C20---O8 22.9 (5) O13---Nd1---O7---C20 −69.4 (4) C17---C19---C20---O7 −156.6 (3) O2^iii^---Nd1---O7---C20 −146.1 (4) O10---C21---C22---C23 8.0 (5) O1^iii^---Nd1---O7---C20 163.4 (4) O9---C21---C22---C23 −174.6 (3) O3---Nd1---O7---C20 −20.0 (4) C21---C22---C23---C28 109.6 (4) C1^iii^---Nd1---O7---C20 −170.7 (4) C21---C22---C23---C24 −70.0 (5) O7---C20---O8---Nd2^iv^ −36.4 (6) C28---C23---C24---C25 −1.3 (7) C19---C20---O8---Nd2^iv^ 144.1 (3) C22---C23---C24---C25 178.3 (4) O10---C21---O9---Nd2^v^ −118.1 (3) C23---C24---C25---C26 2.0 (8) C22---C21---O9---Nd2^v^ 64.4 (4) C24---C25---C26---C27 −1.3 (8) O10---C21---O9---Nd2^vii^ 7.5 (4) C25---C26---C27---C28 0.1 (6) C22---C21---O9---Nd2^vii^ −170.0 (3) C25---C26---C27---C29 177.8 (4) O9---C21---O10---Nd2^vii^ −7.8 (4) C24---C23---C28---C27 0.1 (6) C22---C21---O10---Nd2^vii^ 169.6 (3) C22---C23---C28---C27 −179.5 (3) O12---C30---O11---Nd2 −36.9 (6) C26---C27---C28---C23 0.5 (5) C29---C30---O11---Nd2 144.4 (3) C29---C27---C28---C23 −177.2 (3) O8^iv^---Nd2---O11---C30 100.6 (4) C26---C27---C29---C30 58.1 (5) O9^v^---Nd2---O11---C30 149.5 (4) C28---C27---C29---C30 −124.2 (4) O1^iii^---Nd2---O11---C30 56.7 (4) C27---C29---C30---O11 −170.9 (3) O14---Nd2---O11---C30 −15.2 (4) C27---C29---C30---O12 10.4 (5) O6^ii^---Nd2---O11---C30 −68.1 (4) O2---C1---O1---Nd2^viii^ 126.3 (4) O10^vi^---Nd2---O11---C30 −120.0 (4) C2---C1---O1---Nd2^viii^ −55.3 (6) O5^ii^---Nd2---O11---C30 −15.6 (4) O2---C1---O1---Nd1^viii^ −9.9 (3) O9^vi^---Nd2---O11---C30 −147.7 (4) C2---C1---O1---Nd1^viii^ 168.6 (3) C11^ii^---Nd2---O11---C30 −43.0 (4) O1---C1---O2---Nd1^viii^ 10.1 (3) C21^vi^---Nd2---O11---C30 −134.6 (4) C2---C1---O2---Nd1^viii^ −168.2 (3) O11---C30---O12---Nd1 27.9 (5) O4---C10---O3---Nd1^i^ −163.6 (4) C29---C30---O12---Nd1 −153.5 (3) C9---C10---O3---Nd1^i^ 16.4 (8) O3^i^---Nd1---O12---C30 −142.6 (3) O4---C10---O3---Nd1 0.7 (3) O5^ii^---Nd1---O12---C30 26.1 (3) C9---C10---O3---Nd1 −179.3 (3) O4---Nd1---O12---C30 102.4 (3) O3^i^---Nd1---O3---C10 −173.0 (3) O7---Nd1---O12---C30 24.3 (4) O5^ii^---Nd1---O3---C10 −33.2 (2) O13---Nd1---O12---C30 178.8 (3) O4---Nd1---O3---C10 −0.43 (19) O2^iii^---Nd1---O12---C30 −80.1 (3) O7---Nd1---O3---C10 50.4 (2) O1^iii^---Nd1---O12---C30 −45.4 (3) O12---Nd1---O3---C10 −96.0 (2) O3---Nd1---O12---C30 151.1 (3) O13---Nd1---O3---C10 100.9 (2) C1^iii^---Nd1---O12---C30 −63.8 (3) O2^iii^---Nd1---O3---C10 144.43 (19) -------------------------- ------------- ----------------------------- -------------- ::: Symmetry codes: (i) −x, −y, −z; (ii) −x, −y+1, −z+1; (iii) x, y−1, z; (iv) −x, −y, −z+1; (v) −x+1, −y, −z; (vi) x, y, z+1; (vii) x, y, z−1; (viii) x, y+1, z. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5319 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O13---H1W···O12^i^ 0.88 2.39 2.838 (3) 112 O14---H4W···O7^iv^ 0.86 2.26 2.829 (3) 124 O14---H4W···O2^ii^ 0.86 2.41 3.177 (4) 148 O14---H3W···O7 0.87 2.25 3.024 (3) 149 O14---H3W···O14^iv^ 0.87 2.53 3.100 (5) 123 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x, −y, −z; (iv) −x, −y, −z+1; (ii) −x, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- O13---H1W⋯O12^i^ 0.88 2.39 2.838 (3) 112 O14---H4W⋯O7^ii^ 0.86 2.26 2.829 (3) 124 O14---H4W⋯O2^iii^ 0.86 2.41 3.177 (4) 148 O14---H3W⋯O7 0.87 2.25 3.024 (3) 149 O14---H3W⋯O14^ii^ 0.87 2.53 3.100 (5) 123 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.674145	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052131/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m387", "authors": [ { "first": "Zhu-Qing", "last": "Gao" }, { "first": "Dong-Yu", "last": "Lv" }, { "first": "Hong-Ji", "last": "Li" }, { "first": "Jin-Zhong", "last": "Gu" } ] }
PMC3052132	Related literature {#sec1} ================== The title compound is a precursor for the production of hole-transporting and/or emitting materials, see: Shen et al. (2005[@bb6]). For a related structure, see: Bak et al. (1961[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~22~OM ~r~ = 338.43Orthorhombic,a = 7.5277 (13) Åb = 12.9969 (19) Åc = 18.438 (3) ÅV = 1803.9 (5) Å^3^Z = 4Mo Kα radiationμ = 0.07 mm^−1^T = 100 K0.2 × 0.14 × 0.08 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometer8855 measured reflections2118 independent reflections1518 reflections with I \> 2σ(I)R ~int~ = 0.103 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.058wR(F ^2^) = 0.146S = 1.032118 reflections236 parametersH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e425} Data collection: SMART (Bruker, 2001[@bb2]); cell refinement: SAINT (Bruker, 2001[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb3]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb4]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006957/rn2074sup1.cif](http://dx.doi.org/10.1107/S1600536811006957/rn2074sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006957/rn2074Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006957/rn2074Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rn2074&file=rn2074sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rn2074sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rn2074&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RN2074](http://scripts.iucr.org/cgi-bin/sendsup?rn2074)). This work was partially supported by the Institute of Chemistry, Academia Sinica, and Cardinal Tien College of Healthcare & Management. Comment ======= The title compound, (I), has been shown to be an precursor for the production of hole transporting and/or emitting materials (Shen et al., 2005). A one pot synthesis of a benzofuran substituted in the 2-position has been achieved by Pd(0) complex catalyzed Sonogashira coupling reaction of 2-iodophenol with terminal alkynes, followed by cyclization of the internal alkynes formed, in high yield (see scheme 1). The molecular structure is shown in Fig. 1. The dihedral angle between the benzofuran and fluorene rings is 9.06 (6)°, and that between the two benzene rings at fluorene is 1.78 (12)°. Weak intermolecular C---H···π interactions help to stabilize the crystal structure. Experimental {#experimental} ============ The compound was synthesized by the following procedure. A two-necked round-bottomed flask was charged with PdCl~2~(PPh~3~)~2~ (100 mg), 9,9-diethyl-2-ethynyl-9H-fluorene (1.35 g, 5.46 mmol), CuI (30 mg), 2-iodophenol (1.00 g, 4.55 mmol), triethylamine (1.3 ml), and DMF (10 ml), and the reaction mixture stirred under nitrogen and heated at 333 K for 24 h. After cooling, the mixture was diluted with diethyl ether and the organic phase was washed with water and brine. After drying over anhydrous MgSO~4~ and removing the volatiles, the residue was purified by column chromatography using CH~2~Cl~2~/n-hexane as eluent, followed by recrystallization from CH~2~Cl~2~ and hexane to yield 0.9 g (59%) of (I) as a white solid. Crystals suitable for X-ray diffraction were grown from a CH~2~Cl~2~ solution layered with hexane at room temperature. ^1^H NMR (CDCl~3~): 7.84 (d, 2 H, J = 7.97 Hz), 7.73 (dd, 2 H, J = 7.77 Hz), 7.55 (dd, 2 H, J = 7.64 Hz), 7.35--7.31 (m, 3 H), 7.24 (tt, 2 H, J = 8.31 Hz), 7.06 (s, 1 H), 2.09 (q, 4 H, J = 7.07 Hz), 0.34 (t, 6 H, J = 6.72 Hz). FAB MS (m/e): 338.1 (M^+^) Anal. Calcd for C~25~H~22~O: C, 88.72; H, 6.55. Found: C, 88.92; H, 6.51. Refinement {#refinement} ========== H atoms were located geometrically and treated as riding atoms, with C---H = 0.93 Å, and with U~iso~(H) = 1.2U~eq~(C). In the absence of significant anomalous scattering effects Friedel pairs have been merged. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A molecular structure of (I) with 30% probability displacement ellipsoids, showing the atom-numbering scheme employed. H atoms are shown as small spheres of the arbitrary radii. ::: ![](e-67-0o743-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e156 .table-wrap} ------------------------------- -------------------------------------- C~25~H~22~O F(000) = 720 M~r~ = 338.43 D~x~ = 1.246 Mg m^−3^ Orthorhombic, P2~1~2~1~2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 525 reflections a = 7.5277 (13) Å θ = 2.7--20.4° b = 12.9969 (19) Å µ = 0.07 mm^−1^ c = 18.438 (3) Å T = 100 K V = 1803.9 (5) Å^3^ Prism, colourless Z = 4 0.2 × 0.14 × 0.08 mm ------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e278 .table-wrap} ----------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 1518 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.103 graphite θ~max~ = 26.4°, θ~min~ = 1.9° ω and φ scans h = −8→9 8855 measured reflections k = −16→16 2118 independent reflections l = −17→23 ----------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.058 H-atom parameters constrained wR(F^2^) = 0.146 w = 1/\[σ^2^(F~o~^2^) + (0.P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.03 (Δ/σ)~max~ \< 0.001 2118 reflections Δρ~max~ = 0.23 e Å^−3^ 236 parameters Δρ~min~ = −0.26 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.007 (2) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e554 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. ^1^H NMR (CDCl~3~): 7.77 (d, J = 8.2, 4H), 7.64 (d, J = 8.2, 4H). FAB MS (m/e): 462 (M^+^). Analysis calculated for C~18~H~8~F~6~N~2~O~4~S: C 46.76, H 1.74, N 6.06%; found: C 46.80, H 1.88, N 5.79%. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e686 .table-wrap} ------ ------------ -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O29 0.8727 (4) 0.12706 (16) 0.89298 (15) 0.0233 (6) C1 0.6113 (5) 0.4536 (2) 0.6667 (2) 0.0210 (9) C2 0.5957 (6) 0.4834 (3) 0.5267 (2) 0.0241 (9) H2 0.5355 0.5473 0.5313 0.029\ C3 0.6407 (6) 0.4451 (3) 0.4588 (2) 0.0274 (10) H3 0.6092 0.4828 0.4166 0.033\* C4 0.7307 (6) 0.3529 (2) 0.4517 (2) 0.0248 (9) H4 0.7610 0.3284 0.4048 0.030\* C5 0.7768 (6) 0.2960 (2) 0.5121 (2) 0.0250 (9) H5 0.8382 0.2325 0.5070 0.030\* C6 0.8406 (5) 0.2003 (2) 0.6748 (2) 0.0234 (9) H6 0.8885 0.1541 0.6400 0.028\* C7 0.8484 (5) 0.1773 (3) 0.7477 (2) 0.0246 (9) H7 0.9038 0.1152 0.7628 0.030\* C8 0.7765 (5) 0.2434 (2) 0.7995 (2) 0.0203 (8) C9 0.6972 (5) 0.3362 (2) 0.7766 (2) 0.0221 (9) H9 0.6485 0.3823 0.8113 0.027\* C10 0.6904 (5) 0.3599 (2) 0.7040 (2) 0.0204 (9) C11 0.6400 (5) 0.4271 (2) 0.5872 (2) 0.0197 (9) C12 0.7322 (5) 0.3329 (2) 0.5805 (2) 0.0210 (8) C13 0.7618 (5) 0.2920 (2) 0.6527 (2) 0.0211 (8) C21 0.7791 (5) 0.2166 (2) 0.8762 (2) 0.0218 (9) C22 0.7057 (6) 0.2573 (2) 0.9356 (2) 0.0236 (9) H22 0.6381 0.3189 0.9376 0.028\* C23 0.7468 (6) 0.1913 (2) 0.9960 (2) 0.0238 (9) C24 0.7066 (6) 0.1876 (3) 1.0693 (2) 0.0293 (9) H24 0.6388 0.2407 1.0914 0.035\* C25 0.7675 (6) 0.1048 (3) 1.1097 (2) 0.0311 (10) H25 0.7404 0.1012 1.1600 0.037\* C26 0.8683 (6) 0.0264 (3) 1.0779 (2) 0.0285 (10) H26 0.9081 −0.0295 1.1069 0.034\* C27 0.9113 (6) 0.0287 (3) 1.0048 (2) 0.0251 (9) H27 0.9802 −0.0238 0.9826 0.030\* C28 0.8480 (5) 0.1119 (2) 0.9661 (2) 0.0203 (9) C31 0.7154 (6) 0.5539 (2) 0.6825 (2) 0.0283 (10) H31A 0.8425 0.5409 0.6722 0.034\* H31B 0.6745 0.6072 0.6479 0.034\* C32 0.7009 (6) 0.5975 (3) 0.7583 (2) 0.0326 (10) H32A 0.7727 0.6602 0.7618 0.049\* H32B 0.7441 0.5467 0.7933 0.049\* H32C 0.5764 0.6139 0.7688 0.049\* C33 0.4142 (5) 0.4697 (3) 0.6858 (2) 0.0221 (9) H33A 0.4039 0.4798 0.7388 0.027\* H33B 0.3724 0.5336 0.6620 0.027\* C34 0.2925 (6) 0.3820 (2) 0.6635 (3) 0.0313 (10) H34A 0.1703 0.3980 0.6780 0.047\* H34B 0.3309 0.3185 0.6875 0.047\* H34C 0.2978 0.3730 0.6108 0.047\* ------ ------------ -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1306 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O29 0.0224 (15) 0.0231 (12) 0.0244 (16) 0.0027 (12) −0.0021 (14) 0.0000 (11) C1 0.021 (2) 0.0181 (16) 0.024 (2) 0.0023 (16) 0.0017 (19) −0.0008 (16) C2 0.026 (2) 0.0220 (17) 0.024 (2) 0.0022 (16) 0.000 (2) 0.0014 (16) C3 0.032 (3) 0.0265 (18) 0.024 (2) −0.0026 (18) −0.001 (2) 0.0017 (16) C4 0.027 (2) 0.0283 (17) 0.019 (2) −0.0023 (18) 0.001 (2) −0.0051 (15) C5 0.026 (2) 0.0229 (16) 0.026 (2) 0.0002 (17) 0.000 (2) −0.0015 (16) C6 0.022 (2) 0.0225 (16) 0.025 (2) 0.0038 (16) 0.0009 (19) −0.0049 (16) C7 0.027 (2) 0.0220 (17) 0.025 (2) 0.0029 (16) −0.0023 (19) −0.0009 (16) C8 0.019 (2) 0.0231 (16) 0.0194 (19) −0.0041 (17) 0.0026 (18) −0.0015 (15) C9 0.025 (2) 0.0198 (16) 0.021 (2) −0.0004 (16) 0.0024 (18) −0.0031 (15) C10 0.018 (2) 0.0212 (16) 0.022 (2) 0.0003 (16) −0.0005 (18) −0.0003 (15) C11 0.017 (2) 0.0229 (16) 0.019 (2) −0.0007 (15) 0.0025 (18) −0.0027 (15) C12 0.021 (2) 0.0201 (16) 0.022 (2) −0.0016 (16) 0.0018 (19) −0.0024 (15) C13 0.021 (2) 0.0202 (16) 0.022 (2) −0.0023 (16) −0.0017 (19) −0.0011 (15) C21 0.017 (2) 0.0174 (16) 0.031 (2) 0.0041 (16) −0.0059 (19) 0.0002 (15) C22 0.022 (2) 0.0228 (16) 0.026 (2) 0.0021 (17) 0.0021 (19) 0.0003 (16) C23 0.021 (2) 0.0260 (17) 0.025 (2) 0.0016 (17) −0.0014 (19) 0.0023 (15) C24 0.024 (2) 0.0362 (19) 0.027 (2) −0.0018 (19) 0.004 (2) −0.0003 (18) C25 0.027 (2) 0.039 (2) 0.028 (2) −0.005 (2) 0.000 (2) 0.0063 (18) C26 0.025 (2) 0.0282 (18) 0.032 (3) −0.0032 (18) −0.009 (2) 0.0078 (18) C27 0.025 (2) 0.0238 (17) 0.027 (2) −0.0008 (17) −0.0040 (19) −0.0010 (17) C28 0.022 (2) 0.0253 (17) 0.0139 (19) −0.0060 (17) −0.0019 (17) 0.0008 (15) C31 0.033 (3) 0.0232 (17) 0.029 (2) −0.0009 (18) 0.003 (2) −0.0008 (16) C32 0.034 (3) 0.0305 (19) 0.033 (3) −0.0078 (19) −0.002 (2) −0.0069 (17) C33 0.025 (2) 0.0215 (17) 0.020 (2) 0.0028 (17) 0.0031 (18) 0.0003 (15) C34 0.027 (2) 0.0326 (19) 0.034 (2) −0.0024 (19) −0.001 (2) 0.0010 (18) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1827 .table-wrap} ---------------------- ------------ ----------------------- ------------ O29---C28 1.374 (5) C12---C13 1.452 (5) O29---C21 1.395 (4) C21---C22 1.336 (5) C1---C10 1.520 (5) C22---C23 1.438 (5) C1---C11 1.521 (5) C22---H22 0.9500 C1---C33 1.539 (5) C23---C24 1.386 (6) C1---C31 1.548 (5) C23---C28 1.397 (5) C2---C11 1.375 (5) C24---C25 1.388 (5) C2---C3 1.389 (5) C24---H24 0.9500 C2---H2 0.9500 C25---C26 1.400 (5) C3---C4 1.382 (5) C25---H25 0.9500 C3---H3 0.9500 C26---C27 1.386 (6) C4---C5 1.381 (5) C26---H26 0.9500 C4---H4 0.9500 C27---C28 1.381 (5) C5---C12 1.391 (5) C27---H27 0.9500 C5---H5 0.9500 C31---C32 1.512 (6) C6---C7 1.377 (6) C31---H31A 0.9900 C6---C13 1.391 (5) C31---H31B 0.9900 C6---H6 0.9500 C32---H32A 0.9800 C7---C8 1.396 (5) C32---H32B 0.9800 C7---H7 0.9500 C32---H32C 0.9800 C8---C9 1.410 (5) C33---C34 1.519 (5) C8---C21 1.456 (5) C33---H33A 0.9900 C9---C10 1.374 (5) C33---H33B 0.9900 C9---H9 0.9500 C34---H34A 0.9800 C10---C13 1.401 (5) C34---H34B 0.9800 C11---C12 1.412 (5) C34---H34C 0.9800 C28---O29---C21 105.6 (3) C21---C22---C23 108.0 (3) C10---C1---C11 101.5 (3) C21---C22---H22 126.0 C10---C1---C33 112.6 (3) C23---C22---H22 126.0 C11---C1---C33 112.8 (3) C24---C23---C28 118.6 (3) C10---C1---C31 113.0 (3) C24---C23---C22 136.8 (4) C11---C1---C31 107.4 (3) C28---C23---C22 104.6 (3) C33---C1---C31 109.3 (3) C23---C24---C25 118.6 (4) C11---C2---C3 118.7 (3) C23---C24---H24 120.7 C11---C2---H2 120.6 C25---C24---H24 120.7 C3---C2---H2 120.6 C24---C25---C26 121.2 (4) C4---C3---C2 121.0 (4) C24---C25---H25 119.4 C4---C3---H3 119.5 C26---C25---H25 119.4 C2---C3---H3 119.5 C27---C26---C25 121.3 (4) C5---C4---C3 120.7 (4) C27---C26---H26 119.4 C5---C4---H4 119.6 C25---C26---H26 119.4 C3---C4---H4 119.6 C28---C27---C26 116.0 (4) C4---C5---C12 119.0 (3) C28---C27---H27 122.0 C4---C5---H5 120.5 C26---C27---H27 122.0 C12---C5---H5 120.5 O29---C28---C27 124.9 (3) C7---C6---C13 119.3 (3) O29---C28---C23 110.8 (3) C7---C6---H6 120.3 C27---C28---C23 124.3 (4) C13---C6---H6 120.3 C32---C31---C1 116.9 (3) C6---C7---C8 121.2 (3) C32---C31---H31A 108.1 C6---C7---H7 119.4 C1---C31---H31A 108.1 C8---C7---H7 119.4 C32---C31---H31B 108.1 C7---C8---C9 119.0 (3) C1---C31---H31B 108.1 C7---C8---C21 120.8 (3) H31A---C31---H31B 107.3 C9---C8---C21 120.1 (3) C31---C32---H32A 109.5 C10---C9---C8 120.0 (3) C31---C32---H32B 109.5 C10---C9---H9 120.0 H32A---C32---H32B 109.5 C8---C9---H9 120.0 C31---C32---H32C 109.5 C9---C10---C13 120.1 (3) H32A---C32---H32C 109.5 C9---C10---C1 129.4 (3) H32B---C32---H32C 109.5 C13---C10---C1 110.5 (3) C34---C33---C1 114.7 (3) C2---C11---C12 120.6 (4) C34---C33---H33A 108.6 C2---C11---C1 128.8 (3) C1---C33---H33A 108.6 C12---C11---C1 110.5 (3) C34---C33---H33B 108.6 C5---C12---C11 119.8 (3) C1---C33---H33B 108.6 C5---C12---C13 131.9 (3) H33A---C33---H33B 107.6 C11---C12---C13 108.3 (3) C33---C34---H34A 109.5 C6---C13---C10 120.4 (4) C33---C34---H34B 109.5 C6---C13---C12 130.4 (3) H34A---C34---H34B 109.5 C10---C13---C12 109.2 (3) C33---C34---H34C 109.5 C22---C21---O29 110.9 (3) H34A---C34---H34C 109.5 C22---C21---C8 134.1 (3) H34B---C34---H34C 109.5 O29---C21---C8 115.0 (3) C11---C2---C3---C4 −0.9 (6) C1---C10---C13---C12 −1.4 (4) C2---C3---C4---C5 0.5 (6) C5---C12---C13---C6 −2.2 (7) C3---C4---C5---C12 −0.2 (6) C11---C12---C13---C6 177.5 (4) C13---C6---C7---C8 0.9 (6) C5---C12---C13---C10 179.8 (4) C6---C7---C8---C9 −1.0 (6) C11---C12---C13---C10 −0.5 (4) C6---C7---C8---C21 177.6 (4) C28---O29---C21---C22 2.2 (4) C7---C8---C9---C10 0.5 (6) C28---O29---C21---C8 −175.7 (3) C21---C8---C9---C10 −178.1 (4) C7---C8---C21---C22 −171.3 (4) C8---C9---C10---C13 0.2 (6) C9---C8---C21---C22 7.3 (7) C8---C9---C10---C1 179.4 (4) C7---C8---C21---O29 6.0 (5) C11---C1---C10---C9 −176.8 (4) C9---C8---C21---O29 −175.4 (3) C33---C1---C10---C9 −55.9 (6) O29---C21---C22---C23 −1.4 (5) C31---C1---C10---C9 68.5 (5) C8---C21---C22---C23 175.9 (4) C11---C1---C10---C13 2.5 (4) C21---C22---C23---C24 −177.1 (5) C33---C1---C10---C13 123.3 (3) C21---C22---C23---C28 0.1 (4) C31---C1---C10---C13 −112.2 (4) C28---C23---C24---C25 −0.5 (6) C3---C2---C11---C12 1.1 (6) C22---C23---C24---C25 176.5 (4) C3---C2---C11---C1 177.8 (4) C23---C24---C25---C26 0.3 (6) C10---C1---C11---C2 −179.8 (4) C24---C25---C26---C27 0.1 (6) C33---C1---C11---C2 59.6 (5) C25---C26---C27---C28 −0.4 (6) C31---C1---C11---C2 −61.0 (5) C21---O29---C28---C27 176.8 (4) C10---C1---C11---C12 −2.8 (4) C21---O29---C28---C23 −2.1 (4) C33---C1---C11---C12 −123.5 (3) C26---C27---C28---O29 −178.5 (4) C31---C1---C11---C12 116.0 (3) C26---C27---C28---C23 0.3 (6) C4---C5---C12---C11 0.4 (6) C24---C23---C28---O29 179.1 (4) C4---C5---C12---C13 −179.9 (4) C22---C23---C28---O29 1.2 (4) C2---C11---C12---C5 −0.8 (6) C24---C23---C28---C27 0.2 (6) C1---C11---C12---C5 −178.1 (4) C22---C23---C28---C27 −177.7 (4) C2---C11---C12---C13 179.4 (4) C10---C1---C31---C32 −71.1 (5) C1---C11---C12---C13 2.1 (4) C11---C1---C31---C32 177.8 (3) C7---C6---C13---C10 −0.3 (6) C33---C1---C31---C32 55.1 (5) C7---C6---C13---C12 −178.1 (4) C10---C1---C33---C34 −61.3 (5) C9---C10---C13---C6 −0.3 (6) C11---C1---C33---C34 52.8 (4) C1---C10---C13---C6 −179.6 (3) C31---C1---C33---C34 172.2 (3) C9---C10---C13---C12 178.0 (4) ---------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2887 .table-wrap} ------------------------------------------------------------------------------------------------------------------- Cg1, Cg2, Cg3 and Cg4 are the centroids of the C23--C28, O29/C21--C23/C28 and C2--C5/C11/C12 rings, respectively. ------------------------------------------------------------------------------------------------------------------- ::: ::: {#d1e2891 .table-wrap} ---------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C2---H2···Cg1^i^ 0.95 2.99 3.643 (5) 127 C22---H22···Cg1^ii^ 0.95 2.70 3.500 (4) 143 C24---H24···Cg2^ii^ 0.95 2.85 3.569 (5) 133 C27---H27···Cg2^iii^ 0.95 2.75 3.558 (5) 143 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) x−1/2, −y+1/2, −z+2; (iii) −x+2, y−1/2, −z+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1, Cg2, Cg3 and Cg4 are the centroids of the C23--C28, O29/C21--C23/C28 and C2--C5/C11/C12 rings, respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------------- --------- ------- ----------- ------------- C2---H2⋯Cg1^i^ 0.95 2.99 3.643 (5) 127 C22---H22⋯Cg1^ii^ 0.95 2.70 3.500 (4) 143 C24---H24⋯Cg2^ii^ 0.95 2.85 3.569 (5) 133 C27---H27⋯Cg2^iii^ 0.95 2.75 3.558 (5) 143 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.685120	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052132/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o743", "authors": [ { "first": "Ping-Hsin", "last": "Huang" }, { "first": "Kai-Ling", "last": "Lin" }, { "first": "Yuh-Sheng", "last": "Wen" } ] }
PMC3052133	Related literature {#sec1} ================== The starting compound, Fe(NO)~2~(CO)~2~, was prepared using a published method described by Eisch & King (1965[@bb4]). For the structures of some related dinitrosyl complexes, see: Li et al. (2003[@bb5]); Atkinson et al. (1996[@bb2]); Li Kam Wah et al. (1989[@bb6]); Albano et al. (1974[@bb1]). For general information on metal nitrosyl chemistry, see: Richter-Addo & Legzdins (1992[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Fe(NO)~2~(C~21~H~21~P)~2~\]M ~r~ = 724.57Triclinic,a = 10.240 (2) Åb = 19.409 (4) Åc = 21.040 (4) Åα = 114.508 (5)°β = 93.158 (6)°γ = 94.732 (6)°V = 3773.5 (13) Å^3^Z = 4Mo Kα radiationμ = 0.52 mm^−1^T = 100 K0.34 × 0.29 × 0.29 mm ### Data collection {#sec2.1.2} Bruker APEX CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 2001[@bb8]) T ~min~ = 0.843, T ~max~ = 0.86339881 measured reflections14767 independent reflections12772 reflections with I \> 2σ(I)R ~int~ = 0.025 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.035wR(F ^2^) = 0.095S = 1.0114767 reflections883 parametersH-atom parameters constrainedΔρ~max~ = 0.47 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e394} Data collection: SMART (Bruker, 2007[@bb3]); cell refinement: SAINT (Bruker, 2007[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100465X/fk2034sup1.cif](http://dx.doi.org/10.1107/S160053681100465X/fk2034sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100465X/fk2034Isup2.hkl](http://dx.doi.org/10.1107/S160053681100465X/fk2034Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?fk2034&file=fk2034sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?fk2034sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?fk2034&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [FK2034](http://scripts.iucr.org/cgi-bin/sendsup?fk2034)). We are grateful to the US Department of Education (GAANN Fellowship to MWJ; P200A030196) and the National Science Foundation (CHE-0076640 and CHE-0911537) for funding this work. The authors thank the National Science Foundation (CHE-0130835) and the University of Oklahoma for funds to acquire the diffractometer and computers used in this work. Comment ======= The molecular structure of the title compound is shown in Fig. 1. There are two distinct molecules per asymmetric unit of the cell. Each molecule possesses a distorted tetrahedral geometry around the iron center. The irons are bound to two nitrosyl groups via the nitrogen atoms and to two phosphine ligands via the phosphorous atoms. The Fe(NO)~2~ groups are in the attracto conformation where the bond angles O···Fe···O \< N---Fe---N (Richter-Addo & Legzdins, 1992). The N---Fe---N bond angles for molecule 1 and molecule 2 are 129.89 (7)° and 124.29 (8)° respectively, while the interphosphine angles, P---Fe---P, are 106.00 (2)° and 105.57 (2)° respectively. The Fe---N---O bond angles range between 173.84 (15)° and 179.31 (16)°. For the structures of some related complexes, see: Li et al. (2003), Atkinson et al. (1996), Li Kam Wah et al. (1989), and Albano et al. (1974). Experimental {#experimental} ============ Dark red Fe(NO)~2~(CO)~2~ (20 µL, 0.18 mmol) (Eisch & King, 1965) was added by syringe under nitrogen to a colorless toluene solution (5 ml) of P(C~6~H~4~-p-CH~3~)~3~ (0.111 g, 0.36 mmol) in a Schlenk tube. The mixture was stirred and heated to reflux under nitrogen for a period of \~3 h. A color change from light red to black/dark brown was observed within the first 30 min. The reaction was stopped when the infrared spectrum indicated the absence of characteristic carbonyl stretching frequencies for Fe(NO)~2~(CO)~2~ (ν~CO~ = 2090 cm^-1^ and 2040 cm^-1^). The reaction mixture was filtered through celite under N~2~ and the solvent was subsequently removed under vacuum. Isolated yield of the Fe(NO)~2~L~2~ compound: 31%. IR (toluene, cm^-1^): ν~NO~ = 1714 s and 1670 s. ^31^P{^1^H} NMR (CDCl~3~): δ 58.4 (s) referenced to 85% H~3~PO~4~. Suitable crystals for X-ray diffraction studies were grown by slow evaporation of a chloroform solution of the complex under nitrogen at ambient temperature. Refinement {#refinement} ========== Phenyl H atoms were placed using known geometry with C---H = 0.95 Å. Methyl H atoms were initially located on a difference map and their positions were refined as rigid groups maintaining C---H = 0.98 Å and C---C---H angles to be equal by refining a torsion angle for each of the rigid groups. Once refinement had converged, the additional torsion angles were removed and refinement was repeated. Displacement parameters of phenyl H atoms were set to 1.2 times the isotropic equivalent for the bonded C (1.5 for methyl H atoms). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound showing the relative orientation of the two neighboring molecules. Hydrogen atoms were omitted for clarity. The displacement ellipsoids were drawn at the 50% probability level. ::: ![](e-67-0m331-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e197 .table-wrap} ------------------------------- --------------------------------------- \[Fe(NO)~2~(C~21~H~21~P)~2~\] Z = 4 M~r~ = 724.57 F(000) = 1520 Triclinic, P1 D~x~ = 1.275 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.240 (2) Å Cell parameters from 8062 reflections b = 19.409 (4) Å θ = 2.3--28.3° c = 21.040 (4) Å µ = 0.52 mm^−1^ α = 114.508 (5)° T = 100 K β = 93.158 (6)° Prism, red γ = 94.732 (6)° 0.34 × 0.29 × 0.29 mm V = 3773.5 (13) Å^3^ ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e334 .table-wrap} --------------------------------------------------------------- --------------------------------------- Bruker APEX CCD diffractometer 14767 independent reflections Radiation source: fine-focus sealed tube 12772 reflections with I \> 2σ(I) graphite R~int~ = 0.025 ω scans θ~max~ = 26.0°, θ~min~ = 1.9° Absorption correction: multi-scan (SADABS; Sheldrick, 2001) h = −12→12 T~min~ = 0.843, T~max~ = 0.863 k = −23→23 39881 measured reflections l = −25→25 --------------------------------------------------------------- --------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e448 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.035 Hydrogen site location: geom and difmap wR(F^2^) = 0.095 H-atom parameters constrained S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.052P)^2^ + 1.6P\] where P = (F~o~^2^ + 2F~c~^2^)/3 14767 reflections (Δ/σ)~max~ = 0.002 883 parameters Δρ~max~ = 0.47 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e607 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Fe1 0.39525 (2) 0.721825 (14) 0.379710 (13) 0.01684 (7) P11 0.28352 (4) 0.75740 (2) 0.30476 (2) 0.01665 (10) N11 0.52762 (15) 0.78538 (9) 0.40581 (8) 0.0229 (3) O11 0.62231 (14) 0.83142 (9) 0.42413 (9) 0.0423 (4) C101 0.38308 (17) 0.76140 (10) 0.23620 (9) 0.0187 (4) C102 0.50084 (18) 0.72935 (11) 0.22635 (10) 0.0243 (4) H102 0.5286 0.7048 0.2547 0.029\ C103 0.57844 (19) 0.73288 (12) 0.17537 (10) 0.0296 (4) H103 0.6592 0.7112 0.1699 0.036\* C104 0.54089 (18) 0.76711 (11) 0.13254 (10) 0.0259 (4) C105 0.42240 (19) 0.79844 (11) 0.14174 (10) 0.0272 (4) H105 0.3939 0.8216 0.1124 0.033\* C106 0.34516 (18) 0.79640 (11) 0.19310 (10) 0.0239 (4) H106 0.2654 0.8191 0.1991 0.029\* C107 0.6249 (2) 0.77143 (14) 0.07718 (11) 0.0379 (5) H10A 0.6896 0.8169 0.0982 0.057\* H10B 0.5688 0.7744 0.0393 0.057\* H10C 0.6709 0.7258 0.0581 0.057\* C108 0.23570 (18) 0.85384 (10) 0.34316 (9) 0.0200 (4) C109 0.3295 (2) 0.91604 (10) 0.35781 (10) 0.0251 (4) H109 0.4153 0.9077 0.3434 0.030\* C110 0.2992 (2) 0.98989 (11) 0.39310 (11) 0.0340 (5) H110 0.3646 1.0315 0.4027 0.041\* C111 0.1744 (2) 1.00388 (12) 0.41462 (11) 0.0393 (6) C112 0.0815 (2) 0.94192 (13) 0.40057 (10) 0.0365 (5) H112 −0.0040 0.9505 0.4154 0.044\* C113 0.11095 (19) 0.86772 (12) 0.36529 (10) 0.0269 (4) H113 0.0457 0.8262 0.3562 0.032\* C114 0.1395 (3) 1.08414 (14) 0.45209 (15) 0.0675 (10) H10D 0.0458 1.0851 0.4407 0.101\* H10E 0.1923 1.1181 0.4370 0.101\* H10F 0.1579 1.1013 0.5029 0.101\* C115 0.13121 (17) 0.69818 (10) 0.25660 (9) 0.0187 (4) C116 0.04992 (18) 0.71691 (11) 0.21226 (10) 0.0260 (4) H116 0.0735 0.7621 0.2063 0.031\* C117 −0.06413 (18) 0.67082 (11) 0.17700 (10) 0.0267 (4) H117 −0.1170 0.6841 0.1462 0.032\* C118 −0.10355 (18) 0.60487 (11) 0.18570 (10) 0.0250 (4) C119 −0.02243 (19) 0.58641 (10) 0.22993 (10) 0.0252 (4) H119 −0.0468 0.5417 0.2366 0.030\* C120 0.09349 (18) 0.63199 (10) 0.26454 (9) 0.0214 (4) H120 0.1479 0.6178 0.2941 0.026\* C121 −0.2297 (2) 0.55519 (12) 0.14826 (12) 0.0361 (5) H10G −0.3037 0.5762 0.1748 0.054\* H10H −0.2242 0.5035 0.1445 0.054\* H10I −0.2432 0.5536 0.1012 0.054\* P12 0.27399 (4) 0.74526 (2) 0.47036 (2) 0.01681 (10) N12 0.38322 (14) 0.62764 (9) 0.34965 (8) 0.0214 (3) O12 0.37303 (14) 0.56049 (7) 0.33303 (8) 0.0337 (3) C122 0.34119 (18) 0.70741 (10) 0.53047 (9) 0.0203 (4) C123 0.47703 (19) 0.71779 (12) 0.54674 (10) 0.0280 (4) H123 0.5321 0.7406 0.5242 0.034\* C124 0.5331 (2) 0.69512 (13) 0.59559 (11) 0.0352 (5) H124 0.6258 0.7039 0.6069 0.042\* C125 0.4554 (2) 0.65974 (13) 0.62823 (11) 0.0323 (5) C126 0.3199 (2) 0.64810 (11) 0.61068 (10) 0.0265 (4) H126 0.2651 0.6231 0.6316 0.032\* C127 0.26342 (18) 0.67224 (10) 0.56331 (9) 0.0222 (4) H127 0.1704 0.6647 0.5531 0.027\* C128 0.5146 (2) 0.63598 (17) 0.68217 (14) 0.0505 (7) H10J 0.4522 0.6402 0.7169 0.076\* H10K 0.5962 0.6692 0.7057 0.076\* H10L 0.5340 0.5831 0.6590 0.076\* C129 0.10421 (17) 0.70029 (10) 0.44695 (9) 0.0185 (4) C130 0.07860 (18) 0.62120 (10) 0.42010 (9) 0.0212 (4) H130 0.1489 0.5918 0.4188 0.025\* C131 −0.04789 (18) 0.58485 (11) 0.39528 (10) 0.0242 (4) H131 −0.0632 0.5309 0.3778 0.029\* C132 −0.15330 (18) 0.62621 (11) 0.39555 (10) 0.0260 (4) C133 −0.12697 (18) 0.70518 (11) 0.42229 (10) 0.0262 (4) H133 −0.1971 0.7346 0.4232 0.031\* C134 −0.00062 (18) 0.74192 (10) 0.44770 (9) 0.0218 (4) H134 0.0145 0.7959 0.4658 0.026\* C135 −0.2907 (2) 0.58681 (12) 0.36654 (12) 0.0367 (5) H10M −0.3544 0.6161 0.3968 0.055\* H10N −0.2975 0.5354 0.3649 0.055\* H10O −0.3094 0.5834 0.3191 0.055\* C136 0.26292 (17) 0.84432 (10) 0.53071 (9) 0.0185 (4) C137 0.19553 (18) 0.86158 (11) 0.59036 (9) 0.0234 (4) H137 0.1518 0.8215 0.5988 0.028\* C138 0.19201 (19) 0.93630 (11) 0.63711 (10) 0.0276 (4) H138 0.1456 0.9469 0.6774 0.033\* C139 0.25514 (18) 0.99655 (11) 0.62653 (10) 0.0258 (4) C140 0.32166 (19) 0.97939 (11) 0.56705 (10) 0.0246 (4) H140 0.3648 1.0195 0.5585 0.029\* C141 0.32592 (18) 0.90400 (10) 0.51970 (9) 0.0214 (4) H141 0.3725 0.8933 0.4794 0.026\* C142 0.2541 (2) 1.07824 (12) 0.67967 (11) 0.0372 (5) H10P 0.1701 1.0837 0.7004 0.056\* H10Q 0.2652 1.1124 0.6563 0.056\* H10R 0.3265 1.0914 0.7167 0.056\* Fe2 0.20249 (2) 0.726480 (14) 0.861160 (13) 0.01703 (7) P21 0.07337 (4) 0.78326 (2) 0.81153 (2) 0.01688 (10) N21 0.19663 (14) 0.63819 (9) 0.80051 (8) 0.0217 (3) O21 0.19345 (15) 0.57497 (8) 0.75630 (8) 0.0366 (4) C201 −0.05695 (17) 0.83832 (10) 0.85539 (9) 0.0196 (4) C202 −0.03062 (19) 0.88754 (10) 0.92638 (10) 0.0224 (4) H202 0.0550 0.8936 0.9492 0.027\* C203 −0.1274 (2) 0.92766 (10) 0.96401 (10) 0.0267 (4) H203 −0.1075 0.9607 1.0124 0.032\* C204 −0.25337 (19) 0.92016 (11) 0.93188 (11) 0.0294 (4) C205 −0.27994 (19) 0.87105 (11) 0.86129 (11) 0.0296 (4) H205 −0.3656 0.8651 0.8386 0.036\* C206 −0.18345 (18) 0.83046 (11) 0.82327 (10) 0.0245 (4) H206 −0.2038 0.7971 0.7750 0.029\* C207 −0.3572 (2) 0.96526 (12) 0.97353 (13) 0.0422 (6) H2OA −0.3894 0.9424 1.0042 0.063\* H20B −0.4305 0.9646 0.9413 0.063\* H20C −0.3189 1.0180 1.0021 0.063\* C208 −0.01124 (17) 0.71612 (10) 0.72718 (9) 0.0187 (4) C209 −0.07366 (18) 0.64768 (10) 0.72364 (10) 0.0230 (4) H209 −0.0690 0.6374 0.7641 0.028\* C210 −0.14236 (18) 0.59459 (11) 0.66173 (10) 0.0261 (4) H210 −0.1848 0.5485 0.6604 0.031\* C211 −0.15029 (18) 0.60753 (11) 0.60152 (10) 0.0264 (4) C212 −0.08842 (19) 0.67611 (11) 0.60524 (10) 0.0267 (4) H212 −0.0929 0.6863 0.5648 0.032\* C213 −0.02019 (18) 0.72984 (11) 0.66754 (10) 0.0231 (4) H213 0.0207 0.7764 0.6692 0.028\* C214 −0.2240 (2) 0.54858 (13) 0.53420 (11) 0.0407 (5) H20D −0.2704 0.5742 0.5098 0.061\* H20E −0.2878 0.5155 0.5450 0.061\* H20F −0.1615 0.5178 0.5041 0.061\* C215 0.18434 (17) 0.84965 (10) 0.79286 (9) 0.0199 (4) C216 0.1841 (2) 0.92808 (11) 0.82258 (10) 0.0267 (4) H216 0.1147 0.9503 0.8495 0.032\* C217 0.2857 (2) 0.97461 (12) 0.81311 (11) 0.0341 (5) H217 0.2855 1.0284 0.8347 0.041\* C218 0.3865 (2) 0.94394 (12) 0.77295 (11) 0.0329 (5) C219 0.38517 (19) 0.86522 (12) 0.74230 (10) 0.0286 (4) H219 0.4525 0.8430 0.7137 0.034\* C220 0.28759 (18) 0.81904 (11) 0.75285 (10) 0.0245 (4) H220 0.2902 0.7654 0.7327 0.029\* C221 0.4951 (2) 0.99342 (15) 0.76049 (14) 0.0492 (6) H20G 0.5807 0.9782 0.7694 0.074\* H20H 0.4915 1.0470 0.7923 0.074\* H20I 0.4834 0.9871 0.7118 0.074\* P22 0.09066 (4) 0.71480 (3) 0.94568 (2) 0.01739 (10) N22 0.34007 (15) 0.78364 (9) 0.89869 (8) 0.0247 (3) O22 0.44468 (15) 0.81869 (9) 0.92377 (10) 0.0486 (4) C222 0.16869 (17) 0.65324 (10) 0.97918 (9) 0.0192 (4) C223 0.30279 (17) 0.64885 (10) 0.97346 (9) 0.0207 (4) H223 0.3474 0.6720 0.9476 0.025\* C224 0.37193 (18) 0.61113 (10) 1.00497 (10) 0.0227 (4) H224 0.4634 0.6088 1.0004 0.027\* C225 0.31008 (19) 0.57673 (10) 1.04306 (10) 0.0244 (4) C226 0.1750 (2) 0.57987 (12) 1.04768 (11) 0.0305 (5) H226 0.1303 0.5558 1.0728 0.037\* C227 0.10521 (19) 0.61749 (11) 1.01627 (10) 0.0274 (4) H227 0.0134 0.6190 1.0200 0.033\* C228 0.3873 (2) 0.53776 (12) 1.07865 (11) 0.0337 (5) H20J 0.3826 0.5632 1.1295 0.051\* H20K 0.4794 0.5404 1.0686 0.051\* H20L 0.3501 0.4843 1.0611 0.051\* C229 0.08260 (17) 0.79809 (10) 1.02850 (9) 0.0197 (4) C230 0.17595 (18) 0.86123 (10) 1.04769 (10) 0.0224 (4) H230 0.2380 0.8623 1.0161 0.027\* C231 0.17944 (19) 0.92279 (11) 1.11262 (10) 0.0256 (4) H231 0.2442 0.9654 1.1248 0.031\* C232 0.09016 (19) 0.92330 (11) 1.16006 (10) 0.0262 (4) C233 −0.0038 (2) 0.86033 (12) 1.14066 (10) 0.0282 (4) H233 −0.0663 0.8597 1.1722 0.034\* C234 −0.00769 (19) 0.79843 (11) 1.07609 (10) 0.0247 (4) H234 −0.0723 0.7559 1.0641 0.030\* C235 0.0974 (2) 0.98930 (13) 1.23171 (11) 0.0366 (5) H20M 0.0089 0.9947 1.2474 0.055\* H20N 0.1329 1.0363 1.2289 0.055\* H20O 0.1549 0.9796 1.2651 0.055\* C236 −0.07859 (17) 0.67165 (10) 0.91595 (9) 0.0189 (4) C237 −0.10360 (18) 0.59358 (10) 0.87334 (10) 0.0221 (4) H237 −0.0339 0.5626 0.8666 0.027\* C238 −0.22833 (18) 0.56068 (11) 0.84085 (10) 0.0231 (4) H238 −0.2427 0.5075 0.8116 0.028\* C239 −0.33384 (17) 0.60460 (11) 0.85051 (9) 0.0217 (4) C240 −0.30823 (18) 0.68238 (11) 0.89178 (10) 0.0227 (4) H240 −0.3779 0.7134 0.8982 0.027\* C241 −0.18260 (17) 0.71601 (10) 0.92405 (9) 0.0211 (4) H241 −0.1675 0.7695 0.9518 0.025\* C242 −0.47141 (18) 0.56809 (12) 0.81872 (10) 0.0277 (4) H20P −0.5091 0.5424 0.8461 0.042\* H20Q −0.4685 0.5308 0.7702 0.042\* H20R −0.5261 0.6074 0.8192 0.042\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2971 .table-wrap} ------ -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Fe1 0.01472 (13) 0.01709 (13) 0.01718 (13) 0.00358 (10) 0.00093 (9) 0.00549 (10) P11 0.0145 (2) 0.0170 (2) 0.0172 (2) 0.00310 (17) 0.00163 (17) 0.00579 (18) N11 0.0184 (8) 0.0240 (8) 0.0253 (8) 0.0039 (6) −0.0006 (6) 0.0094 (7) O11 0.0236 (8) 0.0363 (9) 0.0614 (11) −0.0091 (7) −0.0071 (7) 0.0188 (8) C101 0.0159 (8) 0.0178 (9) 0.0177 (8) 0.0002 (7) 0.0020 (7) 0.0030 (7) C102 0.0231 (10) 0.0258 (10) 0.0245 (10) 0.0072 (8) 0.0043 (8) 0.0100 (8) C103 0.0206 (10) 0.0356 (11) 0.0297 (11) 0.0088 (8) 0.0081 (8) 0.0091 (9) C104 0.0221 (10) 0.0282 (10) 0.0197 (9) −0.0035 (8) 0.0035 (7) 0.0036 (8) C105 0.0248 (10) 0.0333 (11) 0.0235 (10) 0.0012 (8) 0.0026 (8) 0.0123 (8) C106 0.0193 (9) 0.0298 (10) 0.0235 (9) 0.0059 (8) 0.0041 (7) 0.0113 (8) C107 0.0297 (11) 0.0493 (14) 0.0320 (11) 0.0007 (10) 0.0116 (9) 0.0142 (10) C108 0.0239 (9) 0.0213 (9) 0.0142 (8) 0.0079 (7) 0.0008 (7) 0.0060 (7) C109 0.0281 (10) 0.0224 (10) 0.0231 (9) 0.0049 (8) −0.0005 (8) 0.0079 (8) C110 0.0476 (13) 0.0210 (10) 0.0280 (11) 0.0041 (9) −0.0114 (9) 0.0067 (8) C111 0.0509 (14) 0.0289 (11) 0.0260 (11) 0.0215 (10) −0.0137 (10) −0.0013 (9) C112 0.0356 (12) 0.0434 (13) 0.0231 (10) 0.0248 (10) 0.0002 (9) 0.0033 (9) C113 0.0255 (10) 0.0318 (11) 0.0218 (9) 0.0103 (8) 0.0018 (8) 0.0085 (8) C114 0.076 (2) 0.0357 (14) 0.0576 (17) 0.0335 (14) −0.0298 (15) −0.0138 (12) C115 0.0154 (8) 0.0198 (9) 0.0180 (8) 0.0030 (7) 0.0031 (7) 0.0048 (7) C116 0.0215 (10) 0.0324 (11) 0.0285 (10) 0.0000 (8) −0.0004 (8) 0.0181 (9) C117 0.0184 (9) 0.0369 (11) 0.0257 (10) 0.0035 (8) −0.0026 (8) 0.0147 (9) C118 0.0186 (9) 0.0241 (10) 0.0232 (9) 0.0020 (7) 0.0001 (7) 0.0013 (8) C119 0.0266 (10) 0.0172 (9) 0.0268 (10) 0.0011 (7) 0.0010 (8) 0.0049 (8) C120 0.0214 (9) 0.0201 (9) 0.0200 (9) 0.0042 (7) −0.0003 (7) 0.0057 (7) C121 0.0278 (11) 0.0294 (11) 0.0399 (12) −0.0030 (9) −0.0094 (9) 0.0062 (9) P12 0.0159 (2) 0.0166 (2) 0.0169 (2) 0.00352 (17) 0.00099 (17) 0.00579 (18) N12 0.0178 (8) 0.0222 (8) 0.0214 (8) 0.0061 (6) 0.0023 (6) 0.0056 (6) O12 0.0325 (8) 0.0175 (7) 0.0456 (9) 0.0052 (6) 0.0036 (7) 0.0075 (6) C122 0.0228 (9) 0.0187 (9) 0.0191 (9) 0.0061 (7) 0.0019 (7) 0.0068 (7) C123 0.0219 (10) 0.0391 (12) 0.0298 (10) 0.0061 (8) 0.0038 (8) 0.0206 (9) C124 0.0230 (10) 0.0535 (14) 0.0369 (12) 0.0113 (10) 0.0022 (9) 0.0257 (11) C125 0.0337 (11) 0.0419 (12) 0.0284 (11) 0.0155 (9) 0.0040 (9) 0.0197 (10) C126 0.0311 (11) 0.0267 (10) 0.0247 (10) 0.0067 (8) 0.0069 (8) 0.0128 (8) C127 0.0222 (9) 0.0225 (9) 0.0205 (9) 0.0040 (7) 0.0021 (7) 0.0073 (8) C128 0.0413 (14) 0.083 (2) 0.0514 (15) 0.0225 (13) 0.0079 (11) 0.0486 (15) C129 0.0169 (9) 0.0206 (9) 0.0172 (8) 0.0032 (7) 0.0028 (7) 0.0068 (7) C130 0.0191 (9) 0.0218 (9) 0.0229 (9) 0.0069 (7) 0.0026 (7) 0.0087 (8) C131 0.0239 (10) 0.0200 (9) 0.0239 (9) 0.0014 (7) 0.0014 (8) 0.0046 (8) C132 0.0192 (9) 0.0279 (10) 0.0244 (10) 0.0031 (8) 0.0003 (7) 0.0049 (8) C133 0.0182 (9) 0.0287 (10) 0.0282 (10) 0.0089 (8) −0.0002 (8) 0.0076 (8) C134 0.0232 (9) 0.0190 (9) 0.0207 (9) 0.0058 (7) 0.0016 (7) 0.0054 (7) C135 0.0212 (10) 0.0334 (12) 0.0433 (13) 0.0006 (9) −0.0037 (9) 0.0054 (10) C136 0.0164 (8) 0.0191 (9) 0.0173 (8) 0.0046 (7) −0.0013 (7) 0.0049 (7) C137 0.0231 (10) 0.0237 (10) 0.0213 (9) 0.0024 (7) 0.0023 (7) 0.0075 (8) C138 0.0255 (10) 0.0309 (11) 0.0194 (9) 0.0043 (8) 0.0042 (8) 0.0031 (8) C139 0.0229 (10) 0.0233 (10) 0.0227 (9) 0.0048 (8) −0.0031 (8) 0.0017 (8) C140 0.0258 (10) 0.0203 (9) 0.0246 (10) 0.0002 (7) −0.0030 (8) 0.0076 (8) C141 0.0225 (9) 0.0219 (9) 0.0170 (9) 0.0035 (7) 0.0005 (7) 0.0054 (7) C142 0.0373 (12) 0.0256 (11) 0.0342 (12) 0.0048 (9) 0.0022 (9) −0.0019 (9) Fe2 0.01515 (13) 0.01775 (13) 0.01839 (13) 0.00327 (10) 0.00339 (10) 0.00735 (10) P21 0.0166 (2) 0.0161 (2) 0.0176 (2) 0.00260 (17) 0.00314 (17) 0.00653 (18) N21 0.0187 (8) 0.0225 (8) 0.0254 (8) 0.0051 (6) 0.0041 (6) 0.0108 (7) O21 0.0392 (9) 0.0199 (7) 0.0389 (8) 0.0069 (6) 0.0010 (7) 0.0004 (6) C201 0.0201 (9) 0.0175 (9) 0.0241 (9) 0.0033 (7) 0.0065 (7) 0.0107 (7) C202 0.0248 (10) 0.0186 (9) 0.0242 (9) 0.0035 (7) 0.0036 (7) 0.0092 (8) C203 0.0320 (11) 0.0187 (9) 0.0275 (10) 0.0030 (8) 0.0101 (8) 0.0071 (8) C204 0.0262 (10) 0.0190 (9) 0.0419 (12) 0.0051 (8) 0.0146 (9) 0.0099 (9) C205 0.0187 (10) 0.0265 (10) 0.0430 (12) 0.0047 (8) 0.0056 (8) 0.0132 (9) C206 0.0221 (10) 0.0235 (10) 0.0270 (10) 0.0039 (8) 0.0035 (8) 0.0095 (8) C207 0.0299 (12) 0.0288 (11) 0.0598 (15) 0.0077 (9) 0.0216 (11) 0.0079 (11) C208 0.0154 (8) 0.0184 (9) 0.0197 (9) 0.0036 (7) 0.0029 (7) 0.0049 (7) C209 0.0223 (9) 0.0224 (9) 0.0246 (9) 0.0044 (7) 0.0017 (7) 0.0099 (8) C210 0.0232 (10) 0.0199 (9) 0.0322 (10) 0.0019 (7) 0.0008 (8) 0.0084 (8) C211 0.0217 (10) 0.0269 (10) 0.0238 (10) 0.0029 (8) 0.0004 (8) 0.0043 (8) C212 0.0255 (10) 0.0332 (11) 0.0206 (9) 0.0022 (8) 0.0025 (8) 0.0108 (8) C213 0.0214 (9) 0.0231 (9) 0.0250 (9) 0.0004 (7) 0.0038 (7) 0.0104 (8) C214 0.0450 (14) 0.0353 (12) 0.0289 (11) −0.0050 (10) −0.0072 (10) 0.0041 (10) C215 0.0198 (9) 0.0215 (9) 0.0189 (9) −0.0006 (7) 0.0001 (7) 0.0097 (7) C216 0.0342 (11) 0.0234 (10) 0.0218 (9) 0.0031 (8) 0.0036 (8) 0.0087 (8) C217 0.0476 (13) 0.0205 (10) 0.0307 (11) −0.0071 (9) −0.0012 (10) 0.0098 (9) C218 0.0303 (11) 0.0382 (12) 0.0308 (11) −0.0124 (9) −0.0062 (9) 0.0192 (10) C219 0.0219 (10) 0.0405 (12) 0.0275 (10) 0.0012 (8) 0.0022 (8) 0.0190 (9) C220 0.0244 (10) 0.0249 (10) 0.0253 (10) 0.0033 (8) 0.0035 (8) 0.0114 (8) C221 0.0409 (14) 0.0538 (15) 0.0561 (16) −0.0189 (12) −0.0036 (12) 0.0317 (13) P22 0.0158 (2) 0.0186 (2) 0.0188 (2) 0.00351 (17) 0.00334 (17) 0.00850 (18) N22 0.0202 (8) 0.0242 (8) 0.0302 (9) 0.0030 (7) 0.0046 (7) 0.0117 (7) O22 0.0238 (8) 0.0433 (10) 0.0653 (11) −0.0094 (7) 0.0005 (8) 0.0124 (9) C222 0.0207 (9) 0.0175 (9) 0.0186 (9) 0.0038 (7) 0.0016 (7) 0.0065 (7) C223 0.0204 (9) 0.0183 (9) 0.0228 (9) 0.0016 (7) 0.0025 (7) 0.0080 (7) C224 0.0185 (9) 0.0212 (9) 0.0253 (9) 0.0026 (7) −0.0001 (7) 0.0070 (8) C225 0.0285 (10) 0.0213 (9) 0.0232 (9) 0.0041 (8) −0.0006 (8) 0.0092 (8) C226 0.0328 (11) 0.0348 (11) 0.0355 (11) 0.0083 (9) 0.0095 (9) 0.0248 (10) C227 0.0217 (10) 0.0325 (11) 0.0344 (11) 0.0063 (8) 0.0073 (8) 0.0193 (9) C228 0.0348 (12) 0.0356 (12) 0.0376 (12) 0.0076 (9) 0.0021 (9) 0.0218 (10) C229 0.0197 (9) 0.0225 (9) 0.0190 (9) 0.0075 (7) 0.0021 (7) 0.0099 (7) C230 0.0210 (9) 0.0253 (10) 0.0224 (9) 0.0051 (7) 0.0027 (7) 0.0109 (8) C231 0.0241 (10) 0.0254 (10) 0.0245 (10) 0.0020 (8) −0.0040 (8) 0.0089 (8) C232 0.0287 (10) 0.0299 (10) 0.0189 (9) 0.0123 (8) 0.0002 (8) 0.0078 (8) C233 0.0292 (11) 0.0362 (11) 0.0226 (10) 0.0119 (9) 0.0083 (8) 0.0137 (9) C234 0.0250 (10) 0.0273 (10) 0.0236 (9) 0.0054 (8) 0.0048 (8) 0.0118 (8) C235 0.0402 (13) 0.0377 (12) 0.0244 (10) 0.0127 (10) 0.0035 (9) 0.0042 (9) C236 0.0170 (9) 0.0235 (9) 0.0195 (9) 0.0028 (7) 0.0045 (7) 0.0118 (7) C237 0.0183 (9) 0.0241 (9) 0.0263 (10) 0.0058 (7) 0.0054 (7) 0.0120 (8) C238 0.0230 (9) 0.0218 (9) 0.0239 (9) 0.0003 (7) 0.0034 (7) 0.0092 (8) C239 0.0185 (9) 0.0303 (10) 0.0198 (9) 0.0020 (7) 0.0024 (7) 0.0141 (8) C240 0.0186 (9) 0.0300 (10) 0.0250 (9) 0.0073 (7) 0.0056 (7) 0.0160 (8) C241 0.0217 (9) 0.0221 (9) 0.0217 (9) 0.0041 (7) 0.0060 (7) 0.0105 (8) C242 0.0206 (10) 0.0366 (11) 0.0271 (10) 0.0009 (8) −0.0002 (8) 0.0154 (9) ------ -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e4563 .table-wrap} --------------------------- -------------- --------------------------- -------------- Fe1---N11 1.6555 (16) Fe2---N21 1.6519 (16) Fe1---N12 1.6590 (16) Fe2---N22 1.6529 (16) Fe1---P12 2.2407 (6) Fe2---P22 2.2451 (6) Fe1---P11 2.2600 (6) Fe2---P21 2.2574 (6) P11---C108 1.8266 (18) P21---C208 1.8232 (18) P11---C115 1.8288 (18) P21---C201 1.8242 (18) P11---C101 1.8352 (18) P21---C215 1.8259 (18) N11---O11 1.191 (2) N21---O21 1.190 (2) C101---C102 1.389 (3) C201---C206 1.394 (3) C101---C106 1.397 (3) C201---C202 1.395 (3) C102---C103 1.390 (3) C202---C203 1.385 (3) C102---H102 0.9500 C202---H202 0.9500 C103---C104 1.379 (3) C203---C204 1.390 (3) C103---H103 0.9500 C203---H203 0.9500 C104---C105 1.389 (3) C204---C205 1.388 (3) C104---C107 1.511 (3) C204---C207 1.511 (3) C105---C106 1.385 (3) C205---C206 1.389 (3) C105---H105 0.9500 C205---H205 0.9500 C106---H106 0.9500 C206---H206 0.9500 C107---H10A 0.9800 C207---H2OA 0.9799 C107---H10B 0.9798 C207---H20B 0.9800 C107---H10C 0.9801 C207---H20C 0.9800 C108---C113 1.393 (3) C208---C213 1.386 (3) C108---C109 1.394 (3) C208---C209 1.397 (3) C109---C110 1.385 (3) C209---C210 1.385 (3) C109---H109 0.9500 C209---H209 0.9500 C110---C111 1.390 (3) C210---C211 1.390 (3) C110---H110 0.9500 C210---H210 0.9500 C111---C112 1.387 (3) C211---C212 1.396 (3) C111---C114 1.510 (3) C211---C214 1.510 (3) C112---C113 1.388 (3) C212---C213 1.392 (3) C112---H112 0.9500 C212---H212 0.9500 C113---H113 0.9500 C213---H213 0.9500 C114---H10D 0.9800 C214---H20D 0.9798 C114---H10E 0.9800 C214---H20E 0.9801 C114---H10F 0.9798 C214---H20F 0.9800 C115---C120 1.390 (3) C215---C216 1.385 (3) C115---C116 1.393 (3) C215---C220 1.402 (3) C116---C117 1.377 (3) C216---C217 1.398 (3) C116---H116 0.9500 C216---H216 0.9500 C117---C118 1.397 (3) C217---C218 1.384 (3) C117---H117 0.9500 C217---H217 0.9500 C118---C119 1.387 (3) C218---C219 1.389 (3) C118---C121 1.507 (3) C218---C221 1.514 (3) C119---C120 1.385 (3) C219---C220 1.376 (3) C119---H119 0.9500 C219---H219 0.9500 C120---H120 0.9500 C220---H220 0.9500 C121---H10G 0.9800 C221---H20G 0.9801 C121---H10H 0.9799 C221---H20H 0.9800 C121---H10I 0.9800 C221---H20I 0.9802 P12---C129 1.8237 (18) P22---C236 1.8174 (18) P12---C136 1.8298 (18) P22---C229 1.8323 (18) P12---C122 1.8361 (18) P22---C222 1.8323 (18) N12---O12 1.195 (2) N22---O22 1.187 (2) C122---C123 1.392 (3) C222---C223 1.392 (3) C122---C127 1.393 (3) C222---C227 1.394 (3) C123---C124 1.390 (3) C223---C224 1.383 (3) C123---H123 0.9500 C223---H223 0.9500 C124---C125 1.392 (3) C224---C225 1.385 (3) C124---H124 0.9500 C224---H224 0.9500 C125---C126 1.391 (3) C225---C226 1.397 (3) C125---C128 1.508 (3) C225---C228 1.504 (3) C126---C127 1.384 (3) C226---C227 1.384 (3) C126---H126 0.9500 C226---H226 0.9500 C127---H127 0.9500 C227---H227 0.9500 C128---H10J 0.9801 C228---H20J 0.9801 C128---H10K 0.9799 C228---H20K 0.9800 C128---H10L 0.9800 C228---H20L 0.9800 C129---C134 1.393 (2) C229---C230 1.390 (3) C129---C130 1.394 (2) C229---C234 1.398 (3) C130---C131 1.385 (3) C230---C231 1.389 (3) C130---H130 0.9500 C230---H230 0.9500 C131---C132 1.396 (3) C231---C232 1.388 (3) C131---H131 0.9500 C231---H231 0.9500 C132---C133 1.392 (3) C232---C233 1.391 (3) C132---C135 1.509 (3) C232---C235 1.513 (3) C133---C134 1.387 (3) C233---C234 1.386 (3) C133---H133 0.9500 C233---H233 0.9500 C134---H134 0.9500 C234---H234 0.9500 C135---H10M 0.9800 C235---H20M 0.9800 C135---H10N 0.9800 C235---H20N 0.9800 C135---H10O 0.9798 C235---H20O 0.9799 C136---C141 1.388 (3) C236---C237 1.396 (3) C136---C137 1.396 (3) C236---C241 1.398 (2) C137---C138 1.379 (3) C237---C238 1.383 (3) C137---H137 0.9500 C237---H237 0.9500 C138---C139 1.394 (3) C238---C239 1.403 (3) C138---H138 0.9500 C238---H238 0.9500 C139---C140 1.388 (3) C239---C240 1.387 (3) C139---C142 1.516 (3) C239---C242 1.507 (3) C140---C141 1.393 (3) C240---C241 1.393 (3) C140---H140 0.9500 C240---H240 0.9500 C141---H141 0.9500 C241---H241 0.9500 C142---H10P 0.9800 C242---H20P 0.9800 C142---H10Q 0.9800 C242---H20Q 0.9800 C142---H10R 0.9800 C242---H20R 0.9799 N11---Fe1---N12 129.89 (7) N21---Fe2---N22 124.29 (8) N11---Fe1---P12 108.61 (6) N21---Fe2---P22 104.14 (6) N12---Fe1---P12 98.23 (5) N22---Fe2---P22 108.24 (6) N11---Fe1---P11 101.15 (6) N21---Fe2---P21 104.17 (6) N12---Fe1---P11 111.19 (5) N22---Fe2---P21 108.98 (6) P12---Fe1---P11 106.00 (2) P22---Fe2---P21 105.57 (2) C108---P11---C115 103.82 (8) C208---P21---C201 102.89 (8) C108---P11---C101 101.42 (8) C208---P21---C215 106.11 (8) C115---P11---C101 104.38 (8) C201---P21---C215 105.07 (8) C108---P11---Fe1 115.61 (6) C208---P21---Fe2 112.38 (6) C115---P11---Fe1 117.49 (6) C201---P21---Fe2 123.08 (6) C101---P11---Fe1 112.28 (6) C215---P21---Fe2 106.05 (6) O11---N11---Fe1 179.31 (16) O21---N21---Fe2 179.10 (16) C102---C101---C106 117.99 (16) C206---C201---C202 118.24 (17) C102---C101---P11 119.80 (14) C206---C201---P21 123.77 (14) C106---C101---P11 122.21 (13) C202---C201---P21 117.86 (14) C101---C102---C103 120.56 (18) C203---C202---C201 120.95 (18) C101---C102---H102 119.7 C203---C202---H202 119.5 C103---C102---H102 119.7 C201---C202---H202 119.5 C104---C103---C102 121.55 (18) C202---C203---C204 120.81 (18) C104---C103---H103 119.2 C202---C203---H203 119.6 C102---C103---H103 119.2 C204---C203---H203 119.6 C103---C104---C105 118.00 (17) C205---C204---C203 118.35 (18) C103---C104---C107 121.88 (19) C205---C204---C207 121.6 (2) C105---C104---C107 120.12 (19) C203---C204---C207 120.06 (19) C106---C105---C104 121.03 (18) C204---C205---C206 121.15 (19) C106---C105---H105 119.5 C204---C205---H205 119.4 C104---C105---H105 119.5 C206---C205---H205 119.4 C105---C106---C101 120.86 (17) C205---C206---C201 120.49 (18) C105---C106---H106 119.6 C205---C206---H206 119.8 C101---C106---H106 119.6 C201---C206---H206 119.8 C104---C107---H10A 109.5 C204---C207---H2OA 109.5 C104---C107---H10B 109.5 C204---C207---H20B 109.5 H10A---C107---H10B 109.5 H2OA---C207---H20B 109.5 C104---C107---H10C 109.5 C204---C207---H20C 109.5 H10A---C107---H10C 109.5 H2OA---C207---H20C 109.5 H10B---C107---H10C 109.5 H20B---C207---H20C 109.5 C113---C108---C109 118.39 (17) C213---C208---C209 118.54 (16) C113---C108---P11 121.57 (15) C213---C208---P21 124.11 (14) C109---C108---P11 119.68 (14) C209---C208---P21 117.32 (14) C110---C109---C108 120.86 (19) C210---C209---C208 120.63 (18) C110---C109---H109 119.6 C210---C209---H209 119.7 C108---C109---H109 119.6 C208---C209---H209 119.7 C109---C110---C111 120.8 (2) C209---C210---C211 121.13 (18) C109---C110---H110 119.6 C209---C210---H210 119.4 C111---C110---H110 119.6 C211---C210---H210 119.4 C112---C111---C110 118.27 (19) C210---C211---C212 118.17 (17) C112---C111---C114 120.4 (2) C210---C211---C214 120.45 (18) C110---C111---C114 121.4 (2) C212---C211---C214 121.38 (18) C111---C112---C113 121.3 (2) C213---C212---C211 120.82 (18) C111---C112---H112 119.4 C213---C212---H212 119.6 C113---C112---H112 119.4 C211---C212---H212 119.6 C112---C113---C108 120.4 (2) C208---C213---C212 120.70 (17) C112---C113---H113 119.8 C208---C213---H213 119.7 C108---C113---H113 119.8 C212---C213---H213 119.7 C111---C114---H10D 109.5 C211---C214---H20D 109.5 C111---C114---H10E 109.5 C211---C214---H20E 109.5 H10D---C114---H10E 109.5 H20D---C214---H20E 109.5 C111---C114---H10F 109.5 C211---C214---H20F 109.5 H10D---C114---H10F 109.5 H20D---C214---H20F 109.5 H10E---C114---H10F 109.5 H20E---C214---H20F 109.5 C120---C115---C116 118.13 (16) C216---C215---C220 118.19 (17) C120---C115---P11 119.21 (13) C216---C215---P21 124.84 (14) C116---C115---P11 122.66 (14) C220---C215---P21 116.40 (14) C117---C116---C115 120.86 (18) C215---C216---C217 120.13 (19) C117---C116---H116 119.6 C215---C216---H216 119.9 C115---C116---H116 119.6 C217---C216---H216 119.9 C116---C117---C118 121.21 (18) C218---C217---C216 121.34 (19) C116---C117---H117 119.4 C218---C217---H217 119.3 C118---C117---H117 119.4 C216---C217---H217 119.3 C119---C118---C117 117.77 (17) C217---C218---C219 118.31 (18) C119---C118---C121 120.96 (18) C217---C218---C221 122.0 (2) C117---C118---C121 121.28 (18) C219---C218---C221 119.7 (2) C120---C119---C118 121.14 (18) C220---C219---C218 120.81 (19) C120---C119---H119 119.4 C220---C219---H219 119.6 C118---C119---H119 119.4 C218---C219---H219 119.6 C119---C120---C115 120.88 (17) C219---C220---C215 121.18 (18) C119---C120---H120 119.6 C219---C220---H220 119.4 C115---C120---H120 119.6 C215---C220---H220 119.4 C118---C121---H10G 109.5 C218---C221---H20G 109.5 C118---C121---H10H 109.5 C218---C221---H20H 109.5 H10G---C121---H10H 109.5 H20G---C221---H20H 109.5 C118---C121---H10I 109.5 C218---C221---H20I 109.5 H10G---C121---H10I 109.5 H20G---C221---H20I 109.5 H10H---C121---H10I 109.5 H20H---C221---H20I 109.5 C129---P12---C136 105.07 (8) C236---P22---C229 105.45 (8) C129---P12---C122 103.58 (8) C236---P22---C222 105.88 (8) C136---P12---C122 101.37 (8) C229---P22---C222 99.71 (8) C129---P12---Fe1 115.06 (6) C236---P22---Fe2 113.70 (6) C136---P12---Fe1 118.82 (6) C229---P22---Fe2 120.17 (6) C122---P12---Fe1 111.08 (6) C222---P22---Fe2 110.27 (6) O12---N12---Fe1 175.05 (15) O22---N22---Fe2 173.84 (15) C123---C122---C127 118.20 (17) C223---C222---C227 118.43 (17) C123---C122---P12 118.11 (14) C223---C222---P22 117.38 (13) C127---C122---P12 123.62 (14) C227---C222---P22 123.83 (14) C124---C123---C122 120.77 (18) C224---C223---C222 120.75 (17) C124---C123---H123 119.6 C224---C223---H223 119.6 C122---C123---H123 119.6 C222---C223---H223 119.6 C123---C124---C125 121.02 (19) C223---C224---C225 121.15 (17) C123---C124---H124 119.5 C223---C224---H224 119.4 C125---C124---H124 119.5 C225---C224---H224 119.4 C126---C125---C124 117.95 (18) C224---C225---C226 118.11 (17) C126---C125---C128 120.5 (2) C224---C225---C228 120.54 (18) C124---C125---C128 121.6 (2) C226---C225---C228 121.34 (18) C127---C126---C125 121.20 (18) C227---C226---C225 121.02 (18) C127---C126---H126 119.4 C227---C226---H226 119.5 C125---C126---H126 119.4 C225---C226---H226 119.5 C126---C127---C122 120.83 (18) C226---C227---C222 120.50 (18) C126---C127---H127 119.6 C226---C227---H227 119.7 C122---C127---H127 119.6 C222---C227---H227 119.7 C125---C128---H10J 109.5 C225---C228---H20J 109.5 C125---C128---H10K 109.5 C225---C228---H20K 109.5 H10J---C128---H10K 109.5 H20J---C228---H20K 109.5 C125---C128---H10L 109.5 C225---C228---H20L 109.5 H10J---C128---H10L 109.5 H20J---C228---H20L 109.5 H10K---C128---H10L 109.5 H20K---C228---H20L 109.5 C134---C129---C130 118.29 (16) C230---C229---C234 118.28 (17) C134---C129---P12 121.71 (14) C230---C229---P22 119.14 (14) C130---C129---P12 119.61 (13) C234---C229---P22 122.39 (14) C131---C130---C129 120.95 (17) C231---C230---C229 120.67 (18) C131---C130---H130 119.5 C231---C230---H230 119.7 C129---C130---H130 119.5 C229---C230---H230 119.7 C130---C131---C132 121.04 (17) C232---C231---C230 121.23 (18) C130---C131---H131 119.5 C232---C231---H231 119.4 C132---C131---H131 119.5 C230---C231---H231 119.4 C133---C132---C131 117.70 (17) C231---C232---C233 118.07 (18) C133---C132---C135 120.95 (17) C231---C232---C235 121.01 (19) C131---C132---C135 121.34 (18) C233---C232---C235 120.89 (18) C134---C133---C132 121.49 (17) C234---C233---C232 121.15 (18) C134---C133---H133 119.3 C234---C233---H233 119.4 C132---C133---H133 119.3 C232---C233---H233 119.4 C133---C134---C129 120.52 (17) C233---C234---C229 120.60 (18) C133---C134---H134 119.7 C233---C234---H234 119.7 C129---C134---H134 119.7 C229---C234---H234 119.7 C132---C135---H10M 109.5 C232---C235---H20M 109.5 C132---C135---H10N 109.5 C232---C235---H20N 109.5 H10M---C135---H10N 109.5 H20M---C235---H20N 109.5 C132---C135---H10O 109.5 C232---C235---H20O 109.5 H10M---C135---H10O 109.5 H20M---C235---H20O 109.5 H10N---C135---H10O 109.5 H20N---C235---H20O 109.5 C141---C136---C137 118.48 (16) C237---C236---C241 118.21 (16) C141---C136---P12 120.68 (13) C237---C236---P22 119.27 (13) C137---C136---P12 120.79 (14) C241---C236---P22 121.57 (14) C138---C137---C136 120.50 (18) C238---C237---C236 121.00 (17) C138---C137---H137 119.7 C238---C237---H237 119.5 C136---C137---H137 119.7 C236---C237---H237 119.5 C137---C138---C139 121.40 (18) C237---C238---C239 120.98 (17) C137---C138---H138 119.3 C237---C238---H238 119.5 C139---C138---H138 119.3 C239---C238---H238 119.5 C140---C139---C138 118.09 (17) C240---C239---C238 117.90 (17) C140---C139---C142 121.17 (19) C240---C239---C242 121.04 (17) C138---C139---C142 120.72 (18) C238---C239---C242 121.04 (17) C139---C140---C141 120.80 (18) C239---C240---C241 121.39 (17) C139---C140---H140 119.6 C239---C240---H240 119.3 C141---C140---H140 119.6 C241---C240---H240 119.3 C136---C141---C140 120.72 (17) C240---C241---C236 120.48 (17) C136---C141---H141 119.6 C240---C241---H241 119.8 C140---C141---H141 119.6 C236---C241---H241 119.8 C139---C142---H10P 109.5 C239---C242---H20P 109.5 C139---C142---H10Q 109.5 C239---C242---H20Q 109.5 H10P---C142---H10Q 109.5 H20P---C242---H20Q 109.5 C139---C142---H10R 109.5 C239---C242---H20R 109.5 H10P---C142---H10R 109.5 H20P---C242---H20R 109.5 H10Q---C142---H10R 109.5 H20Q---C242---H20R 109.5 N11---Fe1---P11---C108 −61.00 (9) N22---Fe2---P21---C208 140.90 (8) N12---Fe1---P11---C108 157.97 (9) P22---Fe2---P21---C208 −103.03 (6) P12---Fe1---P11---C108 52.26 (7) N21---Fe2---P21---C201 130.16 (9) N11---Fe1---P11---C115 175.76 (8) N22---Fe2---P21---C201 −95.31 (9) N12---Fe1---P11---C115 34.73 (9) P22---Fe2---P21---C201 20.77 (7) P12---Fe1---P11---C115 −70.98 (7) N21---Fe2---P21---C215 −109.16 (8) N11---Fe1---P11---C101 54.71 (8) N22---Fe2---P21---C215 25.38 (8) N12---Fe1---P11---C101 −86.32 (8) P22---Fe2---P21---C215 141.45 (6) P12---Fe1---P11---C101 167.97 (6) N22---Fe2---N21---O21 −53 (11) N12---Fe1---N11---O11 130 (19) P22---Fe2---N21---O21 −178 (100) P12---Fe1---N11---O11 −112 (19) P21---Fe2---N21---O21 72 (11) C108---P11---C101---C102 136.85 (15) C208---P21---C201---C206 −5.77 (17) C115---P11---C101---C102 −115.49 (15) C215---P21---C201---C206 105.11 (16) Fe1---P11---C101---C102 12.83 (16) Fe2---P21---C201---C206 −133.75 (14) C108---P11---C101---C106 −42.70 (16) C208---P21---C201---C202 170.03 (14) C115---P11---C101---C106 64.96 (16) C215---P21---C201---C202 −79.08 (15) Fe1---P11---C101---C106 −166.71 (13) Fe2---P21---C201---C202 42.06 (16) C106---C101---C102---C103 0.5 (3) C206---C201---C202---C203 −0.1 (3) P11---C101---C102---C103 −179.03 (15) P21---C201---C202---C203 −176.12 (14) C101---C102---C103---C104 −0.9 (3) C201---C202---C203---C204 −0.3 (3) C102---C103---C104---C105 0.1 (3) C202---C203---C204---C205 0.5 (3) C102---C103---C104---C107 179.78 (18) C202---C203---C204---C207 −179.12 (18) C103---C104---C105---C106 0.9 (3) C203---C204---C205---C206 −0.3 (3) C107---C104---C105---C106 −178.73 (18) C207---C204---C205---C206 179.30 (19) C104---C105---C106---C101 −1.3 (3) C204---C205---C206---C201 −0.1 (3) C102---C101---C106---C105 0.5 (3) C202---C201---C206---C205 0.3 (3) P11---C101---C106---C105 −179.94 (14) P21---C201---C206---C205 176.06 (15) C115---P11---C108---C113 33.99 (17) C201---P21---C208---C213 90.85 (16) C101---P11---C108---C113 142.08 (15) C215---P21---C208---C213 −19.25 (18) Fe1---P11---C108---C113 −96.19 (15) Fe2---P21---C208---C213 −134.73 (14) C115---P11---C108---C109 −152.98 (14) C201---P21---C208---C209 −87.29 (15) C101---P11---C108---C109 −44.89 (16) C215---P21---C208---C209 162.61 (14) Fe1---P11---C108---C109 76.84 (15) Fe2---P21---C208---C209 47.13 (15) C113---C108---C109---C110 −0.4 (3) C213---C208---C209---C210 0.3 (3) P11---C108---C109---C110 −173.66 (15) P21---C208---C209---C210 178.59 (14) C108---C109---C110---C111 −0.2 (3) C208---C209---C210---C211 0.5 (3) C109---C110---C111---C112 0.8 (3) C209---C210---C211---C212 −0.8 (3) C109---C110---C111---C114 −179.0 (2) C209---C210---C211---C214 179.14 (19) C110---C111---C112---C113 −0.7 (3) C210---C211---C212---C213 0.3 (3) C114---C111---C112---C113 179.0 (2) C214---C211---C212---C213 −179.66 (19) C111---C112---C113---C108 0.1 (3) C209---C208---C213---C212 −0.9 (3) C109---C108---C113---C112 0.5 (3) P21---C208---C213---C212 −178.98 (14) P11---C108---C113---C112 173.58 (15) C211---C212---C213---C208 0.6 (3) C108---P11---C115---C120 −132.53 (14) C208---P21---C215---C216 123.32 (16) C101---P11---C115---C120 121.59 (15) C201---P21---C215---C216 14.76 (18) Fe1---P11---C115---C120 −3.49 (16) Fe2---P21---C215---C216 −116.98 (16) C108---P11---C115---C116 46.96 (17) C208---P21---C215---C220 −65.58 (16) C101---P11---C115---C116 −58.92 (17) C201---P21---C215---C220 −174.14 (14) Fe1---P11---C115---C116 176.00 (13) Fe2---P21---C215---C220 54.13 (15) C120---C115---C116---C117 −0.4 (3) C220---C215---C216---C217 −0.8 (3) P11---C115---C116---C117 −179.90 (15) P21---C215---C216---C217 170.19 (15) C115---C116---C117---C118 1.5 (3) C215---C216---C217---C218 1.5 (3) C116---C117---C118---C119 −1.4 (3) C216---C217---C218---C219 −0.4 (3) C116---C117---C118---C121 178.78 (19) C216---C217---C218---C221 178.2 (2) C117---C118---C119---C120 0.3 (3) C217---C218---C219---C220 −1.3 (3) C121---C118---C119---C120 −179.88 (18) C221---C218---C219---C220 179.96 (19) C118---C119---C120---C115 0.8 (3) C218---C219---C220---C215 2.1 (3) C116---C115---C120---C119 −0.7 (3) C216---C215---C220---C219 −1.0 (3) P11---C115---C120---C119 178.82 (14) P21---C215---C220---C219 −172.70 (15) N11---Fe1---P12---C129 163.18 (8) N21---Fe2---P22---C236 −59.05 (8) N12---Fe1---P12---C129 −59.73 (8) N22---Fe2---P22---C236 166.94 (8) P11---Fe1---P12---C129 55.19 (7) P21---Fe2---P22---C236 50.36 (7) N11---Fe1---P12---C136 37.38 (9) N21---Fe2---P22---C229 174.68 (8) N12---Fe1---P12---C136 174.47 (8) N22---Fe2---P22---C229 40.67 (9) P11---Fe1---P12---C136 −70.61 (7) P21---Fe2---P22---C229 −75.91 (7) N11---Fe1---P12---C122 −79.57 (9) N21---Fe2---P22---C222 59.68 (8) N12---Fe1---P12---C122 57.52 (8) N22---Fe2---P22---C222 −74.34 (9) P11---Fe1---P12---C122 172.44 (6) P21---Fe2---P22---C222 169.09 (6) N11---Fe1---N12---O12 97.0 (16) N21---Fe2---N22---O22 −21.2 (15) P12---Fe1---N12---O12 −25.7 (16) P22---Fe2---N22---O22 101.2 (15) P11---Fe1---N12---O12 −136.5 (16) P21---Fe2---N22---O22 −144.4 (15) C129---P12---C122---C123 166.66 (15) C236---P22---C222---C223 149.46 (14) C136---P12---C122---C123 −84.59 (16) C229---P22---C222---C223 −101.29 (15) Fe1---P12---C122---C123 42.60 (16) Fe2---P22---C222---C223 26.06 (15) C129---P12---C122---C127 −16.60 (17) C236---P22---C222---C227 −37.58 (18) C136---P12---C122---C127 92.15 (16) C229---P22---C222---C227 71.67 (17) Fe1---P12---C122---C127 −140.65 (14) Fe2---P22---C222---C227 −160.98 (15) C127---C122---C123---C124 −1.4 (3) C227---C222---C223---C224 −1.2 (3) P12---C122---C123---C124 175.54 (16) P22---C222---C223---C224 172.13 (14) C122---C123---C124---C125 1.6 (3) C222---C223---C224---C225 0.0 (3) C123---C124---C125---C126 −0.3 (3) C223---C224---C225---C226 1.2 (3) C123---C124---C125---C128 −179.0 (2) C223---C224---C225---C228 −178.34 (18) C124---C125---C126---C127 −1.3 (3) C224---C225---C226---C227 −1.2 (3) C128---C125---C126---C127 177.5 (2) C228---C225---C226---C227 178.35 (19) C125---C126---C127---C122 1.5 (3) C225---C226---C227---C222 0.0 (3) C123---C122---C127---C126 −0.2 (3) C223---C222---C227---C226 1.2 (3) P12---C122---C127---C126 −176.92 (14) P22---C222---C227---C226 −171.66 (16) C136---P12---C129---C134 27.42 (17) C236---P22---C229---C230 −149.74 (14) C122---P12---C129---C134 133.38 (15) C222---P22---C229---C230 100.68 (15) Fe1---P12---C129---C134 −105.20 (14) Fe2---P22---C229---C230 −19.72 (17) C136---P12---C129---C130 −159.89 (14) C236---P22---C229---C234 35.53 (17) C122---P12---C129---C130 −53.92 (16) C222---P22---C229---C234 −74.06 (16) Fe1---P12---C129---C130 67.50 (15) Fe2---P22---C229---C234 165.54 (13) C134---C129---C130---C131 −0.5 (3) C234---C229---C230---C231 0.3 (3) P12---C129---C130---C131 −173.45 (14) P22---C229---C230---C231 −174.69 (14) C129---C130---C131---C132 0.8 (3) C229---C230---C231---C232 −0.2 (3) C130---C131---C132---C133 −0.7 (3) C230---C231---C232---C233 −0.3 (3) C130---C131---C132---C135 178.10 (19) C230---C231---C232---C235 177.86 (18) C131---C132---C133---C134 0.2 (3) C231---C232---C233---C234 0.6 (3) C135---C132---C133---C134 −178.60 (19) C235---C232---C233---C234 −177.55 (18) C132---C133---C134---C129 0.1 (3) C232---C233---C234---C229 −0.5 (3) C130---C129---C134---C133 0.0 (3) C230---C229---C234---C233 0.0 (3) P12---C129---C134---C133 172.80 (14) P22---C229---C234---C233 174.83 (14) C129---P12---C136---C141 −128.97 (15) C229---P22---C236---C237 −153.01 (14) C122---P12---C136---C141 123.45 (15) C222---P22---C236---C237 −47.90 (16) Fe1---P12---C136---C141 1.49 (17) Fe2---P22---C236---C237 73.31 (15) C129---P12---C136---C137 53.68 (16) C229---P22---C236---C241 38.41 (16) C122---P12---C136---C137 −53.91 (16) C222---P22---C236---C241 143.52 (15) Fe1---P12---C136---C137 −175.87 (12) Fe2---P22---C236---C241 −95.27 (14) C141---C136---C137---C138 0.0 (3) C241---C236---C237---C238 −1.0 (3) P12---C136---C137---C138 177.39 (14) P22---C236---C237---C238 −169.96 (14) C136---C137---C138---C139 −0.1 (3) C236---C237---C238---C239 −0.9 (3) C137---C138---C139---C140 0.4 (3) C237---C238---C239---C240 2.1 (3) C137---C138---C139---C142 −177.94 (18) C237---C238---C239---C242 −176.25 (17) C138---C139---C140---C141 −0.5 (3) C238---C239---C240---C241 −1.4 (3) C142---C139---C140---C141 177.75 (18) C242---C239---C240---C241 176.92 (16) C137---C136---C141---C140 −0.2 (3) C239---C240---C241---C236 −0.5 (3) P12---C136---C141---C140 −177.58 (14) C237---C236---C241---C240 1.7 (3) C139---C140---C141---C136 0.4 (3) P22---C236---C241---C240 170.36 (13) N21---Fe2---P21---C208 6.36 (8) --------------------------- -------------- --------------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.692323	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052133/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m331", "authors": [ { "first": "Myron W.", "last": "Jones" }, { "first": "Douglas R.", "last": "Powell" }, { "first": "George B.", "last": "Richter-Addo" } ] }
PMC3052134	Related literature {#sec1} ================== For the synthesis of related compounds, see: Contreras et al. (2001[@bb4]); Capuano et al. (2002[@bb3]). For their use as intermediates in the synthesis of anti-inflammatory agents or CCR1 antagonists, see: Rolland & Duhault (1989[@bb7]); Kaufmann (2005[@bb6]); Tanikawa et al. (1995[@bb9]); Xie et al. (2007[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~16~ClFN~2~OM ~r~ = 270.73Orthorhombic,a = 7.9350 (5) Åb = 8.4610 (4) Åc = 19.0040 (11) ÅV = 1275.89 (12) Å^3^Z = 4Mo Kα radiationμ = 0.30 mm^−1^T = 291 K0.30 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2001[@bb1]) T ~min~ = 0.566, T ~max~ = 0.71612886 measured reflections3001 independent reflections2550 reflections with I \> 2σ(I)R ~int~ = 0.033 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.035wR(F ^2^) = 0.085S = 1.013001 reflections165 parametersH-atom parameters constrainedΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.18 e Å^−3^Absolute structure: Flack (1983[@bb5]), 1255 Friedel pairsFlack parameter: 0.03 (7) {#d5e372} Data collection: APEX2 (Bruker, 2003[@bb2]); cell refinement: SAINT (Bruker, 2001[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: DIAMOND (Brandenburg, 1999)[@bb11]; software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006180/si2316sup1.cif](http://dx.doi.org/10.1107/S1600536811006180/si2316sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006180/si2316Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006180/si2316Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2316&file=si2316sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2316sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2316&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2316](http://scripts.iucr.org/cgi-bin/sendsup?si2316)). The authors would like to thank the Ministry of Science and Technology of China (2007AA02Z160, 2009ZX09501--004) and the Chinese National Natural Science Foundation (20872077, 90813013) for financial support. Comment ======= Piperazine derivatives similar to the title compound are well known as being useful for a variety of pharmaceutical indication, particularly as cardiotonic, neurotropic or anti-inflammatory agents (Kaufmann, 2005). The synthesis of related pyridazine compounds and their medicinal and pharmaceutical activity were reported (Contreras et al., 2001; Capuano et al., 2002). The use of related compounds as intermediates in the synthesis of antiinflammatory agents or CCRI antagonists can be studied in various patents (Rolland & Duhault, 1989; Kaufmann, 2005; Tanikawa et al., 1995) and medicinal journal (Xie et al., 2007). Moreover, we recently identified a series of compounds bearing various substituted benzylpiperazine moiety with potent antitumor activity by virtual screening approach (paper was being revised). Herein, we report the synthesis of the title compound as one important representative of piperazine derivatives and its X-ray crystal structure. The molecule of (I) is shown in Fig. 1. The bond lengths and angles are within normal ranges. The piperazine ring in the molecule adopts a chair conformation. The dihedral angle between the fluorophenyl ring and the four planar C atoms (r.m.s. = 0.0055 Å) of the piperazine chair is 78.27 (7)°. Whereas the dihedral angle between the four planar C atoms of the piperazine chair and the ethanone plane is 55.21 (9)Å with the Cl atom about 1.589 (2) Å out of plane. In the crystal, there are no strong intermolecular hydrogen bonds to link the molecules. Experimental {#experimental} ============ All chemicals and solvents were obtained from commercial supplies and used without purification. To a solution of chloroacetic chloride (0.58 ml, 7.15 mmol) in CH~2~Cl~2~ (10 ml) was added, at 0 °C, 1-(2-fluorobenzyl)piperazine(II) (1.15 g, 5.90 mmol) dissolved in CH~2~Cl~2~ (20 ml) which was prepared from the reaction of anhydrous piperazine(III) and 1-(chloromethyl)-2-fluorobenzene(IV). The reaction mixture was stirred at room temperature for about 30 min until no 1-(2-fluorobenzyl)piperazine remained, as monitored by TLC. The mixture was poured into cold H~2~O (50 ml) and rendered alkaline with a 10% NaHCO~3~ aqueous solution and separated. The organic layer, dried over Na~2~SO~4~, was evaporated under reduced pressure to give 1.44 g of pure title compound as a yellow oil. Yield 90%; ^1^H NMR (400 MHz, CDCl~3~) δ 7.35 (dd, J = 7.4, 1.4 Hz, 1H), δ 7.23--7.29 (m, 1H), δ 7.12 (t, J = 7.2 Hz, 1H), δ 7.04 (t, J = 9.2 Hz, 1H), δ 4.05 (s, 2H), δ 3.64 (d, J = 5.2 Hz, 2H), δ 3.62 (d, J = 4.4 Hz, 2H), 3.52 (t, J = 5.0 Hz, 2H), δ 2.51 (dt, J = 15.6, 4.8 Hz, 4H); ^13^C NMR (100.6 MHz, CDCl~3~) δ 161.16, 131.24, 128.88, 123.88, 123.75, 115.27, 115.05, 54.87, 52.41, 52.00, 46.06, 41.93, 40.67. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding model approximation with distances C---H = 0.93 Å for the benzene ring and 0.97 Å for C~sp3~ carbon atoms and U~iso~(H) = 1.2 times U~eq~(C). The absolute structure was determined by using the Flack parameter refinement with the TWIN/BASF instruction, and the coordinates of all atoms were inverted by instruction MOVE 1 1 1 - 1 in the final refinement with SHELXL97. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound showing displacement ellipsoids at the 30% probability level. ::: ![](e-67-0o708-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Synthesis of the title compound ::: ![](e-67-0o708-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e213 .table-wrap} ------------------------------- ------------------------------------- C~13~H~16~ClFN~2~O F(000) = 568 M~r~ = 270.73 D~x~ = 1.409 Mg m^−3^ Orthorhombic, P2~1~2~1~2~1~ Mo Kα radiation, λ = 0.71069 Å Hall symbol: P 2ac 2ab Cell parameters from 25 reflections a = 7.9350 (5) Å θ = 7.5--15° b = 8.4610 (4) Å µ = 0.30 mm^−1^ c = 19.0040 (11) Å T = 291 K V = 1275.89 (12) Å^3^ Block, colorless Z = 4 0.30 × 0.30 × 0.20 mm ------------------------------- ------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e338 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 3001 independent reflections Radiation source: fine-focus sealed tube 2550 reflections with I \> 2σ(I) graphite R~int~ = 0.033 ω scans θ~max~ = 28.4°, θ~min~ = 3.2° Absorption correction: multi-scan (SADABS; Bruker, 2001) h = −10→10 T~min~ = 0.566, T~max~ = 0.716 k = −10→10 12886 measured reflections l = −25→25 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e452 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Hydrogen site location: inferred from neighbouring sites Least-squares matrix: full H-atom parameters constrained R\[F^2^ \> 2σ(F^2^)\] = 0.035 w = 1/\[σ^2^(F~o~^2^) + (0.028P)^2^ + 0.4P\] where P = (F~o~^2^ + 2F~c~^2^)/3 wR(F^2^) = 0.085 (Δ/σ)~max~ \< 0.001 S = 1.01 Δρ~max~ = 0.33 e Å^−3^ 3001 reflections Δρ~min~ = −0.18 e Å^−3^ 165 parameters Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ 0 restraints Extinction coefficient: 0.077 (3) Primary atom site location: structure-invariant direct methods Absolute structure: Flack (1983), 1255 Friedel pairs Secondary atom site location: difference Fourier map Flack parameter: 0.03 (7) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e638 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e737 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O1 1.51486 (16) 0.40256 (17) 0.67832 (8) 0.0512 (3) Cl1 1.23456 (9) 0.09826 (6) 0.64207 (3) 0.06647 (19) F1 0.6313 (2) 0.88072 (19) 0.64912 (8) 0.0801 (4) N1 0.96049 (18) 0.62572 (16) 0.64509 (8) 0.0378 (3) N2 1.2433 (2) 0.46187 (17) 0.70180 (8) 0.0437 (4) C1 0.8356 (2) 0.8253 (2) 0.56706 (9) 0.0415 (4) C2 0.7317 (3) 0.9332 (2) 0.59859 (10) 0.0492 (5) C3 0.7224 (3) 1.0901 (3) 0.58058 (12) 0.0622 (6) H3 0.6497 1.1582 0.6041 0.075\ C4 0.8215 (3) 1.1433 (3) 0.52783 (12) 0.0623 (6) H4 0.8177 1.2491 0.5146 0.075\* C5 0.9276 (3) 1.0405 (3) 0.49380 (12) 0.0588 (6) H5 0.9960 1.0766 0.4574 0.071\* C6 0.9328 (3) 0.8832 (3) 0.51363 (10) 0.0524 (5) H6 1.0047 0.8148 0.4898 0.063\* C7 0.8427 (2) 0.6546 (2) 0.58860 (10) 0.0459 (4) H7A 0.7312 0.6211 0.6034 0.055\* H7B 0.8746 0.5912 0.5482 0.055\* C8 1.1333 (2) 0.6613 (2) 0.62433 (10) 0.0424 (4) H8A 1.1409 0.7723 0.6118 0.051\* H8B 1.1613 0.6000 0.5828 0.051\* C9 1.2590 (2) 0.6266 (2) 0.68052 (10) 0.0459 (4) H9A 1.3719 0.6464 0.6631 0.055\* H9B 1.2395 0.6951 0.7207 0.055\* C10 1.0718 (2) 0.4225 (3) 0.72213 (11) 0.0500 (5) H10A 1.0413 0.4821 0.7638 0.060\* H10B 1.0655 0.3109 0.7336 0.060\* C11 0.9506 (2) 0.4583 (2) 0.66487 (11) 0.0460 (5) H11A 0.9758 0.3931 0.6242 0.055\* H11B 0.8372 0.4337 0.6804 0.055\* C12 1.3729 (2) 0.3613 (2) 0.69620 (9) 0.0388 (4) C13 1.3417 (3) 0.1882 (2) 0.71208 (10) 0.0476 (5) H13A 1.2753 0.1787 0.7547 0.057\* H13B 1.4484 0.1351 0.7197 0.057\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1184 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0326 (7) 0.0537 (8) 0.0671 (9) 0.0000 (6) −0.0001 (6) 0.0034 (7) Cl1 0.0760 (4) 0.0506 (3) 0.0729 (3) −0.0109 (3) −0.0059 (3) −0.0099 (3) F1 0.0805 (10) 0.0910 (10) 0.0688 (8) 0.0264 (8) 0.0272 (8) 0.0187 (8) N1 0.0326 (7) 0.0339 (7) 0.0471 (8) 0.0024 (6) −0.0027 (6) 0.0003 (6) N2 0.0343 (8) 0.0416 (7) 0.0552 (9) 0.0042 (7) 0.0010 (8) 0.0090 (6) C1 0.0373 (9) 0.0480 (10) 0.0393 (9) 0.0030 (8) −0.0091 (7) −0.0007 (8) C2 0.0465 (11) 0.0587 (12) 0.0423 (9) 0.0063 (10) −0.0002 (9) 0.0045 (8) C3 0.0751 (15) 0.0544 (11) 0.0573 (12) 0.0190 (12) 0.0006 (12) −0.0014 (10) C4 0.0801 (17) 0.0479 (12) 0.0590 (13) −0.0008 (11) −0.0167 (11) 0.0099 (10) C5 0.0596 (14) 0.0677 (14) 0.0492 (11) −0.0068 (11) −0.0017 (10) 0.0128 (10) C6 0.0502 (11) 0.0624 (13) 0.0447 (10) 0.0049 (10) −0.0006 (9) −0.0006 (10) C7 0.0400 (10) 0.0464 (10) 0.0512 (10) −0.0017 (8) −0.0089 (9) −0.0047 (9) C8 0.0363 (9) 0.0337 (8) 0.0570 (11) −0.0023 (7) −0.0006 (8) 0.0053 (8) C9 0.0370 (9) 0.0362 (9) 0.0645 (11) −0.0006 (8) −0.0076 (9) 0.0016 (8) C10 0.0393 (11) 0.0497 (11) 0.0610 (12) 0.0068 (8) 0.0094 (9) 0.0158 (10) C11 0.0328 (9) 0.0397 (9) 0.0656 (13) −0.0015 (8) 0.0056 (9) 0.0061 (9) C12 0.0364 (9) 0.0433 (9) 0.0366 (8) 0.0023 (8) −0.0050 (7) −0.0010 (7) C13 0.0479 (11) 0.0442 (11) 0.0506 (11) 0.0067 (9) −0.0049 (9) 0.0071 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1552 .table-wrap} -------------------- -------------- ---------------------- -------------- O1---C12 1.228 (2) C5---H5 0.9300 Cl1---C13 1.753 (2) C6---H6 0.9300 F1---C2 1.324 (2) C7---H7A 0.9700 N1---C7 1.444 (2) C7---H7B 0.9700 N1---C8 1.459 (2) C8---C9 1.490 (3) N1---C11 1.467 (2) C8---H8A 0.9700 N2---C12 1.339 (2) C8---H8B 0.9700 N2---C10 1.454 (2) C9---H9A 0.9700 N2---C9 1.457 (2) C9---H9B 0.9700 C1---C6 1.366 (3) C10---C11 1.483 (3) C1---C2 1.369 (3) C10---H10A 0.9700 C1---C7 1.502 (3) C10---H10B 0.9700 C2---C3 1.373 (3) C11---H11A 0.9700 C3---C4 1.351 (3) C11---H11B 0.9700 C3---H3 0.9300 C12---C13 1.515 (3) C4---C5 1.373 (3) C13---H13A 0.9700 C4---H4 0.9300 C13---H13B 0.9700 C5---C6 1.384 (3) C7---N1---C8 111.87 (15) C9---C8---H8A 108.9 C7---N1---C11 108.62 (14) N1---C8---H8B 108.9 C8---N1---C11 108.59 (13) C9---C8---H8B 108.9 C12---N2---C10 126.45 (15) H8A---C8---H8B 107.7 C12---N2---C9 121.38 (16) N2---C9---C8 109.27 (15) C10---N2---C9 111.92 (15) N2---C9---H9A 109.8 C6---C1---C2 115.21 (18) C8---C9---H9A 109.8 C6---C1---C7 121.77 (18) N2---C9---H9B 109.8 C2---C1---C7 123.02 (18) C8---C9---H9B 109.8 F1---C2---C1 117.11 (18) H9A---C9---H9B 108.3 F1---C2---C3 118.22 (19) N2---C10---C11 111.40 (16) C1---C2---C3 124.7 (2) N2---C10---H10A 109.3 C4---C3---C2 118.4 (2) C11---C10---H10A 109.3 C4---C3---H3 120.8 N2---C10---H10B 109.3 C2---C3---H3 120.8 C11---C10---H10B 109.3 C3---C4---C5 119.7 (2) H10A---C10---H10B 108.0 C3---C4---H4 120.2 N1---C11---C10 110.55 (16) C5---C4---H4 120.2 N1---C11---H11A 109.5 C4---C5---C6 120.0 (2) C10---C11---H11A 109.5 C4---C5---H5 120.0 N1---C11---H11B 109.5 C6---C5---H5 120.0 C10---C11---H11B 109.5 C1---C6---C5 122.1 (2) H11A---C11---H11B 108.1 C1---C6---H6 119.0 O1---C12---N2 123.07 (18) C5---C6---H6 119.0 O1---C12---C13 118.68 (17) N1---C7---C1 112.92 (15) N2---C12---C13 118.24 (17) N1---C7---H7A 109.0 C12---C13---Cl1 110.34 (13) C1---C7---H7A 109.0 C12---C13---H13A 109.6 N1---C7---H7B 109.0 Cl1---C13---H13A 109.6 C1---C7---H7B 109.0 C12---C13---H13B 109.6 H7A---C7---H7B 107.8 Cl1---C13---H13B 109.6 N1---C8---C9 113.25 (16) H13A---C13---H13B 108.1 N1---C8---H8A 108.9 C6---C1---C2---F1 177.86 (18) C11---N1---C8---C9 −57.8 (2) C7---C1---C2---F1 −1.6 (3) C12---N2---C9---C8 120.59 (19) C6---C1---C2---C3 −0.9 (3) C10---N2---C9---C8 −54.0 (2) C7---C1---C2---C3 179.7 (2) N1---C8---C9---N2 56.1 (2) F1---C2---C3---C4 −178.3 (2) C12---N2---C10---C11 −118.1 (2) C1---C2---C3---C4 0.4 (3) C9---N2---C10---C11 56.2 (2) C2---C3---C4---C5 0.1 (3) C7---N1---C11---C10 179.10 (16) C3---C4---C5---C6 0.0 (3) C8---N1---C11---C10 57.2 (2) C2---C1---C6---C5 0.9 (3) N2---C10---C11---N1 −57.6 (2) C7---C1---C6---C5 −179.60 (19) C10---N2---C12---O1 179.59 (18) C4---C5---C6---C1 −0.5 (3) C9---N2---C12---O1 5.8 (3) C8---N1---C7---C1 −63.4 (2) C10---N2---C12---C13 0.2 (3) C11---N1---C7---C1 176.72 (16) C9---N2---C12---C13 −173.64 (16) C6---C1---C7---N1 93.1 (2) O1---C12---C13---Cl1 −103.48 (18) C2---C1---C7---N1 −87.4 (2) N2---C12---C13---Cl1 75.97 (19) C7---N1---C8---C9 −177.68 (15) -------------------- -------------- ---------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.708768	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052134/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o708", "authors": [ { "first": "Cunlong", "last": "Zhang" }, { "first": "Xin", "last": "Zhai" }, { "first": "Furen", "last": "Wan" }, { "first": "Ping", "last": "Gong" }, { "first": "Yuyang", "last": "Jiang" } ] }
PMC3052135	Related literature {#sec1} ================== For background to supramolecular coordination polymers of zinc-triad 1,1-dithiolates, see: Tiekink (2003[@bb10]). For the use of steric effects to control supramolecular aggregation patterns, see: Chen et al. (2006[@bb4]). For structural studies on hydroxyl-substituted dithiocarbamate ligands, see Benson et al. (2007[@bb1]); Song & Tiekink (2009[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cd(C~6~H~12~NOS~2~)~2~(C~12~H~10~N~4~)~2~\]M ~r~ = 889.45Triclinic,a = 8.532 (3) Åb = 10.951 (4) Åc = 11.184 (5) Åα = 79.59 (3)°β = 88.06 (3)°γ = 78.23 (2)°V = 1006.2 (7) Å^3^Z = 1Mo Kα radiationμ = 0.80 mm^−1^T = 98 K0.25 × 0.16 × 0.04 mm ### Data collection {#sec2.1.2} Rigaku AFC12/SATURN724 CCD diffractometerAbsorption correction: multi-scan (ABSCOR; Higashi, 1995[@bb5]) T ~min~ = 0.719, T ~max~ = 110677 measured reflections4150 independent reflections4009 reflections with I \> 2σ(I)R ~int~ = 0.023 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.025wR(F ^2^) = 0.062S = 1.084150 reflections245 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.40 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e576} Data collection: CrystalClear (Molecular Structure Corporation & Rigaku, 2005[@bb7]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: PATTY in DIRDIF (Beurskens et al., 1992[@bb2]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: ORTEPII (Johnson, 1976[@bb6]) and DIAMOND (Brandenburg, 2006[@bb3]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004508/hb5795sup1.cif](http://dx.doi.org/10.1107/S1600536811004508/hb5795sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004508/hb5795Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004508/hb5795Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5795&file=hb5795sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5795sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5795&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5795](http://scripts.iucr.org/cgi-bin/sendsup?hb5795)). Comment ======= Interest in the title compound, (I), relates to controlling supramolecular aggregation patterns in the zinc-triad 1,1-thiolates (Tiekink, 2003; Chen et al., 2006). With functionalized dithiocarbamate ligands carrying hydrogen bonding potential, smaller aggregates can be linked into 2-D and 3-D architectures (Benson et al., 2007; Song & Tiekink, 2009). In (I), the cadmium atom is located on a centre of inversion and is chelated by symmetrically coordinating dithiocarbamate ligands, Table 1 and Fig. 1. The octahedral N~2~S~4~ donor set is completed by two pyridine-N atoms derived from two monodentate 4-pyridinealdazine ligands. The monomeric molecules are connected into a supramolecular chain via O--H···N hydrogen bonds, Table 2, that lead to the formation of 40-membered \[CdSCNC~2~OH···NC~4~N~2~C~4~N\]~2~ synthons, Fig. 2. These chains are linked into layers via C--H···O interactions, Table 1, which that stack along \[1 0 1\]; consolidation of these layers into a 3-D array is afforded by C---H···N~azo~ contacts, Table 2 and Fig. 3. Experimental {#experimental} ============ Compound (I) was prepared following the standard literature procedure (Song & Tiekink, 2009) from the reaction of Cd\[S~2~CN(CH~2~CH~2~OH)(nPr)\]~2~ and 4-\[(1E)-\[(E)-2-(pyridin-4-ylmethylidene)hydrazin-1-ylidene\]methyl\]pyridine (Sigma Aldrich). Yellow plates of (I) were obtained from the slow evaporation of a chloroform/acetonitrile (3/1) solution. Refinement {#refinement} ========== C-bound H-atoms were placed in calculated positions (C--H 0.95--0.99 Å) and were included in the refinement in the riding model approximation with U~iso~(H) set to 1.2--1.5U~eq~(C). The O-bound H-atom was located in a difference Fourier map and refined with an O--H restraint of 0.84±0.01 Å, and with U~iso~(H) = 1.5U~eq~(O). The reflection (81 2) was removed from the final refinement owing to poor agreement. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of (I) showing displacement ellipsoids at the 70% probability level. The Cd atom is located on a centre of inversion and i = 1 - x, 1 - y, 1 - z. ::: ![](e-67-0m320-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Supramolecular chain in (I) mediated by O--H···N (orange dashed lines) hydrogen bonds. Colour code: Cd, orange; S, yellow; O, red; N, blue; C, grey; and H, green. ::: ![](e-67-0m320-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Unit-cell contents in (I) viewed in projection down the a axis. ::: ![](e-67-0m320-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e201 .table-wrap} ----------------------------------------------- --------------------------------------- \[Cd(C~6~H~12~NOS~2~)~2~(C~12~H~10~N~4~)~2~\] Z = 1 M~r~ = 889.45 F(000) = 458 Triclinic, P1 D~x~ = 1.468 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71070 Å a = 8.532 (3) Å Cell parameters from 3485 reflections b = 10.951 (4) Å θ = 2.4--30.3° c = 11.184 (5) Å µ = 0.80 mm^−1^ α = 79.59 (3)° T = 98 K β = 88.06 (3)° Plate, yellow γ = 78.23 (2)° 0.25 × 0.16 × 0.04 mm V = 1006.2 (7) Å^3^ ----------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e351 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku AFC12K/SATURN724 CCD diffractometer 4150 independent reflections Radiation source: fine-focus sealed tube 4009 reflections with I \> 2σ(I) graphite R~int~ = 0.023 ω scans θ~max~ = 26.5°, θ~min~ = 2.4° Absorption correction: multi-scan (ABSCOR; Higashi, 1995) h = −10→10 T~min~ = 0.719, T~max~ = 1 k = −13→12 10677 measured reflections l = −14→14 ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e465 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.062 H atoms treated by a mixture of independent and constrained refinement S = 1.08 w = 1/\[σ^2^(F~o~^2^) + (0.0288P)^2^ + 0.6008P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4150 reflections (Δ/σ)~max~ \< 0.001 245 parameters Δρ~max~ = 0.40 e Å^−3^ 1 restraint Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e622 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e721 .table-wrap} ----- --------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cd 0.5000 0.5000 0.5000 0.01706 (6) S1 0.67567 (5) 0.26992 (4) 0.55937 (3) 0.01562 (9) S2 0.48740 (5) 0.36286 (4) 0.32801 (4) 0.01587 (9) O1 0.88422 (15) 0.05660 (12) 0.17754 (11) 0.0223 (3) H1o 0.954 (2) 0.094 (2) 0.1432 (19) 0.033\ N1 0.67484 (15) 0.13324 (12) 0.38469 (11) 0.0120 (3) N2 0.26143 (17) 0.42763 (14) 0.61140 (13) 0.0192 (3) N3 −0.25800 (17) 0.36129 (14) 0.82625 (13) 0.0194 (3) N4 −0.37162 (17) 0.28924 (14) 0.87834 (12) 0.0191 (3) N5 −0.88990 (18) 0.19365 (15) 1.06431 (14) 0.0245 (3) C1 0.61822 (18) 0.24449 (15) 0.41986 (14) 0.0135 (3) C2 0.62455 (19) 0.10536 (15) 0.26935 (14) 0.0156 (3) H2A 0.5139 0.1526 0.2501 0.019\* H2B 0.6239 0.0138 0.2796 0.019\* C3 0.7325 (2) 0.14035 (16) 0.16368 (15) 0.0196 (3) H3A 0.6824 0.1356 0.0866 0.024\* H3B 0.7465 0.2285 0.1601 0.024\* C4 0.79259 (19) 0.03218 (15) 0.45840 (14) 0.0150 (3) H4A 0.8604 0.0717 0.5037 0.018\* H4B 0.8630 −0.0158 0.4033 0.018\* C5 0.7154 (2) −0.05962 (16) 0.54826 (15) 0.0185 (3) H5A 0.6421 −0.0957 0.5043 0.022\* H5B 0.6517 −0.0137 0.6080 0.022\* C6 0.8430 (2) −0.16666 (17) 0.61485 (17) 0.0239 (4) H6A 0.7911 −0.2254 0.6715 0.036\* H6B 0.9137 −0.1311 0.6602 0.036\* H6C 0.9059 −0.2121 0.5557 0.036\* C7 0.1257 (2) 0.50814 (17) 0.63223 (18) 0.0254 (4) H7 0.1197 0.5963 0.6049 0.031\* C8 −0.0057 (2) 0.46933 (17) 0.69130 (17) 0.0238 (4) H8 −0.0989 0.5297 0.7041 0.029\* C9 0.0008 (2) 0.34018 (16) 0.73174 (14) 0.0169 (3) C10 0.1403 (2) 0.25663 (16) 0.70970 (16) 0.0203 (3) H10 0.1493 0.1679 0.7352 0.024\* C11 0.2661 (2) 0.30418 (16) 0.65018 (16) 0.0205 (3) H11 0.3608 0.2458 0.6362 0.025\* C12 −0.1326 (2) 0.28869 (16) 0.79403 (14) 0.0177 (3) H12 −0.1255 0.1995 0.8107 0.021\* C13 −0.5012 (2) 0.35972 (17) 0.90688 (15) 0.0200 (3) H13 −0.5119 0.4492 0.8929 0.024\* C14 −0.6338 (2) 0.30118 (17) 0.96168 (14) 0.0188 (3) C15 −0.7640 (2) 0.37321 (18) 1.01209 (17) 0.0248 (4) H15 −0.7681 0.4604 1.0127 0.030\* C16 −0.8877 (2) 0.31554 (19) 1.06143 (17) 0.0269 (4) H16 −0.9762 0.3659 1.0952 0.032\* C17 −0.7628 (2) 0.12403 (18) 1.01712 (16) 0.0247 (4) H17 −0.7612 0.0367 1.0192 0.030\* C18 −0.6341 (2) 0.17338 (18) 0.96559 (16) 0.0228 (4) H18 −0.5468 0.1206 0.9332 0.027\* ----- --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1401 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cd 0.01757 (10) 0.01303 (10) 0.02083 (10) −0.00255 (7) 0.00354 (7) −0.00493 (7) S1 0.0170 (2) 0.01481 (19) 0.01487 (19) −0.00153 (15) −0.00065 (15) −0.00389 (15) S2 0.0170 (2) 0.01234 (19) 0.0169 (2) −0.00014 (15) −0.00203 (15) −0.00179 (15) O1 0.0183 (6) 0.0224 (6) 0.0251 (6) −0.0043 (5) 0.0080 (5) −0.0026 (5) N1 0.0114 (6) 0.0119 (6) 0.0122 (6) −0.0014 (5) −0.0004 (5) −0.0016 (5) N2 0.0185 (7) 0.0181 (7) 0.0218 (7) −0.0050 (6) 0.0034 (6) −0.0048 (6) N3 0.0178 (7) 0.0218 (7) 0.0184 (7) −0.0064 (6) 0.0024 (5) −0.0007 (6) N4 0.0188 (7) 0.0228 (7) 0.0161 (7) −0.0080 (6) 0.0024 (5) −0.0003 (6) N5 0.0222 (8) 0.0305 (9) 0.0219 (8) −0.0094 (7) 0.0047 (6) −0.0035 (6) C1 0.0114 (7) 0.0144 (8) 0.0147 (7) −0.0042 (6) 0.0032 (6) −0.0014 (6) C2 0.0165 (8) 0.0145 (8) 0.0158 (8) −0.0018 (6) 0.0002 (6) −0.0037 (6) C3 0.0222 (9) 0.0195 (8) 0.0156 (8) −0.0012 (7) 0.0027 (6) −0.0030 (6) C4 0.0127 (7) 0.0138 (8) 0.0169 (8) 0.0004 (6) −0.0007 (6) −0.0020 (6) C5 0.0167 (8) 0.0168 (8) 0.0210 (8) −0.0043 (7) 0.0009 (6) −0.0003 (6) C6 0.0224 (9) 0.0202 (9) 0.0266 (9) −0.0051 (7) −0.0034 (7) 0.0044 (7) C7 0.0230 (9) 0.0162 (8) 0.0348 (10) −0.0033 (7) 0.0087 (8) −0.0008 (7) C8 0.0174 (9) 0.0198 (9) 0.0320 (10) −0.0012 (7) 0.0055 (7) −0.0023 (7) C9 0.0168 (8) 0.0207 (8) 0.0146 (8) −0.0062 (7) 0.0003 (6) −0.0039 (6) C10 0.0217 (9) 0.0158 (8) 0.0245 (9) −0.0048 (7) 0.0021 (7) −0.0055 (7) C11 0.0193 (8) 0.0175 (8) 0.0259 (9) −0.0031 (7) 0.0036 (7) −0.0083 (7) C12 0.0181 (8) 0.0198 (8) 0.0153 (8) −0.0055 (7) −0.0024 (6) −0.0015 (6) C13 0.0198 (9) 0.0213 (9) 0.0178 (8) −0.0049 (7) 0.0006 (6) 0.0003 (7) C14 0.0171 (8) 0.0241 (9) 0.0146 (8) −0.0054 (7) 0.0000 (6) −0.0003 (6) C15 0.0238 (9) 0.0215 (9) 0.0283 (9) −0.0043 (7) 0.0040 (7) −0.0039 (7) C16 0.0206 (9) 0.0304 (10) 0.0290 (10) −0.0037 (8) 0.0076 (7) −0.0062 (8) C17 0.0255 (9) 0.0246 (9) 0.0260 (9) −0.0096 (8) 0.0052 (7) −0.0056 (7) C18 0.0216 (9) 0.0248 (9) 0.0229 (9) −0.0054 (7) 0.0045 (7) −0.0067 (7) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1967 .table-wrap} ----------------------- -------------- ----------------------- -------------- Cd---S1 2.6379 (10) C4---H4B 0.9900 Cd---S2 2.6626 (10) C5---C6 1.527 (2) Cd---N2 2.5403 (17) C5---H5A 0.9900 Cd---S1^i^ 2.6379 (10) C5---H5B 0.9900 Cd---S2^i^ 2.6626 (10) C6---H6A 0.9800 Cd---N2^i^ 2.5403 (17) C6---H6B 0.9800 S1---C1 1.7369 (17) C6---H6C 0.9800 S2---C1 1.7286 (18) C7---C8 1.385 (2) O1---C3 1.421 (2) C7---H7 0.9500 O1---H1o 0.835 (10) C8---C9 1.395 (2) N1---C1 1.339 (2) C8---H8 0.9500 N1---C2 1.475 (2) C9---C10 1.390 (2) N1---C4 1.479 (2) C9---C12 1.471 (2) N2---C11 1.336 (2) C10---C11 1.386 (2) N2---C7 1.347 (2) C10---H10 0.9500 N3---C12 1.280 (2) C11---H11 0.9500 N3---N4 1.418 (2) C12---H12 0.9500 N4---C13 1.279 (2) C13---C14 1.475 (2) N5---C16 1.333 (3) C13---H13 0.9500 N5---C17 1.344 (2) C14---C15 1.391 (2) C2---C3 1.516 (2) C14---C18 1.393 (3) C2---H2A 0.9900 C15---C16 1.388 (3) C2---H2B 0.9900 C15---H15 0.9500 C3---H3A 0.9900 C16---H16 0.9500 C3---H3B 0.9900 C17---C18 1.385 (2) C4---C5 1.521 (2) C17---H17 0.9500 C4---H4A 0.9900 C18---H18 0.9500 N2^i^---Cd---N2 180 C4---C5---C6 110.58 (14) N2^i^---Cd---S1 89.42 (4) C4---C5---H5A 109.5 N2---Cd---S1 90.58 (4) C6---C5---H5A 109.5 N2^i^---Cd---S1^i^ 90.58 (4) C4---C5---H5B 109.5 N2---Cd---S1^i^ 89.42 (4) C6---C5---H5B 109.5 S1---Cd---S1^i^ 180 H5A---C5---H5B 108.1 N2^i^---Cd---S2 87.62 (4) C5---C6---H6A 109.5 N2---Cd---S2 92.38 (4) C5---C6---H6B 109.5 S1---Cd---S2 68.83 (3) H6A---C6---H6B 109.5 S1^i^---Cd---S2 111.17 (3) C5---C6---H6C 109.5 N2^i^---Cd---S2^i^ 92.38 (4) H6A---C6---H6C 109.5 N2---Cd---S2^i^ 87.62 (4) H6B---C6---H6C 109.5 S1---Cd---S2^i^ 111.17 (3) N2---C7---C8 123.52 (17) S1^i^---Cd---S2^i^ 68.83 (3) N2---C7---H7 118.2 S2---Cd---S2^i^ 180 C8---C7---H7 118.2 C1---S1---Cd 86.05 (6) C7---C8---C9 119.02 (16) C1---S2---Cd 85.43 (6) C7---C8---H8 120.5 C3---O1---H1o 109.5 (16) C9---C8---H8 120.5 C1---N1---C2 121.74 (13) C10---C9---C8 117.67 (15) C1---N1---C4 121.96 (13) C10---C9---C12 118.88 (15) C2---N1---C4 116.29 (13) C8---C9---C12 123.44 (16) C11---N2---C7 116.95 (15) C11---C10---C9 119.30 (16) C11---N2---Cd 119.88 (11) C11---C10---H10 120.3 C7---N2---Cd 123.16 (11) C9---C10---H10 120.3 C12---N3---N4 110.47 (14) N2---C11---C10 123.54 (16) C13---N4---N3 111.93 (14) N2---C11---H11 118.2 C16---N5---C17 116.98 (16) C10---C11---H11 118.2 N1---C1---S2 120.59 (12) N3---C12---C9 121.48 (16) N1---C1---S1 119.77 (12) N3---C12---H12 119.3 S2---C1---S1 119.64 (10) C9---C12---H12 119.3 N1---C2---C3 113.01 (13) N4---C13---C14 119.59 (16) N1---C2---H2A 109.0 N4---C13---H13 120.2 C3---C2---H2A 109.0 C14---C13---H13 120.2 N1---C2---H2B 109.0 C15---C14---C18 117.63 (16) C3---C2---H2B 109.0 C15---C14---C13 120.38 (16) H2A---C2---H2B 107.8 C18---C14---C13 121.99 (16) O1---C3---C2 110.27 (14) C16---C15---C14 118.89 (17) O1---C3---H3A 109.6 C16---C15---H15 120.6 C2---C3---H3A 109.6 C14---C15---H15 120.6 O1---C3---H3B 109.6 N5---C16---C15 123.90 (17) C2---C3---H3B 109.6 N5---C16---H16 118.0 H3A---C3---H3B 108.1 C15---C16---H16 118.0 N1---C4---C5 113.22 (13) N5---C17---C18 123.21 (17) N1---C4---H4A 108.9 N5---C17---H17 118.4 C5---C4---H4A 108.9 C18---C17---H17 118.4 N1---C4---H4B 108.9 C17---C18---C14 119.38 (17) C5---C4---H4B 108.9 C17---C18---H18 120.3 H4A---C4---H4B 107.7 C14---C18---H18 120.3 N2^i^---Cd---S1---C1 −86.27 (7) C4---N1---C2---C3 −87.99 (17) N2---Cd---S1---C1 93.73 (7) N1---C2---C3---O1 70.19 (17) S1^i^---Cd---S1---C1 95 (100) C1---N1---C4---C5 90.95 (18) S2---Cd---S1---C1 1.40 (5) C2---N1---C4---C5 −89.78 (16) S2^i^---Cd---S1---C1 −178.60 (5) N1---C4---C5---C6 175.96 (13) N2^i^---Cd---S2---C1 88.89 (7) C11---N2---C7---C8 0.3 (3) N2---Cd---S2---C1 −91.11 (7) Cd---N2---C7---C8 179.02 (14) S1---Cd---S2---C1 −1.41 (5) N2---C7---C8---C9 −0.1 (3) S1^i^---Cd---S2---C1 178.59 (5) C7---C8---C9---C10 −0.3 (3) S2^i^---Cd---S2---C1 −29 (100) C7---C8---C9---C12 −179.20 (17) N2^i^---Cd---N2---C11 −146 (100) C8---C9---C10---C11 0.5 (2) S1---Cd---N2---C11 −10.78 (13) C12---C9---C10---C11 179.47 (15) S1^i^---Cd---N2---C11 169.22 (13) C7---N2---C11---C10 −0.1 (3) S2---Cd---N2---C11 58.06 (13) Cd---N2---C11---C10 −178.83 (13) S2^i^---Cd---N2---C11 −121.94 (13) C9---C10---C11---N2 −0.3 (3) N2^i^---Cd---N2---C7 35 (100) N4---N3---C12---C9 176.90 (14) S1---Cd---N2---C7 170.58 (14) C10---C9---C12---N3 173.70 (15) S1^i^---Cd---N2---C7 −9.42 (14) C8---C9---C12---N3 −7.4 (3) S2---Cd---N2---C7 −120.58 (14) N3---N4---C13---C14 179.61 (14) S2^i^---Cd---N2---C7 59.42 (14) N4---C13---C14---C15 169.03 (16) C12---N3---N4---C13 −177.28 (14) N4---C13---C14---C18 −10.7 (3) C2---N1---C1---S2 −2.1 (2) C18---C14---C15---C16 −1.1 (3) C4---N1---C1---S2 177.14 (10) C13---C14---C15---C16 179.14 (16) C2---N1---C1---S1 177.52 (10) C17---N5---C16---C15 0.6 (3) C4---N1---C1---S1 −3.2 (2) C14---C15---C16---N5 0.4 (3) Cd---S2---C1---N1 −178.09 (12) C16---N5---C17---C18 −0.8 (3) Cd---S2---C1---S1 2.29 (8) N5---C17---C18---C14 0.1 (3) Cd---S1---C1---N1 178.07 (12) C15---C14---C18---C17 0.9 (3) Cd---S1---C1---S2 −2.31 (8) C13---C14---C18---C17 −179.34 (16) C1---N1---C2---C3 91.28 (18) ----------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) −x+1, −y+1, −z+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3093 .table-wrap} --------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1o···N5^ii^ 0.84 (2) 1.98 (2) 2.810 (2) 176 (2) C10---H10···O1^iii^ 0.95 2.55 3.480 (3) 168 C3---H3a···N4^iv^ 0.99 2.61 3.369 (3) 134 --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (ii) x+2, y, z−1; (iii) −x+1, −y, −z+1; (iv) x+1, y, z−1. Table 1 ::: {.caption} ###### Selected geometric parameters (Å, °) ::: ::: {#d32e574 .table-wrap} --------- ------------- Cd---S1 2.6379 (10) Cd---S2 2.6626 (10) Cd---N2 2.5403 (17) --------- ------------- ::: ::: {#d32e592 .table-wrap} -------------- ----------- S1---Cd---S2 68.83 (3) -------------- ----------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ ---------- ---------- ----------- ------------- O1---H1o⋯N5^i^ 0.84 (2) 1.98 (2) 2.810 (2) 176 (2) C10---H10⋯O1^ii^ 0.95 2.55 3.480 (3) 168 C3---H3a⋯N4^iii^ 0.99 2.61 3.369 (3) 134 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.714569	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052135/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m320-m321", "authors": [ { "first": "Grant A.", "last": "Broker" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }
PMC3052136	Related literature {#sec1} ================== For structural data on isonipecotamide salts, see: Smith et al. (2010[@bb11]); Smith & Wermuth (2010a [@bb6],b [@bb7],c [@bb8],d [@bb9], 2011[@bb10]). For the crystal structure of o-phthalic acid, see: Ermer (1981[@bb1]). For hydrogen-bonding graph-set analysis, see: Etter et al. (1990[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~6~H~13~N~2~O^+^·C~8~H~5~O~4~ ^−^·C~8~H~6~O~4~M ~r~ = 460.43Triclinic,a = 8.7857 (4) Åb = 11.7907 (6) Åc = 12.3188 (6) Åα = 62.496 (5)°β = 85.916 (4)°γ = 82.604 (4)°V = 1122.36 (11) Å^3^Z = 2Mo Kα radiationμ = 0.11 mm^−1^T = 200 K0.40 × 0.30 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini-S CCD-detector diffractometerAbsorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[@bb4]) T ~min~ = 0.923, T ~max~ = 0.98013586 measured reflections4401 independent reflections3444 reflections with I \> 2σ(I)R ~int~ = 0.024 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.037wR(F ^2^) = 0.094S = 1.074401 reflections326 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e690} Data collection: CrysAlis PRO (Oxford Diffraction, 2010[@bb4]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]) within WinGX (Farrugia, 1999[@bb3]); molecular graphics: PLATON (Spek, 2009[@bb12]); software used to prepare material for publication: PLATON. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003825/wn2419sup1.cif](http://dx.doi.org/10.1107/S1600536811003825/wn2419sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003825/wn2419Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003825/wn2419Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wn2419&file=wn2419sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wn2419sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wn2419&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WN2419](http://scripts.iucr.org/cgi-bin/sendsup?wn2419)). The authors acknowledge financial support from the Australian Research Council, the Faculty of Science and Technology and the University Library, Queensland University of Technology and the School of Biomolecular and Physical Sciences, Griffith University. Comment ======= The amide piperidine-4-carboxamide (isonipecotamide, INIPA) has provided the structures of proton-transfer compounds with a range of organic acids, mainly aromatic (Smith & Wermuth, 2010a,b,c,d, 2011; Smith et al., 2010). The title compound, the salt adduct, C~6~H~13~N~2~O^+^ C~8~H~5~O~4~^-^ . C~8~H~6~O~4~, was obtained from the 1:1 stoichiometric reaction of phthalic acid with INIPA in methanol and the crystal structure is reported here; it represents the first example of a salt--adduct of INIPA. The asymmetric unit (Fig. 1) comprises an isonipecotamide cation, (C), a hydrogen phthalate anion (B) and a phthalic acid adduct molecule (A), which together form a two-dimensional hydrogen-bonded network through head-to-tail cation--anion--adduct molecule interactions (Table 1). These include a cyclic heteromolecular amide--carboxylate motif \[graph set R~2~^2^(8) (Etter et al., 1990)\], conjoint cyclic R~2~^2^(6) and R~3~^3^(10) piperidinium N---H···O~carboxyl~ associations, as well as strong carboxylic acid O---H···O~carboxyl~ hydrogen bonds (Fig. 2). There is no occurrence of the cyclic homomolecular amide--amide dimer motif association, such as is found in the INIPA salts of the 2-nitro-, 4-nitro- and 3,5-dinitrobenzoic acids (Smith & Wermuth, 2010b) or of biphenyl-4,4\'-disulfonic acid (Smith et al., 2010). In the hydrogen phthalate anion (B) and the phthalic acid adduct molecule (A), the carboxyl substituent groups are rotated by differing degrees out of the planes of the benzene rings \[torsion angles C1---C2---C21---O22 and C2---C1---C11---O11: -147.67 (6) and 52.9 (2)° \[for B)\] and -117.75 (15) and -157.57 (14)° \[for A)\], which compare with 20.3 (1)° for the parent acid molecule which has two-fold rotational symmetry (Ermer, 1981). Experimental {#experimental} ============ The title compound was synthesized by heating together under reflux for 10 minutes, 1 mmol quantities of piperidine-4-carboxamide (isonipecotamide) and phthalic acid in 50 ml of methanol. After concentration to ca 30 ml, partial room temperature evaporation of the hot-filtered solution gave colourless plates of the title compound, from which a specimen was cleaved for the X-ray crystallographic analysis. Refinement {#refinement} ========== Hydrogen atoms involved in hydrogen-bonding interactions were located by difference methods and their positional and isotropic displacement parameters were refined. Other H-atoms were included in the refinement at calculated positions using a riding-model approximation \[C---H = 0.93--0.98 Å\] and with U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular conformation for the INIPA cation (C), the hydrogen phthalate anion (B) and the phthalic acid adduct molecule (A) in the asymmetric unit. The inter-species hydrogen bonds are shown as dashed lines and displacement ellipsoids are drawn at the 40% probability level. Hydrogen atoms are shown as spheres of arbitrary radius. ::: ![](e-67-0o566-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The hydrogen-bonded chain structure, showing the cyclic R22(8) amide--carboxyl and R22(6) piperidinium--carboxyl cation--anion associations. Non-associative H atoms have been omitted and hydrogen bonds are shown as dashed lines. For symmetry codes, see Table 1. ::: ![](e-67-0o566-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e237 .table-wrap} ------------------------------------------------ --------------------------------------- C~6~H~13~N~2~O^+^·C~8~H~5~O~4~^−^·C~8~H~6~O~4~ Z = 2 M~r~ = 460.43 F(000) = 484 Triclinic, P1 D~x~ = 1.362 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.7857 (4) Å Cell parameters from 6939 reflections b = 11.7907 (6) Å θ = 3.2--28.7° c = 12.3188 (6) Å µ = 0.11 mm^−1^ α = 62.496 (5)° T = 200 K β = 85.916 (4)° Plate, colourless γ = 82.604 (4)° 0.40 × 0.30 × 0.18 mm V = 1122.36 (11) Å^3^ ------------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e395 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Gemini-S CCD-detector diffractometer 4401 independent reflections Radiation source: Enhance (Mo) X-ray source 3444 reflections with I \> 2σ(I) graphite R~int~ = 0.024 Detector resolution: 16.077 pixels mm^-1^ θ~max~ = 26.0°, θ~min~ = 3.3° ω scans h = −10→10 Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) k = −14→14 T~min~ = 0.923, T~max~ = 0.980 l = −15→15 13586 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e515 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.037 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.094 H atoms treated by a mixture of independent and constrained refinement S = 1.07 w = 1/\[σ^2^(F~o~^2^) + (0.0531P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 4401 reflections (Δ/σ)~max~ = 0.001 326 parameters Δρ~max~ = 0.25 e Å^−3^ 0 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e669 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e771 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O41C 0.74423 (12) 0.61632 (11) −0.02736 (9) 0.0416 (3) N1C 1.00683 (14) 0.42772 (13) 0.35653 (11) 0.0325 (4) N41C 0.52124 (15) 0.58014 (14) 0.08017 (12) 0.0383 (4) C2C 0.85240 (17) 0.48482 (14) 0.37702 (12) 0.0316 (5) C3C 0.77366 (16) 0.56671 (13) 0.25569 (12) 0.0279 (4) C4C 0.75894 (15) 0.48525 (13) 0.19015 (12) 0.0255 (4) C5C 0.91666 (17) 0.42485 (15) 0.17252 (13) 0.0352 (5) C6C 0.99655 (17) 0.34593 (15) 0.29489 (13) 0.0355 (5) C41C 0.67380 (16) 0.56532 (14) 0.07155 (12) 0.0287 (4) O11A 0.80799 (12) 0.85845 (10) 0.30180 (10) 0.0382 (3) O12A 1.01504 (12) 0.71996 (11) 0.38418 (9) 0.0457 (4) O21A 1.15402 (13) 0.64611 (10) 0.19609 (10) 0.0428 (4) O22A 1.34884 (12) 0.66738 (10) 0.28975 (10) 0.0350 (3) C1A 1.04746 (16) 0.90657 (13) 0.19787 (11) 0.0257 (4) C2A 1.18683 (15) 0.85461 (13) 0.16830 (12) 0.0273 (4) C3A 1.28238 (18) 0.93696 (15) 0.07974 (14) 0.0388 (5) C4A 1.2394 (2) 1.06857 (16) 0.02235 (15) 0.0456 (5) C5A 1.10150 (19) 1.11900 (15) 0.05043 (14) 0.0402 (5) C6A 1.00445 (17) 1.03847 (13) 0.13774 (12) 0.0321 (4) C11A 0.95520 (16) 0.81938 (13) 0.30320 (12) 0.0270 (4) C21A 1.22700 (16) 0.71181 (14) 0.22139 (12) 0.0285 (4) O11B 0.55460 (12) 0.56551 (9) 0.65124 (9) 0.0375 (3) O12B 0.70819 (11) 0.67951 (10) 0.49932 (9) 0.0365 (3) O21B 0.62518 (11) 0.72888 (11) 0.75928 (9) 0.0380 (3) O22B 0.39403 (12) 0.75761 (11) 0.83676 (9) 0.0443 (4) C1B 0.47554 (15) 0.78671 (12) 0.53468 (12) 0.0234 (4) C2B 0.41733 (15) 0.82601 (12) 0.62266 (12) 0.0250 (4) C3B 0.30225 (17) 0.92762 (14) 0.59082 (14) 0.0332 (5) C4B 0.24536 (18) 0.99166 (14) 0.47329 (15) 0.0400 (5) C5B 0.30399 (18) 0.95471 (14) 0.38598 (14) 0.0380 (5) C6B 0.41770 (17) 0.85304 (13) 0.41663 (13) 0.0309 (4) C11B 0.58924 (15) 0.66926 (13) 0.56461 (12) 0.0251 (4) C21B 0.47720 (16) 0.76662 (13) 0.75001 (12) 0.0282 (4) H4C 0.69780 0.41540 0.24300 0.0310\ H11C 1.068 (2) 0.4933 (17) 0.3102 (16) 0.051 (5)\* H12C 1.0542 (19) 0.3761 (16) 0.4339 (16) 0.048 (5)\* H21C 0.86350 0.53720 0.41730 0.0380\* H22C 0.79060 0.41670 0.42960 0.0380\* H31C 0.83260 0.63760 0.20490 0.0330\* H32C 0.67250 0.60230 0.26930 0.0330\* H41C 0.461 (2) 0.6370 (17) 0.0071 (17) 0.058 (5)\* H42C 0.475 (2) 0.5356 (17) 0.1562 (17) 0.054 (5)\* H51C 0.90570 0.36990 0.13500 0.0420\* H52C 0.97860 0.49200 0.11810 0.0420\* H61C 0.93950 0.27400 0.34670 0.0430\* H62C 1.09880 0.31190 0.28190 0.0430\* H3A 1.37520 0.90370 0.05900 0.0470\* H4A 1.30450 1.12320 −0.03570 0.0550\* H5A 1.07320 1.20730 0.01080 0.0480\* H6A 0.91060 1.07260 0.15610 0.0380\* H11A 0.762 (2) 0.793 (2) 0.3786 (19) 0.078 (6)\* H22A 1.374 (2) 0.583 (2) 0.3154 (18) 0.072 (6)\* H3B 0.26280 0.95300 0.64920 0.0400\* H4B 0.16780 1.05940 0.45310 0.0480\* H5B 0.26690 0.99830 0.30660 0.0460\* H6B 0.45630 0.82850 0.35750 0.0370\* H21B 0.664 (2) 0.691 (2) 0.844 (2) 0.081 (7)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1500 .table-wrap} ------ ------------- ------------ ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O41C 0.0306 (6) 0.0590 (7) 0.0233 (5) −0.0098 (5) 0.0002 (4) −0.0077 (5) N1C 0.0310 (7) 0.0316 (7) 0.0255 (6) −0.0079 (6) −0.0069 (6) −0.0032 (6) N41C 0.0285 (7) 0.0545 (9) 0.0257 (7) −0.0019 (6) −0.0009 (6) −0.0138 (7) C2C 0.0382 (9) 0.0315 (8) 0.0255 (7) −0.0033 (7) −0.0024 (6) −0.0133 (6) C3C 0.0290 (8) 0.0272 (7) 0.0255 (7) −0.0033 (6) −0.0021 (6) −0.0101 (6) C4C 0.0256 (7) 0.0278 (7) 0.0216 (7) −0.0058 (6) 0.0004 (5) −0.0093 (6) C5C 0.0340 (8) 0.0430 (9) 0.0282 (8) 0.0018 (7) −0.0001 (6) −0.0175 (7) C6C 0.0301 (8) 0.0360 (9) 0.0356 (8) 0.0038 (7) −0.0007 (6) −0.0141 (7) C41C 0.0280 (8) 0.0351 (8) 0.0256 (7) −0.0061 (6) −0.0006 (6) −0.0155 (6) O11A 0.0307 (6) 0.0306 (6) 0.0376 (6) 0.0049 (5) 0.0092 (5) −0.0057 (5) O12A 0.0312 (6) 0.0454 (7) 0.0307 (6) 0.0011 (5) 0.0005 (5) 0.0063 (5) O21A 0.0453 (7) 0.0335 (6) 0.0459 (6) −0.0133 (5) −0.0085 (5) −0.0116 (5) O22A 0.0294 (6) 0.0271 (6) 0.0485 (6) 0.0029 (5) −0.0075 (5) −0.0178 (5) C1A 0.0279 (7) 0.0259 (7) 0.0211 (7) −0.0046 (6) −0.0022 (6) −0.0083 (6) C2A 0.0253 (7) 0.0283 (8) 0.0249 (7) −0.0062 (6) −0.0011 (6) −0.0083 (6) C3A 0.0290 (8) 0.0378 (9) 0.0386 (8) −0.0059 (7) 0.0051 (7) −0.0083 (7) C4A 0.0402 (10) 0.0367 (9) 0.0403 (9) −0.0137 (8) 0.0060 (7) 0.0005 (8) C5A 0.0446 (10) 0.0242 (8) 0.0376 (8) −0.0041 (7) −0.0045 (7) −0.0016 (7) C6A 0.0342 (8) 0.0277 (8) 0.0289 (7) 0.0005 (7) −0.0034 (6) −0.0089 (6) C11A 0.0287 (8) 0.0271 (8) 0.0237 (7) −0.0024 (6) −0.0004 (6) −0.0106 (6) C21A 0.0242 (7) 0.0302 (8) 0.0282 (7) −0.0058 (6) 0.0049 (6) −0.0110 (6) O11B 0.0377 (6) 0.0231 (5) 0.0381 (6) 0.0013 (5) 0.0143 (5) −0.0056 (5) O12B 0.0278 (6) 0.0373 (6) 0.0324 (5) 0.0012 (5) 0.0100 (4) −0.0083 (5) O21B 0.0281 (6) 0.0522 (7) 0.0244 (5) −0.0004 (5) −0.0019 (4) −0.0104 (5) O22B 0.0407 (7) 0.0563 (8) 0.0295 (6) 0.0060 (6) 0.0030 (5) −0.0175 (5) C1B 0.0209 (7) 0.0206 (7) 0.0265 (7) −0.0045 (6) 0.0001 (5) −0.0085 (6) C2B 0.0244 (7) 0.0214 (7) 0.0281 (7) −0.0050 (6) 0.0007 (6) −0.0099 (6) C3B 0.0347 (8) 0.0274 (8) 0.0377 (8) 0.0014 (7) 0.0010 (7) −0.0165 (7) C4B 0.0372 (9) 0.0265 (8) 0.0493 (10) 0.0096 (7) −0.0118 (7) −0.0132 (7) C5B 0.0420 (9) 0.0306 (8) 0.0355 (8) 0.0016 (7) −0.0176 (7) −0.0092 (7) C6B 0.0345 (8) 0.0299 (8) 0.0292 (7) −0.0024 (7) −0.0057 (6) −0.0139 (6) C11B 0.0238 (7) 0.0266 (7) 0.0232 (7) −0.0022 (6) 0.0017 (6) −0.0103 (6) C21B 0.0308 (8) 0.0245 (7) 0.0273 (7) −0.0033 (6) 0.0017 (6) −0.0103 (6) ------ ------------- ------------ ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2183 .table-wrap} ------------------------- -------------- ------------------------- -------------- O41C---C41C 1.2413 (17) C5C---H51C 0.9700 O11A---C11A 1.3144 (18) C5C---H52C 0.9700 O12A---C11A 1.2172 (19) C6C---H61C 0.9700 O21A---C21A 1.220 (2) C6C---H62C 0.9700 O22A---C21A 1.3062 (18) C1A---C11A 1.4934 (19) O11A---H11A 1.00 (2) C1A---C2A 1.399 (2) O22A---H22A 0.90 (2) C1A---C6A 1.391 (2) O11B---C11B 1.2537 (18) C2A---C21A 1.500 (2) O12B---C11B 1.2557 (17) C2A---C3A 1.392 (2) O21B---C21B 1.3140 (18) C3A---C4A 1.387 (3) O22B---C21B 1.2211 (17) C4A---C5A 1.373 (3) O21B---H21B 0.99 (2) C5A---C6A 1.386 (2) N1C---C6C 1.491 (2) C3A---H3A 0.9300 N1C---C2C 1.494 (2) C4A---H4A 0.9300 N41C---C41C 1.332 (2) C5A---H5A 0.9300 N1C---H12C 0.953 (18) C6A---H6A 0.9300 N1C---H11C 0.932 (19) C1B---C2B 1.405 (2) N41C---H42C 0.930 (18) C1B---C11B 1.509 (2) N41C---H41C 0.979 (19) C1B---C6B 1.3918 (19) C2C---C3C 1.5123 (19) C2B---C3B 1.386 (2) C3C---C4C 1.534 (2) C2B---C21B 1.4954 (19) C4C---C5C 1.523 (2) C3B---C4B 1.383 (2) C4C---C41C 1.5117 (19) C4B---C5B 1.381 (2) C5C---C6C 1.523 (2) C5B---C6B 1.380 (2) C2C---H21C 0.9700 C3B---H3B 0.9300 C2C---H22C 0.9700 C4B---H4B 0.9300 C3C---H31C 0.9700 C5B---H5B 0.9300 C3C---H32C 0.9700 C6B---H6B 0.9300 C4C---H4C 0.9800 C11A---O11A---H11A 106.6 (12) C2A---C1A---C11A 118.40 (13) C21A---O22A---H22A 112.4 (12) C3A---C2A---C21A 119.76 (14) C21B---O21B---H21B 113.9 (11) C1A---C2A---C3A 119.05 (15) C2C---N1C---C6C 112.01 (12) C1A---C2A---C21A 120.92 (12) H11C---N1C---H12C 107.8 (15) C2A---C3A---C4A 120.14 (16) C6C---N1C---H11C 110.2 (12) C3A---C4A---C5A 120.62 (16) C2C---N1C---H11C 109.5 (12) C4A---C5A---C6A 120.06 (17) C2C---N1C---H12C 108.5 (11) C1A---C6A---C5A 119.96 (15) C6C---N1C---H12C 108.8 (13) O12A---C11A---C1A 121.18 (13) H41C---N41C---H42C 121.8 (16) O11A---C11A---O12A 123.45 (13) C41C---N41C---H42C 118.5 (11) O11A---C11A---C1A 115.38 (13) C41C---N41C---H41C 119.7 (11) O22A---C21A---C2A 114.51 (14) N1C---C2C---C3C 109.73 (11) O21A---C21A---C2A 121.23 (13) C2C---C3C---C4C 110.03 (13) O21A---C21A---O22A 124.16 (16) C5C---C4C---C41C 113.04 (12) C2A---C3A---H3A 120.00 C3C---C4C---C5C 110.14 (12) C4A---C3A---H3A 120.00 C3C---C4C---C41C 110.15 (13) C5A---C4A---H4A 120.00 C4C---C5C---C6C 110.52 (12) C3A---C4A---H4A 120.00 N1C---C6C---C5C 110.09 (14) C4A---C5A---H5A 120.00 O41C---C41C---C4C 120.98 (13) C6A---C5A---H5A 120.00 N41C---C41C---C4C 116.38 (12) C5A---C6A---H6A 120.00 O41C---C41C---N41C 122.62 (13) C1A---C6A---H6A 120.00 N1C---C2C---H21C 110.00 C2B---C1B---C6B 118.78 (14) H21C---C2C---H22C 108.00 C6B---C1B---C11B 118.11 (13) C3C---C2C---H21C 110.00 C2B---C1B---C11B 122.94 (12) C3C---C2C---H22C 110.00 C1B---C2B---C21B 123.27 (13) N1C---C2C---H22C 110.00 C3B---C2B---C21B 117.17 (13) C4C---C3C---H31C 110.00 C1B---C2B---C3B 119.52 (13) C2C---C3C---H32C 110.00 C2B---C3B---C4B 120.84 (15) H31C---C3C---H32C 108.00 C3B---C4B---C5B 119.83 (16) C4C---C3C---H32C 110.00 C4B---C5B---C6B 119.96 (14) C2C---C3C---H31C 110.00 C1B---C6B---C5B 121.06 (14) C41C---C4C---H4C 108.00 O11B---C11B---C1B 116.96 (12) C5C---C4C---H4C 108.00 O12B---C11B---C1B 118.86 (13) C3C---C4C---H4C 108.00 O11B---C11B---O12B 124.11 (15) C4C---C5C---H51C 110.00 O21B---C21B---C2B 114.59 (12) C4C---C5C---H52C 110.00 O22B---C21B---C2B 121.76 (13) C6C---C5C---H51C 110.00 O21B---C21B---O22B 123.64 (13) C6C---C5C---H52C 110.00 C2B---C3B---H3B 120.00 H51C---C5C---H52C 108.00 C4B---C3B---H3B 120.00 C5C---C6C---H61C 110.00 C3B---C4B---H4B 120.00 H61C---C6C---H62C 108.00 C5B---C4B---H4B 120.00 C5C---C6C---H62C 110.00 C4B---C5B---H5B 120.00 N1C---C6C---H61C 110.00 C6B---C5B---H5B 120.00 N1C---C6C---H62C 110.00 C1B---C6B---H6B 119.00 C2A---C1A---C6A 120.16 (13) C5B---C6B---H6B 119.00 C6A---C1A---C11A 121.15 (13) C6C---N1C---C2C---C3C −59.45 (17) C1A---C2A---C21A---O22A −117.75 (15) C2C---N1C---C6C---C5C 58.30 (15) C3A---C2A---C21A---O21A −108.28 (17) N1C---C2C---C3C---C4C 58.11 (16) C3A---C2A---C21A---O22A 68.28 (18) C2C---C3C---C4C---C5C −57.23 (15) C2A---C3A---C4A---C5A −1.1 (3) C2C---C3C---C4C---C41C 177.41 (11) C3A---C4A---C5A---C6A 0.7 (3) C3C---C4C---C5C---C6C 56.17 (17) C4A---C5A---C6A---C1A 0.7 (2) C41C---C4C---C5C---C6C 179.86 (14) C6B---C1B---C2B---C3B 1.3 (2) C3C---C4C---C41C---O41C 97.27 (18) C6B---C1B---C2B---C21B −176.43 (14) C3C---C4C---C41C---N41C −81.09 (18) C11B---C1B---C2B---C3B −173.80 (14) C5C---C4C---C41C---O41C −26.4 (2) C11B---C1B---C2B---C21B 8.5 (2) C5C---C4C---C41C---N41C 155.23 (16) C2B---C1B---C6B---C5B −0.8 (2) C4C---C5C---C6C---N1C −56.27 (17) C11B---C1B---C6B---C5B 174.56 (14) C6A---C1A---C2A---C3A 1.1 (2) C2B---C1B---C11B---O11B 52.9 (2) C6A---C1A---C2A---C21A −172.89 (13) C2B---C1B---C11B---O12B −130.04 (15) C11A---C1A---C2A---C3A −172.71 (14) C6B---C1B---C11B---O11B −122.25 (15) C11A---C1A---C2A---C21A 13.3 (2) C6B---C1B---C11B---O12B 54.86 (19) C2A---C1A---C6A---C5A −1.6 (2) C1B---C2B---C3B---C4B −0.8 (2) C11A---C1A---C6A---C5A 172.11 (14) C21B---C2B---C3B---C4B 177.07 (14) C2A---C1A---C11A---O11A −157.57 (14) C1B---C2B---C21B---O21B 34.0 (2) C2A---C1A---C11A---O12A 23.0 (2) C1B---C2B---C21B---O22B −147.67 (16) C6A---C1A---C11A---O11A 28.7 (2) C3B---C2B---C21B---O21B −143.76 (15) C6A---C1A---C11A---O12A −150.80 (15) C3B---C2B---C21B---O22B 34.6 (2) C1A---C2A---C3A---C4A 0.2 (2) C2B---C3B---C4B---C5B −0.3 (2) C21A---C2A---C3A---C4A 174.29 (15) C3B---C4B---C5B---C6B 0.8 (3) C1A---C2A---C21A---O21A 65.69 (19) C4B---C5B---C6B---C1B −0.3 (2) ------------------------- -------------- ------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3169 .table-wrap} ------------------------- ------------ ------------ ------------- --------------- D---H···A D---H H···A D···A D---H···A N1C---H11C···O21A 0.932 (19) 1.911 (19) 2.8287 (18) 167.7 (16) N1C---H12C···O12A^i^ 0.953 (18) 2.077 (17) 2.8519 (16) 137.4 (14) N1C---H12C···O12B^i^ 0.953 (18) 2.204 (17) 2.9606 (16) 135.6 (14) N41C---H41C···O22B^ii^ 0.979 (19) 1.994 (19) 2.9494 (17) 164.5 (16) N41C---H42C···O11B^iii^ 0.930 (18) 2.120 (19) 3.0122 (17) 160.3 (16) O11A---H11A···O12B 1.00 (2) 1.57 (2) 2.5635 (15) 173 (2) O21B---H21B···O41C^iv^ 0.99 (2) 1.58 (2) 2.5644 (14) 171 (2) O22A---H22A···O11B^i^ 0.90 (2) 1.65 (2) 2.5363 (17) 170.8 (18) C3B---H3B···O11A^v^ 0.93 2.55 3.365 (2) 146 C4C---H4C···O11B^iii^ 0.98 2.53 3.2159 (17) 127 C2C---H21C···O12A 0.97 2.54 3.317 (2) 137 C2C---H21C···O12B 0.97 2.55 3.364 (2) 142 C6C---H62C···O21B^i^ 0.97 2.47 3.4265 (19) 168 ------------------------- ------------ ------------ ------------- --------------- ::: Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) x, y, z−1; (iii) −x+1, −y+1, −z+1; (iv) x, y, z+1; (v) −x+1, −y+2, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ----------------------------- ------------ ------------ ------------- ------------- N1C---H11C⋯O21A 0.932 (19) 1.911 (19) 2.8287 (18) 167.7 (16) N1C---H12C⋯O12A^i^ 0.953 (18) 2.077 (17) 2.8519 (16) 137.4 (14) N1C---H12C⋯O12B^i^ 0.953 (18) 2.204 (17) 2.9606 (16) 135.6 (14) N41C---H41C⋯O22B^ii^ 0.979 (19) 1.994 (19) 2.9494 (17) 164.5 (16) N41C---H42C⋯O11B^iii^ 0.930 (18) 2.120 (19) 3.0122 (17) 160.3 (16) O11A---H11A⋯O12B 1.00 (2) 1.57 (2) 2.5635 (15) 173 (2) O21B---H21B⋯O41C^iv^ 0.99 (2) 1.58 (2) 2.5644 (14) 171 (2) O22A---H22A⋯O11B^i^ 0.90 (2) 1.65 (2) 2.5363 (17) 170.8 (18) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::	PubMed Central	2024-06-05T04:04:18.720666	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052136/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o566", "authors": [ { "first": "Graham", "last": "Smith" }, { "first": "Urs D.", "last": "Wermuth" } ] }
PMC3052137	Related literature {#sec1} ================== For general background to metal complexes with 4,4′-bi-1,3-thiazole ligands, see: Baker & Goodwin (1985[@bb6]); Mahjoub & Morsali (2001[@bb17], 2002a [@bb18],b [@bb19]). For related structures, see: Al-Hashemi et al. (2009[@bb1]); Ali & Al-Far (2007[@bb2]); Amani et al. (2007a [@bb3],b [@bb4], 2009[@bb5]); Craig et al. (1988[@bb9]); Figgis et al. (1983[@bb11]); Jia et al. (2006[@bb13]); Khavasi et al. (2008[@bb14]); Kulkarni et al. (1998[@bb15]); Notash et al. (2008[@bb21], 2009[@bb20]); Rahimi et al. (2009[@bb22]); Safari et al. (2009[@bb23]). For the synthesis of the ligand, see: Erlenmeyer & Ueberwasser (1939[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Fe(C~6~H~4~N~2~S~2~)~3~\]\[FeBr~4~\]BrM ~r~ = 1015.95Trigonal,a = 12.0638 (7) Åc = 17.6907 (13) ÅV = 2229.7 (2) Å^3^Z = 3Mo Kα radiationμ = 8.14 mm^−1^T = 100 K0.45 × 0.35 × 0.30 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2001[@bb7]) T ~min~ = 0.031, T ~max~ = 0.0868430 measured reflections2508 independent reflections2427 reflections with I \> 2σ(I)R ~int~ = 0.099 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.036wR(F ^2^) = 0.085S = 1.012508 reflections112 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.93 e Å^−3^Δρ~min~ = −0.78 e Å^−3^Absolute structure: Flack (1983[@bb12]), 1195 Friedel pairsFlack parameter: 0.021 (9) {#d5e561} Data collection: APEX2 (Bruker, 2007[@bb8]); cell refinement: SAINT (Bruker, 2007[@bb8]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb24]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb24]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb24]) and Mercury (Macrae et al., 2006[@bb16]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004181/hy2404sup1.cif](http://dx.doi.org/10.1107/S1600536811004181/hy2404sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004181/hy2404Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004181/hy2404Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hy2404&file=hy2404sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hy2404sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hy2404&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HY2404](http://scripts.iucr.org/cgi-bin/sendsup?hy2404)). We thank the Graduate Study Councils of the Islamic Azad University, North Tehran Branch, and Shahid Beheshti University for financial support. Comment ======= Erlenmeyer & Ueberwasser (1939) first reported the synthesis of 4,4\'-bi-1,3-thiazole (4,4\'-bit) and Craig et al. (1988) determined the structure of this compound. Although 4,4\'-bit is a good bidentate ligand, a few of its metal complexes have been prepared, such as those of nickel and iron (Baker & Goodwin, 1985), lead (Mahjoub & Morsali, 2001, 2002a) and bismuth (Mahjoub & Morsali, 2002b). We recently introduced the coordination chemistry of 2,2\'-dimethyl-4,4\'-bi-1,3-thiazole with copper (Al-Hashemi et al., 2009), zinc and mercury (Khavasi et al., 2008; Safari et al., 2009), cadmium (Notash et al., 2009) and thallium (Notash et al., 2008). We report here the synthesis and crystal structure of the title compound. The asymmetric unit of the title compound (Fig. 1), contains one third of an \[Fe(4,4\'-bit)~3~\]^2+^ cation, one third of an \[FeBr~4~\]^-^ anion and one third of a Br^-^ anion. In the \[Fe(4,4\'-bit)~3~\]^2+^ cation, the Fe^II^ atom (3 symmetry) is six-coordinated in a distorted octahedral geometry by six N atoms from three 4,4\'-bit ligands. The Fe---N bond lengths are 1.962 (3) and 1.974 (3) Å (Table 1). The average Fe---N bond distances in high-spin iron(II) and (III) complexes with phenanthroline and bipyridine are around 2.2 Å. However, for low-spin iron(II) and (III) complexes, the Fe---N distances less than 2.0 Å have been reported (Amani et al., 2007a,b, 2009; Figgis et al., 1983; Kulkarni et al., 1998; Rahimi et al., 2009). Therefore, in the \[Fe(4,4\'-bit)~3~\]^2+^ cation, the Fe---N bond distances are unambiguous in accord with low-spin iron(II). The N---Fe---N bond angles are in the range of 82.00 (14) to 171.87 (14)°. The bond angles and distances are in good agreement to those of \[Fe(4,4\'-bit)~3~\]^2+^ cations, which have been found in other structures (Baker & Goodwin, 1985). In the \[FeBr~4~\]^-^ anion, the Fe^III^ atom (3 symmetry) is four-coordinated in a distorted tetrahedral geometry by four Br atoms. The Fe---Br bond lengths are 2.3348 (5) and 2.3370 (12) Å. The Br---Fe---Br angles, in turn, span the ranges of 108.64 (3) to 110.29 (3)°, and the bond angles and distances are in good agreement to those of \[FeBr~4~\]^-^ anions, which have been found in other structures (Ali & Al-Far 2007; Jia et al., 2006). Fig. 2 shows significant intermolecular C---H···Br hydrogen bonds in the title compound (Table 2). The hydrogen bonds cause the formation of a supramolecular architecture, best described as built up by Br(thiazol)~9~ supramolecular synthons (Fig. 2) assembled via C---H···Br hydrogen bonds, where nine thiazole groups surround one (central) uncoordinated bromide ion. These synthons are further connected into an adamantoid-like network that extends into a three-dimensional structure. The discrete \[FeBr~4~\]^-^ anions occupy the cavities that result from the three-dimensional assembly of the Br(thiazol)~9~ entities. There also exist intermolecular Br···π interactions between the \[FeBr~4~\]^-^ anions and thiazole rings in the crystal structure (Fig. 3), with Br1···Cg1 = 3.562 (3) and Br1^i^···Cg2 = 3.765 (2) Å \[Cg1 and Cg2 are the centroids of C1, C2, C3, N2, S2 ring and C4, C5, C6, N1, S1 ring. Symmetry code: (i) 1-x+y, 2-x, z\]. The hydrogen bonds and Br···π interactions link the cations and anions, which may be effective in the stabilization of the structure. Experimental {#experimental} ============ 4,4\'-bi-1,3-thiazole (0.11 g, 0.63 mmol) in CH~3~OH (20 ml) was added to a solution of FeBr~3~ (0.06 g, 0.21 mmol) in CH~3~OH (10 ml) and the resulting red solution was stirred at 313 K for 1 h. The red colored precipitated product was recrystallized from CH~3~CN/CH~3~OH (v/v 2:1). After two weeks, dark-red prismatic crystals of the title compound were isolated (yield: 0.08 g, 75.0%; m.p. 464 K). Refinement {#refinement} ========== All H atoms were positioned geometrically and refined as riding atoms, with C---H = 0.93 Å and with U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level. \[Symmetry codes: (i) 1-x+y, 2-x, z; (ii) 2-y, 1+x-y, z; (iii) 1-y, 1+x-y, z; (iv) -x+y, 1-x, z.\] ::: ![](e-67-0m311-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing diagram for the title compound. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0m311-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Intermolecular Br···π interactions (dashed lines) in the title compound. \[Symmetry code: (i) 1-x+y, 2-x, z.\] ::: ![](e-67-0m311-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e275 .table-wrap} ------------------------------------------ --------------------------------------- \[Fe(C~6~H~4~N~2~S~2~)~3~\]\[FeBr~4~\]Br D~x~ = 2.270 Mg m^−3^ M~r~ = 1015.95 Mo Kα radiation, λ = 0.71073 Å Trigonal, R3 Cell parameters from 1635 reflections Hall symbol: R 3 θ = 3.0--28.0° a = 12.0638 (7) Å µ = 8.14 mm^−1^ c = 17.6907 (13) Å T = 100 K V = 2229.7 (2) Å^3^ Prism, dark-red Z = 3 0.45 × 0.35 × 0.30 mm F(000) = 1455 ------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e399 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2508 independent reflections Radiation source: fine-focus sealed tube 2427 reflections with I \> 2σ(I) graphite R~int~ = 0.099 φ and ω scans θ~max~ = 28.9°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Bruker, 2001) h = −16→16 T~min~ = 0.031, T~max~ = 0.086 k = −16→16 8430 measured reflections l = −24→23 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e516 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.036 H-atom parameters constrained wR(F^2^) = 0.085 w = 1/\[σ^2^(F~o~^2^) + (0.0485P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.01 (Δ/σ)~max~ \< 0.001 2508 reflections Δρ~max~ = 0.93 e Å^−3^ 112 parameters Δρ~min~ = −0.78 e Å^−3^ 1 restraint Absolute structure: Flack (1983), 1195 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.021 (9) ---------------------------------------------------------------- ------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e677 .table-wrap} ----- -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.53314 (4) 0.70585 (5) 0.46767 (3) 0.02946 (13) Br2 0.3333 0.6667 0.64196 (3) 0.01401 (14) Br3 1.6667 1.3333 0.53208 (4) 0.01483 (14) Fe1 1.0000 1.0000 0.48640 (5) 0.00941 (17) Fe2 0.3333 0.6667 0.50986 (6) 0.01351 (18) S1 1.25908 (10) 1.31480 (10) 0.64504 (6) 0.0182 (2) S2 1.33303 (9) 1.07879 (10) 0.33584 (6) 0.01552 (19) N1 1.1247 (3) 1.1426 (3) 0.54875 (19) 0.0120 (6) N2 1.1543 (3) 1.0443 (3) 0.42603 (19) 0.0121 (6) C1 1.1756 (4) 1.0038 (4) 0.3613 (2) 0.0141 (7) H1A 1.1107 0.9401 0.3323 0.017\ C2 1.3758 (4) 1.1697 (4) 0.4169 (2) 0.0161 (7) H2A 1.4589 1.2296 0.4310 0.019\* C3 1.2677 (4) 1.1394 (4) 0.4572 (2) 0.0132 (7) C4 1.2524 (4) 1.1950 (4) 0.5268 (2) 0.0127 (7) C5 1.3381 (4) 1.2906 (4) 0.5716 (3) 0.0185 (8) H5A 1.4262 1.3361 0.5639 0.022\* C6 1.1159 (4) 1.1969 (4) 0.6109 (2) 0.0154 (7) H6A 1.0383 1.1732 0.6345 0.019\* ----- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e942 .table-wrap} ----- -------------- -------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0213 (2) 0.0518 (3) 0.0176 (2) 0.0201 (2) 0.00229 (16) −0.0064 (2) Br2 0.01593 (18) 0.01593 (18) 0.0102 (3) 0.00796 (9) 0.000 0.000 Br3 0.01604 (19) 0.01604 (19) 0.0124 (3) 0.00802 (9) 0.000 0.000 Fe1 0.0096 (2) 0.0096 (2) 0.0090 (4) 0.00479 (11) 0.000 0.000 Fe2 0.0153 (3) 0.0153 (3) 0.0099 (4) 0.00764 (13) 0.000 0.000 S1 0.0184 (4) 0.0170 (4) 0.0170 (5) 0.0072 (4) −0.0042 (4) −0.0073 (4) S2 0.0162 (4) 0.0198 (4) 0.0128 (4) 0.0107 (3) 0.0037 (3) 0.0013 (3) N1 0.0113 (13) 0.0118 (14) 0.0122 (14) 0.0052 (12) 0.0016 (11) 0.0003 (11) N2 0.0143 (14) 0.0143 (14) 0.0102 (13) 0.0090 (12) 0.0021 (12) 0.0016 (12) C1 0.0135 (16) 0.0138 (16) 0.0157 (17) 0.0074 (14) 0.0000 (13) −0.0008 (13) C2 0.0161 (16) 0.0175 (17) 0.0139 (18) 0.0078 (14) 0.0027 (14) 0.0035 (14) C3 0.0173 (17) 0.0131 (15) 0.0134 (16) 0.0106 (14) 0.0009 (13) 0.0036 (13) C4 0.0156 (16) 0.0101 (15) 0.0126 (16) 0.0065 (13) 0.0010 (13) 0.0001 (12) C5 0.0168 (17) 0.0198 (19) 0.0192 (19) 0.0092 (15) −0.0020 (14) −0.0002 (15) C6 0.0135 (16) 0.0148 (17) 0.0151 (17) 0.0048 (13) −0.0024 (14) −0.0020 (13) ----- -------------- -------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1228 .table-wrap} -------------------------- ------------- -------------------- ------------ Fe1---N1 1.962 (3) N2---C1 1.320 (5) Fe1---N2 1.974 (3) N2---C3 1.385 (5) Fe2---Br1 2.3348 (5) C1---H1A 0.9300 Fe2---Br2 2.3370 (12) C2---C3 1.366 (6) S1---C6 1.706 (4) C2---H2A 0.9300 S1---C5 1.721 (4) C3---C4 1.458 (5) S2---C1 1.706 (4) C4---C5 1.355 (6) S2---C2 1.720 (4) C5---H5A 0.9300 N1---C6 1.312 (5) C6---H6A 0.9300 N1---C4 1.396 (5) N1---Fe1---N1^i^ 91.50 (14) C6---N1---Fe1 133.8 (3) N1---Fe1---N1^ii^ 91.50 (14) C4---N1---Fe1 115.4 (3) N1^i^---Fe1---N1^ii^ 91.50 (14) C1---N2---C3 111.0 (3) N1---Fe1---N2^i^ 171.87 (13) C1---N2---Fe1 134.5 (3) N1^i^---Fe1---N2^i^ 82.00 (14) C3---N2---Fe1 114.6 (3) N1^ii^---Fe1---N2^i^ 93.53 (13) N2---C1---S2 113.8 (3) N1---Fe1---N2 82.00 (14) N2---C1---H1A 123.1 N1^i^---Fe1---N2 93.53 (13) S2---C1---H1A 123.1 N1^ii^---Fe1---N2 171.87 (13) C3---C2---S2 108.8 (3) N2^i^---Fe1---N2 93.49 (14) C3---C2---H2A 125.6 N1---Fe1---N2^ii^ 93.53 (13) S2---C2---H2A 125.6 N1^i^---Fe1---N2^ii^ 171.87 (14) C2---C3---N2 115.4 (3) N1^ii^---Fe1---N2^ii^ 82.00 (14) C2---C3---C4 129.9 (4) N2^i^---Fe1---N2^ii^ 93.49 (14) N2---C3---C4 114.7 (3) N2---Fe1---N2^ii^ 93.49 (14) C5---C4---N1 115.0 (4) Br1^iii^---Fe2---Br1^iv^ 110.29 (3) C5---C4---C3 131.9 (4) Br1^iii^---Fe2---Br1 110.29 (3) N1---C4---C3 113.0 (3) Br1^iv^---Fe2---Br1 110.29 (3) C4---C5---S1 109.5 (3) Br1^iii^---Fe2---Br2 108.64 (3) C4---C5---H5A 125.2 Br1^iv^---Fe2---Br2 108.64 (3) S1---C5---H5A 125.2 Br1---Fe2---Br2 108.64 (3) N1---C6---S1 114.3 (3) C6---S1---C5 90.4 (2) N1---C6---H6A 122.8 C1---S2---C2 91.01 (19) S1---C6---H6A 122.8 C6---N1---C4 110.7 (3) N1^i^---Fe1---N1---C6 −86.9 (3) S2---C2---C3---N2 1.7 (4) N1^ii^---Fe1---N1---C6 4.6 (4) S2---C2---C3---C4 −175.8 (3) N2---Fe1---N1---C6 179.8 (4) C1---N2---C3---C2 −1.2 (5) N2^ii^---Fe1---N1---C6 86.7 (4) Fe1---N2---C3---C2 178.8 (3) N1^i^---Fe1---N1---C4 88.3 (3) C1---N2---C3---C4 176.7 (3) N1^ii^---Fe1---N1---C4 179.8 (3) Fe1---N2---C3---C4 −3.3 (4) N2---Fe1---N1---C4 −5.1 (3) C6---N1---C4---C5 −1.7 (5) N2^ii^---Fe1---N1---C4 −98.1 (3) Fe1---N1---C4---C5 −178.0 (3) N1---Fe1---N2---C1 −175.5 (4) C6---N1---C4---C3 −179.1 (3) N1^i^---Fe1---N2---C1 93.5 (4) Fe1---N1---C4---C3 4.7 (4) N2^i^---Fe1---N2---C1 11.3 (4) C2---C3---C4---C5 −0.2 (7) N2^ii^---Fe1---N2---C1 −82.4 (3) N2---C3---C4---C5 −177.7 (4) N1---Fe1---N2---C3 4.6 (3) C2---C3---C4---N1 176.7 (4) N1^i^---Fe1---N2---C3 −86.5 (3) N2---C3---C4---N1 −0.8 (5) N2^i^---Fe1---N2---C3 −168.6 (3) N1---C4---C5---S1 1.4 (5) N2^ii^---Fe1---N2---C3 97.6 (3) C3---C4---C5---S1 178.2 (3) C3---N2---C1---S2 0.0 (4) C6---S1---C5---C4 −0.6 (3) Fe1---N2---C1---S2 −180.0 (2) C4---N1---C6---S1 1.2 (4) C2---S2---C1---N2 0.8 (3) Fe1---N1---C6---S1 176.5 (2) C1---S2---C2---C3 −1.4 (3) C5---S1---C6---N1 −0.3 (3) -------------------------- ------------- -------------------- ------------ ::: Symmetry codes: (i) −x+y+1, −x+2, z; (ii) −y+2, x−y+1, z; (iii) −y+1, x−y+1, z; (iv) −x+y, −x+1, z. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1938 .table-wrap} ---------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C2---H2A···Br3 0.93 2.81 3.665 (5) 153 C5---H5A···Br3 0.93 2.97 3.798 (5) 149 ---------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: ----------- ------------- Fe1---N1 1.962 (3) Fe1---N2 1.974 (3) Fe2---Br1 2.3348 (5) Fe2---Br2 2.3370 (12) ----------- ------------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- C2---H2A⋯Br3 0.93 2.81 3.665 (5) 153 C5---H5A⋯Br3 0.93 2.97 3.798 (5) 149 :::	PubMed Central	2024-06-05T04:04:18.726397	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052137/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m311-m312", "authors": [ { "first": "Anita", "last": "Abedi" }, { "first": "Vahid", "last": "Amani" }, { "first": "Nasser", "last": "Safari" } ] }
PMC3052138	Related literature {#sec1} ================== For the appications of phthalimides and N-substituted phthalimides, see: Lima et al. (2002[@bb3]). For a related structure, see: Liang (2008[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~4~H~14~N~2~ ^2+^·2C~9~H~7~O~4~ ^−^·2H~2~OM ~r~ = 484.50Monoclinic,a = 14.0344 (15) Åb = 8.6746 (9) Åc = 10.2304 (11) Åβ = 95.620 (1)°V = 1239.5 (2) Å^3^Z = 2Mo Kα radiationμ = 0.10 mm^−1^T = 298 K0.50 × 0.48 × 0.47 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 1997[@bb1]) T ~min~ = 0.950, T ~max~ = 0.9536001 measured reflections2178 independent reflections1601 reflections with I \> 2σ(I)R ~int~ = 0.037 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.123S = 1.072178 reflections157 parametersH-atom parameters constrainedΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e503} Data collection: SMART (Bruker, 1997[@bb1]); cell refinement: SAINT (Bruker, 1997[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb4]) and PLATON (Spek, 2009[@bb5]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003618/lh5202sup1.cif](http://dx.doi.org/10.1107/S1600536811003618/lh5202sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003618/lh5202Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003618/lh5202Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5202&file=lh5202sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5202sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5202&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5202](http://scripts.iucr.org/cgi-bin/sendsup?lh5202)). The author thanks the Shandong Provincial Natural Science Foundation, China (ZR2009BL027). Comment ======= Phthalimides and N-substituted phthalimides are animportant class of compounds because of their interesting biological activities (Lima et al., 2002). 2-(Methoxycarbonyl)benzoic acid is an intermediate in the preparation of N-substituted phthalimides. In this paper, the structure of the title compound is reported. The asymmetric unit of the title compound (I) contains one half a butane-1,4-diaminium cation, a 2-(methoxycarbonyl)benzoate anion and a solvent water molecule (Fig. 1). The bond lengths and angles agree with those in ethane-1,2-diaminium 2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate methanol solvate (Liang, 2008). In the crystal, intermolecular N---H···O and O---H···O hydrogen bonds link the components of the structure into two-dimensional layers parallel to (100) (Fig. 2 and Table 1). Addtional stabilization within these layers is provided by weak intermolecular C---H···O hydrogen bonds. Experimental {#experimental} ============ A mixture of phthalic anhydride (1.52 g, 0.01 mol) and methanol (15 ml) was refluxed for 0.5 h. 1,4-Butanediamine (0.44 g, 0.005 mol) was added to the above solution and mixed for 10 min at room temperature. The solution was kept at room temperature for 5 d. Natural evaporation gave colourless single crystals of the title compound, suitable for X-ray analysis. Refinement {#refinement} ========== H atoms were initially located in difference maps and then refined in a riding-model approximation with C---H = 0.93--0.97 Å, N---H = 0.89 Å, O---H = 0.82Å and U~iso~(H) = 1.2U~eq~(C, O) or 1.5U~eq~(N, methyl C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of (I), drawn with 30% probability ellipsoids. ::: ![](e-67-0o587-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure of the title compound with hydrogen bonds shown as dashed lines. Only H atoms involved in hydrogen bonds are shown. ::: ![](e-67-0o587-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e113 .table-wrap} ------------------------------------------- --------------------------------------- C~4~H~14~N~2~^2+^·2C~9~H~7~O~4~^−^·2H~2~O F(000) = 516 M~r~ = 484.50 D~x~ = 1.298 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 2198 reflections a = 14.0344 (15) Å θ = 2.8--27.5° b = 8.6746 (9) Å µ = 0.10 mm^−1^ c = 10.2304 (11) Å T = 298 K β = 95.620 (1)° Block, colorless V = 1239.5 (2) Å^3^ 0.50 × 0.48 × 0.47 mm Z = 2 ------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e259 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART CCD diffractometer 2178 independent reflections Radiation source: fine-focus sealed tube 1601 reflections with I \> 2σ(I) graphite R~int~ = 0.037 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.8° Absorption correction: multi-scan (SADABS; Bruker, 1997) h = −12→16 T~min~ = 0.950, T~max~ = 0.953 k = −10→10 6001 measured reflections l = −10→12 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.043 H-atom parameters constrained wR(F^2^) = 0.123 w = 1/\[σ^2^(F~o~^2^) + (0.0556P)^2^ + 0.314P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.07 (Δ/σ)~max~ \< 0.001 2178 reflections Δρ~max~ = 0.17 e Å^−3^ 157 parameters Δρ~min~ = −0.20 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.118 (8) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e557 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e656 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ N1 0.44862 (11) 0.25834 (17) 0.79462 (15) 0.0369 (4) H1A 0.5061 0.2597 0.7647 0.055\ H1B 0.4252 0.3537 0.7944 0.055\* H1C 0.4094 0.1986 0.7432 0.055\* O1 0.13265 (10) 0.39089 (19) 0.54038 (16) 0.0622 (5) O2 0.28346 (10) 0.43510 (19) 0.61583 (16) 0.0596 (5) O3 0.37929 (10) 0.54277 (15) 0.88018 (14) 0.0458 (4) O4 0.35667 (9) 0.74614 (15) 0.74950 (14) 0.0479 (4) O5 0.33244 (12) 0.04093 (17) 0.63792 (15) 0.0628 (5) H5C 0.3453 0.0256 0.5595 0.075\* H5D 0.3382 −0.0443 0.6790 0.075\* C1 0.19982 (14) 0.4525 (2) 0.62583 (19) 0.0376 (5) C2 0.32751 (13) 0.6373 (2) 0.81441 (18) 0.0342 (4) C3 0.15919 (12) 0.5400 (2) 0.73169 (18) 0.0351 (5) C4 0.22064 (13) 0.6245 (2) 0.82091 (18) 0.0344 (5) C5 0.18168 (15) 0.7007 (2) 0.9231 (2) 0.0490 (6) H5 0.2216 0.7570 0.9833 0.059\* C6 0.08535 (16) 0.6941 (3) 0.9366 (2) 0.0587 (6) H6 0.0608 0.7457 1.0056 0.070\* C7 0.02511 (16) 0.6117 (3) 0.8485 (2) 0.0565 (6) H7 −0.0401 0.6075 0.8579 0.068\* C8 0.06155 (14) 0.5354 (2) 0.7462 (2) 0.0469 (5) H8 0.0206 0.4804 0.6863 0.056\* C9 0.16701 (18) 0.2992 (4) 0.4371 (3) 0.0783 (9) H9A 0.2048 0.3625 0.3851 0.117\* H9B 0.1135 0.2580 0.3825 0.117\* H9C 0.2055 0.2161 0.4751 0.117\* C10 0.45726 (13) 0.1967 (2) 0.93045 (17) 0.0337 (4) H10A 0.3955 0.2014 0.9654 0.040\* H10B 0.5020 0.2592 0.9860 0.040\* C11 0.49175 (14) 0.0324 (2) 0.93138 (17) 0.0353 (5) H11A 0.5510 0.0274 0.8901 0.042\* H11B 0.4447 −0.0306 0.8801 0.042\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1097 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ N1 0.0428 (9) 0.0320 (8) 0.0361 (9) 0.0064 (7) 0.0048 (7) 0.0075 (7) O1 0.0412 (8) 0.0820 (12) 0.0614 (11) −0.0001 (8) −0.0048 (7) −0.0318 (9) O2 0.0391 (9) 0.0752 (11) 0.0644 (11) −0.0021 (7) 0.0052 (7) −0.0322 (9) O3 0.0441 (8) 0.0439 (8) 0.0481 (9) 0.0115 (6) −0.0026 (6) 0.0025 (7) O4 0.0462 (9) 0.0374 (8) 0.0612 (10) −0.0023 (6) 0.0106 (7) 0.0063 (7) O5 0.0936 (13) 0.0428 (8) 0.0488 (10) −0.0037 (8) −0.0094 (8) 0.0011 (7) C1 0.0365 (11) 0.0357 (10) 0.0398 (11) −0.0011 (8) 0.0001 (8) −0.0013 (8) C2 0.0391 (10) 0.0279 (9) 0.0351 (10) 0.0004 (8) 0.0008 (8) −0.0071 (8) C3 0.0352 (10) 0.0325 (10) 0.0374 (11) 0.0026 (8) 0.0023 (8) 0.0043 (8) C4 0.0382 (10) 0.0275 (9) 0.0372 (11) 0.0038 (8) 0.0024 (8) 0.0037 (8) C5 0.0479 (13) 0.0505 (12) 0.0486 (13) 0.0046 (10) 0.0041 (10) −0.0111 (10) C6 0.0530 (14) 0.0701 (15) 0.0548 (15) 0.0104 (12) 0.0146 (11) −0.0149 (12) C7 0.0386 (12) 0.0694 (15) 0.0634 (15) 0.0079 (11) 0.0144 (10) −0.0010 (13) C8 0.0378 (11) 0.0493 (12) 0.0530 (14) −0.0004 (9) 0.0014 (9) 0.0017 (10) C9 0.0604 (16) 0.101 (2) 0.0702 (19) 0.0054 (14) −0.0111 (13) −0.0481 (16) C10 0.0425 (11) 0.0302 (9) 0.0286 (10) 0.0033 (8) 0.0044 (8) 0.0020 (8) C11 0.0457 (11) 0.0307 (9) 0.0295 (10) 0.0041 (8) 0.0035 (8) 0.0007 (8) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1434 .table-wrap} ------------------- -------------- ------------------------- ------------- N1---C10 1.483 (2) C5---C6 1.373 (3) N1---H1A 0.8900 C5---H5 0.9300 N1---H1B 0.8900 C6---C7 1.374 (3) N1---H1C 0.8900 C6---H6 0.9300 O1---C1 1.333 (2) C7---C8 1.378 (3) O1---C9 1.443 (3) C7---H7 0.9300 O2---C1 1.198 (2) C8---H8 0.9300 O3---C2 1.248 (2) C9---H9A 0.9600 O4---C2 1.246 (2) C9---H9B 0.9600 O5---H5C 0.8500 C9---H9C 0.9600 O5---H5D 0.8500 C10---C11 1.505 (2) C1---C3 1.481 (3) C10---H10A 0.9700 C2---C4 1.512 (3) C10---H10B 0.9700 C3---C8 1.393 (3) C11---C11^i^ 1.509 (3) C3---C4 1.400 (3) C11---H11A 0.9700 C4---C5 1.393 (3) C11---H11B 0.9700 C10---N1---H1A 109.5 C7---C6---H6 119.9 C10---N1---H1B 109.5 C6---C7---C8 119.8 (2) H1A---N1---H1B 109.5 C6---C7---H7 120.1 C10---N1---H1C 109.5 C8---C7---H7 120.1 H1A---N1---H1C 109.5 C7---C8---C3 120.6 (2) H1B---N1---H1C 109.5 C7---C8---H8 119.7 C1---O1---C9 115.83 (17) C3---C8---H8 119.7 H5C---O5---H5D 108.2 O1---C9---H9A 109.5 O2---C1---O1 121.97 (18) O1---C9---H9B 109.5 O2---C1---C3 125.28 (17) H9A---C9---H9B 109.5 O1---C1---C3 112.75 (16) O1---C9---H9C 109.5 O4---C2---O3 125.51 (18) H9A---C9---H9C 109.5 O4---C2---C4 117.28 (16) H9B---C9---H9C 109.5 O3---C2---C4 117.10 (16) N1---C10---C11 110.12 (14) C8---C3---C4 119.66 (18) N1---C10---H10A 109.6 C8---C3---C1 121.09 (17) C11---C10---H10A 109.6 C4---C3---C1 119.22 (16) N1---C10---H10B 109.6 C5---C4---C3 118.40 (17) C11---C10---H10B 109.6 C5---C4---C2 117.51 (17) H10A---C10---H10B 108.2 C3---C4---C2 124.08 (16) C10---C11---C11^i^ 112.22 (19) C6---C5---C4 121.2 (2) C10---C11---H11A 109.2 C6---C5---H5 119.4 C11^i^---C11---H11A 109.2 C4---C5---H5 119.4 C10---C11---H11B 109.2 C5---C6---C7 120.3 (2) C11^i^---C11---H11B 109.2 C5---C6---H6 119.9 H11A---C11---H11B 107.9 C9---O1---C1---O2 1.4 (3) O3---C2---C4---C5 86.2 (2) C9---O1---C1---C3 −177.8 (2) O4---C2---C4---C3 90.4 (2) O2---C1---C3---C8 −170.6 (2) O3---C2---C4---C3 −93.2 (2) O1---C1---C3---C8 8.6 (3) C3---C4---C5---C6 −0.2 (3) O2---C1---C3---C4 7.4 (3) C2---C4---C5---C6 −179.6 (2) O1---C1---C3---C4 −173.44 (17) C4---C5---C6---C7 −0.1 (4) C8---C3---C4---C5 0.7 (3) C5---C6---C7---C8 0.0 (4) C1---C3---C4---C5 −177.31 (17) C6---C7---C8---C3 0.5 (3) C8---C3---C4---C2 −179.96 (17) C4---C3---C8---C7 −0.8 (3) C1---C3---C4---C2 2.1 (3) C1---C3---C8---C7 177.12 (19) O4---C2---C4---C5 −90.2 (2) N1---C10---C11---C11^i^ 176.08 (19) ------------------- -------------- ------------------------- ------------- ::: Symmetry codes: (i) −x+1, −y, −z+2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1979 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···O4^ii^ 0.89 1.95 2.815 (2) 164 N1---H1B···O3 0.89 2.00 2.823 (2) 154 N1---H1C···O5 0.89 1.99 2.876 (2) 172 O5---H5C···O3^iii^ 0.85 2.03 2.873 (2) 172 O5---H5D···O4^iv^ 0.85 1.96 2.808 (2) 172 C11---H11A···O2^ii^ 0.97 2.46 3.346 (2) 151 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −x+1, y−1/2, −z+3/2; (iii) x, −y+1/2, z−1/2; (iv) x, y−1, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- --------- ------- ----------- ------------- N1---H1A⋯O4^i^ 0.89 1.95 2.815 (2) 164 N1---H1B⋯O3 0.89 2.00 2.823 (2) 154 N1---H1C⋯O5 0.89 1.99 2.876 (2) 172 O5---H5C⋯O3^ii^ 0.85 2.03 2.873 (2) 172 O5---H5D⋯O4^iii^ 0.85 1.96 2.808 (2) 172 C11---H11A⋯O2^i^ 0.97 2.46 3.346 (2) 151 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.731207	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052138/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o587", "authors": [ { "first": "Jian", "last": "Li" } ] }
PMC3052139	Related literature {#sec1} ================== For the related [l]{.smallcaps}-serine methyl ester hydrochloride, see: Schouten & Lutz (2009[@bb6]). For the theory of twin formation, see: Cahn (1954[@bb1]). Twin integration is based on Schreurs et al. (2010[@bb8]) and the twin refinement on Herbst-Irmer & Sheldrick (2002[@bb3]). The methods of Flack (1983[@bb2]) and Hooft et al. (2008[@bb4]) were used for the absolute structure determination. Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~4~H~10~NO~2~ ^+^·Cl^−^·H~2~OM ~r~ = 157.60Triclinic,a = 4.9461 (4) Åb = 6.0134 (4) Åc = 6.6853 (5) Åα = 101.833 (4)°β = 93.533 (3)°γ = 92.112 (4)°V = 194.00 (2) Å^3^Z = 1Mo Kα radiationμ = 0.44 mm^−1^T = 110 K0.39 × 0.29 × 0.12 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (TWINABS-2008/4; Sheldrick, 2008a [@bb9]) T ~min~ = 0.69, T ~max~ = 0.7511388 measured reflections3213 independent reflections3180 reflections with I \> 2σ(I)R ~int~ = 0.019 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.015wR(F ^2^) = 0.043S = 1.053213 reflections133 parameters3 restraintsAll H-atom parameters refinedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.13 e Å^−3^ {#d5e520} Data collection: COLLECT (Nonius, 1999[@bb5]); cell refinement: PEAKREF (Schreurs, 2008[@bb7]); data reduction: Eval15 (Schreurs et al., 2010[@bb8]) and TWINABS-2008/4 (Sheldrick, 2008a [@bb9]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b [@bb10]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008b [@bb10]); molecular graphics: PLATON (Spek, 2009[@bb11]); software used to prepare material for publication: manual editing of SHELXL CIF file. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100420X/ez2229sup1.cif](http://dx.doi.org/10.1107/S160053681100420X/ez2229sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100420X/ez2229Isup2.hkl](http://dx.doi.org/10.1107/S160053681100420X/ez2229Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2229&file=ez2229sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2229sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2229&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2229](http://scripts.iucr.org/cgi-bin/sendsup?ez2229)). Comment ======= In the context of our ongoing studies of absolute structure determinations of hydrochlorides of amino acid esters, we determined the structure of the title compound (I). The related L-serine methyl ester hydrochloride (Schouten & Lutz, 2009) has an extended backbone with O--C--C--N and C--O--C--C torsion angles of -175.99 (7) and 179.72 (7)°, respectively. In (I), the O--C--C--N torsion angle is 155.83 (6)° indicating a significant deviation from an extended backbone. The C--O--C--C torsion angle of 177.22 (6)° is again close to a trans conformation (Fig. 1). Two H atoms of the ammonium moiety are involved in hydrogen bonds with chloride anions as acceptors. This results in a one-dimensional chain in the a-direction. These two hydrogen bonds have significantly different lengths: the N1···Cl1 distance is 3.3007 (7) Å, while the N1···Cl1 (x - 1, y, z) distance is 3.1665 (6) Å. The third ammonium H atom is hydrogen bonded to the co-crystallized lattice water molecule, which itself donates two hydrogen bonds to chlorides. The water thus links the one-dimensional chains into a two-dimensional network, which is parallel to the a,c-plane (Fig. 2). In the b-direction the hydrogen bonded layers of the ammonium moieties, chloride anions and lattice water molecules are alternating with the organic part of the alanine methyl ester. The O atoms of the ester functionality are not involved in strong intermolecular interactions, but there is a weak C---H···O bond with the ester O2 as acceptor (Table 1). The crystal of (I) appeared to be twinned with a twofold rotation about hkl=(0,0,1) as twin operation. This twin relation was taken into account during the intensity integration with Eval15 (Schreurs et al., 2010) and the refinement (Herbst-Irmer & Sheldrick, 2002). As can easily be verified in Fig. 2, the twinning operation results in reversed stacking of the two-dimensional hydrogen bonded networks. At the twinning boundaries the polar and ionic groups involved in the hydrogen bonds must approach each other in the direction of the b axis and the alternation of polar and apolar moieties is broken. These stacking faults might be accompanied by shifts of the layers for a better structural fit. Such dislocations often depend on the way the twin was generated (Cahn, 1954), which has not been investigated in the present study of (I). In the macroscopic shape of the crystal of (I), faces hkl=(0,0,1) and (0,0,1) have the smallest dimensions. For the determination of the absolute structure, reflections with inverted indices were introduced into the dataset using the TWINABS software (Sheldrick, 2008a). Thus there were in total four twin domains included in the refinement. The corresponding twin fractions refined to 0.86 (2) and 0.104 (4) for the non-merohedral domains, and 0.03 (2) and 0.005 (4) for the corresponding inverted domains. The latter values are very close to zero and we can consider the enantiopurity as proven, but it should be noted that the two twin fractions of the inverted domains are in the least-squares refinement highly correlated with each other (correlation -0.999). Because of this correlation we also performed a single-crystal refinement only on the non-overlapping reflections of the major twin domain. This dataset has a completeness of 82% (1447 unique reflections) and the coverage of Bijvoet pairs is 80% (712 pairs). Here, the Flack parameter (Flack, 1983) refined to a value of x=0.04 (3). On these data also an analysis according to Hooft et al. (2008) was performed. Assuming a Gaussian distribution of σ(I) the absolute structure parameter was calculated as y=0.044 (9). A plot of the Bijvoet differences is shown in Fig. 3. Experimental {#experimental} ============ Crystalline L-alanine methyl ester (Aldrich) was dissolved in technical ethanol. Evaporation at room temperature resulted in a viscous liquid. Crystallization was initiated by adding a seed crystal of the crystalline starting material. Refinement {#refinement} ========== The data set in HKLF-5 format (Herbst-Irmer & Sheldrick, 2002) contains non-overlapping reflections of both twin components, respectively, together with the overlapping reflections. Equivalent reflections were merged with TWINABS (Sheldrick, 2008a) prior to the least-squares refinement. The same software was used to introduce the inverted reflections for the absolute structure determination. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms. ::: ![](e-67-0o586-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Formation of two-dimensional sheets parallel to (010) by hydrogen bonding in (I). Hydrogen bonds are drawn as dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o586-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Bijvoet pairs in the non-overlapping reflections of the major twin component in (I). Scatter plot prepared by PLATON (Spek, 2009). 622 pairs are shown with Δobs \> 0.25σ(Δobs). 534 Reflections confirming the absolute structure are drawn in black. 88 Reflections with the wrong sign are shown in red. ::: ![](e-67-0o586-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e177 .table-wrap} ------------------------------- --------------------------------------- C~4~H~10~NO~2~^+^·Cl^−^·H~2~O Z = 1 M~r~ = 157.60 F(000) = 84 Triclinic, P1 D~x~ = 1.349 Mg m^−3^ Hall symbol: P 1 Mo Kα radiation, λ = 0.71073 Å a = 4.9461 (4) Å Cell parameters from 5169 reflections b = 6.0134 (4) Å θ = 3.5--27.5° c = 6.6853 (5) Å µ = 0.44 mm^−1^ α = 101.833 (4)° T = 110 K β = 93.533 (3)° Plate, colourless γ = 92.112 (4)° 0.39 × 0.29 × 0.12 mm V = 194.00 (2) Å^3^ ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e319 .table-wrap} ------------------------------------------------------------------------ -------------------------------------- Nonius KappaCCD diffractometer 3213 independent reflections Radiation source: rotating anode 3180 reflections with I \> 2σ(I) graphite R~int~ = 0.019 φ and ω scans θ~max~ = 27.7°, θ~min~ = 3.1° Absorption correction: multi-scan (TWINABS-2008/4; Sheldrick, 2008a) h = −6→6 T~min~ = 0.69, T~max~ = 0.75 k = −7→7 11388 measured reflections l = −8→8 ------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e436 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.015 Hydrogen site location: difference Fourier map wR(F^2^) = 0.043 All H-atom parameters refined S = 1.05 w = 1/\[σ^2^(F~o~^2^) + (0.0283P)^2^ + 0.0041P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3213 reflections (Δ/σ)~max~ = 0.005 133 parameters Δρ~max~ = 0.20 e Å^−3^ 3 restraints Δρ~min~ = −0.13 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e593 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e692 .table-wrap} ----- --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.52552 (12) 0.30665 (9) 0.60201 (9) 0.01877 (12) O2 0.74232 (12) 0.64013 (9) 0.59202 (9) 0.01863 (12) N1 0.29086 (13) 0.79507 (11) 0.43187 (9) 0.01456 (12) H1N 0.447 (2) 0.8444 (16) 0.3859 (16) 0.018 (2)\ H2N 0.143 (2) 0.8271 (19) 0.3614 (17) 0.021 (3)\* H3N 0.284 (2) 0.8560 (18) 0.5673 (18) 0.021 (2)\* C1 0.54988 (14) 0.50654 (11) 0.54561 (10) 0.01343 (14) C2 0.30541 (15) 0.54425 (12) 0.41118 (12) 0.01473 (14) H2 0.150 (2) 0.4952 (16) 0.4556 (15) 0.016 (2)\* C3 0.3288 (2) 0.42892 (16) 0.18812 (15) 0.02366 (18) H3A 0.171 (3) 0.452 (2) 0.110 (2) 0.047 (4)\* H3B 0.494 (4) 0.489 (3) 0.146 (3) 0.060 (5)\* H3C 0.331 (2) 0.273 (2) 0.1796 (19) 0.031 (3)\* C4 0.75776 (19) 0.25176 (15) 0.72382 (14) 0.02231 (18) H4A 0.909 (3) 0.225 (2) 0.644 (2) 0.040 (3)\* H4B 0.695 (4) 0.118 (3) 0.779 (3) 0.064 (4)\* H4C 0.819 (4) 0.360 (3) 0.821 (3) 0.052 (4)\* Cl1 0.793162 (15) 0.934964 (15) 0.171315 (15) 0.01891 (5) O3 0.26844 (13) 0.86392 (12) 0.85023 (9) 0.02491 (13) H1O 0.415 (4) 0.880 (3) 0.930 (3) 0.057 (5)\* H2O 0.133 (3) 0.878 (2) 0.912 (2) 0.044 (4)\* ----- --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e981 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0167 (3) 0.0218 (3) 0.0201 (3) −0.0007 (2) −0.0021 (2) 0.0111 (2) O2 0.0107 (3) 0.0205 (3) 0.0253 (3) 0.0016 (2) −0.0013 (2) 0.0067 (2) N1 0.0123 (3) 0.0188 (3) 0.0132 (3) 0.0052 (2) 0.0008 (2) 0.0038 (2) C1 0.0107 (4) 0.0182 (3) 0.0123 (3) 0.0038 (3) 0.0042 (3) 0.0038 (3) C2 0.0098 (3) 0.0180 (3) 0.0176 (3) 0.0008 (2) 0.0007 (3) 0.0066 (3) C3 0.0296 (6) 0.0195 (3) 0.0186 (4) 0.0036 (3) −0.0074 (4) −0.0013 (3) C4 0.0195 (4) 0.0277 (4) 0.0231 (4) 0.0026 (3) −0.0034 (4) 0.0143 (3) Cl1 0.01091 (8) 0.03258 (8) 0.01630 (8) 0.00378 (5) 0.00140 (5) 0.01156 (6) O3 0.0129 (3) 0.0475 (4) 0.0132 (3) 0.0008 (3) 0.0011 (2) 0.0038 (2) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1173 .table-wrap} ------------------- ------------- ------------------- ------------ O1---C1 1.3351 (8) C2---H2 0.901 (11) O1---C4 1.4541 (10) C3---H3A 0.939 (14) O2---C1 1.2052 (9) C3---H3B 0.961 (18) N1---C2 1.4909 (9) C3---H3C 0.930 (12) N1---H1N 0.909 (11) C4---H4A 0.947 (14) N1---H2N 0.895 (12) C4---H4B 1.001 (17) N1---H3N 0.908 (12) C4---H4C 0.854 (18) C1---C2 1.5137 (10) O3---H1O 0.860 (18) C2---C3 1.5236 (12) O3---H2O 0.808 (17) C1---O1---C4 115.00 (6) C3---C2---H2 109.9 (6) C2---N1---H1N 106.5 (6) C2---C3---H3A 109.1 (9) C2---N1---H2N 110.3 (7) C2---C3---H3B 107.1 (10) H1N---N1---H2N 112.5 (10) H3A---C3---H3B 114.5 (13) C2---N1---H3N 107.0 (7) C2---C3---H3C 108.4 (8) H1N---N1---H3N 110.0 (10) H3A---C3---H3C 105.7 (11) H2N---N1---H3N 110.2 (10) H3B---C3---H3C 111.9 (12) O2---C1---O1 125.01 (7) O1---C4---H4A 110.8 (9) O2---C1---C2 123.63 (6) O1---C4---H4B 105.5 (10) O1---C1---C2 111.36 (6) H4A---C4---H4B 113.8 (13) N1---C2---C1 106.75 (6) O1---C4---H4C 114.3 (11) N1---C2---C3 110.50 (6) H4A---C4---H4C 102.3 (14) C1---C2---C3 111.57 (6) H4B---C4---H4C 110.4 (15) N1---C2---H2 106.5 (6) H1O---O3---H2O 112.9 (15) C1---C2---H2 111.5 (6) C4---O1---C1---O2 −1.75 (11) O1---C1---C2---N1 155.83 (6) C4---O1---C1---C2 177.22 (6) O2---C1---C2---C3 95.64 (9) O2---C1---C2---N1 −25.18 (9) O1---C1---C2---C3 −83.35 (8) ------------------- ------------- ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1448 .table-wrap} --------------------- ------------ ------------ ------------ --------------- D---H···A D---H H···A D···A D---H···A N1---H1N···Cl1 0.909 (11) 2.418 (11) 3.3007 (7) 163.9 (9) N1---H2N···Cl1^i^ 0.895 (12) 2.275 (12) 3.1665 (6) 174.2 (10) N1---H3N···O3 0.908 (12) 1.888 (12) 2.7519 (9) 158.2 (9) O3---H1O···Cl1^ii^ 0.860 (18) 2.364 (18) 3.2220 (7) 175.1 (15) O3---H2O···Cl1^iii^ 0.808 (17) 2.470 (17) 3.2613 (7) 166.9 (14) C2---H2···O2^i^ 0.901 (11) 2.385 (10) 3.1302 (9) 140.0 (8) --------------------- ------------ ------------ ------------ --------------- ::: Symmetry codes: (i) x−1, y, z; (ii) x, y, z+1; (iii) x−1, y, z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- ------------ ------------ ------------ ------------- N1---H1N⋯Cl1 0.909 (11) 2.418 (11) 3.3007 (7) 163.9 (9) N1---H2N⋯Cl1^i^ 0.895 (12) 2.275 (12) 3.1665 (6) 174.2 (10) N1---H3N⋯O3 0.908 (12) 1.888 (12) 2.7519 (9) 158.2 (9) O3---H1O⋯Cl1^ii^ 0.860 (18) 2.364 (18) 3.2220 (7) 175.1 (15) O3---H2O⋯Cl1^iii^ 0.808 (17) 2.470 (17) 3.2613 (7) 166.9 (14) C2---H2⋯O2^i^ 0.901 (11) 2.385 (10) 3.1302 (9) 140.0 (8) Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.735791	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052139/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o586", "authors": [ { "first": "Martin", "last": "Lutz" }, { "first": "Arie", "last": "Schouten" } ] }
PMC3052140	Related literature {#sec1} ================== For the crystal structure of the tetradecyl-substituted analog, see: Dardouri et al. (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~21~H~20~ClN~3~O~3~M ~r~ = 397.85Triclinic,a = 8.1821 (1) Åb = 9.0741 (1) Åc = 13.3792 (2) Åα = 79.748 (1)°β = 80.142 (1)°γ = 85.910 (1)°V = 962.19 (2) Å^3^Z = 2Mo Kα radiationμ = 0.23 mm^−1^T = 295 K0.40 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Bruker X8 APEXII diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb4]) T ~min~ = 0.915, T ~max~ = 0.95619243 measured reflections4383 independent reflections4056 reflections with I \> 2σ(I)R ~int~ = 0.020 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.066wR(F ^2^) = 0.184S = 1.034383 reflections256 parametersH-atom parameters constrainedΔρ~max~ = 0.83 e Å^−3^Δρ~min~ = −0.44 e Å^−3^ {#d5e375} Data collection: APEX2 (Bruker, 2008[@bb2]); cell refinement: SAINT (Bruker, 2008[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: X-SEED (Barbour, 2001[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100657X/bt5479sup1.cif](http://dx.doi.org/10.1107/S160053681100657X/bt5479sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100657X/bt5479Isup2.hkl](http://dx.doi.org/10.1107/S160053681100657X/bt5479Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5479&file=bt5479sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5479sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5479&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5479](http://scripts.iucr.org/cgi-bin/sendsup?bt5479)). We thank Université Mohammed V-Agdal and the University of Malaya for supporting this study. Comment ======= The methylene part of 1,5-dimethyl-1,5-benzodiazepine-2,4-dione is relatively acidic, and one proton can be abstracted by using potassium t-butoxide; the resulting carbanion can undergo a nucleophlilic subsitution with a dibromoalkane to form 3-substituted derivatives. In a previous study, the compound was reacted with bromotetradecane to give the tetradecyl substitued derivative (Dardouri et al., 2011). The title compound was obtained by using p-chlorobenzaldoxime to react with the ally group to furnish the title isoxazolinyl derivative (Scheme I, Fig. 1). The seven-membered ring of C~21~H~20~ClN~3~O~3~ adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methine C atom as the prow). The substituent at the 3-position occupies an equatorial position. Experimental {#experimental} ============ To a solution of 3-allyl-1,5-dimethyl-1,5-benzodiazepine-2,4-dione (0.25 g, 1 mmol) and p-chlorobenzaldoxime (0.2 g, 1.3 mmol) in chloroform (10 ml) was added to a 4%solution of sodium hypochlorite solution (commerical bleach) (4 ml) at 273 K. Stirring was continued for 4 h. The organic layer was dried and the solvent evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel by using a mixture of hexane and ethyl acetate (1/1) as eluent. Colorless crystals were isolated when the solvent was allowed to evaporate. Refinement {#refinement} ========== H-atoms were placed in calculated positions (C---H 0.93--0.97 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2--1.5U~eq~(C). Omitted from the refinements were the following reflections because of being obscured by the beam stop and/or bad agreement between observed and calculated structure factors: (0 1 0), (1 1 0), (0 2 0), (2 3 0), (0 0 1), (1 1 1), (-1 1 2), (0 1 2) and (1 1 2). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of C21H20ClN3O3 at the 50% probability level; hydrogen atoms are drawn as arbitrary radius. ::: ![](e-67-0o720-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e135 .table-wrap} ----------------------- --------------------------------------- C~21~H~20~ClN~3~O~3~ Z = 2 M~r~ = 397.85 F(000) = 416 Triclinic, P1 D~x~ = 1.373 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.1821 (1) Å Cell parameters from 9887 reflections b = 9.0741 (1) Å θ = 3.0--30.7° c = 13.3792 (2) Å µ = 0.23 mm^−1^ α = 79.748 (1)° T = 295 K β = 80.142 (1)° Block, colorless γ = 85.910 (1)° 0.40 × 0.30 × 0.20 mm V = 962.19 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e271 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker X8 APEXII diffractometer 4383 independent reflections Radiation source: fine-focus sealed tube 4056 reflections with I \> 2σ(I) graphite R~int~ = 0.020 φ and ω scans θ~max~ = 27.5°, θ~min~ = 3.0° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −10→10 T~min~ = 0.915, T~max~ = 0.956 k = −11→11 19243 measured reflections l = −17→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.066 H-atom parameters constrained wR(F^2^) = 0.184 w = 1/\[σ^2^(F~o~^2^) + (0.1062P)^2^ + 0.889P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.03 (Δ/σ)~max~ = 0.001 4383 reflections Δρ~max~ = 0.83 e Å^−3^ 256 parameters Δρ~min~ = −0.44 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.046 (8) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e571 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- x* y z U~iso~\/U~eq~ Cl1 0.00333 (8) 0.14321 (7) 1.07254 (5) 0.0471 (2) O1 0.2880 (2) 1.2329 (2) 0.66476 (13) 0.0428 (4) O2 0.6469 (2) 1.2468 (2) 0.82002 (12) 0.0430 (4) O3 0.6108 (2) 0.79540 (18) 0.76659 (12) 0.0400 (4) N1 0.5122 (2) 1.2697 (2) 0.53908 (14) 0.0337 (4) N2 0.7763 (2) 1.2907 (2) 0.65440 (13) 0.0310 (4) N3 0.5112 (2) 0.6671 (2) 0.78978 (14) 0.0353 (4) C1 0.6816 (3) 1.2379 (2) 0.50002 (15) 0.0309 (4) C2 0.7216 (3) 1.2001 (3) 0.40171 (18) 0.0452 (6) H2 0.6374 1.1910 0.3647 0.054\ C3 0.8856 (4) 1.1760 (4) 0.35894 (19) 0.0504 (7) H3 0.9109 1.1522 0.2931 0.060\* C4 1.0116 (3) 1.1870 (3) 0.4132 (2) 0.0448 (6) H4 1.1216 1.1710 0.3839 0.054\* C5 0.9744 (3) 1.2219 (3) 0.51136 (18) 0.0360 (5) H5 1.0596 1.2275 0.5483 0.043\* C6 0.8100 (3) 1.2487 (2) 0.55536 (15) 0.0284 (4) C7 0.4069 (3) 1.3563 (3) 0.46807 (19) 0.0449 (6) H7A 0.3220 1.4127 0.5059 0.067\* H7B 0.3563 1.2889 0.4359 0.067\* H7C 0.4739 1.4237 0.4163 0.067\* C8 0.4365 (3) 1.2097 (2) 0.63486 (16) 0.0313 (4) C9 0.5486 (3) 1.1145 (2) 0.70220 (15) 0.0293 (4) H9 0.6178 1.0465 0.6616 0.035\* C10 0.6618 (3) 1.2213 (2) 0.73248 (15) 0.0301 (4) C11 0.8826 (3) 1.3976 (3) 0.6799 (2) 0.0437 (6) H11A 0.8160 1.4626 0.7216 0.065\* H11B 0.9365 1.4563 0.6177 0.065\* H11C 0.9648 1.3438 0.7173 0.065\* C12 0.4489 (3) 1.0212 (2) 0.79575 (16) 0.0307 (4) H12A 0.4059 1.0846 0.8463 0.037\* H12B 0.3551 0.9814 0.7752 0.037\* C13 0.5550 (3) 0.8928 (2) 0.84372 (16) 0.0326 (4) H13 0.6499 0.9304 0.8659 0.039\* C14 0.4547 (3) 0.7892 (2) 0.93283 (15) 0.0317 (4) H14A 0.5181 0.7544 0.9881 0.038\* H14B 0.3515 0.8382 0.9599 0.038\* C15 0.4243 (3) 0.6634 (2) 0.87944 (15) 0.0301 (4) C16 0.3142 (2) 0.5391 (2) 0.92464 (15) 0.0290 (4) C17 0.2745 (3) 0.4381 (3) 0.86525 (16) 0.0352 (5) H17 0.3144 0.4520 0.7950 0.042\* C18 0.1772 (3) 0.3186 (3) 0.90967 (18) 0.0367 (5) H18 0.1508 0.2523 0.8698 0.044\* C19 0.1190 (3) 0.2982 (2) 1.01501 (17) 0.0330 (4) C20 0.1526 (3) 0.3979 (2) 1.07529 (16) 0.0310 (4) H20 0.1109 0.3840 1.1453 0.037\* C21 0.2496 (3) 0.5188 (2) 1.02965 (15) 0.0291 (4) H21 0.2718 0.5871 1.0693 0.035\* ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1187 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cl1 0.0506 (4) 0.0392 (3) 0.0554 (4) −0.0106 (2) −0.0094 (3) −0.0145 (3) O1 0.0328 (8) 0.0558 (11) 0.0374 (9) 0.0037 (7) −0.0019 (6) −0.0071 (7) O2 0.0561 (10) 0.0510 (10) 0.0238 (7) −0.0044 (8) −0.0058 (7) −0.0114 (7) O3 0.0490 (9) 0.0360 (8) 0.0274 (7) 0.0054 (7) 0.0083 (6) −0.0011 (6) N1 0.0331 (9) 0.0421 (10) 0.0258 (8) −0.0033 (7) −0.0058 (7) −0.0037 (7) N2 0.0381 (9) 0.0322 (9) 0.0248 (8) −0.0041 (7) −0.0079 (7) −0.0063 (7) N3 0.0432 (10) 0.0348 (9) 0.0241 (8) 0.0085 (8) −0.0014 (7) −0.0026 (7) C1 0.0339 (10) 0.0360 (10) 0.0220 (9) −0.0061 (8) −0.0025 (7) −0.0030 (7) C2 0.0481 (13) 0.0640 (16) 0.0256 (10) −0.0096 (11) −0.0045 (9) −0.0121 (10) C3 0.0542 (15) 0.0698 (18) 0.0267 (11) −0.0104 (13) 0.0074 (10) −0.0166 (11) C4 0.0384 (12) 0.0523 (14) 0.0400 (12) −0.0074 (10) 0.0093 (10) −0.0104 (11) C5 0.0338 (11) 0.0379 (11) 0.0356 (11) −0.0038 (8) −0.0045 (8) −0.0042 (9) C6 0.0346 (10) 0.0284 (9) 0.0214 (9) −0.0045 (7) −0.0037 (7) −0.0018 (7) C7 0.0408 (12) 0.0581 (15) 0.0366 (12) −0.0014 (11) −0.0149 (10) −0.0020 (11) C8 0.0338 (10) 0.0339 (10) 0.0271 (10) −0.0031 (8) −0.0027 (8) −0.0091 (8) C9 0.0326 (10) 0.0301 (9) 0.0235 (9) −0.0002 (7) −0.0005 (7) −0.0045 (7) C10 0.0370 (10) 0.0306 (10) 0.0224 (9) 0.0026 (8) −0.0059 (7) −0.0042 (7) C11 0.0472 (13) 0.0469 (13) 0.0433 (13) −0.0099 (10) −0.0154 (10) −0.0137 (10) C12 0.0292 (9) 0.0346 (10) 0.0267 (9) −0.0003 (8) −0.0023 (7) −0.0030 (8) C13 0.0309 (10) 0.0381 (11) 0.0263 (9) 0.0005 (8) −0.0025 (7) −0.0016 (8) C14 0.0391 (11) 0.0322 (10) 0.0211 (9) −0.0001 (8) −0.0008 (8) −0.0015 (7) C15 0.0358 (10) 0.0327 (10) 0.0202 (8) 0.0085 (8) −0.0057 (7) −0.0033 (7) C16 0.0311 (10) 0.0328 (10) 0.0237 (9) 0.0069 (8) −0.0067 (7) −0.0075 (7) C17 0.0383 (11) 0.0450 (12) 0.0250 (9) 0.0090 (9) −0.0086 (8) −0.0145 (8) C18 0.0383 (11) 0.0415 (12) 0.0374 (11) 0.0085 (9) −0.0143 (9) −0.0216 (9) C19 0.0306 (10) 0.0337 (10) 0.0376 (11) 0.0033 (8) −0.0095 (8) −0.0116 (8) C20 0.0337 (10) 0.0336 (10) 0.0267 (9) 0.0002 (8) −0.0044 (8) −0.0094 (8) C21 0.0349 (10) 0.0304 (10) 0.0231 (9) 0.0029 (8) −0.0056 (7) −0.0085 (7) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1791 .table-wrap} --------------------- -------------- ----------------------- -------------- Cl1---C19 1.738 (2) C9---C12 1.523 (3) O1---C8 1.228 (3) C9---C10 1.536 (3) O2---C10 1.218 (3) C9---H9 0.9800 O3---N3 1.427 (3) C11---H11A 0.9600 O3---C13 1.470 (3) C11---H11B 0.9600 N1---C8 1.360 (3) C11---H11C 0.9600 N1---C1 1.423 (3) C12---C13 1.518 (3) N1---C7 1.477 (3) C12---H12A 0.9700 N2---C10 1.371 (3) C12---H12B 0.9700 N2---C6 1.420 (3) C13---C14 1.534 (3) N2---C11 1.467 (3) C13---H13 0.9800 N3---C15 1.282 (3) C14---C15 1.506 (3) C1---C2 1.397 (3) C14---H14A 0.9700 C1---C6 1.403 (3) C14---H14B 0.9700 C2---C3 1.384 (4) C15---C16 1.471 (3) C2---H2 0.9300 C16---C21 1.398 (3) C3---C4 1.378 (4) C16---C17 1.403 (3) C3---H3 0.9300 C17---C18 1.376 (4) C4---C5 1.383 (3) C17---H17 0.9300 C4---H4 0.9300 C18---C19 1.392 (3) C5---C6 1.396 (3) C18---H18 0.9300 C5---H5 0.9300 C19---C20 1.384 (3) C7---H7A 0.9600 C20---C21 1.388 (3) C7---H7B 0.9600 C20---H20 0.9300 C7---H7C 0.9600 C21---H21 0.9300 C8---C9 1.514 (3) N3---O3---C13 109.02 (15) N2---C11---H11B 109.5 C8---N1---C1 123.46 (18) H11A---C11---H11B 109.5 C8---N1---C7 117.58 (19) N2---C11---H11C 109.5 C1---N1---C7 118.47 (18) H11A---C11---H11C 109.5 C10---N2---C6 122.62 (17) H11B---C11---H11C 109.5 C10---N2---C11 117.51 (18) C13---C12---C9 111.22 (17) C6---N2---C11 119.31 (18) C13---C12---H12A 109.4 C15---N3---O3 109.03 (18) C9---C12---H12A 109.4 C2---C1---C6 119.0 (2) C13---C12---H12B 109.4 C2---C1---N1 118.8 (2) C9---C12---H12B 109.4 C6---C1---N1 122.17 (18) H12A---C12---H12B 108.0 C3---C2---C1 120.5 (2) O3---C13---C12 107.78 (17) C3---C2---H2 119.8 O3---C13---C14 103.57 (17) C1---C2---H2 119.8 C12---C13---C14 112.48 (17) C4---C3---C2 120.5 (2) O3---C13---H13 110.9 C4---C3---H3 119.8 C12---C13---H13 110.9 C2---C3---H3 119.8 C14---C13---H13 110.9 C3---C4---C5 119.9 (2) C15---C14---C13 100.88 (16) C3---C4---H4 120.0 C15---C14---H14A 111.6 C5---C4---H4 120.0 C13---C14---H14A 111.6 C4---C5---C6 120.5 (2) C15---C14---H14B 111.6 C4---C5---H5 119.7 C13---C14---H14B 111.6 C6---C5---H5 119.7 H14A---C14---H14B 109.4 C5---C6---C1 119.58 (19) N3---C15---C16 120.6 (2) C5---C6---N2 119.19 (19) N3---C15---C14 114.1 (2) C1---C6---N2 121.20 (18) C16---C15---C14 125.22 (17) N1---C7---H7A 109.5 C21---C16---C17 118.9 (2) N1---C7---H7B 109.5 C21---C16---C15 119.55 (19) H7A---C7---H7B 109.5 C17---C16---C15 121.59 (19) N1---C7---H7C 109.5 C18---C17---C16 120.8 (2) H7A---C7---H7C 109.5 C18---C17---H17 119.6 H7B---C7---H7C 109.5 C16---C17---H17 119.6 O1---C8---N1 122.1 (2) C17---C18---C19 119.1 (2) O1---C8---C9 122.53 (19) C17---C18---H18 120.4 N1---C8---C9 115.32 (18) C19---C18---H18 120.4 C8---C9---C12 111.58 (17) C20---C19---C18 121.4 (2) C8---C9---C10 107.09 (17) C20---C19---Cl1 119.19 (17) C12---C9---C10 112.23 (17) C18---C19---Cl1 119.38 (17) C8---C9---H9 108.6 C21---C20---C19 119.01 (19) C12---C9---H9 108.6 C21---C20---H20 120.5 C10---C9---H9 108.6 C19---C20---H20 120.5 O2---C10---N2 122.0 (2) C20---C21---C16 120.69 (19) O2---C10---C9 121.92 (19) C20---C21---H21 119.7 N2---C10---C9 116.09 (17) C16---C21---H21 119.7 N2---C11---H11A 109.5 C13---O3---N3---C15 −11.1 (2) C11---N2---C10---C9 177.93 (19) C8---N1---C1---C2 132.2 (2) C8---C9---C10---O2 109.6 (2) C7---N1---C1---C2 −39.5 (3) C12---C9---C10---O2 −13.1 (3) C8---N1---C1---C6 −50.2 (3) C8---C9---C10---N2 −68.0 (2) C7---N1---C1---C6 138.0 (2) C12---C9---C10---N2 169.27 (17) C6---C1---C2---C3 −1.0 (4) C8---C9---C12---C13 162.03 (18) N1---C1---C2---C3 176.6 (2) C10---C9---C12---C13 −77.8 (2) C1---C2---C3---C4 0.9 (4) N3---O3---C13---C12 −101.45 (18) C2---C3---C4---C5 0.2 (4) N3---O3---C13---C14 17.9 (2) C3---C4---C5---C6 −1.1 (4) C9---C12---C13---O3 −61.8 (2) C4---C5---C6---C1 1.0 (3) C9---C12---C13---C14 −175.36 (17) C4---C5---C6---N2 −177.2 (2) O3---C13---C14---C15 −17.1 (2) C2---C1---C6---C5 0.1 (3) C12---C13---C14---C15 99.0 (2) N1---C1---C6---C5 −177.46 (19) O3---N3---C15---C16 −177.74 (17) C2---C1---C6---N2 178.3 (2) O3---N3---C15---C14 −1.2 (2) N1---C1---C6---N2 0.7 (3) C13---C14---C15---N3 12.0 (2) C10---N2---C6---C5 −130.1 (2) C13---C14---C15---C16 −171.60 (18) C11---N2---C6---C5 41.1 (3) N3---C15---C16---C21 165.85 (19) C10---N2---C6---C1 51.7 (3) C14---C15---C16---C21 −10.3 (3) C11---N2---C6---C1 −137.1 (2) N3---C15---C16---C17 −13.0 (3) C1---N1---C8---O1 −176.2 (2) C14---C15---C16---C17 170.9 (2) C7---N1---C8---O1 −4.3 (3) C21---C16---C17---C18 −1.7 (3) C1---N1---C8---C9 4.7 (3) C15---C16---C17---C18 177.11 (19) C7---N1---C8---C9 176.56 (19) C16---C17---C18---C19 −0.4 (3) O1---C8---C9---C12 15.3 (3) C17---C18---C19---C20 2.0 (3) N1---C8---C9---C12 −165.63 (18) C17---C18---C19---Cl1 −177.34 (16) O1---C8---C9---C10 −107.9 (2) C18---C19---C20---C21 −1.4 (3) N1---C8---C9---C10 71.2 (2) Cl1---C19---C20---C21 177.92 (15) C6---N2---C10---O2 171.7 (2) C19---C20---C21---C16 −0.8 (3) C11---N2---C10---O2 0.3 (3) C17---C16---C21---C20 2.3 (3) C6---N2---C10---C9 −10.7 (3) C15---C16---C21---C20 −176.55 (18) --------------------- -------------- ----------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.738749	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052140/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o720", "authors": [ { "first": "Rachida", "last": "Dardouri" }, { "first": "Youssef Kandri", "last": "Rodi" }, { "first": "Sonia", "last": "Ladeira" }, { "first": "El Mokhtar", "last": "Essassi" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052141	Related literature {#sec1} ================== For similar structures, see: Adriaanse et al. (2009[@bb1]); Salas et al. (1999[@bb5]); Caballero et al. (2010[@bb3]). For a description of the geometry of tetrahedrally coordinated metal atoms, see: Yang et al. (2007[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(NCO)~2~(C~7~H~8~N~4~)~2~\]M ~r~ = 445.76Triclinic,a = 10.0023 (15) Åb = 10.8168 (16) Åc = 11.1094 (16) Åα = 116.772 (2)°β = 107.226 (2)°γ = 98.557 (2)°V = 967.2 (2) Å^3^Z = 2Mo Kα radiationμ = 1.31 mm^−1^T = 293 K0.25 × 0.14 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD system diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb6]) T ~min~ = 0.773, T ~max~ = 0.88111387 measured reflections4403 independent reflections3580 reflections with I \> 2σ(I)R ~int~ = 0.025 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.039wR(F ^2^) = 0.106S = 1.014403 reflections266 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e398} Data collection: SMART (Bruker, 2007[@bb2]); cell refinement: SAINT (Bruker, 2007[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: Xtal\_GX (Hall et al., 1999[@bb4]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005769/su2253sup1.cif](http://dx.doi.org/10.1107/S1600536811005769/su2253sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005769/su2253Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005769/su2253Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?su2253&file=su2253sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?su2253sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?su2253&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SU2253](http://scripts.iucr.org/cgi-bin/sendsup?su2253)). Financial support from the Junta de Andalucia (FQM-3705 and FQM-4228) and the Spanish Ministry of Education (FPU fellowship of Ana B. Caballero) is gratefully acknowledged. Comment ======= The coordination chemistry of 1,2,4-triazolo\[1,5-a\]pyrimidine derivatives displays great versatility, binding metal ions in several different ways, either in a monodentate (usually through the N atom in position 3) or in a bidentate fashion, bridging metal atoms and leading to dinuclear or polynuclear species with interesting metal-metal interactions (Salas et al., 1999). Some zinc(II) complexes containing these derivatives together with secondary bridging ligands have been described, for example with the thiocyanate anion (Salas et al., 1999; Adriaanse et al., 2009). In most of these metal complexes, both ligands display monodentate binding leading to mononuclear species with either octahedral or tetrahedral coordination geometries. The title compound continues our studies on a series of triazolopyrimidine and pseudohalide-based metal complexes (Caballero et al., 2010). This zinc(II) complex, together with the analogous complex with the unsubstituted triazolopyrimidine ligand (Caballero et al., 2010), are the only ones that have been obtained with the cyanate anion. The title compound exhibits a distorted tetrahedral coordination geometry (τ~4~ = 0.924, Yang et al., 2007) made of two dmtp ligands (dmtp = 5,7-dimethyl-1,2,4-triazolo\[1,5-a\]pyrimidine) interacting through their more usual coordination position, N3, and two cyanate anions bound through their N atom (Fig. 1). The Zn---N3 bond distances, 2.022 (2) and 2.043 (2) Å, are in the typical range for triazolopyrimidine ligands. In the crystal the stacking interactions between the pyrimidine ring of two triazolopyrimidine aromatic systems leads to the formation of supramolecular centrosymmetric dimers (Fig. 2); the centroid-to-centroid distance, involving ring (N4A,C3A,N8A,C7A,C6A,C5A) and that related by an inversion center \[symmetry code: 1-x, -y, -z\], is 3.5444 (18) Å. Experimental {#experimental} ============ A 10 ml volume of an aqueous solution containing 1 mmol of NaNCO (0.068 g) was slowly added to a 10 ml aqueous solution containing 0.5 mmol of Zn(NO)~3~.4H~2~O (0.131 g) and 1 mmol of dmtp ligand (0.148 g). Immediately after adding NaNCO, a yellow turbidity gradually appeared. The mixture was stirred at 353 K for 15 min. and the precipitate was then filtered off. The resulting clear yellow solution was left to stand for a week at room temperature and yellow crystals of the title compound were collected and used for X-ray diffraction studies. Refinement {#refinement} ========== The pyrimidine H atoms were positioned geometrically and treated as riding with C---H = 0.93 Å (methine) and 0.96 Å (methyl), and with U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the molecular structure of the title molecule with displacement ellipsoids drawn at the 50% probability level. H atoms are represented as spheres of arbitrary radii. ::: ![](e-67-0m345-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view along c axis of the crystal packing of the title compound, showing the formation of the dimers by π···π interactions (dashed lines) involing pyrimidine ring (N4A, C3A, N8A, C7A, C6A, C5A) and that related by an inversion center. ::: ![](e-67-0m345-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e155 .table-wrap} --------------------------------- --------------------------------------- \[Zn(NCO)~2~(C~7~H~8~N~4~)~2~\] Z = 2 M~r~ = 445.76 F(000) = 456 Triclinic, P1 D~x~ = 1.531 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71069 Å a = 10.0023 (15) Å Cell parameters from 3345 reflections b = 10.8168 (16) Å θ = 2.2--23.4° c = 11.1094 (16) Å µ = 1.31 mm^−1^ α = 116.772 (2)° T = 293 K β = 107.226 (2)° Prismatic, colourless γ = 98.557 (2)° 0.25 × 0.14 × 0.10 mm V = 967.2 (2) Å^3^ --------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e295 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD system diffractometer 4403 independent reflections Radiation source: fine-focus sealed tube 3580 reflections with I \> 2σ(I) graphite R~int~ = 0.025 Detector resolution: 8.26 pixels mm^-1^ θ~max~ = 28.4°, θ~min~ = 2.2° φ and ω scans h = −13→12 Absorption correction: multi-scan (SADABS; Sheldrick, 1996) k = −13→14 T~min~ = 0.773, T~max~ = 0.881 l = −14→14 11387 measured reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e418 .table-wrap} ------------------------------------- ----------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: heavy-atom method Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.039 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.106 H-atom parameters constrained S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.060P)^2^ + 0.060P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4403 reflections (Δ/σ)~max~ = 0.001 266 parameters Δρ~max~ = 0.37 e Å^−3^ 0 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ----------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e575 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e674 .table-wrap} ------ ------------- ------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ Zn 0.36171 (3) 0.27490 (3) 0.25442 (3) 0.04810 (12) N1A 0.7252 (2) 0.5596 (2) 0.2847 (2) 0.0566 (5) C2A 0.6371 (3) 0.5067 (3) 0.3287 (3) 0.0552 (6) H2A 0.6552 0.5497 0.4282 0.066\ N3A 0.5182 (2) 0.3860 (2) 0.2224 (2) 0.0477 (4) C3AA 0.5321 (2) 0.3589 (2) 0.0970 (2) 0.0429 (5) N4A 0.4440 (2) 0.2520 (2) −0.0413 (2) 0.0485 (5) C5A 0.4853 (3) 0.2523 (3) −0.1441 (3) 0.0528 (6) C51A 0.3895 (4) 0.1323 (3) −0.3011 (3) 0.0776 (9) H51A 0.4437 0.0690 −0.3384 0.093\* H52A 0.3611 0.1745 −0.3605 0.093\* H53A 0.3022 0.0766 −0.3053 0.093\* C6A 0.6140 (3) 0.3580 (3) −0.1100 (3) 0.0578 (6) H6A 0.6388 0.3529 −0.1861 0.069\* C7A 0.7020 (3) 0.4665 (3) 0.0310 (3) 0.0514 (6) C71A 0.8386 (3) 0.5868 (3) 0.0821 (4) 0.0715 (8) H71A 0.8597 0.5736 −0.0010 0.086\* H72A 0.9207 0.5851 0.1522 0.086\* H73A 0.8231 0.6795 0.1281 0.086\* N8A 0.6577 (2) 0.4640 (2) 0.1343 (2) 0.0455 (4) N1B 0.2927 (2) −0.1274 (2) −0.1076 (3) 0.0627 (6) C2B 0.3459 (3) −0.0230 (3) 0.0314 (3) 0.0560 (6) H2B 0.4302 −0.0160 0.1018 0.067\* N3B 0.2735 (2) 0.0740 (2) 0.0676 (2) 0.0463 (4) C3AB 0.1626 (2) 0.0281 (2) −0.0619 (2) 0.0436 (5) N4B 0.0575 (2) 0.0863 (2) −0.0882 (2) 0.0522 (5) C5B −0.0380 (3) 0.0186 (3) −0.2292 (3) 0.0580 (6) C51B −0.1560 (3) 0.0829 (4) −0.2625 (4) 0.0837 (10) H51B −0.1447 0.1672 −0.1727 0.100\* H52B −0.2519 0.0113 −0.3059 0.100\* H53B −0.1470 0.1118 −0.3305 0.100\* C6B −0.0299 (3) −0.1076 (3) −0.3424 (3) 0.0645 (7) H6B −0.0992 −0.1512 −0.4393 0.077\* C7B 0.0770 (3) −0.1662 (3) −0.3123 (3) 0.0598 (7) C71B 0.0991 (4) −0.2982 (3) −0.4201 (3) 0.0881 (10) H71B 0.1921 −0.2690 −0.4245 0.106\* H72B 0.0200 −0.3420 −0.5161 0.106\* H73B 0.0995 −0.3682 −0.3894 0.106\* N8B 0.1732 (2) −0.0941 (2) −0.1680 (2) 0.0484 (4) N1C 0.2232 (3) 0.3742 (3) 0.2904 (3) 0.0697 (6) C1C 0.1135 (4) 0.3882 (3) 0.2404 (4) 0.0699 (8) O1C −0.0024 (3) 0.4026 (4) 0.1929 (4) 0.1284 (11) N1D 0.4708 (3) 0.2496 (3) 0.4110 (3) 0.0750 (7) C1D 0.5648 (3) 0.2391 (3) 0.4912 (3) 0.0589 (6) O1D 0.6598 (3) 0.2288 (3) 0.5767 (3) 0.0985 (8) ------ ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1342 .table-wrap} ------ -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Zn 0.05173 (19) 0.05143 (19) 0.03623 (16) 0.01493 (13) 0.01566 (13) 0.02134 (13) N1A 0.0559 (12) 0.0492 (12) 0.0424 (11) 0.0070 (9) 0.0145 (10) 0.0137 (9) C2A 0.0582 (15) 0.0539 (14) 0.0382 (12) 0.0137 (12) 0.0182 (11) 0.0150 (11) N3A 0.0519 (11) 0.0467 (11) 0.0359 (10) 0.0134 (9) 0.0181 (9) 0.0159 (9) C3AA 0.0468 (12) 0.0404 (11) 0.0395 (11) 0.0166 (10) 0.0168 (10) 0.0195 (10) N4A 0.0568 (12) 0.0427 (10) 0.0376 (10) 0.0131 (9) 0.0154 (9) 0.0182 (9) C5A 0.0708 (16) 0.0491 (14) 0.0399 (13) 0.0256 (12) 0.0209 (12) 0.0238 (11) C51A 0.102 (2) 0.0684 (19) 0.0408 (15) 0.0189 (17) 0.0195 (15) 0.0212 (14) C6A 0.0741 (17) 0.0644 (16) 0.0534 (15) 0.0314 (14) 0.0354 (14) 0.0368 (14) C7A 0.0539 (14) 0.0562 (14) 0.0579 (15) 0.0245 (12) 0.0265 (12) 0.0362 (13) C71A 0.0649 (18) 0.0762 (19) 0.083 (2) 0.0181 (15) 0.0344 (16) 0.0484 (18) N8A 0.0488 (11) 0.0420 (10) 0.0424 (10) 0.0163 (9) 0.0177 (9) 0.0198 (9) N1B 0.0521 (12) 0.0550 (13) 0.0588 (14) 0.0194 (10) 0.0156 (11) 0.0169 (11) C2B 0.0480 (13) 0.0550 (15) 0.0550 (15) 0.0175 (11) 0.0122 (12) 0.0266 (13) N3B 0.0467 (10) 0.0454 (10) 0.0398 (10) 0.0134 (8) 0.0117 (8) 0.0213 (9) C3AB 0.0428 (12) 0.0406 (12) 0.0401 (12) 0.0076 (9) 0.0123 (9) 0.0204 (10) N4B 0.0487 (11) 0.0485 (11) 0.0544 (12) 0.0142 (9) 0.0135 (10) 0.0285 (10) C5B 0.0471 (14) 0.0557 (15) 0.0606 (16) 0.0056 (11) 0.0058 (12) 0.0359 (14) C51B 0.0582 (18) 0.083 (2) 0.090 (2) 0.0150 (16) −0.0003 (16) 0.0516 (19) C6B 0.0555 (16) 0.0666 (17) 0.0458 (14) −0.0007 (13) 0.0016 (12) 0.0281 (13) C7B 0.0543 (15) 0.0522 (14) 0.0448 (14) −0.0028 (12) 0.0137 (12) 0.0143 (12) C71B 0.081 (2) 0.074 (2) 0.0547 (18) 0.0086 (17) 0.0222 (16) 0.0010 (15) N8B 0.0459 (11) 0.0431 (10) 0.0429 (11) 0.0093 (8) 0.0131 (9) 0.0173 (9) N1C 0.0721 (16) 0.0717 (15) 0.0620 (15) 0.0335 (13) 0.0318 (13) 0.0272 (13) C1C 0.077 (2) 0.0734 (19) 0.073 (2) 0.0326 (17) 0.0411 (18) 0.0403 (17) O1C 0.100 (2) 0.172 (3) 0.157 (3) 0.085 (2) 0.059 (2) 0.103 (3) N1D 0.0783 (17) 0.0876 (18) 0.0526 (14) 0.0202 (14) 0.0111 (13) 0.0437 (14) C1D 0.0783 (19) 0.0609 (16) 0.0416 (13) 0.0249 (14) 0.0291 (14) 0.0266 (12) O1D 0.115 (2) 0.136 (2) 0.0756 (15) 0.0763 (18) 0.0359 (14) 0.0712 (16) ------ -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1830 .table-wrap} -------------------- ------------- -------------------- ------------- Zn---N1C 1.902 (2) N1B---C2B 1.306 (3) Zn---N1D 1.919 (2) N1B---N8B 1.370 (3) Zn---N3B 2.0223 (19) C2B---N3B 1.344 (3) Zn---N3A 2.0430 (19) C2B---H2B 0.9300 N1A---C2A 1.304 (3) N3B---C3AB 1.339 (3) N1A---N8A 1.372 (3) C3AB---N4B 1.329 (3) C2A---N3A 1.353 (3) C3AB---N8B 1.365 (3) C2A---H2A 0.9300 N4B---C5B 1.332 (3) N3A---C3AA 1.344 (3) C5B---C6B 1.414 (4) C3AA---N4A 1.330 (3) C5B---C51B 1.494 (4) C3AA---N8A 1.373 (3) C51B---H51B 0.9600 N4A---C5A 1.326 (3) C51B---H52B 0.9600 C5A---C6A 1.411 (4) C51B---H53B 0.9601 C5A---C51A 1.498 (4) C6B---C7B 1.356 (4) C51A---H51A 0.9603 C6B---H6B 0.9300 C51A---H52A 0.9604 C7B---N8B 1.357 (3) C51A---H53A 0.9604 C7B---C71B 1.494 (4) C6A---C7A 1.351 (4) C71B---H71B 0.9602 C6A---H6A 0.9300 C71B---H72B 0.9602 C7A---N8A 1.357 (3) C71B---H73B 0.9602 C7A---C71A 1.493 (4) N1C---C1C 1.140 (4) C71A---H71A 0.9601 C1C---O1C 1.188 (4) C71A---H72A 0.9601 N1D---C1D 1.148 (3) C71A---H73A 0.9601 C1D---O1D 1.188 (3) N1C---Zn---N1D 115.09 (11) N1A---N8A---C3AA 110.40 (18) N1C---Zn---N3B 114.59 (9) C2B---N1B---N8B 101.30 (19) N1D---Zn---N3B 106.30 (9) N1B---C2B---N3B 116.8 (2) N1C---Zn---N3A 111.07 (9) N1B---C2B---H2B 121.5 N1D---Zn---N3A 105.50 (10) N3B---C2B---H2B 121.6 N3B---Zn---N3A 103.25 (8) C3AB---N3B---C2B 103.40 (19) C2A---N1A---N8A 101.70 (19) C3AB---N3B---Zn 128.57 (15) N1A---C2A---N3A 116.7 (2) C2B---N3B---Zn 124.47 (16) N1A---C2A---H2A 121.6 N4B---C3AB---N3B 128.1 (2) N3A---C2A---H2A 121.6 N4B---C3AB---N8B 124.0 (2) C3AA---N3A---C2A 103.34 (19) N3B---C3AB---N8B 107.9 (2) C3AA---N3A---Zn 130.18 (16) C3AB---N4B---C5B 115.2 (2) C2A---N3A---Zn 126.47 (16) N4B---C5B---C6B 122.5 (2) N4A---C3AA---N3A 128.6 (2) N4B---C5B---C51B 116.4 (3) N4A---C3AA---N8A 123.6 (2) C6B---C5B---C51B 121.1 (3) N3A---C3AA---N8A 107.82 (19) C5B---C51B---H51B 109.6 C5A---N4A---C3AA 115.4 (2) C5B---C51B---H52B 109.7 N4A---C5A---C6A 122.6 (2) H51B---C51B---H52B 109.5 N4A---C5A---C51A 116.8 (2) C5B---C51B---H53B 109.2 C6A---C5A---C51A 120.5 (2) H51B---C51B---H53B 109.5 C5A---C51A---H51A 109.6 H52B---C51B---H53B 109.5 C5A---C51A---H52A 109.5 C7B---C6B---C5B 121.2 (2) H51A---C51A---H52A 109.4 C7B---C6B---H6B 119.4 C5A---C51A---H53A 109.5 C5B---C6B---H6B 119.4 H51A---C51A---H53A 109.4 C6B---C7B---N8B 114.9 (2) H52A---C51A---H53A 109.4 C6B---C7B---C71B 127.0 (3) C7A---C6A---C5A 121.3 (2) N8B---C7B---C71B 118.1 (3) C7A---C6A---H6A 119.3 C7B---C71B---H71B 109.2 C5A---C6A---H6A 119.3 C7B---C71B---H72B 109.3 C6A---C7A---N8A 115.0 (2) H71B---C71B---H72B 109.5 C6A---C7A---C71A 126.8 (2) C7B---C71B---H73B 109.9 N8A---C7A---C71A 118.1 (2) H71B---C71B---H73B 109.5 C7A---C71A---H71A 109.7 H72B---C71B---H73B 109.4 C7A---C71A---H72A 109.5 C7B---N8B---C3AB 122.2 (2) H71A---C71A---H72A 109.5 C7B---N8B---N1B 127.2 (2) C7A---C71A---H73A 109.3 C3AB---N8B---N1B 110.57 (19) H71A---C71A---H73A 109.5 C1C---N1C---Zn 146.6 (2) H72A---C71A---H73A 109.5 N1C---C1C---O1C 177.2 (4) C7A---N8A---N1A 127.6 (2) C1D---N1D---Zn 161.5 (3) C7A---N8A---C3AA 122.0 (2) N1D---C1D---O1D 178.1 (3) -------------------- ------------- -------------------- ------------- :::	PubMed Central	2024-06-05T04:04:18.744564	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052141/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m345", "authors": [ { "first": "Ana B.", "last": "Caballero" }, { "first": "Miguel", "last": "Quirós" }, { "first": "Antonio", "last": "Rodríguez-Diéguez" }, { "first": "Juan M.", "last": "Salas" } ] }
PMC3052142	Related literature {#sec1} ================== For structures and properties of luminescent lanthanide coordination compounds, see: Kustaryono et al. (2010[@bb7]); He et al. (2010[@bb6]); Li et al. (2008[@bb8]); Luo et al. (2008[@bb9]). For the use of multi-carboxylate and heterocyclic acids in coordination chemistry, see: Li et al. (2008[@bb8]); Luo et al. (2008[@bb9]). For the dicarboxylate ligand 4-oxido-pyridine-2,6-dicarboxylate, see: Gao et al. (2008[@bb5]). For the isotypic structures of the Dy and Eu analogues, see: Gao et al. (2006[@bb4]) and Lv et al. (2010[@bb10]), respectively. For bond lengths and angles in other complexes with eight-coordinate Tb^III^, see: Chen et al. (2008[@bb3]); Ramya et al. (2010[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]·H~2~OM ~r~ = 411.08Monoclinic,a = 9.953 (2) Åb = 7.5454 (16) Åc = 15.461 (3) Åβ = 105.126 (2)°V = 1120.9 (4) Å^3^Z = 4Mo Kα radiationμ = 6.35 mm^−1^T = 293 K0.30 × 0.25 × 0.22 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2004[@bb2]) T ~min~ = 0.162, T ~max~ = 0.2477828 measured reflections2080 independent reflections1929 reflections with I \> 2σ(I)R ~int~ = 0.032 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.019wR(F ^2^) = 0.051S = 1.102080 reflections196 parameters12 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 1.34 e Å^−3^Δρ~min~ = −0.60 e Å^−3^ {#d5e721} Data collection: APEX2 (Bruker, 2004[@bb2]); cell refinement: SAINT (Bruker, 2004[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb12]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb12]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb12]) and DIAMOND (Brandenburg & Putz, 2005[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb13]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005447/wm2449sup1.cif](http://dx.doi.org/10.1107/S1600536811005447/wm2449sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005447/wm2449Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005447/wm2449Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2449&file=wm2449sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2449sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2449&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2449](http://scripts.iucr.org/cgi-bin/sendsup?wm2449)). Comment ======= The design and synthesis of luminescent lanthanide coordination polymers have achieved great progress during the last years owing to their potential applications in biomedical imaging, as luminescent sensors or as fluorescent probes (Kustaryono et al., 2010; He et al., 2010). Eu and Tb are the most useful lanthanides due to their good fluorescence properties (Li et al., 2008; Luo et al., 2008). Many multi-carboxylate or heterocylic carboxylic acids are used for designing such materials (Li et al., 2008; Luo et al., 2008). For lanthanide coordination polymers, 4-hydroxy-pyridine-2,6-dicarboxylic acid is an excellent bridging pyridine dicarboxylate ligand (Lv et al., 2010; Gao et al., 2008), which can provide at most one nitrogen atom and five O coordination sites. In order to extend the investigation in this field, we synthesized the lanthanide coordination polymer {\[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]^.^H~2~O}, and report its structure here. The title compound is isotypic with its Dy (Gao et al., 2006) and Eu (Lv et al., 2010) analogues. As shown in Fig.1, the asymmetric unit contains one Tb(III) ion, one 4-oxidopyridine-2,6-dicarboxylate anion, three coordinated water molecules, and one water molecule of crystallisation. The Tb atom is eight-coordinated by seven oxygen atoms from three anions and three coordinated water molecules and by one nitrogen atom from one tridentate anion (the other two anions are monodentate), forming a distorted bicapped trigonal-prismatic coordination environment. Important bond distances and angles are presented in Table 1. The Tb---O bond lengths \[2.3035 (19) to 2.424 (2) Å\] are shorter than the Tb---N bond length \[2.471 (2) Å\], which is in agreement with the bond lengths observed in other Tb(III) complexes (Chen et al., 2008; Ramya et al., 2010). The anion adopts a µ~3~-pentadentate coordination mode, as shown in Fig. 1. The anions bridge adjacent Tb^III^ ions to form infinite double chains (Fig. 2). Adjacent chains are further connected by the coordination of the anions and Tb(III) ions into a two-dimensional sheet parallel to (101) (Fig. 3), which are further extended into a three-dimensional framework through O---H···O hydrogen-bonding interactions including both coordinated and uncoordinated water molecules (Table 2). Experimental {#experimental} ============ To a solution of terbium(III) nitrate hexahydrate (0.136 g, 0.3 mmol) in water (5 ml) was added an aqueous solution (5 ml) of the ligand (0.060 g, 0.3 mmol) and a drop of triethylamine. The reactants were sealed in a 25-ml Teflon-lined stainless-steel Parr bomb. The bomb was heated at 433 K for 3 days. The cool solution contained single crystals in ca 60% yield. Anal. Calcd for C~7~H~10~TbNO~9~: C, 20.45; H, 2.45; N, 3.41. Found: C, 20.16; H, 2.17; N, 3.74. Refinement {#refinement} ========== The coordinated water H atoms were located in a different Fourier map and refined with distance constraints of O--H = 0.83 (3) Å. The free water H atoms were placed at calculated positions and refined with a riding model, considering the position of oxygen atoms and the quantity of H atoms. The carbon-bound H atoms were placed in geometrically idealized positions, with C---H = 0.93 Å and constrained to ride on their respective parent atoms, with Uiso(H) = 1.2 Ueq(C). The two highest remaining electron denstity peaks greater than one electron per Å^3^ are located at (0.4907 0.8249 0.2004) and (0.5006 0.8231 0.3054), repectively. The corresponding distances to the nearest atom (heavy atom Tb1) are ca 0.80 Å. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Drawing of the asymmetric unit of the title compound, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0m357-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### View along the b axis of the title compound, showing the double chain. ::: ![](e-67-0m357-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### View approximately along the a axis, showing the sheet structure of {\[Tb(C7H2NO5)(H2O)3\].H2O}. ::: ![](e-67-0m357-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e228 .table-wrap} --------------------------------------- --------------------------------------- \[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]·H~2~O F(000) = 784 M~r~ = 411.08 D~x~ = 2.436 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 5700 reflections a = 9.953 (2) Å θ = 2.2--28.3° b = 7.5454 (16) Å µ = 6.35 mm^−1^ c = 15.461 (3) Å T = 293 K β = 105.126 (2)° Block, colorless V = 1120.9 (4) Å^3^ 0.30 × 0.25 × 0.22 mm Z = 4 --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e366 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2080 independent reflections Radiation source: fine-focus sealed tube 1929 reflections with I \> 2σ(I) graphite R~int~ = 0.032 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.2° Absorption correction: multi-scan (SADABS; Bruker, 2004) h = −12→11 T~min~ = 0.162, T~max~ = 0.247 k = −9→8 7828 measured reflections l = −18→18 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e483 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.019 H atoms treated by a mixture of independent and constrained refinement wR(F^2^) = 0.051 w = 1/\[σ^2^(F~o~^2^) + (0.0227P)^2^ + 0.941P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.10 (Δ/σ)~max~ = 0.001 2080 reflections Δρ~max~ = 1.34 e Å^−3^ 196 parameters Δρ~min~ = −0.60 e Å^−3^ 12 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0244 (6) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e664 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e763 .table-wrap} ----- --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Tb1 0.499147 (11) 0.823001 (18) 0.253250 (7) 0.01168 (10) C1 0.5913 (3) 0.8297 (4) 0.06235 (18) 0.0145 (6) C2 0.4542 (3) 0.7331 (4) 0.03360 (17) 0.0137 (6) C3 0.3928 (3) 0.6833 (4) −0.05345 (18) 0.0157 (6) H3 0.4367 0.7069 −0.0984 0.019\ C4 0.2628 (3) 0.5961 (4) −0.07393 (17) 0.0150 (6) C5 0.2059 (3) 0.5615 (4) −0.00148 (17) 0.0166 (6) H5 0.1218 0.5012 −0.0109 0.020\* C6 0.2739 (3) 0.6163 (4) 0.08284 (17) 0.0149 (6) C7 0.2160 (3) 0.5940 (4) 0.16200 (17) 0.0176 (6) H1W 0.685 (3) 0.519 (5) 0.3081 (14) 0.033 (10)\* H2W 0.678 (4) 0.555 (5) 0.2179 (17) 0.049 (12)\* H3W 0.507 (4) 0.547 (2) 0.394 (2) 0.049 (13)\* H4W 0.477 (4) 0.706 (4) 0.433 (2) 0.039 (12)\* H5W 0.378 (3) 1.090 (5) 0.1149 (12) 0.032 (10)\* H6W 0.339 (4) 1.121 (5) 0.196 (2) 0.051 (13)\* H7W 0.348 (2) 0.664 (5) 0.544 (3) 0.051 (14)\* H8W 0.457 (5) 0.756 (7) 0.608 (3) 0.11 (2)\* N1 0.3970 (3) 0.7017 (3) 0.10190 (15) 0.0144 (5) O1 0.6315 (2) 0.8714 (3) 0.14414 (12) 0.0198 (5) O2 0.6576 (2) 0.8598 (3) 0.00587 (13) 0.0232 (5) O3 0.2780 (2) 0.6745 (3) 0.23225 (14) 0.0273 (6) O4 0.1088 (2) 0.5009 (3) 0.15414 (12) 0.0222 (5) O5 0.1971 (2) 0.5510 (3) −0.15625 (12) 0.0191 (5) O6 0.6360 (2) 0.5619 (3) 0.25964 (14) 0.0286 (5) O7 0.5014 (3) 0.6624 (3) 0.38879 (14) 0.0254 (5) O8 0.3974 (3) 1.0761 (3) 0.17129 (14) 0.0294 (6) O9 0.4360 (3) 0.6777 (3) 0.5670 (2) 0.0376 (6) ----- --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1149 .table-wrap} ----- -------------- -------------- -------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Tb1 0.00900 (13) 0.01520 (14) 0.01068 (12) −0.00006 (5) 0.00229 (7) −0.00069 (4) C1 0.0132 (15) 0.0153 (15) 0.0153 (13) 0.0025 (11) 0.0043 (11) 0.0017 (10) C2 0.0126 (15) 0.0137 (14) 0.0153 (12) 0.0009 (12) 0.0044 (11) 0.0017 (11) C3 0.0146 (16) 0.0195 (16) 0.0137 (13) 0.0016 (11) 0.0047 (11) 0.0008 (10) C4 0.0133 (15) 0.0159 (15) 0.0145 (12) 0.0045 (12) 0.0013 (10) −0.0021 (10) C5 0.0121 (15) 0.0184 (15) 0.0186 (13) −0.0034 (12) 0.0030 (11) −0.0012 (11) C6 0.0113 (14) 0.0165 (15) 0.0168 (13) −0.0007 (12) 0.0036 (11) 0.0023 (11) C7 0.0136 (15) 0.0219 (16) 0.0170 (13) 0.0004 (13) 0.0035 (11) 0.0018 (11) N1 0.0099 (13) 0.0182 (13) 0.0148 (11) −0.0016 (10) 0.0027 (9) −0.0013 (9) O1 0.0145 (11) 0.0288 (12) 0.0164 (10) −0.0054 (9) 0.0048 (8) −0.0030 (8) O2 0.0189 (12) 0.0352 (13) 0.0178 (10) −0.0049 (10) 0.0087 (8) 0.0022 (9) O3 0.0229 (13) 0.0446 (16) 0.0165 (10) −0.0167 (10) 0.0087 (9) −0.0084 (9) O4 0.0184 (12) 0.0307 (13) 0.0178 (9) −0.0134 (10) 0.0050 (8) −0.0016 (8) O5 0.0155 (11) 0.0272 (12) 0.0126 (9) 0.0033 (9) −0.0001 (8) −0.0052 (8) O6 0.0329 (14) 0.0328 (14) 0.0226 (11) 0.0189 (11) 0.0118 (10) 0.0066 (10) O7 0.0338 (15) 0.0226 (14) 0.0218 (11) 0.0025 (10) 0.0107 (10) 0.0009 (9) O8 0.0394 (15) 0.0339 (14) 0.0198 (11) 0.0178 (11) 0.0163 (10) 0.0098 (10) O9 0.0222 (15) 0.0273 (15) 0.0595 (18) 0.0038 (11) 0.0041 (13) 0.0031 (12) ----- -------------- -------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1499 .table-wrap} ---------------------- ------------- -------------------- ------------- Tb1---O5^i^ 2.3035 (19) C5---C6 1.367 (4) Tb1---O8 2.368 (2) C5---H5 0.9300 Tb1---O6 2.383 (2) C6---N1 1.347 (4) Tb1---O4^ii^ 2.4106 (19) C6---C7 1.492 (4) Tb1---O3 2.415 (2) C7---O4 1.256 (3) Tb1---O7 2.416 (2) C7---O3 1.257 (3) Tb1---O1 2.424 (2) O4---Tb1^iii^ 2.4106 (19) Tb1---N1 2.471 (2) O5---Tb1^iv^ 2.3035 (19) C1---O2 1.245 (3) O6---H1W 0.85 (4) C1---O1 1.263 (3) O6---H2W 0.86 (4) C1---C2 1.508 (4) O7---H3W 0.875 (16) C2---N1 1.345 (4) O7---H4W 0.85 (4) C2---C3 1.377 (4) O8---H5W 0.849 (16) C3---C4 1.412 (4) O8---H6W 0.85 (4) C3---H3 0.9300 O9---H7W 0.86 (4) C4---O5 1.315 (3) O9---H8W 0.85 (4) C4---C5 1.405 (4) O5^i^---Tb1---O8 99.83 (8) C3---C2---C1 123.8 (2) O5^i^---Tb1---O6 85.81 (8) C2---C3---C4 119.5 (3) O8---Tb1---O6 148.11 (7) C2---C3---H3 120.2 O5^i^---Tb1---O4^ii^ 81.52 (7) C4---C3---H3 120.2 O8---Tb1---O4^ii^ 70.97 (7) O5---C4---C5 121.4 (3) O6---Tb1---O4^ii^ 140.77 (7) O5---C4---C3 122.2 (2) O5^i^---Tb1---O3 151.44 (7) C5---C4---C3 116.4 (2) O8---Tb1---O3 93.13 (9) C6---C5---C4 120.1 (3) O6---Tb1---O3 96.50 (8) C6---C5---H5 120.0 O4^ii^---Tb1---O3 78.83 (7) C4---C5---H5 120.0 O5^i^---Tb1---O7 82.37 (8) N1---C6---C5 123.3 (3) O8---Tb1---O7 140.75 (8) N1---C6---C7 113.5 (2) O6---Tb1---O7 70.95 (8) C5---C6---C7 123.2 (3) O4^ii^---Tb1---O7 70.65 (7) O4---C7---O3 124.5 (3) O3---Tb1---O7 71.68 (8) O4---C7---C6 118.9 (2) O5^i^---Tb1---O1 80.00 (7) O3---C7---C6 116.5 (3) O8---Tb1---O1 74.95 (7) C2---N1---C6 117.4 (2) O6---Tb1---O1 75.22 (8) C2---N1---Tb1 121.61 (19) O4^ii^---Tb1---O1 137.48 (7) C6---N1---Tb1 120.69 (18) O3---Tb1---O1 128.19 (7) C1---O1---Tb1 124.88 (18) O7---Tb1---O1 142.73 (8) C7---O3---Tb1 124.41 (18) O5^i^---Tb1---N1 143.47 (8) C7---O4---Tb1^iii^ 138.84 (17) O8---Tb1---N1 77.25 (8) C4---O5---Tb1^iv^ 127.69 (17) O6---Tb1---N1 79.77 (8) Tb1---O6---H1W 123 (2) O4^ii^---Tb1---N1 129.18 (8) Tb1---O6---H2W 114 (3) O3---Tb1---N1 64.24 (7) H1W---O6---H2W 112 (3) O7---Tb1---N1 122.96 (8) Tb1---O7---H3W 124 (2) O1---Tb1---N1 63.95 (7) Tb1---O7---H4W 125 (2) O2---C1---O1 124.7 (3) H3W---O7---H4W 110 (3) O2---C1---C2 119.1 (2) Tb1---O8---H5W 127 (2) O1---C1---C2 116.2 (2) Tb1---O8---H6W 109 (3) N1---C2---C3 123.2 (3) H5W---O8---H6W 115 (3) N1---C2---C1 112.9 (2) H7W---O9---H8W 114 (3) ---------------------- ------------- -------------------- ------------- ::: Symmetry codes: (i) x+1/2, −y+3/2, z+1/2; (ii) −x+1/2, y+1/2, −z+1/2; (iii) −x+1/2, y−1/2, −z+1/2; (iv) x−1/2, −y+3/2, z−1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2065 .table-wrap} --------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O6---H1W···O1^v^ 0.85 (4) 2.10 (3) 2.799 (3) 139 (3) O6---H2W···O5^vi^ 0.86 (4) 1.93 (3) 2.725 (3) 154 (3) O7---H3W···O9^vii^ 0.88 (2) 1.84 (2) 2.687 (3) 162 (4) O7---H4W···O9 0.85 (4) 2.23 (3) 2.995 (4) 151 (3) O8---H5W···O2^viii^ 0.85 (2) 1.85 (2) 2.693 (3) 175 (4) O8---H6W···O3^ii^ 0.85 (4) 1.85 (4) 2.680 (3) 167 (4) O9---H7W···O2^ix^ 0.86 (4) 1.84 (2) 2.699 (3) 175 (4) O9---H8W···O4^i^ 0.85 (4) 2.37 (4) 3.073 (4) 141 (5) --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (v) −x+3/2, y−1/2, −z+1/2; (vi) −x+1, −y+1, −z; (vii) −x+1, −y+1, −z+1; (viii) −x+1, −y+2, −z; (ii) −x+1/2, y+1/2, −z+1/2; (ix) x−1/2, −y+3/2, z+1/2; (i) x+1/2, −y+3/2, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: -------------- ------------- Tb1---O5^i^ 2.3035 (19) Tb1---O8 2.368 (2) Tb1---O6 2.383 (2) Tb1---O4^ii^ 2.4106 (19) Tb1---O3 2.415 (2) Tb1---O7 2.416 (2) Tb1---O1 2.424 (2) Tb1---N1 2.471 (2) -------------- ------------- Symmetry codes: (i) ; (ii) . ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- ---------- ---------- ----------- ------------- O6---H1W⋯O1^iii^ 0.85 (4) 2.10 (3) 2.799 (3) 139 (3) O6---H2W⋯O5^iv^ 0.86 (4) 1.93 (3) 2.725 (3) 154 (3) O7---H3W⋯O9^v^ 0.88 (2) 1.84 (2) 2.687 (3) 162 (4) O7---H4W⋯O9 0.85 (4) 2.23 (3) 2.995 (4) 151 (3) O8---H5W⋯O2^vi^ 0.85 (2) 1.85 (2) 2.693 (3) 175 (4) O8---H6W⋯O3^ii^ 0.85 (4) 1.85 (4) 2.680 (3) 167 (4) O9---H7W⋯O2^vii^ 0.86 (4) 1.84 (2) 2.699 (3) 175 (4) O9---H8W⋯O4^i^ 0.85 (4) 2.37 (4) 3.073 (4) 141 (5) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) . :::	PubMed Central	2024-06-05T04:04:18.749239	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052142/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m357-m358", "authors": [ { "first": "Dong-Yu", "last": "Lv" }, { "first": "Zhu-Qing", "last": "Gao" }, { "first": "Jin-Zhong", "last": "Gu" } ] }
PMC3052143	Related literature {#sec1} ================== For related structures and background references, see: Al-abbasi et al. (2010[@bb1]); Hung et al. (2010[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~16~N~2~OSM ~r~ = 284.37Triclinic,a = 7.735 (2) Åb = 8.013 (2) Åc = 12.540 (3) Åα = 101.837 (5)°β = 96.908 (5)°γ = 94.205 (6)°V = 751.3 (4) Å^3^Z = 2Mo Kα radiationμ = 0.21 mm^−1^T = 298 K0.53 × 0.38 × 0.19 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2000[@bb2]) T ~min~ = 0.908, T ~max~ = 0.9617829 measured reflections2648 independent reflections2329 reflections with I \> 2σ(I)R ~int~ = 0.023 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.054wR(F ^2^) = 0.144S = 1.062648 reflections189 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.30 e Å^−3^ {#d5e388} Data collection: SMART (Bruker, 2000[@bb2]); cell refinement: SAINT (Bruker, 2000[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb5]); software used to prepare material for publication: SHELXTL, PARST (Nardelli, 1995[@bb4]) and PLATON (Spek, 2009[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004326/gk2345sup1.cif](http://dx.doi.org/10.1107/S1600536811004326/gk2345sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004326/gk2345Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004326/gk2345Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2345&file=gk2345sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2345sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2345&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2345](http://scripts.iucr.org/cgi-bin/sendsup?gk2345)). The authors thank Universiti Kebangsaan Malaysia for providing the facilities and grants (UKM-GUP-BTT-07--30--190 & UKMST-06-FRGS0111--2009) and the Libyan Government and Sabha University, Libya, for providing a scholarship for AA. Comment ======= The ethyl group and S-atom are in cis-configuration with respect to the N2---C8 bond, however, the N2-phenyl and benzoyl groups are trans to S-atom with respect to both C---N thiourea bonds (Fig. 1). The benzene ring \[C1/C2/C3/C4/C5/C6/C7\] (A), phenyl ring \[N2/C9/C10/C11/C12/C13/C14\] (B) and the thiourea \[(S1/N1/N2/C8/\] (C) fragment are essentially planar. The dihedral angle between the plane A and the plane B is 75.93 (15)° whereas, the dihedral angle between thiourea plane (C) and both planes (A, B) are 87.99 (11) and 62.44 (16)°, respectively. Furthermore, the amide group \[N2/C9/C10/C11/C12/C13/C14\] (D) is twisted relative to the thiourea fragment (C) forming a dihedral angle of 62.44 (16)°. In addition, the molecules are linked by N1---H···S1 hydrogen bonds (Table 1, Fig. 2) to form centrosymmetric dimers. Experimental {#experimental} ============ The reaction scheme involved a reaction of benzoyl chloride (10 mmol) with ammonium thiocyanate (10 mmol) in acetone. The product, benzoyl isothiocyanate was reacted with N-ethylaniline (10 mmol) to give the title compound with 80% yield. A slow evaporation of the reaction mixture give light yellow crystals suitable for X-ray analysis. Refinement {#refinement} ========== Positions of C-bound H atoms were calculated. These H atoms were refined using a riding model with U~iso~=1.5U~eq~(C~methyl~ ) and U~iso~=1.5U~eq~(C) for the remaining H atoms. The amide-group H atom was located in a diffrence Fourier map and freely refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title molecule with displacement ellipsods drawn at the 50% probability level. ::: ![](e-67-0o611-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing viewed down the a-axis. Hydrogen bonds are drawn as dashed lines. ::: ![](e-67-0o611-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e126 .table-wrap} ---------------------- --------------------------------------- C~16~H~16~N~2~OS Z = 2 M~r~ = 284.37 F(000) = 300 Triclinic, P1 D~x~ = 1.257 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 7.735 (2) Å Cell parameters from 4273 reflections b = 8.013 (2) Å θ = 1.7--25.0° c = 12.540 (3) Å µ = 0.21 mm^−1^ α = 101.837 (5)° T = 298 K β = 96.908 (5)° Blok, colorless γ = 94.205 (6)° 0.53 × 0.38 × 0.19 mm V = 751.3 (4) Å^3^ ---------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e260 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEX CCD area-detector diffractometer 2648 independent reflections Radiation source: fine-focus sealed tube 2329 reflections with I \> 2σ(I) graphite R~int~ = 0.023 ω scan θ~max~ = 25.0°, θ~min~ = 1.7° Absorption correction: multi-scan (SADABS; Bruker, 2000) h = −9→9 T~min~ = 0.908, T~max~ = 0.961 k = −9→9 7829 measured reflections l = −14→14 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e374 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.054 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.144 H atoms treated by a mixture of independent and constrained refinement S = 1.06 w = 1/\[σ^2^(F~o~^2^) + (0.0752P)^2^ + 0.3013P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2648 reflections (Δ/σ)~max~ \< 0.001 189 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e531 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e630 .table-wrap} ------ ------------- ------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ S1 0.23483 (8) 1.04861 (8) 0.44047 (5) 0.0590 (2) O1 0.2723 (2) 0.5506 (2) 0.26763 (17) 0.0716 (5) N1 0.4237 (2) 0.8089 (2) 0.34962 (15) 0.0467 (4) N2 0.2081 (3) 0.8877 (3) 0.23101 (16) 0.0663 (6) C1 0.5519 (4) 0.3888 (3) 0.3646 (2) 0.0629 (6) H1B 0.4418 0.3356 0.3670 0.076\ C2 0.6996 (6) 0.3080 (4) 0.3850 (2) 0.0855 (10) H2A 0.6892 0.2010 0.4029 0.103\* C3 0.8618 (5) 0.3839 (5) 0.3793 (2) 0.0900 (11) H3A 0.9606 0.3276 0.3922 0.108\* C4 0.8789 (4) 0.5418 (5) 0.3545 (2) 0.0821 (9) H4A 0.9892 0.5925 0.3502 0.099\* C5 0.7326 (3) 0.6268 (3) 0.33594 (19) 0.0567 (6) H5A 0.7447 0.7354 0.3204 0.068\* C6 0.5686 (3) 0.5503 (3) 0.34046 (16) 0.0453 (5) C7 0.4073 (3) 0.6313 (3) 0.31503 (18) 0.0475 (5) C8 0.2875 (3) 0.9101 (3) 0.33425 (18) 0.0497 (5) C9 0.2909 (5) 0.8135 (4) 0.1373 (2) 0.0757 (9) C10 0.4569 (5) 0.8773 (4) 0.1275 (2) 0.0858 (9) H10A 0.5164 0.9661 0.1822 0.103\* C11 0.5366 (7) 0.8103 (6) 0.0365 (3) 0.1170 (15) H11A 0.6502 0.8520 0.0317 0.140\* C12 0.4498 (11) 0.6856 (8) −0.0443 (4) 0.146 (2) H12A 0.5042 0.6398 −0.1044 0.175\* C13 0.2835 (10) 0.6260 (7) −0.0388 (3) 0.146 (2) H13A 0.2219 0.5451 −0.0975 0.175\* C14 0.2019 (7) 0.6853 (6) 0.0554 (3) 0.1116 (15) H14A 0.092 (4) 0.660 (4) 0.063 (2) 0.067 (10)\* C15 0.0405 (4) 0.9631 (4) 0.2081 (3) 0.0865 (9) H15A −0.0407 0.8796 0.1550 0.104\* H15B −0.0115 0.9914 0.2754 0.104\* C16 0.0708 (5) 1.1179 (5) 0.1650 (3) 0.1049 (11) H16A −0.0382 1.1650 0.1512 0.157\* H16B 0.1200 1.0893 0.0976 0.157\* H16C 0.1506 1.2009 0.2178 0.157\* H1A 0.499 (3) 0.850 (3) 0.403 (2) 0.050 (6)\* ------ ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1115 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ S1 0.0635 (4) 0.0613 (4) 0.0516 (4) 0.0281 (3) 0.0083 (3) 0.0032 (3) O1 0.0501 (9) 0.0559 (10) 0.1014 (14) 0.0015 (8) 0.0001 (9) 0.0070 (9) N1 0.0474 (10) 0.0455 (10) 0.0438 (10) 0.0136 (8) −0.0009 (8) 0.0026 (8) N2 0.0700 (13) 0.0692 (13) 0.0521 (11) 0.0319 (10) −0.0102 (9) −0.0027 (9) C1 0.0841 (17) 0.0513 (13) 0.0569 (14) 0.0164 (12) 0.0139 (12) 0.0139 (11) C2 0.134 (3) 0.0642 (17) 0.0625 (17) 0.0491 (19) 0.0039 (17) 0.0151 (13) C3 0.099 (2) 0.097 (2) 0.0681 (18) 0.062 (2) −0.0074 (16) −0.0040 (16) C4 0.0544 (15) 0.103 (2) 0.0796 (19) 0.0283 (15) 0.0084 (13) −0.0085 (17) C5 0.0528 (13) 0.0592 (13) 0.0578 (13) 0.0148 (10) 0.0140 (10) 0.0049 (11) C6 0.0545 (12) 0.0439 (11) 0.0376 (10) 0.0146 (9) 0.0101 (8) 0.0036 (8) C7 0.0476 (12) 0.0452 (11) 0.0505 (12) 0.0088 (9) 0.0110 (9) 0.0086 (9) C8 0.0499 (11) 0.0465 (11) 0.0509 (12) 0.0119 (9) 0.0031 (9) 0.0061 (9) C9 0.109 (2) 0.0675 (16) 0.0456 (13) 0.0460 (16) −0.0089 (14) 0.0000 (12) C10 0.130 (3) 0.0819 (19) 0.0523 (15) 0.043 (2) 0.0186 (16) 0.0165 (14) C11 0.183 (4) 0.120 (3) 0.070 (2) 0.074 (3) 0.049 (2) 0.033 (2) C12 0.262 (7) 0.135 (4) 0.056 (2) 0.116 (5) 0.027 (4) 0.020 (3) C13 0.245 (6) 0.110 (3) 0.060 (2) 0.085 (4) −0.032 (3) −0.029 (2) C14 0.139 (4) 0.103 (3) 0.071 (2) 0.045 (3) −0.023 (2) −0.0209 (19) C15 0.089 (2) 0.084 (2) 0.0754 (18) 0.0332 (16) −0.0183 (15) 0.0005 (15) C16 0.119 (3) 0.104 (3) 0.096 (2) 0.046 (2) 0.007 (2) 0.024 (2) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1485 .table-wrap} -------------------- -------------- ----------------------- ------------ S1---C8 1.662 (2) C6---C7 1.479 (3) O1---C7 1.207 (3) C9---C14 1.370 (5) N1---C7 1.392 (3) C9---C10 1.375 (5) N1---C8 1.394 (3) C10---C11 1.392 (4) N1---H1A 0.83 (2) C10---H10A 0.9300 N2---C8 1.335 (3) C11---C12 1.341 (7) N2---C9 1.448 (3) C11---H11A 0.9300 N2---C15 1.491 (3) C12---C13 1.354 (8) C1---C2 1.377 (4) C12---H12A 0.9300 C1---C6 1.389 (3) C13---C14 1.418 (7) C1---H1B 0.9300 C13---H13A 0.9300 C2---C3 1.370 (5) C14---H14A 0.88 (3) C2---H2A 0.9300 C15---C16 1.467 (5) C3---C4 1.364 (5) C15---H15A 0.9700 C3---H3A 0.9300 C15---H15B 0.9700 C4---C5 1.383 (4) C16---H16A 0.9600 C4---H4A 0.9300 C16---H16B 0.9600 C5---C6 1.380 (3) C16---H16C 0.9600 C5---H5A 0.9300 C7---N1---C8 123.84 (19) C14---C9---C10 119.6 (4) C7---N1---H1A 116.1 (17) C14---C9---N2 120.4 (4) C8---N1---H1A 114.8 (16) C10---C9---N2 120.0 (3) C8---N2---C9 122.1 (2) C9---C10---C11 120.7 (4) C8---N2---C15 120.0 (2) C9---C10---H10A 119.7 C9---N2---C15 117.2 (2) C11---C10---H10A 119.7 C2---C1---C6 119.4 (3) C12---C11---C10 120.0 (5) C2---C1---H1B 120.3 C12---C11---H11A 120.0 C6---C1---H1B 120.3 C10---C11---H11A 120.0 C3---C2---C1 120.6 (3) C11---C12---C13 120.3 (5) C3---C2---H2A 119.7 C11---C12---H12A 119.8 C1---C2---H2A 119.7 C13---C12---H12A 119.8 C4---C3---C2 120.2 (3) C12---C13---C14 120.9 (5) C4---C3---H3A 119.9 C12---C13---H13A 119.5 C2---C3---H3A 119.9 C14---C13---H13A 119.5 C3---C4---C5 120.2 (3) C9---C14---C13 118.3 (6) C3---C4---H4A 119.9 C9---C14---H14A 115 (2) C5---C4---H4A 119.9 C13---C14---H14A 126 (2) C6---C5---C4 119.9 (3) C16---C15---N2 110.7 (3) C6---C5---H5A 120.0 C16---C15---H15A 109.5 C4---C5---H5A 120.0 N2---C15---H15A 109.5 C5---C6---C1 119.7 (2) C16---C15---H15B 109.5 C5---C6---C7 122.05 (19) N2---C15---H15B 109.5 C1---C6---C7 118.2 (2) H15A---C15---H15B 108.1 O1---C7---N1 122.5 (2) C15---C16---H16A 109.5 O1---C7---C6 122.96 (19) C15---C16---H16B 109.5 N1---C7---C6 114.58 (18) H16A---C16---H16B 109.5 N2---C8---N1 115.58 (19) C15---C16---H16C 109.5 N2---C8---S1 124.27 (16) H16A---C16---H16C 109.5 N1---C8---S1 120.15 (16) H16B---C16---H16C 109.5 C6---C1---C2---C3 −1.5 (4) C15---N2---C8---S1 −12.3 (4) C1---C2---C3---C4 0.8 (4) C7---N1---C8---N2 −53.4 (3) C2---C3---C4---C5 0.5 (4) C7---N1---C8---S1 127.2 (2) C3---C4---C5---C6 −1.2 (4) C8---N2---C9---C14 132.1 (3) C4---C5---C6---C1 0.5 (3) C15---N2---C9---C14 −57.0 (4) C4---C5---C6---C7 −176.4 (2) C8---N2---C9---C10 −51.0 (4) C2---C1---C6---C5 0.8 (3) C15---N2---C9---C10 120.0 (3) C2---C1---C6---C7 177.9 (2) C14---C9---C10---C11 −1.4 (5) C8---N1---C7---O1 0.6 (3) N2---C9---C10---C11 −178.4 (3) C8---N1---C7---C6 −179.73 (19) C9---C10---C11---C12 1.9 (5) C5---C6---C7---O1 143.2 (2) C10---C11---C12---C13 1.0 (7) C1---C6---C7---O1 −33.8 (3) C11---C12---C13---C14 −4.3 (8) C5---C6---C7---N1 −36.4 (3) C10---C9---C14---C13 −1.8 (5) C1---C6---C7---N1 146.6 (2) N2---C9---C14---C13 175.2 (3) C9---N2---C8---N1 −21.0 (4) C12---C13---C14---C9 4.7 (7) C15---N2---C8---N1 168.3 (2) C8---N2---C15---C16 102.9 (3) C9---N2---C8---S1 158.4 (2) C9---N2---C15---C16 −68.3 (3) -------------------- -------------- ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2141 .table-wrap} ------------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···S1^i^ 0.83 (2) 2.62 (2) 3.444 (2) 172 (2) C4---H4A···O1^ii^ 0.93 2.55 3.354 (4) 145 ------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ ---------- ---------- ----------- ------------- N1---H1A⋯S1^i^ 0.83 (2) 2.62 (2) 3.444 (2) 172 (2) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.753835	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052143/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o611", "authors": [ { "first": "Aisha A.", "last": "Al-abbasi" }, { "first": "Mohammad B.", "last": "Kassim" } ] }
PMC3052144	Related literature {#sec1} ================== For the structures of Schiff bases and their complexes, see: Ali et al. (2008[@bb1]); Eltayeb et al. (2007[@bb4]); Datta et al. (2009[@bb3]); Zhao et al. (2010[@bb9]); Temel et al. (2010[@bb8]); Naveenkumar et al. (2010[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(C~13~H~10~ClN~2~O)I(CH~4~O)\]M ~r~ = 469.99Monoclinic,a = 7.0769 (9) Åb = 12.7212 (16) Åc = 18.225 (2) Åβ = 98.994 (1)°V = 1620.5 (3) Å^3^Z = 4Mo Kα radiationμ = 3.59 mm^−1^T = 298 K0.20 × 0.20 × 0.18 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb6]) T ~min~ = 0.534, T ~max~ = 0.5649273 measured reflections3522 independent reflections2947 reflections with I \> 2σ(I)R ~int~ = 0.021 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.025wR(F ^2^) = 0.058S = 1.043522 reflections195 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.91 e Å^−3^ {#d5e413} Data collection: SMART (Bruker, 1998[@bb2]); cell refinement: SAINT (Bruker, 1998[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb7]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100417X/rz2553sup1.cif](http://dx.doi.org/10.1107/S160053681100417X/rz2553sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100417X/rz2553Isup2.hkl](http://dx.doi.org/10.1107/S160053681100417X/rz2553Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2553&file=rz2553sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2553sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2553&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2553](http://scripts.iucr.org/cgi-bin/sendsup?rz2553)). This work was supported by Yichun University. Comment ======= Schiff bases and their complexes have attracted much attention for their interesting structures (Ali et al., 2008; Eltayeb et al., 2007; Datta et al., 2009; Zhao et al., 2010; Temel et al., 2010; Naveenkumar et al., 2010). In this paper, the title new Schiff base zinc(II) complex, Fig. 1, is reported. The Zn atom in the complex is five-coordinated by one phenolate O atom, one imine and one pyridine N atoms of the Schiff base ligand, one methanol O atom, and one iodide atom to form a distorted square pyramidal geometry. The dihedral angle between the benzene and the pyridine rings is 22.9 (2)°. In the crystal structure (Fig. 2), centrosymmetrically related molecules are linked through intermolecular O---H···N hydrogen bonds (Table 1) to form dimers. Experimental {#experimental} ============ Equimolar quantities (0.1 mmol each) of 5-chlorosalicylaldehyde, 2-aminomethylpyridine, and zinc iodide were mixed and stirred in methanol for 30 min at reflux. After keeping the filtrate in air for a few days, colourless block crystals suitable for X-ray analysis were formed. Refinement {#refinement} ========== H2 attached to O2 was located from a difference Fourier map, and refined with the O--H distance restrained to 0.85 (1) Å, and with U~iso~ restrained to 0.08 Å^2^. The remaining H atoms were placed in calculated positions and constrained to ride on their parent atoms, with C---H distances of 0.93--0.97 Å, and with U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(C) for methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, with 30% displacements ellipsoids. ::: ![](e-67-0m313-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular packing of the title compound, viewed along the c axis. Hydrogen atoms not involved in hydrogen bonds (dashed lines) are omitted for clarity. ::: ![](e-67-0m313-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------------------ --------------------------------------- \[Zn(C~13~H~10~ClN~2~O)I(CH~4~O)\] F(000) = 912 M~r~ = 469.99 D~x~ = 1.926 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 3746 reflections a = 7.0769 (9) Å θ = 2.7--27.8° b = 12.7212 (16) Å µ = 3.59 mm^−1^ c = 18.225 (2) Å T = 298 K β = 98.994 (1)° Block, colorless V = 1620.5 (3) Å^3^ 0.20 × 0.20 × 0.18 mm Z = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e274 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3522 independent reflections Radiation source: fine-focus sealed tube 2947 reflections with I \> 2σ(I) graphite R~int~ = 0.021 ω scans θ~max~ = 27.0°, θ~min~ = 2.0° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −9→8 T~min~ = 0.534, T~max~ = 0.564 k = −16→15 9273 measured reflections l = −23→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.058 H atoms treated by a mixture of independent and constrained refinement S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0266P)^2^ + 0.3654P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3522 reflections (Δ/σ)~max~ = 0.003 195 parameters Δρ~max~ = 0.37 e Å^−3^ 1 restraint Δρ~min~ = −0.91 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e545 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e644 .table-wrap} ------ -------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Zn1 0.56550 (5) 1.00055 (2) 0.370141 (16) 0.03411 (9) Cl1 0.80941 (15) 0.43991 (6) 0.42899 (5) 0.0673 (3) I1 0.20664 (3) 1.054046 (16) 0.337917 (10) 0.04454 (7) O1 0.5675 (3) 0.87992 (14) 0.44157 (10) 0.0428 (5) O2 0.6619 (3) 1.10027 (17) 0.45789 (11) 0.0461 (5) N1 0.6673 (3) 0.89862 (17) 0.29675 (11) 0.0343 (5) N2 0.6831 (3) 1.10583 (17) 0.29614 (12) 0.0353 (5) C1 0.6966 (4) 0.7424 (2) 0.37342 (14) 0.0331 (6) C2 0.6271 (4) 0.7827 (2) 0.43675 (14) 0.0350 (6) C3 0.6226 (5) 0.7138 (2) 0.49658 (16) 0.0502 (8) H3 0.5819 0.7388 0.5394 0.060\ C4 0.6768 (5) 0.6104 (2) 0.49358 (17) 0.0517 (8) H4 0.6702 0.5664 0.5338 0.062\* C5 0.7407 (5) 0.5715 (2) 0.43160 (17) 0.0443 (7) C6 0.7511 (4) 0.6356 (2) 0.37262 (16) 0.0394 (6) H6 0.7951 0.6086 0.3310 0.047\* C7 0.7123 (4) 0.8024 (2) 0.30781 (15) 0.0357 (6) H7 0.7599 0.7676 0.2697 0.043\* C8 0.6893 (5) 0.9462 (2) 0.22567 (15) 0.0450 (7) H8A 0.5762 0.9319 0.1896 0.054\* H8B 0.7983 0.9150 0.2076 0.054\* C9 0.7177 (4) 1.0624 (2) 0.23317 (15) 0.0364 (6) C10 0.7742 (4) 1.1230 (3) 0.17688 (15) 0.0451 (7) H10 0.7966 1.0917 0.1329 0.054\* C11 0.7966 (4) 1.2294 (3) 0.18702 (17) 0.0492 (8) H11 0.8336 1.2712 0.1499 0.059\* C12 0.7637 (4) 1.2735 (2) 0.25260 (17) 0.0480 (7) H12 0.7803 1.3452 0.2610 0.058\* C13 0.7061 (4) 1.2099 (2) 0.30520 (17) 0.0437 (7) H13 0.6817 1.2400 0.3493 0.052\* C14 0.8502 (5) 1.1310 (3) 0.48795 (17) 0.0548 (8) H14A 0.8972 1.0869 0.5296 0.082\* H14B 0.8498 1.2029 0.5040 0.082\* H14C 0.9315 1.1240 0.4507 0.082\* H2 0.585 (4) 1.104 (2) 0.4897 (14) 0.055 (9)\* ------ -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1103 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Zn1 0.03959 (19) 0.03446 (17) 0.03043 (16) 0.00566 (13) 0.01222 (13) 0.00098 (12) Cl1 0.0921 (7) 0.0349 (4) 0.0725 (6) 0.0165 (4) 0.0054 (5) −0.0032 (4) I1 0.03836 (12) 0.05586 (13) 0.04069 (12) 0.01147 (9) 0.01019 (8) 0.00744 (8) O1 0.0617 (13) 0.0352 (10) 0.0351 (10) 0.0147 (9) 0.0191 (9) 0.0028 (8) O2 0.0553 (14) 0.0511 (12) 0.0363 (11) −0.0032 (10) 0.0210 (10) −0.0105 (9) N1 0.0387 (13) 0.0371 (12) 0.0285 (11) 0.0009 (10) 0.0102 (9) −0.0023 (9) N2 0.0354 (13) 0.0385 (12) 0.0333 (12) 0.0014 (10) 0.0096 (10) 0.0029 (10) C1 0.0311 (14) 0.0365 (14) 0.0320 (13) 0.0031 (11) 0.0055 (11) −0.0022 (11) C2 0.0359 (15) 0.0360 (14) 0.0327 (14) 0.0056 (11) 0.0045 (11) −0.0002 (11) C3 0.072 (2) 0.0460 (17) 0.0355 (15) 0.0140 (16) 0.0157 (15) 0.0035 (13) C4 0.072 (2) 0.0411 (16) 0.0431 (17) 0.0130 (16) 0.0112 (15) 0.0108 (14) C5 0.0494 (18) 0.0337 (14) 0.0481 (17) 0.0080 (13) 0.0023 (14) −0.0022 (12) C6 0.0381 (16) 0.0379 (15) 0.0421 (16) 0.0038 (12) 0.0063 (12) −0.0065 (12) C7 0.0356 (15) 0.0401 (15) 0.0330 (14) 0.0003 (12) 0.0104 (11) −0.0102 (12) C8 0.061 (2) 0.0469 (17) 0.0299 (14) 0.0002 (14) 0.0149 (14) −0.0022 (12) C9 0.0304 (15) 0.0473 (16) 0.0323 (14) 0.0017 (12) 0.0079 (11) 0.0051 (12) C10 0.0418 (17) 0.061 (2) 0.0338 (15) 0.0001 (14) 0.0104 (13) 0.0063 (13) C11 0.0449 (18) 0.0580 (19) 0.0461 (17) −0.0019 (14) 0.0111 (14) 0.0198 (15) C12 0.0471 (18) 0.0418 (16) 0.0557 (19) 0.0003 (14) 0.0101 (15) 0.0103 (14) C13 0.0485 (18) 0.0404 (16) 0.0433 (16) 0.0046 (13) 0.0108 (13) 0.0030 (13) C14 0.057 (2) 0.066 (2) 0.0415 (17) −0.0016 (17) 0.0095 (15) 0.0005 (15) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1488 .table-wrap} ---------------- ------------- ------------------- ----------- Zn1---O1 2.0111 (18) C4---C5 1.373 (4) Zn1---N1 2.071 (2) C4---H4 0.9300 Zn1---O2 2.071 (2) C5---C6 1.361 (4) Zn1---N2 2.158 (2) C6---H6 0.9300 Zn1---I1 2.6060 (5) C7---H7 0.9300 Cl1---C5 1.746 (3) C8---C9 1.496 (4) O1---C2 1.314 (3) C8---H8A 0.9700 O2---C14 1.415 (4) C8---H8B 0.9700 O2---H2 0.86 (3) C9---C10 1.391 (4) N1---C7 1.272 (3) C10---C11 1.372 (4) N1---C8 1.460 (3) C10---H10 0.9300 N2---C9 1.330 (3) C11---C12 1.372 (4) N2---C13 1.340 (3) C11---H11 0.9300 C1---C6 1.412 (4) C12---C13 1.365 (4) C1---C2 1.419 (3) C12---H12 0.9300 C1---C7 1.438 (4) C13---H13 0.9300 C2---C3 1.403 (4) C14---H14A 0.9600 C3---C4 1.373 (4) C14---H14B 0.9600 C3---H3 0.9300 C14---H14C 0.9600 O1---Zn1---N1 88.42 (8) C4---C5---Cl1 119.8 (2) O1---Zn1---O2 89.96 (8) C5---C6---C1 121.3 (3) N1---Zn1---O2 140.91 (9) C5---C6---H6 119.4 O1---Zn1---N2 156.05 (8) C1---C6---H6 119.4 N1---Zn1---N2 77.17 (8) N1---C7---C1 126.4 (2) O2---Zn1---N2 89.42 (8) N1---C7---H7 116.8 O1---Zn1---I1 104.65 (6) C1---C7---H7 116.8 N1---Zn1---I1 116.29 (6) N1---C8---C9 111.1 (2) O2---Zn1---I1 101.87 (6) N1---C8---H8A 109.4 N2---Zn1---I1 98.90 (6) C9---C8---H8A 109.4 C2---O1---Zn1 130.13 (16) N1---C8---H8B 109.4 C14---O2---Zn1 130.14 (18) C9---C8---H8B 109.4 C14---O2---H2 112 (2) H8A---C8---H8B 108.0 Zn1---O2---H2 113 (2) N2---C9---C10 121.3 (3) C7---N1---C8 118.7 (2) N2---C9---C8 116.7 (2) C7---N1---Zn1 127.11 (18) C10---C9---C8 122.0 (2) C8---N1---Zn1 114.18 (16) C11---C10---C9 119.2 (3) C9---N2---C13 118.8 (2) C11---C10---H10 120.4 C9---N2---Zn1 115.00 (17) C9---C10---H10 120.4 C13---N2---Zn1 125.93 (18) C12---C11---C10 119.2 (3) C6---C1---C2 119.1 (2) C12---C11---H11 120.4 C6---C1---C7 116.5 (2) C10---C11---H11 120.4 C2---C1---C7 124.4 (2) C13---C12---C11 118.7 (3) O1---C2---C3 119.3 (2) C13---C12---H12 120.7 O1---C2---C1 123.4 (2) C11---C12---H12 120.7 C3---C2---C1 117.3 (2) N2---C13---C12 122.9 (3) C4---C3---C2 121.8 (3) N2---C13---H13 118.6 C4---C3---H3 119.1 C12---C13---H13 118.6 C2---C3---H3 119.1 O2---C14---H14A 109.5 C5---C4---C3 120.5 (3) O2---C14---H14B 109.5 C5---C4---H4 119.7 H14A---C14---H14B 109.5 C3---C4---H4 119.7 O2---C14---H14C 109.5 C6---C5---C4 120.0 (3) H14A---C14---H14C 109.5 C6---C5---Cl1 120.2 (2) H14B---C14---H14C 109.5 ---------------- ------------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1990 .table-wrap} ----------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O2---H2···O1^i^ 0.86 (3) 1.79 (3) 2.643 (3) 176 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+2, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- ---------- ---------- ----------- ------------- O2---H2⋯O1^i^ 0.86 (3) 1.79 (3) 2.643 (3) 176 (3) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.759110	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052144/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m313", "authors": [ { "first": "Hong-Wei", "last": "Huang" } ] }
PMC3052145	Related literature {#sec1} ================== For the pharmacological applications of 7-oxabicyclo\[2.2.1\]hept-5-ene-2,3-dicarboxylic anhydride and its derivatives, see: Deng & Hu (2007[@bb2]); Hart et al. (2004[@bb4]). For related structures, see: Li (2010a [@bb5],b [@bb6]); Goh et al. (2008[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~12~N~2~O~3~M ~r~ = 256.26Orthorhombic,a = 10.4457 (11) Åb = 8.8245 (9) Åc = 13.2114 (15) ÅV = 1217.8 (2) Å^3^Z = 4Mo Kα radiationμ = 0.10 mm^−1^T = 298 K0.38 × 0.33 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 1997[@bb1]) T ~min~ = 0.963, T ~max~ = 0.9805021 measured reflections1131 independent reflections827 reflections with I \> 2σ(I)R ~int~ = 0.061 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.041wR(F ^2^) = 0.084S = 1.011131 reflections173 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.14 e Å^−3^Δρ~min~ = −0.12 e Å^−3^ {#d5e408} Data collection: SMART (Bruker, 1997[@bb1]); cell refinement: SAINT (Bruker, 1997[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb7]) and PLATON (Spek, 2009[@bb8]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100362X/lh5200sup1.cif](http://dx.doi.org/10.1107/S160053681100362X/lh5200sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100362X/lh5200Isup2.hkl](http://dx.doi.org/10.1107/S160053681100362X/lh5200Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5200&file=lh5200sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5200sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5200&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5200](http://scripts.iucr.org/cgi-bin/sendsup?lh5200)). The author thanks the Shandong Provincial Natural Science Foundation, China (ZR2009BL027). Comment ======= 7-Oxa-bicyclo\[2,2,1\]hept-5-ene-2,3-dicarboxylic anhydride has been widely employed in clinical practice, as it has low toxicity and is relatively easy to synthesize (Deng & Hu, 2007). Its derivatives are pharmacologically active (Hart et al., 2004). In this paper, the structure of the title compound, (I), is reported. The molecular structure of (I) is shown in Fig. 1. The bond lengths and bond angles are as expected and they are comparable to those in similar compounds (Li, 2010a,b; Goh, et al., 2008). The essentially planar pyrrole ring (maximum deviation = 0.037 (4)Å for atom C2) and the benzene ring form a dihedral angle of 69.5 (2) °. In the crystal, intermolecular N---H···O hydrogen bonds connect molecules into one-dimensional chains along \[001\]. Additional stabilization is provided by weak intermolecular C---H···O hydrogen bonds. Experimental {#experimental} ============ A mixture of exo-7-oxa-bicyclo\[2,2,1\]hept-5-ene-2,3-dicarboxylic anhydride (0.332 g, 2 mmol) and benzene-1,2-diamine (0.216 g, 2 mmol) in methanol (5 ml) was stirred for 5 h at room temperature, and then refluxed for 1 h. After cooling the precipitate was filtered and dried, the title compound was obtained. The crude product of 20 mg was dissolved in methanol of 10 ml. The solution was filtered to remove impurities, and then the filtrate was left for crystallization at room temperature. The single-crystal suitable for X-ray determination was obtained by evaporation of a methanol solution of the title compound after 5 days. Refinement {#refinement} ========== In the absence of significant anomalous dispersion effects the Friedel pairs were merged. H atoms were initially located in difference maps and then refined in a riding-model approximation with C---H = 0.93--0.98 Å, N---H = 0.86Å and U~iso~(H) = 1.2U~eq~(C,N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I), with displacement ellipsoide drawn at the 30% probability level. ::: ![](e-67-0o588-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds shown as dashed lines. ::: ![](e-67-0o588-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e120 .table-wrap} ------------------------- -------------------------------------- C~14~H~12~N~2~O~3~ F(000) = 536 M~r~ = 256.26 D~x~ = 1.398 Mg m^−3^ Orthorhombic, Pca2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2c -2ac Cell parameters from 975 reflections a = 10.4457 (11) Å θ = 3.1--20.1° b = 8.8245 (9) Å µ = 0.10 mm^−1^ c = 13.2114 (15) Å T = 298 K V = 1217.8 (2) Å^3^ Block, pale yellow Z = 4 0.38 × 0.33 × 0.20 mm ------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e245 .table-wrap} ------------------------------------------------------------ ------------------------------------- Bruker SMART CCD diffractometer 1131 independent reflections Radiation source: fine-focus sealed tube 827 reflections with I \> 2σ(I) graphite R~int~ = 0.061 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Bruker, 1997) h = −12→11 T~min~ = 0.963, T~max~ = 0.980 k = −10→10 5021 measured reflections l = −15→12 ------------------------------------------------------------ ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e362 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.084 H-atom parameters constrained S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.0348P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 1131 reflections (Δ/σ)~max~ \< 0.001 173 parameters Δρ~max~ = 0.14 e Å^−3^ 1 restraint Δρ~min~ = −0.12 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e516 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e615 .table-wrap} ----- ------------- ------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ N1 0.0406 (3) 0.1444 (3) 0.0863 (2) 0.0401 (7) N2 0.2069 (3) 0.1868 (4) 0.2520 (3) 0.0729 (11) H2A 0.2110 0.1054 0.2164 0.087\ H2B 0.2577 0.1992 0.3025 0.087\* O1 −0.0454 (3) −0.0189 (3) 0.20351 (18) 0.0680 (9) O2 0.1232 (3) 0.2521 (3) −0.0577 (2) 0.0671 (9) O3 0.2418 (2) −0.1090 (3) 0.03190 (19) 0.0562 (7) C1 −0.0025 (4) 0.0040 (4) 0.1192 (3) 0.0467 (9) C2 0.0207 (4) −0.1091 (4) 0.0363 (3) 0.0476 (9) H2 −0.0560 −0.1684 0.0201 0.057\* C3 0.0677 (3) −0.0159 (4) −0.0536 (3) 0.0469 (10) H3 0.0115 −0.0229 −0.1128 0.056\* C4 0.0818 (3) 0.1439 (5) −0.0139 (3) 0.0462 (10) C5 0.0363 (4) 0.2805 (4) 0.1474 (3) 0.0442 (9) C6 0.1193 (4) 0.2968 (4) 0.2282 (3) 0.0490 (10) C7 0.1108 (5) 0.4281 (5) 0.2857 (3) 0.0709 (14) H7 0.1657 0.4417 0.3404 0.085\* C8 0.0224 (6) 0.5379 (5) 0.2631 (4) 0.0818 (16) H8 0.0173 0.6247 0.3029 0.098\* C9 −0.0598 (5) 0.5204 (5) 0.1810 (4) 0.0783 (14) H9 −0.1187 0.5958 0.1652 0.094\* C10 −0.0533 (4) 0.3914 (5) 0.1239 (3) 0.0588 (11) H10 −0.1087 0.3780 0.0695 0.071\* C11 0.1408 (4) −0.2123 (4) 0.0576 (3) 0.0555 (11) H11 0.1455 −0.2562 0.1256 0.067\* C12 0.1452 (4) −0.3243 (5) −0.0286 (3) 0.0640 (12) H12 0.1251 −0.4269 −0.0259 0.077\* C13 0.1827 (4) −0.2477 (5) −0.1075 (3) 0.0629 (13) H13 0.1946 −0.2846 −0.1728 0.075\* C14 0.2030 (4) −0.0868 (4) −0.0717 (3) 0.0548 (11) H14 0.2615 −0.0259 −0.1130 0.066\* ----- ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1087 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ N1 0.0467 (17) 0.0387 (18) 0.0349 (15) −0.0027 (15) 0.0028 (13) 0.0024 (14) N2 0.076 (3) 0.068 (2) 0.075 (3) −0.004 (2) −0.025 (2) 0.004 (2) O1 0.094 (2) 0.066 (2) 0.0437 (16) −0.0215 (16) 0.0186 (16) 0.0025 (14) O2 0.093 (2) 0.0526 (19) 0.0561 (17) −0.0006 (16) 0.0217 (16) 0.0131 (14) O3 0.0502 (17) 0.0539 (16) 0.0644 (17) −0.0025 (15) −0.0137 (14) −0.0007 (13) C1 0.051 (2) 0.049 (2) 0.040 (2) −0.008 (2) −0.0003 (18) −0.0011 (17) C2 0.052 (2) 0.048 (2) 0.0433 (19) −0.009 (2) 0.0000 (18) −0.0039 (19) C3 0.051 (2) 0.051 (2) 0.038 (2) 0.005 (2) −0.0063 (17) 0.0006 (18) C4 0.047 (2) 0.050 (3) 0.042 (2) 0.006 (2) 0.0011 (18) 0.009 (2) C5 0.046 (2) 0.042 (2) 0.045 (2) 0.002 (2) 0.0095 (18) 0.0005 (18) C6 0.053 (3) 0.049 (2) 0.045 (2) −0.004 (2) 0.0000 (19) −0.0003 (19) C7 0.086 (4) 0.065 (3) 0.062 (3) −0.027 (3) 0.014 (2) −0.019 (2) C8 0.095 (4) 0.053 (3) 0.097 (4) −0.012 (3) 0.049 (3) −0.028 (3) C9 0.068 (4) 0.051 (3) 0.115 (4) 0.016 (3) 0.027 (3) 0.003 (3) C10 0.055 (3) 0.047 (2) 0.075 (3) 0.003 (2) 0.008 (2) 0.004 (2) C11 0.067 (3) 0.050 (2) 0.050 (2) −0.003 (2) −0.006 (2) 0.0055 (18) C12 0.076 (3) 0.046 (3) 0.070 (3) 0.005 (2) 0.001 (2) −0.008 (2) C13 0.069 (3) 0.061 (3) 0.059 (3) 0.014 (2) 0.002 (2) −0.013 (2) C14 0.056 (3) 0.061 (3) 0.047 (2) 0.006 (2) 0.0046 (19) 0.003 (2) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1466 .table-wrap} --------------------- ------------ ----------------------- ------------ N1---C1 1.388 (4) C5---C6 1.383 (5) N1---C4 1.392 (4) C5---C10 1.390 (5) N1---C5 1.447 (4) C6---C7 1.388 (5) N2---C6 1.370 (5) C7---C8 1.372 (7) N2---H2A 0.8600 C7---H7 0.9300 N2---H2B 0.8600 C8---C9 1.392 (7) O1---C1 1.217 (4) C8---H8 0.9300 O2---C4 1.198 (4) C9---C10 1.367 (6) O3---C11 1.434 (4) C9---H9 0.9300 O3---C14 1.440 (4) C10---H10 0.9300 C1---C2 1.502 (5) C11---C12 1.508 (5) C2---C3 1.525 (5) C11---H11 0.9800 C2---C11 1.576 (5) C12---C13 1.303 (6) C2---H2 0.9800 C12---H12 0.9300 C3---C4 1.512 (5) C13---C14 1.512 (5) C3---C14 1.564 (5) C13---H13 0.9300 C3---H3 0.9800 C14---H14 0.9800 C1---N1---C4 113.3 (3) C8---C7---C6 120.9 (5) C1---N1---C5 123.8 (3) C8---C7---H7 119.5 C4---N1---C5 122.9 (3) C6---C7---H7 119.5 C6---N2---H2A 120.0 C7---C8---C9 120.4 (4) C6---N2---H2B 120.0 C7---C8---H8 119.8 H2A---N2---H2B 120.0 C9---C8---H8 119.8 C11---O3---C14 96.0 (3) C10---C9---C8 119.5 (4) O1---C1---N1 123.6 (3) C10---C9---H9 120.3 O1---C1---C2 128.1 (4) C8---C9---H9 120.3 N1---C1---C2 108.2 (3) C9---C10---C5 119.8 (4) C1---C2---C3 105.2 (3) C9---C10---H10 120.1 C1---C2---C11 112.4 (3) C5---C10---H10 120.1 C3---C2---C11 101.2 (3) O3---C11---C12 102.5 (3) C1---C2---H2 112.4 O3---C11---C2 100.2 (3) C3---C2---H2 112.4 C12---C11---C2 105.5 (3) C11---C2---H2 112.4 O3---C11---H11 115.6 C4---C3---C2 105.3 (3) C12---C11---H11 115.6 C4---C3---C14 109.8 (3) C2---C11---H11 115.6 C2---C3---C14 101.2 (3) C13---C12---C11 105.9 (4) C4---C3---H3 113.2 C13---C12---H12 127.1 C2---C3---H3 113.2 C11---C12---H12 127.1 C14---C3---H3 113.2 C12---C13---C14 106.1 (4) O2---C4---N1 124.7 (4) C12---C13---H13 126.9 O2---C4---C3 127.7 (4) C14---C13---H13 126.9 N1---C4---C3 107.6 (3) O3---C14---C13 102.1 (3) C6---C5---C10 121.4 (3) O3---C14---C3 99.4 (3) C6---C5---N1 119.9 (3) C13---C14---C3 107.3 (3) C10---C5---N1 118.7 (3) O3---C14---H14 115.4 N2---C6---C5 121.4 (3) C13---C14---H14 115.4 N2---C6---C7 120.6 (4) C3---C14---H14 115.4 C5---C6---C7 118.0 (4) C4---N1---C1---O1 −178.2 (4) C10---C5---C6---C7 0.0 (5) C5---N1---C1---O1 −1.7 (5) N1---C5---C6---C7 −179.1 (3) C4---N1---C1---C2 4.9 (4) N2---C6---C7---C8 −179.2 (4) C5---N1---C1---C2 −178.6 (3) C5---C6---C7---C8 0.1 (6) O1---C1---C2---C3 176.8 (4) C6---C7---C8---C9 −0.7 (7) N1---C1---C2---C3 −6.4 (4) C7---C8---C9---C10 1.1 (7) O1---C1---C2---C11 −73.9 (5) C8---C9---C10---C5 −0.9 (6) N1---C1---C2---C11 102.8 (3) C6---C5---C10---C9 0.4 (6) C1---C2---C3---C4 5.6 (4) N1---C5---C10---C9 179.5 (3) C11---C2---C3---C4 −111.6 (3) C14---O3---C11---C12 48.6 (3) C1---C2---C3---C14 119.9 (3) C14---O3---C11---C2 −59.9 (3) C11---C2---C3---C14 2.7 (3) C1---C2---C11---O3 −77.4 (3) C1---N1---C4---O2 −179.7 (4) C3---C2---C11---O3 34.3 (3) C5---N1---C4---O2 3.7 (6) C1---C2---C11---C12 176.5 (3) C1---N1---C4---C3 −1.1 (4) C3---C2---C11---C12 −71.8 (4) C5---N1---C4---C3 −177.7 (3) O3---C11---C12---C13 −31.7 (4) C2---C3---C4---O2 175.5 (4) C2---C11---C12---C13 72.7 (4) C14---C3---C4---O2 67.3 (5) C11---C12---C13---C14 0.3 (5) C2---C3---C4---N1 −3.0 (4) C11---O3---C14---C13 −48.3 (3) C14---C3---C4---N1 −111.2 (3) C11---O3---C14---C3 61.8 (3) C1---N1---C5---C6 72.1 (4) C12---C13---C14---O3 31.1 (4) C4---N1---C5---C6 −111.7 (4) C12---C13---C14---C3 −72.9 (4) C1---N1---C5---C10 −107.0 (4) C4---C3---C14---O3 72.1 (3) C4---N1---C5---C10 69.2 (5) C2---C3---C14---O3 −38.9 (3) C10---C5---C6---N2 179.4 (3) C4---C3---C14---C13 178.0 (3) N1---C5---C6---N2 0.3 (5) C2---C3---C14---C13 67.0 (3) --------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2210 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N2---H2B···O2^i^ 0.86 2.28 3.131 (5) 174 C3---H3···O1^ii^ 0.98 2.48 3.232 (5) 133 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1/2, y, z+1/2; (ii) −x, −y, z−1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ --------- ------- ----------- ------------- N2---H2B⋯O2^i^ 0.86 2.28 3.131 (5) 174 C3---H3⋯O1^ii^ 0.98 2.48 3.232 (5) 133 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.763029	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052145/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o588", "authors": [ { "first": "Jian", "last": "Li" } ] }
PMC3052146	Related literature {#sec1} ================== For the structure of 4,4′-bis(prop-2-ynyloxy)biphenyl, see: Zhang et al. (2008[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~14~I~4~O~2~M ~r~ = 769.89Triclinic,a = 10.0470 (4) Åb = 10.2267 (4) Åc = 11.3581 (4) Åα = 105.760 (4)°β = 101.433 (3)°γ = 108.211 (4)°V = 1014.45 (7) Å^3^Z = 2Mo Kα radiationμ = 6.15 mm^−1^T = 100 K0.20 × 0.10 × 0.05 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb1]) T ~min~ = 0.467, T ~max~ = 1.0008121 measured reflections4502 independent reflections4118 reflections with I \> 2σ(I)R ~int~ = 0.026 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.030wR(F ^2^) = 0.079S = 1.044502 reflections217 parametersH-atom parameters constrainedΔρ~max~ = 3.38 e Å^−3^Δρ~min~ = −1.69 e Å^−3^ {#d5e353} Data collection: CrysAlis PRO (Agilent, 2010[@bb1]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb3]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb3]); molecular graphics: X-SEED (Barbour, 2001[@bb2]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb4]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003874/jh2264sup1.cif](http://dx.doi.org/10.1107/S1600536811003874/jh2264sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003874/jh2264Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003874/jh2264Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2264&file=jh2264sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2264sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2264&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2264](http://scripts.iucr.org/cgi-bin/sendsup?jh2264)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= We have intended to activate the triple bond of 4,4\'-bis(prop-2-ynyloxy)biphenyl (Zhang et al., 2008) in order to polymerize the compound by using a cuprous iodide/iodine catalytic system. The attempt yielded instead the iodinated title compound (Scheme I, Fig. 1). The aromatic rings are twisted 37.8 (2) °. Experimental {#experimental} ============ Potassium carbonate (3 g, 1 mmol) and biphenyl-4,4\'-diol (1 g, 5.3 mmol) were dissolved in ethanol (30 ml). The solution was heated for 1 h. This was followed by the addition propargyl bromide (1.5 ml, 17 mmol). The mixture was heated for another 8 h. The solvent was removed and the residue dissolved in a mixture of water (30 ml) and dichloromethane (30 ml). The aqueous layer was extracted three times with dichloromethane. Slow evaporation of dichloromethane gave colorless crystals (70%) of 4,4\'-bis(prop-2-ynyloxy)biphenyl. This compound (1 g, 3.8 mmol) was dissolved an ethanol solution of cuprous iodide and iodine in an attempt to activate the triple bond. Slow evaporation of the solvent yielded the iodinated product in 80% yield. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.99 Å, U~iso~(H) 1.2U~eq~(C)\] and were included in the refinement in the riding model approximation. The final difference Fourier map had a peak at 0.96 Å from I2 and a hole at 0.60 Å from the same atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C18H14I4O4 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o568-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e115 .table-wrap} ------------------------ --------------------------------------- C~18~H~14~I~4~O~2~ Z = 2 M~r~ = 769.89 F(000) = 700 Triclinic, P1 D~x~ = 2.520 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.0470 (4) Å Cell parameters from 5987 reflections b = 10.2267 (4) Å θ = 2.4--29.2° c = 11.3581 (4) Å µ = 6.15 mm^−1^ α = 105.760 (4)° T = 100 K β = 101.433 (3)° Prism, colorless γ = 108.211 (4)° 0.20 × 0.10 × 0.05 mm V = 1014.45 (7) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e251 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 4502 independent reflections Radiation source: SuperNova (Mo) X-ray Source 4118 reflections with I \> 2σ(I) Mirror R~int~ = 0.026 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.4° ω scans h = −12→9 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −13→13 T~min~ = 0.467, T~max~ = 1.000 l = −9→14 8121 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e371 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.079 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0391P)^2^ + 2.8781P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4502 reflections (Δ/σ)~max~ = 0.001 217 parameters Δρ~max~ = 3.38 e Å^−3^ 0 restraints Δρ~min~ = −1.69 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e530 .table-wrap} ------ ------------- -------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ I1 0.52321 (3) 0.89339 (3) 0.77411 (3) 0.02006 (8) I2 0.05784 (3) 0.47289 (3) 0.70014 (3) 0.02903 (10) I3 0.69630 (3) −0.38925 (3) 0.56256 (3) 0.02370 (9) I4 1.15769 (3) −0.03766 (3) 0.91544 (3) 0.02524 (9) O1 0.5470 (4) 0.7096 (3) 0.9645 (3) 0.0202 (6) O2 0.8521 (4) −0.0703 (3) 0.5344 (3) 0.0200 (6) C1 0.2354 (5) 0.6460 (5) 0.6979 (5) 0.0207 (9) H1 0.2259 0.6735 0.6242 0.025\ C2 0.3610 (5) 0.7193 (5) 0.7945 (4) 0.0181 (9) C3 0.3993 (5) 0.7013 (5) 0.9214 (4) 0.0194 (9) H3A 0.3862 0.7788 0.9867 0.023\* H3B 0.3297 0.6046 0.9150 0.023\* C4 0.5783 (5) 0.5922 (5) 0.9042 (4) 0.0177 (9) C5 0.7224 (5) 0.6043 (5) 0.9543 (4) 0.0182 (9) H5 0.7893 0.6881 1.0270 0.022\* C6 0.7679 (5) 0.4940 (5) 0.8981 (4) 0.0184 (9) H6 0.8666 0.5044 0.9316 0.022\* C7 0.6700 (5) 0.3677 (5) 0.7927 (4) 0.0167 (8) C8 0.5257 (5) 0.3563 (5) 0.7479 (4) 0.0193 (9) H8 0.4568 0.2704 0.6782 0.023\* C9 0.4797 (5) 0.4667 (5) 0.8023 (4) 0.0194 (9) H9 0.3806 0.4559 0.7696 0.023\* C10 0.7198 (5) 0.2529 (5) 0.7296 (4) 0.0160 (8) C11 0.6679 (5) 0.1820 (5) 0.5947 (4) 0.0189 (9) H11 0.5995 0.2077 0.5448 0.023\* C12 0.7143 (5) 0.0756 (5) 0.5334 (4) 0.0191 (9) H12 0.6784 0.0294 0.4424 0.023\* C13 0.8144 (5) 0.0367 (4) 0.6066 (4) 0.0163 (8) C14 0.8670 (5) 0.1041 (5) 0.7393 (4) 0.0181 (9) H14 0.9346 0.0775 0.7891 0.022\* C15 0.8192 (5) 0.2116 (5) 0.7992 (4) 0.0172 (8) H15 0.8558 0.2579 0.8902 0.021\* C16 0.9582 (5) −0.1128 (5) 0.6013 (4) 0.0192 (9) H16A 1.0423 −0.0230 0.6631 0.023\* H16B 0.9961 −0.1666 0.5386 0.023\* C17 0.8964 (5) −0.2085 (5) 0.6726 (4) 0.0172 (8) C18 0.9551 (5) −0.1992 (5) 0.7908 (4) 0.0201 (9) H18 0.9018 −0.2705 0.8211 0.024\* ------ ------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1043 .table-wrap} ----- -------------- -------------- -------------- -------------- --------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ I1 0.01788 (15) 0.02009 (15) 0.01828 (15) 0.00200 (11) 0.00372 (11) 0.00864 (12) I2 0.01896 (17) 0.01891 (16) 0.0441 (2) 0.00325 (12) 0.01327 (14) 0.00592 (14) I3 0.01724 (16) 0.02002 (16) 0.02533 (16) 0.00179 (12) 0.00369 (12) 0.00383 (13) I4 0.02077 (16) 0.02426 (17) 0.02344 (16) 0.01197 (13) −0.00226 (12) 0.00046 (13) O1 0.0246 (17) 0.0183 (15) 0.0189 (15) 0.0112 (13) 0.0053 (13) 0.0061 (13) O2 0.0263 (17) 0.0199 (16) 0.0201 (15) 0.0149 (13) 0.0081 (13) 0.0091 (13) C1 0.014 (2) 0.014 (2) 0.031 (2) 0.0025 (17) 0.0072 (18) 0.0052 (19) C2 0.016 (2) 0.014 (2) 0.025 (2) 0.0055 (16) 0.0100 (18) 0.0060 (18) C3 0.025 (2) 0.019 (2) 0.020 (2) 0.0116 (18) 0.0126 (18) 0.0093 (18) C4 0.024 (2) 0.016 (2) 0.019 (2) 0.0100 (17) 0.0108 (18) 0.0092 (17) C5 0.022 (2) 0.014 (2) 0.018 (2) 0.0051 (17) 0.0054 (17) 0.0076 (17) C6 0.016 (2) 0.020 (2) 0.020 (2) 0.0060 (17) 0.0037 (17) 0.0105 (18) C7 0.020 (2) 0.016 (2) 0.018 (2) 0.0073 (17) 0.0059 (17) 0.0100 (17) C8 0.019 (2) 0.018 (2) 0.021 (2) 0.0078 (18) 0.0058 (17) 0.0058 (18) C9 0.018 (2) 0.021 (2) 0.022 (2) 0.0095 (18) 0.0062 (18) 0.0090 (19) C10 0.016 (2) 0.014 (2) 0.018 (2) 0.0027 (16) 0.0060 (16) 0.0086 (17) C11 0.017 (2) 0.020 (2) 0.021 (2) 0.0087 (18) 0.0041 (17) 0.0096 (18) C12 0.021 (2) 0.019 (2) 0.017 (2) 0.0074 (18) 0.0055 (17) 0.0070 (18) C13 0.017 (2) 0.0123 (19) 0.022 (2) 0.0045 (16) 0.0078 (17) 0.0088 (17) C14 0.019 (2) 0.016 (2) 0.021 (2) 0.0067 (17) 0.0061 (17) 0.0113 (18) C15 0.016 (2) 0.014 (2) 0.018 (2) 0.0037 (16) 0.0021 (16) 0.0054 (17) C16 0.020 (2) 0.019 (2) 0.025 (2) 0.0107 (18) 0.0099 (18) 0.0131 (19) C17 0.014 (2) 0.014 (2) 0.021 (2) 0.0053 (16) 0.0051 (17) 0.0041 (17) C18 0.019 (2) 0.017 (2) 0.023 (2) 0.0063 (17) 0.0042 (18) 0.0077 (18) ----- -------------- -------------- -------------- -------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1451 .table-wrap} --------------------- -------------- ----------------------- ------------ I1---C2 2.107 (4) C7---C10 1.482 (6) I2---C1 2.094 (4) C8---C9 1.389 (6) I3---C17 2.109 (4) C8---H8 0.9500 I4---C18 2.089 (5) C9---H9 0.9500 O1---C4 1.372 (5) C10---C15 1.390 (6) O1---C3 1.435 (6) C10---C11 1.410 (6) O2---C13 1.381 (5) C11---C12 1.386 (6) O2---C16 1.432 (5) C11---H11 0.9500 C1---C2 1.331 (7) C12---C13 1.400 (6) C1---H1 0.9500 C12---H12 0.9500 C2---C3 1.493 (6) C13---C14 1.386 (6) C3---H3A 0.9900 C14---C15 1.398 (6) C3---H3B 0.9900 C14---H14 0.9500 C4---C9 1.383 (6) C15---H15 0.9500 C4---C5 1.399 (6) C16---C17 1.500 (6) C5---C6 1.392 (6) C16---H16A 0.9900 C5---H5 0.9500 C16---H16B 0.9900 C6---C7 1.403 (6) C17---C18 1.319 (6) C6---H6 0.9500 C18---H18 0.9500 C7---C8 1.395 (6) C4---O1---C3 118.0 (3) C8---C9---H9 120.1 C13---O2---C16 117.6 (3) C15---C10---C11 117.5 (4) C2---C1---I2 123.3 (4) C15---C10---C7 122.1 (4) C2---C1---H1 118.3 C11---C10---C7 120.4 (4) I2---C1---H1 118.3 C12---C11---C10 121.5 (4) C1---C2---C3 128.2 (4) C12---C11---H11 119.3 C1---C2---I1 117.0 (3) C10---C11---H11 119.3 C3---C2---I1 114.7 (3) C11---C12---C13 119.5 (4) O1---C3---C2 113.8 (4) C11---C12---H12 120.2 O1---C3---H3A 108.8 C13---C12---H12 120.2 C2---C3---H3A 108.8 C14---C13---O2 125.7 (4) O1---C3---H3B 108.8 C14---C13---C12 120.3 (4) C2---C3---H3B 108.8 O2---C13---C12 114.0 (4) H3A---C3---H3B 107.7 C13---C14---C15 119.2 (4) O1---C4---C9 125.3 (4) C13---C14---H14 120.4 O1---C4---C5 115.2 (4) C15---C14---H14 120.4 C9---C4---C5 119.5 (4) C10---C15---C14 122.0 (4) C6---C5---C4 120.2 (4) C10---C15---H15 119.0 C6---C5---H5 119.9 C14---C15---H15 119.0 C4---C5---H5 119.9 O2---C16---C17 113.0 (4) C5---C6---C7 120.9 (4) O2---C16---H16A 109.0 C5---C6---H6 119.5 C17---C16---H16A 109.0 C7---C6---H6 119.5 O2---C16---H16B 109.0 C8---C7---C6 117.5 (4) C17---C16---H16B 109.0 C8---C7---C10 121.5 (4) H16A---C16---H16B 107.8 C6---C7---C10 121.0 (4) C18---C17---C16 128.5 (4) C9---C8---C7 122.0 (4) C18---C17---I3 116.8 (3) C9---C8---H8 119.0 C16---C17---I3 114.6 (3) C7---C8---H8 119.0 C17---C18---I4 124.2 (4) C4---C9---C8 119.8 (4) C17---C18---H18 117.9 C4---C9---H9 120.1 I4---C18---H18 117.9 I2---C1---C2---C3 −3.1 (7) C8---C7---C10---C11 37.3 (6) I2---C1---C2---I1 −178.41 (19) C6---C7---C10---C11 −141.2 (4) C4---O1---C3---C2 −73.4 (5) C15---C10---C11---C12 −0.3 (7) C1---C2---C3---O1 139.5 (5) C7---C10---C11---C12 179.2 (4) I1---C2---C3---O1 −45.1 (4) C10---C11---C12---C13 0.3 (7) C3---O1---C4---C9 1.6 (6) C16---O2---C13---C14 −2.1 (6) C3---O1---C4---C5 −177.3 (4) C16---O2---C13---C12 177.8 (4) O1---C4---C5---C6 −177.9 (4) C11---C12---C13---C14 −0.1 (7) C9---C4---C5---C6 3.1 (6) C11---C12---C13---O2 −179.9 (4) C4---C5---C6---C7 −1.5 (7) O2---C13---C14---C15 179.6 (4) C5---C6---C7---C8 −0.9 (6) C12---C13---C14---C15 −0.2 (6) C5---C6---C7---C10 177.6 (4) C11---C10---C15---C14 0.0 (6) C6---C7---C8---C9 1.8 (7) C7---C10---C15---C14 −179.5 (4) C10---C7---C8---C9 −176.8 (4) C13---C14---C15---C10 0.3 (7) O1---C4---C9---C8 178.9 (4) C13---O2---C16---C17 74.9 (5) C5---C4---C9---C8 −2.3 (7) O2---C16---C17---C18 −135.0 (5) C7---C8---C9---C4 −0.2 (7) O2---C16---C17---I3 49.6 (4) C8---C7---C10---C15 −143.3 (4) C16---C17---C18---I4 1.3 (7) C6---C7---C10---C15 38.2 (6) I3---C17---C18---I4 176.6 (2) --------------------- -------------- ----------------------- ------------ :::	PubMed Central	2024-06-05T04:04:18.767551	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052146/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o568", "authors": [ { "first": "Kiramat", "last": "Shah" }, { "first": "M.", "last": "Raza Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052147	Related literature {#sec1} ================== For the structure of 2-bromonitrobenzene, see: Fronczek (2006[@bb4]). For the structure of 3-bromonitrobenzene, see: Charlton & Trotter (1963[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~6~H~4~BrNO~2~M ~r~ = 202.01Triclinic,a = 6.3676 (6) Åb = 7.3635 (7) Åc = 7.6798 (7) Åα = 65.554 (9)°β = 87.705 (8)°γ = 88.884 (8)°V = 327.54 (5) Å^3^Z = 2Mo Kα radiationμ = 6.20 mm^−1^T = 100 K0.20 × 0.10 × 0.05 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (CrysAlis PRO; Agilent, 2010[@bb1]) T ~min~ = 0.414, T ~max~ = 1.0002142 measured reflections1443 independent reflections1365 reflections with I \> 2σ(I)R ~int~ = 0.052 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.045wR(F ^2^) = 0.119S = 1.071443 reflections92 parametersH-atom parameters constrainedΔρ~max~ = 0.91 e Å^−3^Δρ~min~ = −1.58 e Å^−3^ {#d5e407} Data collection: CrysAlis PRO (Agilent, 2010[@bb1]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: X-SEED (Barbour, 2001[@bb2]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003394/xu5150sup1.cif](http://dx.doi.org/10.1107/S1600536811003394/xu5150sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003394/xu5150Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003394/xu5150Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5150&file=xu5150sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5150sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5150&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5150](http://scripts.iucr.org/cgi-bin/sendsup?xu5150)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= 4-Bromo-1-nitrobenzene (Scheme I) was synthesized as a precursor that will be used in the synthesis of 4,4\'-bis(aminophenoxy)biphenyl (the compound is also commercially available: http://www.chemindustry.com/chemicals/815494.html). The molecule is flat (Fig. 1) as the nitro substituent is co-planar with the aromatic ring. π-π stacking occrs between parallel benzene rings of adjacent molecules, centroids distance between C1-ring and C1^i^-ring (symmetry code: (i) 1-x, -5, 1-z) is 3.643 (3) Å and that between C1-ring and C1^ii^-ring (symmetry code: (ii) 1-x, 1-y, 1-z) is 3.741 (3) Å. Intermolecular weak C---H···O hydrogen bonding (Table 1) and the short Br···O contacts \[3.227 (4), 3.401 (4) Å\] are observed in the crystal structure. Experimental {#experimental} ============ The nitrating mixture cosisted of 5 ml conc. HNO~3~ and 5 ml conc. H~2~SO~4~ kept at 273 K. Bromobenzene (2.6 ml) was added. The temperature was then raised to about 333 K for 3 h. The mixture was added to water (200 ml); the organic compound was extracted by using dichloromethane. The solvent was dried and then alllowed to evaporate to yield the product in 70% yield. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 Å, U~iso~(H) 1.2U~eq~(C)\] and were included in the refinement in the riding model approximation. The crystal is a non-merohedral twin; the separation of the two domains was effected by CrysAlis PRO (Agilent, 2010). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C6H4BrNO2 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o548-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e133 .table-wrap} ----------------------- --------------------------------------- C~6~H~4~BrNO~2~ Z = 2 M~r~ = 202.01 F(000) = 196 Triclinic, P1 D~x~ = 2.048 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 6.3676 (6) Å Cell parameters from 1590 reflections b = 7.3635 (7) Å θ = 2.9--28.3° c = 7.6798 (7) Å µ = 6.20 mm^−1^ α = 65.554 (9)° T = 100 K β = 87.705 (8)° Block, colorless γ = 88.884 (8)° 0.20 × 0.10 × 0.05 mm V = 327.54 (5) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e266 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 1443 independent reflections Radiation source: SuperNova (Mo) X-ray Source 1365 reflections with I \> 2σ(I) Mirror R~int~ = 0.052 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.9° ω scans h = −8→8 Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010) k = −9→9 T~min~ = 0.414, T~max~ = 1.000 l = −9→9 2142 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e386 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.119 H-atom parameters constrained S = 1.07 w = 1/\[σ^2^(F~o~^2^) + (0.0671P)^2^ + 0.4717P\] where P = (F~o~^2^ + 2F~c~^2^)/3 1443 reflections (Δ/σ)~max~ = 0.001 92 parameters Δρ~max~ = 0.91 e Å^−3^ 0 restraints Δρ~min~ = −1.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e545 .table-wrap} ----- ------------- ------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 0.83556 (7) 0.24763 (7) 0.14671 (6) 0.01978 (19) O1 0.0573 (5) 0.3167 (6) 0.7390 (5) 0.0238 (8) O2 0.3071 (6) 0.2117 (6) 0.9389 (5) 0.0245 (8) N1 0.2383 (6) 0.2623 (6) 0.7787 (5) 0.0151 (7) C6 0.7151 (7) 0.1751 (7) 0.5288 (7) 0.0173 (9) H6 0.8526 0.1212 0.5575 0.021\ C5 0.5810 (7) 0.1811 (7) 0.6722 (6) 0.0146 (9) H5 0.6251 0.1326 0.8004 0.018\* C2 0.4465 (7) 0.3256 (7) 0.2969 (7) 0.0173 (9) H2 0.4024 0.3750 0.1687 0.021\* C3 0.3121 (7) 0.3291 (7) 0.4408 (6) 0.0159 (9) H3 0.1731 0.3792 0.4130 0.019\* C1 0.6478 (7) 0.2483 (6) 0.3429 (6) 0.0157 (9) C4 0.3809 (7) 0.2594 (6) 0.6254 (6) 0.0125 (8) ----- ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e750 .table-wrap} ----- ------------- ------------- ------------- --------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.0204 (3) 0.0213 (3) 0.0206 (3) −0.00244 (19) 0.00662 (18) −0.0122 (2) O1 0.0149 (16) 0.038 (2) 0.0232 (18) 0.0024 (15) 0.0001 (13) −0.0174 (16) O2 0.0299 (19) 0.032 (2) 0.0131 (16) 0.0028 (16) −0.0003 (14) −0.0107 (15) N1 0.0173 (18) 0.0152 (18) 0.0156 (18) −0.0013 (14) 0.0010 (14) −0.0093 (15) C6 0.015 (2) 0.017 (2) 0.021 (2) −0.0008 (17) 0.0000 (17) −0.0089 (19) C5 0.016 (2) 0.015 (2) 0.014 (2) 0.0014 (16) −0.0023 (16) −0.0076 (17) C2 0.020 (2) 0.018 (2) 0.016 (2) −0.0004 (18) 0.0001 (17) −0.0094 (18) C3 0.018 (2) 0.016 (2) 0.015 (2) 0.0020 (17) −0.0041 (17) −0.0072 (17) C1 0.019 (2) 0.014 (2) 0.019 (2) −0.0005 (18) 0.0015 (18) −0.0113 (19) C4 0.0133 (19) 0.015 (2) 0.012 (2) −0.0005 (16) 0.0005 (15) −0.0090 (17) ----- ------------- ------------- ------------- --------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e982 .table-wrap} -------------------- ------------ ------------------- ------------ Br1---C1 1.887 (4) C5---C4 1.387 (6) O1---N1 1.220 (5) C5---H5 0.9500 O2---N1 1.226 (5) C2---C3 1.379 (6) N1---C4 1.464 (5) C2---C1 1.390 (6) C6---C1 1.384 (6) C2---H2 0.9500 C6---C5 1.381 (6) C3---C4 1.380 (6) C6---H6 0.9500 C3---H3 0.9500 O1---N1---O2 123.6 (4) C1---C2---H2 120.6 O1---N1---C4 117.9 (4) C4---C3---C2 119.6 (4) O2---N1---C4 118.4 (4) C4---C3---H3 120.2 C1---C6---C5 119.5 (4) C2---C3---H3 120.2 C1---C6---H6 120.2 C6---C1---C2 121.5 (4) C5---C6---H6 120.2 C6---C1---Br1 119.2 (3) C4---C5---C6 118.7 (4) C2---C1---Br1 119.3 (3) C4---C5---H5 120.6 C3---C4---C5 121.8 (4) C6---C5---H5 120.6 C3---C4---N1 119.7 (4) C3---C2---C1 118.8 (4) C5---C4---N1 118.4 (4) C3---C2---H2 120.6 C1---C6---C5---C4 0.5 (7) C2---C3---C4---N1 −179.8 (4) C1---C2---C3---C4 1.1 (7) C6---C5---C4---C3 0.7 (7) C5---C6---C1---C2 −0.9 (7) C6---C5---C4---N1 179.0 (4) C5---C6---C1---Br1 177.9 (3) O1---N1---C4---C3 4.1 (6) C3---C2---C1---C6 0.1 (7) O2---N1---C4---C3 −175.3 (4) C3---C2---C1---Br1 −178.7 (3) O1---N1---C4---C5 −174.3 (4) C2---C3---C4---C5 −1.5 (7) O2---N1---C4---C5 6.3 (6) -------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1246 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C3---H3···O1^i^ 0.95 2.52 3.359 (6) 147 C5---H5···O2^ii^ 0.95 2.54 3.276 (6) 135 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x+1, −y, −z+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- C3---H3⋯O1^i^ 0.95 2.52 3.359 (6) 147 C5---H5⋯O2^ii^ 0.95 2.54 3.276 (6) 135 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.772362	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052147/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o548", "authors": [ { "first": "Qamar", "last": "Ali" }, { "first": "M.", "last": "Raza Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052148	Related literature {#sec1} ================== For general background to the method proposed by our group for obtaining 2-oxa-6-azabenzobicyclononanes using commercially available dibenzyl ketone, salicylic aldehyde and ammonium acetate as starting materials, see: Baliah et al. (1983[@bb1]); Soldatenkov et al. (1996[@bb7]); Le Tuan Anh et al. (2008[@bb4]). For related compounds, see: Soldatenkov et al. (2002[@bb8], 2010[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~36~H~31~N~2~O~3~ ^+^·C~2~H~3~O~2~ ^−^·2C~2~H~6~OM ~r~ = 690.81Monoclinic,a = 13.5464 (10) Åb = 20.1124 (15) Åc = 14.2535 (11) Åβ = 105.118 (2)°V = 3749.0 (5) Å^3^Z = 4Mo Kα radiationμ = 0.08 mm^−1^T = 100 K0.28 × 0.15 × 0.13 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 2003[@bb5]) T ~min~ = 0.977, T ~max~ = 0.98935569 measured reflections7399 independent reflections4951 reflections with I \> 2σ(I)R ~int~ = 0.062 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.044wR(F ^2^) = 0.107S = 1.017399 reflections463 parametersH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.24 e Å^−3^ {#d5e582} Data collection: APEX2 (Bruker, 2005[@bb3]); cell refinement: SAINT-Plus (Bruker, 2001[@bb2]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100376X/rk2264sup1.cif](http://dx.doi.org/10.1107/S160053681100376X/rk2264sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100376X/rk2264Isup2.hkl](http://dx.doi.org/10.1107/S160053681100376X/rk2264Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rk2264&file=rk2264sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rk2264sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rk2264&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RK2264](http://scripts.iucr.org/cgi-bin/sendsup?rk2264)). Comment ======= Recently our group has found an efficient method of the one-step synthesis of potentially bioactive substances having oxazocine skeletal structure. These molecules are formed by domino condensation from commercially available dibenzyl ketone, salicylic aldehyde and ammonium acetate as starting materials (Soldatenkov et al., 2010). The key step of this condensation is Petrenko--Kritchenko reaction (Baliah et al., 1983) leading to the formation of the substituted γ-piperidone (Le Tuan Anh et al., 2008), which then reacts with the excess of ammonium acetate and aldehyde. This work reports the structural characterization of a product of such reaction - 2-oxa-6-aza-3,4-benzobicyclo\[3.3.1^1,5^\]nonan-6-ium acetate (I). Compound I crystallizes as diethanol solvate, i.e., C~38~H~34~N~2~O~5~^.^2(C~2~H~6~O). The cation of the salt I comprises a fused tricyclic system containing three six-membered rings (piperidine, dihydro-2H-pyran and benzene) (Fig. 1). The piperidine ring has the usual chair conformation, while the dihydropyran ring adopts the slightly distorted sofa conformation (the C13 carbon atom deviates from the plane passed through the other atoms of the ring by 0.691 (2) Å). The phenyl substituents at the C10 and C11 carbon atoms occupy the sterically favorable equatorial positions, whereas the phenyl substituent at the C13 carbon atom is axially disposed. The cation of I possesses four asymmetric centers at the C1, C10, C11, and C13 carbon atoms and can have potentially numerous diastereomers. The crystal of I is racemic and consists of enantiomeric pairs with the following relative configuration of the centers: rac-1S\,10R\*,11S\*, 13S\*. In the crystal, there are six (one intra- and five intermolecular) independent hydrogen bonding interactions (Table 1). The intermolecular hydrogen bonds link the cations and anions of I and ethanol solvate molecules into ribbons along the direction \[0 0 1\] (Fig. 2). The crystal packing of the ribbons is stacked along the a* axis. Experimental {#experimental} ============ Ammonium acetate (4.0 g, 52 mmol) was added to a solution of dibenzyl ketone (2.1 g, 10 mmol) and salicylic aldehyde (3.66 g, 30 mmol) in ethanol (50 ml) (Fig. 3). The reaction mixture was stirred for 96 h at 293 K (monitoring by TLC until disappearance of the starting ketone spot). At the end of the reaction, the formed precipitate was filtered off, one half of the mother liquid solvent removed under reduced pressure and the residue was cooled to give 1.45 g of light-yellow crystals of I. Yield is 21%. M.p. = 451--453 K. IR (KBr), ν/cm^-1^: 1623, 1748, 3405, 3460. ^1^H NMR (DMSO-d~6~, 400 MHz, 300 K): δ = 1.08 (t, 6H, CH~3~CH~2~O, J = 6.8), 3.30 (s, 3H, CH~3~CO), 3.47 (q, 4H, CH~3~CH~2~O, J = 6.8), 3.77 (d, 1H, H8, J~7.8~ = 9.0), 4.23 (d, 1H, H9, J~5,9~ = 1.5), 4.32 (d, 1H, H7, J~7,8~= 9.0), 4.41 (br, 4H, 2(Alk)OH, ^+^NH~2~), 4.48 (d, 1H, H5, J~5,9~ = 1.5), 6.41--7.50 (br m, 22H, H~arom~), 7.94 (s, 1H, N=CH), 10.63 (br, 1H, (Ar)OH), 12.48 (s, 1H, (Ar)OH). Anal. Calcd. for C~42~H~46~N~2~O~7~: C, 73.04; H, 6.67; N, 4.06. Found: C, 73.13; H, 6.79; N, 4.23. Refinement {#refinement} ========== The hydrogen atoms of the hydroxy and amino groups were localized in the difference Fourier map and included in the refinement with fixed positional and isotropic displacement parameters \[U~iso~(H) = 1.5U~eq~(O) and 1.2U~eq~(N)\]. The other hydrogen atoms were placed in calculated positions with C---H = 0.95--1.00Å and refined in the riding model with fixed isotropic displacement parameters \[U~iso~(H) = 1.5U~eq~(C) for CH~3~-groups and U~iso~(H) = 1.2U~eq~(C) for the other groups\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of I with the atom numbering scheme. Displacement ellipsoids are shown at the 50% probability level. H atoms are presented as a small spheres of arbitrary radius. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o560-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing of I. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o560-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Domino condensation of dibenzyl ketone with salicylic aldehyde and ammonium acetate. ::: ![](e-67-0o560-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e338 .table-wrap} -------------------------------------------------- --------------------------------------- C~36~H~31~N~2~O~3~^+^·C~2~H~3~O~2~^−^·2C~2~H~6~O F(000) = 1472 M~r~ = 690.81 D~x~ = 1.224 Mg m^−3^ Monoclinic, P2~1~/c Melting point = 451--453 K Hall symbol: -P 2ybc Mo Kα radiation, λ = 0.71073 Å a = 13.5464 (10) Å Cell parameters from 4349 reflections b = 20.1124 (15) Å θ = 2.5--23.7° c = 14.2535 (11) Å µ = 0.08 mm^−1^ β = 105.118 (2)° T = 100 K V = 3749.0 (5) Å^3^ Prism, light-yellow Z = 4 0.28 × 0.15 × 0.13 mm -------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e491 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 7399 independent reflections Radiation source: fine-focus sealed tube 4951 reflections with I \> 2σ(I) graphite R~int~ = 0.062 φ and ω scans θ~max~ = 26.1°, θ~min~ = 1.6° Absorption correction: multi-scan (SADABS; Sheldrick, 2003) h = −16→16 T~min~ = 0.977, T~max~ = 0.989 k = −24→24 35569 measured reflections l = −17→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e608 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.044 Hydrogen site location: difference Fourier map wR(F^2^) = 0.107 H-atom parameters constrained S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.044P)^2^ + 0.8P\] where P = (F~o~^2^ + 2F~c~^2^)/3 7399 reflections (Δ/σ)~max~ = 0.001 463 parameters Δρ~max~ = 0.23 e Å^−3^ 0 restraints Δρ~min~ = −0.24 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e765 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e864 .table-wrap} ------ --------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.31447 (13) 0.45725 (9) 0.26034 (13) 0.0241 (4) H1 0.3562 0.4309 0.3162 0.029\ C2 0.27020 (13) 0.41161 (8) 0.17702 (13) 0.0238 (4) C3 0.31983 (14) 0.35414 (9) 0.15984 (14) 0.0286 (4) H3 0.3835 0.3423 0.2031 0.034\* C4 0.27796 (14) 0.31398 (9) 0.08085 (15) 0.0332 (5) H4 0.3128 0.2749 0.0698 0.040\* C5 0.18468 (14) 0.33100 (9) 0.01773 (14) 0.0308 (4) H5 0.1562 0.3036 −0.0370 0.037\* C6 0.13298 (13) 0.38735 (8) 0.03375 (13) 0.0253 (4) H6 0.0687 0.3985 −0.0089 0.030\* C7 0.17631 (13) 0.42725 (8) 0.11278 (12) 0.0224 (4) O8 0.11919 (8) 0.48161 (5) 0.12638 (8) 0.0223 (3) C9 0.16377 (13) 0.52919 (8) 0.20072 (12) 0.0218 (4) C10 0.22947 (12) 0.58026 (8) 0.16205 (13) 0.0229 (4) H10 0.2529 0.6143 0.2143 0.027\* C11 0.32643 (12) 0.54871 (8) 0.14383 (12) 0.0222 (4) H11 0.3046 0.5182 0.0867 0.027\* N12 0.38139 (10) 0.50797 (7) 0.22941 (10) 0.0226 (3) H12A 0.4342 0.4854 0.2119 0.027\* H12B 0.4088 0.5347 0.2840 0.027\* C13 0.23087 (12) 0.49527 (8) 0.29266 (12) 0.0235 (4) H13 0.2660 0.5317 0.3365 0.028\* N1 0.08334 (10) 0.56563 (7) 0.22658 (10) 0.0232 (3) C14 −0.00930 (13) 0.54651 (9) 0.20077 (13) 0.0256 (4) H14 −0.0258 0.5075 0.1623 0.031\* C15 −0.09103 (13) 0.58249 (9) 0.22817 (13) 0.0260 (4) C16 −0.07164 (14) 0.64102 (10) 0.28307 (14) 0.0335 (5) O1 0.02500 (10) 0.66495 (7) 0.31689 (12) 0.0508 (4) H1O 0.0648 0.6343 0.2931 0.076\* C17 −0.15130 (15) 0.67540 (10) 0.30517 (16) 0.0420 (5) H17 −0.1381 0.7155 0.3416 0.050\* C18 −0.24953 (15) 0.65141 (11) 0.27434 (15) 0.0411 (5) H18 −0.3037 0.6752 0.2899 0.049\* C19 −0.27084 (15) 0.59328 (10) 0.22123 (15) 0.0392 (5) H19 −0.3388 0.5768 0.2012 0.047\* C20 −0.19200 (14) 0.55965 (10) 0.19783 (14) 0.0333 (5) H20 −0.2064 0.5201 0.1603 0.040\* C21 0.16999 (12) 0.61709 (8) 0.07242 (13) 0.0239 (4) C22 0.15273 (13) 0.58968 (9) −0.01999 (13) 0.0264 (4) H22 0.1762 0.5460 −0.0273 0.032\* C23 0.10186 (13) 0.62515 (9) −0.10155 (14) 0.0301 (4) H23 0.0917 0.6059 −0.1642 0.036\* C24 0.06575 (14) 0.68840 (10) −0.09224 (15) 0.0347 (5) H24 0.0309 0.7127 −0.1482 0.042\* C25 0.08082 (14) 0.71584 (9) −0.00093 (16) 0.0366 (5) H25 0.0554 0.7591 0.0060 0.044\* C26 0.13278 (13) 0.68080 (9) 0.08103 (15) 0.0298 (4) H26 0.1431 0.7004 0.1435 0.036\* C27 0.39849 (12) 0.59989 (9) 0.12015 (13) 0.0241 (4) C28 0.43138 (13) 0.59222 (9) 0.03550 (13) 0.0257 (4) O2 0.39434 (9) 0.54015 (6) −0.02342 (9) 0.0311 (3) H2O 0.4183 0.5416 −0.0816 0.047\* C29 0.49980 (14) 0.63804 (10) 0.01430 (14) 0.0340 (5) H29 0.5235 0.6326 −0.0423 0.041\* C30 0.53299 (15) 0.69114 (10) 0.07520 (16) 0.0394 (5) H30 0.5798 0.7220 0.0603 0.047\* C31 0.49895 (15) 0.70016 (10) 0.15790 (15) 0.0361 (5) H31 0.5206 0.7376 0.1988 0.043\* C32 0.43302 (13) 0.65386 (9) 0.18001 (14) 0.0293 (4) H32 0.4109 0.6592 0.2376 0.035\* C33 0.17145 (13) 0.45525 (9) 0.35001 (13) 0.0268 (4) C34 0.12157 (14) 0.39565 (10) 0.31830 (14) 0.0332 (5) H34 0.1256 0.3769 0.2582 0.040\* C35 0.06608 (16) 0.36341 (11) 0.37368 (15) 0.0427 (5) H35 0.0325 0.3227 0.3513 0.051\* C36 0.05916 (17) 0.39003 (12) 0.46139 (16) 0.0477 (6) H36 0.0200 0.3682 0.4987 0.057\* C37 0.10967 (17) 0.44863 (11) 0.49416 (16) 0.0464 (6) H37 0.1066 0.4667 0.5549 0.056\* C38 0.16484 (15) 0.48112 (10) 0.43867 (14) 0.0357 (5) H38 0.1986 0.5217 0.4615 0.043\* O5 0.46371 (10) 0.57558 (7) 0.39577 (9) 0.0374 (3) H5O 0.4207 0.5946 0.4335 0.056\* C41 0.56962 (14) 0.57329 (10) 0.44520 (15) 0.0351 (5) H41A 0.6090 0.5584 0.3995 0.042\* H41B 0.5804 0.5405 0.4987 0.042\* C42 0.60860 (16) 0.63970 (10) 0.48591 (17) 0.0454 (6) H42A 0.6826 0.6371 0.5146 0.068\* H42B 0.5747 0.6526 0.5360 0.068\* H42C 0.5941 0.6729 0.4338 0.068\* O6 0.66244 (10) 0.37980 (6) 0.50427 (10) 0.0369 (3) H6O 0.6265 0.3937 0.4387 0.055\* C43 0.70231 (18) 0.31419 (11) 0.50708 (16) 0.0468 (6) H43A 0.7738 0.3162 0.5021 0.056\* H43B 0.6617 0.2886 0.4508 0.056\* C44 0.69941 (17) 0.27955 (11) 0.59883 (16) 0.0474 (6) H44A 0.7292 0.2351 0.5997 0.071\* H44B 0.6284 0.2757 0.6024 0.071\* H44C 0.7388 0.3051 0.6546 0.071\* C39 0.59166 (14) 0.42003 (10) 0.25775 (14) 0.0321 (4) C40 0.69533 (16) 0.39181 (13) 0.25958 (17) 0.0524 (6) H40A 0.7006 0.3464 0.2854 0.079\* H40B 0.7487 0.4195 0.3010 0.079\* H40C 0.7040 0.3911 0.1934 0.079\* O3 0.54470 (9) 0.45292 (6) 0.18438 (9) 0.0316 (3) O4 0.55567 (10) 0.41052 (8) 0.32869 (10) 0.0459 (4) ------ --------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2120 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0223 (9) 0.0253 (9) 0.0253 (10) −0.0004 (7) 0.0072 (7) 0.0040 (8) C2 0.0242 (9) 0.0216 (9) 0.0288 (10) −0.0005 (7) 0.0125 (8) 0.0047 (7) C3 0.0266 (10) 0.0247 (10) 0.0386 (11) 0.0017 (7) 0.0159 (8) 0.0058 (8) C4 0.0349 (11) 0.0221 (10) 0.0505 (13) −0.0001 (8) 0.0252 (10) −0.0016 (9) C5 0.0350 (11) 0.0241 (10) 0.0391 (11) −0.0062 (8) 0.0200 (9) −0.0069 (8) C6 0.0261 (10) 0.0251 (10) 0.0277 (10) −0.0021 (7) 0.0125 (8) −0.0005 (8) C7 0.0257 (9) 0.0186 (9) 0.0282 (10) −0.0005 (7) 0.0161 (8) 0.0007 (7) O8 0.0229 (6) 0.0206 (6) 0.0247 (7) 0.0012 (5) 0.0084 (5) −0.0030 (5) C9 0.0227 (9) 0.0214 (9) 0.0232 (9) 0.0003 (7) 0.0092 (7) −0.0042 (7) C10 0.0204 (9) 0.0220 (9) 0.0281 (10) −0.0014 (7) 0.0095 (7) −0.0032 (7) C11 0.0217 (9) 0.0233 (9) 0.0223 (9) 0.0008 (7) 0.0070 (7) 0.0004 (7) N12 0.0196 (7) 0.0264 (8) 0.0233 (8) 0.0020 (6) 0.0082 (6) 0.0002 (6) C13 0.0232 (9) 0.0252 (9) 0.0231 (9) −0.0017 (7) 0.0077 (7) −0.0021 (7) N1 0.0222 (8) 0.0225 (8) 0.0281 (8) −0.0005 (6) 0.0122 (6) −0.0022 (6) C14 0.0298 (10) 0.0239 (9) 0.0257 (10) −0.0014 (8) 0.0117 (8) −0.0019 (8) C15 0.0266 (10) 0.0263 (10) 0.0271 (10) 0.0006 (7) 0.0103 (8) 0.0003 (8) C16 0.0303 (11) 0.0330 (11) 0.0398 (12) −0.0020 (8) 0.0138 (9) −0.0090 (9) O1 0.0290 (8) 0.0438 (9) 0.0836 (12) −0.0086 (6) 0.0216 (8) −0.0343 (8) C17 0.0369 (12) 0.0369 (12) 0.0552 (14) 0.0023 (9) 0.0178 (10) −0.0153 (10) C18 0.0308 (11) 0.0492 (13) 0.0459 (13) 0.0067 (9) 0.0145 (10) −0.0095 (11) C19 0.0261 (11) 0.0481 (13) 0.0455 (13) −0.0007 (9) 0.0130 (9) −0.0105 (10) C20 0.0295 (11) 0.0368 (11) 0.0352 (11) −0.0037 (8) 0.0115 (9) −0.0082 (9) C21 0.0168 (9) 0.0237 (9) 0.0329 (10) −0.0022 (7) 0.0095 (7) 0.0018 (8) C22 0.0222 (9) 0.0248 (10) 0.0334 (11) 0.0013 (7) 0.0093 (8) 0.0024 (8) C23 0.0260 (10) 0.0335 (11) 0.0321 (11) −0.0022 (8) 0.0098 (8) 0.0061 (9) C24 0.0261 (10) 0.0317 (11) 0.0447 (13) −0.0012 (8) 0.0066 (9) 0.0136 (9) C25 0.0313 (11) 0.0211 (10) 0.0584 (15) 0.0014 (8) 0.0134 (10) 0.0061 (9) C26 0.0266 (10) 0.0234 (10) 0.0414 (12) −0.0015 (8) 0.0125 (9) −0.0015 (8) C27 0.0191 (9) 0.0246 (9) 0.0293 (10) 0.0007 (7) 0.0073 (7) 0.0024 (8) C28 0.0211 (9) 0.0276 (10) 0.0281 (10) 0.0017 (7) 0.0062 (8) 0.0022 (8) O2 0.0320 (7) 0.0357 (8) 0.0297 (7) −0.0059 (6) 0.0151 (6) −0.0045 (6) C29 0.0336 (11) 0.0381 (12) 0.0342 (11) −0.0049 (9) 0.0156 (9) 0.0045 (9) C30 0.0366 (12) 0.0350 (12) 0.0502 (13) −0.0092 (9) 0.0179 (10) 0.0060 (10) C31 0.0329 (11) 0.0288 (10) 0.0461 (13) −0.0074 (8) 0.0094 (9) −0.0046 (9) C32 0.0253 (10) 0.0318 (11) 0.0322 (11) −0.0015 (8) 0.0099 (8) −0.0021 (8) C33 0.0237 (9) 0.0326 (10) 0.0248 (10) −0.0006 (8) 0.0075 (8) 0.0018 (8) C34 0.0349 (11) 0.0405 (12) 0.0261 (10) −0.0098 (9) 0.0113 (8) −0.0003 (9) C35 0.0465 (13) 0.0471 (13) 0.0373 (12) −0.0188 (10) 0.0163 (10) −0.0013 (10) C36 0.0536 (14) 0.0591 (15) 0.0381 (13) −0.0189 (11) 0.0259 (11) 0.0012 (11) C37 0.0578 (14) 0.0557 (15) 0.0352 (12) −0.0153 (11) 0.0289 (11) −0.0087 (11) C38 0.0383 (11) 0.0382 (12) 0.0351 (11) −0.0071 (9) 0.0178 (9) −0.0051 (9) O5 0.0285 (7) 0.0497 (9) 0.0331 (8) −0.0006 (6) 0.0064 (6) −0.0104 (7) C41 0.0284 (10) 0.0357 (11) 0.0389 (12) −0.0008 (8) 0.0045 (9) −0.0025 (9) C42 0.0394 (12) 0.0343 (12) 0.0590 (15) −0.0062 (9) 0.0067 (11) 0.0009 (11) O6 0.0375 (8) 0.0375 (8) 0.0361 (8) 0.0077 (6) 0.0102 (6) −0.0005 (6) C43 0.0541 (14) 0.0419 (13) 0.0465 (14) 0.0159 (11) 0.0171 (11) 0.0013 (11) C44 0.0503 (14) 0.0439 (13) 0.0507 (14) 0.0129 (10) 0.0177 (11) 0.0050 (11) C39 0.0282 (10) 0.0365 (11) 0.0344 (11) 0.0031 (8) 0.0133 (9) 0.0011 (9) C40 0.0419 (13) 0.0696 (17) 0.0522 (15) 0.0227 (12) 0.0238 (11) 0.0142 (12) O3 0.0268 (7) 0.0401 (8) 0.0302 (7) 0.0057 (6) 0.0117 (6) 0.0035 (6) O4 0.0382 (8) 0.0664 (11) 0.0376 (9) 0.0189 (7) 0.0181 (7) 0.0160 (7) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3050 .table-wrap} ----------------------- -------------- ----------------------- -------------- C1---C2 1.497 (2) C24---C25 1.379 (3) C1---N12 1.505 (2) C24---H24 0.9500 C1---C13 1.533 (2) C25---C26 1.388 (3) C1---H1 1.0000 C25---H25 0.9500 C2---C3 1.391 (2) C26---H26 0.9500 C2---C7 1.396 (2) C27---C32 1.384 (2) C3---C4 1.382 (3) C27---C28 1.400 (2) C3---H3 0.9500 C28---O2 1.354 (2) C4---C5 1.389 (3) C28---C29 1.395 (2) C4---H4 0.9500 O2---H2O 0.9659 C5---C6 1.382 (2) C29---C30 1.376 (3) C5---H5 0.9500 C29---H29 0.9500 C6---C7 1.383 (2) C30---C31 1.385 (3) C6---H6 0.9500 C30---H30 0.9500 C7---O8 1.3820 (19) C31---C32 1.382 (3) O8---C9 1.438 (2) C31---H31 0.9500 C9---N1 1.439 (2) C32---H32 0.9500 C9---C13 1.545 (2) C33---C38 1.391 (3) C9---C10 1.551 (2) C33---C34 1.392 (3) C10---C21 1.514 (2) C34---C35 1.385 (3) C10---C11 1.541 (2) C34---H34 0.9500 C10---H10 1.0000 C35---C36 1.385 (3) C11---N12 1.497 (2) C35---H35 0.9500 C11---C27 1.516 (2) C36---C37 1.382 (3) C11---H11 1.0000 C36---H36 0.9500 N12---H12A 0.9347 C37---C38 1.386 (3) N12---H12B 0.9381 C37---H37 0.9500 C13---C33 1.519 (2) C38---H38 0.9500 C13---H13 1.0000 O5---C41 1.425 (2) N1---C14 1.272 (2) O5---H5O 0.9692 C14---C15 1.459 (2) C41---C42 1.497 (3) C14---H14 0.9500 C41---H41A 0.9900 C15---C16 1.400 (3) C41---H41B 0.9900 C15---C20 1.400 (3) C42---H42A 0.9800 C16---O1 1.360 (2) C42---H42B 0.9800 C16---C17 1.385 (3) C42---H42C 0.9800 O1---H1O 0.9389 O6---C43 1.422 (2) C17---C18 1.375 (3) O6---H6O 0.9752 C17---H17 0.9500 C43---C44 1.491 (3) C18---C19 1.382 (3) C43---H43A 0.9900 C18---H18 0.9500 C43---H43B 0.9900 C19---C20 1.377 (3) C44---H44A 0.9800 C19---H19 0.9500 C44---H44B 0.9800 C20---H20 0.9500 C44---H44C 0.9800 C21---C22 1.390 (3) C39---O4 1.246 (2) C21---C26 1.394 (2) C39---O3 1.261 (2) C22---C23 1.385 (2) C39---C40 1.509 (3) C22---H22 0.9500 C40---H40A 0.9800 C23---C24 1.382 (3) C40---H40B 0.9800 C23---H23 0.9500 C40---H40C 0.9800 C2---C1---N12 109.30 (14) C24---C23---C22 120.32 (19) C2---C1---C13 111.69 (14) C24---C23---H23 119.8 N12---C1---C13 107.37 (13) C22---C23---H23 119.8 C2---C1---H1 109.5 C25---C24---C23 119.36 (18) N12---C1---H1 109.5 C25---C24---H24 120.3 C13---C1---H1 109.5 C23---C24---H24 120.3 C3---C2---C7 118.13 (16) C24---C25---C26 120.58 (18) C3---C2---C1 122.50 (16) C24---C25---H25 119.7 C7---C2---C1 119.36 (15) C26---C25---H25 119.7 C4---C3---C2 120.99 (18) C25---C26---C21 120.53 (18) C4---C3---H3 119.5 C25---C26---H26 119.7 C2---C3---H3 119.5 C21---C26---H26 119.7 C3---C4---C5 119.63 (17) C32---C27---C28 119.04 (16) C3---C4---H4 120.2 C32---C27---C11 121.92 (16) C5---C4---H4 120.2 C28---C27---C11 119.03 (15) C6---C5---C4 120.63 (18) O2---C28---C29 122.43 (16) C6---C5---H5 119.7 O2---C28---C27 118.04 (15) C4---C5---H5 119.7 C29---C28---C27 119.53 (17) C5---C6---C7 118.99 (17) C28---O2---H2O 110.8 C5---C6---H6 120.5 C30---C29---C28 120.17 (18) C7---C6---H6 120.5 C30---C29---H29 119.9 O8---C7---C6 116.05 (15) C28---C29---H29 119.9 O8---C7---C2 122.28 (15) C29---C30---C31 120.79 (18) C6---C7---C2 121.61 (16) C29---C30---H30 119.6 C7---O8---C9 119.13 (13) C31---C30---H30 119.6 O8---C9---N1 109.09 (13) C32---C31---C30 118.95 (18) O8---C9---C13 111.85 (13) C32---C31---H31 120.5 N1---C9---C13 108.96 (13) C30---C31---H31 120.5 O8---C9---C10 110.38 (13) C31---C32---C27 121.48 (18) N1---C9---C10 107.26 (13) C31---C32---H32 119.3 C13---C9---C10 109.18 (13) C27---C32---H32 119.3 C21---C10---C11 110.40 (14) C38---C33---C34 118.44 (17) C21---C10---C9 113.29 (14) C38---C33---C13 117.35 (16) C11---C10---C9 112.37 (14) C34---C33---C13 124.20 (16) C21---C10---H10 106.8 C35---C34---C33 120.51 (18) C11---C10---H10 106.8 C35---C34---H34 119.7 C9---C10---H10 106.8 C33---C34---H34 119.7 N12---C11---C27 109.93 (13) C34---C35---C36 120.53 (19) N12---C11---C10 110.66 (13) C34---C35---H35 119.7 C27---C11---C10 112.63 (14) C36---C35---H35 119.7 N12---C11---H11 107.8 C37---C36---C35 119.38 (19) C27---C11---H11 107.8 C37---C36---H36 120.3 C10---C11---H11 107.8 C35---C36---H36 120.3 C11---N12---C1 113.59 (13) C36---C37---C38 120.18 (19) C11---N12---H12A 107.5 C36---C37---H37 119.9 C1---N12---H12A 108.1 C38---C37---H37 119.9 C11---N12---H12B 111.5 C37---C38---C33 120.95 (19) C1---N12---H12B 106.5 C37---C38---H38 119.5 H12A---N12---H12B 109.5 C33---C38---H38 119.5 C33---C13---C1 115.72 (14) C41---O5---H5O 114.3 C33---C13---C9 114.42 (14) O5---C41---C42 111.77 (16) C1---C13---C9 106.41 (13) O5---C41---H41A 109.3 C33---C13---H13 106.6 C42---C41---H41A 109.3 C1---C13---H13 106.6 O5---C41---H41B 109.3 C9---C13---H13 106.6 C42---C41---H41B 109.3 C14---N1---C9 121.86 (15) H41A---C41---H41B 107.9 N1---C14---C15 122.22 (16) C41---C42---H42A 109.5 N1---C14---H14 118.9 C41---C42---H42B 109.5 C15---C14---H14 118.9 H42A---C42---H42B 109.5 C16---C15---C20 118.30 (17) C41---C42---H42C 109.5 C16---C15---C14 121.47 (16) H42A---C42---H42C 109.5 C20---C15---C14 120.21 (16) H42B---C42---H42C 109.5 O1---C16---C17 118.54 (17) C43---O6---H6O 112.5 O1---C16---C15 121.25 (16) O6---C43---C44 111.19 (17) C17---C16---C15 120.21 (18) O6---C43---H43A 109.4 C16---O1---H1O 103.3 C44---C43---H43A 109.4 C18---C17---C16 119.89 (19) O6---C43---H43B 109.4 C18---C17---H17 120.1 C44---C43---H43B 109.4 C16---C17---H17 120.1 H43A---C43---H43B 108.0 C17---C18---C19 121.22 (18) C43---C44---H44A 109.5 C17---C18---H18 119.4 C43---C44---H44B 109.5 C19---C18---H18 119.4 H44A---C44---H44B 109.5 C20---C19---C18 118.95 (18) C43---C44---H44C 109.5 C20---C19---H19 120.5 H44A---C44---H44C 109.5 C18---C19---H19 120.5 H44B---C44---H44C 109.5 C19---C20---C15 121.41 (18) O4---C39---O3 122.28 (17) C19---C20---H20 119.3 O4---C39---C40 119.18 (18) C15---C20---H20 119.3 O3---C39---C40 118.54 (17) C22---C21---C26 118.20 (17) C39---C40---H40A 109.5 C22---C21---C10 121.76 (15) C39---C40---H40B 109.5 C26---C21---C10 120.03 (16) H40A---C40---H40B 109.5 C23---C22---C21 121.00 (17) C39---C40---H40C 109.5 C23---C22---H22 119.5 H40A---C40---H40C 109.5 C21---C22---H22 119.5 H40B---C40---H40C 109.5 N12---C1---C2---C3 88.45 (19) C20---C15---C16---O1 178.30 (18) C13---C1---C2---C3 −152.89 (16) C14---C15---C16---O1 −3.1 (3) N12---C1---C2---C7 −90.60 (18) C20---C15---C16---C17 −0.8 (3) C13---C1---C2---C7 28.1 (2) C14---C15---C16---C17 177.75 (18) C7---C2---C3---C4 0.7 (3) O1---C16---C17---C18 −178.2 (2) C1---C2---C3---C4 −178.39 (16) C15---C16---C17---C18 1.0 (3) C2---C3---C4---C5 −0.3 (3) C16---C17---C18---C19 −0.1 (3) C3---C4---C5---C6 −0.6 (3) C17---C18---C19---C20 −1.0 (3) C4---C5---C6---C7 1.1 (3) C18---C19---C20---C15 1.2 (3) C5---C6---C7---O8 −178.01 (15) C16---C15---C20---C19 −0.3 (3) C5---C6---C7---C2 −0.6 (3) C14---C15---C20---C19 −178.86 (18) C3---C2---C7---O8 176.98 (15) C11---C10---C21---C22 44.7 (2) C1---C2---C7---O8 −3.9 (2) C9---C10---C21---C22 −82.32 (19) C3---C2---C7---C6 −0.2 (2) C11---C10---C21---C26 −133.91 (16) C1---C2---C7---C6 178.88 (15) C9---C10---C21---C26 99.07 (18) C6---C7---O8---C9 −173.46 (14) C26---C21---C22---C23 1.3 (2) C2---C7---O8---C9 9.2 (2) C10---C21---C22---C23 −177.29 (16) C7---O8---C9---N1 −158.67 (13) C21---C22---C23---C24 −1.0 (3) C7---O8---C9---C13 −38.05 (18) C22---C23---C24---C25 0.0 (3) C7---O8---C9---C10 83.72 (17) C23---C24---C25---C26 0.8 (3) O8---C9---C10---C21 57.51 (18) C24---C25---C26---C21 −0.4 (3) N1---C9---C10---C21 −61.23 (18) C22---C21---C26---C25 −0.6 (3) C13---C9---C10---C21 −179.16 (14) C10---C21---C26---C25 178.05 (16) O8---C9---C10---C11 −68.47 (17) N12---C11---C27---C32 −70.3 (2) N1---C9---C10---C11 172.79 (13) C10---C11---C27---C32 53.6 (2) C13---C9---C10---C11 54.86 (18) N12---C11---C27---C28 109.50 (17) C21---C10---C11---N12 −175.72 (13) C10---C11---C27---C28 −126.60 (17) C9---C10---C11---N12 −48.19 (18) C32---C27---C28---O2 −178.12 (15) C21---C10---C11---C27 60.78 (18) C11---C27---C28---O2 2.1 (2) C9---C10---C11---C27 −171.69 (14) C32---C27---C28---C29 1.5 (3) C27---C11---N12---C1 177.98 (13) C11---C27---C28---C29 −178.31 (16) C10---C11---N12---C1 52.95 (18) O2---C28---C29---C30 178.19 (17) C2---C1---N12---C11 58.31 (18) C27---C28---C29---C30 −1.4 (3) C13---C1---N12---C11 −63.00 (17) C28---C29---C30---C31 −0.3 (3) C2---C1---C13---C33 74.96 (19) C29---C30---C31---C32 1.8 (3) N12---C1---C13---C33 −165.24 (14) C30---C31---C32---C27 −1.7 (3) C2---C1---C13---C9 −53.37 (18) C28---C27---C32---C31 0.1 (3) N12---C1---C13---C9 66.44 (16) C11---C27---C32---C31 179.82 (17) O8---C9---C13---C33 −69.97 (18) C1---C13---C33---C38 127.54 (18) N1---C9---C13---C33 50.72 (19) C9---C13---C33---C38 −108.19 (18) C10---C9---C13---C33 167.57 (14) C1---C13---C33---C34 −54.1 (2) O8---C9---C13---C1 59.12 (16) C9---C13---C33---C34 70.1 (2) N1---C9---C13---C1 179.81 (13) C38---C33---C34---C35 0.5 (3) C10---C9---C13---C1 −63.34 (16) C13---C33---C34---C35 −177.78 (18) O8---C9---N1---C14 13.6 (2) C33---C34---C35---C36 0.1 (3) C13---C9---N1---C14 −108.74 (18) C34---C35---C36---C37 −1.1 (4) C10---C9---N1---C14 133.19 (16) C35---C36---C37---C38 1.4 (4) C9---N1---C14---C15 178.85 (16) C36---C37---C38---C33 −0.7 (3) N1---C14---C15---C16 1.3 (3) C34---C33---C38---C37 −0.2 (3) N1---C14---C15---C20 179.83 (17) C13---C33---C38---C37 178.19 (19) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4848 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1O···N1 0.94 1.73 2.608 (2) 154 O2---H2O···O3^i^ 0.97 1.67 2.637 (2) 177 O5---H5O···O6^ii^ 0.97 1.69 2.651 (2) 174 O6---H6O···O4 0.98 1.65 2.617 (2) 173 N12---H12A···O3 0.93 1.77 2.697 (2) 172 N12---H12B···O5 0.94 1.77 2.709 (2) 173 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- --------- ------- ----------- ------------- O1---H1O⋯N1 0.94 1.73 2.608 (2) 154 O2---H2O⋯O3^i^ 0.97 1.67 2.637 (2) 177 O5---H5O⋯O6^ii^ 0.97 1.69 2.651 (2) 174 O6---H6O⋯O4 0.98 1.65 2.617 (2) 173 N12---H12A⋯O3 0.93 1.77 2.697 (2) 172 N12---H12B⋯O5 0.94 1.77 2.709 (2) 173 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.774870	2011-2-05	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052148/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o560-o561", "authors": [ { "first": "Le Tuan", "last": "Anh" }, { "first": "Truong Hong", "last": "Hieu" }, { "first": "Anatoly T.", "last": "Soldatenkov" }, { "first": "Svetlana A.", "last": "Soldatova" }, { "first": "Victor N.", "last": "Khrustalev" } ] }
PMC3052149	Related literature {#sec1} ================== For tripodal Schiff base ligands, see: Kanesato et al. (2000[@bb5]) and for azo compounds, see: Butcher et al. (2005[@bb3]). For further synthetic details, see: Dinçalp et al. (2007[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~48~H~48~N~10~O~6~M ~r~ = 860.96Triclinic,a = 10.5613 (9) Åb = 12.1234 (5) Åc = 17.2107 (9) Åα = 86.418 (3)°β = 89.308 (2)°γ = 88.084 (3)°V = 2198.0 (2) Å^3^Z = 2Mo Kα radiationμ = 0.09 mm^−1^T = 150 K0.22 × 0.20 × 0.16 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (SORTAV; Blessing, 1995[@bb2]) T ~min~ = 0.827, T ~max~ = 0.99019855 measured reflections9781 independent reflections4152 reflections with I \> 2σ(I)R ~int~ = 0.071 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.062wR(F ^2^) = 0.187S = 0.999781 reflections589 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.23 e Å^−3^ {#d5e447} Data collection: COLLECT (Nonius, 2002[@bb6]); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997[@bb7]); data reduction: DENZO-SMN; program(s) used to solve structure: SIR92 (Altomare et al., 1994[@bb1]); program(s) used to refine structure: SHELXTL (Sheldrick, 2008[@bb8]); molecular graphics: PLATON (Spek, 2009[@bb9]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004405/hb5798sup1.cif](http://dx.doi.org/10.1107/S1600536811004405/hb5798sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004405/hb5798Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004405/hb5798Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5798&file=hb5798sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5798sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5798&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5798](http://scripts.iucr.org/cgi-bin/sendsup?hb5798)). We are grateful to Bu-Ali Sina University for financial support. Comment ======= Herein, we report the synthesis and X-ray crystal structure of the title compound, (I), (Fig. 1), a tripodal Schiff base ligand containing three azo groups. For tripodal Schiff base ligands see: Kanesato et al. (2000) and for azo compounds see: Butcher et al. (2005). The title compound adopts a cage-like conformation in the solid state. The geometry around the bridghead N atom of the compound is approximately pyramidal, since the angles C1--N1--C33, C1--N1--C17 and C33--N1--C17 have values of 112.3 (2), 113.5 (2) and 112.8 (2)°, respectively. The average of N═N bond lengths\[1.25 (3) Å\] is in the expected range and is in good agreement with values found in other similar compounds. Interestingly the hydrogen atom of one of three OH groups has transferred to one of three imine groups through intramolecular hydrogen bonding producing a zwitterionic compound. Three arms of tripodal ligand are located close to each other and in all of them there is an intramolecularhydrogen bonding (table 1). Experimental {#experimental} ============ Azo dye (5-(4-methoxyphenylazo)salicylaldehyde) was synthesized according to the literature procedure (Dinçalp et al., 2007). Then to a solution of above aldehyde (3 mmol) in ethanol (70 ml) was added tren (1 mmol) in the same solvent (10 ml) (see Scheme I). The solution was stirred for 12 h at 40°C. The resulting orange precipitate was filtered and dried in vacuum. Orange blocks of (I) were obtained by slow evaporation from a acetonitril solution at room temperature after 24 h. Refinement {#refinement} ========== The H(C) atom positions were calculated and refined in isotropic approximatiom within riding model with the U~iso~(H) parameters equal to 1.2 U~eq~(Ci) where U(Ci) is the equivalent thermal parameters of the carbon atoms to which corresponding H atoms are bonded. \'H atoms bonded to C atoms were placed in calculated positions with C-H distances in the range 0.95-0.99 Å and were included in the refinement in a riding-model approximation with U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(C~methyl~). H atoms bonded to O and N atoms were refined independently with isotropic displacement parameters. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the structure of (I), with displacement ellipsoids drawn at the 50% probability level. All C-bonded H atoms omitted for clarity. ::: ![](e-67-0o606-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e125 .table-wrap} ----------------------- --------------------------------------- C~48~H~48~N~10~O~6~ Z = 2 M~r~ = 860.96 F(000) = 908 Triclinic, P1 D~x~ = 1.301 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.5613 (9) Å Cell parameters from 7794 reflections b = 12.1234 (5) Å θ = 2.6--27.5° c = 17.2107 (9) Å µ = 0.09 mm^−1^ α = 86.418 (3)° T = 150 K β = 89.308 (2)° Block, orange γ = 88.084 (3)° 0.22 × 0.20 × 0.16 mm V = 2198.0 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e261 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 9781 independent reflections Radiation source: fine-focus sealed tube 4152 reflections with I \> 2σ(I) graphite R~int~ = 0.071 Detector resolution: 9 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.6° φ scans and ω scans with κ offsets h = −13→13 Absorption correction: multi-scan (SORTAV; Blessing, 1995) k = −15→15 T~min~ = 0.827, T~max~ = 0.990 l = −22→22 19855 measured reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e387 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.062 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.187 H atoms treated by a mixture of independent and constrained refinement S = 0.99 w = 1/\[σ^2^(F~o~^2^) + (0.0768P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 9781 reflections (Δ/σ)~max~ = 0.001 589 parameters Δρ~max~ = 0.37 e Å^−3^ 2 restraints Δρ~min~ = −0.23 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e541 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e640 .table-wrap} ------ --------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.2448 (2) 0.82743 (16) 0.82789 (12) 0.0474 (6) O2 0.43622 (18) 0.45882 (17) 0.57762 (12) 0.0495 (6) O3 −0.0630 (2) 0.8117 (2) 0.50993 (12) 0.0576 (6) O4 −0.1109 (2) −0.08081 (19) 0.91613 (15) 0.0776 (8) O5 −0.47340 (19) −0.00203 (17) 0.79102 (13) 0.0582 (6) O6 −0.57085 (19) 0.29892 (18) 1.01599 (12) 0.0571 (6) N1 0.3726 (2) 0.8543 (2) 0.56017 (14) 0.0444 (6) N2 0.3882 (2) 0.74854 (19) 0.72451 (13) 0.0403 (6) N3 0.3183 (3) 0.6273 (2) 0.50901 (14) 0.0431 (6) N4 0.0959 (2) 0.8958 (2) 0.59704 (14) 0.0438 (6) N5 0.0284 (2) 0.4183 (2) 0.88438 (14) 0.0460 (6) N6 0.0856 (2) 0.3371 (2) 0.85796 (14) 0.0427 (6) N7 −0.0348 (2) 0.3043 (2) 0.66786 (13) 0.0418 (6) N8 −0.0348 (2) 0.2007 (2) 0.68282 (13) 0.0425 (6) N9 −0.2363 (2) 0.5682 (2) 0.77249 (14) 0.0457 (6) N10 −0.3386 (2) 0.5194 (2) 0.76315 (14) 0.0475 (7) C1 0.4720 (3) 0.8657 (2) 0.61690 (17) 0.0468 (8) H1A 0.4489 0.9278 0.6495 0.056\ H1B 0.5521 0.8835 0.5891 0.056\* C2 0.4926 (3) 0.7609 (2) 0.66887 (17) 0.0439 (8) H2A 0.4983 0.6961 0.6366 0.053\* H2B 0.5733 0.7644 0.6972 0.053\* C3 0.3336 (3) 0.6552 (2) 0.73432 (15) 0.0368 (7) H3A 0.3584 0.5963 0.7029 0.044\* C4 0.2343 (2) 0.6388 (2) 0.79291 (15) 0.0355 (7) C5 0.1799 (3) 0.5360 (2) 0.80621 (16) 0.0393 (7) H5A 0.2052 0.4766 0.7754 0.047\* C6 0.0884 (3) 0.5204 (3) 0.86465 (17) 0.0422 (7) C7 0.0480 (3) 0.6087 (3) 0.90776 (17) 0.0476 (8) H7A −0.0164 0.5984 0.9463 0.057\* C8 0.1006 (3) 0.7108 (3) 0.89495 (16) 0.0459 (8) H8A 0.0728 0.7705 0.9248 0.055\* C9 0.1939 (3) 0.7264 (2) 0.83858 (16) 0.0384 (7) C10 0.0247 (3) 0.2334 (2) 0.87651 (16) 0.0405 (7) C11 0.0921 (3) 0.1410 (3) 0.85677 (18) 0.0494 (8) H11A 0.1733 0.1485 0.8330 0.059\* C12 0.0447 (3) 0.0371 (3) 0.87057 (19) 0.0574 (9) H12A 0.0926 −0.0264 0.8564 0.069\* C13 −0.0730 (3) 0.0262 (3) 0.90515 (19) 0.0508 (8) C14 −0.1426 (3) 0.1186 (3) 0.92557 (17) 0.0520 (9) H14A −0.2237 0.1114 0.9495 0.062\* C15 −0.0925 (3) 0.2223 (3) 0.91061 (16) 0.0468 (8) H15A −0.1399 0.2863 0.9242 0.056\* C16 −0.2313 (4) −0.0982 (3) 0.9522 (2) 0.0927 (15) H16A −0.2475 −0.1775 0.9563 0.139\* H16B −0.2974 −0.0590 0.9208 0.139\* H16C −0.2318 −0.0701 1.0044 0.139\* C17 0.4180 (3) 0.8058 (3) 0.48855 (17) 0.0487 (8) H17A 0.4997 0.7654 0.4989 0.058\* H17B 0.4333 0.8659 0.4482 0.058\* C18 0.3250 (3) 0.7275 (2) 0.45807 (17) 0.0489 (8) H18A 0.2401 0.7645 0.4544 0.059\* H18B 0.3515 0.7080 0.4052 0.059\* C19 0.2148 (3) 0.5907 (2) 0.54053 (16) 0.0422 (7) H19A 0.1382 0.6330 0.5325 0.051\* C20 0.2118 (3) 0.4892 (2) 0.58677 (16) 0.0391 (7) C21 0.0946 (3) 0.4468 (2) 0.61236 (16) 0.0392 (7) H21A 0.0193 0.4910 0.6044 0.047\* C22 0.0871 (3) 0.3435 (2) 0.64833 (16) 0.0397 (7) C23 0.2004 (3) 0.2813 (2) 0.66447 (16) 0.0411 (7) H23A 0.1959 0.2101 0.6906 0.049\* C24 0.3155 (3) 0.3206 (2) 0.64355 (15) 0.0413 (7) H24A 0.3897 0.2777 0.6573 0.050\* C25 0.3276 (3) 0.4250 (2) 0.60136 (16) 0.0393 (7) C26 −0.1541 (3) 0.1589 (2) 0.70770 (16) 0.0404 (7) C27 −0.1660 (3) 0.0458 (3) 0.7050 (2) 0.0548 (9) H27A −0.0983 0.0027 0.6844 0.066\* C28 −0.2738 (3) −0.0052 (3) 0.7316 (2) 0.0573 (9) H28A −0.2810 −0.0826 0.7283 0.069\* C29 −0.3711 (3) 0.0563 (3) 0.76274 (18) 0.0453 (8) C30 −0.3613 (3) 0.1697 (2) 0.76609 (16) 0.0430 (8) H30A −0.4288 0.2125 0.7873 0.052\* C31 −0.2526 (3) 0.2202 (2) 0.73831 (16) 0.0413 (7) H31A −0.2459 0.2979 0.7404 0.050\* C32 −0.5733 (3) 0.0585 (3) 0.8261 (2) 0.0722 (11) H32A −0.6401 0.0081 0.8435 0.108\* H32B −0.6081 0.1147 0.7881 0.108\* H32C −0.5410 0.0945 0.8709 0.108\* C33 0.2976 (3) 0.9573 (3) 0.54508 (19) 0.0515 (9) H33A 0.2576 0.9564 0.4934 0.062\* H33B 0.3547 1.0206 0.5436 0.062\* C34 0.1956 (3) 0.9737 (3) 0.60625 (18) 0.0497 (8) H34A 0.2325 0.9617 0.6588 0.060\* H34B 0.1600 1.0503 0.6006 0.060\* C35 0.0569 (3) 0.8342 (2) 0.65497 (18) 0.0420 (7) H35A 0.0957 0.8376 0.7042 0.050\* C36 −0.0453 (3) 0.7596 (2) 0.64655 (17) 0.0379 (7) C37 −0.0930 (3) 0.6951 (2) 0.71012 (17) 0.0413 (7) H37A −0.0565 0.7003 0.7599 0.050\* C38 −0.1911 (3) 0.6244 (2) 0.70259 (17) 0.0412 (7) C39 −0.2429 (3) 0.6148 (3) 0.62893 (18) 0.0484 (8) H39A −0.3081 0.5641 0.6225 0.058\* C40 −0.1999 (3) 0.6784 (3) 0.56589 (18) 0.0491 (8) H40A −0.2370 0.6725 0.5164 0.059\* C41 −0.1031 (3) 0.7508 (3) 0.57366 (17) 0.0436 (8) C42 −0.3878 (3) 0.4641 (2) 0.83188 (18) 0.0424 (7) C43 −0.3285 (3) 0.4523 (2) 0.90327 (18) 0.0476 (8) H43A −0.2474 0.4822 0.9091 0.057\* C44 −0.3864 (3) 0.3974 (2) 0.96617 (19) 0.0484 (8) H44A −0.3451 0.3892 1.0150 0.058\* C45 −0.5053 (3) 0.3540 (2) 0.95763 (18) 0.0437 (8) C46 −0.5658 (3) 0.3664 (2) 0.88634 (18) 0.0466 (8) H46A −0.6480 0.3384 0.8807 0.056\* C47 −0.5060 (3) 0.4197 (2) 0.82372 (18) 0.0445 (8) H47A −0.5461 0.4260 0.7745 0.053\* C48 −0.5098 (3) 0.2782 (3) 1.08894 (19) 0.0662 (10) H48A −0.5668 0.2386 1.1255 0.099\* H48B −0.4884 0.3486 1.1097 0.099\* H48C −0.4322 0.2331 1.0819 0.099\* H1 0.308 (4) 0.816 (3) 0.787 (2) 0.103 (14)\* H2 0.392 (4) 0.573 (3) 0.519 (2) 0.100 (14)\* H3 0.005 (4) 0.867 (3) 0.529 (2) 0.103 (13)\* ------ --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2158 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0573 (14) 0.0363 (13) 0.0490 (14) −0.0036 (11) 0.0010 (11) −0.0046 (10) O2 0.0392 (12) 0.0557 (14) 0.0529 (13) −0.0072 (11) 0.0028 (10) 0.0031 (11) O3 0.0633 (15) 0.0720 (16) 0.0368 (13) −0.0080 (13) −0.0009 (11) 0.0047 (11) O4 0.0704 (17) 0.0500 (15) 0.110 (2) −0.0222 (14) −0.0129 (15) 0.0250 (14) O5 0.0429 (13) 0.0481 (14) 0.0844 (17) −0.0111 (11) 0.0115 (12) −0.0067 (12) O6 0.0515 (13) 0.0604 (15) 0.0587 (15) −0.0159 (12) −0.0064 (11) 0.0113 (12) N1 0.0423 (14) 0.0430 (16) 0.0467 (16) −0.0039 (13) 0.0005 (12) 0.0069 (12) N2 0.0393 (14) 0.0391 (15) 0.0419 (15) −0.0059 (12) −0.0013 (11) 0.0052 (12) N3 0.0450 (16) 0.0394 (16) 0.0443 (16) −0.0041 (14) −0.0011 (12) 0.0046 (12) N4 0.0435 (15) 0.0435 (16) 0.0435 (16) −0.0001 (13) 0.0017 (12) 0.0037 (13) N5 0.0510 (16) 0.0430 (15) 0.0435 (16) −0.0004 (13) 0.0029 (12) 0.0005 (13) N6 0.0430 (14) 0.0414 (16) 0.0436 (16) 0.0015 (13) −0.0007 (12) −0.0027 (13) N7 0.0406 (15) 0.0424 (16) 0.0421 (15) −0.0036 (13) −0.0012 (11) 0.0010 (12) N8 0.0380 (14) 0.0400 (16) 0.0494 (16) −0.0053 (12) 0.0022 (11) 0.0001 (12) N9 0.0362 (14) 0.0437 (16) 0.0563 (17) 0.0001 (13) 0.0005 (12) 0.0020 (13) N10 0.0423 (15) 0.0434 (16) 0.0563 (17) −0.0005 (13) 0.0014 (13) −0.0011 (13) C1 0.0449 (18) 0.0451 (19) 0.0500 (19) −0.0146 (16) 0.0008 (15) 0.0068 (15) C2 0.0349 (16) 0.0456 (19) 0.0502 (19) −0.0052 (15) 0.0028 (14) 0.0069 (15) C3 0.0391 (16) 0.0346 (17) 0.0362 (17) −0.0026 (14) −0.0023 (13) 0.0011 (13) C4 0.0361 (16) 0.0338 (17) 0.0363 (17) −0.0036 (14) −0.0021 (13) 0.0022 (14) C5 0.0417 (17) 0.0373 (18) 0.0386 (17) −0.0049 (14) −0.0070 (14) 0.0043 (14) C6 0.0416 (17) 0.0457 (18) 0.0383 (17) −0.0076 (15) −0.0042 (14) 0.0091 (15) C7 0.0518 (19) 0.053 (2) 0.0372 (18) 0.0022 (17) 0.0066 (15) 0.0029 (16) C8 0.058 (2) 0.0410 (19) 0.0384 (18) −0.0017 (16) 0.0006 (15) −0.0017 (15) C9 0.0428 (17) 0.0359 (18) 0.0363 (17) −0.0045 (15) −0.0029 (14) 0.0027 (14) C10 0.0433 (18) 0.0397 (19) 0.0377 (18) −0.0064 (16) −0.0026 (14) 0.0071 (14) C11 0.0462 (19) 0.043 (2) 0.058 (2) 0.0001 (17) 0.0081 (16) −0.0002 (16) C12 0.060 (2) 0.037 (2) 0.075 (2) −0.0009 (17) 0.0048 (19) −0.0001 (17) C13 0.054 (2) 0.043 (2) 0.054 (2) −0.0083 (18) −0.0071 (16) 0.0164 (16) C14 0.0422 (18) 0.068 (2) 0.044 (2) −0.0058 (19) 0.0040 (15) 0.0052 (17) C15 0.0526 (19) 0.045 (2) 0.0428 (19) −0.0007 (16) −0.0025 (15) −0.0013 (15) C16 0.070 (3) 0.095 (3) 0.110 (3) −0.047 (3) −0.019 (2) 0.045 (3) C17 0.0464 (18) 0.052 (2) 0.046 (2) −0.0053 (16) 0.0106 (15) 0.0057 (16) C18 0.0484 (18) 0.053 (2) 0.0441 (19) −0.0024 (17) −0.0008 (15) 0.0067 (16) C19 0.0408 (17) 0.0424 (17) 0.0440 (18) −0.0059 (15) 0.0021 (14) −0.0053 (13) C20 0.0423 (17) 0.0392 (16) 0.0362 (17) −0.0047 (15) 0.0038 (13) −0.0053 (12) C21 0.0374 (17) 0.0362 (18) 0.0443 (18) 0.0005 (14) 0.0031 (13) −0.0066 (14) C22 0.0361 (17) 0.0387 (18) 0.0442 (18) −0.0038 (15) 0.0024 (14) −0.0021 (14) C23 0.0442 (18) 0.0394 (18) 0.0398 (18) −0.0033 (15) −0.0009 (14) −0.0015 (14) C24 0.0404 (17) 0.0441 (19) 0.0394 (18) 0.0001 (15) −0.0052 (14) −0.0016 (15) C25 0.0413 (18) 0.0425 (19) 0.0350 (17) −0.0046 (15) −0.0008 (13) −0.0070 (14) C26 0.0352 (17) 0.0413 (19) 0.0447 (18) −0.0060 (15) 0.0000 (14) 0.0003 (15) C27 0.0396 (18) 0.041 (2) 0.084 (3) −0.0007 (16) 0.0092 (17) −0.0078 (18) C28 0.0412 (19) 0.040 (2) 0.092 (3) −0.0058 (17) 0.0081 (18) −0.0106 (18) C29 0.0367 (17) 0.043 (2) 0.056 (2) −0.0108 (16) 0.0003 (15) −0.0011 (16) C30 0.0397 (17) 0.0408 (19) 0.0478 (19) 0.0021 (15) 0.0069 (14) −0.0010 (15) C31 0.0443 (18) 0.0352 (17) 0.0441 (18) −0.0046 (15) 0.0001 (14) 0.0022 (14) C32 0.054 (2) 0.062 (3) 0.100 (3) −0.010 (2) 0.029 (2) −0.003 (2) C33 0.052 (2) 0.044 (2) 0.057 (2) −0.0073 (17) −0.0002 (16) 0.0115 (16) C34 0.0513 (19) 0.0378 (19) 0.059 (2) 0.0016 (16) −0.0034 (16) 0.0024 (16) C35 0.0391 (17) 0.0427 (19) 0.0432 (19) 0.0066 (15) −0.0024 (14) 0.0002 (15) C36 0.0352 (16) 0.0368 (17) 0.0410 (18) 0.0071 (14) 0.0008 (13) −0.0004 (14) C37 0.0365 (16) 0.0456 (19) 0.0416 (18) 0.0012 (15) −0.0070 (13) 0.0000 (15) C38 0.0345 (16) 0.0414 (18) 0.0465 (19) 0.0064 (15) 0.0035 (14) 0.0016 (15) C39 0.0434 (18) 0.048 (2) 0.055 (2) −0.0021 (16) 0.0027 (16) −0.0147 (17) C40 0.0484 (19) 0.061 (2) 0.0383 (18) 0.0025 (17) −0.0013 (15) −0.0097 (16) C41 0.0406 (17) 0.050 (2) 0.0397 (19) 0.0070 (16) 0.0021 (14) −0.0007 (15) C42 0.0376 (17) 0.0347 (18) 0.054 (2) 0.0017 (14) 0.0000 (15) 0.0007 (15) C43 0.0365 (17) 0.0442 (19) 0.062 (2) 0.0005 (15) −0.0075 (16) 0.0000 (16) C44 0.0391 (18) 0.051 (2) 0.055 (2) −0.0069 (16) −0.0086 (15) 0.0059 (16) C45 0.0391 (17) 0.0350 (18) 0.057 (2) −0.0041 (15) 0.0034 (15) 0.0004 (15) C46 0.0372 (17) 0.0437 (19) 0.059 (2) −0.0045 (15) −0.0053 (16) −0.0011 (16) C47 0.0399 (17) 0.0423 (19) 0.051 (2) 0.0005 (15) −0.0059 (15) −0.0035 (15) C48 0.066 (2) 0.072 (3) 0.060 (2) −0.018 (2) −0.0120 (19) 0.0141 (19) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3374 .table-wrap} ------------------- ----------- ------------------- ----------- O1---C9 1.355 (3) C17---C18 1.509 (4) O1---H1 0.98 (4) C17---H17A 0.9900 O2---C25 1.284 (3) C17---H17B 0.9900 O3---C41 1.355 (3) C18---H18A 0.9900 O3---H3 1.07 (4) C18---H18B 0.9900 O4---C13 1.371 (3) C19---C20 1.424 (4) O4---C16 1.425 (4) C19---H19A 0.9500 O5---C29 1.378 (3) C20---C21 1.411 (4) O5---C32 1.416 (4) C20---C25 1.444 (4) O6---C45 1.366 (3) C21---C22 1.366 (4) O6---C48 1.423 (3) C21---H21A 0.9500 N1---C1 1.459 (3) C22---C23 1.414 (4) N1---C33 1.467 (4) C23---C24 1.357 (4) N1---C17 1.467 (4) C23---H23A 0.9500 N2---C3 1.288 (3) C24---C25 1.428 (4) N2---C2 1.457 (3) C24---H24A 0.9500 N3---C19 1.294 (3) C26---C31 1.377 (4) N3---C18 1.457 (4) C26---C27 1.385 (4) N3---H2 1.02 (4) C27---C28 1.373 (4) N4---C35 1.281 (3) C27---H27A 0.9500 N4---C34 1.454 (3) C28---C29 1.372 (4) N5---N6 1.245 (3) C28---H28A 0.9500 N5---C6 1.429 (3) C29---C30 1.388 (4) N6---C10 1.447 (3) C30---C31 1.385 (4) N7---N8 1.266 (3) C30---H30A 0.9500 N7---C22 1.417 (3) C31---H31A 0.9500 N8---C26 1.425 (3) C32---H32A 0.9800 N9---N10 1.266 (3) C32---H32B 0.9800 N9---C38 1.430 (4) C32---H32C 0.9800 N10---C42 1.424 (4) C33---C34 1.514 (4) C1---C2 1.518 (4) C33---H33A 0.9900 C1---H1A 0.9900 C33---H33B 0.9900 C1---H1B 0.9900 C34---H34A 0.9900 C2---H2A 0.9900 C34---H34B 0.9900 C2---H2B 0.9900 C35---C36 1.445 (4) C3---C4 1.456 (4) C35---H35A 0.9500 C3---H3A 0.9500 C36---C37 1.403 (4) C4---C5 1.395 (3) C36---C41 1.414 (4) C4---C9 1.412 (4) C37---C38 1.380 (4) C5---C6 1.395 (4) C37---H37A 0.9500 C5---H5A 0.9500 C38---C39 1.400 (4) C6---C7 1.393 (4) C39---C40 1.373 (4) C7---C8 1.378 (4) C39---H39A 0.9500 C7---H7A 0.9500 C40---C41 1.382 (4) C8---C9 1.384 (4) C40---H40A 0.9500 C8---H8A 0.9500 C42---C43 1.383 (4) C10---C11 1.366 (4) C42---C47 1.388 (4) C10---C15 1.371 (4) C43---C44 1.382 (4) C11---C12 1.376 (4) C43---H43A 0.9500 C11---H11A 0.9500 C44---C45 1.390 (4) C12---C13 1.379 (4) C44---H44A 0.9500 C12---H12A 0.9500 C45---C46 1.388 (4) C13---C14 1.381 (4) C46---C47 1.379 (4) C14---C15 1.388 (4) C46---H46A 0.9500 C14---H14A 0.9500 C47---H47A 0.9500 C15---H15A 0.9500 C48---H48A 0.9800 C16---H16A 0.9800 C48---H48B 0.9800 C16---H16B 0.9800 C48---H48C 0.9800 C16---H16C 0.9800 C9---O1---H1 102 (2) C22---C21---H21A 119.3 C41---O3---H3 107 (2) C20---C21---H21A 119.3 C13---O4---C16 117.4 (3) C21---C22---C23 118.8 (3) C29---O5---C32 117.3 (2) C21---C22---N7 117.9 (3) C45---O6---C48 117.7 (2) C23---C22---N7 123.2 (3) C1---N1---C33 112.3 (2) C24---C23---C22 121.7 (3) C1---N1---C17 113.5 (2) C24---C23---H23A 119.2 C33---N1---C17 112.8 (2) C22---C23---H23A 119.2 C3---N2---C2 119.8 (3) C23---C24---C25 121.5 (3) C19---N3---C18 124.2 (3) C23---C24---H24A 119.2 C19---N3---H2 111 (2) C25---C24---H24A 119.2 C18---N3---H2 124 (2) O2---C25---C24 121.2 (3) C35---N4---C34 120.9 (3) O2---C25---C20 122.4 (3) N6---N5---C6 113.1 (2) C24---C25---C20 116.4 (3) N5---N6---C10 113.6 (2) C31---C26---C27 118.7 (3) N8---N7---C22 113.0 (3) C31---C26---N8 125.4 (3) N7---N8---C26 114.7 (3) C27---C26---N8 115.8 (3) N10---N9---C38 113.0 (2) C28---C27---C26 121.3 (3) N9---N10---C42 114.6 (2) C28---C27---H27A 119.4 N1---C1---C2 111.9 (2) C26---C27---H27A 119.4 N1---C1---H1A 109.2 C29---C28---C27 119.7 (3) C2---C1---H1A 109.2 C29---C28---H28A 120.1 N1---C1---H1B 109.2 C27---C28---H28A 120.1 C2---C1---H1B 109.2 C28---C29---O5 116.0 (3) H1A---C1---H1B 107.9 C28---C29---C30 120.1 (3) N2---C2---C1 110.1 (2) O5---C29---C30 123.9 (3) N2---C2---H2A 109.6 C31---C30---C29 119.6 (3) C1---C2---H2A 109.6 C31---C30---H30A 120.2 N2---C2---H2B 109.6 C29---C30---H30A 120.2 C1---C2---H2B 109.6 C26---C31---C30 120.7 (3) H2A---C2---H2B 108.2 C26---C31---H31A 119.7 N2---C3---C4 120.8 (3) C30---C31---H31A 119.7 N2---C3---H3A 119.6 O5---C32---H32A 109.5 C4---C3---H3A 119.6 O5---C32---H32B 109.5 C5---C4---C9 119.0 (2) H32A---C32---H32B 109.5 C5---C4---C3 120.7 (3) O5---C32---H32C 109.5 C9---C4---C3 120.3 (2) H32A---C32---H32C 109.5 C4---C5---C6 120.1 (3) H32B---C32---H32C 109.5 C4---C5---H5A 120.0 N1---C33---C34 112.5 (2) C6---C5---H5A 120.0 N1---C33---H33A 109.1 C7---C6---C5 119.9 (3) C34---C33---H33A 109.1 C7---C6---N5 115.3 (3) N1---C33---H33B 109.1 C5---C6---N5 124.9 (3) C34---C33---H33B 109.1 C8---C7---C6 120.6 (3) H33A---C33---H33B 107.8 C8---C7---H7A 119.7 N4---C34---C33 109.4 (2) C6---C7---H7A 119.7 N4---C34---H34A 109.8 C7---C8---C9 120.0 (3) C33---C34---H34A 109.8 C7---C8---H8A 120.0 N4---C34---H34B 109.8 C9---C8---H8A 120.0 C33---C34---H34B 109.8 O1---C9---C8 118.7 (3) H34A---C34---H34B 108.2 O1---C9---C4 120.9 (2) N4---C35---C36 121.0 (3) C8---C9---C4 120.5 (3) N4---C35---H35A 119.5 C11---C10---C15 119.3 (3) C36---C35---H35A 119.5 C11---C10---N6 115.4 (3) C37---C36---C41 117.3 (3) C15---C10---N6 125.4 (3) C37---C36---C35 121.8 (3) C10---C11---C12 121.3 (3) C41---C36---C35 120.9 (3) C10---C11---H11A 119.3 C38---C37---C36 122.0 (3) C12---C11---H11A 119.3 C38---C37---H37A 119.0 C11---C12---C13 119.3 (3) C36---C37---H37A 119.0 C11---C12---H12A 120.4 C37---C38---C39 119.0 (3) C13---C12---H12A 120.4 C37---C38---N9 116.7 (3) O4---C13---C12 114.4 (3) C39---C38---N9 124.2 (3) O4---C13---C14 125.3 (3) C40---C39---C38 120.3 (3) C12---C13---C14 120.3 (3) C40---C39---H39A 119.9 C13---C14---C15 119.1 (3) C38---C39---H39A 119.9 C13---C14---H14A 120.5 C39---C40---C41 120.7 (3) C15---C14---H14A 120.5 C39---C40---H40A 119.6 C10---C15---C14 120.8 (3) C41---C40---H40A 119.6 C10---C15---H15A 119.6 O3---C41---C40 118.9 (3) C14---C15---H15A 119.6 O3---C41---C36 120.5 (3) O4---C16---H16A 109.5 C40---C41---C36 120.6 (3) O4---C16---H16B 109.5 C43---C42---C47 119.4 (3) H16A---C16---H16B 109.5 C43---C42---N10 125.8 (3) O4---C16---H16C 109.5 C47---C42---N10 114.8 (3) H16A---C16---H16C 109.5 C44---C43---C42 120.5 (3) H16B---C16---H16C 109.5 C44---C43---H43A 119.8 N1---C17---C18 112.3 (2) C42---C43---H43A 119.8 N1---C17---H17A 109.1 C43---C44---C45 119.7 (3) C18---C17---H17A 109.1 C43---C44---H44A 120.1 N1---C17---H17B 109.1 C45---C44---H44A 120.1 C18---C17---H17B 109.1 O6---C45---C46 115.5 (2) H17A---C17---H17B 107.9 O6---C45---C44 124.4 (3) N3---C18---C17 110.9 (2) C46---C45---C44 120.1 (3) N3---C18---H18A 109.5 C47---C46---C45 119.5 (3) C17---C18---H18A 109.5 C47---C46---H46A 120.2 N3---C18---H18B 109.5 C45---C46---H46A 120.2 C17---C18---H18B 109.5 C46---C47---C42 120.7 (3) H18A---C18---H18B 108.1 C46---C47---H47A 119.6 N3---C19---C20 122.2 (3) C42---C47---H47A 119.6 N3---C19---H19A 118.9 O6---C48---H48A 109.5 C20---C19---H19A 118.9 O6---C48---H48B 109.5 C21---C20---C19 120.0 (3) H48A---C48---H48B 109.5 C21---C20---C25 120.0 (3) O6---C48---H48C 109.5 C19---C20---C25 119.8 (3) H48A---C48---H48C 109.5 C22---C21---C20 121.4 (3) H48B---C48---H48C 109.5 ------------------- ----------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4793 .table-wrap} ----------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O3---H3···N4 1.07 (4) 1.58 (4) 2.543 (3) 146 (3) O1---H1···N2 0.98 (4) 1.61 (4) 2.534 (3) 157 (3) N3---H2···O2 1.02 (4) 1.71 (4) 2.585 (3) 142 (3) N3---H2···O2^i^ 1.02 (4) 2.48 (4) 3.155 (3) 123 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- ---------- ---------- ----------- ------------- O3---H3⋯N4 1.07 (4) 1.58 (4) 2.543 (3) 146 (3) O1---H1⋯N2 0.98 (4) 1.61 (4) 2.534 (3) 157 (3) N3---H2⋯O2 1.02 (4) 1.71 (4) 2.585 (3) 142 (3) N3---H2⋯O2^i^ 1.02 (4) 2.48 (4) 3.155 (3) 123 (3) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.785910	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052149/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o606", "authors": [ { "first": "Sadegh", "last": "Salehzadeh" }, { "first": "Mahsa", "last": "Mahdavian" }, { "first": "Mehdi", "last": "Khalaj" } ] }
PMC3052150	Related literature {#sec1} ================== For general background to aroylhydrazines and their metal complexes, see: Cariati et al. (2002[@bb2]); Chen et al. (2010[@bb4]); Fun et al. (1996[@bb5]); Liao et al. (2000[@bb7]); Liu & Gao (1998[@bb8]); Lu et al. (1996[@bb9]); Tai et al. (2003[@bb13]); Xue & Liu (2006[@bb16]); Yang & Pan (2004[@bb17]). For related structures, see: Chen & Liu (2006[@bb3]); Tan et al. (2010[@bb14]); Wu & Liu (2004[@bb15]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co(C~15~H~12~N~3~O~4~)~2~Cl(C~6~H~7~N)\]M ~r~ = 784.06Triclinic,a = 10.530 (2) Åb = 14.028 (3) Åc = 14.794 (3) Åα = 62.203 (3)°β = 85.669 (3)°γ = 72.275 (3)°V = 1835.6 (7) Å^3^Z = 2Mo Kα radiationμ = 0.60 mm^−1^T = 293 K0.12 × 0.10 × 0.08 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID diffractometerAbsorption correction: multi-scan (ABSCOR; Higashi, 1995[@bb6]) T ~min~ = 0.931, T ~max~ = 0.95412688 measured reflections6308 independent reflections3144 reflections with I \> 2σ(I)R ~int~ = 0.064 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.063wR(F ^2^) = 0.157S = 0.946308 reflections478 parametersH-atom parameters constrainedΔρ~max~ = 0.73 e Å^−3^Δρ~min~ = −0.29 e Å^−3^ {#d5e483} Data collection: RAPID-AUTO (Rigaku, 1998[@bb10]); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002[@bb11]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb12]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb12]); molecular graphics: DIAMOND (Brandenburg, 1999[@bb1]); software used to prepare material for publication: SHELXTL (Sheldrick, 2008[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003321/hy2400sup1.cif](http://dx.doi.org/10.1107/S1600536811003321/hy2400sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003321/hy2400Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003321/hy2400Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hy2400&file=hy2400sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hy2400sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hy2400&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HY2400](http://scripts.iucr.org/cgi-bin/sendsup?hy2400)). The authors acknowledge financial support from the Young Teachers' Foundation of Fujian Agriculture and Forest University (grant No. 08B10). Comment ======= Recently, much attention has been paid to the chemistry of aroylhydrazines and their complexes with metal ions (Cariati et al., 2002; Chen et al., 2010; Liu & Gao 1998; Tai et al., 2003; Xue & Liu, 2006). These compounds can serve as potential chelating agents (Fun et al., 1996; Lu et al., 1996) and possess biological activity (Liao et al., 2000; Yang & Pan, 2004). Here we report the synthesis and crystal structure of the title compound. As shown in Fig. 1, the Co^III^ ion exists in a distorted octahedral N~3~O~2~Cl coordination geometry. The equatorial plane is defined by three donor atoms (O3, O7 and N3) from two hydrazine ligands and N7 atom from a 4-methylpyridine ligand, with an r.m.s. deviation of 0.0305 Å from the mean plane. The axial sites are occupied by N6 of one hydrazine ligand and Cl1. The Co^III^ ion is displaced towards the axial Cl1 atom by 0.038 (2)Å from the equatorial plane. Bond distances (Table 1) and bond angles around Co1 atom are compared with those in the reported cobalt complexes (Chen & Liu, 2006; Tan et al., 2010; Wu & Liu, 2004). Experimental {#experimental} ============ The hydrazine ligand (HL) was prepared by the reaction of o-methoxybenzaldehyde and p-nitrobenzoylhydrazine in a molar ratio of 1:1 under reflux in ethanol for 3 h. The yellow product obtained on cooling was recrystallized from methanol. To HL (1 mmol) in DMF (5 ml) was added an equimolar amount of CoCl~2~ in methanol (5 ml). After stirring for 15 min, 0.2 ml p-methylpyridine was added to the solution. The resulting mixture was stirred at room temperature for an additional period of 1 h and then filtered. Brown prism-shaped crystals were obtained from the solution after two weeks. Analysis, calculated for C~36~H~31~ClCoN~7~O~8~: C 54.98, H 4.01, N 12.43%; found: C 55.10, H 3.95, N 12.50%. Refinement {#refinement} ========== H atoms were placed at calculated positions and treated as riding on their parent atoms, with C---H = 0.93 (CH) and 0.96 (CH~3~) Å and with U~iso~(H) = 1.2(1.5 for methyl)U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids. ::: ![](e-67-0m293-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e162 .table-wrap} -------------------------------------------- --------------------------------------- \[Co(C~15~H~12~N~3~O~4~)~2~Cl(C~6~H~7~N)\] Z = 2 M~r~ = 784.06 F(000) = 808 Triclinic, P1 D~x~ = 1.419 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.530 (2) Å Cell parameters from 3144 reflections b = 14.028 (3) Å θ = 2.0--25.0° c = 14.794 (3) Å µ = 0.60 mm^−1^ α = 62.203 (3)° T = 293 K β = 85.669 (3)° Prism, brown γ = 72.275 (3)° 0.12 × 0.10 × 0.08 mm V = 1835.6 (7) Å^3^ -------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e309 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID diffractometer 6308 independent reflections Radiation source: rotation anode 3144 reflections with I \> 2σ(I) graphite R~int~ = 0.064 ω scans θ~max~ = 25.0°, θ~min~ = 2.0° Absorption correction: multi-scan (ABSCOR; Higashi, 1995) h = −12→12 T~min~ = 0.931, T~max~ = 0.954 k = −16→14 12688 measured reflections l = −17→17 ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e423 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.063 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.157 H-atom parameters constrained S = 0.94 w = 1/\[σ^2^(F~o~^2^) + (0.0697P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 6308 reflections (Δ/σ)~max~ = 0.001 478 parameters Δρ~max~ = 0.73 e Å^−3^ 0 restraints Δρ~min~ = −0.29 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e579 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Co1 0.37392 (7) 0.10485 (6) 0.26462 (5) 0.0404 (2) Cl1 0.56482 (14) −0.04002 (12) 0.31714 (10) 0.0594 (4) O1 0.7244 (6) 0.5110 (5) 0.4349 (4) 0.128 (2) O2 0.6499 (5) 0.4123 (4) 0.5748 (4) 0.1036 (16) O3 0.4228 (3) 0.1646 (3) 0.3428 (2) 0.0454 (9) O4 0.4954 (4) 0.2019 (3) −0.1040 (3) 0.0698 (11) O5 −0.0960 (7) 0.1461 (6) −0.2398 (5) 0.145 (3) O6 0.0849 (7) 0.0090 (6) −0.2185 (5) 0.134 (2) O7 0.3203 (3) 0.0612 (3) 0.1748 (2) 0.0427 (8) O8 0.1019 (4) 0.4428 (4) 0.3188 (4) 0.0871 (14) N1 0.6684 (6) 0.4408 (5) 0.4845 (4) 0.0769 (16) N2 0.5113 (4) 0.2641 (4) 0.1940 (3) 0.0493 (11) N3 0.4654 (4) 0.2001 (3) 0.1626 (3) 0.0439 (10) N4 0.0158 (9) 0.0820 (8) −0.1975 (5) 0.103 (2) N5 0.1387 (4) 0.2219 (4) 0.1352 (3) 0.0468 (11) N6 0.2066 (4) 0.2250 (4) 0.2103 (3) 0.0435 (11) N7 0.2841 (4) 0.0135 (3) 0.3809 (3) 0.0409 (10) C1 0.5279 (5) 0.2942 (4) 0.3384 (4) 0.0439 (13) C2 0.4979 (5) 0.2702 (4) 0.4383 (4) 0.0496 (14) H2B 0.4478 0.2211 0.4725 0.060\ C3 0.5420 (5) 0.3184 (5) 0.4871 (4) 0.0558 (15) H3A 0.5225 0.3027 0.5540 0.067\* C4 0.6163 (6) 0.3909 (5) 0.4334 (4) 0.0527 (14) C5 0.6444 (6) 0.4179 (5) 0.3343 (4) 0.0570 (15) H5B 0.6917 0.4693 0.2996 0.068\* C6 0.6020 (5) 0.3684 (5) 0.2872 (4) 0.0543 (15) H6A 0.6227 0.3843 0.2204 0.065\* C7 0.4835 (5) 0.2372 (4) 0.2892 (4) 0.0425 (12) C8 0.4890 (5) 0.2082 (4) 0.0719 (3) 0.0481 (14) H8A 0.4581 0.1616 0.0565 0.058\* C9 0.5563 (5) 0.2793 (5) −0.0091 (4) 0.0532 (14) C10 0.5598 (6) 0.2723 (5) −0.1022 (4) 0.0565 (15) C11 0.6177 (6) 0.3369 (6) −0.1841 (4) 0.0749 (19) H11A 0.6169 0.3330 −0.2450 0.090\* C12 0.6774 (7) 0.4083 (7) −0.1765 (5) 0.090 (2) H12A 0.7174 0.4516 −0.2324 0.108\* C13 0.6782 (7) 0.4160 (6) −0.0861 (5) 0.091 (2) H13A 0.7186 0.4641 −0.0813 0.109\* C14 0.6187 (7) 0.3515 (6) −0.0040 (4) 0.0764 (19) H14A 0.6200 0.3562 0.0566 0.092\* C15 0.4867 (8) 0.1978 (6) −0.1990 (5) 0.100 (2) H15A 0.4389 0.1461 −0.1904 0.151\* H15B 0.5752 0.1726 −0.2179 0.151\* H15C 0.4403 0.2718 −0.2520 0.151\* C16 0.1556 (6) 0.1187 (4) 0.0397 (4) 0.0505 (14) C17 0.2401 (6) 0.0517 (5) 0.0012 (4) 0.0685 (17) H17A 0.3286 0.0142 0.0279 0.082\* C18 0.1936 (7) 0.0404 (6) −0.0764 (5) 0.0777 (19) H18A 0.2501 −0.0052 −0.1019 0.093\* C19 0.0650 (8) 0.0960 (6) −0.1154 (5) 0.0727 (19) C20 −0.0214 (7) 0.1636 (6) −0.0792 (5) 0.0756 (19) H20A −0.1092 0.2016 −0.1075 0.091\* C21 0.0238 (6) 0.1743 (5) −0.0009 (4) 0.0667 (17) H21A −0.0339 0.2189 0.0250 0.080\* C22 0.2089 (6) 0.1335 (5) 0.1225 (4) 0.0441 (13) C23 0.1556 (6) 0.3046 (5) 0.2358 (4) 0.0490 (14) H23A 0.2047 0.2987 0.2888 0.059\* C24 0.0358 (5) 0.4014 (5) 0.1967 (4) 0.0472 (13) C25 0.0126 (7) 0.4728 (5) 0.2425 (5) 0.0591 (16) C26 −0.0976 (8) 0.5700 (6) 0.2070 (6) 0.077 (2) H26A −0.1120 0.6183 0.2359 0.093\* C27 −0.1858 (7) 0.5946 (6) 0.1285 (6) 0.0777 (19) H27A −0.2587 0.6600 0.1049 0.093\* C28 −0.1675 (7) 0.5250 (6) 0.0855 (5) 0.0713 (18) H28A −0.2287 0.5417 0.0341 0.086\* C29 −0.0568 (6) 0.4283 (5) 0.1188 (4) 0.0626 (16) H29A −0.0442 0.3811 0.0888 0.075\* C30 0.0780 (8) 0.5059 (8) 0.3742 (7) 0.133 (3) H30A 0.1499 0.4739 0.4260 0.199\* H30B −0.0047 0.5033 0.4059 0.199\* H30C 0.0728 0.5831 0.3280 0.199\* C31 0.2877 (5) 0.0132 (5) 0.4712 (4) 0.0539 (15) H31A 0.3369 0.0541 0.4792 0.065\* C32 0.2223 (5) −0.0445 (5) 0.5528 (4) 0.0597 (16) H32A 0.2257 −0.0399 0.6133 0.072\* C33 0.1520 (5) −0.1088 (5) 0.5453 (5) 0.0617 (16) C34 0.1506 (6) −0.1112 (5) 0.4531 (5) 0.0687 (18) H34A 0.1052 −0.1541 0.4445 0.082\* C35 0.2171 (6) −0.0495 (5) 0.3735 (4) 0.0632 (16) H35A 0.2149 −0.0522 0.3121 0.076\* C36 0.0757 (6) −0.1717 (5) 0.6334 (5) 0.088 (2) H36A 0.0882 −0.1598 0.6905 0.131\* H36B 0.1087 −0.2512 0.6534 0.131\* H36C −0.0178 −0.1439 0.6116 0.131\* ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1730 .table-wrap} ----- ------------ ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Co1 0.0446 (5) 0.0485 (5) 0.0383 (4) −0.0235 (4) 0.0059 (3) −0.0229 (3) Cl1 0.0574 (9) 0.0657 (10) 0.0590 (9) −0.0195 (8) 0.0010 (7) −0.0313 (8) O1 0.187 (6) 0.188 (6) 0.110 (4) −0.154 (5) 0.063 (4) −0.097 (4) O2 0.162 (5) 0.130 (4) 0.067 (3) −0.087 (4) 0.019 (3) −0.060 (3) O3 0.053 (2) 0.058 (2) 0.0385 (19) −0.032 (2) 0.0124 (16) −0.0246 (17) O4 0.097 (3) 0.080 (3) 0.047 (2) −0.029 (3) 0.009 (2) −0.041 (2) O5 0.149 (6) 0.187 (6) 0.124 (5) −0.029 (5) −0.057 (4) −0.095 (5) O6 0.157 (6) 0.192 (7) 0.131 (5) −0.073 (5) 0.017 (4) −0.127 (5) O7 0.045 (2) 0.047 (2) 0.043 (2) −0.0155 (19) −0.0015 (17) −0.0251 (17) O8 0.073 (3) 0.118 (4) 0.117 (4) −0.027 (3) 0.008 (3) −0.094 (3) N1 0.102 (4) 0.101 (4) 0.063 (4) −0.055 (4) 0.018 (3) −0.054 (3) N2 0.065 (3) 0.057 (3) 0.044 (3) −0.035 (3) 0.014 (2) −0.030 (2) N3 0.055 (3) 0.047 (3) 0.039 (2) −0.022 (2) 0.005 (2) −0.024 (2) N4 0.125 (7) 0.135 (7) 0.074 (4) −0.060 (6) −0.016 (4) −0.053 (5) N5 0.048 (3) 0.050 (3) 0.047 (3) −0.015 (2) −0.001 (2) −0.026 (2) N6 0.049 (3) 0.048 (3) 0.037 (2) −0.021 (2) 0.005 (2) −0.019 (2) N7 0.040 (3) 0.045 (3) 0.040 (2) −0.018 (2) 0.0019 (19) −0.018 (2) C1 0.048 (3) 0.051 (3) 0.042 (3) −0.024 (3) 0.007 (2) −0.025 (3) C2 0.063 (4) 0.050 (3) 0.045 (3) −0.031 (3) 0.016 (3) −0.023 (3) C3 0.079 (4) 0.072 (4) 0.042 (3) −0.040 (3) 0.018 (3) −0.038 (3) C4 0.072 (4) 0.060 (4) 0.045 (3) −0.035 (3) 0.007 (3) −0.031 (3) C5 0.075 (4) 0.067 (4) 0.048 (3) −0.043 (3) 0.016 (3) −0.030 (3) C6 0.070 (4) 0.068 (4) 0.046 (3) −0.041 (3) 0.018 (3) −0.034 (3) C7 0.050 (3) 0.045 (3) 0.035 (3) −0.022 (3) 0.009 (2) −0.018 (2) C8 0.055 (3) 0.061 (4) 0.036 (3) −0.024 (3) 0.009 (3) −0.026 (3) C9 0.062 (4) 0.061 (4) 0.038 (3) −0.020 (3) 0.009 (3) −0.024 (3) C10 0.057 (4) 0.060 (4) 0.041 (3) −0.008 (3) 0.003 (3) −0.020 (3) C11 0.075 (5) 0.103 (5) 0.041 (4) −0.026 (4) 0.016 (3) −0.030 (4) C12 0.078 (5) 0.113 (6) 0.055 (4) −0.041 (5) 0.027 (4) −0.017 (4) C13 0.111 (6) 0.111 (6) 0.073 (5) −0.074 (5) 0.036 (4) −0.041 (4) C14 0.111 (5) 0.099 (5) 0.053 (4) −0.076 (5) 0.030 (3) −0.038 (4) C15 0.139 (7) 0.122 (6) 0.057 (4) −0.037 (5) 0.004 (4) −0.057 (4) C16 0.065 (4) 0.047 (3) 0.046 (3) −0.024 (3) −0.006 (3) −0.021 (3) C17 0.064 (4) 0.084 (5) 0.072 (4) −0.010 (4) −0.011 (3) −0.053 (4) C18 0.082 (5) 0.094 (5) 0.082 (5) −0.027 (4) 0.004 (4) −0.062 (4) C19 0.084 (5) 0.098 (5) 0.056 (4) −0.044 (5) −0.004 (4) −0.040 (4) C20 0.073 (5) 0.086 (5) 0.083 (5) −0.028 (4) −0.017 (4) −0.046 (4) C21 0.060 (4) 0.076 (5) 0.073 (4) −0.021 (4) −0.011 (3) −0.040 (4) C22 0.049 (4) 0.052 (4) 0.038 (3) −0.028 (3) 0.007 (3) −0.020 (3) C23 0.063 (4) 0.052 (4) 0.045 (3) −0.027 (3) 0.013 (3) −0.029 (3) C24 0.047 (4) 0.043 (3) 0.054 (3) −0.020 (3) 0.011 (3) −0.023 (3) C25 0.064 (4) 0.058 (4) 0.074 (4) −0.033 (4) 0.023 (4) −0.039 (4) C26 0.085 (5) 0.062 (5) 0.103 (6) −0.034 (4) 0.040 (5) −0.051 (4) C27 0.075 (5) 0.059 (5) 0.084 (5) −0.015 (4) 0.021 (4) −0.027 (4) C28 0.075 (5) 0.066 (5) 0.061 (4) −0.011 (4) 0.000 (3) −0.026 (4) C29 0.073 (4) 0.051 (4) 0.060 (4) −0.012 (4) 0.003 (3) −0.025 (3) C30 0.099 (6) 0.204 (9) 0.186 (9) −0.052 (6) 0.032 (6) −0.163 (8) C31 0.054 (4) 0.067 (4) 0.046 (3) −0.032 (3) 0.009 (3) −0.023 (3) C32 0.068 (4) 0.063 (4) 0.046 (3) −0.032 (4) 0.014 (3) −0.019 (3) C33 0.048 (4) 0.057 (4) 0.060 (4) −0.016 (3) 0.007 (3) −0.012 (3) C34 0.065 (4) 0.069 (4) 0.072 (4) −0.042 (4) 0.007 (3) −0.020 (4) C35 0.069 (4) 0.071 (4) 0.056 (4) −0.034 (4) −0.002 (3) −0.026 (3) C36 0.064 (4) 0.073 (5) 0.081 (4) −0.026 (4) 0.024 (3) −0.001 (4) ----- ------------ ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2805 .table-wrap} ---------------------- ------------- ----------------------- ------------ Co1---O3 1.887 (3) C12---H12A 0.9300 Co1---O7 1.882 (3) C13---C14 1.375 (7) Co1---N3 1.917 (4) C13---H13A 0.9300 Co1---N6 1.932 (4) C14---H14A 0.9300 Co1---N7 1.983 (4) C15---H15A 0.9600 Co1---Cl1 2.2472 (17) C15---H15B 0.9600 O1---N1 1.213 (6) C15---H15C 0.9600 O2---N1 1.221 (6) C16---C17 1.384 (7) O3---C7 1.281 (5) C16---C21 1.387 (7) O4---C10 1.367 (7) C16---C22 1.507 (7) O4---C15 1.445 (6) C17---C18 1.371 (7) O5---N4 1.235 (8) C17---H17A 0.9300 O6---N4 1.218 (8) C18---C19 1.353 (8) O7---C22 1.298 (6) C18---H18A 0.9300 O8---C25 1.346 (7) C19---C20 1.374 (9) O8---C30 1.424 (8) C20---C21 1.371 (7) N1---C4 1.467 (7) C20---H20A 0.9300 N2---C7 1.311 (6) C21---H21A 0.9300 N2---N3 1.395 (5) C23---C24 1.450 (7) N3---C8 1.304 (5) C23---H23A 0.9300 N4---C19 1.470 (8) C24---C29 1.400 (7) N5---C22 1.326 (6) C24---C25 1.408 (7) N5---N6 1.390 (5) C25---C26 1.393 (8) N6---C23 1.294 (6) C26---C27 1.387 (8) N7---C35 1.332 (6) C26---H26A 0.9300 N7---C31 1.336 (6) C27---C28 1.357 (9) C1---C2 1.388 (6) C27---H27A 0.9300 C1---C6 1.392 (6) C28---C29 1.394 (7) C1---C7 1.487 (7) C28---H28A 0.9300 C2---C3 1.374 (6) C29---H29A 0.9300 C2---H2B 0.9300 C30---H30A 0.9600 C3---C4 1.385 (7) C30---H30B 0.9600 C3---H3A 0.9300 C30---H30C 0.9600 C4---C5 1.365 (7) C31---C32 1.374 (6) C5---C6 1.362 (7) C31---H31A 0.9300 C5---H5B 0.9300 C32---C33 1.374 (7) C6---H6A 0.9300 C32---H32A 0.9300 C8---C9 1.456 (7) C33---C34 1.381 (8) C8---H8A 0.9300 C33---C36 1.524 (7) C9---C14 1.395 (7) C34---C35 1.385 (7) C9---C10 1.424 (7) C34---H34A 0.9300 C10---C11 1.364 (8) C35---H35A 0.9300 C11---C12 1.381 (9) C36---H36A 0.9600 C11---H11A 0.9300 C36---H36B 0.9600 C12---C13 1.393 (9) C36---H36C 0.9600 O7---Co1---O3 173.83 (15) C9---C14---H14A 119.1 O7---Co1---N3 93.09 (15) O4---C15---H15A 109.5 O3---Co1---N3 82.36 (15) O4---C15---H15B 109.5 O7---Co1---N6 82.64 (17) H15A---C15---H15B 109.5 O3---Co1---N6 93.15 (17) O4---C15---H15C 109.5 N3---Co1---N6 90.00 (16) H15A---C15---H15C 109.5 O7---Co1---N7 93.80 (15) H15B---C15---H15C 109.5 O3---Co1---N7 90.72 (15) C17---C16---C21 119.4 (5) N3---Co1---N7 173.07 (18) C17---C16---C22 119.7 (5) N6---Co1---N7 90.18 (16) C21---C16---C22 120.9 (5) O7---Co1---Cl1 91.96 (12) C18---C17---C16 120.2 (6) O3---Co1---Cl1 92.19 (11) C18---C17---H17A 119.9 N3---Co1---Cl1 89.84 (13) C16---C17---H17A 119.9 N6---Co1---Cl1 174.59 (14) C19---C18---C17 119.5 (6) N7---Co1---Cl1 90.63 (12) C19---C18---H18A 120.2 C7---O3---Co1 110.7 (3) C17---C18---H18A 120.2 C10---O4---C15 117.6 (5) C18---C19---C20 121.8 (6) C22---O7---Co1 110.5 (3) C18---C19---N4 119.1 (7) C25---O8---C30 119.5 (6) C20---C19---N4 119.2 (7) O1---N1---O2 122.7 (5) C21---C20---C19 119.1 (6) O1---N1---C4 118.8 (5) C21---C20---H20A 120.5 O2---N1---C4 118.4 (5) C19---C20---H20A 120.5 C7---N2---N3 108.7 (4) C20---C21---C16 120.1 (6) C8---N3---N2 119.5 (4) C20---C21---H21A 120.0 C8---N3---Co1 127.2 (4) C16---C21---H21A 120.0 N2---N3---Co1 113.3 (3) O7---C22---N5 124.6 (5) O6---N4---O5 124.6 (7) O7---C22---C16 118.5 (5) O6---N4---C19 119.2 (8) N5---C22---C16 116.9 (5) O5---N4---C19 116.2 (8) N6---C23---C24 131.7 (5) C22---N5---N6 108.6 (4) N6---C23---H23A 114.1 C23---N6---N5 119.3 (5) C24---C23---H23A 114.1 C23---N6---Co1 127.2 (4) C29---C24---C25 118.4 (6) N5---N6---Co1 113.5 (3) C29---C24---C23 125.6 (5) C35---N7---C31 116.7 (4) C25---C24---C23 116.0 (5) C35---N7---Co1 122.3 (4) O8---C25---C26 123.5 (6) C31---N7---Co1 121.0 (3) O8---C25---C24 116.7 (6) C2---C1---C6 119.7 (5) C26---C25---C24 119.8 (6) C2---C1---C7 119.2 (4) C27---C26---C25 120.0 (6) C6---C1---C7 121.2 (4) C27---C26---H26A 120.0 C3---C2---C1 120.4 (5) C25---C26---H26A 120.0 C3---C2---H2B 119.8 C28---C27---C26 121.1 (7) C1---C2---H2B 119.8 C28---C27---H27A 119.5 C2---C3---C4 117.9 (5) C26---C27---H27A 119.5 C2---C3---H3A 121.1 C27---C28---C29 119.8 (6) C4---C3---H3A 121.1 C27---C28---H28A 120.1 C5---C4---C3 122.8 (5) C29---C28---H28A 120.1 C5---C4---N1 118.1 (5) C28---C29---C24 120.9 (6) C3---C4---N1 119.1 (5) C28---C29---H29A 119.6 C6---C5---C4 118.9 (5) C24---C29---H29A 119.6 C6---C5---H5B 120.6 O8---C30---H30A 109.5 C4---C5---H5B 120.6 O8---C30---H30B 109.5 C5---C6---C1 120.4 (5) H30A---C30---H30B 109.5 C5---C6---H6A 119.8 O8---C30---H30C 109.5 C1---C6---H6A 119.8 H30A---C30---H30C 109.5 O3---C7---N2 124.8 (5) H30B---C30---H30C 109.5 O3---C7---C1 118.0 (4) N7---C31---C32 123.4 (5) N2---C7---C1 117.2 (4) N7---C31---H31A 118.3 N3---C8---C9 129.8 (5) C32---C31---H31A 118.3 N3---C8---H8A 115.1 C33---C32---C31 120.1 (5) C9---C8---H8A 115.1 C33---C32---H32A 119.9 C14---C9---C10 117.3 (5) C31---C32---H32A 119.9 C14---C9---C8 126.8 (5) C32---C33---C34 116.8 (5) C10---C9---C8 115.9 (5) C32---C33---C36 121.6 (6) C11---C10---O4 123.9 (6) C34---C33---C36 121.6 (6) C11---C10---C9 121.0 (6) C33---C34---C35 119.9 (6) O4---C10---C9 115.0 (5) C33---C34---H34A 120.1 C10---C11---C12 120.1 (6) C35---C34---H34A 120.1 C10---C11---H11A 120.0 N7---C35---C34 123.0 (5) C12---C11---H11A 120.0 N7---C35---H35A 118.5 C11---C12---C13 120.6 (6) C34---C35---H35A 118.5 C11---C12---H12A 119.7 C33---C36---H36A 109.5 C13---C12---H12A 119.7 C33---C36---H36B 109.5 C14---C13---C12 119.2 (6) H36A---C36---H36B 109.5 C14---C13---H13A 120.4 C33---C36---H36C 109.5 C12---C13---H13A 120.4 H36A---C36---H36C 109.5 C13---C14---C9 121.8 (6) H36B---C36---H36C 109.5 C13---C14---H14A 119.1 N3---Co1---O3---C7 2.5 (3) C15---O4---C10---C9 175.4 (5) N6---Co1---O3---C7 −87.1 (3) C14---C9---C10---C11 −2.3 (8) N7---Co1---O3---C7 −177.3 (3) C8---C9---C10---C11 178.5 (5) Cl1---Co1---O3---C7 92.1 (3) C14---C9---C10---O4 −178.9 (5) N3---Co1---O7---C22 −86.5 (3) C8---C9---C10---O4 2.0 (7) N6---Co1---O7---C22 3.1 (3) O4---C10---C11---C12 178.1 (6) N7---Co1---O7---C22 92.8 (3) C9---C10---C11---C12 1.8 (9) Cl1---Co1---O7---C22 −176.4 (3) C10---C11---C12---C13 −0.6 (10) C7---N2---N3---C8 −176.1 (4) C11---C12---C13---C14 0.0 (11) C7---N2---N3---Co1 2.8 (5) C12---C13---C14---C9 −0.6 (11) O7---Co1---N3---C8 −8.4 (4) C10---C9---C14---C13 1.7 (9) O3---Co1---N3---C8 175.8 (4) C8---C9---C14---C13 −179.3 (6) N6---Co1---N3---C8 −91.0 (4) C21---C16---C17---C18 −0.1 (9) Cl1---Co1---N3---C8 83.6 (4) C22---C16---C17---C18 −178.0 (5) O7---Co1---N3---N2 172.8 (3) C16---C17---C18---C19 0.6 (9) O3---Co1---N3---N2 −3.0 (3) C17---C18---C19---C20 −0.3 (10) Cl1---Co1---N3---N2 −95.2 (3) C17---C18---C19---N4 −179.2 (6) C22---N5---N6---C23 −179.7 (4) O6---N4---C19---C18 10.4 (10) C22---N5---N6---Co1 1.0 (4) O5---N4---C19---C18 −170.5 (7) O7---Co1---N6---C23 178.4 (4) O6---N4---C19---C20 −168.5 (7) O3---Co1---N6---C23 −6.1 (4) O5---N4---C19---C20 10.6 (10) N3---Co1---N6---C23 −88.5 (4) C18---C19---C20---C21 −0.5 (10) N7---Co1---N6---C23 84.6 (4) N4---C19---C20---C21 178.4 (5) O7---Co1---N6---N5 −2.3 (3) C19---C20---C21---C16 1.0 (9) O3---Co1---N6---N5 173.1 (3) C17---C16---C21---C20 −0.7 (8) N3---Co1---N6---N5 90.8 (3) C22---C16---C21---C20 177.2 (5) N7---Co1---N6---N5 −96.1 (3) Co1---O7---C22---N5 −3.8 (5) O7---Co1---N7---C35 0.5 (4) Co1---O7---C22---C16 174.8 (3) O3---Co1---N7---C35 176.3 (4) N6---N5---C22---O7 1.9 (6) N6---Co1---N7---C35 83.1 (4) N6---N5---C22---C16 −176.8 (4) Cl1---Co1---N7---C35 −91.5 (4) C17---C16---C22---O7 −18.2 (7) O7---Co1---N7---C31 −179.1 (4) C21---C16---C22---O7 163.9 (5) O3---Co1---N7---C31 −3.3 (4) C17---C16---C22---N5 160.5 (5) N6---Co1---N7---C31 −96.5 (4) C21---C16---C22---N5 −17.4 (7) Cl1---Co1---N7---C31 88.9 (4) N5---N6---C23---C24 −3.0 (7) C6---C1---C2---C3 −0.5 (8) Co1---N6---C23---C24 176.2 (4) C7---C1---C2---C3 177.6 (5) N6---C23---C24---C29 1.5 (8) C1---C2---C3---C4 0.0 (8) N6---C23---C24---C25 −178.8 (5) C2---C3---C4---C5 1.5 (9) C30---O8---C25---C26 6.5 (9) C2---C3---C4---N1 −178.0 (5) C30---O8---C25---C24 −174.6 (6) O1---N1---C4---C5 6.1 (9) C29---C24---C25---O8 178.4 (5) O2---N1---C4---C5 −176.1 (6) C23---C24---C25---O8 −1.3 (7) O1---N1---C4---C3 −174.3 (6) C29---C24---C25---C26 −2.6 (7) O2---N1---C4---C3 3.5 (9) C23---C24---C25---C26 177.7 (5) C3---C4---C5---C6 −2.5 (9) O8---C25---C26---C27 −179.5 (5) N1---C4---C5---C6 177.1 (5) C24---C25---C26---C27 1.6 (8) C4---C5---C6---C1 1.9 (8) C25---C26---C27---C28 0.5 (9) C2---C1---C6---C5 −0.4 (8) C26---C27---C28---C29 −1.5 (9) C7---C1---C6---C5 −178.5 (5) C27---C28---C29---C24 0.5 (8) Co1---O3---C7---N2 −1.8 (6) C25---C24---C29---C28 1.6 (7) Co1---O3---C7---C1 179.2 (3) C23---C24---C29---C28 −178.7 (5) N3---N2---C7---O3 −0.7 (7) C35---N7---C31---C32 −2.6 (8) N3---N2---C7---C1 178.4 (4) Co1---N7---C31---C32 177.0 (4) C2---C1---C7---O3 −2.3 (7) N7---C31---C32---C33 2.1 (8) C6---C1---C7---O3 175.7 (5) C31---C32---C33---C34 −0.4 (8) C2---C1---C7---N2 178.6 (5) C31---C32---C33---C36 −178.6 (5) C6---C1---C7---N2 −3.4 (7) C32---C33---C34---C35 −0.7 (8) N2---N3---C8---C9 −1.9 (8) C36---C33---C34---C35 177.6 (5) Co1---N3---C8---C9 179.3 (4) C31---N7---C35---C34 1.5 (8) N3---C8---C9---C14 4.1 (10) Co1---N7---C35---C34 −178.1 (4) N3---C8---C9---C10 −176.9 (5) C33---C34---C35---N7 0.1 (9) C15---O4---C10---C11 −1.0 (8) ---------------------- ------------- ----------------------- ------------ ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: ----------- ------------- Co1---O3 1.887 (3) Co1---O7 1.882 (3) Co1---N3 1.917 (4) Co1---N6 1.932 (4) Co1---N7 1.983 (4) Co1---Cl1 2.2472 (17) ----------- ------------- :::	PubMed Central	2024-06-05T04:04:18.797767	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052150/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):m293", "authors": [ { "first": "Qiong-Jie", "last": "Wu" }, { "first": "Xiao-Hua", "last": "Chen" }, { "first": "Jiang", "last": "Jiang" }, { "first": "Bi-Qiong", "last": "Cai" }, { "first": "Yong-Ping", "last": "Xie" } ] }
PMC3052151	Related literature {#sec1} ================== For the pharmacological effects, biological activity and synthesis of 3(2H)-pyridazinones, see: Şüküroğlu et al. 2006[@bb10]; Brogden 1986[@bb3]. For bond-length data, see: Allen et al. (1987[@bb1]). For ring conformational analysis, see: Cremer & Pople (1975[@bb4]). For the quantum mechanical CNDO/2 approximation, see: Pople & Beveridge (1970[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~26~H~28~FN~5~O~3~M ~r~ = 477.53Triclinic,a = 8.9168 (5) Åb = 10.7106 (6) Åc = 13.5147 (8) Åα = 73.489 (4)°β = 71.309 (4)°γ = 83.486 (4)°V = 1171.87 (12) Å^3^Z = 2Mo Kα radiationμ = 0.10 mm^−1^T = 296 K0.60 × 0.49 × 0.20 mm ### Data collection {#sec2.1.2} STOE IPDS 2 diffractometerAbsorption correction: integration (X-RED32; Stoe & Cie, 2002[@bb9]) T ~min~ = 0.945, T ~max~ = 0.98113273 measured reflections4861 independent reflections3479 reflections with I \> 2σ(I)R ~int~ = 0.029 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.036wR(F ^2^) = 0.091S = 1.034861 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.14 e Å^−3^ {#d5e525} Data collection: X-AREA (Stoe & Cie, 2002[@bb9]); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002[@bb9]); program(s) used to solve structure: SIR97 (Altomare et al., 1999[@bb2]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb5]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005071/ez2227sup1.cif](http://dx.doi.org/10.1107/S1600536811005071/ez2227sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005071/ez2227Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005071/ez2227Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2227&file=ez2227sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2227sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2227&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2227](http://scripts.iucr.org/cgi-bin/sendsup?ez2227)). The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund). Comment ======= In recent years, the 3(2H)-pyridazinone system has aroused a great deal of attention due to its structural relationship to pyrazolone derivatives such as aminopyrine and dipyrone in view of the ring enlargement of pyrazolone to pyridazinone. These drugs possess analgesic and anti-inflammatory activities although they have limitations for their clinical use due to serious side effects such as blood dyscrasias (Şüküroğlu et al., 2006; Brogden, 1986). A series of 6-morpholino-4-aryl-3(2H)-pyridazinone alkanoic acids, their ester and amide derivatives were prepared and tested for their in vivo analgesic activity by using the p-benzoquinone-induced writhing test. The title compound, C~26~H~28~FN~5~O~3~, generally showed higher activity but caused gastric ulceration in the animals (Şüküroğlu et al., 2006). In the title molecule (I), Fig. 1, the morpholine ring (N3/O2/C11--C14) adopts a chair conformation. The piperazine ring (N4/N5/C17--C20) is puckered. The conformation of this ring is described by three puckering parameters: Q~T~ = 0.5437 (15) Å, θ = 8.89 (15) ° and, φ = 357.2 (11) ° (Cremer & Pople, 1975). The 1,6-dihydropyridazine ring (N1/N2/C7--C10) makes dihedral angles of 28.03 (7) and 77.46 (7) ° with the C1--C6 phenyl and C21--C26 benzene rings, respectively. The phenyl and benzene rings make a dihedral angle of 50.17 (8) ° with each other. In the crystal structure, molecules are linked along the c-axis direction and are flattened parallel to the plane containing the a and c axes. Furthermore, C--H···π interactions contribute to the stability of the structure (Table 1). Fig. 2 shows the packing diagram of (I) down the b axis. Theoretical calculations were carried out using the semiempirical quantum-mechanical CNDO/2 (Complete Neglect of Differential Overlap) method (Pople and Beveridge, 1970). The spatial view of the single molecule calculated as closed-shell in a vacuum is shown in Fig. 3 with atomic labels. The calculated dipole moment of (I) is about 2.795 Debye. The HOMO and LUMO energy levels are -10.013 and 0.832 eV, respectively. According to the theoretical CNDO/2 and experimental X-ray structural results, the values of the geometric parameters of (I) are almost comparable within the experimental error interval (Allen et al., 1987). The 1,6-dihydropyridazine ring (N1/N2/C7--C10) forms dihedral angles of 2.24 and 60.48° with the C1--C6 phenyl and C21--C26 benzene rings, respectively. The dihedral angle between the phenyl and benzene rings is 62.62°. The orientations of the planes of the rings are however, slightly different in the CNDO/2 and X-ray results. That is, intermolecular interactions play an important role in determining the crystal state conformation of (I). Experimental {#experimental} ============ A reaction mixture containing 2-\[4-phenyl-6-(morpholin-4-yl)-3(2H)- pyridazinone-2-yl\]acetic acid (0.01 mole) and triethylamine (0.011 mole) in 20 ml dichloromethane at 273 K (ice-bath) was treated with ethyl chloroformate (0,01 mole). After stirring the reaction mixture at 273 K for 15 min, 0.011 mole of 4-(4-fluorophenyl)-piperazine derivative was added to this solution. The final mixture was stirred at room temperature for 24 h and evaporated to dryness and then acetone was added. All undissolved salts were filtered off, the filtrate was evaporated to dryness and the residue was recrystallized from acetone-water (1:1) to yield 62%, \[m.p.: 457 K\]. ^1^H-NMR (CDCl~3~), δ 7.75 (m, 2H, phenyl-H2, H6), 7.43 (m, 3H, phenyl-H3, H4, H5), 7.23 (s, 1H, pyridazinone-H5), 6.99 (m, 4H, 4-fluorophenyl-H2, H3, H5, H6), 4.98 (s, 2H, N---CH~2~---CO), 3.82 (m, 6H, morpholine-H2, H6, piperazine- H2(6)), 3.71 (m, 2H, piperazine-H6(2)), 3.31 (t, 8H, morpholine-H3, H5), 3.15 (m, 4H, piperazine-H3, H5) p.p.m.. IR v~max~ cm^-1^ (KBr): 2845, 1661, 1643. Anal. C, H, N (C~26~H~28~FN~5~O~3~) (Şüküroğlu et al., 2006). Elemental analysis: C~26~H~28~FN~5~O~3~, Calc.(%) / Found (%): C: 65.39/65.54, H: 5.91/5.49, N: 14.67/14.28. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding model with C---H = 0.93 and 0.97 Å, and U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title molecule with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level. ::: ![](e-67-0o666-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing and hydrogen bonding interactions of (I) down the b axis. H atoms not participating in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o666-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The spatial view of the title molecule (I), calculated by the CNDO/2 aproximation. ::: ![](e-67-0o666-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e262 .table-wrap} ------------------------- ---------------------------------------- C~26~H~28~FN~5~O~3~ Z = 2 M~r~ = 477.53 F(000) = 504 Triclinic, P1 D~x~ = 1.353 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.9168 (5) Å Cell parameters from 19046 reflections b = 10.7106 (6) Å θ = 1.7--28.2° c = 13.5147 (8) Å µ = 0.10 mm^−1^ α = 73.489 (4)° T = 296 K β = 71.309 (4)° Prism, yellow γ = 83.486 (4)° 0.60 × 0.49 × 0.20 mm V = 1171.87 (12) Å^3^ ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e398 .table-wrap} ------------------------------------------------------------------ -------------------------------------- STOE IPDS 2 diffractometer 4861 independent reflections Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus 3479 reflections with I \> 2σ(I) plane graphite R~int~ = 0.029 Detector resolution: 6.67 pixels mm^-1^ θ~max~ = 26.5°, θ~min~ = 1.7° ω scans h = −11→11 Absorption correction: integration (X-RED32; Stoe & Cie, 2002) k = −13→13 T~min~ = 0.945, T~max~ = 0.981 l = −16→16 13273 measured reflections ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e518 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.036 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.091 H-atom parameters constrained S = 1.03 w = 1/\[σ^2^(F~o~^2^) + (0.0469P)^2^ + 0.0141P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4861 reflections (Δ/σ)~max~ \< 0.001 316 parameters Δρ~max~ = 0.12 e Å^−3^ 0 restraints Δρ~min~ = −0.14 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e675 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on F^2^ for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The observed criterion of F^2^ \> σ(F^2^) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e777 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ F1 1.31808 (14) 0.32221 (10) 1.12298 (8) 0.0875 (4) O1 0.65668 (12) 0.66791 (10) 0.43998 (8) 0.0635 (4) O2 0.02122 (12) 1.05391 (10) 0.84902 (8) 0.0626 (3) O3 0.84333 (12) 0.78850 (9) 0.56875 (9) 0.0627 (3) N1 0.44450 (12) 0.78805 (9) 0.66593 (8) 0.0437 (3) N2 0.54428 (12) 0.72130 (10) 0.59688 (8) 0.0438 (3) N3 0.25440 (13) 0.94880 (10) 0.69277 (8) 0.0471 (3) N4 0.93182 (13) 0.58003 (10) 0.61148 (9) 0.0473 (4) N5 1.09333 (13) 0.46726 (10) 0.76728 (8) 0.0459 (3) C1 0.43486 (15) 0.84428 (12) 0.33963 (10) 0.0425 (4) C2 0.38220 (17) 0.96206 (13) 0.28338 (11) 0.0530 (5) C3 0.3712 (2) 0.97650 (17) 0.18124 (13) 0.0668 (6) C4 0.4089 (2) 0.87442 (18) 0.13408 (12) 0.0671 (6) C5 0.46053 (19) 0.75785 (16) 0.18863 (12) 0.0622 (6) C6 0.47474 (17) 0.74228 (13) 0.29017 (11) 0.0523 (5) C7 0.44320 (14) 0.82808 (11) 0.45042 (10) 0.0402 (4) C8 0.55601 (15) 0.73397 (12) 0.49132 (10) 0.0445 (4) C9 0.35078 (14) 0.87626 (11) 0.62510 (10) 0.0406 (4) C10 0.34782 (15) 0.89739 (11) 0.51700 (10) 0.0429 (4) C11 0.10441 (17) 1.00413 (13) 0.67498 (11) 0.0546 (5) C12 0.04171 (18) 1.10537 (13) 0.73676 (12) 0.0615 (5) C13 0.17058 (19) 1.00733 (16) 0.86405 (13) 0.0641 (6) C14 0.24172 (18) 0.90257 (14) 0.80774 (11) 0.0533 (5) C15 0.64791 (15) 0.62509 (12) 0.64412 (11) 0.0462 (4) C16 0.81643 (16) 0.67228 (12) 0.60443 (10) 0.0444 (4) C17 1.09342 (16) 0.61613 (15) 0.59093 (11) 0.0578 (5) C18 1.12789 (17) 0.59830 (13) 0.69637 (12) 0.0553 (5) C19 0.93822 (16) 0.42227 (12) 0.78027 (11) 0.0460 (4) C20 0.90918 (17) 0.44392 (12) 0.67254 (11) 0.0484 (4) C21 1.14574 (15) 0.43318 (12) 0.85944 (10) 0.0446 (4) C22 1.24267 (18) 0.51424 (13) 0.87566 (12) 0.0532 (5) C23 1.2999 (2) 0.47658 (15) 0.96358 (13) 0.0611 (6) C24 1.26051 (19) 0.35931 (15) 1.03610 (12) 0.0599 (5) C25 1.16453 (19) 0.27695 (15) 1.02480 (12) 0.0596 (5) C26 1.10713 (17) 0.31386 (13) 0.93713 (11) 0.0530 (5) H2 0.35420 1.03140 0.31490 0.0640\ H3 0.33800 1.05620 0.14380 0.0800\* H4 0.39940 0.88440 0.06570 0.0810\* H5 0.48620 0.68860 0.15690 0.0750\* H6 0.51130 0.66300 0.32590 0.0630\* H10 0.27860 0.96040 0.49140 0.0510\* H11A 0.02810 0.93570 0.69910 0.0660\* H11B 0.12070 1.04350 0.59830 0.0660\* H12A 0.11470 1.17670 0.70830 0.0740\* H12B −0.05910 1.13980 0.72630 0.0740\* H13A 0.15730 0.97320 0.94090 0.0770\* H13B 0.24260 1.07930 0.83630 0.0770\* H14A 0.34600 0.87750 0.81590 0.0640\* H14B 0.17600 0.82650 0.84070 0.0640\* H15A 0.64680 0.54450 0.62510 0.0550\* H15B 0.60890 0.60740 0.72240 0.0550\* H17A 1.10820 0.70640 0.54920 0.0690\* H17B 1.16660 0.56240 0.54900 0.0690\* H18A 1.23860 0.61530 0.68140 0.0660\* H18B 1.06480 0.66110 0.73320 0.0660\* H19A 0.85690 0.46850 0.82480 0.0550\* H19B 0.93100 0.33020 0.81730 0.0550\* H20A 0.98170 0.38910 0.63140 0.0580\* H20B 0.80200 0.41990 0.68420 0.0580\* H22 1.26910 0.59500 0.82640 0.0640\* H23 1.36500 0.53130 0.97310 0.0730\* H25 1.13830 0.19710 1.07550 0.0720\* H26 1.04120 0.25820 0.92940 0.0630\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1576 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ F1 0.1156 (9) 0.0924 (7) 0.0722 (6) 0.0160 (6) −0.0589 (6) −0.0215 (5) O1 0.0598 (7) 0.0678 (6) 0.0611 (6) 0.0271 (5) −0.0168 (5) −0.0268 (5) O2 0.0534 (6) 0.0630 (6) 0.0617 (6) 0.0020 (5) 0.0024 (5) −0.0255 (5) O3 0.0606 (6) 0.0408 (5) 0.0794 (7) −0.0021 (4) −0.0271 (5) 0.0026 (5) N1 0.0414 (6) 0.0417 (5) 0.0441 (6) 0.0032 (4) −0.0094 (5) −0.0111 (5) N2 0.0391 (6) 0.0427 (5) 0.0463 (6) 0.0082 (4) −0.0124 (5) −0.0108 (5) N3 0.0453 (6) 0.0442 (6) 0.0463 (6) 0.0071 (5) −0.0075 (5) −0.0140 (5) N4 0.0395 (6) 0.0438 (6) 0.0548 (7) 0.0038 (5) −0.0182 (5) −0.0045 (5) N5 0.0445 (6) 0.0450 (6) 0.0459 (6) −0.0017 (5) −0.0163 (5) −0.0053 (5) C1 0.0356 (7) 0.0440 (7) 0.0459 (7) −0.0017 (5) −0.0097 (5) −0.0114 (5) C2 0.0543 (9) 0.0500 (8) 0.0552 (8) 0.0054 (6) −0.0206 (7) −0.0127 (6) C3 0.0701 (11) 0.0693 (10) 0.0592 (9) 0.0068 (8) −0.0283 (8) −0.0077 (8) C4 0.0657 (11) 0.0914 (12) 0.0465 (8) −0.0052 (9) −0.0193 (7) −0.0179 (8) C5 0.0626 (10) 0.0713 (10) 0.0561 (9) −0.0032 (8) −0.0116 (7) −0.0288 (8) C6 0.0543 (9) 0.0508 (8) 0.0516 (8) 0.0003 (6) −0.0137 (6) −0.0166 (6) C7 0.0357 (7) 0.0375 (6) 0.0452 (7) −0.0016 (5) −0.0101 (5) −0.0095 (5) C8 0.0389 (7) 0.0434 (7) 0.0497 (7) 0.0048 (5) −0.0112 (6) −0.0145 (6) C9 0.0371 (7) 0.0360 (6) 0.0450 (7) −0.0004 (5) −0.0082 (5) −0.0100 (5) C10 0.0388 (7) 0.0386 (6) 0.0492 (7) 0.0048 (5) −0.0136 (5) −0.0102 (5) C11 0.0529 (9) 0.0497 (7) 0.0521 (8) 0.0148 (6) −0.0100 (6) −0.0122 (6) C12 0.0565 (9) 0.0448 (7) 0.0671 (10) 0.0079 (6) −0.0004 (7) −0.0142 (7) C13 0.0578 (10) 0.0736 (10) 0.0607 (9) −0.0014 (8) −0.0060 (7) −0.0310 (8) C14 0.0518 (8) 0.0563 (8) 0.0478 (8) 0.0018 (6) −0.0088 (6) −0.0158 (6) C15 0.0420 (7) 0.0415 (6) 0.0503 (7) 0.0058 (5) −0.0156 (6) −0.0057 (6) C16 0.0471 (8) 0.0411 (7) 0.0432 (7) 0.0035 (5) −0.0178 (6) −0.0053 (5) C17 0.0400 (8) 0.0661 (9) 0.0545 (8) −0.0036 (6) −0.0137 (6) 0.0039 (7) C18 0.0478 (8) 0.0533 (8) 0.0591 (9) −0.0096 (6) −0.0200 (7) 0.0015 (7) C19 0.0476 (8) 0.0372 (6) 0.0512 (7) 0.0004 (5) −0.0142 (6) −0.0100 (5) C20 0.0513 (8) 0.0384 (6) 0.0588 (8) 0.0083 (5) −0.0240 (6) −0.0131 (6) C21 0.0442 (7) 0.0434 (7) 0.0448 (7) 0.0072 (5) −0.0134 (6) −0.0126 (5) C22 0.0596 (9) 0.0455 (7) 0.0574 (8) 0.0032 (6) −0.0224 (7) −0.0144 (6) C23 0.0685 (10) 0.0594 (9) 0.0690 (10) 0.0083 (7) −0.0328 (8) −0.0282 (8) C24 0.0682 (10) 0.0666 (9) 0.0525 (8) 0.0179 (8) −0.0302 (7) −0.0213 (7) C25 0.0634 (10) 0.0571 (8) 0.0518 (8) 0.0062 (7) −0.0197 (7) −0.0045 (7) C26 0.0534 (9) 0.0490 (7) 0.0551 (8) 0.0000 (6) −0.0203 (7) −0.0077 (6) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2301 .table-wrap} ---------------------- -------------- ----------------------- -------------- F1---C24 1.369 (2) C21---C26 1.3999 (19) O1---C8 1.2343 (17) C22---C23 1.380 (2) O2---C12 1.4173 (18) C23---C24 1.357 (2) O2---C13 1.424 (2) C24---C25 1.366 (2) O3---C16 1.2215 (17) C25---C26 1.378 (2) N1---N2 1.3698 (15) C2---H2 0.9300 N1---C9 1.3098 (17) C3---H3 0.9300 N2---C8 1.3646 (16) C4---H4 0.9300 N2---C15 1.4531 (18) C5---H5 0.9300 N3---C9 1.3883 (16) C6---H6 0.9300 N3---C11 1.464 (2) C10---H10 0.9300 N3---C14 1.4612 (17) C11---H11A 0.9700 N4---C16 1.3501 (18) C11---H11B 0.9700 N4---C17 1.4532 (19) C12---H12A 0.9700 N4---C20 1.4571 (17) C12---H12B 0.9700 N5---C18 1.4586 (18) C13---H13A 0.9700 N5---C19 1.4572 (19) C13---H13B 0.9700 N5---C21 1.4067 (17) C14---H14A 0.9700 C1---C2 1.393 (2) C14---H14B 0.9700 C1---C6 1.3933 (19) C15---H15A 0.9700 C1---C7 1.4827 (18) C15---H15B 0.9700 C2---C3 1.379 (2) C17---H17A 0.9700 C3---C4 1.375 (3) C17---H17B 0.9700 C4---C5 1.371 (3) C18---H18A 0.9700 C5---C6 1.380 (2) C18---H18B 0.9700 C7---C8 1.4639 (19) C19---H19A 0.9700 C7---C10 1.3528 (18) C19---H19B 0.9700 C9---C10 1.4219 (18) C20---H20A 0.9700 C11---C12 1.504 (2) C20---H20B 0.9700 C13---C14 1.502 (2) C22---H22 0.9300 C15---C16 1.518 (2) C23---H23 0.9300 C17---C18 1.508 (2) C25---H25 0.9300 C19---C20 1.509 (2) C26---H26 0.9300 C21---C22 1.396 (2) F1···H3^i^ 2.7700 H2···H10 2.1900 F1···H15B^ii^ 2.6900 H2···O3^iii^ 2.9100 F1···H19A^ii^ 2.7100 H2···N1^iii^ 2.9000 O1···C6 2.8742 (19) H3···F1^xii^ 2.7700 O1···C16 3.0123 (18) H3···C25^xii^ 3.0300 O2···N3 2.8383 (15) H3···H25^xii^ 2.4400 O3···N2 2.7209 (16) H5···C22^iv^ 3.0700 O3···C11^iii^ 3.3306 (18) H5···C23^iv^ 2.8800 O3···C8 3.2257 (18) H5···C24^iv^ 2.9800 O1···H12A^iii^ 2.6800 H6···O1 2.3200 O1···H15A 2.4500 H6···C8 2.7100 O1···H6 2.3200 H6···H15A^xi^ 2.5800 O1···H17B^iv^ 2.7700 H10···C2 2.6600 O2···H13A^v^ 2.7200 H10···C11 2.6100 O2···H26^vi^ 2.7500 H10···H2 2.1900 O3···H17A 2.3800 H10···H11B 2.0000 O3···H2^iii^ 2.9100 H10···O3^iii^ 2.7800 O3···H10^iii^ 2.7800 H11B···C10 2.5700 O3···H11B^iii^ 2.4100 H11B···H10 2.0000 N2···O3 2.7209 (16) H11B···O3^iii^ 2.4100 N3···O2 2.8383 (15) H12A···H13B 2.3100 N4···N5 2.8407 (16) H12A···H20A^vi^ 2.5500 N5···N4 2.8407 (16) H12A···O1^iii^ 2.6800 N1···H22^vii^ 2.7300 H12B···C3^x^ 2.9200 N1···H2^iii^ 2.9000 H12B···C4^x^ 3.0800 N1···H18A^vii^ 2.6700 H13A···O2^v^ 2.7200 N1···H14A 2.3600 H13B···H12A 2.3100 N1···H14B 2.8600 H13B···C6^iii^ 3.0700 N2···H18A^vii^ 2.8300 H14A···N1 2.3600 C2···C14^iii^ 3.508 (2) H14A···C2^iii^ 2.8600 C6···O1 2.8742 (19) H14B···N1 2.8600 C7···C9^iii^ 3.5673 (18) H14B···H22^vii^ 2.5600 C8···O3 3.2257 (18) H15A···O1 2.4500 C9···C7^iii^ 3.5673 (18) H15A···C20 2.6500 C9···C18^vii^ 3.497 (2) H15A···H20B 2.0000 C9···C10^iii^ 3.5089 (18) H15A···H6^xi^ 2.5800 C10···C9^iii^ 3.5089 (18) H15B···C20 3.0200 C10···C10^iii^ 3.5197 (19) H15B···H20B 2.5500 C11···O3^iii^ 3.3306 (18) H15B···F1^ii^ 2.6900 C12···C19^vi^ 3.577 (2) H17A···O3 2.3800 C14···C2^iii^ 3.508 (2) H17A···C10^viii^ 2.9700 C16···O1 3.0123 (18) H17B···H20A 2.4000 C18···C9^viii^ 3.497 (2) H17B···O1^iv^ 2.7700 C19···C12^ix^ 3.577 (2) H18A···N1^viii^ 2.6700 C2···H14A^iii^ 2.8600 H18A···N2^viii^ 2.8300 C2···H10 2.6600 H18A···C9^viii^ 2.8900 C3···H12B^x^ 2.9200 H18A···C22 2.5500 C4···H12B^x^ 3.0800 H18A···H22 2.0100 C5···H20B^xi^ 2.9400 H18B···C22 2.8900 C6···H20B^xi^ 3.0500 H18B···H22 2.4700 C6···H13B^iii^ 3.0700 H19A···F1^ii^ 2.7100 C8···H6 2.7100 H19A···C23^ii^ 2.9500 C9···H18A^vii^ 2.8900 H19A···C24^ii^ 2.8800 C10···H17A^vii^ 2.9700 H19B···C12^ix^ 2.8700 C10···H2 2.6900 H19B···C26 2.5500 C10···H11B 2.5700 H19B···H26 1.9900 C11···H10 2.6100 H20A···C12^ix^ 3.0300 C12···H20A^vi^ 3.0300 H20A···H12A^ix^ 2.5500 C12···H19B^vi^ 2.8700 H20A···H17B 2.4000 C13···H26^vi^ 3.0500 H20B···C15 2.4800 C15···H20B 2.4800 H20B···H15A 2.0000 C18···H22 2.4600 H20B···H15B 2.5500 C19···H26 2.6100 H20B···C5^xi^ 2.9400 C20···H15A 2.6500 H20B···C6^xi^ 3.0500 C20···H15B 3.0200 H22···N1^viii^ 2.7300 C22···H18A 2.5500 H22···C18 2.4600 C22···H18B 2.8900 H22···H14B^viii^ 2.5600 C22···H5^iv^ 3.0700 H22···H18A 2.0100 C23···H5^iv^ 2.8800 H22···H18B 2.4700 C23···H19A^ii^ 2.9500 H25···H3^i^ 2.4400 C24···H5^iv^ 2.9800 H26···O2^ix^ 2.7500 C24···H19A^ii^ 2.8800 H26···C13^ix^ 3.0500 C25···H3^i^ 3.0300 H26···C19 2.6100 C26···H19B 2.5500 H26···H19B 1.9900 H2···C10 2.6900 C12---O2---C13 108.95 (12) C4---C5---H5 120.00 N2---N1---C9 116.01 (10) C6---C5---H5 120.00 N1---N2---C8 127.91 (11) C1---C6---H6 120.00 N1---N2---C15 114.75 (10) C5---C6---H6 120.00 C8---N2---C15 117.34 (11) C7---C10---H10 119.00 C9---N3---C11 119.14 (11) C9---C10---H10 119.00 C9---N3---C14 117.13 (11) N3---C11---H11A 110.00 C11---N3---C14 112.25 (11) N3---C11---H11B 110.00 C16---N4---C17 120.60 (12) C12---C11---H11A 110.00 C16---N4---C20 126.08 (12) C12---C11---H11B 110.00 C17---N4---C20 110.06 (12) H11A---C11---H11B 108.00 C18---N5---C19 114.00 (11) O2---C12---H12A 109.00 C18---N5---C21 116.78 (11) O2---C12---H12B 109.00 C19---N5---C21 117.13 (10) C11---C12---H12A 109.00 C2---C1---C6 118.22 (12) C11---C12---H12B 109.00 C2---C1---C7 120.29 (12) H12A---C12---H12B 108.00 C6---C1---C7 121.46 (12) O2---C13---H13A 109.00 C1---C2---C3 120.40 (14) O2---C13---H13B 109.00 C2---C3---C4 120.71 (16) C14---C13---H13A 109.00 C3---C4---C5 119.50 (15) C14---C13---H13B 109.00 C4---C5---C6 120.59 (15) H13A---C13---H13B 108.00 C1---C6---C5 120.57 (14) N3---C14---H14A 110.00 C1---C7---C8 120.11 (11) N3---C14---H14B 110.00 C1---C7---C10 122.01 (12) C13---C14---H14A 110.00 C8---C7---C10 117.88 (11) C13---C14---H14B 110.00 O1---C8---N2 119.12 (12) H14A---C14---H14B 108.00 O1---C8---C7 126.40 (12) N2---C15---H15A 109.00 N2---C8---C7 114.49 (11) N2---C15---H15B 109.00 N1---C9---N3 116.54 (11) C16---C15---H15A 109.00 N1---C9---C10 121.96 (11) C16---C15---H15B 109.00 N3---C9---C10 121.49 (11) H15A---C15---H15B 108.00 C7---C10---C9 121.60 (12) N4---C17---H17A 110.00 N3---C11---C12 109.61 (12) N4---C17---H17B 110.00 O2---C12---C11 112.03 (12) C18---C17---H17A 110.00 O2---C13---C14 112.09 (14) C18---C17---H17B 110.00 N3---C14---C13 110.40 (12) H17A---C17---H17B 108.00 N2---C15---C16 111.27 (11) N5---C18---H18A 109.00 O3---C16---N4 122.80 (14) N5---C18---H18B 109.00 O3---C16---C15 120.54 (13) C17---C18---H18A 109.00 N4---C16---C15 116.67 (11) C17---C18---H18B 109.00 N4---C17---C18 110.23 (12) H18A---C18---H18B 108.00 N5---C18---C17 112.17 (12) N5---C19---H19A 109.00 N5---C19---C20 111.62 (11) N5---C19---H19B 109.00 N4---C20---C19 110.40 (11) C20---C19---H19A 109.00 N5---C21---C22 121.73 (12) C20---C19---H19B 109.00 N5---C21---C26 121.14 (12) H19A---C19---H19B 108.00 C22---C21---C26 117.10 (13) N4---C20---H20A 110.00 C21---C22---C23 121.10 (14) N4---C20---H20B 110.00 C22---C23---C24 119.61 (16) C19---C20---H20A 110.00 F1---C24---C23 119.38 (15) C19---C20---H20B 110.00 F1---C24---C25 118.95 (14) H20A---C20---H20B 108.00 C23---C24---C25 121.67 (15) C21---C22---H22 119.00 C24---C25---C26 119.02 (14) C23---C22---H22 119.00 C21---C26---C25 121.49 (14) C22---C23---H23 120.00 C1---C2---H2 120.00 C24---C23---H23 120.00 C3---C2---H2 120.00 C24---C25---H25 121.00 C2---C3---H3 120.00 C26---C25---H25 120.00 C4---C3---H3 120.00 C21---C26---H26 119.00 C3---C4---H4 120.00 C25---C26---H26 119.00 C5---C4---H4 120.00 C13---O2---C12---C11 60.78 (16) C6---C1---C7---C10 −151.12 (14) C12---O2---C13---C14 −59.74 (16) C6---C1---C7---C8 28.3 (2) C9---N1---N2---C8 −1.23 (19) C6---C1---C2---C3 −0.4 (2) N2---N1---C9---C10 2.71 (18) C7---C1---C2---C3 −178.64 (14) C9---N1---N2---C15 179.39 (11) C2---C1---C7---C8 −153.52 (13) N2---N1---C9---N3 −177.06 (11) C2---C1---C6---C5 −0.7 (2) C15---N2---C8---O1 −2.74 (19) C7---C1---C6---C5 177.56 (14) N1---N2---C8---C7 −2.13 (19) C2---C1---C7---C10 27.1 (2) C15---N2---C8---C7 177.24 (11) C1---C2---C3---C4 1.3 (3) N1---N2---C15---C16 −105.23 (12) C2---C3---C4---C5 −1.1 (3) C8---N2---C15---C16 75.32 (14) C3---C4---C5---C6 0.1 (3) N1---N2---C8---O1 177.89 (12) C4---C5---C6---C1 0.9 (3) C14---N3---C11---C12 52.25 (15) C1---C7---C10---C9 176.59 (12) C14---N3---C9---N1 −12.56 (18) C8---C7---C10---C9 −2.82 (19) C14---N3---C9---C10 167.66 (13) C1---C7---C8---O1 4.6 (2) C9---N3---C14---C13 165.09 (13) C10---C7---C8---N2 3.99 (18) C11---N3---C14---C13 −51.70 (16) C1---C7---C8---N2 −175.43 (12) C9---N3---C11---C12 −165.36 (11) C10---C7---C8---O1 −176.03 (14) C11---N3---C9---N1 −153.17 (12) N1---C9---C10---C7 −0.7 (2) C11---N3---C9---C10 27.06 (18) N3---C9---C10---C7 179.07 (12) C16---N4---C20---C19 −98.68 (16) N3---C11---C12---O2 −57.26 (16) C17---N4---C16---O3 8.9 (2) O2---C13---C14---N3 55.52 (17) C17---N4---C16---C15 −170.73 (11) N2---C15---C16---N4 −158.32 (11) C20---N4---C16---C15 −13.24 (19) N2---C15---C16---O3 22.07 (17) C20---N4---C17---C18 −60.28 (15) N4---C17---C18---N5 53.86 (16) C16---N4---C17---C18 100.50 (15) N5---C19---C20---N4 −54.43 (15) C20---N4---C16---O3 166.37 (13) N5---C21---C22---C23 −176.61 (14) C17---N4---C20---C19 60.79 (15) C26---C21---C22---C23 1.2 (2) C19---N5---C18---C17 −48.75 (16) N5---C21---C26---C25 176.70 (14) C21---N5---C19---C20 −169.67 (11) C22---C21---C26---C25 −1.1 (2) C19---N5---C21---C26 34.26 (18) C21---C22---C23---C24 −0.5 (2) C18---N5---C19---C20 48.87 (15) C22---C23---C24---F1 179.76 (15) C18---N5---C21---C26 174.65 (13) C22---C23---C24---C25 −0.3 (3) C18---N5---C21---C22 −7.63 (19) F1---C24---C25---C26 −179.68 (14) C21---N5---C18---C17 169.65 (12) C23---C24---C25---C26 0.4 (3) C19---N5---C21---C22 −148.02 (13) C24---C25---C26---C21 0.4 (2) ---------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) x+1, y−1, z+1; (ii) −x+2, −y+1, −z+2; (iii) −x+1, −y+2, −z+1; (iv) −x+2, −y+1, −z+1; (v) −x, −y+2, −z+2; (vi) x−1, y+1, z; (vii) x−1, y, z; (viii) x+1, y, z; (ix) x+1, y−1, z; (x) −x, −y+2, −z+1; (xi) −x+1, −y+1, −z+1; (xii) x−1, y+1, z−1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4545 .table-wrap} --------------------------------------------------------------------------------------------------- Cg2, Cg4 and Cg5 are the centroids of the N1/N2/C7--C10, C1--C6 and C21--C26 rings, respectively. --------------------------------------------------------------------------------------------------- ::: ::: {#d1e4549 .table-wrap} ------------------------ --------- --------- ------------- --------------- D---H···A D---H H···A D···A D---H···A C6---H6···O1 0.93 2.32 2.8742 (19) 117 C11---H11B···O3^iii^ 0.97 2.41 3.3306 (18) 159 C17---H17A···O3 0.97 2.38 2.7660 (19) 103 C5---H5···Cg5^iv^ 0.93 2.86 3.4941 (18) 127 C13---H13B···Cg4^iii^ 0.97 2.92 3.7395 (19) 143 C18---H18A···Cg2^viii^ 0.97 2.73 3.5079 (16) 138 ------------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (iii) −x+1, −y+2, −z+1; (iv) −x+2, −y+1, −z+1; (viii) x+1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg2, Cg4 and Cg5 are the centroids of the N1/N2/C7--C10, C1--C6 and C21--C26 rings, respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------------- --------- ------- ------------- ------------- C11---H11B⋯O3^i^ 0.97 2.41 3.3306 (18) 159 C5---H5⋯Cg5^ii^ 0.93 2.86 3.4941 (18) 127 C13---H13B⋯Cg4^i^ 0.97 2.92 3.7395 (19) 143 C18---H18A⋯Cg2^iii^ 0.97 2.73 3.5079 (16) 138 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.808558	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052151/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o666-o667", "authors": [ { "first": "Abdullah", "last": "Aydın" }, { "first": "Murat", "last": "Şüküroğlu" }, { "first": "Mehmet", "last": "Akkurt" }, { "first": "Orhan", "last": "Büyükgüngör" } ] }
PMC3052152	Related literature {#sec1} ================== For the biological activity of sydnones, see: Holla et al. (1986[@bb6], 1987[@bb7], 1992[@bb8]); Rai et al. (2008[@bb9]). For related structures, see: Fun et al. (2010[@bb4], 2011[@bb5]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). For bond-length data, see: Allen et al. (1987[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~9~Br~2~NO~4~M ~r~ = 403.03Triclinic,a = 8.6939 (7) Åb = 8.7834 (8) Åc = 10.4722 (9) Åα = 89.334 (2)°β = 69.846 (2)°γ = 68.114 (2)°V = 690.32 (10) Å^3^Z = 2Mo Kα radiationμ = 5.88 mm^−1^T = 100 K0.28 × 0.18 × 0.08 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2009[@bb2]) T ~min~ = 0.292, T ~max~ = 0.64410644 measured reflections4015 independent reflections3390 reflections with I \> 2σ(I)R ~int~ = 0.030 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.100S = 1.334015 reflections216 parametersH-atom parameters constrainedΔρ~max~ = 0.71 e Å^−3^Δρ~min~ = −0.60 e Å^−3^ {#d5e457} Data collection: APEX2 (Bruker, 2009[@bb2]); cell refinement: SAINT (Bruker, 2009[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb10]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003552/sj5095sup1.cif](http://dx.doi.org/10.1107/S1600536811003552/sj5095sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003552/sj5095Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003552/sj5095Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5095&file=sj5095sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5095sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5095&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5095](http://scripts.iucr.org/cgi-bin/sendsup?sj5095)). HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSH also thanks USM for the award of a research fellowship. Comment ======= Nitrofurans belong to a class of synthetic compounds characterized by the presence of the 5-nitro-2-furyl group. The presence of a nitro group at the 5-position of the molecule conferred antibacterial activity (Holla et al.1986). A large number of nitrofurans have attained commercial utility as antibacterial agents in humans and in veterinary medicine because of their broad spectrum of activity (Holla & Kalluraya et al.1992; Holla et al. 1987). Dibromopropanones were obtained by the bromination of 1-aryl-3-(5-nitro-2-furyl)-2-propen-1-ones. Acid-catalysed condensation of acetophenones with nitrofural diacetate in acetic acid yielded the required 1-aryl-3-(5-nitro-2-furyl)-2-propen-1-ones known as chalcones (Rai et al., 2008). The title compound, C~13~H~9~Br~2~NO~4~, (Fig. 1), consist of phenyl (C1--C6) and 2-nitrofuran (C10--C13/O2--O4/N1) rings linked by a 2,3-dibromopropanal group (O1/C7--C9/Br1/Br2). Six atoms (C8--C10/Br1/Br2/O2) of this linking group including a furyl C atom are disordered over two positions with a site-occupancy ratio of 0.733 (11): 0.267 (11). The dihedral angle between the furan (C11--C13/O2/C10) (maximum deviation of 0.028 (4) Å of at atom C12) and phenyl rings in the major component is 16.9 (3)°. In the minor component, the corresponding values are 0.87 (4) Å at atom C12 and 23.3 (5)°. Bond lengths (Allen et al., 1987) and angles are normal and comparable to those in related structures (Fun et al., 2010, 2011). In the crystal packing (Fig. 2), intermolecular C9A---H9AA···O1 and C4---H4A···O4 hydrogen bonds (Table 1) link the molecules into two-dimensional arrays parallel to the ab plane. Experimental {#experimental} ============ 1-Phenyl-3-(5-nitro-2-furyl)-2-propen-1-one (0.01 mol) was dissolved in glacial acetic acid (25 ml) by gentle warming. A solution of bromine in glacial acetic acid (30% w/v) was added to it with constant stirring till the yellow color of the bromine persisted. The reaction mixture was kept aside at room temperature for overnight. Crystals of dibromopropanone that separated out were collected by filtration and washed with petroleum ether and dried. They were then recrystallized from glacial acetic acid. Crystals suitable for X-ray analysis were obtained from 1:2 mixtures of DMF and ethanol by slow evaporation. Refinement {#refinement} ========== All the H atoms were positioned geometrically \[C--H = 0.9300 or 0.9800 Å\] and were refined using a riding model, with U~iso~(H) = 1.2 U~eq~ (C). Six atoms are disordered over two positions with a refined occupany ratio of 0.733 (11):0.267 (11). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme. Both major and minor components are shown with bonds to atoms of the minor component drawn as open lines. ::: ![](e-67-0o546-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound, viewed along the c axis. Only the major disordered component is shown. ::: ![](e-67-0o546-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e152 .table-wrap} ------------------------ --------------------------------------- C~13~H~9~Br~2~NO~4~ Z = 2 M~r~ = 403.03 F(000) = 392 Triclinic, P1 D~x~ = 1.939 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.6939 (7) Å Cell parameters from 4381 reflections b = 8.7834 (8) Å θ = 2.7--29.9° c = 10.4722 (9) Å µ = 5.88 mm^−1^ α = 89.334 (2)° T = 100 K β = 69.846 (2)° Block, colourless γ = 68.114 (2)° 0.28 × 0.18 × 0.08 mm V = 690.32 (10) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e288 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 4015 independent reflections Radiation source: fine-focus sealed tube 3390 reflections with I \> 2σ(I) graphite R~int~ = 0.030 φ and ω scans θ~max~ = 30.1°, θ~min~ = 2.1° Absorption correction: multi-scan (SADABS; Bruker, 2009) h = −12→12 T~min~ = 0.292, T~max~ = 0.644 k = −12→12 10644 measured reflections l = −14→14 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e405 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.100 H-atom parameters constrained S = 1.33 w = 1/\[σ^2^(F~o~^2^) + (0.P)^2^ + 1.8339P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4015 reflections (Δ/σ)~max~ = 0.004 216 parameters Δρ~max~ = 0.71 e Å^−3^ 0 restraints Δρ~min~ = −0.60 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e562 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e667 .table-wrap} ------ ------------- -------------- ------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) Br1A 0.5867 (5) −0.0270 (6) 0.3027 (5) 0.0390 (6) 0.733 (11) Br2A 0.3391 (5) 0.3650 (6) 0.0580 (4) 0.0351 (7) 0.733 (11) Br1B 0.3448 (12) 0.3749 (13) 0.0447 (8) 0.0197 (10) 0.267 (11) Br2B 0.5581 (11) −0.0069 (17) 0.3178 (13) 0.0296 (14) 0.267 (11) O1 0.2667 (4) 0.0406 (4) 0.1625 (3) 0.0338 (7) O2A 0.6226 (6) 0.3610 (7) 0.2085 (5) 0.0189 (9) 0.733 (11) O2B 0.6469 (19) 0.3223 (18) 0.2302 (15) 0.018 (3)\ 0.267 (11) O3 0.6434 (4) 0.5677 (4) 0.3755 (3) 0.0325 (6) O4 0.8888 (4) 0.5635 (4) 0.2207 (3) 0.0415 (8) N1 0.7672 (4) 0.5148 (4) 0.2642 (3) 0.0249 (6) C1 −0.0571 (5) 0.1488 (5) 0.3829 (4) 0.0212 (7) H1A −0.0479 0.0924 0.3043 0.025\* C2 −0.2122 (5) 0.1970 (5) 0.4979 (4) 0.0253 (7) H2A −0.3084 0.1755 0.4960 0.030\* C3 −0.2236 (5) 0.2777 (5) 0.6167 (4) 0.0294 (8) H3A −0.3274 0.3095 0.6943 0.035\* C4 −0.0827 (5) 0.3104 (6) 0.6197 (4) 0.0323 (9) H4A −0.0907 0.3625 0.7000 0.039\* C5 0.0721 (5) 0.2667 (5) 0.5041 (4) 0.0292 (8) H5A 0.1662 0.2918 0.5062 0.035\* C6 0.0856 (5) 0.1849 (5) 0.3846 (4) 0.0228 (7) C7 0.2483 (5) 0.1296 (5) 0.2579 (4) 0.0247 (7) C8A 0.4061 (7) 0.1730 (7) 0.2557 (5) 0.0216 (12) 0.733 (11) H8AA 0.3645 0.2723 0.3204 0.026\* 0.733 (11) C9A 0.5127 (6) 0.1929 (6) 0.1129 (5) 0.0193 (12) 0.733 (11) H9AA 0.5601 0.0895 0.0515 0.023\* 0.733 (11) C10A 0.6591 (8) 0.2419 (8) 0.1058 (6) 0.0203 (11) 0.733 (11) C8B 0.3734 (19) 0.229 (2) 0.2179 (16) 0.021 (3)\* 0.267 (11) H8BA 0.3511 0.3022 0.2981 0.025\* 0.267 (11) C9B 0.5672 (17) 0.1115 (16) 0.1590 (13) 0.018 (3)\* 0.267 (11) H9BA 0.5921 0.0391 0.0776 0.022\* 0.267 (11) C10B 0.688 (2) 0.200 (2) 0.1295 (18) 0.019 (4)\* 0.267 (11) C11 0.8299 (5) 0.1960 (5) 0.0144 (4) 0.0253 (8) H11A 0.8883 0.1133 −0.0605 0.030\* C12 0.9001 (5) 0.2992 (5) 0.0562 (4) 0.0240 (7) H12A 1.0104 0.3042 0.0109 0.029\* C13 0.7741 (5) 0.3889 (5) 0.1753 (4) 0.0214 (7) ------ ------------- -------------- ------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1189 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1A 0.0594 (17) 0.0360 (9) 0.0387 (12) −0.0285 (13) −0.0276 (13) 0.0186 (8) Br2A 0.0317 (11) 0.0294 (7) 0.0539 (16) −0.0122 (6) −0.0269 (10) 0.0123 (8) Br1B 0.0144 (15) 0.026 (2) 0.0159 (13) −0.0064 (14) −0.0040 (10) 0.0003 (13) Br2B 0.0210 (13) 0.049 (4) 0.0275 (18) −0.0201 (15) −0.0118 (11) 0.017 (2) O1 0.0328 (15) 0.0468 (19) 0.0237 (14) −0.0266 (14) 0.0000 (12) −0.0101 (12) O2A 0.0164 (18) 0.022 (2) 0.018 (2) −0.0095 (17) −0.0035 (16) −0.0004 (17) O3 0.0296 (14) 0.0340 (16) 0.0319 (15) −0.0137 (13) −0.0073 (12) −0.0056 (12) O4 0.0337 (16) 0.053 (2) 0.0443 (18) −0.0308 (16) −0.0064 (14) −0.0062 (15) N1 0.0224 (14) 0.0256 (16) 0.0300 (17) −0.0107 (13) −0.0117 (13) 0.0014 (13) C1 0.0196 (15) 0.0248 (18) 0.0199 (16) −0.0109 (14) −0.0055 (13) 0.0004 (13) C2 0.0197 (16) 0.029 (2) 0.0276 (19) −0.0124 (15) −0.0056 (14) 0.0034 (15) C3 0.0229 (18) 0.034 (2) 0.029 (2) −0.0116 (16) −0.0062 (15) −0.0009 (16) C4 0.0281 (19) 0.042 (2) 0.0228 (19) −0.0168 (18) −0.0010 (15) −0.0096 (16) C5 0.0233 (17) 0.039 (2) 0.0235 (18) −0.0166 (17) −0.0010 (14) −0.0095 (16) C6 0.0211 (16) 0.0255 (18) 0.0207 (17) −0.0118 (14) −0.0033 (13) −0.0018 (13) C7 0.0212 (16) 0.0291 (19) 0.0222 (17) −0.0146 (15) −0.0008 (14) −0.0042 (14) C8A 0.020 (2) 0.024 (3) 0.022 (2) −0.012 (2) −0.0047 (19) 0.001 (2) C9A 0.018 (2) 0.021 (3) 0.018 (2) −0.0080 (18) −0.0042 (17) −0.0023 (17) C10A 0.022 (3) 0.019 (3) 0.021 (3) −0.008 (2) −0.008 (2) 0.002 (2) C11 0.0210 (17) 0.029 (2) 0.0205 (17) −0.0097 (15) −0.0014 (14) −0.0038 (14) C12 0.0154 (15) 0.029 (2) 0.0251 (18) −0.0089 (14) −0.0039 (13) 0.0019 (14) C13 0.0183 (15) 0.0254 (18) 0.0239 (17) −0.0126 (14) −0.0074 (13) 0.0026 (13) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1674 .table-wrap} ------------------------- ------------- ------------------------- ------------- Br1A---C8A 2.061 (7) C4---H4A 0.9300 Br2A---C9A 1.942 (7) C5---C6 1.398 (5) Br1B---C8B 2.24 (2) C5---H5A 0.9300 Br2B---C9B 1.944 (18) C6---C7 1.485 (5) O1---C7 1.205 (5) C7---C8A 1.547 (6) O2A---C13 1.356 (5) C7---C8B 1.586 (15) O2A---C10A 1.376 (7) C8A---C9A 1.512 (7) O2B---C10B 1.37 (2) C8A---H8AA 0.9800 O2B---C13 1.390 (15) C9A---C10A 1.468 (7) O3---N1 1.228 (4) C9A---H9AA 0.9800 O4---N1 1.229 (4) C10A---C11 1.366 (6) N1---C13 1.424 (5) C8B---C9B 1.513 (19) C1---C2 1.384 (5) C8B---H8BA 0.9800 C1---C6 1.396 (5) C9B---C10B 1.48 (2) C1---H1A 0.9300 C9B---H9BA 0.9800 C2---C3 1.394 (6) C10B---C11 1.382 (17) C2---H2A 0.9300 C11---C12 1.411 (5) C3---C4 1.369 (6) C11---H11A 0.9300 C3---H3A 0.9300 C12---C13 1.347 (5) C4---C5 1.388 (5) C12---H12A 0.9300 C13---O2A---C10A 104.7 (4) C8A---C9A---Br2A 104.1 (3) C10B---O2B---C13 103.9 (12) C10A---C9A---H9AA 109.5 O3---N1---O4 124.8 (3) C8A---C9A---H9AA 109.5 O3---N1---C13 119.5 (3) Br2A---C9A---H9AA 109.5 O4---N1---C13 115.7 (3) C11---C10A---O2A 110.5 (4) C2---C1---C6 120.1 (3) C11---C10A---C9A 133.2 (5) C2---C1---H1A 119.9 O2A---C10A---C9A 116.3 (4) C6---C1---H1A 119.9 C9B---C8B---C7 110.4 (11) C1---C2---C3 119.8 (3) C9B---C8B---Br1B 102.2 (9) C1---C2---H2A 120.1 C7---C8B---Br1B 112.9 (9) C3---C2---H2A 120.1 C9B---C8B---H8BA 110.4 C4---C3---C2 120.3 (4) C7---C8B---H8BA 110.4 C4---C3---H3A 119.8 Br1B---C8B---H8BA 110.4 C2---C3---H3A 119.8 C10B---C9B---C8B 111.8 (12) C3---C4---C5 120.7 (4) C10B---C9B---Br2B 114.8 (11) C3---C4---H4A 119.7 C8B---C9B---Br2B 95.2 (9) C5---C4---H4A 119.7 C10B---C9B---H9BA 111.3 C4---C5---C6 119.6 (4) C8B---C9B---H9BA 111.3 C4---C5---H5A 120.2 Br2B---C9B---H9BA 111.3 C6---C5---H5A 120.2 O2B---C10B---C11 111.1 (14) C1---C6---C5 119.6 (3) O2B---C10B---C9B 115.5 (14) C1---C6---C7 117.5 (3) C11---C10B---C9B 133.2 (15) C5---C6---C7 123.0 (3) C10A---C11---C10B 20.1 (6) O1---C7---C6 122.0 (3) C10A---C11---C12 106.3 (4) O1---C7---C8A 119.2 (3) C10B---C11---C12 105.3 (8) C6---C7---C8A 118.5 (3) C10A---C11---H11A 126.8 O1---C7---C8B 113.5 (6) C10B---C11---H11A 124.3 C6---C7---C8B 121.2 (6) C12---C11---H11A 126.8 C8A---C7---C8B 24.7 (5) C13---C12---C11 105.7 (3) C9A---C8A---C7 111.9 (4) C13---C12---H12A 127.1 C9A---C8A---Br1A 103.2 (3) C11---C12---H12A 127.1 C7---C8A---Br1A 108.7 (4) C12---C13---O2A 112.5 (4) C9A---C8A---H8AA 110.9 C12---C13---O2B 111.5 (7) C7---C8A---H8AA 110.9 O2A---C13---O2B 18.2 (5) Br1A---C8A---H8AA 110.9 C12---C13---N1 131.7 (3) C10A---C9A---C8A 114.2 (4) O2A---C13---N1 115.6 (3) C10A---C9A---Br2A 109.9 (4) O2B---C13---N1 115.6 (7) C6---C1---C2---C3 −1.7 (6) C7---C8B---C9B---C10B −176.0 (12) C1---C2---C3---C4 0.4 (6) Br1B---C8B---C9B---C10B 63.7 (13) C2---C3---C4---C5 1.2 (7) C7---C8B---C9B---Br2B −56.6 (11) C3---C4---C5---C6 −1.6 (7) Br1B---C8B---C9B---Br2B −176.9 (7) C2---C1---C6---C5 1.3 (6) C13---O2B---C10B---C11 −2.7 (15) C2---C1---C6---C7 179.9 (4) C13---O2B---C10B---C9B −177.7 (12) C4---C5---C6---C1 0.3 (6) C8B---C9B---C10B---O2B 45.3 (18) C4---C5---C6---C7 −178.2 (4) Br2B---C9B---C10B---O2B −61.8 (16) C1---C6---C7---O1 −8.5 (6) C8B---C9B---C10B---C11 −128.2 (19) C5---C6---C7---O1 170.0 (4) Br2B---C9B---C10B---C11 124.7 (17) C1---C6---C7---C8A 178.1 (4) O2A---C10A---C11---C10B 86 (3) C5---C6---C7---C8A −3.4 (6) C9A---C10A---C11---C10B −96 (3) C1---C6---C7---C8B 149.7 (8) O2A---C10A---C11---C12 −4.1 (7) C5---C6---C7---C8B −31.8 (9) C9A---C10A---C11---C12 174.2 (7) O1---C7---C8A---C9A 36.3 (6) O2B---C10B---C11---C10A −84 (3) C6---C7---C8A---C9A −150.1 (4) C9B---C10B---C11---C10A 89 (3) C8B---C7---C8A---C9A −46.6 (14) O2B---C10B---C11---C12 11.5 (14) O1---C7---C8A---Br1A −77.1 (5) C9B---C10B---C11---C12 −174.8 (16) C6---C7---C8A---Br1A 96.5 (4) C10A---C11---C12---C13 5.3 (5) C8B---C7---C8A---Br1A −159.9 (15) C10B---C11---C12---C13 −15.6 (9) C7---C8A---C9A---C10A 177.2 (5) C11---C12---C13---O2A −4.7 (5) Br1A---C8A---C9A---C10A −66.1 (5) C11---C12---C13---O2B 14.9 (7) C7---C8A---C9A---Br2A 57.4 (5) C11---C12---C13---N1 −178.8 (4) Br1A---C8A---C9A---Br2A 174.0 (3) C10A---O2A---C13---C12 2.2 (6) C13---O2A---C10A---C11 1.3 (7) C10A---O2A---C13---O2B −88 (3) C13---O2A---C10A---C9A −177.3 (5) C10A---O2A---C13---N1 177.3 (4) C8A---C9A---C10A---C11 139.8 (8) C10B---O2B---C13---C12 −7.8 (12) Br2A---C9A---C10A---C11 −103.6 (8) C10B---O2B---C13---O2A 89 (3) C8A---C9A---C10A---O2A −41.9 (7) C10B---O2B---C13---N1 −176.6 (9) Br2A---C9A---C10A---O2A 74.7 (6) O3---N1---C13---C12 −172.8 (4) O1---C7---C8B---C9B −59.4 (13) O4---N1---C13---C12 7.9 (6) C6---C7---C8B---C9B 140.8 (9) O3---N1---C13---O2A 13.3 (6) C8A---C7---C8B---C9B 49.9 (13) O4---N1---C13---O2A −166.0 (4) O1---C7---C8B---Br1B 54.3 (9) O3---N1---C13---O2B −6.9 (8) C6---C7---C8B---Br1B −105.5 (7) O4---N1---C13---O2B 173.8 (7) C8A---C7---C8B---Br1B 163.6 (19) ------------------------- ------------- ------------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2615 .table-wrap} -------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C9A---H9AA···O1^i^ 0.98 2.25 3.098 (6) 145 C4---H4A···O4^ii^ 0.93 2.46 3.200 (6) 136 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y, −z; (ii) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------------- --------- ------- ----------- ------------- C9A---H9AA⋯O1^i^ 0.98 2.25 3.098 (6) 145 C4---H4A⋯O4^ii^ 0.93 2.46 3.200 (6) 136 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.	PubMed Central	2024-06-05T04:04:18.818219	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052152/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o546", "authors": [ { "first": "Tara", "last": "Shahani" }, { "first": "Hoong-Kun", "last": "Fun" }, { "first": null, "last": "Nithinchandra" }, { "first": "Balakrishna", "last": "Kalluraya" } ] }
PMC3052153	Related literature {#sec1} ================== For the structures of CuCl~2~ complexes with similar ligands, see: Saleh Salga et al. (2010[@bb4]); Wang et al. (2009[@bb7]). For the structure of a CdCl~2~ complex with the same Schiff base ligand, see: Ikmal Hisham et al. (2010[@bb3]). For a description of the geometry of complexes with a five-coordinate metal atom, see: Addison et al. (1984[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[CuCl~2~(C~13~H~19~N~3~O)\]·H~2~OM ~r~ = 385.77Monoclinic,a = 7.9194 (8) Åb = 8.5793 (8) Åc = 22.925 (2) Åβ = 91.981 (1)°V = 1556.6 (3) Å^3^Z = 4Mo Kα radiationμ = 1.75 mm^−1^T = 100 K0.18 × 0.16 × 0.09 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb5]) T ~min~ = 0.743, T ~max~ = 0.8589634 measured reflections3348 independent reflections2948 reflections with I \> 2σ(I)R ~int~ = 0.023 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.025wR(F ^2^) = 0.060S = 1.053348 reflections197 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.34 e Å^−3^ {#d5e573} Data collection: APEX2 (Bruker, 2007[@bb2]); cell refinement: SAINT (Bruker, 2007[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: X-SEED (Barbour, 2001)[@bb9]; software used to prepare material for publication: SHELXL97 and publCIF (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004892/is2674sup1.cif](http://dx.doi.org/10.1107/S1600536811004892/is2674sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004892/is2674Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004892/is2674Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2674&file=is2674sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2674sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2674&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2674](http://scripts.iucr.org/cgi-bin/sendsup?is2674)). The authors thank University of Malaya for funding this study (FRGS grant No. FP004/2010B). Comment ======= The asymmetric unit of the title compound consists of a copper(II) complex and one molecule of water. Like the CdCl~2~ complex of the Schiff base, 2-morpholino-N-\[1-(2-pyridyl)ethylidene\]ethanamine, (Ikmal Hisham et al., 2010) the metal ion in the present structure is five-coordinated by the N,N\',N\"-tridentate Schiff base ligand and two Cl atoms in a distorted square-pyramidal geometry, the τ value (Addison et al.,1984) being 0.15. The Cu---Cl and Cu---N interatomic distances are comparable to the values reported in the literature (Saleh Salga et al., 2010; Wang et al., 2009). In the crystal, the adjacent metal complexes and water molecules are linked into a three-dimensional network via O---H···Cl, C---H···Cl and C---H···O interactions. In addition, intramolecular C---H···Cl hydrogen bonding is observed. Experimental {#experimental} ============ A mixture of 2-acetylpyridine (0.20 g, 1.65 mmol) and 4-(2-aminoethyl)morpholine (0.21 g, 1.65 mmol) in ethanol (20 ml) was refluxed. After 2 hr a solution of copper(II) chloride dihydrate (0.28 g, 1.65 mmol) in a minimum amount of ethanol was added and the resulting solution was refluxed for 30 min, then set aside at room temperature. The crystals of the title complex were obtained after a few days. Refinement {#refinement} ========== The C-bound hydrogen atoms were placed at calculated positions (C---H 0.95--0.99 Å) and were treated as riding on their parent atoms. The O-bound H atoms were placed in a difference Fourier map, and were refined with distance restraint of O---H 0.84 (2) Å. For all hydrogen atoms U~iso~(H) were set to 1.2--1.5 times U~eq~(carrier atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Displacement ellipsoid plot of the title compound at the 50% probability level. Hydrogen atoms are drawn as spheres of arbitrary radii. ::: ![](e-67-0m334-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e126 .table-wrap} ------------------------------------ --------------------------------------- \[CuCl~2~(C~13~H~19~N~3~O)\]·H~2~O F(000) = 796 M~r~ = 385.77 D~x~ = 1.646 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 4229 reflections a = 7.9194 (8) Å θ = 2.5--28.2° b = 8.5793 (8) Å µ = 1.75 mm^−1^ c = 22.925 (2) Å T = 100 K β = 91.981 (1)° Block, green V = 1556.6 (3) Å^3^ 0.18 × 0.16 × 0.09 mm Z = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e260 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 3348 independent reflections Radiation source: fine-focus sealed tube 2948 reflections with I \> 2σ(I) graphite R~int~ = 0.023 φ and ω scans θ~max~ = 27.0°, θ~min~ = 2.5° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −10→10 T~min~ = 0.743, T~max~ = 0.858 k = −10→10 9634 measured reflections l = −29→28 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e377 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.060 H atoms treated by a mixture of independent and constrained refinement S = 1.05 w = 1/\[σ^2^(F~o~^2^) + (0.0258P)^2^ + 0.893P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3348 reflections (Δ/σ)~max~ = 0.001 197 parameters Δρ~max~ = 0.37 e Å^−3^ 2 restraints Δρ~min~ = −0.34 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e534 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e633 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cu1 0.60251 (3) 0.86379 (2) 0.122328 (9) 0.01099 (7) Cl1 0.49087 (6) 0.62132 (5) 0.11931 (2) 0.01873 (11) Cl2 0.90458 (6) 0.85029 (5) 0.15951 (2) 0.01773 (11) O1 0.32231 (17) 0.82636 (16) 0.30317 (6) 0.0183 (3) N1 0.68558 (19) 0.86674 (17) 0.03959 (7) 0.0129 (3) N2 0.60269 (19) 1.09006 (17) 0.10733 (7) 0.0119 (3) N3 0.51025 (18) 0.92685 (17) 0.20213 (6) 0.0114 (3) C1 0.7350 (2) 0.7448 (2) 0.00826 (8) 0.0159 (4) H1 0.7128 0.6427 0.0221 0.019\ C2 0.8177 (2) 0.7617 (2) −0.04381 (8) 0.0167 (4) H2 0.8513 0.6729 −0.0653 0.020\* C3 0.8501 (2) 0.9106 (2) −0.06373 (8) 0.0156 (4) H3 0.9077 0.9254 −0.0990 0.019\* C4 0.7975 (2) 1.0386 (2) −0.03157 (8) 0.0147 (4) H4 0.8168 1.1417 −0.0449 0.018\* C5 0.7169 (2) 1.0126 (2) 0.01989 (8) 0.0121 (4) C6 0.6645 (2) 1.1396 (2) 0.05987 (8) 0.0127 (4) C7 0.6910 (2) 1.3055 (2) 0.04320 (8) 0.0172 (4) H7A 0.6395 1.3737 0.0719 0.026\* H7B 0.6385 1.3247 0.0045 0.026\* H7C 0.8124 1.3271 0.0422 0.026\* C8 0.5483 (2) 1.1856 (2) 0.15617 (8) 0.0127 (4) H8A 0.4272 1.2127 0.1510 0.015\* H8B 0.6148 1.2832 0.1587 0.015\* C9 0.5779 (2) 1.0881 (2) 0.21117 (8) 0.0132 (4) H9A 0.7005 1.0830 0.2210 0.016\* H9B 0.5212 1.1379 0.2442 0.016\* C10 0.5778 (2) 0.8179 (2) 0.24813 (8) 0.0139 (4) H10A 0.7017 0.8316 0.2522 0.017\* H10B 0.5557 0.7094 0.2353 0.017\* C11 0.5017 (2) 0.8419 (2) 0.30720 (8) 0.0174 (4) H11A 0.5492 0.7642 0.3352 0.021\* H11B 0.5316 0.9471 0.3221 0.021\* C12 0.2547 (2) 0.9419 (2) 0.26393 (8) 0.0171 (4) H12A 0.2853 1.0468 0.2789 0.021\* H12B 0.1299 0.9340 0.2620 0.021\* C13 0.3217 (2) 0.9220 (2) 0.20293 (8) 0.0130 (4) H13A 0.2818 0.8210 0.1867 0.016\* H13B 0.2749 1.0057 0.1774 0.016\* O2 0.0878 (2) 0.59912 (18) 0.08146 (7) 0.0273 (3) H2A 0.035 (3) 0.659 (3) 0.1032 (10) 0.033\* H2B 0.183 (2) 0.602 (3) 0.0978 (11) 0.033\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1188 .table-wrap} ----- -------------- -------------- -------------- --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cu1 0.01348 (12) 0.00927 (11) 0.01044 (12) 0.00023 (8) 0.00364 (8) 0.00007 (8) Cl1 0.0256 (3) 0.0112 (2) 0.0200 (2) −0.00334 (17) 0.00966 (19) −0.00245 (17) Cl2 0.0123 (2) 0.0245 (2) 0.0165 (2) 0.00191 (17) 0.00273 (17) 0.00437 (18) O1 0.0157 (7) 0.0231 (7) 0.0165 (7) −0.0002 (5) 0.0050 (5) 0.0047 (6) N1 0.0131 (7) 0.0133 (7) 0.0124 (8) 0.0007 (6) 0.0013 (6) 0.0005 (6) N2 0.0124 (7) 0.0112 (7) 0.0120 (8) 0.0006 (6) 0.0008 (6) −0.0010 (6) N3 0.0109 (7) 0.0114 (7) 0.0120 (8) −0.0005 (6) 0.0013 (6) −0.0006 (6) C1 0.0190 (10) 0.0125 (9) 0.0162 (10) 0.0001 (7) 0.0019 (8) −0.0010 (7) C2 0.0175 (9) 0.0177 (9) 0.0151 (10) 0.0032 (7) 0.0029 (7) −0.0031 (7) C3 0.0142 (9) 0.0215 (10) 0.0113 (9) 0.0014 (7) 0.0017 (7) 0.0002 (7) C4 0.0145 (9) 0.0155 (9) 0.0142 (9) 0.0001 (7) 0.0004 (7) 0.0017 (7) C5 0.0127 (9) 0.0130 (8) 0.0107 (9) 0.0010 (7) 0.0003 (7) −0.0004 (7) C6 0.0108 (8) 0.0141 (9) 0.0130 (9) 0.0002 (7) 0.0003 (7) 0.0008 (7) C7 0.0229 (10) 0.0124 (9) 0.0169 (10) 0.0016 (7) 0.0070 (8) 0.0016 (7) C8 0.0150 (9) 0.0109 (8) 0.0124 (9) −0.0008 (7) 0.0031 (7) −0.0010 (7) C9 0.0145 (9) 0.0126 (9) 0.0126 (9) −0.0025 (7) 0.0007 (7) −0.0029 (7) C10 0.0127 (9) 0.0155 (9) 0.0134 (9) 0.0024 (7) 0.0007 (7) 0.0033 (7) C11 0.0160 (9) 0.0228 (10) 0.0134 (9) 0.0002 (8) 0.0021 (7) 0.0025 (8) C12 0.0152 (9) 0.0194 (9) 0.0171 (10) 0.0013 (7) 0.0056 (8) −0.0004 (8) C13 0.0099 (8) 0.0144 (9) 0.0148 (9) −0.0005 (7) 0.0009 (7) 0.0000 (7) O2 0.0307 (9) 0.0231 (8) 0.0285 (9) 0.0035 (7) 0.0053 (7) −0.0013 (7) ----- -------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1581 .table-wrap} ----------------- -------------- ------------------- ------------- Cu1---N2 1.9715 (15) C5---C6 1.491 (2) Cu1---N1 2.0290 (15) C6---C7 1.490 (2) Cu1---N3 2.0654 (15) C7---H7A 0.9800 Cu1---Cl1 2.2604 (5) C7---H7B 0.9800 Cu1---Cl2 2.5143 (5) C7---H7C 0.9800 O1---C11 1.427 (2) C8---C9 1.524 (2) O1---C12 1.430 (2) C8---H8A 0.9900 N1---C1 1.336 (2) C8---H8B 0.9900 N1---C5 1.356 (2) C9---H9A 0.9900 N2---C6 1.281 (2) C9---H9B 0.9900 N2---C8 1.464 (2) C10---C11 1.515 (3) N3---C10 1.494 (2) C10---H10A 0.9900 N3---C13 1.495 (2) C10---H10B 0.9900 N3---C9 1.495 (2) C11---H11A 0.9900 C1---C2 1.389 (3) C11---H11B 0.9900 C1---H1 0.9500 C12---C13 1.522 (3) C2---C3 1.383 (3) C12---H12A 0.9900 C2---H2 0.9500 C12---H12B 0.9900 C3---C4 1.395 (3) C13---H13A 0.9900 C3---H3 0.9500 C13---H13B 0.9900 C4---C5 1.379 (3) O2---H2A 0.837 (16) C4---H4 0.9500 O2---H2B 0.831 (16) N2---Cu1---N1 79.77 (6) C6---C7---H7B 109.5 N2---Cu1---N3 84.20 (6) H7A---C7---H7B 109.5 N1---Cu1---N3 163.90 (6) C6---C7---H7C 109.5 N2---Cu1---Cl1 154.62 (5) H7A---C7---H7C 109.5 N1---Cu1---Cl1 97.01 (4) H7B---C7---H7C 109.5 N3---Cu1---Cl1 96.79 (4) N2---C8---C9 106.53 (14) N2---Cu1---Cl2 95.63 (5) N2---C8---H8A 110.4 N1---Cu1---Cl2 88.97 (5) C9---C8---H8A 110.4 N3---Cu1---Cl2 94.20 (4) N2---C8---H8B 110.4 Cl1---Cu1---Cl2 109.544 (19) C9---C8---H8B 110.4 C11---O1---C12 109.02 (14) H8A---C8---H8B 108.6 C1---N1---C5 118.92 (16) N3---C9---C8 110.42 (14) C1---N1---Cu1 127.12 (12) N3---C9---H9A 109.6 C5---N1---Cu1 113.06 (12) C8---C9---H9A 109.6 C6---N2---C8 126.51 (15) N3---C9---H9B 109.6 C6---N2---Cu1 118.51 (13) C8---C9---H9B 109.6 C8---N2---Cu1 114.57 (11) H9A---C9---H9B 108.1 C10---N3---C13 107.88 (14) N3---C10---C11 113.72 (15) C10---N3---C9 111.29 (14) N3---C10---H10A 108.8 C13---N3---C9 112.19 (14) C11---C10---H10A 108.8 C10---N3---Cu1 109.42 (11) N3---C10---H10B 108.8 C13---N3---Cu1 112.81 (11) C11---C10---H10B 108.8 C9---N3---Cu1 103.24 (10) H10A---C10---H10B 107.7 N1---C1---C2 122.40 (17) O1---C11---C10 110.79 (15) N1---C1---H1 118.8 O1---C11---H11A 109.5 C2---C1---H1 118.8 C10---C11---H11A 109.5 C3---C2---C1 118.62 (17) O1---C11---H11B 109.5 C3---C2---H2 120.7 C10---C11---H11B 109.5 C1---C2---H2 120.7 H11A---C11---H11B 108.1 C2---C3---C4 119.35 (17) O1---C12---C13 111.41 (15) C2---C3---H3 120.3 O1---C12---H12A 109.3 C4---C3---H3 120.3 C13---C12---H12A 109.3 C5---C4---C3 118.75 (17) O1---C12---H12B 109.3 C5---C4---H4 120.6 C13---C12---H12B 109.3 C3---C4---H4 120.6 H12A---C12---H12B 108.0 N1---C5---C4 121.95 (16) N3---C13---C12 112.83 (15) N1---C5---C6 114.30 (15) N3---C13---H13A 109.0 C4---C5---C6 123.69 (16) C12---C13---H13A 109.0 N2---C6---C7 126.57 (17) N3---C13---H13B 109.0 N2---C6---C5 113.71 (16) C12---C13---H13B 109.0 C7---C6---C5 119.70 (16) H13A---C13---H13B 107.8 C6---C7---H7A 109.5 H2A---O2---H2B 101 (2) ----------------- -------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2183 .table-wrap} -------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A O2---H2A···Cl2^i^ 0.84 (2) 2.35 (2) 3.1829 (16) 173 (2) O2---H2B···Cl1 0.83 (2) 2.48 (2) 3.2841 (18) 164 (2) C2---H2···O2^ii^ 0.95 2.41 3.307 (2) 156 C3---H3···Cl2^iii^ 0.95 2.82 3.619 (2) 142 C4---H4···O2^iv^ 0.95 2.50 3.445 (2) 172 C7---H7A···Cl1^v^ 0.98 2.68 3.6179 (19) 161 C8---H8A···O1^vi^ 0.99 2.47 3.336 (2) 146 C10---H10B···Cl1 0.99 2.79 3.4496 (19) 124 C10---H10A···Cl2 0.99 2.71 3.3566 (19) 123 -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) x−1, y, z; (ii) −x+1, −y+1, −z; (iii) −x+2, −y+2, −z; (iv) −x+1, −y+2, −z; (v) x, y+1, z; (vi) −x+1/2, y+1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------- ---------- ---------- ------------- ------------- O2---H2A⋯Cl2^i^ 0.84 (2) 2.35 (2) 3.1829 (16) 173 (2) O2---H2B⋯Cl1 0.83 (2) 2.48 (2) 3.2841 (18) 164 (2) C2---H2⋯O2^ii^ 0.95 2.41 3.307 (2) 156 C3---H3⋯Cl2^iii^ 0.95 2.82 3.619 (2) 142 C4---H4⋯O2^iv^ 0.95 2.50 3.445 (2) 172 C7---H7A⋯Cl1^v^ 0.98 2.68 3.6179 (19) 161 C8---H8A⋯O1^vi^ 0.99 2.47 3.336 (2) 146 C10---H10B⋯Cl1 0.99 2.79 3.4496 (19) 124 C10---H10A⋯Cl2 0.99 2.71 3.3566 (19) 123 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) . :::	PubMed Central	2024-06-05T04:04:18.824821	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052153/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m334", "authors": [ { "first": "Nura", "last": "Suleiman Gwaram" }, { "first": "Hamid", "last": "Khaledi" }, { "first": "Hapipah", "last": "Mohd Ali" } ] }
PMC3052154	Related literature {#sec1} ================== For the synthesis of the starting material, see: Tolmachev et al. (2006[@bb6]). For a related structure, see: Ha et al. (2009[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~17~N~3~M ~r~ = 275.35Monoclinic,a = 11.5580 (7) Åb = 9.9179 (6) Åc = 13.9268 (7) Åβ = 105.707 (2)°V = 1536.83 (15) Å^3^Z = 4Mo Kα radiationμ = 0.07 mm^−1^T = 100 K0.5 × 0.4 × 0.2 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID II-S diffractometerAbsorption correction: multi-scan (RAPID-AUTO; Rigaku, 2008[@bb4]) T ~min~ = 0.966, T ~max~ = 0.98613505 measured reflections3185 independent reflections2321 reflections with I \> 2σ(I)R ~int~ = 0.077 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.049wR(F ^2^) = 0.134S = 1.073185 reflections193 parametersH-atom parameters constrainedΔρ~max~ = 0.22 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e330} Data collection: RAPID-AUTO (Rigaku, 2008[@bb4]); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb1]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb2]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005587/bq2278sup1.cif](http://dx.doi.org/10.1107/S1600536811005587/bq2278sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005587/bq2278Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005587/bq2278Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bq2278&file=bq2278sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bq2278sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bq2278&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BQ2278](http://scripts.iucr.org/cgi-bin/sendsup?bq2278)). This study was supported financially by Chonnam National University. CHK thanks the RIC, Sunchon National University, for financial support. Comment ======= Recently we have reported the structure of 2-(1-propyl-2,6-distyryl-1,4-pyridin-4-ylidene)malononitrile as a fluorescent dye (Ha et al., 2009). Continuing our study on the (1,4-pyridin-4-ylidene)malononitrile derivatives, the title compound was synthesized and its structure was confirmed by ^1^H NMR and X-ray crystal analysis. In the title compound, C~18~H~17~N~3~, the dihedral angles between the central pyridine and phenyl ring is 72.57 (5)° and that between the pyridine ring and malonitrile plane (N2 C13 C12 C14 N3 plane) is 5.19 (20)°. The bond distances of C---C bonds in the pyridine ring are considerably shorter than those of normal single bonds (D(C1---C2) = D(C1---C5) = 1.413 (3) Å). These results suggest that the electrons on the pyridine ring including non-bonding electrons of N1 are delocalized on the ring (Fig. 1). Experimental {#experimental} ============ A mixture of 2-(2-methyl-6-phenyl-4H-pyran-4-ylidene)malononitrile (1.5 g, 6.4 mmol) and n-propylamine (20 ml) was heated at 150 °C for 3 h. The mixture was cooled and concentrated under vacuum. Crude product was recrystallized from MeOH to give crystals suitable for X-ray analysis (1.20 g, 68%). Mp 166--167 °C. ^1^H NMR (300 MHz, CDCl~3~) δ 7.52--7.26 (m, 5H, Ph), 6.79 (d, 1H, J = 2.5 Hz, C---CH=C---N), 6.70 (d, 1H, J = 2.5 Hz), 3.75 (t, 2H, J = 8.1 Hz, NCH~2~CH~2~CH~3~), 2.50 (s, 3H, CH~3~), 1.52 (m, 2H, NCH~2~CH~2~CH~3~), 0.70 (t, 3H, J = 7.4 Hz, NCH~2~CH~2~CH~3~) Refinement {#refinement} ========== H atoms were positioned geometrically and allowed to ride on their respective parent atoms \[C---H = 0.93 (CH, sp^2^), 0.96 (CH~3~), 0.97Å (CH~2~), respectively and U~iso~(H) = 1.2U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the title compound with displacement ellipsoids drawn at the 50% probability level for non-H atoms. ::: ![](e-67-0o670-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e186 .table-wrap} ------------------------- ---------------------------------------- C~18~H~17~N~3~ F(000) = 584 M~r~ = 275.35 Z = 4 Monoclinic, P2~1~/c D~x~ = 1.190 Mg m^−3^ Hall symbol: -P 2ybc Mo Kα radiation, λ = 0.71073 Å a = 11.5580 (7) Å Cell parameters from 15051 reflections b = 9.9179 (6) Å θ = 27.5--3.0° c = 13.9268 (7) Å µ = 0.07 mm^−1^ β = 105.707 (2)° T = 100 K V = 1536.83 (15) Å^3^ Block, yellow Z = 4 0.5 × 0.4 × 0.2 mm ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e314 .table-wrap} ---------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID II-S diffractometer 3185 independent reflections Radiation source: fine-focus sealed tube 2321 reflections with I \> 2σ(I) graphite R~int~ = 0.077 ω scans θ~max~ = 26.5°, θ~min~ = 3.0° Absorption correction: multi-scan (RAPID-AUTO; Rigaku, 2008) h = −14→14 T~min~ = 0.966, T~max~ = 0.986 k = −12→12 13505 measured reflections l = −16→17 ---------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e428 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.049 H-atom parameters constrained wR(F^2^) = 0.134 w = 1/\[σ^2^(F~o~^2^) + (0.0522P)^2^ + 0.3213P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.07 (Δ/σ)~max~ \< 0.001 3185 reflections Δρ~max~ = 0.22 e Å^−3^ 193 parameters Δρ~min~ = −0.20 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.013 (3) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e609 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e708 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.86513 (14) 0.37654 (15) 0.41005 (10) 0.0322 (4) C2 0.94627 (14) 0.43142 (16) 0.36078 (11) 0.0350 (4) H2 1.0277 0.4120 0.3851 0.042\ C3 0.90918 (14) 0.51234 (16) 0.27834 (11) 0.0345 (4) C4 0.70719 (14) 0.49082 (15) 0.28609 (10) 0.0311 (4) C5 0.74344 (14) 0.41302 (16) 0.36931 (11) 0.0332 (4) H5 0.6864 0.3829 0.4004 0.040\* C6 0.57636 (14) 0.51915 (15) 0.24329 (11) 0.0325 (4) C7 0.51068 (15) 0.45459 (18) 0.15657 (12) 0.0402 (4) H7 0.5498 0.3993 0.1214 0.048\* C8 0.38795 (16) 0.4724 (2) 0.12290 (13) 0.0466 (4) H8 0.3443 0.4281 0.0657 0.056\* C9 0.32989 (16) 0.55609 (19) 0.17404 (13) 0.0467 (5) H9 0.2473 0.5686 0.1506 0.056\* C10 0.39303 (17) 0.62090 (19) 0.25902 (14) 0.0478 (5) H10 0.3534 0.6773 0.2931 0.057\* C11 0.51660 (15) 0.60193 (18) 0.29407 (12) 0.0409 (4) H11 0.5594 0.6452 0.3521 0.049\* C12 0.90262 (14) 0.28936 (16) 0.49335 (11) 0.0357 (4) C13 0.82087 (16) 0.24072 (17) 0.54461 (12) 0.0399 (4) C14 1.02361 (17) 0.24658 (18) 0.52802 (12) 0.0436 (4) C15 0.74831 (15) 0.63071 (16) 0.15180 (11) 0.0366 (4) H15A 0.6704 0.5997 0.1122 0.044\* H15B 0.8041 0.6235 0.1110 0.044\* C16 0.73834 (19) 0.77697 (18) 0.17897 (12) 0.0481 (5) H16A 0.8174 0.8115 0.2129 0.058\* H16B 0.6877 0.7844 0.2241 0.058\* C17 0.6847 (2) 0.8605 (2) 0.08532 (15) 0.0669 (6) H17A 0.6826 0.9537 0.1032 0.100\* H17B 0.6045 0.8298 0.0542 0.100\* H17C 0.7333 0.8503 0.0397 0.100\* C18 0.99893 (17) 0.5697 (2) 0.22903 (14) 0.0500 (5) H18A 0.9884 0.6655 0.2224 0.075\* H18B 0.9869 0.5300 0.1642 0.075\* H18C 1.0788 0.5500 0.2690 0.075\* N1 0.78979 (11) 0.54168 (13) 0.24021 (9) 0.0320 (3) N2 0.75433 (16) 0.20179 (18) 0.58685 (12) 0.0569 (5) N3 1.12223 (16) 0.2122 (2) 0.55469 (12) 0.0672 (5) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1203 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0369 (9) 0.0294 (8) 0.0286 (7) −0.0009 (7) 0.0057 (6) −0.0046 (6) C2 0.0321 (8) 0.0349 (9) 0.0361 (8) 0.0006 (7) 0.0058 (6) −0.0010 (6) C3 0.0334 (9) 0.0337 (9) 0.0367 (8) −0.0020 (7) 0.0100 (6) −0.0031 (6) C4 0.0342 (9) 0.0282 (8) 0.0299 (7) −0.0015 (6) 0.0069 (6) −0.0038 (6) C5 0.0332 (8) 0.0354 (8) 0.0303 (8) −0.0013 (7) 0.0073 (6) −0.0003 (6) C6 0.0333 (8) 0.0324 (8) 0.0306 (7) 0.0024 (7) 0.0068 (6) 0.0039 (6) C7 0.0382 (9) 0.0434 (10) 0.0372 (8) 0.0010 (7) 0.0070 (7) −0.0041 (7) C8 0.0399 (10) 0.0557 (11) 0.0386 (9) −0.0008 (8) 0.0012 (7) 0.0013 (8) C9 0.0350 (10) 0.0525 (11) 0.0496 (10) 0.0065 (8) 0.0063 (8) 0.0144 (8) C10 0.0476 (11) 0.0480 (11) 0.0518 (10) 0.0119 (9) 0.0204 (8) 0.0050 (8) C11 0.0431 (10) 0.0425 (10) 0.0364 (8) 0.0032 (8) 0.0097 (7) −0.0027 (7) C12 0.0371 (9) 0.0361 (9) 0.0320 (8) 0.0022 (7) 0.0062 (6) 0.0017 (6) C13 0.0469 (10) 0.0386 (9) 0.0326 (8) 0.0038 (8) 0.0081 (7) 0.0025 (7) C14 0.0484 (11) 0.0502 (11) 0.0321 (8) 0.0099 (9) 0.0105 (7) 0.0071 (7) C15 0.0431 (9) 0.0387 (9) 0.0276 (7) 0.0021 (7) 0.0091 (7) 0.0022 (6) C16 0.0662 (13) 0.0414 (10) 0.0380 (9) 0.0068 (9) 0.0163 (8) 0.0044 (7) C17 0.0989 (18) 0.0518 (12) 0.0534 (11) 0.0250 (12) 0.0265 (11) 0.0160 (9) C18 0.0451 (11) 0.0524 (11) 0.0554 (11) −0.0005 (8) 0.0185 (8) 0.0122 (9) N1 0.0356 (7) 0.0310 (7) 0.0287 (6) 0.0000 (5) 0.0075 (5) 0.0001 (5) N2 0.0670 (11) 0.0572 (11) 0.0521 (9) 0.0020 (9) 0.0258 (9) 0.0113 (8) N3 0.0545 (11) 0.0899 (14) 0.0562 (10) 0.0296 (10) 0.0130 (8) 0.0229 (9) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1590 .table-wrap} --------------------- -------------- ---------------------- -------------- C1---C2 1.412 (2) C10---H10 0.9300 C1---C5 1.414 (2) C11---H11 0.9300 C1---C12 1.417 (2) C12---C13 1.414 (2) C2---C3 1.371 (2) C12---C14 1.415 (2) C2---H2 0.9300 C13---N2 1.154 (2) C3---N1 1.369 (2) C14---N3 1.151 (2) C3---C18 1.502 (2) C15---N1 1.4852 (18) C4---C5 1.361 (2) C15---C16 1.511 (2) C4---N1 1.3801 (19) C15---H15A 0.9700 C4---C6 1.494 (2) C15---H15B 0.9700 C5---H5 0.9300 C16---C17 1.527 (2) C6---C11 1.384 (2) C16---H16A 0.9700 C6---C7 1.396 (2) C16---H16B 0.9700 C7---C8 1.380 (2) C17---H17A 0.9600 C7---H7 0.9300 C17---H17B 0.9600 C8---C9 1.380 (3) C17---H17C 0.9600 C8---H8 0.9300 C18---H18A 0.9600 C9---C10 1.371 (3) C18---H18B 0.9600 C9---H9 0.9300 C18---H18C 0.9600 C10---C11 1.391 (2) C2---C1---C5 115.20 (13) C13---C12---C14 117.32 (14) C2---C1---C12 122.45 (14) C13---C12---C1 121.55 (14) C5---C1---C12 122.34 (14) C14---C12---C1 121.13 (15) C3---C2---C1 122.29 (15) N2---C13---C12 179.5 (2) C3---C2---H2 118.9 N3---C14---C12 178.88 (18) C1---C2---H2 118.9 N1---C15---C16 113.11 (12) N1---C3---C2 120.21 (14) N1---C15---H15A 109.0 N1---C3---C18 119.37 (14) C16---C15---H15A 109.0 C2---C3---C18 120.42 (15) N1---C15---H15B 109.0 C5---C4---N1 120.64 (14) C16---C15---H15B 109.0 C5---C4---C6 119.44 (13) H15A---C15---H15B 107.8 N1---C4---C6 119.92 (12) C15---C16---C17 110.33 (14) C4---C5---C1 122.03 (14) C15---C16---H16A 109.6 C4---C5---H5 119.0 C17---C16---H16A 109.6 C1---C5---H5 119.0 C15---C16---H16B 109.6 C11---C6---C7 118.97 (15) C17---C16---H16B 109.6 C11---C6---C4 119.92 (14) H16A---C16---H16B 108.1 C7---C6---C4 120.90 (14) C16---C17---H17A 109.5 C8---C7---C6 120.24 (16) C16---C17---H17B 109.5 C8---C7---H7 119.9 H17A---C17---H17B 109.5 C6---C7---H7 119.9 C16---C17---H17C 109.5 C7---C8---C9 120.04 (16) H17A---C17---H17C 109.5 C7---C8---H8 120.0 H17B---C17---H17C 109.5 C9---C8---H8 120.0 C3---C18---H18A 109.5 C10---C9---C8 120.53 (17) C3---C18---H18B 109.5 C10---C9---H9 119.7 H18A---C18---H18B 109.5 C8---C9---H9 119.7 C3---C18---H18C 109.5 C9---C10---C11 119.70 (16) H18A---C18---H18C 109.5 C9---C10---H10 120.1 H18B---C18---H18C 109.5 C11---C10---H10 120.1 C3---N1---C4 119.59 (12) C6---C11---C10 120.52 (15) C3---N1---C15 120.88 (13) C6---C11---H11 119.7 C4---N1---C15 119.51 (13) C10---C11---H11 119.7 C5---C1---C2---C3 −1.1 (2) C4---C6---C11---C10 −175.04 (15) C12---C1---C2---C3 177.93 (14) C9---C10---C11---C6 0.6 (3) C1---C2---C3---N1 −0.6 (2) C2---C1---C12---C13 176.88 (15) C1---C2---C3---C18 179.35 (15) C5---C1---C12---C13 −4.2 (2) N1---C4---C5---C1 −2.5 (2) C2---C1---C12---C14 −3.7 (2) C6---C4---C5---C1 176.43 (14) C5---C1---C12---C14 175.28 (15) C2---C1---C5---C4 2.6 (2) N1---C15---C16---C17 −174.92 (16) C12---C1---C5---C4 −176.36 (14) C2---C3---N1---C4 0.9 (2) C5---C4---C6---C11 69.6 (2) C18---C3---N1---C4 −179.09 (15) N1---C4---C6---C11 −111.43 (17) C2---C3---N1---C15 179.15 (14) C5---C4---C6---C7 −105.08 (17) C18---C3---N1---C15 −0.8 (2) N1---C4---C6---C7 73.9 (2) C5---C4---N1---C3 0.7 (2) C11---C6---C7---C8 −0.6 (2) C6---C4---N1---C3 −178.28 (13) C4---C6---C7---C8 174.15 (15) C5---C4---N1---C15 −177.62 (13) C6---C7---C8---C9 1.1 (3) C6---C4---N1---C15 3.4 (2) C7---C8---C9---C10 −0.7 (3) C16---C15---N1---C3 −93.10 (18) C8---C9---C10---C11 −0.1 (3) C16---C15---N1---C4 85.16 (18) C7---C6---C11---C10 −0.2 (2) --------------------- -------------- ---------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.829911	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052154/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o670", "authors": [ { "first": "Young Hyun", "last": "Kim" }, { "first": "Hyung Jin", "last": "Kim" }, { "first": "Enkhzul", "last": "Otgonbaatar" }, { "first": "Chee-Hun", "last": "Kwak" } ] }
PMC3052155	Related literature {#sec1} ================== For crystalline metal complexes of styphnic acid, see: Cui et al. (2008*a[@bb3],b* [@bb4]); Orbovic & Codoceo (2008[@bb7]); Zheng et al. (2006a [@bb12],b [@bb13]); Zhu & Xiao (2009[@bb14]). For crystalline adducts of styphnic acid with organic bases, see: Abashev et al. (2001[@bb1]); Liu et al. (2008[@bb6]); Tenishev et al. (2002[@bb10]); For related molecular salts, see: Kalaivani & Malarvizhi (2010[@bb5]); Vogel (1978[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~7~H~10~NO^+^·C~6~H~2~N~3~O~8~ ^−^M ~r~ = 368.27Monoclinic,a = 10.6957 (4) Åb = 17.8368 (5) Åc = 8.0527 (3) Åβ = 91.991 (2)°V = 1535.34 (9) Å^3^Z = 4Mo Kα radiationμ = 0.14 mm^−1^T = 293 K0.22 × 0.18 × 0.12 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2008[@bb2]) T ~min~ = 0.978, T ~max~ = 0.98819208 measured reflections4930 independent reflections3539 reflections with I \> 2σ(I)R ~int~ = 0.028 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.050wR(F ^2^) = 0.142S = 1.044930 reflections238 parametersH-atom parameters constrainedΔρ~max~ = 0.45 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e585} Data collection: APEX2 (Bruker, 2008[@bb2]); cell refinement: SAINT (Bruker, 2008[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: PLATON (Spek, 2009[@bb9]); software used to prepare material for publication: PLATON. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005708/bv2174sup1.cif](http://dx.doi.org/10.1107/S1600536811005708/bv2174sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005708/bv2174Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005708/bv2174Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bv2174&file=bv2174sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bv2174sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bv2174&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BV2174](http://scripts.iucr.org/cgi-bin/sendsup?bv2174)). The authors thank the DST-India (FIST programme) for the use of the Bruker SMART APEXII diffractometer at the School of Chemistry, Bharathidasan University. Comment ======= In spite of the fact that many crystalline complexes have been derived from styphnic acid and metals in recent years \[(Cui et al., 2008*a,* 2008b), (Orbovic et al., 2008), (Zheng et al., 2006a, 2006b), (Zhu & Xiao, 2009)\], only a few crystalline complexes are known from styphnic acid and organic molecules \[(Abashev et al., 2001), (Liu et al., 2008), (Tenishev et al., 2002)\]. It has also been pointed out that aromatic hydrocarbons (and also some amines) form 1:1 adducts with styphnic acid and these derivatives do not crystallize as well as the corresponding picrates (Vogel, 1978). In the present work an elegant method has been proposed to prepare a crystalline molecular salt from 2-methoxyaniline and styphnic acid. The title compound (I), is shown in Fig 1. The adduct formation between styphnic acid and 2-methoxyaniline may involve two important types of charge-transfer interactions (i) π-π^\^ transition and (ii) proton transfer. A view of the crystal packing is shown in Fig 2. The proton transfer from phenolic OH to amino group is the main contributing factor which stabilizes the title molecular salt. The same observation has been reported by us in a related molecular salt (Kalaivani & Malarvizhi, 2010). The 3-hydroxy-2,4,6-trinitrophenolate ions self-assemble via* O---H···O hydrogen bonds to from a supramolecular chain the b axis, with the graph-set notation C(9); this is shown in Fig. 3. Experimental {#experimental} ============ 2,4,6-Trinitro-1,3-benzenediol (styphnic acid: 2.45 g, 0.01 mol) was dissolved in the minimum quantity of dimethyl sulphoxide. 2-Methoxyaniline (1.23 g, 0.01 mol) dissolved in the minimum amount of dimethyl sulphoxide was added to styphnic acid solution. The mixture was stirred well for 3 h and kept as such for another 12 h. The mixture was then poured into ice cold water with stirring. The molecular salt (adduct) formed was filtered and washed first with water and then with alcohol and dried. The dried adduct was washed several times with ether and recrystallized from ethanol (yield 70--75%, mp.455 K). Good pale yellow crystals of the molecular salt were obtained by slow evaporation of ethanol at room temperature. The same molecular salt was obtained when styphnic acid (0.01 mol) was mixed with excess of 2-methoxyaniline (0.03 mol). Refinement {#refinement} ========== All hydrogen atoms were positioned geometrically and were refined using a riding model. The C---H, O---H and N---H bond lengths are 0.93--0.96, 0.82 and 0.89 Å, respectively \[U~iso~ (H)=1.2 U~eq~(parent atom)\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of (I), showing 50% probability displacement ellipsoids. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o686-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing view of 2-methoxyanilinium 3-hydroxy- 2,4,6-trinitrophenolate.Dashed lines indicate hydrogen bonds H atoms not involved in hydrogen bonding have been omitted \[symmetry codes: (i) x, -y + 1/2, z + 1/2; (vi) -x + 1, y - 1/2, -z + 1/2\]. ::: ![](e-67-0o686-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Hydrogen-bonding patterns in the supramolecular chain in compound (I). Dashed lines indicate hydrogen bonds H atoms not involved in hydrogen bonding have been omitted \[symmetry codes: (vi) -x + 1, y - 1/2, -z + 1/2\]. ::: ![](e-67-0o686-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e189 .table-wrap} ------------------------------------ --------------------------------------- C~7~H~10~NO^+^·C~6~H~2~N~3~O~8~^−^ F(000) = 760 M~r~ = 368.27 D~x~ = 1.593 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 4930 reflections a = 10.6957 (4) Å θ = 1.9--31.8° b = 17.8368 (5) Å µ = 0.14 mm^−1^ c = 8.0527 (3) Å T = 293 K β = 91.991 (2)° Prism, colourless V = 1535.34 (9) Å^3^ 0.22 × 0.18 × 0.12 mm Z = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e332 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 4930 independent reflections Radiation source: fine-focus sealed tube 3539 reflections with I \> 2σ(I) graphite R~int~ = 0.028 φ and ω scans θ~max~ = 31.8°, θ~min~ = 1.9° Absorption correction: multi-scan (SADABS; Bruker, 2008) h = −15→15 T~min~ = 0.978, T~max~ = 0.988 k = −25→26 19208 measured reflections l = −11→11 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e449 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.050 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.142 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0626P)^2^ + 0.4547P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4930 reflections (Δ/σ)~max~ \< 0.001 238 parameters Δρ~max~ = 0.45 e Å^−3^ 0 restraints Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e606 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on F^2^ for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The observed criterion of F^2^ \> σ(F^2^) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e708 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ O1 −0.00430 (12) 0.14533 (7) 0.45345 (16) 0.0536 (4) N1 0.18296 (12) 0.21738 (7) 0.59909 (15) 0.0366 (3) C1 0.08388 (13) 0.26071 (8) 0.51522 (17) 0.0344 (4) C2 −0.01386 (14) 0.22085 (9) 0.43872 (19) 0.0400 (4) C3 −0.10912 (16) 0.26008 (12) 0.3561 (2) 0.0529 (6) C4 −0.10434 (19) 0.33740 (12) 0.3498 (3) 0.0592 (6) C5 −0.0059 (2) 0.37645 (11) 0.4229 (3) 0.0580 (6) C6 0.08921 (16) 0.33785 (9) 0.5076 (2) 0.0450 (5) C7 −0.1013 (2) 0.10034 (13) 0.3781 (3) 0.0712 (8) O2 0.30956 (10) 0.18764 (5) 0.31638 (13) 0.0372 (3) O3 0.18239 (12) 0.01420 (9) 0.30014 (18) 0.0662 (5) O4 0.26170 (13) 0.05325 (8) 0.53302 (15) 0.0569 (4) O5 0.43465 (12) −0.06180 (6) 0.30043 (17) 0.0508 (4) O6 0.64034 (12) −0.08887 (6) 0.14078 (16) 0.0519 (4) O7 0.76246 (12) 0.00182 (7) 0.07391 (18) 0.0585 (4) O8 0.63270 (16) 0.25143 (8) 0.0819 (3) 0.0929 (7) O9 0.46083 (14) 0.28678 (7) 0.1770 (3) 0.0813 (7) N2 0.26692 (12) 0.04141 (7) 0.38421 (16) 0.0376 (4) N3 0.66485 (12) −0.02118 (7) 0.12862 (16) 0.0405 (4) N4 0.53537 (12) 0.23793 (7) 0.14816 (19) 0.0428 (4) C8 0.39391 (12) 0.14238 (7) 0.27345 (16) 0.0299 (3) C9 0.38107 (13) 0.06399 (7) 0.30251 (17) 0.0323 (4) C10 0.46368 (14) 0.00851 (7) 0.26041 (18) 0.0346 (4) C11 0.57235 (13) 0.03198 (8) 0.17977 (18) 0.0346 (4) C12 0.59200 (13) 0.10722 (8) 0.14638 (18) 0.0353 (4) C13 0.50678 (13) 0.16065 (7) 0.19047 (17) 0.0326 (4) H1A 0.23360 0.19870 0.52400 0.0550\ H1B 0.14930 0.18000 0.65560 0.0550\* H1C 0.22640 0.24700 0.66890 0.0550\* H3 −0.17580 0.23450 0.30530 0.0630\* H4 −0.16870 0.36360 0.29510 0.0710\* H5A −0.00330 0.42850 0.41560 0.0700\* H6 0.15570 0.36370 0.55850 0.0540\* H7A −0.17980 0.11290 0.42510 0.1070\* H7B −0.08320 0.04830 0.39790 0.1070\* H7C −0.10580 0.10960 0.26060 0.1070\* H5 0.49030 −0.09010 0.27160 0.0760\* H12 0.66400 0.12170 0.09330 0.0420\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1235 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0559 (7) 0.0422 (6) 0.0617 (8) −0.0173 (5) −0.0108 (6) −0.0007 (5) N1 0.0394 (6) 0.0344 (6) 0.0360 (6) −0.0046 (5) 0.0009 (5) −0.0036 (5) C1 0.0349 (7) 0.0371 (7) 0.0316 (6) −0.0025 (5) 0.0071 (5) −0.0028 (5) C2 0.0382 (7) 0.0448 (8) 0.0372 (7) −0.0080 (6) 0.0054 (6) −0.0011 (6) C3 0.0390 (8) 0.0708 (12) 0.0487 (9) −0.0041 (8) −0.0011 (7) 0.0013 (8) C4 0.0530 (10) 0.0678 (12) 0.0567 (11) 0.0164 (9) 0.0010 (9) 0.0078 (9) C5 0.0692 (12) 0.0435 (9) 0.0616 (11) 0.0104 (8) 0.0064 (10) 0.0029 (8) C6 0.0491 (9) 0.0380 (8) 0.0484 (9) −0.0038 (6) 0.0070 (7) −0.0043 (6) C7 0.0722 (13) 0.0657 (12) 0.0750 (14) −0.0377 (11) −0.0093 (11) −0.0021 (10) O2 0.0427 (5) 0.0302 (5) 0.0391 (5) 0.0093 (4) 0.0059 (4) 0.0036 (4) O3 0.0518 (7) 0.0849 (10) 0.0619 (9) −0.0254 (7) 0.0013 (6) −0.0089 (7) O4 0.0685 (8) 0.0630 (8) 0.0397 (6) −0.0072 (6) 0.0112 (6) 0.0038 (5) O5 0.0551 (7) 0.0250 (5) 0.0729 (8) 0.0048 (5) 0.0093 (6) 0.0032 (5) O6 0.0591 (7) 0.0340 (6) 0.0626 (8) 0.0103 (5) 0.0011 (6) −0.0118 (5) O7 0.0470 (7) 0.0551 (7) 0.0744 (9) 0.0086 (6) 0.0155 (6) −0.0091 (6) O8 0.0737 (10) 0.0508 (8) 0.1580 (18) −0.0022 (7) 0.0568 (11) 0.0234 (10) O9 0.0604 (8) 0.0281 (6) 0.1575 (17) 0.0013 (6) 0.0329 (10) 0.0079 (8) N2 0.0429 (7) 0.0294 (5) 0.0407 (7) −0.0008 (5) 0.0036 (5) 0.0046 (5) N3 0.0436 (7) 0.0376 (6) 0.0400 (7) 0.0088 (5) −0.0023 (5) −0.0090 (5) N4 0.0378 (6) 0.0310 (6) 0.0595 (8) −0.0029 (5) 0.0004 (6) 0.0055 (5) C8 0.0339 (6) 0.0269 (6) 0.0286 (6) 0.0017 (5) −0.0021 (5) −0.0003 (4) C9 0.0346 (6) 0.0269 (6) 0.0353 (7) 0.0002 (5) 0.0018 (5) 0.0003 (5) C10 0.0407 (7) 0.0257 (6) 0.0371 (7) 0.0021 (5) −0.0037 (6) −0.0022 (5) C11 0.0355 (7) 0.0317 (6) 0.0363 (7) 0.0059 (5) −0.0017 (5) −0.0052 (5) C12 0.0326 (6) 0.0359 (7) 0.0373 (7) 0.0010 (5) −0.0003 (5) −0.0026 (5) C13 0.0338 (6) 0.0262 (6) 0.0375 (7) −0.0012 (5) −0.0020 (5) 0.0002 (5) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1744 .table-wrap} --------------------- -------------- ----------------------- -------------- O1---C2 1.356 (2) C1---C6 1.379 (2) O1---C7 1.430 (3) C2---C3 1.387 (2) O2---C8 1.2676 (16) C3---C4 1.381 (3) O3---N2 1.2119 (19) C4---C5 1.377 (3) O4---N2 1.2200 (18) C5---C6 1.388 (3) O5---C10 1.3342 (17) C3---H3 0.9300 O6---N3 1.2401 (17) C4---H4 0.9300 O7---N3 1.2183 (18) C5---H5A 0.9300 O8---N4 1.210 (2) C6---H6 0.9300 O9---N4 1.2090 (19) C7---H7C 0.9600 O5---H5 0.8200 C7---H7A 0.9600 N1---C1 1.4583 (19) C7---H7B 0.9600 N1---H1C 0.8900 C8---C13 1.4374 (19) N1---H1A 0.8900 C8---C9 1.4251 (18) N1---H1B 0.8900 C9---C10 1.3769 (19) N2---C9 1.4634 (19) C10---C11 1.414 (2) N3---C11 1.4408 (19) C11---C12 1.386 (2) N4---C13 1.4550 (18) C12---C13 1.3739 (19) C1---C2 1.390 (2) C12---H12 0.9300 O1···N1 2.6221 (18) N3···C10^iii^ 3.3846 (19) O1···C4^i^ 3.415 (3) N4···O2 2.9496 (17) O2···C1 3.2183 (17) N3···H5 2.5400 O2···N1^ii^ 2.7569 (16) C1···O2 3.2183 (17) O2···C6^ii^ 3.397 (2) C1···C3^i^ 3.511 (2) O2···O4 3.0189 (17) C2···C3^i^ 3.562 (2) O2···O9 2.6703 (19) C3···C2^ii^ 3.562 (2) O2···N1 2.7408 (16) C3···O8^xi^ 3.365 (3) O2···N2 2.7068 (15) C3···C1^ii^ 3.511 (2) O2···N4 2.9496 (17) C4···O1^ii^ 3.415 (3) O3···O5 3.0194 (18) C6···O7^ix^ 3.402 (2) O3···O7^iii^ 3.103 (2) C6···O2^i^ 3.397 (2) O4···N1 3.0974 (19) C7···O7^xii^ 3.311 (3) O4···O2 3.0189 (17) C7···O4^v^ 3.324 (3) O4···C11^iv^ 3.2443 (19) C10···N3^iii^ 3.3846 (19) O4···C7^v^ 3.324 (3) C11···C11^iii^ 3.431 (2) O4···N3^iv^ 2.8670 (18) C11···O4^iv^ 3.2443 (19) O4···O6^iv^ 2.8654 (18) C12···O6^iii^ 3.3512 (19) O5···N3 2.9560 (18) C13···O6^iii^ 3.3074 (19) O5···O6 2.6311 (18) C3···H7C 2.7900 O5···O9^vi^ 2.9263 (17) C3···H7A 2.7900 O5···N2 2.6733 (17) C5···H7C^i^ 2.9700 O5···O3 3.0194 (18) C5···H1B^ii^ 2.9400 O6···O9^vi^ 2.890 (2) C6···H1B^ii^ 2.9500 O6···C13^iii^ 3.3074 (19) C7···H3 2.5800 O6···C12^iii^ 3.3512 (19) C8···H6^ii^ 3.0300 O6···O5 2.6311 (18) C8···H1A 2.8700 O6···O4^iv^ 2.8654 (18) C8···H1C^ii^ 2.7800 O7···C6^vi^ 3.402 (2) H1A···O1 2.7600 O7···O3^iii^ 3.103 (2) H1A···O9^i^ 2.7000 O7···C7^vii^ 3.311 (3) H1A···O2 1.8900 O8···C3^viii^ 3.365 (3) H1A···O4 2.6100 O9···O6^ix^ 2.890 (2) H1A···C8 2.8700 O9···O5^ix^ 2.9263 (17) H1B···C5^i^ 2.9400 O9···N1^ii^ 3.017 (2) H1B···C6^i^ 2.9500 O9···O2 2.6703 (19) H1B···O4 2.7600 O1···H1A 2.7600 H1B···O1 2.3500 O1···H1B 2.3500 H1C···H6 2.3800 O2···H1C^ii^ 1.8700 H1C···O9^i^ 2.5800 O2···H1A 1.8900 H1C···C8^i^ 2.7800 O2···H6^ii^ 2.7600 H1C···O2^i^ 1.8700 O3···H7B^v^ 2.9100 H3···H7A 2.3700 O3···H4^x^ 2.8000 H3···H7C 2.3800 O4···H1B 2.7600 H3···O8^xii^ 2.7000 O4···H7B^v^ 2.7000 H3···C7 2.5800 O4···H1A 2.6100 H4···O3^xiii^ 2.8000 O6···H6^vi^ 2.8800 H5···N3 2.5400 O6···H5 1.9500 H5···O9^vi^ 2.2900 O7···H7C^vii^ 2.7900 H5···O6 1.9500 O7···H12 2.3900 H5A···O7^ix^ 2.8900 O7···H6^vi^ 2.8400 H6···H1C 2.3800 O7···H5A^vi^ 2.8900 H6···O6^ix^ 2.8800 O8···H3^vii^ 2.7000 H6···O7^ix^ 2.8400 O8···H12 2.3400 H6···O2^i^ 2.7600 O9···H1A^ii^ 2.7000 H6···C8^i^ 3.0300 O9···H5^ix^ 2.2900 H7A···H3 2.3700 O9···H1C^ii^ 2.5800 H7A···C3 2.7900 N1···O9^i^ 3.017 (2) H7B···O4^v^ 2.7000 N1···O2 2.7408 (16) H7B···O3^v^ 2.9100 N1···O1 2.6221 (18) H7C···O7^xii^ 2.7900 N1···O4 3.0974 (19) H7C···H3 2.3800 N1···O2^i^ 2.7569 (16) H7C···C5^ii^ 2.9700 N2···O5 2.6733 (17) H7C···C3 2.7900 N2···O2 2.7068 (15) H12···O7 2.3900 N3···O4^iv^ 2.8670 (18) H12···O8 2.3400 N3···O5 2.9560 (18) C2---O1---C7 117.97 (14) C5---C4---H4 119.00 C10---O5---H5 109.00 C6---C5---H5A 120.00 H1B---N1---H1C 109.00 C4---C5---H5A 120.00 C1---N1---H1B 109.00 C5---C6---H6 120.00 C1---N1---H1A 109.00 C1---C6---H6 120.00 H1A---N1---H1C 110.00 O1---C7---H7C 109.00 C1---N1---H1C 109.00 O1---C7---H7B 109.00 H1A---N1---H1B 109.00 H7B---C7---H7C 109.00 O4---N2---C9 117.47 (13) H7A---C7---H7B 110.00 O3---N2---C9 118.49 (13) H7A---C7---H7C 110.00 O3---N2---O4 124.01 (14) O1---C7---H7A 109.00 O6---N3---C11 117.97 (12) O2---C8---C9 120.43 (12) O7---N3---C11 119.17 (12) C9---C8---C13 112.71 (11) O6---N3---O7 122.86 (13) O2---C8---C13 126.84 (12) O8---N4---O9 121.62 (15) N2---C9---C10 117.74 (12) O9---N4---C13 119.50 (14) C8---C9---C10 126.76 (13) O8---N4---C13 118.86 (13) N2---C9---C8 115.50 (11) C2---C1---C6 121.49 (14) O5---C10---C11 126.23 (13) N1---C1---C6 121.27 (13) C9---C10---C11 116.42 (12) N1---C1---C2 117.21 (13) O5---C10---C9 117.35 (13) C1---C2---C3 118.89 (15) N3---C11---C12 118.13 (12) O1---C2---C1 114.58 (13) C10---C11---C12 120.54 (13) O1---C2---C3 126.53 (15) N3---C11---C10 121.33 (12) C2---C3---C4 119.60 (17) C11---C12---C13 121.00 (13) C3---C4---C5 121.20 (19) N4---C13---C12 116.74 (12) C4---C5---C6 119.71 (18) C8---C13---C12 122.57 (12) C1---C6---C5 119.10 (16) N4---C13---C8 120.69 (12) C4---C3---H3 120.00 C11---C12---H12 119.00 C2---C3---H3 120.00 C13---C12---H12 120.00 C3---C4---H4 119.00 C7---O1---C2---C1 179.98 (15) C3---C4---C5---C6 −1.4 (3) C7---O1---C2---C3 −0.4 (2) C4---C5---C6---C1 0.8 (3) O4---N2---C9---C10 105.00 (16) O2---C8---C9---C10 178.89 (14) O3---N2---C9---C8 102.38 (16) C13---C8---C9---C10 0.3 (2) O4---N2---C9---C8 −75.60 (17) O2---C8---C13---N4 0.7 (2) O3---N2---C9---C10 −77.02 (18) C9---C8---C13---N4 179.16 (13) O7---N3---C11---C10 −173.12 (14) C13---C8---C9---N2 −179.01 (12) O6---N3---C11---C12 −171.69 (14) O2---C8---C13---C12 −178.89 (14) O7---N3---C11---C12 7.5 (2) C9---C8---C13---C12 −0.44 (19) O6---N3---C11---C10 7.7 (2) O2---C8---C9---N2 −0.45 (19) O8---N4---C13---C8 178.25 (17) N2---C9---C10---O5 −1.3 (2) O9---N4---C13---C8 −3.1 (2) C8---C9---C10---C11 −0.1 (2) O8---N4---C13---C12 −2.1 (2) N2---C9---C10---C11 179.24 (12) O9---N4---C13---C12 176.54 (18) C8---C9---C10---O5 179.33 (14) N1---C1---C6---C5 178.46 (16) C9---C10---C11---N3 −179.46 (13) C2---C1---C6---C5 0.6 (2) C9---C10---C11---C12 −0.1 (2) N1---C1---C2---C3 −179.29 (13) O5---C10---C11---C12 −179.44 (15) C6---C1---C2---O1 178.32 (14) O5---C10---C11---N3 1.2 (2) N1---C1---C2---O1 0.41 (19) C10---C11---C12---C13 0.0 (2) C6---C1---C2---C3 −1.4 (2) N3---C11---C12---C13 179.36 (13) C1---C2---C3---C4 0.8 (2) C11---C12---C13---N4 −179.30 (13) O1---C2---C3---C4 −178.90 (17) C11---C12---C13---C8 0.3 (2) C2---C3---C4---C5 0.6 (3) --------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) x, −y+1/2, z−1/2; (iii) −x+1, −y, −z; (iv) −x+1, −y, −z+1; (v) −x, −y, −z+1; (vi) −x+1, y−1/2, −z+1/2; (vii) x+1, y, z; (viii) x+1, −y+1/2, z−1/2; (ix) −x+1, y+1/2, −z+1/2; (x) −x, y−1/2, −z+1/2; (xi) x−1, −y+1/2, z+1/2; (xii) x−1, y, z; (xiii) −x, y+1/2, −z+1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3342 .table-wrap} ------------------ --------- --------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···O2 0.89 1.89 2.7408 (16) 158 N1---H1C···O2^i^ 0.89 1.87 2.7569 (16) 177 N1---H1C···O9^i^ 0.89 2.58 3.017 (2) 111 O5---H5···O6 0.82 1.95 2.6311 (18) 140 O5---H5···N3 0.82 2.54 2.9560 (18) 112 O5---H5···O9^vi^ 0.82 2.29 2.9263 (17) 135 C12---H12···O8 0.93 2.34 2.663 (2) 100 ------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (i) x, −y+1/2, z+1/2; (vi) −x+1, y−1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ --------- ------- ------------- ------------- N1---H1A⋯O2 0.89 1.89 2.7408 (16) 158 N1---H1C⋯O2^i^ 0.89 1.87 2.7569 (16) 177 O5---H5⋯O6 0.82 1.95 2.6311 (18) 140 O5---H5⋯O9^ii^ 0.82 2.29 2.9263 (17) 135 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.834810	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052155/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o686", "authors": [ { "first": "Doraisamyraja", "last": "Kalaivani" }, { "first": "Rangasamy", "last": "Malarvizhi" }, { "first": "Kaliyaperumal", "last": "Thanigaimani" }, { "first": "Packianathan Thomas", "last": "Muthiah" } ] }
PMC3052156	Related literature {#sec1} ================== For the preparation of 1,2-dihydroquinoline, see: Edwards et al. (1998[@bb5]); Yan et al. (2004[@bb27]); Petasis & Butkevich (2009[@bb19]); Johnson et al. (1989[@bb13]); Gültekin et al. (2010[@bb9]); Waldmann et al. (2008[@bb26]). For the biological activity of dihydroquinolines, see: Elmore et al. (2001[@bb6]); Dillard et al. (1973[@bb4]); Muren & Weissman (1971[@bb18]). For the preparation of quinolines, see: Dauphinee & Forrest (1978[@bb3]); Yan et al. (2004[@bb27]); Tom & Ruel (2001[@bb25]); Tokuyama et al. (2001[@bb24]); Sarma & Prajapati (2008[@bb21]); Martinez et al. (2008[@bb17]); Huang et al. (2009[@bb12]); Katritzky et al. (1996[@bb14]). For the biological activity of quinolines, see: Hamann et al. (1998[@bb10]); He et al. (2003[@bb11]); LaMontagne et al. (1989[@bb15]). For hydorgen-bond motifs, see: Bernstein et al. (1995[@bb1]). For ring puckering parameters, see: Cremer & Pople (1975[@bb2]). For the melting point, see: Rueping & Gültekin (2009[@bb20]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~15~NO~4~M ~r~ = 261.27Monoclinic,a = 7.9917 (12) Åb = 8.8886 (11) Åc = 18.9855 (18) Åβ = 99.194 (9)°V = 1331.3 (3) Å^3^Z = 4Mo Kα radiationμ = 0.10 mm^−1^T = 294 K0.6 × 0.6 × 0.5 mm ### Data collection {#sec2.1.2} Nicolet P3 diffractometer4144 measured reflections3890 independent reflections3097 reflections with I \> 2σ(I)R ~int~ = 0.0533 standard reflections every 50 reflections intensity decay: 1% ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.052wR(F ^2^) = 0.159S = 1.053890 reflections180 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e523} Data collection: XSCANS (Siemens, 1996[@bb23]); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 2008[@bb22]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb22]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb22]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb7]) and Mercury (Macrae et al., 2006[@bb16]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005605/bv2176sup1.cif](http://dx.doi.org/10.1107/S1600536811005605/bv2176sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005605/bv2176Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005605/bv2176Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bv2176&file=bv2176sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bv2176sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bv2176&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BV2176](http://scripts.iucr.org/cgi-bin/sendsup?bv2176)). This research was carried out at RWTH Aachen University. The authors thank Professor Magnus Rueping of RWTH Aachen University, Germany, for helpful discussions. Comment ======= Dihydroquinolines have been widely studied and found to be an important structural unit in synthetic organic and medicinal chemistry (Elmore et al., 2001; Dillard et al., 1973; Muren & Weissman, 1971). Many dihydroquinoline derivatives have been reported in the literature (Edwards et al., 1998; Yan et al., 2004; Petasis & Butkevich, 2009; Gültekin et al., 2010) and some of them have biological effects. For example, 2,2,4-substituted 1,2-dihydroquinolines have been shown to possess antibacterial activities (Johnson et al., 1989). They are also important intermediates for the preparation of quinolines (Dauphinee & Forrest, 1978; Yan et al., 2004; Tom & Ruel, 2001; Tokuyama et al., 2001) and 1,2,3,4-tetrahydroquinolines (Katritzky et al., 1996). Many synthetic methods have been developed for the preparation of quinolines (Sarma & Prajapati, 2008; Martinez et al., 2008; Huang et al., 2009; Waldmann et al., 2008) and many quinolines display biological effects (Hamann et al., 1998; He et al., 2003; LaMontagne et al., 1989; Muren & Weissman, 1971). In the title compound, (I), (Fig. 1), the ring A (C1-C4/C9/N1) is not planar with the puckering parameters (Cremer & Pople, 1975) Q~T~ = 0.364 (2) Å, φ = -143.4 (3)° and θ = 113.9 (2)°. In the crystal structure, intermolecular N-H···O hydrogen bonds (Table 1) link the molecules into centrosymmetric R~2~^2^(10) dimers (Bernstein et al., 1995). These dimers are further connected via intermolecular C-H···O hydrogen bonds (Table 1) to form a three-dimensional network (Fig. 2). Experimental {#experimental} ============ The title compound was synthesized by the literature method (Waldmann et al., 2008). Aniline (100 mg, 1 eq) was dissolved in chloroform (1.5 ml) in a screw-capped test tube and Bi(OTf)~3~ (5 mol%, 0.05 eq) was added to the mixture. The mixture was stirred at room temperature for 4h until the starting material was completely consumed as monitored by TLC. The resultant residue was directly purified by flash chromatography on silica (EtOAc:Cylohexane 2:98) gave in 63% yield as a yellow solid. Recrystallized over pentane and ethyl acetate (70:30) gave yellow crystalline solid R~f~ 0.53 (2:1 Cyclohexane/EtOAc) mp 346 K (Rueping & Gültekin, 2009). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o672-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A partial packing diagram viewed down the b-axis. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o672-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e163 .table-wrap} ------------------------- ------------------------------------- C~14~H~15~NO~4~ F(000) = 552 M~r~ = 261.27 D~x~ = 1.304 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 49 reflections a = 7.9917 (12) Å θ = 17--18° b = 8.8886 (11) Å µ = 0.10 mm^−1^ c = 18.9855 (18) Å T = 294 K β = 99.194 (9)° Block, colourless V = 1331.3 (3) Å^3^ 0.6 × 0.6 × 0.5 mm Z = 4 ------------------------- ------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e290 .table-wrap} ------------------------------------------ --------------------------------------------- Nicolet P3 diffractometer R~int~ = 0.053 Radiation source: fine-focus sealed tube θ~max~ = 30.0°, θ~min~ = 2.2° graphite h = 0→11 Wyckoff--Scan scans k = 0→12 4144 measured reflections l = −26→26 3890 independent reflections 3 standard reflections every 50 reflections 3097 reflections with I \> 2σ(I) intensity decay: 1% ------------------------------------------ --------------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e382 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.052 H atoms treated by a mixture of independent and constrained refinement wR(F^2^) = 0.159 w = 1/\[σ^2^(F~o~^2^) + (0.0757P)^2^ + 0.2951P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.05 (Δ/σ)~max~ \< 0.001 3890 reflections Δρ~max~ = 0.24 e Å^−3^ 180 parameters Δρ~min~ = −0.18 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.076 (5) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e563 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e608 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- x* y z U~iso~\/U~eq~ O1 0.16885 (15) 0.61815 (14) 0.96958 (6) 0.0632 (3) O2 0.15641 (17) 0.84306 (14) 0.91740 (6) 0.0671 (4) O3 −0.04420 (19) 0.60887 (14) 0.63398 (6) 0.0688 (4) O4 0.00900 (15) 0.83447 (13) 0.68455 (5) 0.0538 (3) N1 −0.12790 (17) 0.52602 (16) 0.88407 (7) 0.0527 (3) H1 −0.137 (3) 0.491 (3) 0.9282 (12) 0.080 (6)\ C1 −0.08128 (18) 0.68333 (17) 0.88397 (7) 0.0447 (3) C2 −0.07661 (18) 0.73116 (16) 0.80816 (7) 0.0441 (3) H2 −0.1036 0.8299 0.7946 0.053\* C3 −0.03445 (17) 0.63452 (15) 0.76014 (7) 0.0411 (3) C4 −0.00240 (17) 0.47523 (15) 0.77879 (7) 0.0439 (3) C5 0.0730 (2) 0.37209 (18) 0.73815 (9) 0.0551 (4) H5 0.1104 0.4042 0.6967 0.066\* C6 0.0929 (2) 0.22295 (19) 0.75842 (11) 0.0675 (5) H6 0.1440 0.1557 0.7309 0.081\* C7 0.0370 (3) 0.17430 (19) 0.81939 (12) 0.0723 (5) H7 0.0479 0.0734 0.8323 0.087\* C8 −0.0351 (2) 0.27357 (19) 0.86154 (10) 0.0630 (4) H8 −0.0718 0.2393 0.9028 0.076\* C9 −0.05340 (17) 0.42528 (16) 0.84272 (8) 0.0468 (3) C10 −0.2084 (2) 0.7764 (2) 0.91791 (10) 0.0689 (5) H10A −0.2112 0.7408 0.9654 0.103\* H10B −0.3191 0.7667 0.8899 0.103\* H10C −0.1749 0.8802 0.9197 0.103\* C11 0.09548 (18) 0.70811 (16) 0.92869 (6) 0.0432 (3) C12 0.3182 (3) 0.8827 (3) 0.95860 (10) 0.0782 (6) H12A 0.3519 0.9801 0.9441 0.117\* H12B 0.4015 0.8094 0.9507 0.117\* H12C 0.3087 0.8848 1.0084 0.117\* C13 −0.02495 (18) 0.68793 (17) 0.68624 (7) 0.0455 (3) C14 0.0372 (3) 0.8942 (2) 0.61686 (9) 0.0639 (4) H14A 0.0545 1.0009 0.6209 0.096\* H14B −0.0598 0.8739 0.5813 0.096\* H14C 0.1355 0.8477 0.6032 0.096\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1089 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0643 (7) 0.0639 (7) 0.0556 (6) −0.0034 (5) −0.0082 (5) 0.0187 (5) O2 0.0860 (9) 0.0569 (7) 0.0495 (6) −0.0208 (6) −0.0163 (6) 0.0115 (5) O3 0.1070 (10) 0.0603 (7) 0.0347 (5) 0.0046 (7) −0.0018 (6) −0.0064 (5) O4 0.0706 (7) 0.0516 (6) 0.0369 (5) −0.0038 (5) 0.0014 (4) 0.0041 (4) N1 0.0563 (7) 0.0561 (7) 0.0457 (6) −0.0088 (6) 0.0077 (5) 0.0054 (5) C1 0.0484 (7) 0.0491 (7) 0.0360 (6) 0.0029 (6) 0.0048 (5) 0.0012 (5) C2 0.0518 (7) 0.0421 (6) 0.0356 (6) 0.0049 (5) −0.0014 (5) 0.0021 (5) C3 0.0438 (6) 0.0423 (6) 0.0340 (5) 0.0002 (5) −0.0033 (5) 0.0004 (5) C4 0.0449 (6) 0.0411 (6) 0.0415 (6) −0.0011 (5) −0.0056 (5) −0.0011 (5) C5 0.0600 (9) 0.0502 (8) 0.0507 (8) 0.0060 (7) −0.0046 (6) −0.0072 (6) C6 0.0735 (11) 0.0476 (8) 0.0732 (11) 0.0094 (8) −0.0133 (9) −0.0119 (8) C7 0.0816 (12) 0.0385 (8) 0.0861 (13) −0.0058 (8) −0.0198 (10) 0.0041 (8) C8 0.0688 (10) 0.0475 (8) 0.0666 (10) −0.0150 (7) −0.0081 (8) 0.0117 (7) C9 0.0450 (7) 0.0444 (7) 0.0470 (7) −0.0092 (5) −0.0054 (5) 0.0037 (5) C10 0.0674 (10) 0.0854 (13) 0.0559 (9) 0.0197 (9) 0.0157 (8) −0.0024 (9) C11 0.0522 (7) 0.0478 (7) 0.0296 (5) −0.0014 (5) 0.0063 (5) 0.0015 (5) C12 0.0917 (13) 0.0891 (14) 0.0472 (9) −0.0413 (12) −0.0086 (8) 0.0045 (9) C13 0.0498 (7) 0.0487 (7) 0.0343 (6) 0.0046 (6) −0.0042 (5) −0.0008 (5) C14 0.0774 (11) 0.0698 (11) 0.0430 (8) −0.0016 (8) 0.0053 (7) 0.0141 (7) ----- ------------- ------------- ------------- -------------- -------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1480 .table-wrap} --------------------- -------------- -------------------- -------------- O1---C11 1.2001 (17) C5---C6 1.382 (2) O2---C11 1.3249 (18) C5---H5 0.9300 O2---C12 1.443 (2) C6---C7 1.376 (3) O3---C13 1.2055 (17) C6---H6 0.9300 O4---C13 1.3319 (19) C7---C8 1.377 (3) O4---C14 1.4410 (18) C7---H7 0.9300 N1---C1 1.447 (2) C8---C9 1.397 (2) N1---C9 1.386 (2) C8---H8 0.9300 N1---H1 0.91 (2) C10---H10A 0.9600 C1---C2 1.5070 (18) C10---H10B 0.9600 C1---C10 1.530 (2) C10---H10C 0.9600 C1---C11 1.5432 (19) C12---H12A 0.9600 C2---C3 1.3344 (19) C12---H12B 0.9600 C2---H2 0.9300 C12---H12C 0.9600 C3---C4 1.4720 (19) C14---H14A 0.9600 C3---C13 1.4944 (18) C14---H14B 0.9600 C4---C5 1.395 (2) C14---H14C 0.9600 C4---C9 1.412 (2) C11---O2---C12 116.97 (13) C7---C8---H8 119.8 C13---O4---C14 116.33 (13) C9---C8---H8 119.8 C1---N1---H1 112.9 (15) N1---C9---C4 119.52 (13) C9---N1---C1 119.30 (12) N1---C9---C8 121.05 (15) C9---N1---H1 114.2 (14) C8---C9---C4 119.37 (15) N1---C1---C2 108.63 (12) C1---C10---H10A 109.5 N1---C1---C10 109.48 (14) C1---C10---H10B 109.5 N1---C1---C11 110.51 (12) C1---C10---H10C 109.5 C2---C1---C10 111.66 (13) H10A---C10---H10B 109.5 C2---C1---C11 108.97 (11) H10A---C10---H10C 109.5 C10---C1---C11 107.59 (13) H10B---C10---H10C 109.5 C1---C2---H2 119.4 O1---C11---O2 123.62 (14) C3---C2---C1 121.23 (12) O1---C11---C1 124.78 (13) C3---C2---H2 119.4 O2---C11---C1 111.59 (12) C2---C3---C4 120.53 (12) O2---C12---H12A 109.5 C2---C3---C13 119.55 (12) O2---C12---H12B 109.5 C4---C3---C13 119.90 (12) O2---C12---H12C 109.5 C5---C4---C3 124.94 (13) H12A---C12---H12B 109.5 C5---C4---C9 118.56 (14) H12A---C12---H12C 109.5 C9---C4---C3 116.50 (13) H12B---C12---H12C 109.5 C4---C5---H5 119.4 O3---C13---O4 123.36 (14) C6---C5---C4 121.12 (17) O3---C13---C3 124.65 (14) C6---C5---H5 119.4 O4---C13---C3 111.99 (11) C5---C6---H6 120.1 O4---C14---H14A 109.5 C7---C6---C5 119.82 (18) O4---C14---H14B 109.5 C7---C6---H6 120.1 O4---C14---H14C 109.5 C6---C7---C8 120.64 (16) H14A---C14---H14B 109.5 C6---C7---H7 119.7 H14A---C14---H14C 109.5 C8---C7---H7 119.7 H14B---C14---H14C 109.5 C7---C8---C9 120.43 (18) C12---O2---C11---O1 −1.7 (2) C2---C3---C4---C5 −167.06 (14) C12---O2---C11---C1 177.32 (15) C2---C3---C4---C9 13.20 (19) C14---O4---C13---O3 −5.3 (2) C13---C3---C4---C5 14.8 (2) C14---O4---C13---C3 174.17 (13) C13---C3---C4---C9 −164.94 (12) C9---N1---C1---C2 44.10 (17) C2---C3---C13---O3 −154.18 (16) C9---N1---C1---C10 166.27 (14) C2---C3---C13---O4 26.33 (18) C9---N1---C1---C11 −75.40 (16) C4---C3---C13---O3 24.0 (2) C1---N1---C9---C4 −30.23 (19) C4---C3---C13---O4 −155.51 (12) C1---N1---C9---C8 152.77 (14) C3---C4---C5---C6 −177.69 (14) N1---C1---C2---C3 −31.14 (18) C9---C4---C5---C6 2.0 (2) C10---C1---C2---C3 −151.98 (15) C3---C4---C9---N1 −0.52 (18) C11---C1---C2---C3 89.32 (16) C3---C4---C9---C8 176.53 (13) N1---C1---C11---O1 −14.36 (19) C5---C4---C9---N1 179.73 (13) N1---C1---C11---O2 166.68 (12) C5---C4---C9---C8 −3.2 (2) C2---C1---C11---O1 −133.65 (15) C4---C5---C6---C7 0.4 (3) C2---C1---C11---O2 47.38 (16) C5---C6---C7---C8 −1.6 (3) C10---C1---C11---O1 105.13 (18) C6---C7---C8---C9 0.4 (3) C10---C1---C11---O2 −73.84 (16) C7---C8---C9---N1 179.06 (15) C1---C2---C3---C4 4.2 (2) C7---C8---C9---C4 2.1 (2) C1---C2---C3---C13 −177.68 (12) --------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2154 .table-wrap} ---------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1···O1^i^ 0.91 (2) 2.22 (2) 3.1241 (18) 174 (2) C12---H12A···O3^ii^ 0.96 2.57 3.377 (3) 142 C12---H12C···O3^iii^ 0.96 2.49 3.336 (2) 148 ---------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −x, −y+1, −z+2; (ii) −x+1/2, y+1/2, −z+3/2; (iii) x+1/2, −y+3/2, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------------- ---------- ---------- ------------- ------------- N1---H1⋯O1^i^ 0.91 (2) 2.22 (2) 3.1241 (18) 174 (2) C12---H12A⋯O3^ii^ 0.96 2.57 3.377 (3) 142 C12---H12C⋯O3^iii^ 0.96 2.49 3.336 (2) 148 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.841734	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052156/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o672-o673", "authors": [ { "first": "Zeynep", "last": "Gültekin" }, { "first": "Wolfgang", "last": "Frey" }, { "first": "Barış", "last": "Tercan" }, { "first": "Tuncer", "last": "Hökelek" } ] }
PMC3052157	Related literature {#sec1} ================== For general background to inorganic--organic hybrid compounds, see: Zhang et al. (2009[@bb7]); Descalzo et al. (2006[@bb2]); Li et al. (2007[@bb3]), Sanchez et al. (2005[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~8~H~10~NO~2~)~4~\[SnCl~6~\]Cl~2~M ~r~ = 1010.97Monoclinic,a = 30.748 (3) Åb = 7.1172 (8) Åc = 22.113 (2) Åβ = 119.424 (2)°V = 4215.0 (7) Å^3^Z = 4Mo Kα radiationμ = 1.16 mm^−1^T = 298 K0.50 × 0.46 × 0.46 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb5]) T ~min~ = 0.594, T ~max~ = 0.61710221 measured reflections3719 independent reflections2969 reflections with I \> 2σ(I)R ~int~ = 0.035 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.031wR(F ^2^) = 0.090S = 1.013719 reflections245 parametersH-atom parameters constrainedΔρ~max~ = 0.51 e Å^−3^Δρ~min~ = −0.44 e Å^−3^ {#d5e550} Data collection: SMART (Bruker, 2007[@bb1]); cell refinement: SAINT (Bruker, 2007[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: XP in SHELXTL (Sheldrick, 2008[@bb6]); software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003692/cv5035sup1.cif](http://dx.doi.org/10.1107/S1600536811003692/cv5035sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003692/cv5035Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003692/cv5035Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?cv5035&file=cv5035sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?cv5035sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?cv5035&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [CV5035](http://scripts.iucr.org/cgi-bin/sendsup?cv5035)). The authors acknowledge the financial support of the National Science Foundation of China (grant Nos. 50672090 and 50702053). Comment ======= Considerable attention has been devoted to inorganic-organic hybrid materials over recent years (Zhang et al., 2009). These hybrid materials have potential applications in many areas including gas storage, separation, catalysis, magnetism, optics as well as electrical conductivity (Descalzo et al., 2006; Li et al., 2007; Sanchez et al., 2005\]. Herein we report the structure of the title compound (Fig.1.), This title compound contains SnCl~6~ inorganic anions, organic cations and dissociated chloride anions. The SnCl~6~ inorganic anion adopts a regular octahedron geometry, with average Sn---Cl distance of 2.4262 Å. In the organic cation, the dihedral angle between the ester group and the phenyl ring is 14.86(0.19)°. In the crystal structure, intermolecular N---H···Cl and C---H···O hydrogen bonds (Table 1) link cations and anions into layers with alternating inorganic and organic species. Experimental {#experimental} ============ 4-Aminobenzoic acid (10 mmol) was dissolved to acid methanol solution (10 ml). Ten minutes later, a methanol solution (10 ml) of tin tetrachloride(5 mmol) was added with stirring. The mixture was stirred for 4 h. Crystals of the title compound suitable for X-ray analysis were grown from the saturation ethanol solution after about two weeks. Refinement {#refinement} ========== All H-atoms were positioned geometrically and refined using a riding model, with C---H = 0.96 Å (methyl), 0.93 Å (aromatic), N---H =0.89 Å (ammonium) and U~iso~(H) =1.5U~eq~(C), U~iso~(H) =1.2U~eq~(C),U~iso~(H) =1.5U~eq~(N) Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A portion of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme in asymmetric unit \[symmetry code (A): -x, y, -z + 1/2\]. Dashed lines denote N---H···Cl hydrogen bonds. ::: ![](e-67-0m297-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e150 .table-wrap} ------------------------------------- --------------------------------------- (C~8~H~10~NO~2~)~4~\[SnCl~6~\]Cl~2~ F(000) = 2040 M~r~ = 1010.97 D~x~ = 1.593 Mg m^−3^ Monoclinic, C2/c Mo Kα radiation, λ = 0.71073 Å a = 30.748 (3) Å Cell parameters from 4623 reflections b = 7.1172 (8) Å θ = 2.7--27.7° c = 22.113 (2) Å µ = 1.16 mm^−1^ β = 119.424 (2)° T = 298 K V = 4215.0 (7) Å^3^ Block, yellow Z = 4 0.50 × 0.46 × 0.46 mm ------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e280 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3719 independent reflections Radiation source: fine-focus sealed tube 2969 reflections with I \> 2σ(I) graphite R~int~ = 0.035 φ and ω scans θ~max~ = 25.0°, θ~min~ = 1.5° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −29→36 T~min~ = 0.594, T~max~ = 0.617 k = −7→8 10221 measured reflections l = −26→25 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e397 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.031 H-atom parameters constrained wR(F^2^) = 0.090 w = 1/\[σ^2^(F~o~^2^) + (0.045P)^2^ + 5.2918P\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 1.01 (Δ/σ)~max~ \< 0.001 3719 reflections Δρ~max~ = 0.51 e Å^−3^ 245 parameters Δρ~min~ = −0.44 e Å^−3^ 0 restraints Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^\^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.00204 (13) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e578 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR* and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e677 .table-wrap} ------ --------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Sn1 0.0000 0.88525 (4) 0.2500 0.03147 (14) Cl1 0.05414 (3) 1.12542 (12) 0.24657 (5) 0.0448 (2) Cl2 0.04668 (3) 0.88401 (13) 0.37614 (4) 0.0446 (2) Cl3 0.05329 (3) 0.64043 (12) 0.24497 (5) 0.0452 (2) Cl4 0.01937 (4) 0.27991 (19) 0.05504 (6) 0.0745 (4) N1 0.05296 (13) 0.8682 (5) 0.09640 (19) 0.0681 (11) H1A 0.0488 0.8145 0.1295 0.102\ H1B 0.0354 0.8058 0.0568 0.102\* H1C 0.0425 0.9868 0.0908 0.102\* O1 0.28945 (11) 0.8266 (5) 0.23899 (19) 0.0801 (9) O2 0.27319 (15) 0.8654 (6) 0.1308 (2) 0.1100 (15) C1 0.25910 (17) 0.8534 (6) 0.1724 (3) 0.0614 (12) C2 0.20539 (15) 0.8609 (5) 0.1534 (2) 0.0488 (9) C3 0.19023 (15) 0.8011 (7) 0.1997 (2) 0.0596 (11) H3 0.2138 0.7596 0.2437 0.071\* C4 0.14066 (15) 0.8028 (7) 0.1808 (2) 0.0627 (12) H4 0.1305 0.7621 0.2119 0.075\* C5 0.10627 (15) 0.8642 (5) 0.1165 (2) 0.0510 (10) C6 0.12064 (16) 0.9276 (6) 0.0699 (2) 0.0563 (10) H6 0.0971 0.9721 0.0265 0.068\* C7 0.17023 (16) 0.9236 (6) 0.0889 (2) 0.0571 (11) H7 0.1803 0.9640 0.0577 0.069\* C8 0.34155 (17) 0.8066 (9) 0.2610 (3) 0.0977 (18) H8A 0.3466 0.6959 0.2404 0.146\* H8B 0.3601 0.7958 0.3107 0.146\* H8C 0.3528 0.9148 0.2467 0.146\* N2 −0.04641 (12) 0.3799 (4) 0.12080 (17) 0.0549 (8) H2A −0.0469 0.2835 0.1461 0.082\* H2B −0.0329 0.4794 0.1481 0.082\* H2C −0.0284 0.3495 0.1008 0.082\* O3 −0.27704 (11) 0.5652 (5) −0.06223 (17) 0.0754 (9) O4 −0.25318 (15) 0.6482 (7) −0.1379 (2) 0.1235 (17) C9 −0.24390 (17) 0.5845 (7) −0.0834 (2) 0.0649 (12) C10 −0.19295 (13) 0.5235 (6) −0.03008 (18) 0.0475 (9) C11 −0.15324 (15) 0.5639 (6) −0.0409 (2) 0.0530 (10) H11 −0.1591 0.6244 −0.0814 0.064\* C12 −0.10518 (13) 0.5155 (5) 0.00777 (19) 0.0460 (9) H12 −0.0785 0.5435 0.0007 0.055\* C13 −0.09772 (13) 0.4248 (5) 0.06700 (18) 0.0412 (8) C14 −0.13659 (14) 0.3806 (5) 0.07820 (19) 0.0484 (9) H14 −0.1306 0.3179 0.1185 0.058\* C15 −0.18453 (14) 0.4296 (6) 0.0293 (2) 0.0538 (10) H15 −0.2112 0.3995 0.0363 0.065\* C16 −0.32747 (17) 0.6233 (8) −0.1111 (3) 0.100 (2) H16A −0.3402 0.5467 −0.1521 0.150\* H16B −0.3274 0.7526 −0.1234 0.150\* H16C −0.3483 0.6091 −0.0903 0.150\* ------ --------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1343 .table-wrap} ----- ------------- ------------ ------------ -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Sn1 0.0315 (2) 0.0292 (2) 0.0350 (2) 0.000 0.01734 (15) 0.000 Cl1 0.0388 (5) 0.0417 (5) 0.0498 (5) −0.0108 (4) 0.0187 (4) 0.0027 (4) Cl2 0.0430 (5) 0.0531 (6) 0.0319 (5) 0.0061 (4) 0.0138 (4) 0.0043 (4) Cl3 0.0441 (5) 0.0385 (5) 0.0611 (6) 0.0090 (4) 0.0322 (5) 0.0006 (4) Cl4 0.0609 (7) 0.0948 (9) 0.0812 (8) 0.0232 (6) 0.0452 (6) 0.0309 (7) N1 0.054 (2) 0.094 (3) 0.063 (2) 0.0182 (18) 0.0344 (19) 0.021 (2) O1 0.0490 (18) 0.115 (3) 0.080 (2) 0.0101 (17) 0.0348 (18) −0.003 (2) O2 0.084 (3) 0.174 (4) 0.107 (3) 0.001 (2) 0.074 (3) 0.016 (3) C1 0.063 (3) 0.055 (3) 0.086 (4) −0.006 (2) 0.052 (3) −0.008 (2) C2 0.056 (2) 0.045 (2) 0.060 (3) 0.0003 (17) 0.040 (2) −0.0021 (18) C3 0.051 (2) 0.083 (3) 0.052 (2) 0.013 (2) 0.031 (2) 0.017 (2) C4 0.056 (3) 0.091 (3) 0.056 (3) 0.019 (2) 0.038 (2) 0.028 (2) C5 0.052 (2) 0.056 (3) 0.055 (2) 0.0110 (18) 0.034 (2) 0.0093 (19) C6 0.063 (3) 0.065 (3) 0.047 (2) 0.009 (2) 0.032 (2) 0.0141 (19) C7 0.072 (3) 0.062 (3) 0.056 (3) 0.003 (2) 0.046 (2) 0.008 (2) C8 0.053 (3) 0.114 (4) 0.128 (5) 0.012 (3) 0.046 (3) −0.002 (4) N2 0.0470 (19) 0.057 (2) 0.052 (2) 0.0027 (15) 0.0173 (16) −0.0006 (16) O3 0.0418 (16) 0.094 (2) 0.075 (2) 0.0087 (16) 0.0164 (16) −0.0012 (18) O4 0.081 (3) 0.201 (5) 0.063 (2) 0.034 (3) 0.015 (2) 0.051 (3) C9 0.055 (3) 0.073 (3) 0.047 (3) 0.008 (2) 0.010 (2) −0.002 (2) C10 0.046 (2) 0.053 (2) 0.039 (2) 0.0024 (17) 0.0163 (18) −0.0014 (18) C11 0.063 (3) 0.055 (2) 0.041 (2) 0.0008 (19) 0.025 (2) 0.0055 (18) C12 0.046 (2) 0.046 (2) 0.051 (2) −0.0042 (17) 0.0277 (19) 0.0003 (18) C13 0.040 (2) 0.042 (2) 0.038 (2) 0.0015 (15) 0.0161 (16) −0.0023 (16) C14 0.048 (2) 0.056 (2) 0.040 (2) 0.0017 (18) 0.0207 (18) 0.0097 (17) C15 0.042 (2) 0.070 (3) 0.048 (2) −0.0043 (19) 0.0216 (19) 0.004 (2) C16 0.039 (3) 0.114 (5) 0.103 (4) 0.013 (3) 0.002 (3) −0.023 (3) ----- ------------- ------------ ------------ -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1823 .table-wrap} ----------------------- ------------ ------------------- ----------- Sn1---Cl1 2.4131 (8) C8---H8A 0.9600 Sn1---Cl1^i^ 2.4131 (8) C8---H8B 0.9600 Sn1---Cl2^i^ 2.4305 (9) C8---H8C 0.9600 Sn1---Cl2 2.4305 (9) N2---C13 1.471 (4) Sn1---Cl3 2.4315 (8) N2---H2A 0.8900 Sn1---Cl3^i^ 2.4315 (8) N2---H2B 0.8900 N1---C5 1.473 (5) N2---H2C 0.8900 N1---H1A 0.8900 O3---C9 1.320 (5) N1---H1B 0.8900 O3---C16 1.448 (5) N1---H1C 0.8900 O4---C9 1.185 (5) O1---C1 1.314 (6) C9---C10 1.489 (5) O1---C8 1.434 (5) C10---C15 1.380 (5) O2---C1 1.197 (5) C10---C11 1.384 (5) C1---C2 1.492 (5) C11---C12 1.377 (5) C2---C7 1.373 (6) C11---H11 0.9300 C2---C3 1.384 (5) C12---C13 1.375 (5) C3---C4 1.368 (5) C12---H12 0.9300 C3---H3 0.9300 C13---C14 1.371 (5) C4---C5 1.362 (5) C14---C15 1.378 (5) C4---H4 0.9300 C14---H14 0.9300 C5---C6 1.380 (5) C15---H15 0.9300 C6---C7 1.369 (5) C16---H16A 0.9600 C6---H6 0.9300 C16---H16B 0.9600 C7---H7 0.9300 C16---H16C 0.9600 Cl1---Sn1---Cl1^i^ 89.79 (5) C2---C7---H7 119.5 Cl1---Sn1---Cl2^i^ 89.66 (3) O1---C8---H8A 109.5 Cl1^i^---Sn1---Cl2^i^ 90.63 (3) O1---C8---H8B 109.5 Cl1---Sn1---Cl2 90.63 (3) H8A---C8---H8B 109.5 Cl1^i^---Sn1---Cl2 89.66 (3) O1---C8---H8C 109.5 Cl2^i^---Sn1---Cl2 179.58 (4) H8A---C8---H8C 109.5 Cl1---Sn1---Cl3 90.88 (3) H8B---C8---H8C 109.5 Cl1^i^---Sn1---Cl3 179.00 (3) C13---N2---H2A 109.5 Cl2^i^---Sn1---Cl3 88.64 (3) C13---N2---H2B 109.5 Cl2---Sn1---Cl3 91.06 (3) H2A---N2---H2B 109.5 Cl1---Sn1---Cl3^i^ 179.00 (3) C13---N2---H2C 109.5 Cl1^i^---Sn1---Cl3^i^ 90.88 (3) H2A---N2---H2C 109.5 Cl2^i^---Sn1---Cl3^i^ 91.06 (3) H2B---N2---H2C 109.5 Cl2---Sn1---Cl3^i^ 88.64 (3) C9---O3---C16 115.8 (4) Cl3---Sn1---Cl3^i^ 88.45 (4) O4---C9---O3 124.0 (4) C5---N1---H1A 109.5 O4---C9---C10 123.4 (5) C5---N1---H1B 109.5 O3---C9---C10 112.6 (4) H1A---N1---H1B 109.5 C15---C10---C11 119.7 (3) C5---N1---H1C 109.5 C15---C10---C9 121.8 (4) H1A---N1---H1C 109.5 C11---C10---C9 118.5 (4) H1B---N1---H1C 109.5 C12---C11---C10 120.8 (4) C1---O1---C8 117.0 (4) C12---C11---H11 119.6 O2---C1---O1 123.1 (4) C10---C11---H11 119.6 O2---C1---C2 123.4 (5) C13---C12---C11 118.3 (3) O1---C1---C2 113.5 (4) C13---C12---H12 120.9 C7---C2---C3 119.2 (4) C11---C12---H12 120.9 C7---C2---C1 120.1 (4) C14---C13---C12 121.8 (3) C3---C2---C1 120.6 (4) C14---C13---N2 119.2 (3) C4---C3---C2 120.1 (4) C12---C13---N2 118.9 (3) C4---C3---H3 120.0 C13---C14---C15 119.5 (4) C2---C3---H3 120.0 C13---C14---H14 120.3 C5---C4---C3 119.9 (4) C15---C14---H14 120.3 C5---C4---H4 120.0 C14---C15---C10 119.8 (4) C3---C4---H4 120.0 C14---C15---H15 120.1 C4---C5---C6 121.0 (4) C10---C15---H15 120.1 C4---C5---N1 119.9 (3) O3---C16---H16A 109.5 C6---C5---N1 119.0 (4) O3---C16---H16B 109.5 C7---C6---C5 118.8 (4) H16A---C16---H16B 109.5 C7---C6---H6 120.6 O3---C16---H16C 109.5 C5---C6---H6 120.6 H16A---C16---H16C 109.5 C6---C7---C2 121.0 (3) H16B---C16---H16C 109.5 C6---C7---H7 119.5 ----------------------- ------------ ------------------- ----------- ::: Symmetry codes: (i) −x, y, −z+1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2498 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···Cl3 0.89 2.78 3.659 (4) 170 N2---H2B···Cl3 0.89 2.71 3.479 (3) 145 N2---H2C···Cl4 0.89 2.21 3.098 (4) 177 N1---H1B···Cl4^ii^ 0.89 2.29 3.155 (4) 165 N1---H1C···Cl4^iii^ 0.89 2.22 3.092 (4) 166 N2---H2A···Cl1^iv^ 0.89 3.01 3.482 (3) 115 C3---H3···O4^v^ 0.93 2.39 3.148 (6) 139 C15---H15···O2^vi^ 0.93 2.38 3.130 (5) 138 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −x, −y+1, −z; (iii) x, y+1, z; (iv) x, y−1, z; (v) x+1/2, −y+3/2, z+1/2; (vi) x−1/2, y−1/2, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- N1---H1A⋯Cl3 0.89 2.78 3.659 (4) 170 N2---H2B⋯Cl3 0.89 2.71 3.479 (3) 145 N2---H2C⋯Cl4 0.89 2.21 3.098 (4) 177 N1---H1B⋯Cl4^i^ 0.89 2.29 3.155 (4) 165 N1---H1C⋯Cl4^ii^ 0.89 2.22 3.092 (4) 166 N2---H2A⋯Cl1^iii^ 0.89 3.01 3.482 (3) 115 C3---H3⋯O4^iv^ 0.93 2.39 3.148 (6) 139 C15---H15⋯O2^v^ 0.93 2.38 3.130 (5) 138 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) . :::	PubMed Central	2024-06-05T04:04:18.847055	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052157/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):m297", "authors": [ { "first": "Wenzhi", "last": "Xiao" }, { "first": "Ruiting", "last": "Xue" }, { "first": "Yansheng", "last": "Yin" } ] }
PMC3052158	Related literature {#sec1} ================== For general background to the synthesis of thiophene-based conjugated polymers, see: Cheng et al. (2009[@bb4]). For the synthesis of the title compound, see: Brzezinski & Reynolds (2002[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~9~H~4~I~2~OS~2~M ~r~ = 446.04Monoclinic,a = 10.1908 (9) Åb = 11.4832 (10) Åc = 10.9083 (10) Åβ = 107.600 (1)°V = 1216.77 (19) Å^3^Z = 4Mo Kα radiationμ = 5.48 mm^−1^T = 298 K0.16 × 0.12 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb5]) T ~min~ = 0.474, T ~max~ = 0.6108022 measured reflections3003 independent reflections2541 reflections with I \> 2σ(I)R ~int~ = 0.084 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.103S = 1.113003 reflections127 parametersH-atom parameters constrainedΔρ~max~ = 1.08 e Å^−3^Δρ~min~ = −0.67 e Å^−3^ {#d5e387} Data collection: SMART (Bruker, 2001[@bb2]); cell refinement: SAINT (Bruker, 1999[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb6]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb6]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb6]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005472/cv5050sup1.cif](http://dx.doi.org/10.1107/S1600536811005472/cv5050sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005472/cv5050Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005472/cv5050Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?cv5050&file=cv5050sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?cv5050sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?cv5050&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [CV5050](http://scripts.iucr.org/cgi-bin/sendsup?cv5050)). The author acknowledges financial support from Xiangfan University. Comment ======= The title compound, (I), is an important organic intermediate for the synthesis of conjugated polymers for organic solar cell applications (Brzezinski & Reynolds, 2002; Cheng et al., 2009). In (I) (Fig. 1), two five-membered rings form a dihedral angle of 64.2 (2)°. Weak intermolecular C---H···O hydrogen bonds link the molecules into layers parallel to ab plane. The crystal packing exhibits short C···I contacts of 3.442 (5) Å between the molecules from the neighbouring layers. Experimental {#experimental} ============ The title compound was synthesized according to the reported method by Brzezinski & Reynolds (2002). After being dissolved in the mixture of MeOH-Hexane (1:3) for seversal days, colourless crystals suitable for single-crystal X-ray diffraction were obtained. Refinement {#refinement} ========== All hydrogen atoms were positioned geometrically (C---H = 0.93 Å) and allowed to ride on their parent atoms, with U~iso~(H) = 1.2 U~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The title molecule with the atom-numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o691-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e104 .table-wrap} ------------------------- --------------------------------------- C~9~H~4~I~2~OS~2~ F(000) = 816 M~r~ = 446.04 D~x~ = 2.435 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2906 reflections a = 10.1908 (9) Å θ = 2.4--26.9° b = 11.4832 (10) Å µ = 5.48 mm^−1^ c = 10.9083 (10) Å T = 298 K β = 107.600 (1)° Block, colourless V = 1216.77 (19) Å^3^ 0.16 × 0.12 × 0.10 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e234 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3003 independent reflections Radiation source: fine-focus sealed tube 2541 reflections with I \> 2σ(I) graphite R~int~ = 0.084 φ and ω scans θ~max~ = 28.2°, θ~min~ = 2.4° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −13→7 T~min~ = 0.474, T~max~ = 0.610 k = −15→12 8022 measured reflections l = −14→14 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e351 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.103 H-atom parameters constrained S = 1.11 w = 1/\[σ^2^(F~o~^2^) + (0.0342P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 3003 reflections (Δ/σ)~max~ = 0.001 127 parameters Δρ~max~ = 1.08 e Å^−3^ 0 restraints Δρ~min~ = −0.67 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e505 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e604 .table-wrap} ---- -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.7428 (5) 0.3871 (4) 0.9017 (5) 0.0377 (10) C2 0.6198 (5) 0.3657 (4) 0.8086 (4) 0.0328 (9) C3 0.6258 (5) 0.2588 (4) 0.7431 (5) 0.0392 (11) H3 0.5515 0.2291 0.6783 0.047\ C4 0.7482 (6) 0.2053 (5) 0.7835 (5) 0.0486 (13) H4 0.7688 0.1359 0.7495 0.058\* C5 0.5029 (5) 0.4469 (4) 0.7705 (5) 0.0349 (10) C6 0.3643 (5) 0.3977 (4) 0.7066 (5) 0.0350 (10) C7 0.3112 (6) 0.2950 (4) 0.7492 (5) 0.0438 (12) H7 0.3628 0.2488 0.8166 0.053\* C8 0.1801 (6) 0.2717 (5) 0.6827 (6) 0.0499 (13) H8 0.1300 0.2093 0.6996 0.060\* C9 0.2680 (5) 0.4481 (4) 0.6055 (5) 0.0372 (10) I1 0.79608 (5) 0.51950 (4) 1.03536 (4) 0.05838 (16) I2 0.28839 (4) 0.58784 (3) 0.49276 (4) 0.05046 (14) O1 0.5191 (4) 0.5512 (3) 0.7870 (5) 0.0569 (10) S1 0.86152 (15) 0.28059 (13) 0.90534 (14) 0.0517 (4) S2 0.11662 (14) 0.37150 (14) 0.56270 (15) 0.0512 (3) ---- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e857 .table-wrap} ---- ------------ ------------- ------------ --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.043 (3) 0.035 (3) 0.034 (2) 0.002 (2) 0.012 (2) 0.0020 (19) C2 0.036 (3) 0.033 (2) 0.030 (2) 0.0025 (19) 0.011 (2) 0.0009 (18) C3 0.043 (3) 0.037 (3) 0.034 (2) 0.004 (2) 0.006 (2) −0.003 (2) C4 0.059 (4) 0.044 (3) 0.042 (3) 0.010 (2) 0.012 (3) −0.006 (2) C5 0.034 (2) 0.030 (2) 0.043 (3) 0.0002 (18) 0.014 (2) 0.000 (2) C6 0.039 (3) 0.028 (2) 0.042 (2) 0.0007 (18) 0.018 (2) −0.0017 (19) C7 0.049 (3) 0.036 (3) 0.047 (3) −0.002 (2) 0.014 (2) 0.006 (2) C8 0.048 (3) 0.040 (3) 0.066 (4) −0.011 (2) 0.023 (3) 0.003 (3) C9 0.035 (3) 0.035 (2) 0.043 (3) −0.0045 (19) 0.014 (2) −0.002 (2) I1 0.0753 (3) 0.0496 (2) 0.0436 (2) −0.01260 (18) 0.0080 (2) −0.01168 (16) I2 0.0553 (3) 0.0435 (2) 0.0549 (2) 0.00141 (15) 0.02021 (19) 0.01160 (16) O1 0.041 (2) 0.0288 (18) 0.094 (3) 0.0001 (15) 0.011 (2) −0.005 (2) S1 0.0430 (8) 0.0537 (9) 0.0501 (8) 0.0140 (6) 0.0018 (6) 0.0014 (6) S2 0.0357 (7) 0.0542 (8) 0.0600 (8) −0.0072 (6) 0.0092 (6) 0.0008 (7) ---- ------------ ------------- ------------ --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1135 .table-wrap} ------------------- ------------ ------------------- ------------ C1---C2 1.376 (7) C5---C6 1.485 (7) C1---S1 1.712 (5) C6---C9 1.364 (7) C1---I1 2.063 (5) C6---C7 1.433 (6) C2---C3 1.431 (7) C7---C8 1.339 (8) C2---C5 1.471 (7) C7---H7 0.9300 C3---C4 1.339 (8) C8---S2 1.713 (6) C3---H3 0.9300 C8---H8 0.9300 C4---S1 1.709 (6) C9---S2 1.714 (5) C4---H4 0.9300 C9---I2 2.070 (5) C5---O1 1.215 (6) C2---C1---S1 111.7 (4) C9---C6---C7 111.2 (4) C2---C1---I1 129.8 (4) C9---C6---C5 124.6 (4) S1---C1---I1 118.5 (3) C7---C6---C5 124.1 (4) C1---C2---C3 110.8 (4) C8---C7---C6 113.7 (5) C1---C2---C5 125.1 (4) C8---C7---H7 123.2 C3---C2---C5 123.8 (4) C6---C7---H7 123.2 C4---C3---C2 113.9 (5) C7---C8---S2 111.4 (4) C4---C3---H3 123.1 C7---C8---H8 124.3 C2---C3---H3 123.1 S2---C8---H8 124.3 C3---C4---S1 111.6 (4) C6---C9---S2 111.8 (4) C3---C4---H4 124.2 C6---C9---I2 129.3 (4) S1---C4---H4 124.2 S2---C9---I2 118.7 (3) O1---C5---C2 121.4 (4) C4---S1---C1 92.1 (3) O1---C5---C6 120.8 (4) C8---S2---C9 92.0 (3) C2---C5---C6 117.8 (4) S1---C1---C2---C3 1.2 (5) C2---C5---C6---C7 44.7 (7) I1---C1---C2---C3 −175.7 (4) C9---C6---C7---C8 −0.8 (6) S1---C1---C2---C5 −172.4 (4) C5---C6---C7---C8 175.3 (5) I1---C1---C2---C5 10.6 (7) C6---C7---C8---S2 1.6 (6) C1---C2---C3---C4 −1.6 (6) C7---C6---C9---S2 −0.3 (5) C5---C2---C3---C4 172.2 (5) C5---C6---C9---S2 −176.4 (4) C2---C3---C4---S1 1.2 (6) C7---C6---C9---I2 −173.7 (4) C1---C2---C5---O1 24.2 (7) C5---C6---C9---I2 10.1 (7) C3---C2---C5---O1 −148.6 (5) C3---C4---S1---C1 −0.4 (5) C1---C2---C5---C6 −158.0 (5) C2---C1---S1---C4 −0.5 (4) C3---C2---C5---C6 29.2 (7) I1---C1---S1---C4 176.8 (3) O1---C5---C6---C9 38.0 (7) C7---C8---S2---C9 −1.5 (5) C2---C5---C6---C9 −139.7 (5) C6---C9---S2---C8 1.0 (4) O1---C5---C6---C7 −137.6 (5) I2---C9---S2---C8 175.2 (3) ------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1539 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C4---H4···O1^i^ 0.93 2.51 3.233 (7) 135 C8---H8···O1^ii^ 0.93 2.40 3.324 (6) 172 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+3/2, y−1/2, −z+3/2; (ii) −x+1/2, y−1/2, −z+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- C4---H4⋯O1^i^ 0.93 2.51 3.233 (7) 135 C8---H8⋯O1^ii^ 0.93 2.40 3.324 (6) 172 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.852631	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052158/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o691", "authors": [ { "first": "Hua", "last": "Cheng" } ] }
PMC3052159	Related literature {#sec1} ================== For related structures, see: Subha Nandhini et al. (2003[@bb11]); Nithya et al. (2009[@bb8]); Aravindhan et al. (2009[@bb1]); Aridoss et al. (2009[@bb2], 2010[@bb3]). For ring conformational analysis, see: Cremer & Pople (1975[@bb5]); Nardelli (1983[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~27~H~25~NO~4~M ~r~ = 427.48Triclinic,a = 8.2784 (7) Åb = 10.6116 (9) Åc = 12.7572 (11) Åα = 85.681 (4)°β = 89.963 (4)°γ = 82.508 (5)°V = 1107.91 (16) Å^3^Z = 2Mo Kα radiationμ = 0.09 mm^−1^T = 293 K0.25 × 0.23 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2008[@bb4]) T ~min~ = 0.979, T ~max~ = 0.98320295 measured reflections5526 independent reflections4179 reflections with I \> 2σ(I)R ~int~ = 0.024 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.120S = 1.045526 reflections290 parametersH-atom parameters constrainedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e414} Data collection: APEX2 (Bruker, 2008[@bb4]); cell refinement: SAINT (Bruker, 2008[@bb4]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb9]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb9]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb6]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003266/is2669sup1.cif](http://dx.doi.org/10.1107/S1600536811003266/is2669sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003266/is2669Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003266/is2669Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2669&file=is2669sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2669sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2669&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2669](http://scripts.iucr.org/cgi-bin/sendsup?is2669)). This research was supported by the Industrial Technology Development Program, which was conducted by the Ministry of Knowledge Economy of the Korean Government. SS and DV thank the TBI X-ray Facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection and the University Grants Commission (UGC&SAP) for financial support. Comment ======= Owing to the relevance of piperidine-containing bioactive compounds, the development of new piperidine based derivatives continues to be a subject of considerable interest. The pharmacological effects of potential new drugs depend entirely on the stereochemistry and ring conformations of the compounds and hence the crystallographic study of the title compound has been carried out. The ORTEP diagram of the title compound is shown in Fig. 1. The tetrahydropyridine ring adopts a half-chair conformation. The puckering parameters (Cremer & Pople, 1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) for this ring are q~2~ = 0.344 (1) Å, q~3~ = -0.288 (1) Å; Q~T~ = 0.4485 Å and θ = 130.02 (2)°, φ~2~ = 205.6 (2)°, respectively. The three phenyl rings are twisted away from the best plane of the tetrahydropyridine ring by 66.33 (7), 87.36 (8) and 36.90 (7)°, respectively. The sum of the bond angles around the atom N1 \[360.09 (10)°\] of the tetrahydropyridine ring in the molecule is in accordance with sp^2^ hybridization. The ethyl acetate group shows an extended conformation \[C18---O3---C19---C20 = 90.67 (2)°\]. The molecular structure is stabilized by a strong O---H···O hydrogen bond, wherein, atom O1 acts as a donor to O2, generating an S(6) motif. Experimental {#experimental} ============ To a mixture of 3-carboxyethyl-2,6-diphenylpiperidin-4-one (1 equiv.) and triethylamine (1.5 equiv.) in benzene, freshly distilled benzoyl chloride in benzene was added dropwise and stirred well at room temperature until completion. The crude mass obtained by the base work upon purification and recrystallization in distilled ethanol gave fine white crystals suitable for X-ray study. Refinement {#refinement} ========== The C bound H atoms positioned geometrically (C---H = 0.93--0.98 Å) and allowed to ride on their parent atoms, with 1.5U~eq~(C) for methyl H and 1.2U~eq~(C) for other H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Perspective view of the title compound, showing displacement ellipsoids drawn at the 30% probability level. ::: ![](e-67-0o540-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing of the title compound, viewed down the a axis. For clarity, hydrogen atoms not involved in hydrogen bonding have been omitted. ::: ![](e-67-0o540-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e139 .table-wrap} ------------------------- --------------------------------------- C~27~H~25~NO~4~ Z = 2 M~r~ = 427.48 F(000) = 452 Triclinic, P1 D~x~ = 1.281 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.2784 (7) Å Cell parameters from 1225 reflections b = 10.6116 (9) Å θ = 1.6--28.4° c = 12.7572 (11) Å µ = 0.09 mm^−1^ α = 85.681 (4)° T = 293 K β = 89.963 (4)° Block, white γ = 82.508 (5)° 0.25 × 0.23 × 0.20 mm V = 1107.91 (16) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e272 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII area-detector diffractometer 5526 independent reflections Radiation source: fine-focus sealed tube 4179 reflections with I \> 2σ(I) graphite R~int~ = 0.024 ω and φ scans θ~max~ = 28.4°, θ~min~ = 1.6° Absorption correction: multi-scan (SADABS; Bruker, 2008) h = −11→11 T~min~ = 0.979, T~max~ = 0.983 k = −14→14 20295 measured reflections l = −17→17 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e389 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.120 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0497P)^2^ + 0.2116P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5526 reflections (Δ/σ)~max~ \< 0.001 290 parameters Δρ~max~ = 0.20 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e546 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e645 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.35152 (15) 0.26735 (12) 0.41384 (9) 0.0431 (3) H1 0.3276 0.2416 0.4870 0.052\ C2 0.44264 (18) 0.38303 (14) 0.41541 (11) 0.0551 (3) H2A 0.4025 0.4326 0.4731 0.066\* H2B 0.5573 0.3539 0.4285 0.066\* C3 0.42551 (17) 0.46663 (12) 0.31645 (11) 0.0483 (3) C4 0.31584 (15) 0.45704 (11) 0.23982 (9) 0.0421 (3) C5 0.19897 (14) 0.35828 (11) 0.24886 (9) 0.0382 (2) H5 0.0906 0.4048 0.2328 0.046\* C6 0.22569 (15) 0.25498 (11) 0.17071 (9) 0.0410 (3) C7 0.34280 (18) 0.25430 (15) 0.09352 (12) 0.0585 (4) H7 0.4142 0.3152 0.0911 0.070\* C8 0.3555 (2) 0.16428 (18) 0.01975 (15) 0.0758 (5) H8 0.4340 0.1660 −0.0324 0.091\* C9 0.2530 (2) 0.07296 (16) 0.02343 (14) 0.0739 (5) H9 0.2626 0.0117 −0.0255 0.089\* C10 0.1359 (2) 0.07199 (15) 0.09956 (12) 0.0663 (4) H10 0.0657 0.0102 0.1020 0.080\* C11 0.12177 (19) 0.16256 (13) 0.17261 (11) 0.0528 (3) H11 0.0416 0.1614 0.2236 0.063\* C12 0.44595 (15) 0.15211 (13) 0.36780 (10) 0.0447 (3) C13 0.59156 (19) 0.15546 (17) 0.31517 (14) 0.0692 (4) H13 0.6367 0.2313 0.3062 0.083\* C14 0.6700 (2) 0.0462 (2) 0.27598 (19) 0.0929 (7) H14 0.7676 0.0494 0.2403 0.112\* C15 0.6072 (2) −0.0660 (2) 0.28857 (17) 0.0873 (6) H15 0.6602 −0.1385 0.2606 0.105\* C16 0.4653 (2) −0.07137 (17) 0.34282 (16) 0.0748 (5) H16 0.4226 −0.1482 0.3531 0.090\* C17 0.38547 (18) 0.03709 (14) 0.38216 (12) 0.0573 (4) H17 0.2892 0.0326 0.4190 0.069\* C18 0.29783 (17) 0.55330 (12) 0.15177 (10) 0.0477 (3) C19 0.1465 (2) 0.63209 (17) −0.00422 (12) 0.0685 (4) H19A 0.1880 0.7112 0.0078 0.082\* H19B 0.0311 0.6514 −0.0203 0.082\* C20 0.2327 (2) 0.5731 (2) −0.09393 (13) 0.0832 (6) H20A 0.3479 0.5599 −0.0799 0.125\* H20B 0.2108 0.6286 −0.1567 0.125\* H20C 0.1954 0.4927 −0.1033 0.125\* C21 0.04496 (15) 0.30444 (11) 0.40464 (10) 0.0416 (3) C22 0.03654 (15) 0.27946 (12) 0.52150 (10) 0.0433 (3) C23 −0.04315 (18) 0.18014 (14) 0.56215 (11) 0.0549 (3) H23 −0.0836 0.1265 0.5172 0.066\* C24 −0.0628 (2) 0.16050 (17) 0.66984 (12) 0.0655 (4) H24 −0.1142 0.0925 0.6971 0.079\* C25 −0.0065 (2) 0.24121 (17) 0.73612 (12) 0.0643 (4) H25 −0.0203 0.2280 0.8083 0.077\* C26 0.0700 (2) 0.34139 (15) 0.69651 (12) 0.0620 (4) H26 0.1068 0.3965 0.7417 0.074\* C27 0.09253 (18) 0.36049 (13) 0.58943 (11) 0.0531 (3) H27 0.1454 0.4280 0.5628 0.064\* N1 0.19330 (12) 0.30648 (9) 0.35920 (7) 0.0388 (2) O1 0.52511 (14) 0.55669 (10) 0.31367 (9) 0.0663 (3) H1A 0.5089 0.6028 0.2592 0.099\* O2 0.38767 (14) 0.63583 (10) 0.13602 (9) 0.0687 (3) O3 0.17091 (12) 0.54509 (9) 0.08975 (7) 0.0530 (2) O4 −0.08244 (11) 0.32515 (10) 0.35338 (8) 0.0563 (3) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1408 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0447 (6) 0.0496 (7) 0.0359 (6) −0.0114 (5) −0.0075 (5) −0.0002 (5) C2 0.0608 (8) 0.0598 (8) 0.0487 (7) −0.0218 (7) −0.0139 (6) −0.0056 (6) C3 0.0527 (7) 0.0446 (7) 0.0511 (7) −0.0167 (6) −0.0007 (6) −0.0096 (5) C4 0.0474 (7) 0.0384 (6) 0.0417 (6) −0.0098 (5) 0.0013 (5) −0.0042 (5) C5 0.0418 (6) 0.0381 (6) 0.0350 (6) −0.0079 (5) −0.0044 (5) −0.0006 (4) C6 0.0457 (6) 0.0398 (6) 0.0372 (6) −0.0047 (5) −0.0091 (5) −0.0016 (5) C7 0.0539 (8) 0.0606 (9) 0.0643 (9) −0.0121 (7) 0.0074 (7) −0.0191 (7) C8 0.0766 (11) 0.0824 (12) 0.0721 (11) −0.0086 (9) 0.0160 (9) −0.0333 (9) C9 0.0989 (13) 0.0620 (10) 0.0636 (10) −0.0070 (9) −0.0032 (9) −0.0282 (8) C10 0.0967 (12) 0.0514 (8) 0.0556 (9) −0.0254 (8) −0.0139 (8) −0.0085 (7) C11 0.0701 (9) 0.0494 (7) 0.0417 (7) −0.0193 (6) −0.0052 (6) −0.0026 (5) C12 0.0398 (6) 0.0529 (7) 0.0400 (6) −0.0036 (5) −0.0081 (5) 0.0025 (5) C13 0.0483 (8) 0.0712 (10) 0.0847 (12) −0.0031 (7) 0.0098 (8) 0.0087 (9) C14 0.0584 (10) 0.0983 (16) 0.1135 (17) 0.0163 (10) 0.0255 (10) 0.0017 (13) C15 0.0693 (12) 0.0831 (13) 0.1018 (15) 0.0267 (10) −0.0038 (10) −0.0202 (11) C16 0.0639 (10) 0.0571 (9) 0.1021 (14) 0.0026 (8) −0.0138 (9) −0.0147 (9) C17 0.0485 (8) 0.0558 (8) 0.0685 (9) −0.0080 (6) 0.0002 (7) −0.0080 (7) C18 0.0531 (7) 0.0427 (7) 0.0476 (7) −0.0077 (6) 0.0080 (6) −0.0022 (5) C19 0.0756 (10) 0.0728 (10) 0.0521 (8) −0.0055 (8) −0.0031 (7) 0.0214 (7) C20 0.0807 (12) 0.1220 (16) 0.0467 (9) −0.0197 (11) 0.0016 (8) 0.0062 (9) C21 0.0462 (7) 0.0372 (6) 0.0424 (6) −0.0089 (5) −0.0010 (5) −0.0027 (5) C22 0.0443 (6) 0.0419 (6) 0.0430 (6) −0.0025 (5) 0.0029 (5) −0.0030 (5) C23 0.0579 (8) 0.0568 (8) 0.0518 (8) −0.0168 (6) 0.0020 (6) −0.0002 (6) C24 0.0652 (9) 0.0736 (10) 0.0566 (9) −0.0149 (8) 0.0087 (7) 0.0130 (8) C25 0.0656 (9) 0.0780 (11) 0.0440 (8) 0.0082 (8) 0.0107 (7) −0.0014 (7) C26 0.0753 (10) 0.0596 (9) 0.0489 (8) 0.0073 (7) −0.0004 (7) −0.0188 (7) C27 0.0654 (9) 0.0428 (7) 0.0514 (8) −0.0055 (6) 0.0025 (6) −0.0085 (6) N1 0.0415 (5) 0.0405 (5) 0.0347 (5) −0.0073 (4) −0.0034 (4) −0.0013 (4) O1 0.0744 (7) 0.0620 (6) 0.0700 (7) −0.0369 (5) −0.0074 (5) −0.0056 (5) O2 0.0769 (7) 0.0583 (6) 0.0731 (7) −0.0273 (5) 0.0042 (6) 0.0116 (5) O3 0.0599 (6) 0.0546 (5) 0.0427 (5) −0.0073 (4) −0.0006 (4) 0.0081 (4) O4 0.0445 (5) 0.0718 (7) 0.0530 (6) −0.0128 (5) −0.0049 (4) 0.0030 (5) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2071 .table-wrap} ----------------------- -------------- ----------------------- -------------- C1---N1 1.4798 (15) C14---H14 0.9300 C1---C12 1.5197 (19) C15---C16 1.369 (3) C1---C2 1.5237 (18) C15---H15 0.9300 C1---H1 0.9800 C16---C17 1.379 (2) C2---C3 1.4831 (19) C16---H16 0.9300 C2---H2A 0.9700 C17---H17 0.9300 C2---H2B 0.9700 C18---O2 1.2263 (16) C3---O1 1.3397 (15) C18---O3 1.3315 (17) C3---C4 1.3531 (18) C19---O3 1.4545 (16) C4---C18 1.4543 (18) C19---C20 1.484 (2) C4---C5 1.5145 (16) C19---H19A 0.9700 C5---N1 1.4751 (14) C19---H19B 0.9700 C5---C6 1.5315 (16) C20---H20A 0.9600 C5---H5 0.9800 C20---H20B 0.9600 C6---C7 1.3812 (19) C20---H20C 0.9600 C6---C11 1.3852 (18) C21---O4 1.2276 (15) C7---C8 1.385 (2) C21---N1 1.3597 (16) C7---H7 0.9300 C21---C22 1.4976 (17) C8---C9 1.367 (3) C22---C23 1.3833 (19) C8---H8 0.9300 C22---C27 1.3863 (18) C9---C10 1.372 (3) C23---C24 1.387 (2) C9---H9 0.9300 C23---H23 0.9300 C10---C11 1.383 (2) C24---C25 1.371 (2) C10---H10 0.9300 C24---H24 0.9300 C11---H11 0.9300 C25---C26 1.372 (2) C12---C17 1.3782 (19) C25---H25 0.9300 C12---C13 1.383 (2) C26---C27 1.382 (2) C13---C14 1.381 (3) C26---H26 0.9300 C13---H13 0.9300 C27---H27 0.9300 C14---C15 1.359 (3) O1---H1A 0.8200 N1---C1---C12 111.53 (9) C14---C15---C16 119.40 (17) N1---C1---C2 108.76 (10) C14---C15---H15 120.3 C12---C1---C2 114.90 (11) C16---C15---H15 120.3 N1---C1---H1 107.1 C15---C16---C17 120.01 (18) C12---C1---H1 107.1 C15---C16---H16 120.0 C2---C1---H1 107.1 C17---C16---H16 120.0 C3---C2---C1 113.62 (10) C12---C17---C16 121.14 (15) C3---C2---H2A 108.8 C12---C17---H17 119.4 C1---C2---H2A 108.8 C16---C17---H17 119.4 C3---C2---H2B 108.8 O2---C18---O3 122.55 (12) C1---C2---H2B 108.8 O2---C18---C4 124.16 (13) H2A---C2---H2B 107.7 O3---C18---C4 113.28 (11) O1---C3---C4 123.70 (12) O3---C19---C20 109.75 (14) O1---C3---C2 112.47 (11) O3---C19---H19A 109.7 C4---C3---C2 123.74 (11) C20---C19---H19A 109.7 C3---C4---C18 118.69 (11) O3---C19---H19B 109.7 C3---C4---C5 122.01 (11) C20---C19---H19B 109.7 C18---C4---C5 118.95 (11) H19A---C19---H19B 108.2 N1---C5---C4 109.42 (9) C19---C20---H20A 109.5 N1---C5---C6 113.34 (9) C19---C20---H20B 109.5 C4---C5---C6 115.47 (10) H20A---C20---H20B 109.5 N1---C5---H5 105.9 C19---C20---H20C 109.5 C4---C5---H5 105.9 H20A---C20---H20C 109.5 C6---C5---H5 105.9 H20B---C20---H20C 109.5 C7---C6---C11 118.09 (12) O4---C21---N1 122.22 (11) C7---C6---C5 122.82 (11) O4---C21---C22 118.89 (11) C11---C6---C5 118.96 (11) N1---C21---C22 118.87 (11) C6---C7---C8 121.02 (14) C23---C22---C27 119.20 (13) C6---C7---H7 119.5 C23---C22---C21 118.91 (12) C8---C7---H7 119.5 C27---C22---C21 121.59 (12) C9---C8---C7 120.12 (16) C22---C23---C24 120.09 (14) C9---C8---H8 119.9 C22---C23---H23 120.0 C7---C8---H8 119.9 C24---C23---H23 120.0 C8---C9---C10 119.73 (14) C25---C24---C23 120.07 (15) C8---C9---H9 120.1 C25---C24---H24 120.0 C10---C9---H9 120.1 C23---C24---H24 120.0 C9---C10---C11 120.26 (15) C24---C25---C26 120.31 (14) C9---C10---H10 119.9 C24---C25---H25 119.8 C11---C10---H10 119.9 C26---C25---H25 119.8 C10---C11---C6 120.77 (14) C25---C26---C27 120.03 (14) C10---C11---H11 119.6 C25---C26---H26 120.0 C6---C11---H11 119.6 C27---C26---H26 120.0 C17---C12---C13 118.23 (14) C26---C27---C22 120.27 (14) C17---C12---C1 118.10 (12) C26---C27---H27 119.9 C13---C12---C1 123.64 (13) C22---C27---H27 119.9 C14---C13---C12 120.02 (17) C21---N1---C5 118.15 (10) C14---C13---H13 120.0 C21---N1---C1 124.93 (10) C12---C13---H13 120.0 C5---N1---C1 116.82 (9) C15---C14---C13 121.17 (18) C3---O1---H1A 109.5 C15---C14---H14 119.4 C18---O3---C19 118.01 (12) C13---C14---H14 119.4 N1---C1---C2---C3 −39.33 (16) C1---C12---C17---C16 −179.77 (14) C12---C1---C2---C3 86.47 (15) C15---C16---C17---C12 0.1 (3) C1---C2---C3---O1 −170.79 (12) C3---C4---C18---O2 8.2 (2) C1---C2---C3---C4 12.3 (2) C5---C4---C18---O2 −178.52 (12) O1---C3---C4---C18 −3.4 (2) C3---C4---C18---O3 −170.63 (12) C2---C3---C4---C18 173.15 (13) C5---C4---C18---O3 2.68 (17) O1---C3---C4---C5 −176.51 (12) O4---C21---C22---C23 57.04 (17) C2---C3---C4---C5 0.1 (2) N1---C21---C22---C23 −124.55 (13) C3---C4---C5---N1 15.95 (16) O4---C21---C22---C27 −116.66 (15) C18---C4---C5---N1 −157.13 (11) N1---C21---C22---C27 61.75 (17) C3---C4---C5---C6 −113.35 (13) C27---C22---C23---C24 −1.6 (2) C18---C4---C5---C6 73.57 (14) C21---C22---C23---C24 −175.44 (13) N1---C5---C6---C7 −130.38 (13) C22---C23---C24---C25 1.5 (2) C4---C5---C6---C7 −3.03 (17) C23---C24---C25---C26 −0.3 (2) N1---C5---C6---C11 53.88 (14) C24---C25---C26---C27 −0.8 (2) C4---C5---C6---C11 −178.77 (11) C25---C26---C27---C22 0.6 (2) C11---C6---C7---C8 0.4 (2) C23---C22---C27---C26 0.5 (2) C5---C6---C7---C8 −175.42 (14) C21---C22---C27---C26 174.22 (13) C6---C7---C8---C9 −1.0 (3) O4---C21---N1---C5 11.51 (17) C7---C8---C9---C10 1.0 (3) C22---C21---N1---C5 −166.85 (10) C8---C9---C10---C11 −0.3 (3) O4---C21---N1---C1 −172.21 (11) C9---C10---C11---C6 −0.4 (2) C22---C21---N1---C1 9.43 (17) C7---C6---C11---C10 0.3 (2) C4---C5---N1---C21 129.05 (11) C5---C6---C11---C10 176.29 (13) C6---C5---N1---C21 −100.50 (12) N1---C1---C12---C17 −68.07 (15) C4---C5---N1---C1 −47.53 (13) C2---C1---C12---C17 167.57 (11) C6---C5---N1---C1 82.92 (12) N1---C1---C12---C13 113.98 (14) C12---C1---N1---C21 116.28 (12) C2---C1---C12---C13 −10.38 (18) C2---C1---N1---C21 −115.98 (13) C17---C12---C13---C14 1.8 (2) C12---C1---N1---C5 −67.39 (13) C1---C12---C13---C14 179.77 (16) C2---C1---N1---C5 60.35 (13) C12---C13---C14---C15 −0.4 (3) O2---C18---O3---C19 4.6 (2) C13---C14---C15---C16 −1.3 (3) C4---C18---O3---C19 −176.56 (12) C14---C15---C16---C17 1.4 (3) C20---C19---O3---C18 90.67 (17) C13---C12---C17---C16 −1.7 (2) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3206 .table-wrap} --------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1A···O2 0.82 1.85 2.570 (2) 146 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- --------- ------- ----------- ------------- O1---H1A⋯O2 0.82 1.85 2.570 (2) 146 :::	PubMed Central	2024-06-05T04:04:18.855678	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052159/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o540", "authors": [ { "first": "G.", "last": "Aridoss" }, { "first": "S.", "last": "Sundaramoorthy" }, { "first": "D.", "last": "Velmurugan" }, { "first": "Y. T.", "last": "Jeong" } ] }
PMC3052160	Related literature {#sec1} ================== For related structures, see: Li (2011[@bb2]); Liang (2008[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~3~H~10~N^+^·C~9~H~3~Cl~4~O~4~ ^−^M ~r~ = 377.03Monoclinic,a = 28.387 (3) Åb = 14.9600 (13) Åc = 7.8054 (6) Åβ = 93.216 (1)°V = 3309.5 (5) Å^3^Z = 8Mo Kα radiationμ = 0.73 mm^−1^T = 298 K0.47 × 0.32 × 0.23 mm ### Data collection {#sec2.1.2} Bruker SMART diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 1997[@bb1]) T ~min~ = 0.726, T ~max~ = 0.8518267 measured reflections2920 independent reflections1405 reflections with I \> 2σ(I)R ~int~ = 0.069 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.054wR(F ^2^) = 0.135S = 1.022920 reflections193 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e464} Data collection: SMART (Bruker, 1997[@bb1]); cell refinement: SAINT (Bruker, 1997[@bb1]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb4]) and PLATON (Spek, 2009[@bb5]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004879/ng5113sup1.cif](http://dx.doi.org/10.1107/S1600536811004879/ng5113sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004879/ng5113Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004879/ng5113Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5113&file=ng5113sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5113sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5113&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5113](http://scripts.iucr.org/cgi-bin/sendsup?ng5113)). The author thanks Shandong Provincial Natural Science Foundation, China (ZR2009BL027) for support. Comment ======= We have been studying synthesis of 4,5,6,7-tetrachloro-2-propylisoindoline-1,3-dione. In the present work, the reaction of 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoic acid and propylamine in methanol is expected to yield 4,5,6,7-tetrachloro-2-propylisoindoline-1,3-dione. However, the product is propylaminium 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoate (Scheme I, Fig. 1), the reason may be shorter time and cooler temperature in the reaction. The asymmetric unit of the title compound (I) contains one propylaminium cation and one 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoate anion (Fig. 1). The cation adopts N---C---C---C torsion angle of -178.6 (3) °, the dihedral angles of benzene ring with the methoxycarbonyl and carboxylate groups are 57.8 (3) and 62.5 (3) °, respectively, in the antion. The bond lengths and angles are in agreement with those in ethylammonium 2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate methanol solvate (Li, 2011) and in ethane-1,2-diammonium bis(2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate) methanol solvate (Liang, 2008). In the crystal structure the cations and anions are connected by intermolecular N---H···O hydrogen bonds into one-dimensional chains along \[001\](Fig. 2 and Table 1). Experimental {#experimental} ============ A mixture of 4,5,6,7-tetrachloroisobenzofuran-1,3-dione (2.86 g, 0.01 mol) and methanol (15 ml) was refluxed for 0.5 h. And then Propylamine (0.59 g, 0.01 mol) was added to the above solution, being mixed round for 10 min at room temperature. And then the solution was kept at room temperature for 5 d. Natural evaporation gave colourless single crystals of the title compound, suitable for X-ray analysis. Refinement {#refinement} ========== H atoms were initially located from difference maps and then refined in a riding model with C---H = 0.96--0.97 Å, N---H = 0.89 Å, O---H = 0.82Å and U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(O, N, methyl C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I), drawn with 30% probability ellipsoids. ::: ![](e-67-0o630-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of (I), viewed along c axis. Hydrogen bonds are indicated by dashed lines. ::: ![](e-67-0o630-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e113 .table-wrap} ------------------------------------ --------------------------------------- C~3~H~10~N^+^·C~9~H~3~Cl~4~O~4~^−^ F(000) = 1536 M~r~ = 377.03 D~x~ = 1.513 Mg m^−3^ Monoclinic, C2/c Mo Kα radiation, λ = 0.71073 Å a = 28.387 (3) Å Cell parameters from 1429 reflections b = 14.9600 (13) Å θ = 2.9--23.7° c = 7.8054 (6) Å µ = 0.73 mm^−1^ β = 93.216 (1)° T = 298 K V = 3309.5 (5) Å^3^ Block, colorless Z = 8 0.47 × 0.32 × 0.23 mm ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e249 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART diffractometer 2920 independent reflections Radiation source: fine-focus sealed tube 1405 reflections with I \> 2σ(I) graphite R~int~ = 0.069 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.6° Absorption correction: multi-scan (SADABS; Bruker, 1997) h = −23→33 T~min~ = 0.726, T~max~ = 0.851 k = −17→17 8267 measured reflections l = −9→9 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e366 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.054 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.135 H-atom parameters constrained S = 1.02 w = 1/\[σ^2^(F~o~^2^) + (0.0475P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 2920 reflections (Δ/σ)~max~ \< 0.001 193 parameters Δρ~max~ = 0.37 e Å^−3^ 0 restraints Δρ~min~ = −0.20 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e520 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e619 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cl1 0.50360 (3) 0.81553 (7) 0.52072 (18) 0.0958 (5) Cl2 0.55595 (5) 0.99424 (7) 0.6113 (3) 0.1375 (7) Cl3 0.66359 (4) 0.99436 (7) 0.6998 (2) 0.1342 (7) Cl4 0.72101 (4) 0.81799 (7) 0.68593 (18) 0.0961 (5) N1 0.44237 (10) 0.58365 (18) 0.4533 (4) 0.0630 (9) H1A 0.4637 0.6137 0.3968 0.095\ H1B 0.4443 0.5257 0.4286 0.095\* H1C 0.4480 0.5915 0.5657 0.095\* O1 0.68601 (9) 0.63305 (17) 0.7732 (4) 0.0749 (8) O2 0.66423 (10) 0.5995 (2) 0.5002 (4) 0.0908 (10) O3 0.56435 (9) 0.59345 (17) 0.6786 (4) 0.0749 (8) O4 0.54157 (9) 0.63029 (17) 0.4104 (4) 0.0710 (8) C1 0.66366 (13) 0.6473 (3) 0.6217 (7) 0.0604 (11) C2 0.56159 (12) 0.6450 (2) 0.5521 (6) 0.0530 (10) C3 0.63685 (11) 0.7345 (2) 0.6219 (5) 0.0527 (10) C4 0.58827 (12) 0.7341 (2) 0.5810 (5) 0.0522 (9) C5 0.56380 (12) 0.8150 (2) 0.5743 (5) 0.0665 (12) C6 0.58697 (14) 0.8952 (2) 0.6135 (6) 0.0797 (14) C7 0.63492 (14) 0.8952 (2) 0.6518 (6) 0.0779 (13) C8 0.66020 (12) 0.8156 (2) 0.6525 (5) 0.0619 (11) C9 0.71825 (15) 0.5576 (3) 0.7804 (7) 0.1017 (16) H9A 0.7007 0.5031 0.7637 0.153\* H9B 0.7352 0.5562 0.8904 0.153\* H9C 0.7402 0.5635 0.6919 0.153\* C10 0.39403 (12) 0.6172 (2) 0.4012 (5) 0.0634 (11) H10A 0.3714 0.5914 0.4756 0.076\* H10B 0.3856 0.5984 0.2846 0.076\* C11 0.39174 (14) 0.7179 (2) 0.4118 (5) 0.0731 (12) H11A 0.4139 0.7436 0.3354 0.088\* H11B 0.4010 0.7367 0.5278 0.088\* C12 0.34187 (16) 0.7531 (3) 0.3628 (6) 0.0944 (15) H12A 0.3335 0.7382 0.2454 0.142\* H12B 0.3413 0.8168 0.3767 0.142\* H12C 0.3197 0.7262 0.4357 0.142\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1066 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cl1 0.0429 (6) 0.0713 (7) 0.1698 (14) 0.0085 (5) −0.0226 (7) −0.0073 (7) Cl2 0.0788 (9) 0.0531 (7) 0.276 (2) 0.0161 (6) −0.0340 (11) −0.0109 (9) Cl3 0.0782 (9) 0.0619 (7) 0.259 (2) −0.0211 (6) −0.0221 (10) −0.0134 (9) Cl4 0.0379 (6) 0.0906 (8) 0.1587 (13) −0.0099 (5) −0.0041 (7) −0.0034 (8) N1 0.053 (2) 0.0559 (18) 0.080 (2) −0.0011 (15) 0.0030 (17) −0.0029 (17) O1 0.0562 (17) 0.0818 (19) 0.085 (2) 0.0207 (14) −0.0071 (16) 0.0062 (16) O2 0.087 (2) 0.090 (2) 0.094 (3) 0.0328 (17) −0.0111 (18) −0.0228 (19) O3 0.085 (2) 0.0574 (17) 0.083 (2) −0.0072 (14) 0.0046 (16) 0.0042 (16) O4 0.0572 (17) 0.0811 (19) 0.073 (2) −0.0115 (14) −0.0083 (15) −0.0113 (16) C1 0.041 (2) 0.059 (3) 0.081 (4) 0.0008 (19) −0.001 (2) 0.002 (2) C2 0.035 (2) 0.050 (2) 0.075 (3) −0.0007 (17) 0.005 (2) 0.000 (2) C3 0.039 (2) 0.048 (2) 0.071 (3) 0.0034 (18) −0.0019 (18) 0.0013 (19) C4 0.042 (2) 0.048 (2) 0.067 (3) −0.0035 (18) −0.0029 (18) 0.0037 (19) C5 0.038 (2) 0.054 (2) 0.106 (4) 0.0011 (18) −0.008 (2) −0.001 (2) C6 0.047 (3) 0.049 (2) 0.141 (4) 0.0082 (19) −0.010 (3) −0.002 (2) C7 0.053 (3) 0.049 (2) 0.130 (4) −0.009 (2) −0.009 (3) 0.002 (2) C8 0.033 (2) 0.062 (2) 0.090 (3) −0.0047 (18) −0.003 (2) 0.003 (2) C9 0.071 (3) 0.101 (3) 0.132 (4) 0.040 (3) −0.002 (3) 0.032 (3) C10 0.050 (2) 0.059 (2) 0.081 (3) −0.0034 (18) 0.000 (2) −0.002 (2) C11 0.076 (3) 0.062 (3) 0.081 (3) −0.005 (2) 0.000 (2) 0.002 (2) C12 0.080 (3) 0.087 (3) 0.115 (4) 0.022 (3) −0.005 (3) 0.005 (3) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1501 .table-wrap} -------------------- ------------ ---------------------- ------------ Cl1---C5 1.736 (3) C4---C5 1.396 (4) Cl2---C6 1.724 (4) C5---C6 1.393 (5) Cl3---C7 1.723 (4) C6---C7 1.377 (5) Cl4---C8 1.732 (3) C7---C8 1.391 (5) N1---C10 1.496 (4) C9---H9A 0.9600 N1---H1A 0.8900 C9---H9B 0.9600 N1---H1B 0.8900 C9---H9C 0.9600 N1---H1C 0.8900 C10---C11 1.510 (5) O1---C1 1.327 (5) C10---H10A 0.9700 O1---C9 1.453 (4) C10---H10B 0.9700 O2---C1 1.189 (4) C11---C12 1.538 (5) O3---C2 1.251 (4) C11---H11A 0.9700 O4---C2 1.234 (4) C11---H11B 0.9700 C1---C3 1.511 (5) C12---H12A 0.9600 C2---C4 1.544 (5) C12---H12B 0.9600 C3---C8 1.396 (4) C12---H12C 0.9600 C3---C4 1.398 (4) C10---N1---H1A 109.5 C7---C8---C3 120.2 (3) C10---N1---H1B 109.5 C7---C8---Cl4 119.5 (3) H1A---N1---H1B 109.5 C3---C8---Cl4 120.2 (3) C10---N1---H1C 109.5 O1---C9---H9A 109.5 H1A---N1---H1C 109.5 O1---C9---H9B 109.5 H1B---N1---H1C 109.5 H9A---C9---H9B 109.5 C1---O1---C9 115.3 (3) O1---C9---H9C 109.5 O2---C1---O1 126.0 (4) H9A---C9---H9C 109.5 O2---C1---C3 123.4 (4) H9B---C9---H9C 109.5 O1---C1---C3 110.7 (4) N1---C10---C11 111.2 (3) O4---C2---O3 127.1 (3) N1---C10---H10A 109.4 O4---C2---C4 118.8 (4) C11---C10---H10A 109.4 O3---C2---C4 114.1 (4) N1---C10---H10B 109.4 C8---C3---C4 119.7 (3) C11---C10---H10B 109.4 C8---C3---C1 121.1 (3) H10A---C10---H10B 108.0 C4---C3---C1 119.1 (3) C10---C11---C12 111.7 (3) C5---C4---C3 119.1 (3) C10---C11---H11A 109.3 C5---C4---C2 120.3 (3) C12---C11---H11A 109.3 C3---C4---C2 120.5 (3) C10---C11---H11B 109.3 C6---C5---C4 120.7 (3) C12---C11---H11B 109.3 C6---C5---Cl1 119.7 (3) H11A---C11---H11B 107.9 C4---C5---Cl1 119.6 (3) C11---C12---H12A 109.5 C7---C6---C5 119.8 (3) C11---C12---H12B 109.5 C7---C6---Cl2 120.0 (3) H12A---C12---H12B 109.5 C5---C6---Cl2 120.2 (3) C11---C12---H12C 109.5 C6---C7---C8 120.2 (3) H12A---C12---H12C 109.5 C6---C7---Cl3 119.8 (3) H12B---C12---H12C 109.5 C8---C7---Cl3 120.0 (3) C9---O1---C1---O2 7.9 (6) C4---C5---C6---C7 2.9 (7) C9---O1---C1---C3 −171.6 (3) Cl1---C5---C6---C7 −178.3 (4) O2---C1---C3---C8 −119.1 (4) C4---C5---C6---Cl2 −178.0 (3) O1---C1---C3---C8 60.5 (5) Cl1---C5---C6---Cl2 0.8 (6) O2---C1---C3---C4 57.3 (6) C5---C6---C7---C8 −0.4 (7) O1---C1---C3---C4 −123.1 (4) Cl2---C6---C7---C8 −179.5 (4) C8---C3---C4---C5 −1.0 (6) C5---C6---C7---Cl3 179.9 (4) C1---C3---C4---C5 −177.4 (4) Cl2---C6---C7---Cl3 0.7 (6) C8---C3---C4---C2 −178.1 (4) C6---C7---C8---C3 −2.8 (7) C1---C3---C4---C2 5.5 (6) Cl3---C7---C8---C3 176.9 (3) O4---C2---C4---C5 64.5 (5) C6---C7---C8---Cl4 175.4 (4) O3---C2---C4---C5 −117.7 (4) Cl3---C7---C8---Cl4 −4.9 (6) O4---C2---C4---C3 −118.5 (4) C4---C3---C8---C7 3.5 (6) O3---C2---C4---C3 59.3 (5) C1---C3---C8---C7 179.8 (4) C3---C4---C5---C6 −2.2 (6) C4---C3---C8---Cl4 −174.7 (3) C2---C4---C5---C6 174.9 (4) C1---C3---C8---Cl4 1.6 (5) C3---C4---C5---Cl1 179.1 (3) N1---C10---C11---C12 −178.6 (3) C2---C4---C5---Cl1 −3.8 (5) -------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2129 .table-wrap} -------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1A···O4 0.89 2.22 2.938 (4) 137 N1---H1A···O4^i^ 0.89 2.41 2.984 (4) 123 N1---H1B···O3^ii^ 0.89 1.98 2.845 (4) 164 N1---H1C···O3^iii^ 0.89 2.05 2.894 (4) 159 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, y, −z+1/2; (ii) −x+1, −y+1, −z+1; (iii) −x+1, y, −z+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------------- --------- ------- ----------- ------------- N1---H1A⋯O4 0.89 2.22 2.938 (4) 137 N1---H1A⋯O4^i^ 0.89 2.41 2.984 (4) 123 N1---H1B⋯O3^ii^ 0.89 1.98 2.845 (4) 164 N1---H1C⋯O3^iii^ 0.89 2.05 2.894 (4) 159 Symmetry codes: (i) ; (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.862848	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052160/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o630", "authors": [ { "first": "Jian", "last": "Li" } ] }
PMC3052161	Related literature {#sec1} ================== For the structure of dinuclear \[Pb(C~6~H~5~N~2~O~2~)~2~\]~2~, see: Najafi et al. (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Pb(C~6~H~5~N~2~O~2~)~2~(C~12~H~8~N~2~)\]M ~r~ = 661.63Monoclinic,a = 7.7033 (4) Åb = 15.9948 (8) Åc = 18.8929 (10) Åβ = 100.919 (1)°V = 2285.7 (2) Å^3^Z = 4Mo Kα radiationμ = 7.43 mm^−1^T = 100 K0.20 × 0.10 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb4]) T ~min~ = 0.318, T ~max~ = 0.52421418 measured reflections5233 independent reflections4676 reflections with I \> 2σ(I)R ~int~ = 0.028 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.018wR(F ^2^) = 0.047S = 0.915233 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.74 e Å^−3^Δρ~min~ = −0.53 e Å^−3^ {#d5e448} Data collection: APEX2 (Bruker, 2009[@bb2]); cell refinement: SAINT (Bruker, 2009[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: X-SEED (Barbour, 2001[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006787/bt5481sup1.cif](http://dx.doi.org/10.1107/S1600536811006787/bt5481sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006787/bt5481Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006787/bt5481Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5481&file=bt5481sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5481sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5481&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5481](http://scripts.iucr.org/cgi-bin/sendsup?bt5481)). We thank Shahid Beheshti University and the University of Malaya for supporting this study. Comment ======= The cupferronate ion is a common ion used for the complexation of metals; the lead(II) derivative exists as a dinuclear compound, the four cupferronate ions in dinuclear \[Pb(C~6~H~5~N~2~O~2~)~2~\]~2~O,O\'-chelate to the lead(II) atom, and two of the four nitroso O atoms are also involved in bridging. The geometry of both five-coordinate lead atoms is Ψ-octahedral; if another longer intermolecular Pb···O interactions (approx. 3.0 Å) are considered, the geometry is a Ψ-square-antiprism (Najafi et al., 2011). The 1,10-phenanthroline adduct is monomeric (Scheme I, Fig. 1). The two cupferronate ions and the N-heterocycle in mononuclear Pb(C~12~H~8~N~2~)(C~6~H~5~N~2~O~2~)~2~ chelate to the lead(II) atom; the geometry of the lead atom is a Ψ-pentagonal bipyramid. Experimental {#experimental} ============ Lead(II) nitrate (0.33 g, 1 mmol) dissolved in ethanol (20 ml) was added to the cupferron ligand (0.31 g, 2 mmol) and 1,10-phenanthroline hydrate (0.40, 2 mmol) dissolved in ethanol (20 ml). The mixture was stirred and then set aside for the growth of brown colored crystals. Refinement {#refinement} ========== Hydrogen atoms were placed in calculated positions (C--H 0.95 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2U~eq~(C). Omitted from the refinement were the following reflections owing to bad disagreement between the observed and calculated F^2^ values: (0 0 1), (0 1 2), (1 0 1), (0 0 2), (11 4 7), (-9 - 11 5), (11 3 8), (11 5 6), (-4 - 9 10), (-9 - 9 2) and (3 - 2 14). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of Pb(C12H8N2)(C6H5N2O2)2 at the 70% probability level. Hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0m378-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e193 .table-wrap} -------------------------------------------- --------------------------------------- \[Pb(C~6~H~5~N~2~O~2~)~2~(C~12~H~8~N~2~)\] F(000) = 1272 M~r~ = 661.63 D~x~ = 1.923 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 9896 reflections a = 7.7033 (4) Å θ = 2.2--28.3° b = 15.9948 (8) Å µ = 7.43 mm^−1^ c = 18.8929 (10) Å T = 100 K β = 100.919 (1)° Prism, brown V = 2285.7 (2) Å^3^ 0.20 × 0.10 × 0.10 mm Z = 4 -------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e337 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX diffractometer 5233 independent reflections Radiation source: fine-focus sealed tube 4676 reflections with I \> 2σ(I) graphite R~int~ = 0.028 ω scans θ~max~ = 27.5°, θ~min~ = 2.2° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −9→10 T~min~ = 0.318, T~max~ = 0.524 k = −20→18 21418 measured reflections l = −24→24 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e451 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.018 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.047 H-atom parameters constrained S = 0.91 w = 1/\[σ^2^(F~o~^2^) + (0.0315P)^2^ + 1.0382P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5233 reflections (Δ/σ)~max~ = 0.001 316 parameters Δρ~max~ = 0.74 e Å^−3^ 0 restraints Δρ~min~ = −0.53 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e610 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Pb1 0.545412 (12) 0.564925 (6) 0.707994 (5) 0.01407 (4) O1 0.6518 (3) 0.57008 (11) 0.83910 (10) 0.0215 (4) O2 0.6004 (3) 0.43217 (11) 0.77043 (10) 0.0221 (4) O3 0.3666 (2) 0.67625 (11) 0.74664 (10) 0.0171 (4) O4 0.2682 (2) 0.52341 (11) 0.72411 (10) 0.0168 (4) N1 0.6651 (3) 0.49786 (14) 0.87218 (11) 0.0167 (4) N2 0.6420 (3) 0.42654 (14) 0.84043 (12) 0.0207 (5) N3 0.2048 (3) 0.65180 (13) 0.74731 (10) 0.0123 (4) N4 0.1479 (3) 0.57674 (12) 0.73517 (11) 0.0139 (4) N5 0.4379 (3) 0.44824 (13) 0.60458 (12) 0.0156 (4) N6 0.3223 (3) 0.61102 (14) 0.58176 (11) 0.0160 (4) C1 0.7119 (4) 0.49851 (17) 0.94969 (14) 0.0189 (5) C2 0.6692 (4) 0.43069 (17) 0.98924 (15) 0.0228 (6) H2 0.6111 0.3831 0.9657 0.027\ C3 0.7135 (5) 0.43430 (18) 1.06373 (16) 0.0298 (7) H3 0.6877 0.3882 1.0917 0.036\* C4 0.7955 (5) 0.5050 (2) 1.09786 (15) 0.0355 (8) H4 0.8229 0.5075 1.1490 0.043\* C5 0.8371 (5) 0.57181 (19) 1.05735 (16) 0.0345 (8) H5 0.8947 0.6196 1.0808 0.041\* C6 0.7950 (4) 0.56902 (18) 0.98277 (15) 0.0254 (6) H6 0.8225 0.6147 0.9548 0.031\* C7 0.0758 (3) 0.71352 (15) 0.75744 (13) 0.0132 (5) C8 −0.0737 (3) 0.68857 (16) 0.78329 (13) 0.0159 (5) H8 −0.0865 0.6325 0.7980 0.019\* C9 −0.2042 (4) 0.74779 (17) 0.78711 (14) 0.0193 (5) H9 −0.3089 0.7319 0.8034 0.023\* C10 −0.1817 (4) 0.83009 (17) 0.76720 (14) 0.0211 (6) H10 −0.2722 0.8701 0.7686 0.025\* C11 −0.0270 (4) 0.85391 (16) 0.74523 (14) 0.0187 (5) H11 −0.0099 0.9108 0.7338 0.022\* C12 0.1030 (3) 0.79543 (15) 0.73976 (13) 0.0156 (5) H12 0.2084 0.8115 0.7242 0.019\* C13 0.4890 (4) 0.36929 (17) 0.61474 (14) 0.0195 (6) H13 0.5640 0.3550 0.6590 0.023\* C14 0.4390 (4) 0.30593 (17) 0.56419 (14) 0.0213 (6) H14 0.4786 0.2502 0.5743 0.026\* C15 0.3320 (4) 0.32538 (17) 0.49995 (14) 0.0202 (6) H15 0.2974 0.2832 0.4647 0.024\* C16 0.2737 (3) 0.40803 (17) 0.48634 (14) 0.0174 (5) C17 0.3300 (3) 0.46863 (17) 0.54094 (13) 0.0153 (5) C18 0.1582 (4) 0.43202 (17) 0.42116 (14) 0.0204 (6) H18 0.1205 0.3912 0.3850 0.024\* C19 0.1015 (4) 0.51195 (18) 0.41007 (14) 0.0198 (6) H19 0.0243 0.5263 0.3664 0.024\* C20 0.1563 (4) 0.57524 (16) 0.46329 (14) 0.0177 (5) C21 0.2698 (3) 0.55380 (16) 0.52921 (13) 0.0156 (5) C22 0.0991 (4) 0.65833 (18) 0.45407 (14) 0.0210 (6) H22 0.0237 0.6750 0.4106 0.025\* C23 0.1520 (4) 0.71536 (18) 0.50770 (14) 0.0217 (6) H23 0.1136 0.7718 0.5021 0.026\* C24 0.2643 (3) 0.68889 (17) 0.57130 (14) 0.0194 (5) H24 0.3002 0.7287 0.6085 0.023\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1302 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Pb1 0.01178 (6) 0.01599 (6) 0.01461 (5) −0.00027 (4) 0.00298 (4) −0.00125 (3) O1 0.0316 (12) 0.0155 (10) 0.0164 (9) −0.0056 (8) 0.0021 (8) 0.0018 (7) O2 0.0287 (12) 0.0188 (10) 0.0172 (9) 0.0091 (8) 0.0003 (8) −0.0034 (7) O3 0.0097 (8) 0.0152 (9) 0.0267 (9) −0.0040 (7) 0.0043 (7) −0.0032 (7) O4 0.0155 (9) 0.0112 (9) 0.0250 (9) 0.0015 (7) 0.0073 (7) −0.0010 (7) N1 0.0163 (11) 0.0166 (11) 0.0173 (10) 0.0003 (9) 0.0031 (8) 0.0008 (9) N2 0.0243 (13) 0.0184 (12) 0.0181 (11) 0.0058 (9) 0.0008 (9) −0.0022 (9) N3 0.0109 (10) 0.0117 (10) 0.0137 (9) 0.0006 (8) 0.0006 (8) 0.0003 (8) N4 0.0140 (11) 0.0102 (10) 0.0175 (10) −0.0011 (8) 0.0033 (8) 0.0001 (8) N5 0.0143 (11) 0.0172 (11) 0.0162 (10) 0.0009 (9) 0.0049 (9) 0.0002 (8) N6 0.0139 (11) 0.0187 (11) 0.0160 (10) 0.0012 (9) 0.0047 (8) 0.0001 (9) C1 0.0192 (14) 0.0211 (14) 0.0157 (12) 0.0002 (11) 0.0015 (10) 0.0006 (10) C2 0.0258 (16) 0.0186 (14) 0.0225 (14) −0.0020 (11) 0.0004 (11) 0.0013 (11) C3 0.043 (2) 0.0256 (16) 0.0197 (14) −0.0043 (14) 0.0019 (13) 0.0061 (11) C4 0.058 (2) 0.0329 (18) 0.0131 (13) −0.0125 (16) −0.0011 (13) 0.0020 (12) C5 0.053 (2) 0.0283 (17) 0.0179 (14) −0.0126 (15) −0.0028 (14) −0.0020 (12) C6 0.0319 (17) 0.0239 (16) 0.0197 (13) −0.0081 (12) 0.0031 (12) 0.0041 (11) C7 0.0126 (12) 0.0131 (12) 0.0128 (11) 0.0004 (9) −0.0002 (9) −0.0021 (9) C8 0.0152 (13) 0.0117 (12) 0.0204 (12) −0.0026 (10) 0.0025 (10) −0.0019 (10) C9 0.0158 (13) 0.0186 (14) 0.0237 (13) −0.0008 (11) 0.0041 (11) −0.0066 (10) C10 0.0202 (14) 0.0175 (13) 0.0249 (13) 0.0068 (11) 0.0023 (11) −0.0047 (11) C11 0.0245 (15) 0.0108 (12) 0.0193 (12) 0.0002 (11) 0.0007 (11) −0.0009 (10) C12 0.0167 (13) 0.0130 (12) 0.0163 (11) −0.0010 (10) 0.0010 (10) −0.0005 (10) C13 0.0178 (14) 0.0215 (14) 0.0202 (13) 0.0035 (11) 0.0059 (11) −0.0002 (11) C14 0.0225 (14) 0.0148 (13) 0.0288 (14) 0.0008 (11) 0.0100 (11) −0.0006 (11) C15 0.0197 (14) 0.0196 (14) 0.0230 (13) −0.0040 (11) 0.0082 (11) −0.0043 (11) C16 0.0140 (13) 0.0218 (13) 0.0186 (12) −0.0045 (11) 0.0085 (10) −0.0022 (10) C17 0.0101 (12) 0.0196 (13) 0.0175 (12) −0.0046 (10) 0.0059 (10) −0.0019 (10) C18 0.0192 (14) 0.0249 (15) 0.0180 (12) −0.0082 (11) 0.0060 (11) −0.0036 (11) C19 0.0163 (13) 0.0294 (15) 0.0135 (12) −0.0051 (11) 0.0020 (10) 0.0003 (10) C20 0.0145 (13) 0.0254 (15) 0.0146 (12) −0.0024 (11) 0.0062 (10) 0.0024 (10) C21 0.0127 (13) 0.0206 (14) 0.0152 (12) −0.0025 (10) 0.0068 (10) −0.0008 (10) C22 0.0143 (13) 0.0293 (15) 0.0188 (12) 0.0008 (11) 0.0018 (10) 0.0078 (11) C23 0.0207 (14) 0.0219 (15) 0.0238 (13) 0.0004 (11) 0.0073 (11) 0.0044 (11) C24 0.0198 (13) 0.0187 (13) 0.0212 (12) 0.0003 (11) 0.0080 (10) −0.0002 (10) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1958 .table-wrap} --------------------- -------------- ----------------------- -------------- Pb1---O4 2.3106 (18) C7---C8 1.392 (3) Pb1---O2 2.4270 (18) C8---C9 1.393 (4) Pb1---O3 2.4457 (17) C8---H8 0.9500 Pb1---O1 2.4586 (19) C9---C10 1.389 (4) Pb1---N5 2.715 (2) C9---H9 0.9500 Pb1---N6 2.763 (2) C10---C11 1.387 (4) O1---N1 1.308 (3) C10---H10 0.9500 O2---N2 1.304 (3) C11---C12 1.389 (4) O3---N3 1.309 (3) C11---H11 0.9500 O4---N4 1.305 (3) C12---H12 0.9500 N1---N2 1.285 (3) C13---C14 1.396 (4) N1---C1 1.440 (3) C13---H13 0.9500 N3---N4 1.284 (3) C14---C15 1.367 (4) N3---C7 1.439 (3) C14---H14 0.9500 N5---C13 1.326 (3) C15---C16 1.404 (4) N5---C17 1.365 (3) C15---H15 0.9500 N6---C24 1.325 (3) C16---C17 1.422 (4) N6---C21 1.354 (3) C16---C18 1.428 (4) C1---C6 1.386 (4) C17---C21 1.443 (4) C1---C2 1.392 (4) C18---C19 1.354 (4) C2---C3 1.385 (4) C18---H18 0.9500 C2---H2 0.9500 C19---C20 1.433 (4) C3---C4 1.392 (4) C19---H19 0.9500 C3---H3 0.9500 C20---C22 1.401 (4) C4---C5 1.387 (4) C20---C21 1.421 (4) C4---H4 0.9500 C22---C23 1.367 (4) C5---C6 1.385 (4) C22---H22 0.9500 C5---H5 0.9500 C23---C24 1.406 (4) C6---H6 0.9500 C23---H23 0.9500 C7---C12 1.378 (3) C24---H24 0.9500 O4---Pb1---O2 76.42 (7) C8---C7---N3 119.2 (2) O4---Pb1---O3 65.37 (6) C7---C8---C9 118.5 (2) O2---Pb1---O3 123.25 (6) C7---C8---H8 120.8 O4---Pb1---O1 90.97 (7) C9---C8---H8 120.8 O2---Pb1---O1 62.97 (6) C10---C9---C8 120.1 (2) O3---Pb1---O1 76.93 (6) C10---C9---H9 119.9 O4---Pb1---N5 74.56 (6) C8---C9---H9 119.9 O2---Pb1---N5 75.51 (6) C11---C10---C9 120.0 (2) O3---Pb1---N5 127.08 (6) C11---C10---H10 120.0 O1---Pb1---N5 138.25 (6) C9---C10---H10 120.0 O4---Pb1---N6 75.59 (6) C10---C11---C12 120.7 (2) O2---Pb1---N6 132.52 (7) C10---C11---H11 119.7 O3---Pb1---N6 76.70 (6) C12---C11---H11 119.7 O1---Pb1---N6 153.50 (7) C7---C12---C11 118.5 (2) N5---Pb1---N6 60.47 (6) C7---C12---H12 120.8 N1---O1---Pb1 115.64 (14) C11---C12---H12 120.8 N2---O2---Pb1 122.70 (14) N5---C13---C14 123.8 (3) N3---O3---Pb1 112.12 (13) N5---C13---H13 118.1 N4---O4---Pb1 122.37 (14) C14---C13---H13 118.1 N2---N1---O1 124.7 (2) C15---C14---C13 118.9 (3) N2---N1---C1 117.8 (2) C15---C14---H14 120.5 O1---N1---C1 117.5 (2) C13---C14---H14 120.5 N1---N2---O2 113.4 (2) C14---C15---C16 119.7 (2) N4---N3---O3 124.9 (2) C14---C15---H15 120.2 N4---N3---C7 116.4 (2) C16---C15---H15 120.2 O3---N3---C7 118.64 (19) C15---C16---C17 117.8 (2) N3---N4---O4 114.2 (2) C15---C16---C18 122.4 (2) C13---N5---C17 118.0 (2) C17---C16---C18 119.8 (3) C13---N5---Pb1 120.57 (17) N5---C17---C16 121.8 (2) C17---N5---Pb1 121.42 (16) N5---C17---C21 119.0 (2) C24---N6---C21 118.7 (2) C16---C17---C21 119.2 (2) C24---N6---Pb1 121.10 (17) C19---C18---C16 121.1 (2) C21---N6---Pb1 120.19 (16) C19---C18---H18 119.4 C6---C1---C2 121.9 (2) C16---C18---H18 119.4 C6---C1---N1 118.0 (2) C18---C19---C20 121.0 (2) C2---C1---N1 120.1 (2) C18---C19---H19 119.5 C3---C2---C1 118.4 (3) C20---C19---H19 119.5 C3---C2---H2 120.8 C22---C20---C21 117.7 (2) C1---C2---H2 120.8 C22---C20---C19 122.6 (2) C2---C3---C4 120.5 (3) C21---C20---C19 119.7 (2) C2---C3---H3 119.8 N6---C21---C20 121.9 (2) C4---C3---H3 119.8 N6---C21---C17 118.9 (2) C5---C4---C3 120.2 (3) C20---C21---C17 119.3 (2) C5---C4---H4 119.9 C23---C22---C20 119.9 (3) C3---C4---H4 119.9 C23---C22---H22 120.0 C6---C5---C4 120.1 (3) C20---C22---H22 120.0 C6---C5---H5 119.9 C22---C23---C24 118.8 (3) C4---C5---H5 119.9 C22---C23---H23 120.6 C1---C6---C5 119.0 (3) C24---C23---H23 120.6 C1---C6---H6 120.5 N6---C24---C23 123.1 (3) C5---C6---H6 120.5 N6---C24---H24 118.5 C12---C7---C8 122.1 (2) C23---C24---H24 118.5 C12---C7---N3 118.6 (2) O4---Pb1---O1---N1 68.29 (18) C1---C2---C3---C4 1.3 (5) O2---Pb1---O1---N1 −5.91 (16) C2---C3---C4---C5 −1.4 (6) O3---Pb1---O1---N1 132.71 (18) C3---C4---C5---C6 1.0 (6) N5---Pb1---O1---N1 0.7 (2) C2---C1---C6---C5 0.3 (5) N6---Pb1---O1---N1 126.70 (18) N1---C1---C6---C5 178.4 (3) O4---Pb1---O2---N2 −92.0 (2) C4---C5---C6---C1 −0.4 (5) O3---Pb1---O2---N2 −44.2 (2) N4---N3---C7---C12 −152.2 (2) O1---Pb1---O2---N2 6.17 (19) O3---N3---C7---C12 23.7 (3) N5---Pb1---O2---N2 −169.3 (2) N4---N3---C7---C8 26.5 (3) N6---Pb1---O2---N2 −147.37 (18) O3---N3---C7---C8 −157.6 (2) O4---Pb1---O3---N3 −7.02 (13) C12---C7---C8---C9 3.9 (4) O2---Pb1---O3---N3 −59.47 (16) N3---C7---C8---C9 −174.7 (2) O1---Pb1---O3---N3 −104.23 (15) C7---C8---C9---C10 −1.7 (4) N5---Pb1---O3---N3 37.44 (17) C8---C9---C10---C11 −1.7 (4) N6---Pb1---O3---N3 73.02 (14) C9---C10---C11---C12 2.9 (4) O2---Pb1---O4---N4 146.36 (18) C8---C7---C12---C11 −2.7 (4) O3---Pb1---O4---N4 9.37 (16) N3---C7---C12---C11 176.0 (2) O1---Pb1---O4---N4 84.50 (17) C10---C11---C12---C7 −0.8 (4) N5---Pb1---O4---N4 −135.20 (18) C17---N5---C13---C14 0.0 (4) N6---Pb1---O4---N4 −72.39 (17) Pb1---N5---C13---C14 179.90 (19) Pb1---O1---N1---N2 6.5 (3) N5---C13---C14---C15 0.5 (4) Pb1---O1---N1---C1 −174.66 (17) C13---C14---C15---C16 −0.5 (4) O1---N1---N2---O2 −1.0 (4) C14---C15---C16---C17 0.2 (4) C1---N1---N2---O2 −179.9 (2) C14---C15---C16---C18 −178.3 (2) Pb1---O2---N2---N1 −5.4 (3) C13---N5---C17---C16 −0.4 (4) Pb1---O3---N3---N4 5.5 (3) Pb1---N5---C17---C16 179.72 (17) Pb1---O3---N3---C7 −170.04 (15) C13---N5---C17---C21 178.8 (2) O3---N3---N4---O4 2.4 (3) Pb1---N5---C17---C21 −1.1 (3) C7---N3---N4---O4 177.98 (19) C15---C16---C17---N5 0.3 (4) Pb1---O4---N4---N3 −10.2 (3) C18---C16---C17---N5 178.9 (2) O4---Pb1---N5---C13 −96.9 (2) C15---C16---C17---C21 −178.9 (2) O2---Pb1---N5---C13 −17.25 (19) C18---C16---C17---C21 −0.3 (4) O3---Pb1---N5---C13 −138.21 (18) C15---C16---C18---C19 178.8 (3) O1---Pb1---N5---C13 −23.3 (2) C17---C16---C18---C19 0.3 (4) N6---Pb1---N5---C13 −178.8 (2) C16---C18---C19---C20 0.3 (4) O4---Pb1---N5---C17 83.03 (18) C18---C19---C20---C22 −179.3 (3) O2---Pb1---N5---C17 162.6 (2) C18---C19---C20---C21 −0.9 (4) O3---Pb1---N5---C17 41.7 (2) C24---N6---C21---C20 0.6 (4) O1---Pb1---N5---C17 156.59 (17) Pb1---N6---C21---C20 −179.48 (18) N6---Pb1---N5---C17 1.10 (17) C24---N6---C21---C17 −178.8 (2) O4---Pb1---N6---C24 98.62 (19) Pb1---N6---C21---C17 1.0 (3) O2---Pb1---N6---C24 154.25 (17) C22---C20---C21---N6 −0.1 (4) O3---Pb1---N6---C24 31.04 (18) C19---C20---C21---N6 −178.6 (2) O1---Pb1---N6---C24 37.1 (3) C22---C20---C21---C17 179.4 (2) N5---Pb1---N6---C24 178.8 (2) C19---C20---C21---C17 0.9 (4) O4---Pb1---N6---C21 −81.27 (18) N5---C17---C21---N6 0.0 (3) O2---Pb1---N6---C21 −25.6 (2) C16---C17---C21---N6 179.2 (2) O3---Pb1---N6---C21 −148.84 (19) N5---C17---C21---C20 −179.5 (2) O1---Pb1---N6---C21 −142.83 (17) C16---C17---C21---C20 −0.3 (4) N5---Pb1---N6---C21 −1.08 (17) C21---C20---C22---C23 −0.4 (4) N2---N1---C1---C6 158.2 (3) C19---C20---C22---C23 178.1 (2) O1---N1---C1---C6 −20.8 (4) C20---C22---C23---C24 0.3 (4) N2---N1---C1---C2 −23.7 (4) C21---N6---C24---C23 −0.7 (4) O1---N1---C1---C2 157.4 (3) Pb1---N6---C24---C23 179.37 (18) C6---C1---C2---C3 −0.7 (5) C22---C23---C24---N6 0.3 (4) N1---C1---C2---C3 −178.8 (3) --------------------- -------------- ----------------------- -------------- :::	PubMed Central	2024-06-05T04:04:18.867365	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052161/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m378", "authors": [ { "first": "Ezzatollah", "last": "Najafi" }, { "first": "Mostafa M.", "last": "Amini" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052162	Related literature {#sec1} ================== For background to the synthesis: see: Yadigarov et al. (2010[@bb7]). For the structure of tolperisone hydrochloride, see: Tanaka & Hirayama (2007[@bb5]). For a related structure, see: Maharramov et al. (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~17~H~27~NOM ~r~ = 261.40Monoclinic,a = 11.7992 (12) Åb = 8.0940 (8) Åc = 17.0196 (17) Åβ = 107.489 (1)°V = 1550.3 (3) Å^3^Z = 4Mo Kα radiationμ = 0.07 mm^−1^T = 100 K0.30 × 0.20 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometer6615 measured reflections3537 independent reflections2964 reflections with I \> 2σ(I)R ~int~ = 0.016 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.040wR(F ^2^) = 0.110S = 1.023537 reflections179 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.36 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e377} Data collection: APEX2 (Bruker, 2005[@bb2]); cell refinement: SAINT (Bruker, 2005[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: X-SEED (Barbour, 2001[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006568/bt5478sup1.cif](http://dx.doi.org/10.1107/S1600536811006568/bt5478sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006568/bt5478Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006568/bt5478Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5478&file=bt5478sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5478sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5478&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5478](http://scripts.iucr.org/cgi-bin/sendsup?bt5478)). We thank Baku State University and the University of Malaya for supporting this study. Comment ======= A recent study reported the reaction of 1-chloro-3-(2,4,6-trimethylphenyl)propan-2-one and primary amines. The chlorine atom in the α-chloro ketone is not replaced directly by the amino RNH-- group; the intermediate product undergoes a Favorskii rearrangement that furnishes a compound having two methylene groups between the aromatic system and the amido unit (Yadigarov et al., 2010). A recent study used thiourea as the amino reactant (Maharramov et al., 2011). The present study employs a cyclic secondary amine as the amino reactant in the synthesis of a compound having a formulation similar to that of tolperisone (a piperidine derivative that is commercially used as a muscle relaxant), which has been characterized as a hydrochloride (Tanaka & Hirayama, 2007). The title compound, C~17~H~27~NO, (Scheme I) is a bufferfly-shaped substituted 2-propanol having an aromatic ring on one carbon end and a piperidinyl ring on the other. The hydroxy group interacts with the N atom of an inversion-related molecule to generate a hydrogen-bonded dimer (Fig. 1). Experimental {#experimental} ============ 1-Chloro-3-(2,4,6-trimethylphenyl)propan-2-one (1 mol) and piperidine (1 mmol) were stirred in water for 18 h at 53 K. The water was decanted and the oil was distilled in vacuum. The distallate was a liquid; the liquid crystallized after 6 months; yield 70%. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C--H 0.95 to 0.99 Å; U(H) 1.2 to 1.5U(C)\] and were included in the refinement in the riding model approximation, with U(H) set to 1.2 to 1.5U(C). The hydroxy H-atom was located in a difference Fourier map, and was refined with a distance restraint of O--H 0.84±0.01 Å. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of the hydrogen-bonded dimeric structure of C17H27NO at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o739-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e123 .table-wrap} ------------------------- --------------------------------------- C~17~H~27~NO F(000) = 576 M~r~ = 261.40 D~x~ = 1.120 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 1896 reflections a = 11.7992 (12) Å θ = 2.8--29.2° b = 8.0940 (8) Å µ = 0.07 mm^−1^ c = 17.0196 (17) Å T = 100 K β = 107.489 (1)° Prism, colorless V = 1550.3 (3) Å^3^ 0.30 × 0.20 × 0.20 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e248 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII diffractometer 2964 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.016 graphite θ~max~ = 27.5°, θ~min~ = 2.5° φ and ω scans h = −13→15 6615 measured reflections k = −8→10 3537 independent reflections l = −15→22 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e346 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.040 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.110 H atoms treated by a mixture of independent and constrained refinement S = 1.02 w = 1/\[σ^2^(F~o~^2^) + (0.0565P)^2^ + 0.4799P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3537 reflections (Δ/σ)~max~ = 0.001 179 parameters Δρ~max~ = 0.36 e Å^−3^ 1 restraint Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e505 .table-wrap} ------ --------------- -------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ O1 0.42350 (7) 0.36548 (10) 0.53159 (5) 0.0213 (2) H1 0.4165 (15) 0.373 (2) 0.4804 (6) 0.042 (5)\ N1 0.54620 (8) 0.67399 (12) 0.62908 (6) 0.0164 (2) C1 0.64459 (10) 0.66941 (15) 0.70653 (7) 0.0196 (2) H1A 0.6716 0.5539 0.7190 0.023\* H1B 0.6161 0.7100 0.7522 0.023\* C2 0.74826 (10) 0.77528 (15) 0.70081 (7) 0.0219 (3) H2A 0.7807 0.7296 0.6580 0.026\* H2B 0.8121 0.7723 0.7541 0.026\* C3 0.70960 (11) 0.95379 (15) 0.67944 (7) 0.0229 (3) H3A 0.7759 1.0172 0.6697 0.027\* H3B 0.6890 1.0054 0.7261 0.027\* C4 0.60210 (11) 0.95923 (15) 0.60243 (7) 0.0225 (3) H4A 0.5717 1.0738 0.5930 0.027\* H4B 0.6263 0.9249 0.5540 0.027\* C5 0.50422 (10) 0.84561 (14) 0.61153 (7) 0.0196 (2) H5A 0.4751 0.8863 0.6568 0.024\* H5B 0.4369 0.8481 0.5601 0.024\* C6 0.44843 (10) 0.56903 (15) 0.63656 (7) 0.0194 (2) H6A 0.4001 0.6329 0.6644 0.023\* H6B 0.4825 0.4734 0.6721 0.023\* C7 0.36711 (10) 0.50483 (14) 0.55465 (7) 0.0173 (2) H7 0.3549 0.5928 0.5116 0.021\* C8 0.24722 (10) 0.45733 (15) 0.56663 (7) 0.0186 (2) H8A 0.2625 0.3806 0.6140 0.022\* H8B 0.2107 0.5583 0.5813 0.022\* C9 0.15852 (10) 0.37740 (14) 0.49344 (7) 0.0162 (2) C10 0.08491 (10) 0.47543 (14) 0.43015 (7) 0.0170 (2) C11 −0.00046 (10) 0.40041 (14) 0.36511 (7) 0.0177 (2) H11 −0.0496 0.4676 0.3226 0.021\* C12 −0.01591 (10) 0.22964 (14) 0.36054 (7) 0.0175 (2) C13 0.05775 (10) 0.13441 (14) 0.42312 (7) 0.0178 (2) H13 0.0488 0.0177 0.4209 0.021\* C14 0.14458 (10) 0.20477 (14) 0.48924 (7) 0.0172 (2) C15 0.21904 (11) 0.09380 (15) 0.55627 (7) 0.0229 (3) H15A 0.2038 −0.0219 0.5394 0.034\* H15B 0.1984 0.1125 0.6072 0.034\* H15C 0.3034 0.1187 0.5657 0.034\* C16 −0.11163 (11) 0.15251 (15) 0.29073 (7) 0.0245 (3) H16A −0.0934 0.0354 0.2861 0.037\* H16B −0.1153 0.2092 0.2391 0.037\* H16C −0.1884 0.1627 0.3015 0.037\* C17 0.09396 (11) 0.66162 (14) 0.43230 (8) 0.0213 (3) H17A 0.0326 0.7081 0.3851 0.032\* H17B 0.1726 0.6948 0.4297 0.032\* H17C 0.0825 0.7028 0.4835 0.032\* ------ --------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1113 .table-wrap} ----- ------------ ------------ ------------ ------------- ------------ ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O1 0.0219 (4) 0.0226 (4) 0.0206 (4) 0.0023 (3) 0.0080 (4) −0.0009 (3) N1 0.0141 (4) 0.0170 (5) 0.0163 (5) −0.0008 (4) 0.0017 (4) 0.0007 (4) C1 0.0176 (5) 0.0214 (6) 0.0169 (5) −0.0004 (4) 0.0010 (4) 0.0011 (4) C2 0.0172 (6) 0.0247 (6) 0.0214 (6) −0.0025 (5) 0.0022 (4) −0.0019 (5) C3 0.0249 (6) 0.0212 (6) 0.0227 (6) −0.0065 (5) 0.0074 (5) −0.0038 (5) C4 0.0275 (6) 0.0180 (5) 0.0216 (6) −0.0005 (5) 0.0066 (5) 0.0007 (5) C5 0.0189 (6) 0.0187 (5) 0.0194 (6) 0.0029 (4) 0.0028 (4) 0.0000 (4) C6 0.0185 (6) 0.0233 (6) 0.0164 (5) −0.0042 (4) 0.0050 (4) −0.0009 (4) C7 0.0161 (5) 0.0185 (5) 0.0169 (5) −0.0018 (4) 0.0045 (4) −0.0011 (4) C8 0.0175 (5) 0.0210 (5) 0.0179 (5) −0.0027 (4) 0.0064 (4) −0.0035 (4) C9 0.0142 (5) 0.0177 (5) 0.0180 (5) −0.0015 (4) 0.0067 (4) −0.0027 (4) C10 0.0167 (5) 0.0156 (5) 0.0205 (6) −0.0002 (4) 0.0083 (4) −0.0012 (4) C11 0.0157 (5) 0.0185 (5) 0.0186 (5) 0.0011 (4) 0.0048 (4) 0.0012 (4) C12 0.0158 (5) 0.0193 (5) 0.0181 (5) −0.0018 (4) 0.0059 (4) −0.0024 (4) C13 0.0192 (6) 0.0140 (5) 0.0214 (6) −0.0017 (4) 0.0079 (5) −0.0014 (4) C14 0.0164 (5) 0.0174 (5) 0.0187 (5) 0.0009 (4) 0.0068 (4) 0.0015 (4) C15 0.0227 (6) 0.0204 (6) 0.0236 (6) 0.0005 (5) 0.0040 (5) 0.0033 (5) C16 0.0256 (6) 0.0236 (6) 0.0209 (6) −0.0052 (5) 0.0017 (5) −0.0025 (5) C17 0.0226 (6) 0.0152 (5) 0.0261 (6) −0.0010 (4) 0.0072 (5) −0.0009 (4) ----- ------------ ------------ ------------ ------------- ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1495 .table-wrap} -------------------- -------------- ----------------------- -------------- O1---C7 1.4233 (14) C8---C9 1.5106 (15) O1---H1 0.852 (9) C8---H8A 0.9900 N1---C6 1.4687 (14) C8---H8B 0.9900 N1---C1 1.4720 (14) C9---C14 1.4062 (15) N1---C5 1.4749 (14) C9---C10 1.4079 (16) C1---C2 1.5205 (16) C10---C11 1.3923 (15) C1---H1A 0.9900 C10---C17 1.5104 (15) C1---H1B 0.9900 C11---C12 1.3933 (16) C2---C3 1.5258 (17) C11---H11 0.9500 C2---H2A 0.9900 C12---C13 1.3883 (16) C2---H2B 0.9900 C12---C16 1.5068 (15) C3---C4 1.5262 (17) C13---C14 1.3955 (16) C3---H3A 0.9900 C13---H13 0.9500 C3---H3B 0.9900 C14---C15 1.5092 (16) C4---C5 1.5203 (17) C15---H15A 0.9800 C4---H4A 0.9900 C15---H15B 0.9800 C4---H4B 0.9900 C15---H15C 0.9800 C5---H5A 0.9900 C16---H16A 0.9800 C5---H5B 0.9900 C16---H16B 0.9800 C6---C7 1.5265 (15) C16---H16C 0.9800 C6---H6A 0.9900 C17---H17A 0.9800 C6---H6B 0.9900 C17---H17B 0.9800 C7---C8 1.5375 (15) C17---H17C 0.9800 C7---H7 1.0000 C7---O1---H1 108.5 (12) C6---C7---H7 109.8 C6---N1---C1 109.65 (9) C8---C7---H7 109.8 C6---N1---C5 109.73 (9) C9---C8---C7 115.77 (9) C1---N1---C5 109.36 (9) C9---C8---H8A 108.3 N1---C1---C2 111.20 (9) C7---C8---H8A 108.3 N1---C1---H1A 109.4 C9---C8---H8B 108.3 C2---C1---H1A 109.4 C7---C8---H8B 108.3 N1---C1---H1B 109.4 H8A---C8---H8B 107.4 C2---C1---H1B 109.4 C14---C9---C10 119.03 (10) H1A---C1---H1B 108.0 C14---C9---C8 120.59 (10) C1---C2---C3 111.12 (10) C10---C9---C8 120.32 (10) C1---C2---H2A 109.4 C11---C10---C9 119.67 (10) C3---C2---H2A 109.4 C11---C10---C17 118.91 (10) C1---C2---H2B 109.4 C9---C10---C17 121.40 (10) C3---C2---H2B 109.4 C10---C11---C12 121.89 (11) H2A---C2---H2B 108.0 C10---C11---H11 119.1 C2---C3---C4 110.11 (10) C12---C11---H11 119.1 C2---C3---H3A 109.6 C13---C12---C11 117.82 (10) C4---C3---H3A 109.6 C13---C12---C16 121.53 (10) C2---C3---H3B 109.6 C11---C12---C16 120.64 (10) C4---C3---H3B 109.6 C12---C13---C14 122.05 (10) H3A---C3---H3B 108.2 C12---C13---H13 119.0 C5---C4---C3 110.84 (10) C14---C13---H13 119.0 C5---C4---H4A 109.5 C13---C14---C9 119.52 (10) C3---C4---H4A 109.5 C13---C14---C15 119.10 (10) C5---C4---H4B 109.5 C9---C14---C15 121.35 (10) C3---C4---H4B 109.5 C14---C15---H15A 109.5 H4A---C4---H4B 108.1 C14---C15---H15B 109.5 N1---C5---C4 111.78 (9) H15A---C15---H15B 109.5 N1---C5---H5A 109.3 C14---C15---H15C 109.5 C4---C5---H5A 109.3 H15A---C15---H15C 109.5 N1---C5---H5B 109.3 H15B---C15---H15C 109.5 C4---C5---H5B 109.3 C12---C16---H16A 109.5 H5A---C5---H5B 107.9 C12---C16---H16B 109.5 N1---C6---C7 114.35 (9) H16A---C16---H16B 109.5 N1---C6---H6A 108.7 C12---C16---H16C 109.5 C7---C6---H6A 108.7 H16A---C16---H16C 109.5 N1---C6---H6B 108.7 H16B---C16---H16C 109.5 C7---C6---H6B 108.7 C10---C17---H17A 109.5 H6A---C6---H6B 107.6 C10---C17---H17B 109.5 O1---C7---C6 107.70 (9) H17A---C17---H17B 109.5 O1---C7---C8 111.31 (9) C10---C17---H17C 109.5 C6---C7---C8 108.36 (9) H17A---C17---H17C 109.5 O1---C7---H7 109.8 H17B---C17---H17C 109.5 C6---N1---C1---C2 179.35 (9) C14---C9---C10---C11 0.41 (16) C5---N1---C1---C2 −60.29 (12) C8---C9---C10---C11 −176.83 (10) N1---C1---C2---C3 57.57 (13) C14---C9---C10---C17 178.63 (10) C1---C2---C3---C4 −52.80 (13) C8---C9---C10---C17 1.39 (16) C2---C3---C4---C5 52.23 (13) C9---C10---C11---C12 0.14 (17) C6---N1---C5---C4 −179.48 (9) C17---C10---C11---C12 −178.12 (11) C1---N1---C5---C4 60.20 (12) C10---C11---C12---C13 −0.52 (17) C3---C4---C5---N1 −56.81 (13) C10---C11---C12---C16 178.08 (10) C1---N1---C6---C7 −155.49 (10) C11---C12---C13---C14 0.34 (16) C5---N1---C6---C7 84.37 (12) C16---C12---C13---C14 −178.24 (11) N1---C6---C7---O1 81.03 (12) C12---C13---C14---C9 0.20 (17) N1---C6---C7---C8 −158.46 (9) C12---C13---C14---C15 178.26 (10) O1---C7---C8---C9 −56.80 (13) C10---C9---C14---C13 −0.57 (16) C6---C7---C8---C9 −175.04 (10) C8---C9---C14---C13 176.66 (10) C7---C8---C9---C14 98.81 (13) C10---C9---C14---C15 −178.59 (10) C7---C8---C9---C10 −84.00 (13) C8---C9---C14---C15 −1.36 (16) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2315 .table-wrap} ----------------- ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1···N1^i^ 0.85 (1) 2.07 (1) 2.880 (1) 158.(2) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+1, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------- ---------- ---------- ----------- ------------- O1---H1⋯N1^i^ 0.85 (1) 2.07 (1) 2.880 (1) 158 (2) Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.874164	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052162/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o739", "authors": [ { "first": "Abel M.", "last": "Maharramov" }, { "first": "Ali N.", "last": "Khalilov" }, { "first": "Atash V.", "last": "Gurbanov" }, { "first": "Mirze A.", "last": "Allahverdiyev" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052163	Related literature {#sec1} ================== For related structures, see: Bikas et al. (2010[@bb1]); Silva et al. (2006[@bb5]); Zimmer et al. (1959[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~16~N~2~O~3~SM ~r~ = 340.40Monoclinic,a = 15.740 (3) Åb = 10.573 (2) Åc = 10.322 (2) Åβ = 103.86 (3)°V = 1667.8 (6) Å^3^Z = 4Mo Kα radiationμ = 0.21 mm^−1^T = 298 K0.35 × 0.25 × 0.2 mm ### Data collection {#sec2.1.2} Stoe IPDS 2T diffractometerAbsorption correction: numerical (X-SHAPE; Stoe & Cie, 2005[@bb6]) T ~min~ = 0.935, T ~max~ = 0.95713245 measured reflections4474 independent reflections2439 reflections with I \> 2σ(I)R ~int~ = 0.080 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.053wR(F ^2^) = 0.143S = 0.924474 reflections219 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.28 e Å^−3^ {#d5e514} Data collection: X-AREA (Stoe & Cie, 2005[@bb6]); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb2]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb3]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006088/vm2077sup1.cif](http://dx.doi.org/10.1107/S1600536811006088/vm2077sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006088/vm2077Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006088/vm2077Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?vm2077&file=vm2077sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?vm2077sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?vm2077&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [VM2077](http://scripts.iucr.org/cgi-bin/sendsup?vm2077)). The authors are grateful to the Islamic Azad University, Tabriz Branch, and Shahid Beheshti University for financial support. Comment ======= Sulfonyl hydrazones are found to exhibit large medicinal applications. Similar to sulfonamides, sulfonyl hydrazones also have various biological activities. For example, imidosulfonylhydrazones have antibacterial and antineociceptive properties (Silva et al., 2006). Acidic sulfonyl hydrazone derivatives have analgesic and anti-inflammatory activities. 4-Substituted benzenesulfonylhydrazone has been found to have antibacterial activity (Zimmer et al., 1959). As part of our studies on the synthesis and characterization of hydrazone derivatives (Bikas et al., 2010), we report here the crystal structure of (E)-N\'-((2-hydroxynaphthalen-1-yl)methylene)-4-methylbenzenesulfonohydrazide. The asymmetric unit of the title compound contains one molecule, which is shown in Fig. 1. The packing diagram of the title compound is shown in Fig. 2. The structure is stabilized by an intramolecular O---H···N hydrogen bond, with the nitrogen of the azomethine group (--C=N--) acting as hydrogen bond acceptor and intermolecular N---H···O hydrogen bonds with the S=O group as hydrogen bond acceptor (Table 1 and Fig. 2). The packing is characterized by a π-π interaction between the naphthyl rings (Fig. 3) with Cg2···Cg3^ii^ distance = 3.7556 (15) Å where Cg2 and Cg3 are the centroids of C9-C13/C18 and C13-C18, respectively (symmetry code ii: -x,1 - y,-z). Furthermore, C---H~naphthyl~···π~tolyl~ and C---H~naphthyl~···π~naphthyl~ interactions are observed with distances equal to 2.72 and 2.75 Å, respectively (Table 1 & Fig. 3). Experimental {#experimental} ============ All reagents were commercially available and used as received. A methanol (10 ml) solution of 2-hydroxy-1-naphtaldehyde (1.63 mmol) was dropwise added to a methanol solution (10 ml) of 4-methyl-benzenesulfonic acid hydrazide (1.63 mmol), and the mixture was refluxed for 3 hrs. Then the solution was evaporated on a steam bath to 5 ml and cooled to room temperature. A yellow precipitate of the title compound was separated and filtered off, washed with 5 ml of cooled methanol and then dried in air. X-ray quality crystals of the title compound were obtained from methanol by slow solvent evaporation. Yield: 81%, mp: 167.8--168.2 °C. Refinement {#refinement} ========== The hydrogen atom of N---H and O---H group were positioned geometrically and refined as riding atoms with, N---H = 0.86 Å and Uiso(H) = 1.2 Ueq(N) and O---H = 0.82 Å and Uiso(H) = 1.5 Ueq(O). The C---H protons were positioned geometrically and refined as riding atoms with C---H = 0.93 Å and Uiso(H) = 1.2 Ueq(C) for imine and aromatic C---H groups and C---H = 0.96 Å and Uiso(H) = 1.5 Ueq(C) for methyl group. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, with atom labels and anisotropic displacement ellipsoids (drawn at 30% probability level) for non-H atoms. ::: ![](e-67-0o713-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram of the title compound. Hydrogen bonds are shown as blue dashed line. ::: ![](e-67-0o713-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The packing diagram of the title compound showing π-π and C---H···π interactions as blue and orange dashed lines, respectively. Cg1, Cg2 and Cg3 are the centroids of rings C1-C3/C5-C7, C9-C13/C18 and C13-C18, respectively; symmetry codes: (i) x, -y + 1/2, z - 1/2; (ii) -x, -y + 1, -z.). ::: ![](e-67-0o713-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e221 .table-wrap} ------------------------- --------------------------------------- C~18~H~16~N~2~O~3~S F(000) = 712 M~r~ = 340.40 D~x~ = 1.356 Mg m^−3^ Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 4474 reflections a = 15.740 (3) Å θ = 2.3--29.2° b = 10.573 (2) Å µ = 0.21 mm^−1^ c = 10.322 (2) Å T = 298 K β = 103.86 (3)° Plate, yellow V = 1667.8 (6) Å^3^ 0.35 × 0.25 × 0.2 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ---------------------------------------------------------------- -------------------------------------- Stoe IPDS 2T diffractometer 4474 independent reflections Radiation source: fine-focus sealed tube 2439 reflections with I \> 2σ(I) graphite R~int~ = 0.080 Detector resolution: 0.15 mm pixels mm^-1^ θ~max~ = 29.2°, θ~min~ = 2.3° rotation method scans h = −21→21 Absorption correction: numerical (X-SHAPE; Stoe & Cie, 2005) k = −14→13 T~min~ = 0.935, T~max~ = 0.957 l = −13→14 13245 measured reflections ---------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e470 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.053 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.143 H-atom parameters constrained S = 0.92 w = 1/\[σ^2^(F~o~^2^) + (0.0771P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 4474 reflections (Δ/σ)~max~ \< 0.001 219 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.28 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e624 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e723 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C6 0.41858 (14) 0.4904 (3) 0.3196 (2) 0.0705 (8) H6 0.4426 0.4414 0.2626 0.085\ S1 0.34568 (3) 0.27206 (7) 0.38051 (5) 0.0577 (2) O2 0.31790 (11) 0.23002 (19) 0.49498 (15) 0.0713 (5) N1 0.26101 (10) 0.25594 (19) 0.25177 (17) 0.0534 (5) H1A 0.2632 0.2147 0.1808 0.064\* O1 0.41463 (10) 0.2084 (2) 0.34045 (19) 0.0783 (6) N2 0.18558 (10) 0.31574 (17) 0.26935 (16) 0.0474 (4) C8 0.11925 (12) 0.3191 (2) 0.16968 (19) 0.0436 (5) H8 0.1228 0.2816 0.0896 0.052\* C9 0.03862 (12) 0.38038 (19) 0.17943 (18) 0.0414 (4) O3 0.10297 (10) 0.45363 (19) 0.40269 (14) 0.0656 (5) H3 0.1464 0.4217 0.3853 0.098\* C18 −0.03826 (12) 0.37537 (19) 0.07041 (19) 0.0429 (4) C7 0.36860 (12) 0.4348 (3) 0.39778 (19) 0.0553 (6) C17 −0.04179 (15) 0.3112 (2) −0.0504 (2) 0.0539 (6) H17 0.0077 0.2688 −0.0618 0.065\* C10 0.03447 (13) 0.4460 (2) 0.29415 (19) 0.0489 (5) C1 0.33366 (15) 0.5089 (3) 0.4823 (2) 0.0660 (7) H1 0.3007 0.4723 0.5361 0.079\* C11 −0.04155 (15) 0.5093 (2) 0.3048 (2) 0.0610 (6) H11 −0.0425 0.5538 0.3821 0.073\* C15 −0.19112 (16) 0.3721 (3) −0.1373 (3) 0.0675 (7) H15 −0.2415 0.3704 −0.2062 0.081\* C13 −0.11516 (13) 0.4395 (2) 0.0837 (2) 0.0500 (5) C14 −0.19068 (14) 0.4359 (3) −0.0229 (3) 0.0637 (7) H14 −0.2410 0.4779 −0.0145 0.076\* C12 −0.11397 (15) 0.5057 (2) 0.2025 (2) 0.0598 (6) H12 −0.1641 0.5481 0.2110 0.072\* C16 −0.11621 (17) 0.3097 (3) −0.1513 (2) 0.0653 (7) H16 −0.1166 0.2664 −0.2299 0.078\* C3 0.39614 (15) 0.6954 (3) 0.4084 (3) 0.0700 (8) C5 0.43222 (16) 0.6196 (3) 0.3274 (3) 0.0787 (9) H5 0.4668 0.6565 0.2762 0.094\* C2 0.34799 (17) 0.6369 (3) 0.4863 (3) 0.0738 (8) H2 0.3243 0.6860 0.5437 0.089\* C4 0.4090 (2) 0.8355 (4) 0.4087 (4) 0.0969 (10) H4A 0.3725 0.8711 0.3290 0.145\* H4B 0.4692 0.8539 0.4117 0.145\* H4C 0.3937 0.8715 0.4854 0.145\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1284 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C6 0.0495 (12) 0.105 (3) 0.0628 (15) 0.0036 (13) 0.0256 (11) 0.0034 (14) S1 0.0488 (3) 0.0843 (5) 0.0418 (3) 0.0121 (3) 0.0145 (2) 0.0078 (3) O2 0.0796 (10) 0.0930 (15) 0.0447 (9) 0.0094 (9) 0.0215 (8) 0.0149 (8) N1 0.0489 (9) 0.0698 (14) 0.0440 (9) 0.0081 (8) 0.0159 (7) −0.0049 (9) O1 0.0576 (9) 0.1076 (16) 0.0717 (11) 0.0291 (9) 0.0196 (8) 0.0054 (10) N2 0.0468 (8) 0.0557 (12) 0.0426 (9) 0.0048 (7) 0.0168 (7) 0.0009 (8) C8 0.0503 (10) 0.0455 (13) 0.0370 (10) 0.0002 (9) 0.0145 (8) 0.0005 (8) C9 0.0483 (10) 0.0396 (12) 0.0377 (9) 0.0012 (8) 0.0133 (8) 0.0014 (8) O3 0.0641 (9) 0.0914 (14) 0.0413 (8) 0.0074 (9) 0.0124 (7) −0.0137 (8) C18 0.0508 (10) 0.0363 (12) 0.0429 (10) 0.0012 (8) 0.0138 (8) 0.0052 (8) C7 0.0388 (9) 0.0851 (19) 0.0410 (10) 0.0006 (10) 0.0075 (8) 0.0010 (11) C17 0.0605 (12) 0.0487 (14) 0.0489 (12) 0.0027 (10) 0.0059 (9) −0.0041 (10) C10 0.0554 (11) 0.0537 (14) 0.0398 (10) 0.0019 (9) 0.0157 (9) 0.0001 (9) C1 0.0621 (13) 0.092 (2) 0.0478 (12) −0.0105 (13) 0.0207 (10) −0.0082 (12) C11 0.0748 (15) 0.0609 (17) 0.0533 (13) 0.0125 (12) 0.0269 (11) −0.0063 (11) C15 0.0601 (13) 0.0675 (19) 0.0645 (15) −0.0075 (12) −0.0053 (11) 0.0088 (13) C13 0.0517 (11) 0.0447 (14) 0.0549 (12) 0.0014 (9) 0.0151 (9) 0.0091 (10) C14 0.0495 (11) 0.0630 (18) 0.0763 (16) 0.0046 (11) 0.0106 (11) 0.0169 (13) C12 0.0584 (12) 0.0594 (16) 0.0669 (15) 0.0153 (11) 0.0255 (11) 0.0050 (12) C16 0.0759 (15) 0.0604 (17) 0.0513 (13) −0.0027 (12) −0.0011 (11) −0.0032 (11) C3 0.0472 (12) 0.096 (2) 0.0622 (15) −0.0087 (12) 0.0032 (11) 0.0008 (14) C5 0.0523 (13) 0.105 (3) 0.0819 (19) −0.0119 (14) 0.0222 (13) 0.0181 (17) C2 0.0712 (15) 0.094 (2) 0.0565 (14) −0.0097 (15) 0.0160 (12) −0.0129 (14) C4 0.0861 (19) 0.099 (3) 0.098 (2) −0.0163 (18) 0.0068 (17) 0.0056 (19) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1723 .table-wrap} ----------------------- -------------- ----------------------- -------------- C6---C5 1.383 (4) C10---C11 1.398 (3) C6---C7 1.386 (3) C1---C2 1.370 (4) C6---H6 0.9300 C1---H1 0.9300 S1---O1 1.4204 (17) C11---C12 1.356 (3) S1---O2 1.4257 (17) C11---H11 0.9300 S1---N1 1.6499 (18) C15---C14 1.359 (4) S1---C7 1.758 (3) C15---C16 1.389 (4) N1---N2 1.395 (2) C15---H15 0.9300 N1---H1A 0.8600 C13---C12 1.408 (3) N2---C8 1.279 (2) C13---C14 1.413 (3) C8---C9 1.450 (3) C14---H14 0.9300 C8---H8 0.9300 C12---H12 0.9300 C9---C10 1.387 (3) C16---H16 0.9300 C9---C18 1.443 (3) C3---C5 1.375 (4) O3---C10 1.358 (2) C3---C2 1.376 (4) O3---H3 0.8200 C3---C4 1.496 (5) C18---C17 1.409 (3) C5---H5 0.9300 C18---C13 1.422 (3) C2---H2 0.9300 C7---C1 1.382 (3) C4---H4A 0.9600 C17---C16 1.368 (3) C4---H4B 0.9600 C17---H17 0.9300 C4---H4C 0.9600 C5---C6---C7 119.2 (3) C7---C1---H1 120.3 C5---C6---H6 120.4 C12---C11---C10 120.1 (2) C7---C6---H6 120.4 C12---C11---H11 120.0 O1---S1---O2 120.06 (12) C10---C11---H11 120.0 O1---S1---N1 104.04 (10) C14---C15---C16 119.9 (2) O2---S1---N1 106.64 (10) C14---C15---H15 120.1 O1---S1---C7 109.94 (12) C16---C15---H15 120.1 O2---S1---C7 108.50 (11) C12---C13---C14 121.6 (2) N1---S1---C7 106.82 (10) C12---C13---C18 119.13 (18) N2---N1---S1 113.38 (13) C14---C13---C18 119.3 (2) N2---N1---H1A 123.3 C15---C14---C13 121.2 (2) S1---N1---H1A 123.3 C15---C14---H14 119.4 C8---N2---N1 117.67 (17) C13---C14---H14 119.4 N2---C8---C9 121.08 (18) C11---C12---C13 121.7 (2) N2---C8---H8 119.5 C11---C12---H12 119.2 C9---C8---H8 119.5 C13---C12---H12 119.2 C10---C9---C18 118.81 (18) C17---C16---C15 120.6 (2) C10---C9---C8 120.25 (17) C17---C16---H16 119.7 C18---C9---C8 120.94 (17) C15---C16---H16 119.7 C10---O3---H3 109.5 C5---C3---C2 117.3 (3) C17---C18---C13 117.44 (18) C5---C3---C4 120.1 (3) C17---C18---C9 123.77 (18) C2---C3---C4 122.5 (3) C13---C18---C9 118.79 (18) C3---C5---C6 122.0 (3) C1---C7---C6 119.7 (3) C3---C5---H5 119.0 C1---C7---S1 121.08 (19) C6---C5---H5 119.0 C6---C7---S1 119.2 (2) C1---C2---C3 122.4 (3) C16---C17---C18 121.6 (2) C1---C2---H2 118.8 C16---C17---H17 119.2 C3---C2---H2 118.8 C18---C17---H17 119.2 C3---C4---H4A 109.5 O3---C10---C9 122.90 (18) C3---C4---H4B 109.5 O3---C10---C11 115.60 (19) H4A---C4---H4B 109.5 C9---C10---C11 121.50 (19) C3---C4---H4C 109.5 C2---C1---C7 119.4 (2) H4A---C4---H4C 109.5 C2---C1---H1 120.3 H4B---C4---H4C 109.5 O1---S1---N1---N2 −178.38 (16) C8---C9---C10---C11 178.0 (2) O2---S1---N1---N2 53.77 (18) C6---C7---C1---C2 0.9 (3) C7---S1---N1---N2 −62.10 (17) S1---C7---C1---C2 −175.48 (18) S1---N1---N2---C8 173.14 (15) O3---C10---C11---C12 −179.0 (2) N1---N2---C8---C9 −179.48 (18) C9---C10---C11---C12 1.1 (4) N2---C8---C9---C10 5.5 (3) C17---C18---C13---C12 −179.4 (2) N2---C8---C9---C18 −175.04 (19) C9---C18---C13---C12 0.0 (3) C10---C9---C18---C17 −179.7 (2) C17---C18---C13---C14 0.2 (3) C8---C9---C18---C17 0.8 (3) C9---C18---C13---C14 179.6 (2) C10---C9---C18---C13 0.9 (3) C16---C15---C14---C13 −0.4 (4) C8---C9---C18---C13 −178.56 (19) C12---C13---C14---C15 179.7 (2) C5---C6---C7---C1 −0.3 (3) C18---C13---C14---C15 0.1 (4) C5---C6---C7---S1 176.16 (18) C10---C11---C12---C13 −0.1 (4) O1---S1---C7---C1 −154.14 (17) C14---C13---C12---C11 180.0 (2) O2---S1---C7---C1 −21.0 (2) C18---C13---C12---C11 −0.4 (4) N1---S1---C7---C1 93.57 (18) C18---C17---C16---C15 0.1 (4) O1---S1---C7---C6 29.5 (2) C14---C15---C16---C17 0.3 (4) O2---S1---C7---C6 162.58 (17) C2---C3---C5---C6 2.3 (4) N1---S1---C7---C6 −82.81 (18) C4---C3---C5---C6 −177.0 (2) C13---C18---C17---C16 −0.3 (3) C7---C6---C5---C3 −1.4 (4) C9---C18---C17---C16 −179.7 (2) C7---C1---C2---C3 0.1 (4) C18---C9---C10---O3 178.6 (2) C5---C3---C2---C1 −1.7 (4) C8---C9---C10---O3 −1.9 (3) C4---C3---C2---C1 177.6 (2) C18---C9---C10---C11 −1.5 (3) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2511 .table-wrap} ----------------------------------------------------------------------------------------- Cg1 and Cg2 are the centroids of the C1--C3/C5--C7 and C9--C13/C18 rings, respectively. ----------------------------------------------------------------------------------------- ::: ::: {#d1e2515 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O3---H3···N2 0.82 1.85 2.563 (2) 145. N1---H1A···O2^i^ 0.86 2.36 2.998 (2) 132. C15---H15···Cg1^ii^ 0.92 2.72 3.625 (3) 164 C16---H16···Cg2^i^ 0.92 2.75 3.501 (3) 139 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x, −y+1, −z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 and Cg2 are the centroids of the C1--C3/C5--C7 and C9--C13/C18 rings, respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- O3---H3⋯N2 0.82 1.85 2.563 (2) 145 N1---H1A⋯O2^i^ 0.86 2.36 2.998 (2) 132 C15---H15⋯Cg1^ii^ 0.92 2.72 3.625 (3) 164 C16---H16⋯Cg2^i^ 0.92 2.75 3.501 (3) 139 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.879638	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052163/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o713", "authors": [ { "first": "Gholam Hossein", "last": "Shahverdizadeh" }, { "first": "Rahman", "last": "Bikas" }, { "first": "Maryam", "last": "Eivazi" }, { "first": "Parisa", "last": "Mahboubi Anarjan" }, { "first": "Behrouz", "last": "Notash" } ] }
PMC3052164	Related literature {#sec1} ================== For hydrogen bonds and crystal engineering, see: Aakeröy & Seddon (1993[@bb1]). For potential applications of transition metal complexes, see: Liu et al. (2007[@bb3]); Shibasaki & Yoshikawa (2002[@bb8]). For carboxylate compounds with six-coordinate metal atoms, see: Liu et al. (2010[@bb4]); Su et al. (2005[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cu(C~8~H~7~O~3~)~2~(C~10~H~8~N~2~)\]·H~2~OM ~r~ = 540.01Monoclinic,a = 19.888 (4) Åb = 10.887 (2) Åc = 11.612 (2) Åβ = 103.62 (3)°V = 2443.5 (8) Å^3^Z = 4Mo Kα radiationμ = 0.94 mm^−1^T = 293 K0.1 × 0.1 × 0.1 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID diffractometerAbsorption correction: multi-scan (ABSCOR; Higashi, 1995[@bb2]) T ~min~ = 0.710, T ~max~ = 0.78012080 measured reflections2796 independent reflections2391 reflections with I \> 2σ(I)R ~int~ = 0.054 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.041wR(F ^2^) = 0.113S = 1.052796 reflections165 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e530} Data collection: RAPID-AUTO (Rigaku, 1998[@bb5]); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004[@bb6]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: ORTEPII (Johnson, 1976)[@bb10]; software used to prepare material for publication: SHELXL97. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005563/rn2078sup1.cif](http://dx.doi.org/10.1107/S1600536811005563/rn2078sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005563/rn2078Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005563/rn2078Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rn2078&file=rn2078sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rn2078sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rn2078&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RN2078](http://scripts.iucr.org/cgi-bin/sendsup?rn2078)). This project was supported by the Education Department of Zhejiang Province and the scientific research fund of Nibong University (grant No. XKL069). Thanks are also extended to the K. C. Wong Magna Fund, Ningbo University. Comment ======= In the past decade, a variety of supramolecular architectures based on hydrogen bonds, π···π interactions have been achieved by using transition metal centers and organic ligands (Aakeroy et al., 1993), they have potential application in catalysis, gas storage, and in molecular--based magnetic materials (Liu et al., 2007, Shibasaki et al., 2002). Herein, we are interested in self-assemblies of Cu^2+^ ions and bipy with 3--methoxybenzoic acid, which led to the preparation of \[Cu(bipy)~2~(C~8~H~8~O~3~)~2~\].H~2~O. The title compound, \[Cu(bipy)~2~(C~8~H~8~O~3~)~2~\].H~2~O, is comprised of a Cu^II^ ion, two 3--methoxybenzoate ligands, a 2,2\'--bipyridine(bipy) ligand and one lattice H~2~O molecule. As illustrated in Fig.1, the Cu ion and water O atom lie on a two fold axis. The Cu^II^ ion has a six--coordinate distorted octahedral geometry with two N atoms from the bipy ligand \[Cu--N = 1.9996 (16) Å\] and four O atoms from two 3--methoxybenzoate ligands \[Cu--O = 1.9551 (15) and 2.6016 (16) Å\]. Owing to geometric constraints and the Jahn--Teller effect, the Cu--O bonds in the axial direction are longer than in the equatorial plane. Two O atoms and two N atoms occupy the equatorial plane position with the r.m.s. deviation from the ideal plane of 0.214 Å, while two O atoms lie in the apical positions with an axis angle of 140.53 (5)° showing a large deviation from the normal 180°,which is also seen in similar carboxylate complexes (Liu et al., 2010; Su et al., 2005). For 3--methoxybenzoate anions, the plane of benzene ring and carboxylate group are nearly co--planar where the dihedral angle between the benzene ring and carboxylate plane is 5.2 (3)°. The water molecules are not coordinated to Cu and the distance between copper and water oxygen atoms is 4.019 (2) Å. The molecules are linked via hydrogen bonds (O4--H41···O1, C12--H12A···O4, C11--H11A···O3) into one-dimensional supramolecular chains extending along the \[100\] direction, which are linked by hydrogen bonds (C5--H5A···O2) into two dimensional layers parallel to (100) (Fig. 2). The layers are arranged alternately in an ···ABAB···sequence and further assembled into there--dimensional network by hydrogen bonds (C10--H10A···O2). Experimental {#experimental} ============ CuCl~2~.2H~2~O (0.1705 g, 1.000 mmol) was successively added to 20 ml C~2~H~5~OH--H~2~O(1:1, v/v), 3--methoxybenzoate (0.1520 g, 1.000 mmol) and bipy (0.1569 g, 1.004 mmol) were subsequently added, then 1.4 ml (1 M) NaOH was added dropwise and stirred continuously for 1 h to give a blue suspension. After filtration, the blue filtrate (pH = 5.80) was allowed to stand at room temperature for several weeks to give blue block--shaped crystals Refinement {#refinement} ========== H atoms bonded to C atoms were placed in geometrically calculated positions and were refined using a riding model, with U~iso~(H) = 1.2 U~eq~(C). H atoms attached to O atoms were found in a difference Fourier synthesis and were refined using a riding model, with the O---H distances fixed as initially found and with U~iso~(H) values set at 1.2 Ueq(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound,with atom labels and 45% probability displacement ellipsoids for non-H atoms. Symmetry code for the symbol \'A\': -x, y + 1, 0.5 - z. ::: ![](e-67-0m352-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The two-dimensional supramolecular layers of the title compound parallel to (100) showing O--H···O, C--H···O hydrogen bonds. ::: ![](e-67-0m352-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e226 .table-wrap} ---------------------------------------------- ---------------------------------------- \[Cu(C~8~H~7~O~3~)~2~(C~10~H~8~N~2~)\]·H~2~O F(000) = 1116 M~r~ = 540.01 D~x~ = 1.468 Mg m^−3^ Monoclinic, C2/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -C 2yc Cell parameters from 12080 reflections a = 19.888 (4) Å θ = 3.6--27.5° b = 10.887 (2) Å µ = 0.94 mm^−1^ c = 11.612 (2) Å T = 293 K β = 103.62 (3)° Block, blue V = 2443.5 (8) Å^3^ 0.1 × 0.1 × 0.1 mm Z = 4 ---------------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e367 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID diffractometer 2796 independent reflections Radiation source: fine-focus sealed tube 2391 reflections with I \> 2σ(I) graphite R~int~ = 0.054 Detector resolution: 0 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 3.6° ω scans h = −25→25 Absorption correction: multi-scan (ABSCOR; Higashi, 1995) k = −14→14 T~min~ = 0.710, T~max~ = 0.78 l = −15→14 12080 measured reflections ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.113 H-atom parameters constrained S = 1.05 w = 1/\[σ^2^(F~o~^2^) + (0.0638P)^2^ + 0.7842P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2796 reflections (Δ/σ)~max~ = 0.001 165 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ Cu 0.0000 0.52776 (3) 0.7500 0.04304 (15) O1 −0.04555 (7) 0.40392 (14) 0.82712 (14) 0.0539 (4) O2 −0.12489 (8) 0.44707 (15) 0.66421 (15) 0.0598 (4) O3 −0.15000 (9) 0.11263 (17) 1.05759 (15) 0.0669 (5) N1 −0.03034 (8) 0.66715 (15) 0.83787 (14) 0.0426 (4) C1 −0.10582 (10) 0.39069 (18) 0.75900 (19) 0.0470 (5) C2 −0.15286 (10) 0.30133 (18) 0.79947 (19) 0.0475 (5) C3 −0.21724 (12) 0.2726 (2) 0.7265 (2) 0.0611 (6) H3A −0.2317 0.3089 0.6523 0.073\ C4 −0.25923 (13) 0.1895 (3) 0.7658 (3) 0.0724 (7) H4A −0.3021 0.1702 0.7170 0.087\* C5 −0.23949 (12) 0.1344 (2) 0.8754 (3) 0.0646 (6) H5A −0.2688 0.0790 0.9003 0.078\* C6 −0.17571 (11) 0.16247 (19) 0.9479 (2) 0.0534 (5) C7 −0.13269 (10) 0.24562 (19) 0.9099 (2) 0.0498 (5) H7A −0.0898 0.2643 0.9590 0.060\* C8 −0.19197 (18) 0.0270 (3) 1.1014 (3) 0.0818 (9) H8A −0.1674 −0.0022 1.1777 0.123\* H8B −0.2028 −0.0410 1.0476 0.123\* H8C −0.2340 0.0664 1.1085 0.123\* C9 −0.06227 (11) 0.6578 (2) 0.92759 (18) 0.0492 (5) H9A −0.0705 0.5802 0.9549 0.059\* C10 −0.08304 (12) 0.7594 (2) 0.97979 (19) 0.0557 (5) H10A −0.1055 0.7507 1.0411 0.067\* C11 −0.07033 (13) 0.8737 (2) 0.9407 (2) 0.0599 (6) H11A −0.0838 0.9434 0.9757 0.072\* C12 −0.03730 (12) 0.8849 (2) 0.8490 (2) 0.0552 (5) H12A −0.0282 0.9619 0.8215 0.066\* C13 −0.01811 (10) 0.77943 (18) 0.79901 (17) 0.0426 (4) O4 0.0000 0.1586 (2) 0.7500 0.0842 (8) H41 −0.0138 0.2109 0.7975 0.126\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1215 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Cu 0.0395 (2) 0.0333 (2) 0.0560 (2) 0.000 0.01071 (15) 0.000 O1 0.0423 (8) 0.0427 (8) 0.0740 (10) −0.0074 (6) 0.0083 (7) 0.0071 (7) O2 0.0532 (9) 0.0576 (9) 0.0692 (10) 0.0083 (7) 0.0159 (8) 0.0082 (8) O3 0.0646 (10) 0.0641 (11) 0.0774 (11) −0.0110 (8) 0.0277 (9) 0.0081 (8) N1 0.0407 (9) 0.0405 (9) 0.0468 (9) −0.0013 (7) 0.0108 (7) 0.0020 (6) C1 0.0435 (11) 0.0356 (10) 0.0642 (12) 0.0055 (8) 0.0174 (9) −0.0021 (9) C2 0.0367 (10) 0.0361 (10) 0.0696 (13) 0.0015 (8) 0.0125 (9) −0.0064 (9) C3 0.0457 (12) 0.0546 (13) 0.0777 (15) −0.0014 (10) 0.0040 (11) −0.0038 (11) C4 0.0400 (12) 0.0667 (16) 0.103 (2) −0.0126 (11) 0.0024 (12) −0.0111 (15) C5 0.0459 (13) 0.0512 (13) 0.1009 (19) −0.0111 (10) 0.0258 (12) −0.0081 (12) C6 0.0478 (12) 0.0425 (11) 0.0754 (14) −0.0041 (9) 0.0254 (10) −0.0069 (10) C7 0.0383 (10) 0.0447 (11) 0.0671 (13) −0.0052 (8) 0.0135 (9) −0.0048 (9) C8 0.093 (2) 0.0693 (19) 0.098 (2) −0.0154 (15) 0.0526 (19) 0.0040 (14) C9 0.0461 (11) 0.0513 (12) 0.0508 (11) −0.0028 (9) 0.0127 (9) 0.0042 (9) C10 0.0557 (13) 0.0657 (14) 0.0502 (11) 0.0017 (11) 0.0211 (10) −0.0018 (10) C11 0.0696 (15) 0.0536 (13) 0.0614 (13) 0.0079 (11) 0.0255 (11) −0.0082 (10) C12 0.0679 (14) 0.0386 (11) 0.0629 (13) 0.0042 (10) 0.0232 (11) −0.0006 (9) C13 0.0430 (10) 0.0384 (10) 0.0462 (10) 0.0013 (8) 0.0100 (8) −0.0011 (7) O4 0.124 (3) 0.0464 (14) 0.0887 (18) 0.000 0.0370 (17) 0.000 ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1588 .table-wrap} -------------------- ------------- -------------------- ------------- Cu---O1^i^ 1.9551 (15) C5---C6 1.381 (3) Cu---O1 1.9551 (15) C5---H5A 0.9300 Cu---N1^i^ 1.9996 (16) C6---C7 1.387 (3) Cu---N1 1.9996 (16) C7---H7A 0.9300 O1---C1 1.279 (3) C8---H8A 0.9600 O2---C1 1.239 (3) C8---H8B 0.9600 O3---C6 1.368 (3) C8---H8C 0.9600 O3---C8 1.423 (3) C9---C10 1.371 (3) N1---C13 1.345 (2) C9---H9A 0.9300 N1---C9 1.346 (3) C10---C11 1.369 (3) C1---C2 1.500 (3) C10---H10A 0.9300 C2---C7 1.390 (3) C11---C12 1.382 (3) C2---C3 1.395 (3) C11---H11A 0.9300 C3---C4 1.380 (4) C12---C13 1.380 (3) C3---H3A 0.9300 C12---H12A 0.9300 C4---C5 1.378 (4) C13---C13^i^ 1.483 (4) C4---H4A 0.9300 O4---H41 0.8800 O1^i^---Cu---O1 92.80 (10) O3---C6---C7 115.6 (2) O1^i^---Cu---N1^i^ 93.53 (7) C5---C6---C7 119.8 (2) O1---Cu---N1^i^ 170.12 (6) C6---C7---C2 120.8 (2) O1^i^---Cu---N1 170.12 (6) C6---C7---H7A 119.6 O1---Cu---N1 93.53 (7) C2---C7---H7A 119.6 N1^i^---Cu---N1 81.25 (9) O3---C8---H8A 109.5 C1---O1---Cu 105.20 (13) O3---C8---H8B 109.5 C6---O3---C8 118.1 (2) H8A---C8---H8B 109.5 C13---N1---C9 118.97 (17) O3---C8---H8C 109.5 C13---N1---Cu 114.74 (12) H8A---C8---H8C 109.5 C9---N1---Cu 126.27 (14) H8B---C8---H8C 109.5 O2---C1---O1 122.66 (19) N1---C9---C10 121.83 (19) O2---C1---C2 121.1 (2) N1---C9---H9A 119.1 O1---C1---C2 116.23 (18) C10---C9---H9A 119.1 C7---C2---C3 119.2 (2) C11---C10---C9 119.26 (19) C7---C2---C1 120.43 (19) C11---C10---H10A 120.4 C3---C2---C1 120.4 (2) C9---C10---H10A 120.4 C4---C3---C2 119.1 (2) C10---C11---C12 119.6 (2) C4---C3---H3A 120.4 C10---C11---H11A 120.2 C2---C3---H3A 120.4 C12---C11---H11A 120.2 C5---C4---C3 121.9 (2) C13---C12---C11 118.6 (2) C5---C4---H4A 119.1 C13---C12---H12A 120.7 C3---C4---H4A 119.1 C11---C12---H12A 120.7 C4---C5---C6 119.2 (2) N1---C13---C12 121.68 (17) C4---C5---H5A 120.4 N1---C13---C13^i^ 114.60 (10) C6---C5---H5A 120.4 C12---C13---C13^i^ 123.71 (12) O3---C6---C5 124.6 (2) -------------------- ------------- -------------------- ------------- ::: Symmetry codes: (i) −x, y, −z+3/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2046 .table-wrap} ---------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O4---H41···O1 0.88 2.24 3.023 (3) 147 C12---H12A···O4^ii^ 0.93 2.41 3.339 (3) 178 C11---H11A···O3^ii^ 0.93 2.57 3.483 (3) 166 C10---H10A···O2^iii^ 0.93 2.66 3.342 (3) 131 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) x, y+1, z; (iii) x, −y+1, z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------------- --------- ------- ----------- ------------- O4---H41⋯O1 0.88 2.24 3.023 (3) 147 C12---H12A⋯O4^ii^ 0.93 2.41 3.339 (3) 178 C11---H11A⋯O3^ii^ 0.93 2.57 3.483 (3) 166 C10---H10A⋯O2^iii^ 0.93 2.66 3.342 (3) 131 Symmetry codes: (ii) ; (iii) . :::	PubMed Central	2024-06-05T04:04:18.885418	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052164/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m352", "authors": [ { "first": "Ming-Hao", "last": "Lin" }, { "first": "Jing-Fan", "last": "Zhou" }, { "first": "Bin-Bin", "last": "Liu" }, { "first": "Jian-Li", "last": "Lin" } ] }
PMC3052165	Related literature {#sec1} ================== For the structures of some Zn^II^--pyridine complexes, see: Le Querler et al. (1977[@bb5]); Pasaoglu et al. (2006[@bb7]); Fan & Wu (2006[@bb2]). For the structure of a mixed-ligand Pt^II^ complex with 4-(4-nitrobenzyl)pyridine, see: Chan et al. (1993[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\]M ~r~ = 747.61Orthorhombic,a = 18.2091 (2) Åb = 15.8998 (3) Åc = 19.0327 (3) ÅV = 5510.37 (15) Å^3^Z = 8Mo Kα radiationμ = 3.17 mm^−1^T = 200 K0.40 × 0.22 × 0.15 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini-S Ultra CCD detector diffractometerAbsorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[@bb6]) T ~min~ = 0.865, T ~max~ = 0.98018536 measured reflections10102 independent reflections7499 reflections with I \> 2σ(I)R ~int~ = 0.024 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.032wR(F ^2^) = 0.056S = 0.8910102 reflections627 parameters25 restraintsH-atom parameters not refinedΔρ~max~ = 0.63 e Å^−3^Δρ~min~ = −0.47 e Å^−3^Absolute structure: Flack (1983[@bb4]), 4516 Friedel pairsFlack parameter: 0.430 (14) {#d5e387} Data collection: CrysAlis PRO (Oxford Diffraction, 2010[@bb6]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]) within WinGX (Farrugia, 1999[@bb3]); molecular graphics: PLATON (Spek, 2009[@bb9]); software used to prepare material for publication: PLATON. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005939/ng5114sup1.cif](http://dx.doi.org/10.1107/S1600536811005939/ng5114sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005939/ng5114Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005939/ng5114Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5114&file=ng5114sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5114sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5114&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5114](http://scripts.iucr.org/cgi-bin/sendsup?ng5114)). The authors acknowledge financial support from the Australian Research Committee, the Faculty of Science and Technology and the University Library, Queensland University of Technology, and the School of Biomolecular and Physical Sciences, Griffith University. Comment ======= The structures of complexes of ZnI~2~ with pyridine and substituted pyridine ligands, of the type \[ZnI~2~(py)~2~\] are common in the crystallographic literature e.g. with pyridine (Le Querler et al., 1977), and with nicotinamide and isonicotinamide (Pasaoglu et al., 2006). These complexes are usually discrete with distorted tetrahedral stereochemistry. Polymeric complexes having similar stereochemistry are also formed with bifunctional pyridines such as 4,4\'-bipyridine (Fan & Wu, 2006). We obtained the title compound \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\] (I) from the reaction of zinc(II) iodide with 4-(4-nitrobenzyl)pyridine (L) and the structure is reported here. This substituted pyridine has only occasionally been used as a ligand in metal complex formation e.g. in the mixed-ligand Pt^II^ complex with 2,9-diphenyl-1,10-phenanthroline (Chan et al., 1993). In the structure of (I), the asymmetric unit contains two independent discrete distorted tetrahedral \[ZnI~2~L~2~\] complex units, involving Zn1 and Zn2 (Figs. 1, 2). The Zn---I range is 2.5472 (8)--2.5666 (7) Å, the Zn---N range is 2.044 (4)--2.052 (4) Å and the bond angle range about Zn is 98.99 (17)--119.96 (2)° (for I1---Zn1---I2 and N1A---Zn1---N1B, respectively). The two complex molecules are essentially identical conformationally and are related by pseudo-symmetry, being treated as a racemic twin in the structure refinement. In the crystal packing of (I) there are only weak intermolecular aromatic C---H···O~nitro~ interactions \[C5A---H···O41D, 3.211 (9) Å and C6B---H···O41B, 3.295 Å\] but there are some aromatic ring π--π associations involving the C11B--C61B rings: ring centroid separation, 3.591 (3) Å; inter-ring dihedral angle, 3.46 (1)°\] (Fig. 3). Experimental {#experimental} ============ The title compound was synthesized by heating together under reflux for 10 minutes, 1 mmol of zinc(II) iodide and 2 mmol of 4-(4-nitrobenzyl)pyridine in 50 ml of 50% ethanol--water. After concentration to ca 30 ml, partial room temperature evaporation of the hot-filtered solution gave pale yellow flattened prisms of (I) from which a suitable specimen was cleaved for the X-ray analysis. Refinement {#refinement} ========== Hydrogen atoms were included in the refinement in calculated positions with C--H = 0.93 Å (aromatic) or 0.97 Å (aliphatic) and allowed to ride, with U~iso~(H) = 1.2U~eq~(C). A racemic twin was identified and treated as such using the appropriate SHELXL97 function \[BASF factor, 0.430 (14)\]. Oxygen atoms of the terminal nitro groups were significantly disordered, one in particular (O41C, U~iso~ = 0.142 Å^2^) subsequently being refined isotropically. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular configuration and atom-numbering scheme for the first of the two independent complex units (about Zn1) in the asymmetric unit of (I), with non-H atoms drawn as 30% probability ellipsoids. ::: ![](e-67-0m359-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular configuration and atom-numbering scheme for the second complex unit (about Zn2) in (I) (30% probability). ::: ![](e-67-0m359-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The packing of (I) in the unit cell, viewed down the a cell direction. Hydrogen atoms are omitted. ::: ![](e-67-0m359-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e215 .table-wrap} ----------------------------------- --------------------------------------- \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\] D~x~ = 1.802 Mg m^−3^ M~r~ = 747.61 Melting point = 473--475 K Orthorhombic, Pca2~1~ Mo Kα radiation, λ = 0.71073 Å Hall symbol: P 2c -2ac Cell parameters from 5528 reflections a = 18.2091 (2) Å θ = 3.3--28.7° b = 15.8998 (3) Å µ = 3.17 mm^−1^ c = 19.0327 (3) Å T = 200 K V = 5510.37 (15) Å^3^ Prism, pale yellow Z = 8 0.40 × 0.22 × 0.15 mm F(000) = 2880 ----------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Gemini-S Ultra CCD detector diffractometer 10102 independent reflections Radiation source: Enhance (Mo) X-ray source 7499 reflections with I \> 2σ(I) graphite R~int~ = 0.024 Detector resolution: 16.077 pixels mm^-1^ θ~max~ = 26.0°, θ~min~ = 3.4° ω scans h = −22→22 Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) k = −19→19 T~min~ = 0.865, T~max~ = 0.980 l = −23→22 18536 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e472 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites R\[F^2^ \> 2σ(F^2^)\] = 0.032 H-atom parameters not refined wR(F^2^) = 0.056 w = 1/\[σ^2^(F~o~^2^) + (0.0262P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 S = 0.89 (Δ/σ)~max~ = 0.024 10102 reflections Δρ~max~ = 0.63 e Å^−3^ 627 parameters Δρ~min~ = −0.47 e Å^−3^ 25 restraints Absolute structure: Flack (1983), 4516 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.430 (14) ---------------------------------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e631 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e733 .table-wrap} ------ ------------- ------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ I1 0.95618 (2) 0.12807 (3) 0.69072 (2) 0.0518 (1) I2 1.15212 (2) 0.14231 (3) 0.82772 (2) 0.0567 (1) Zn1 1.01354 (3) 0.12528 (4) 0.81338 (3) 0.0432 (2) O41A 0.6840 (4) 0.3754 (6) 1.2662 (4) 0.179 (5) O41B 0.6256 (3) −0.0954 (3) 1.1910 (3) 0.0767 (19) O42A 0.7998 (4) 0.3645 (5) 1.3010 (4) 0.123 (3) O42B 0.5740 (3) −0.1013 (4) 1.0908 (3) 0.100 (3) N1A 0.9587 (2) 0.2149 (3) 0.8705 (2) 0.0440 (17) N1B 0.9820 (2) 0.0205 (3) 0.8686 (2) 0.0393 (16) N41A 0.7532 (6) 0.3685 (6) 1.2560 (5) 0.146 (5) N41B 0.6283 (3) −0.1037 (3) 1.1280 (4) 0.060 (2) C2A 0.8847 (3) 0.2146 (4) 0.8703 (3) 0.064 (3) C2B 1.0121 (3) 0.0043 (3) 0.9320 (3) 0.0413 (19) C3A 0.8434 (3) 0.2746 (4) 0.9017 (3) 0.065 (3) C3B 0.9891 (3) −0.0596 (4) 0.9745 (3) 0.0447 (19) C4A 0.8780 (4) 0.3398 (4) 0.9357 (3) 0.053 (2) C4B 0.9333 (3) −0.1124 (3) 0.9535 (3) 0.038 (2) C5A 0.9519 (4) 0.3414 (4) 0.9358 (4) 0.066 (3) C5B 0.9039 (3) −0.0982 (4) 0.8879 (3) 0.045 (2) C6A 0.9918 (3) 0.2776 (4) 0.9036 (3) 0.058 (3) C6B 0.9289 (3) −0.0329 (3) 0.8476 (3) 0.0440 (19) C11A 0.8119 (4) 0.3939 (4) 1.0439 (4) 0.056 (3) C11B 0.8332 (3) −0.1589 (3) 1.0348 (3) 0.0343 (19) C21A 0.7428 (4) 0.3758 (6) 1.0609 (5) 0.098 (4) C21B 0.7678 (3) −0.1709 (3) 0.9985 (4) 0.049 (2) C31A 0.7239 (4) 0.3700 (6) 1.1283 (5) 0.107 (4) C31B 0.7012 (3) −0.1499 (4) 1.0273 (3) 0.052 (2) C41A 0.7739 (4) 0.3750 (5) 1.1802 (5) 0.078 (3) C41B 0.7001 (3) −0.1210 (3) 1.0951 (3) 0.040 (2) C42A 0.8329 (4) 0.4105 (4) 0.9687 (4) 0.080 (3) C42B 0.9056 (3) −0.1818 (3) 1.0005 (3) 0.0453 (19) C51A 0.8454 (4) 0.3902 (4) 1.1653 (5) 0.072 (3) C51B 0.7630 (3) −0.1092 (3) 1.1331 (3) 0.042 (2) C61A 0.8651 (4) 0.3999 (4) 1.0951 (4) 0.068 (3) C61B 0.8296 (3) −0.1277 (4) 1.1026 (4) 0.048 (2) I3 1.16361 (2) 0.37425 (3) 0.36527 (2) 0.0519 (2) I4 0.97184 (2) 0.40341 (3) 0.50705 (2) 0.0539 (1) Zn2 1.02497 (3) 0.39353 (4) 0.38352 (4) 0.0426 (2) O41C 0.6595 (4) 0.1413 (4) −0.0106 (4) 0.142 (3)\ O41D 0.6107 (3) 0.6158 (3) −0.0002 (4) 0.087 (3) O42C 0.7457 (4) 0.0960 (4) −0.0805 (4) 0.111 (3) O42D 0.5606 (3) 0.6355 (4) 0.0996 (3) 0.100 (3) N1C 0.9779 (2) 0.2952 (3) 0.3310 (2) 0.0397 (16) N1D 0.9879 (2) 0.4909 (3) 0.3227 (2) 0.0410 (16) N41C 0.7239 (3) 0.1135 (5) −0.0243 (4) 0.095 (3) N41D 0.6136 (3) 0.6286 (4) 0.0638 (4) 0.072 (3) C2C 0.9348 (3) 0.2378 (4) 0.3602 (3) 0.0467 (19) C2D 1.0279 (3) 0.5244 (4) 0.2716 (3) 0.060 (2) C3C 0.9099 (3) 0.1676 (4) 0.3250 (3) 0.050 (2) C3D 1.0007 (3) 0.5839 (4) 0.2253 (3) 0.056 (2) C4C 0.9291 (3) 0.1548 (4) 0.2565 (4) 0.048 (2) C4D 0.9294 (3) 0.6108 (3) 0.2306 (3) 0.0383 (19) C5C 0.9721 (3) 0.2143 (4) 0.2250 (3) 0.0510 (19) C5D 0.8890 (3) 0.5774 (4) 0.2850 (3) 0.055 (2) C6C 0.9953 (3) 0.2838 (4) 0.2631 (3) 0.054 (2) C6D 0.9198 (3) 0.5191 (3) 0.3297 (3) 0.053 (2) C11C 0.8593 (3) 0.0910 (3) 0.1544 (3) 0.0437 (19) C11D 0.8235 (3) 0.6580 (3) 0.1517 (3) 0.0400 (19) C21C 0.8846 (3) 0.0790 (4) 0.0877 (4) 0.056 (3) C21D 0.8159 (3) 0.6233 (3) 0.0871 (3) 0.040 (2) C31C 0.8426 (3) 0.0866 (4) 0.0299 (4) 0.060 (3) C31D 0.7475 (3) 0.6113 (3) 0.0565 (4) 0.049 (2) C41C 0.7692 (3) 0.1101 (4) 0.0397 (4) 0.058 (3) C41D 0.6878 (3) 0.6352 (4) 0.0956 (3) 0.044 (2) C42C 0.9073 (4) 0.0765 (4) 0.2176 (3) 0.061 (3) C42D 0.8996 (3) 0.6763 (4) 0.1819 (3) 0.049 (2) C51C 0.7415 (4) 0.1250 (5) 0.1052 (4) 0.085 (4) C51D 0.6927 (3) 0.6680 (4) 0.1617 (3) 0.050 (2) C61C 0.7878 (3) 0.1152 (4) 0.1627 (4) 0.069 (3) C61D 0.7615 (3) 0.6803 (3) 0.1900 (4) 0.051 (2) H2A 0.86070 0.17080 0.84750 0.0770\* H2B 1.05040 0.03830 0.94750 0.0500\* H3A 0.79250 0.27180 0.90020 0.0770\* H3B 1.01130 −0.06760 1.01810 0.0540\* H5A 0.97650 0.38550 0.95760 0.0800\* H5B 0.86700 −0.13300 0.87090 0.0540\* H6A 1.04280 0.27900 0.90520 0.0690\* H6B 0.90830 −0.02500 0.80340 0.0530\* H21A 0.70790 0.36740 1.02590 0.1180\* H21B 0.76920 −0.19370 0.95350 0.0590\* H31A 0.67470 0.36220 1.13990 0.1280\* H31B 0.65800 −0.15520 1.00160 0.0630\* H42A 0.86090 0.46230 0.96660 0.0960\* H42B 0.94180 −0.19310 1.03670 0.0540\* H43A 0.78850 0.41860 0.94130 0.0960\* H43B 0.89930 −0.23270 0.97310 0.0540\* H51A 0.88020 0.39410 1.20090 0.0860\* H51B 0.76080 −0.08890 1.17890 0.0500\* H61A 0.91370 0.41040 1.08290 0.0820\* H61B 0.87270 −0.11920 1.12790 0.0570\* H2C 0.92080 0.24520 0.40670 0.0560\* H2D 1.07640 0.50710 0.26670 0.0720\* H3C 0.87990 0.12900 0.34790 0.0600\* H3D 1.03090 0.60580 0.19040 0.0670\* H5C 0.98570 0.20820 0.17820 0.0610\* H5D 0.84060 0.59430 0.29160 0.0660\* H6 0.89140 0.49860 0.36650 0.0630\* H6C 1.02390 0.32410 0.24070 0.0650\* H21C 0.93370 0.06470 0.08190 0.0670\* H21D 0.85770 0.60700 0.06250 0.0480\* H31C 0.86160 0.07670 −0.01470 0.0720\* H31D 0.74240 0.58810 0.01190 0.0580\* H42C 0.88150 0.03960 0.24980 0.0730\* H42D 0.93370 0.68300 0.14310 0.0590\* H43C 0.95150 0.04760 0.20250 0.0730\* H43D 0.89760 0.72940 0.20680 0.0590\* H51C 0.69290 0.14130 0.11120 0.1020\* H51D 0.65060 0.68170 0.18700 0.0600\* H61C 0.76970 0.12520 0.20770 0.0830\* H61D 0.76650 0.70340 0.23460 0.0610\* ------ ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2155 .table-wrap} ------ ------------ ------------ ------------ ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ I1 0.0442 (2) 0.0799 (3) 0.0313 (2) −0.0069 (2) −0.0057 (2) 0.0026 (2) I2 0.0398 (2) 0.0944 (3) 0.0359 (2) −0.0126 (2) −0.0025 (2) 0.0057 (2) Zn1 0.0402 (3) 0.0605 (4) 0.0289 (4) −0.0065 (3) −0.0014 (3) 0.0019 (3) O41A 0.108 (6) 0.285 (11) 0.143 (8) 0.053 (6) 0.055 (5) 0.074 (6) O41B 0.081 (3) 0.107 (4) 0.042 (3) 0.013 (3) 0.015 (3) −0.013 (3) O42A 0.097 (4) 0.186 (6) 0.085 (5) 0.013 (5) 0.010 (4) 0.029 (5) O42B 0.048 (3) 0.181 (6) 0.070 (4) 0.016 (3) 0.000 (3) −0.004 (4) N1A 0.046 (3) 0.055 (3) 0.031 (3) −0.008 (2) −0.001 (2) −0.005 (2) N1B 0.036 (2) 0.054 (3) 0.028 (3) −0.002 (2) −0.001 (2) 0.003 (2) N41A 0.100 (6) 0.260 (12) 0.079 (7) 0.001 (8) 0.027 (5) 0.046 (8) N41B 0.068 (4) 0.062 (4) 0.051 (4) 0.005 (3) 0.011 (3) 0.002 (3) C2A 0.061 (4) 0.063 (4) 0.068 (5) −0.004 (3) 0.005 (4) −0.009 (4) C2B 0.036 (3) 0.058 (4) 0.030 (3) −0.006 (3) −0.001 (3) 0.000 (3) C3A 0.057 (4) 0.070 (5) 0.067 (5) 0.009 (4) −0.003 (3) −0.007 (4) C3B 0.036 (3) 0.070 (4) 0.028 (3) 0.004 (3) −0.001 (3) 0.002 (3) C4A 0.062 (4) 0.056 (4) 0.041 (4) 0.013 (4) 0.010 (3) 0.005 (3) C4B 0.036 (3) 0.047 (4) 0.032 (4) 0.007 (3) 0.006 (3) −0.004 (3) C5A 0.084 (5) 0.066 (5) 0.049 (4) −0.013 (4) −0.002 (4) −0.006 (4) C5B 0.043 (3) 0.050 (4) 0.041 (4) −0.008 (3) −0.008 (3) −0.002 (3) C6A 0.057 (4) 0.072 (5) 0.045 (4) −0.001 (4) −0.003 (3) −0.003 (3) C6B 0.046 (3) 0.059 (4) 0.027 (3) −0.004 (3) −0.009 (2) 0.002 (3) C11A 0.063 (4) 0.055 (4) 0.049 (5) 0.023 (3) −0.007 (4) −0.008 (3) C11B 0.038 (3) 0.031 (3) 0.034 (4) 0.003 (3) 0.006 (2) 0.002 (3) C21A 0.048 (4) 0.168 (9) 0.079 (7) 0.006 (5) −0.014 (4) −0.020 (6) C21B 0.044 (3) 0.064 (4) 0.039 (4) 0.004 (3) 0.001 (3) −0.007 (3) C31A 0.056 (5) 0.196 (10) 0.068 (6) −0.019 (6) 0.003 (4) 0.014 (7) C31B 0.044 (3) 0.066 (4) 0.046 (4) 0.003 (3) −0.013 (3) −0.001 (3) C41A 0.063 (4) 0.108 (6) 0.064 (6) 0.008 (4) 0.005 (4) 0.004 (5) C41B 0.041 (3) 0.036 (4) 0.042 (4) 0.007 (3) 0.008 (3) 0.005 (3) C42A 0.090 (5) 0.062 (5) 0.089 (6) 0.034 (4) −0.017 (5) −0.002 (4) C42B 0.045 (3) 0.041 (3) 0.050 (4) 0.003 (3) −0.004 (3) 0.006 (3) C51A 0.050 (4) 0.096 (6) 0.069 (6) 0.012 (4) −0.003 (4) 0.000 (4) C51B 0.059 (4) 0.039 (4) 0.027 (4) 0.005 (3) 0.007 (3) 0.005 (3) C61A 0.049 (4) 0.080 (5) 0.076 (6) 0.004 (4) 0.000 (4) 0.000 (4) C61B 0.046 (3) 0.053 (4) 0.045 (4) −0.006 (3) −0.005 (3) 0.006 (3) I3 0.0382 (2) 0.0769 (3) 0.0405 (3) 0.0048 (2) −0.0001 (2) −0.0048 (2) I4 0.0483 (2) 0.0798 (3) 0.0335 (2) 0.0107 (2) 0.0042 (2) 0.0021 (2) Zn2 0.0391 (3) 0.0570 (5) 0.0317 (4) 0.0012 (3) −0.0014 (3) 0.0019 (3) O41D 0.075 (3) 0.112 (5) 0.075 (5) −0.010 (3) −0.030 (3) 0.002 (3) O42C 0.101 (4) 0.171 (6) 0.062 (5) −0.020 (4) −0.020 (4) 0.002 (4) O42D 0.045 (3) 0.154 (5) 0.100 (5) 0.004 (3) 0.000 (3) −0.028 (4) N1C 0.035 (2) 0.049 (3) 0.035 (3) −0.003 (2) 0.003 (2) −0.001 (2) N1D 0.038 (2) 0.056 (3) 0.029 (3) 0.001 (2) 0.001 (2) 0.003 (2) N41C 0.049 (4) 0.158 (7) 0.077 (6) −0.013 (4) −0.012 (4) 0.017 (5) N41D 0.057 (4) 0.086 (5) 0.073 (5) −0.001 (3) −0.016 (4) 0.001 (4) C2C 0.044 (3) 0.062 (4) 0.034 (3) 0.007 (3) 0.003 (3) −0.001 (3) C2D 0.035 (3) 0.086 (5) 0.060 (4) 0.013 (3) 0.006 (3) 0.019 (4) C3C 0.050 (3) 0.056 (4) 0.044 (4) −0.008 (3) 0.003 (3) 0.011 (3) C3D 0.037 (3) 0.081 (5) 0.050 (4) −0.002 (3) 0.011 (3) 0.031 (4) C4C 0.045 (3) 0.044 (4) 0.055 (5) 0.002 (3) −0.018 (3) 0.008 (3) C4D 0.047 (3) 0.040 (4) 0.028 (3) −0.007 (3) −0.004 (3) 0.002 (3) C5C 0.055 (3) 0.065 (4) 0.033 (3) −0.003 (3) 0.003 (3) −0.004 (3) C5D 0.043 (3) 0.074 (5) 0.047 (4) 0.011 (3) 0.010 (3) 0.020 (4) C6C 0.045 (3) 0.074 (5) 0.043 (4) −0.010 (3) −0.003 (3) 0.007 (3) C6D 0.046 (3) 0.069 (4) 0.043 (4) −0.003 (3) 0.003 (3) 0.012 (3) C11C 0.044 (3) 0.035 (3) 0.052 (4) −0.004 (3) −0.006 (3) −0.007 (3) C11D 0.043 (3) 0.038 (3) 0.039 (4) −0.010 (3) −0.002 (3) 0.017 (3) C21C 0.048 (3) 0.066 (5) 0.054 (5) 0.006 (3) 0.003 (3) −0.005 (4) C21D 0.051 (3) 0.039 (4) 0.030 (4) 0.002 (3) 0.006 (3) −0.001 (3) C31C 0.051 (4) 0.072 (5) 0.056 (5) −0.003 (3) 0.009 (3) −0.001 (4) C31D 0.054 (3) 0.054 (4) 0.038 (4) 0.006 (3) −0.007 (3) −0.003 (3) C41C 0.045 (3) 0.082 (5) 0.048 (5) −0.016 (3) −0.015 (3) 0.006 (4) C41D 0.043 (3) 0.046 (4) 0.042 (4) 0.005 (3) −0.009 (3) −0.002 (3) C42C 0.083 (5) 0.050 (4) 0.049 (4) 0.001 (3) −0.011 (4) −0.009 (3) C42D 0.047 (3) 0.062 (4) 0.038 (4) −0.002 (3) 0.002 (3) 0.002 (3) C51C 0.042 (4) 0.160 (8) 0.054 (6) 0.012 (4) 0.007 (4) −0.003 (5) C51D 0.040 (3) 0.060 (4) 0.050 (4) 0.004 (3) 0.006 (3) 0.002 (3) C61C 0.053 (4) 0.107 (6) 0.048 (5) 0.004 (4) 0.014 (3) −0.011 (4) C61D 0.057 (4) 0.064 (4) 0.031 (3) −0.004 (3) 0.006 (3) −0.004 (3) ------ ------------ ------------ ------------ ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3427 .table-wrap} --------------------------- ------------- --------------------------- ------------ I1---Zn1 2.5578 (7) C6A---H6A 0.9300 I2---Zn1 2.5525 (7) C6B---H6B 0.9300 I3---Zn2 2.5666 (7) C21A---H21A 0.9300 I4---Zn2 2.5472 (8) C21B---H21B 0.9300 Zn1---N1A 2.052 (4) C31A---H31A 0.9300 Zn1---N1B 2.052 (4) C31B---H31B 0.9300 Zn2---N1C 2.044 (4) C42A---H42A 0.9700 Zn2---N1D 2.048 (4) C42A---H43A 0.9700 O41A---N41A 1.280 (13) C42B---H42B 0.9700 O41B---N41B 1.207 (9) C42B---H43B 0.9700 O42A---N41A 1.207 (13) C51A---H51A 0.9300 O42B---N41B 1.217 (8) C51B---H51B 0.9300 O41C---N41C 1.280 (9) C61A---H61A 0.9300 O41D---N41D 1.236 (11) C61B---H61B 0.9300 O42C---N41C 1.174 (11) C2C---C3C 1.379 (9) O42D---N41D 1.187 (8) C2D---C3D 1.385 (8) N1A---C2A 1.348 (7) C3C---C4C 1.365 (9) N1A---C6A 1.324 (7) C3D---C4D 1.371 (8) N1B---C2B 1.350 (7) C4C---C5C 1.367 (9) N1B---C6B 1.347 (7) C4C---C42C 1.502 (9) N41A---C41A 1.495 (13) C4D---C5D 1.377 (8) N41B---C41B 1.476 (8) C4D---C42D 1.496 (8) N1C---C6C 1.343 (7) C5C---C6C 1.388 (9) N1C---C2C 1.326 (7) C5D---C6D 1.378 (8) N1D---C6D 1.325 (7) C11C---C21C 1.364 (9) N1D---C2D 1.327 (7) C11C---C42C 1.505 (8) N41C---C41C 1.472 (10) C11C---C61C 1.367 (8) N41D---C41D 1.484 (8) C11D---C21D 1.355 (8) C2A---C3A 1.354 (8) C11D---C42D 1.528 (8) C2B---C3B 1.365 (8) C11D---C61D 1.390 (8) C3A---C4A 1.375 (9) C21C---C31C 1.345 (10) C3B---C4B 1.377 (8) C21D---C31D 1.388 (8) C4A---C5A 1.346 (10) C31C---C41C 1.400 (8) C4A---C42A 1.527 (9) C31D---C41D 1.371 (8) C4B---C42B 1.507 (7) C41C---C51C 1.366 (11) C4B---C5B 1.377 (8) C41D---C51D 1.365 (8) C5A---C6A 1.390 (9) C51C---C61C 1.390 (10) C5B---C6B 1.369 (8) C51D---C61D 1.378 (8) C11A---C61A 1.377 (11) C2C---H2C 0.9300 C11A---C21A 1.331 (10) C2D---H2D 0.9300 C11A---C42A 1.505 (11) C3C---H3C 0.9300 C11B---C42B 1.516 (8) C3D---H3D 0.9300 C11B---C61B 1.384 (9) C5C---H5C 0.9300 C11B---C21B 1.390 (8) C5D---H5D 0.9300 C21A---C31A 1.331 (13) C6C---H6C 0.9300 C21B---C31B 1.372 (8) C6D---H6 0.9300 C31A---C41A 1.346 (12) C21C---H21C 0.9300 C31B---C41B 1.370 (8) C21D---H21D 0.9300 C41A---C51A 1.354 (10) C31C---H31C 0.9300 C41B---C51B 1.368 (8) C31D---H31D 0.9300 C51A---C61A 1.392 (12) C42C---H42C 0.9700 C51B---C61B 1.376 (8) C42C---H43C 0.9700 C2A---H2A 0.9300 C42D---H42D 0.9700 C2B---H2B 0.9300 C42D---H43D 0.9700 C3A---H3A 0.9300 C51C---H51C 0.9300 C3B---H3B 0.9300 C51D---H51D 0.9300 C5A---H5A 0.9300 C61C---H61C 0.9300 C5B---H5B 0.9300 C61D---H61D 0.9300 I1---Zn1---I2 119.96 (2) C4A---C42A---H43A 109.00 I1---Zn1---N1A 105.83 (11) C4A---C42A---H42A 109.00 I1---Zn1---N1B 111.55 (11) H42A---C42A---H43A 108.00 I2---Zn1---N1A 110.54 (11) C11A---C42A---H43A 109.00 I2---Zn1---N1B 107.94 (11) C11A---C42A---H42A 109.00 N1A---Zn1---N1B 98.99 (17) C11B---C42B---H42B 109.00 I4---Zn2---N1D 110.49 (11) C4B---C42B---H43B 109.00 N1C---Zn2---N1D 99.42 (17) C4B---C42B---H42B 109.00 I3---Zn2---I4 120.39 (3) C11B---C42B---H43B 109.00 I3---Zn2---N1C 104.77 (11) H42B---C42B---H43B 108.00 I3---Zn2---N1D 109.76 (11) C41A---C51A---H51A 121.00 I4---Zn2---N1C 109.83 (11) C61A---C51A---H51A 121.00 Zn1---N1A---C6A 123.6 (3) C61B---C51B---H51B 120.00 C2A---N1A---C6A 117.3 (5) C41B---C51B---H51B 120.00 Zn1---N1A---C2A 118.9 (4) C11A---C61A---H61A 120.00 Zn1---N1B---C6B 124.1 (3) C51A---C61A---H61A 120.00 Zn1---N1B---C2B 119.9 (3) C11B---C61B---H61B 120.00 C2B---N1B---C6B 115.9 (4) C51B---C61B---H61B 120.00 O41A---N41A---C41A 112.9 (8) N1C---C2C---C3C 123.3 (5) O41A---N41A---O42A 126.1 (9) N1D---C2D---C3D 123.0 (5) O42A---N41A---C41A 120.7 (9) C2C---C3C---C4C 120.0 (6) O42B---N41B---C41B 118.6 (7) C2D---C3D---C4D 120.4 (5) O41B---N41B---O42B 122.8 (6) C3C---C4C---C5C 117.6 (6) O41B---N41B---C41B 118.6 (6) C3C---C4C---C42C 121.8 (6) Zn2---N1C---C2C 124.7 (4) C5C---C4C---C42C 120.6 (6) Zn2---N1C---C6C 118.4 (4) C3D---C4D---C5D 116.2 (5) C2C---N1C---C6C 116.8 (5) C3D---C4D---C42D 121.0 (5) Zn2---N1D---C2D 122.5 (4) C5D---C4D---C42D 122.7 (5) Zn2---N1D---C6D 120.5 (3) C4C---C5C---C6C 119.8 (6) C2D---N1D---C6D 116.8 (5) C4D---C5D---C6D 120.4 (5) O41C---N41C---O42C 125.2 (7) N1C---C6C---C5C 122.6 (5) O41C---N41C---C41C 110.9 (7) N1D---C6D---C5D 123.1 (5) O42C---N41C---C41C 123.8 (6) C21C---C11C---C42C 121.8 (5) O41D---N41D---C41D 116.9 (6) C21C---C11C---C61C 118.0 (6) O42D---N41D---C41D 120.0 (7) C42C---C11C---C61C 120.3 (6) O41D---N41D---O42D 123.1 (6) C21D---C11D---C42D 120.8 (5) N1A---C2A---C3A 123.5 (5) C21D---C11D---C61D 119.8 (5) N1B---C2B---C3B 123.2 (5) C42D---C11D---C61D 119.4 (5) C2A---C3A---C4A 119.0 (5) C11C---C21C---C31C 123.8 (5) C2B---C3B---C4B 120.6 (5) C11D---C21D---C31D 121.9 (5) C3A---C4A---C5A 118.2 (6) C21C---C31C---C41C 117.2 (7) C3A---C4A---C42A 120.1 (6) C21D---C31D---C41D 116.5 (6) C5A---C4A---C42A 121.5 (6) N41C---C41C---C31C 115.8 (6) C3B---C4B---C5B 116.7 (5) N41C---C41C---C51C 122.8 (6) C3B---C4B---C42B 121.4 (5) C31C---C41C---C51C 121.4 (7) C5B---C4B---C42B 121.9 (5) N41D---C41D---C31D 118.7 (6) C4A---C5A---C6A 120.5 (6) N41D---C41D---C51D 117.5 (5) C4B---C5B---C6B 120.2 (5) C31D---C41D---C51D 123.7 (5) N1A---C6A---C5A 121.4 (5) C4C---C42C---C11C 114.9 (5) N1B---C6B---C5B 123.4 (5) C4D---C42D---C11D 115.4 (5) C21A---C11A---C42A 120.6 (7) C41C---C51C---C61C 118.4 (6) C42A---C11A---C61A 118.8 (6) C41D---C51D---C61D 118.3 (5) C21A---C11A---C61A 120.5 (8) C11C---C61C---C51C 121.2 (7) C21B---C11B---C61B 118.2 (5) C11D---C61D---C51D 119.8 (6) C42B---C11B---C61B 121.9 (5) N1C---C2C---H2C 118.00 C21B---C11B---C42B 119.9 (5) C3C---C2C---H2C 118.00 C11A---C21A---C31A 119.6 (8) N1D---C2D---H2D 118.00 C11B---C21B---C31B 121.7 (6) C3D---C2D---H2D 119.00 C21A---C31A---C41A 121.9 (7) C2C---C3C---H3C 120.00 C21B---C31B---C41B 118.1 (5) C4C---C3C---H3C 120.00 N41A---C41A---C51A 117.2 (8) C2D---C3D---H3D 120.00 C31A---C41A---C51A 120.5 (9) C4D---C3D---H3D 120.00 N41A---C41A---C31A 122.3 (8) C4C---C5C---H5C 120.00 N41B---C41B---C51B 119.5 (5) C6C---C5C---H5C 120.00 C31B---C41B---C51B 122.1 (5) C4D---C5D---H5D 120.00 N41B---C41B---C31B 118.4 (5) C6D---C5D---H5D 120.00 C4A---C42A---C11A 113.5 (5) N1C---C6C---H6C 119.00 C4B---C42B---C11B 111.8 (4) C5C---C6C---H6C 119.00 C41A---C51A---C61A 117.9 (8) N1D---C6D---H6 119.00 C41B---C51B---C61B 119.1 (6) C5D---C6D---H6 118.00 C11A---C61A---C51A 119.4 (7) C11C---C21C---H21C 118.00 C11B---C61B---C51B 120.8 (5) C31C---C21C---H21C 118.00 N1A---C2A---H2A 118.00 C11D---C21D---H21D 119.00 C3A---C2A---H2A 118.00 C31D---C21D---H21D 119.00 N1B---C2B---H2B 118.00 C21C---C31C---H31C 121.00 C3B---C2B---H2B 118.00 C41C---C31C---H31C 121.00 C2A---C3A---H3A 120.00 C21D---C31D---H31D 122.00 C4A---C3A---H3A 121.00 C41D---C31D---H31D 122.00 C4B---C3B---H3B 120.00 C4C---C42C---H42C 109.00 C2B---C3B---H3B 120.00 C4C---C42C---H43C 109.00 C4A---C5A---H5A 120.00 C11C---C42C---H42C 108.00 C6A---C5A---H5A 120.00 C11C---C42C---H43C 109.00 C4B---C5B---H5B 120.00 H42C---C42C---H43C 108.00 C6B---C5B---H5B 120.00 C4D---C42D---H42D 108.00 N1A---C6A---H6A 119.00 C4D---C42D---H43D 108.00 C5A---C6A---H6A 119.00 C11D---C42D---H42D 108.00 C5B---C6B---H6B 118.00 C11D---C42D---H43D 108.00 N1B---C6B---H6B 118.00 H42D---C42D---H43D 107.00 C11A---C21A---H21A 120.00 C41C---C51C---H51C 121.00 C31A---C21A---H21A 120.00 C61C---C51C---H51C 121.00 C11B---C21B---H21B 119.00 C41D---C51D---H51D 121.00 C31B---C21B---H21B 119.00 C61D---C51D---H51D 121.00 C41A---C31A---H31A 119.00 C11C---C61C---H61C 119.00 C21A---C31A---H31A 119.00 C51C---C61C---H61C 119.00 C21B---C31B---H31B 121.00 C11D---C61D---H61D 120.00 C41B---C31B---H31B 121.00 C51D---C61D---H61D 120.00 I1---Zn1---N1A---C2A 49.9 (4) C5B---C4B---C42B---C11B −76.6 (7) I1---Zn1---N1A---C6A −124.7 (4) C3B---C4B---C42B---C11B 102.9 (6) I2---Zn1---N1A---C2A −178.7 (4) C4A---C5A---C6A---N1A 1.8 (10) I2---Zn1---N1A---C6A 6.7 (5) C4B---C5B---C6B---N1B −0.3 (9) N1B---Zn1---N1A---C2A −65.6 (4) C42A---C11A---C61A---C51A 175.8 (6) N1B---Zn1---N1A---C6A 119.8 (4) C61A---C11A---C21A---C31A 5.3 (13) I1---Zn1---N1B---C2B 173.9 (3) C21A---C11A---C42A---C4A −108.2 (8) I1---Zn1---N1B---C6B −9.9 (4) C42A---C11A---C21A---C31A −173.0 (8) I2---Zn1---N1B---C2B 40.1 (4) C21A---C11A---C61A---C51A −2.6 (10) I2---Zn1---N1B---C6B −143.7 (4) C61A---C11A---C42A---C4A 73.5 (8) N1A---Zn1---N1B---C2B −75.0 (4) C61B---C11B---C21B---C31B 2.3 (8) N1A---Zn1---N1B---C6B 101.1 (4) C42B---C11B---C21B---C31B −179.1 (5) I3---Zn2---N1D---C6D −171.8 (4) C21B---C11B---C42B---C4B 83.4 (6) I4---Zn2---N1D---C2D 148.3 (4) C61B---C11B---C42B---C4B −98.1 (6) I4---Zn2---N1D---C6D −36.8 (4) C21B---C11B---C61B---C51B 0.1 (8) N1C---Zn2---N1D---C2D −96.3 (4) C42B---C11B---C61B---C51B −178.5 (5) N1C---Zn2---N1D---C6D 78.6 (4) C11A---C21A---C31A---C41A −5.6 (14) I4---Zn2---N1C---C2C −9.4 (5) C11B---C21B---C31B---C41B −3.8 (9) I4---Zn2---N1C---C6C 175.3 (4) C21A---C31A---C41A---N41A −180.0 (9) N1D---Zn2---N1C---C2C −125.4 (4) C21A---C31A---C41A---C51A 3.1 (14) N1D---Zn2---N1C---C6C 59.4 (4) C21B---C31B---C41B---N41B −176.0 (5) I3---Zn2---N1D---C2D 13.3 (5) C21B---C31B---C41B---C51B 2.9 (8) I3---Zn2---N1C---C2C 121.2 (4) C31A---C41A---C51A---C61A −0.3 (11) I3---Zn2---N1C---C6C −54.1 (4) N41A---C41A---C51A---C61A −177.4 (7) C2A---N1A---C6A---C5A −1.1 (8) N41B---C41B---C51B---C61B 178.2 (5) Zn1---N1A---C6A---C5A 173.6 (5) C31B---C41B---C51B---C61B −0.7 (8) Zn1---N1A---C2A---C3A −174.7 (5) C41A---C51A---C61A---C11A 0.1 (10) C6A---N1A---C2A---C3A 0.2 (8) C41B---C51B---C61B---C11B −0.9 (9) Zn1---N1B---C6B---C5B −173.9 (4) N1C---C2C---C3C---C4C −0.4 (9) C2B---N1B---C6B---C5B 2.4 (8) N1D---C2D---C3D---C4D −0.3 (9) Zn1---N1B---C2B---C3B 173.8 (4) C2C---C3C---C4C---C5C −1.1 (9) C6B---N1B---C2B---C3B −2.7 (8) C2C---C3C---C4C---C42C 176.0 (6) O41A---N41A---C41A---C51A 163.4 (8) C2D---C3D---C4D---C5D 2.0 (8) O41A---N41A---C41A---C31A −13.6 (13) C2D---C3D---C4D---C42D 178.8 (5) O42A---N41A---C41A---C31A 172.3 (9) C3C---C4C---C5C---C6C 0.9 (9) O42A---N41A---C41A---C51A −10.7 (13) C42C---C4C---C5C---C6C −176.2 (6) O41B---N41B---C41B---C31B 164.8 (5) C3C---C4C---C42C---C11C 118.7 (6) O42B---N41B---C41B---C31B −12.7 (8) C5C---C4C---C42C---C11C −64.4 (8) O42B---N41B---C41B---C51B 168.3 (5) C3D---C4D---C5D---C6D −1.3 (8) O41B---N41B---C41B---C51B −14.2 (7) C42D---C4D---C5D---C6D −178.0 (5) Zn2---N1C---C6C---C5C 173.4 (4) C3D---C4D---C42D---C11D 135.3 (6) Zn2---N1C---C2C---C3C −173.3 (4) C5D---C4D---C42D---C11D −48.1 (8) C6C---N1C---C2C---C3C 2.1 (8) C4C---C5C---C6C---N1C 0.8 (9) C2C---N1C---C6C---C5C −2.2 (8) C4D---C5D---C6D---N1D −1.3 (9) Zn2---N1D---C2D---C3D 172.8 (4) C42C---C11C---C21C---C31C 176.1 (6) C6D---N1D---C2D---C3D −2.3 (8) C61C---C11C---C21C---C31C −2.5 (9) C2D---N1D---C6D---C5D 3.1 (8) C21C---C11C---C42C---C4C 110.0 (6) Zn2---N1D---C6D---C5D −172.2 (4) C61C---C11C---C42C---C4C −71.4 (7) O42C---N41C---C41C---C31C 1.9 (11) C21C---C11C---C61C---C51C 1.8 (9) O42C---N41C---C41C---C51C −175.3 (8) C42C---C11C---C61C---C51C −176.9 (6) O41C---N41C---C41C---C31C −175.3 (6) C42D---C11D---C21D---C31D −175.6 (5) O41C---N41C---C41C---C51C 7.5 (10) C61D---C11D---C21D---C31D 1.9 (8) O41D---N41D---C41D---C51D 165.3 (6) C21D---C11D---C42D---C4D −97.1 (6) O42D---N41D---C41D---C31D 167.7 (6) C61D---C11D---C42D---C4D 85.4 (6) O42D---N41D---C41D---C51D −14.8 (10) C21D---C11D---C61D---C51D −0.8 (8) O41D---N41D---C41D---C31D −12.3 (9) C42D---C11D---C61D---C51D 176.7 (5) N1A---C2A---C3A---C4A 0.1 (9) C11C---C21C---C31C---C41C 1.5 (10) N1B---C2B---C3B---C4B 0.9 (9) C11D---C21D---C31D---C41D −1.0 (8) C2A---C3A---C4A---C42A 177.2 (6) C21C---C31C---C41C---N41C −176.9 (6) C2A---C3A---C4A---C5A 0.5 (9) C21C---C31C---C41C---C51C 0.3 (10) C2B---C3B---C4B---C42B −178.2 (5) C21D---C31D---C41D---N41D 176.4 (5) C2B---C3B---C4B---C5B 1.3 (8) C21D---C31D---C41D---C51D −1.1 (9) C3A---C4A---C42A---C11A 89.9 (7) N41C---C41C---C51C---C61C 176.1 (7) C42A---C4A---C5A---C6A −178.1 (6) C31C---C41C---C51C---C61C −0.9 (11) C3A---C4A---C5A---C6A −1.4 (10) N41D---C41D---C51D---C61D −175.3 (6) C5A---C4A---C42A---C11A −93.5 (8) C31D---C41D---C51D---C61D 2.1 (10) C3B---C4B---C5B---C6B −1.6 (8) C41C---C51C---C61C---C11C −0.2 (10) C42B---C4B---C5B---C6B 177.9 (5) C41D---C51D---C61D---C11D −1.1 (9) --------------------------- ------------- --------------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5613 .table-wrap} ---------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C5A---H5A···O41D^i^ 0.93 2.57 3.211 (9) 126 C6B---H6B···O41B^ii^ 0.93 2.49 3.295 (8) 145 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) x+1/2, −y+1, z+1; (ii) −x+3/2, y, z−1/2.	PubMed Central	2024-06-05T04:04:18.889453	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052165/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m359", "authors": [ { "first": "Graham", "last": "Smith" }, { "first": "Urs D.", "last": "Wermuth" }, { "first": "Michael L.", "last": "Williams" } ] }
PMC3052166	Related literature {#sec1} ================== For another ammonium tetrachlorido(pyridine-2-carboxylato)stannate, see: Najafi et al. (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~6~H~16~N)\[SnCl~4~(C~6~H~4~NO~2~)\]M ~r~ = 484.79Monoclinic,a = 11.6310 (7) Åb = 10.4912 (6) Åc = 16.4452 (9) Åβ = 109.672 (1)°V = 1889.57 (19) Å^3^Z = 4Mo Kα radiationμ = 1.92 mm^−1^T = 100 K0.30 × 0.25 × 0.05 mm ### Data collection {#sec2.1.2} Bruker SMART APEX diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1996[@bb4]) T ~min~ = 0.596, T ~max~ = 0.91017476 measured reflections4344 independent reflections3896 reflections with I \> 2σ(I)R ~int~ = 0.033 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.019wR(F ^2^) = 0.048S = 1.014344 reflections242 parameters25 restraintsH-atom parameters constrainedΔρ~max~ = 0.41 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e459} Data collection: APEX2 (Bruker, 2009[@bb2]); cell refinement: SAINT (Bruker, 2009[@bb2]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb5]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb5]); molecular graphics: X-SEED (Barbour, 2001[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005460/si2335sup1.cif](http://dx.doi.org/10.1107/S1600536811005460/si2335sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005460/si2335Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005460/si2335Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2335&file=si2335sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2335sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2335&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2335](http://scripts.iucr.org/cgi-bin/sendsup?si2335)). We thank the University of Malaya for supporting this study. Comment ======= In the reaction of pyridine-2-carboxylic acid and stannic chloride in methanol, one equivalent of the carboxylic acid is protonated at the amino site and is also esterified, the reaction yielding the salt, (C~7~H~8~NO~2~)^+^ \[SnCl~4~(C~6~H~4~NO~2~)\]^-^. The Sn^IV^ atom in the anion is N,O-chelated by the pyridine-2-carboxylate in a cis-SnNOCl~4~ octahedral geometry (Najafi et al., 2011). In the present study, triethylamine was added to function as proton abstractor. The reaction affords a similar salt, (Et~3~NH)^+^ \[SnCl~4~(C~6~H~4~NO~2~)\]^-^ (Scheme I, Fig. 1). The tin atom in the stannate is chelated by the pyridine-2-carboxylate group and it exists in a cis-SnCl~4~NO octahedral geometry. Experimental {#experimental} ============ The reaction was carried out under a nitrogen atmosphere. Pyridine-2-carboxylic acid (1.0 mmol, 0.12 g) and the triethylamine (1.0 mmol, 0.10 g) were dissolved in dry methanol (20 ml). Stannic chloride ((1.0 mmol, 0.35 g) was added to the mixture and stirred for 12 h. Suitable crystals were obtained by slow evaporation of the solvent. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.95 to 0.99, N--H 0.88 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2 to 1.5U(C). The triethylammonium cation is disordered over two positions in a 56.4 (1): 43.6 (1) ratio. The N--C distances were restrained to within 0.01 Å of each other, as were the C--C distances. Because the C11\' atom is close to the C11 atom (the C12\' atom is also close to the C12 atom), the temperature factors of the C11\' atom were restrained to those of the C11 atom; those of the C12\' atom were set to those of the C12 atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of (Et3NH)+ \[SnCl4(C6H4NO2)\]- at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. The disorder in the cation is not shown. ::: ![](e-67-0m351-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e195 .table-wrap} ---------------------------------------- --------------------------------------- (C~6~H~16~N)\[SnCl~4~(C~6~H~4~NO~2~)\] F(000) = 960 M~r~ = 484.79 D~x~ = 1.704 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 8286 reflections a = 11.6310 (7) Å θ = 2.3--28.3° b = 10.4912 (6) Å µ = 1.92 mm^−1^ c = 16.4452 (9) Å T = 100 K β = 109.672 (1)° Prism, colorless V = 1889.57 (19) Å^3^ 0.30 × 0.25 × 0.05 mm Z = 4 ---------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e333 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX diffractometer 4344 independent reflections Radiation source: fine-focus sealed tube 3896 reflections with I \> 2σ(I) graphite R~int~ = 0.033 ω scans θ~max~ = 27.5°, θ~min~ = 2.3° Absorption correction: multi-scan (SADABS; Sheldrick, 1996) h = −15→15 T~min~ = 0.596, T~max~ = 0.910 k = −13→13 17476 measured reflections l = −19→21 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e447 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.019 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.048 H-atom parameters constrained S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.0213P)^2^ + 0.5451P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4344 reflections (Δ/σ)~max~ = 0.001 242 parameters Δρ~max~ = 0.41 e Å^−3^ 25 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e606 .table-wrap} ------- --------------- --------------- -------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) Sn1 0.563342 (11) 0.304590 (11) 0.743404 (8) 0.01440 (5) Cl1 0.37811 (4) 0.38342 (5) 0.64455 (3) 0.02443 (11) Cl2 0.47250 (5) 0.23860 (5) 0.84821 (3) 0.02561 (11) Cl3 0.56293 (4) 0.08950 (4) 0.69586 (3) 0.01948 (10) Cl4 0.67771 (4) 0.36886 (4) 0.65317 (3) 0.01872 (10) O1 0.59288 (12) 0.48336 (12) 0.80497 (8) 0.0200 (3) O2 0.69627 (13) 0.58704 (13) 0.92554 (9) 0.0263 (3) N1 0.74369 (14) 0.28596 (14) 0.84631 (10) 0.0150 (3) C1 0.68201 (17) 0.49487 (17) 0.87734 (12) 0.0187 (4) C2 0.77238 (17) 0.38638 (17) 0.90022 (11) 0.0151 (4) C3 0.87950 (17) 0.39107 (17) 0.96906 (12) 0.0183 (4) H3 0.8968 0.4612 1.0079 0.022\ C4 0.96192 (18) 0.29127 (18) 0.98084 (12) 0.0207 (4) H4 1.0377 0.2933 1.0269 0.025\* C5 0.93224 (19) 0.18882 (18) 0.92456 (12) 0.0208 (4) H5 0.9873 0.1195 0.9317 0.025\* C6 0.82192 (18) 0.18857 (17) 0.85810 (12) 0.0189 (4) H6 0.8009 0.1178 0.8199 0.023\* N2 0.5100 (3) 0.7717 (3) 0.8635 (2) 0.0168 (8) 0.564 (3) H2 0.5718 0.7181 0.8804 0.020\* 0.564 (3) C7 0.5607 (4) 0.9017 (4) 0.8956 (3) 0.0209 (9) 0.564 (3) H7A 0.6002 0.9376 0.8559 0.025\* 0.564 (3) H7B 0.4927 0.9589 0.8948 0.025\* 0.564 (3) C8 0.6523 (4) 0.8976 (4) 0.9858 (3) 0.0289 (9) 0.564 (3) H8A 0.6834 0.9837 1.0035 0.043\* 0.564 (3) H8B 0.7203 0.8416 0.9868 0.043\* 0.564 (3) H8C 0.6130 0.8648 1.0256 0.043\* 0.564 (3) C9 0.4203 (3) 0.7295 (3) 0.9059 (2) 0.0227 (8) 0.564 (3) H9A 0.3543 0.7936 0.8941 0.027\* 0.564 (3) H9B 0.4623 0.7263 0.9691 0.027\* 0.564 (3) C10 0.3642 (5) 0.6008 (5) 0.8754 (4) 0.0307 (12) 0.564 (3) H10A 0.3067 0.5791 0.9053 0.046\* 0.564 (3) H10B 0.4286 0.5361 0.8882 0.046\* 0.564 (3) H10C 0.3207 0.6036 0.8130 0.046\* 0.564 (3) C11 0.4630 (14) 0.7685 (17) 0.7665 (4) 0.0215 (11) 0.564 (3) H11A 0.4388 0.6801 0.7472 0.026\* 0.564 (3) H11B 0.5297 0.7934 0.7450 0.026\* 0.564 (3) C12 0.3551 (13) 0.8558 (13) 0.7272 (9) 0.0279 (18) 0.564 (3) H12A 0.3340 0.8565 0.6643 0.042\* 0.564 (3) H12B 0.3762 0.9423 0.7497 0.042\* 0.564 (3) H12C 0.2852 0.8250 0.7422 0.042\* 0.564 (3) N2\' 0.4707 (4) 0.7281 (4) 0.8540 (3) 0.0178 (10) 0.436 (3) H2\' 0.5376 0.6845 0.8801 0.021\* 0.436 (3) C7\' 0.4711 (4) 0.8380 (4) 0.9124 (3) 0.0232 (11) 0.436 (3) H7\'A 0.4561 0.8058 0.9645 0.028\* 0.436 (3) H7\'B 0.4036 0.8968 0.8822 0.028\* 0.436 (3) C8\' 0.5902 (5) 0.9107 (6) 0.9395 (5) 0.0281 (14) 0.436 (3) H8\'A 0.5857 0.9819 0.9770 0.042\* 0.436 (3) H8\'B 0.6050 0.9438 0.8882 0.042\* 0.436 (3) H8\'C 0.6570 0.8537 0.9711 0.042\* 0.436 (3) C9\' 0.3664 (5) 0.6386 (5) 0.8450 (4) 0.0206 (12) 0.436 (3) H9\'A 0.3600 0.5777 0.7977 0.025\* 0.436 (3) H9\'B 0.2895 0.6881 0.8289 0.025\* 0.436 (3) C10\' 0.3807 (5) 0.5650 (5) 0.9267 (4) 0.0288 (12) 0.436 (3) H10D 0.3119 0.5061 0.9166 0.043\* 0.436 (3) H10E 0.3822 0.6245 0.9730 0.043\* 0.436 (3) H10F 0.4572 0.5167 0.9435 0.043\* 0.436 (3) C11\' 0.4774 (19) 0.765 (2) 0.7673 (6) 0.0215 (11) 0.44 H11C 0.4877 0.6871 0.7366 0.026\* 0.436 (3) H11D 0.5502 0.8194 0.7762 0.026\* 0.436 (3) C12\' 0.3646 (18) 0.8367 (19) 0.7110 (11) 0.0279 (18) 0.44 H12D 0.3698 0.8490 0.6533 0.042\* 0.436 (3) H12E 0.3603 0.9198 0.7370 0.042\* 0.436 (3) H12F 0.2913 0.7872 0.7066 0.042\* 0.436 (3) ------- --------------- --------------- -------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1462 .table-wrap} ------- ------------- ------------- ------------- --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Sn1 0.01336 (7) 0.01342 (7) 0.01478 (7) 0.00074 (5) 0.00259 (5) −0.00027 (5) Cl1 0.0152 (2) 0.0307 (3) 0.0233 (2) 0.00400 (19) 0.00109 (19) 0.00435 (19) Cl2 0.0271 (3) 0.0307 (3) 0.0228 (2) 0.0027 (2) 0.0133 (2) 0.0037 (2) Cl3 0.0254 (2) 0.0132 (2) 0.0181 (2) −0.00356 (17) 0.00515 (18) −0.00112 (17) Cl4 0.0195 (2) 0.0163 (2) 0.0205 (2) −0.00436 (17) 0.00697 (18) −0.00023 (17) O1 0.0195 (7) 0.0164 (6) 0.0194 (7) 0.0054 (5) 0.0005 (6) −0.0035 (5) O2 0.0283 (8) 0.0197 (7) 0.0251 (7) 0.0066 (6) 0.0015 (6) −0.0080 (6) N1 0.0164 (8) 0.0141 (7) 0.0131 (7) 0.0015 (6) 0.0033 (6) −0.0008 (6) C1 0.0198 (10) 0.0157 (9) 0.0197 (9) 0.0019 (7) 0.0054 (8) −0.0004 (7) C2 0.0180 (9) 0.0149 (8) 0.0139 (9) 0.0008 (7) 0.0072 (7) 0.0005 (7) C3 0.0204 (10) 0.0179 (9) 0.0146 (9) 0.0006 (7) 0.0033 (7) −0.0012 (7) C4 0.0187 (10) 0.0236 (10) 0.0159 (9) 0.0029 (8) 0.0008 (8) 0.0029 (7) C5 0.0234 (10) 0.0183 (9) 0.0191 (10) 0.0073 (8) 0.0049 (8) 0.0024 (7) C6 0.0221 (10) 0.0152 (9) 0.0192 (9) 0.0031 (7) 0.0069 (8) −0.0005 (7) N2 0.0134 (19) 0.018 (2) 0.0199 (17) 0.0040 (13) 0.0071 (15) 0.0005 (15) C7 0.021 (2) 0.0159 (18) 0.028 (2) 0.0027 (15) 0.012 (2) −0.0004 (19) C8 0.036 (3) 0.028 (2) 0.026 (2) −0.0108 (19) 0.015 (2) −0.0077 (18) C9 0.0178 (17) 0.0273 (19) 0.0266 (19) −0.0008 (14) 0.0120 (15) −0.0011 (15) C10 0.030 (2) 0.027 (3) 0.038 (4) −0.012 (2) 0.015 (3) −0.003 (2) C11 0.021 (3) 0.0250 (13) 0.0191 (10) 0.0037 (17) 0.0075 (11) 0.0019 (8) C12 0.026 (2) 0.029 (4) 0.026 (5) 0.004 (2) 0.006 (2) 0.005 (3) N2\' 0.015 (3) 0.018 (3) 0.022 (2) 0.0004 (17) 0.009 (2) 0.0004 (19) C7\' 0.021 (2) 0.019 (2) 0.030 (3) −0.0010 (18) 0.010 (2) −0.0072 (19) C8\' 0.030 (4) 0.023 (3) 0.032 (4) −0.005 (3) 0.012 (3) −0.009 (3) C9\' 0.020 (3) 0.018 (3) 0.027 (3) −0.002 (2) 0.013 (2) −0.001 (2) C10\' 0.036 (3) 0.027 (3) 0.027 (3) −0.005 (2) 0.016 (3) 0.001 (2) C11\' 0.021 (3) 0.0250 (13) 0.0191 (10) 0.0037 (17) 0.0075 (11) 0.0019 (8) C12\' 0.026 (2) 0.029 (4) 0.026 (5) 0.004 (2) 0.006 (2) 0.005 (3) ------- ------------- ------------- ------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1978 .table-wrap} --------------------- -------------- ----------------------------- -------------- Sn1---O1 2.1039 (13) C10---H10A 0.9800 Sn1---N1 2.2163 (15) C10---H10B 0.9800 Sn1---Cl1 2.3686 (5) C10---H10C 0.9800 Sn1---Cl3 2.3876 (5) C11---C12 1.512 (8) Sn1---Cl4 2.3990 (5) C11---H11A 0.9900 Sn1---Cl2 2.4066 (5) C11---H11B 0.9900 O1---C1 1.294 (2) C12---H12A 0.9800 O2---C1 1.226 (2) C12---H12B 0.9800 N1---C6 1.338 (2) C12---H12C 0.9800 N1---C2 1.345 (2) N2\'---C7\' 1.499 (5) C1---C2 1.509 (2) N2\'---C9\' 1.501 (5) C2---C3 1.374 (3) N2\'---C11\' 1.504 (7) C3---C4 1.388 (3) N2\'---H2\' 0.8800 C3---H3 0.9500 C7\'---C8\' 1.511 (6) C4---C5 1.384 (3) C7\'---H7\'A 0.9900 C4---H4 0.9500 C7\'---H7\'B 0.9900 C5---C6 1.377 (3) C8\'---H8\'A 0.9800 C5---H5 0.9500 C8\'---H8\'B 0.9800 C6---H6 0.9500 C8\'---H8\'C 0.9800 N2---C11 1.503 (6) C9\'---C10\' 1.509 (6) N2---C9 1.503 (4) C9\'---H9\'A 0.9900 N2---C7 1.508 (5) C9\'---H9\'B 0.9900 N2---H2 0.8800 C10\'---H10D 0.9800 C7---C8 1.508 (5) C10\'---H10E 0.9800 C7---H7A 0.9900 C10\'---H10F 0.9800 C7---H7B 0.9900 C11\'---C12\' 1.524 (13) C8---H8A 0.9800 C11\'---H11C 0.9900 C8---H8B 0.9800 C11\'---H11D 0.9900 C8---H8C 0.9800 C12\'---H12D 0.9800 C9---C10 1.510 (5) C12\'---H12E 0.9800 C9---H9A 0.9900 C12\'---H12F 0.9800 C9---H9B 0.9900 O1---Sn1---N1 75.63 (5) C9---C10---H10A 109.5 O1---Sn1---Cl1 89.00 (4) C9---C10---H10B 109.5 N1---Sn1---Cl1 164.42 (4) H10A---C10---H10B 109.5 O1---Sn1---Cl3 169.14 (4) C9---C10---H10C 109.5 N1---Sn1---Cl3 93.66 (4) H10A---C10---H10C 109.5 Cl1---Sn1---Cl3 101.778 (17) H10B---C10---H10C 109.5 O1---Sn1---Cl4 90.71 (4) N2---C11---C12 113.1 (11) N1---Sn1---Cl4 85.28 (4) N2---C11---H11A 108.9 Cl1---Sn1---Cl4 92.462 (18) C12---C11---H11A 108.9 Cl3---Sn1---Cl4 90.200 (16) N2---C11---H11B 108.9 O1---Sn1---Cl2 87.23 (4) C12---C11---H11B 108.9 N1---Sn1---Cl2 87.63 (4) H11A---C11---H11B 107.8 Cl1---Sn1---Cl2 94.290 (18) C11---C12---H12A 109.5 Cl3---Sn1---Cl2 90.554 (18) C11---C12---H12B 109.5 Cl4---Sn1---Cl2 172.905 (17) H12A---C12---H12B 109.5 C1---O1---Sn1 118.44 (11) C11---C12---H12C 109.5 C6---N1---C2 119.80 (16) H12A---C12---H12C 109.5 C6---N1---Sn1 126.91 (12) H12B---C12---H12C 109.5 C2---N1---Sn1 113.29 (12) C7\'---N2\'---C9\' 111.9 (4) O2---C1---O1 124.09 (17) C7\'---N2\'---C11\' 114.7 (10) O2---C1---C2 120.18 (17) C9\'---N2\'---C11\' 111.5 (10) O1---C1---C2 115.73 (16) C7\'---N2\'---H2\' 106.0 N1---C2---C3 121.77 (16) C9\'---N2\'---H2\' 106.0 N1---C2---C1 115.42 (16) C11\'---N2\'---H2\' 106.0 C3---C2---C1 122.75 (16) N2\'---C7\'---C8\' 112.5 (4) C2---C3---C4 118.69 (17) N2\'---C7\'---H7\'A 109.1 C2---C3---H3 120.7 C8\'---C7\'---H7\'A 109.1 C4---C3---H3 120.7 N2\'---C7\'---H7\'B 109.1 C5---C4---C3 119.16 (18) C8\'---C7\'---H7\'B 109.1 C5---C4---H4 120.4 H7\'A---C7\'---H7\'B 107.8 C3---C4---H4 120.4 C7\'---C8\'---H8\'A 109.5 C6---C5---C4 119.22 (17) C7\'---C8\'---H8\'B 109.5 C6---C5---H5 120.4 H8\'A---C8\'---H8\'B 109.5 C4---C5---H5 120.4 C7\'---C8\'---H8\'C 109.5 N1---C6---C5 121.32 (17) H8\'A---C8\'---H8\'C 109.5 N1---C6---H6 119.3 H8\'B---C8\'---H8\'C 109.5 C5---C6---H6 119.3 N2\'---C9\'---C10\' 112.9 (5) C11---N2---C9 115.1 (7) N2\'---C9\'---H9\'A 109.0 C11---N2---C7 110.6 (8) C10\'---C9\'---H9\'A 109.0 C9---N2---C7 110.8 (3) N2\'---C9\'---H9\'B 109.0 C11---N2---H2 106.6 C10\'---C9\'---H9\'B 109.0 C9---N2---H2 106.6 H9\'A---C9\'---H9\'B 107.8 C7---N2---H2 106.6 C9\'---C10\'---H10D 109.5 C8---C7---N2 112.4 (4) C9\'---C10\'---H10E 109.5 C8---C7---H7A 109.1 H10D---C10\'---H10E 109.5 N2---C7---H7A 109.1 C9\'---C10\'---H10F 109.5 C8---C7---H7B 109.1 H10D---C10\'---H10F 109.5 N2---C7---H7B 109.1 H10E---C10\'---H10F 109.5 H7A---C7---H7B 107.8 N2\'---C11\'---C12\' 113.2 (14) C7---C8---H8A 109.5 N2\'---C11\'---H11C 108.9 C7---C8---H8B 109.5 C12\'---C11\'---H11C 108.9 H8A---C8---H8B 109.5 N2\'---C11\'---H11D 108.9 C7---C8---H8C 109.5 C12\'---C11\'---H11D 108.9 H8A---C8---H8C 109.5 H11C---C11\'---H11D 107.7 H8B---C8---H8C 109.5 C11\'---C12\'---H12D 109.5 N2---C9---C10 113.6 (3) C11\'---C12\'---H12E 109.5 N2---C9---H9A 108.8 H12D---C12\'---H12E 109.5 C10---C9---H9A 108.8 C11\'---C12\'---H12F 109.5 N2---C9---H9B 108.8 H12D---C12\'---H12F 109.5 C10---C9---H9B 108.8 H12E---C12\'---H12F 109.5 H9A---C9---H9B 107.7 N1---Sn1---O1---C1 −11.42 (13) O1---C1---C2---N1 −5.5 (2) Cl1---Sn1---O1---C1 171.18 (14) O2---C1---C2---C3 −7.3 (3) Cl3---Sn1---O1---C1 −1.6 (3) O1---C1---C2---C3 171.81 (17) Cl4---Sn1---O1---C1 −96.37 (14) N1---C2---C3---C4 2.5 (3) Cl2---Sn1---O1---C1 76.84 (14) C1---C2---C3---C4 −174.58 (18) O1---Sn1---N1---C6 −171.97 (17) C2---C3---C4---C5 −1.8 (3) Cl1---Sn1---N1---C6 −162.25 (12) C3---C4---C5---C6 0.2 (3) Cl3---Sn1---N1---C6 9.87 (16) C2---N1---C6---C5 −0.2 (3) Cl4---Sn1---N1---C6 −80.03 (15) Sn1---N1---C6---C5 179.52 (14) Cl2---Sn1---N1---C6 100.27 (16) C4---C5---C6---N1 0.8 (3) O1---Sn1---N1---C2 7.73 (12) C11---N2---C7---C8 −156.5 (7) Cl1---Sn1---N1---C2 17.5 (2) C9---N2---C7---C8 74.7 (4) Cl3---Sn1---N1---C2 −170.42 (12) C11---N2---C9---C10 52.6 (8) Cl4---Sn1---N1---C2 99.68 (12) C7---N2---C9---C10 179.0 (4) Cl2---Sn1---N1---C2 −80.02 (12) C9---N2---C11---C12 61.6 (14) Sn1---O1---C1---O2 −167.96 (16) C7---N2---C11---C12 −64.9 (13) Sn1---O1---C1---C2 12.9 (2) C9\'---N2\'---C7\'---C8\' 166.0 (5) C6---N1---C2---C3 −1.5 (3) C11\'---N2\'---C7\'---C8\' −65.8 (10) Sn1---N1---C2---C3 178.74 (14) C7\'---N2\'---C9\'---C10\' −69.7 (6) C6---N1---C2---C1 175.77 (17) C11\'---N2\'---C9\'---C10\' 160.4 (10) Sn1---N1---C2---C1 −4.0 (2) C7\'---N2\'---C11\'---C12\' −66.1 (18) O2---C1---C2---N1 175.38 (18) C9\'---N2\'---C11\'---C12\' 62.3 (19) --------------------- -------------- ----------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3088 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N2---H2···O2 0.88 1.95 2.828 (4) 172 N2\'---H2\'···O2 0.88 2.02 2.895 (5) 173 ------------------ --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A -------------- --------- ------- ----------- ------------- N2---H2⋯O2 0.88 1.95 2.828 (4) 172 N2′---H2′⋯O2 0.88 2.02 2.895 (5) 173 :::	PubMed Central	2024-06-05T04:04:18.898715	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052166/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m351", "authors": [ { "first": "Ezzatollah", "last": "Najafi" }, { "first": "Mostafa M.", "last": "Amini" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052167	Related literature {#sec1} ================== For polymorphism and pseudopolymorphs, see: Bernstein (2002[@bb3]); Byrn et al. (1999[@bb4]); Aitipamula et al. (2010[@bb1]). For nitrofurantoin hydrate and anhydrate crystal structures, see: Otsuka et al. (1991[@bb9]); Pienaar et al. (1993a [@bb10],b [@bb11]); Bertolasi et al. (1993)[@bb17] and for nitrofurantoin pseudopolymorphs, see: Caira et al. (1996[@bb5]); Tutughamiarso et al. (2011[@bb15]). For a 1:1 co-crystal involving nitrofurantoin and 4-hydroxybenzoic acid, see: Vangala et al. (2011[@bb16]). For hydrogen bonding, see: Desiraju & Steiner (1999[@bb8]); Desiraju (2002[@bb6], 2007[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~8~H~6~N~4~O~5~·CH~4~OM ~r~ = 270.21Monoclinic,a = 6.4084 (13) Åb = 6.5941 (13) Åc = 26.705 (5) Åβ = 91.70 (3)°V = 1128.0 (4) Å^3^Z = 4Mo Kα radiationμ = 0.14 mm^−1^T = 110 K0.13 × 0.11 × 0.11 mm ### Data collection {#sec2.1.2} Rigaku Saturn 70 CCD area-deterctor diffractometerAbsorption correction: multi-scan (CrystalClear; Rigaku, 2008[@bb12]) T ~min~ = 0.983, T ~max~ = 0.98517441 measured reflections3299 independent reflections2849 reflections with I \> 2σ(I)R ~int~ = 0.048 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.071wR(F ^2^) = 0.129S = 1.243299 reflections212 parametersAll H-atom parameters refinedΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e532} Data collection: CrystalClear (Rigaku, 2008)[@bb12]; cell refinement: CrystalClear [@bb12]; data reduction: CrystalClear [@bb12]; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb13]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb13]); molecular graphics: X-SEED (Barbour, 2001[@bb2]); software used to prepare material for publication: SHELXTL (Sheldrick, 2008[@bb13]) and PLATON (Spek, 2009[@bb14]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003679/ng5112sup1.cif](http://dx.doi.org/10.1107/S1600536811003679/ng5112sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003679/ng5112Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003679/ng5112Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5112&file=ng5112sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5112sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5112&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5112](http://scripts.iucr.org/cgi-bin/sendsup?ng5112)). This work was supported by the Science and Engineering Research Council of A\STAR (Agency for Science, Technology and Research), Singapore. Comment ======= Polymorphism is an ability of a molecule to exist in two or more crystal structures. Incorporation of solvent molecules into the crystalline lattice are routinely referred to as solvates, inclusion complexes and/or pseudopolymorphs (Bernstein, 2002; Byrn et al., 1999; Aitipamula et al., 2010). A full characterization of various crystal forms of an active pharmaceutical ingredient (API) may reveal desired physical form. Thus, it is relevant to pharmaceutical industry. Nitrofurantoin {(E)-1-\[(5-nitro-2-furyl)methylideneamino\]imidazoldine-2,4-dione} is an antibacterial agent used in the treatment of genitourinary tract infections. It exists in both anhydrous (α- and β-) and hydrate forms (Forms I and II) (Pienaar et al., 1993a, 1993b; Bertolasi et al., 1993), and literature findings show that nitrofurantoin has poor physical properties (Otsuka et al., 1991; Caira et al., 1996). We have recently reported a 1:1 co-crystal involving nitrofurantoin and 4-hydroxybenzoic acid and shown that co-crystal displayed superior physicochemical and photo-stability to that of nitrofurantoin. However, co-crystallization attempt of nitrofurantoin with fumaric acid in methanol instead yielded the title pseudopolymorph, nitrofurantoin methanol monosolvate. It was reported that this API is known to form inclusion complexes with dimethylformamide, dimethyl sulfoxide and dimethylacetamide (Caira et al., 1996; Tutughamiarso et al., 2011). Herein we report the structural features of a 1:1 pseudopolymorph involving nitrofurantoin and methanol (Fig. 1). Thermogravimetric analysis (TGA traces) of the title compound is shown in Fig. 2. The measured weight loss (11.6% w/w) in the temperature range of 110--140 °C is in agreement with the stoichiometric weight content for a methanol monosolvate (11.8% w/w). Single crystal X-ray diffraction analysis reveals that the crystal structure contains one molecule each of nitrofurantoin and methanol in the asymmetric unit (Fig. 1). It has crystallized in the monoclinic crystal system with P2~1~/c* space group. In the structure, nitrofurantoin and methanol molecules were essentially held together by a primary co-operative synthon of N---H···O---H···O \[D/Å, θ/°: 2.755 (2), 170 (3); 2.787 (2), 172 (3)\] between amide N4---H4, methanolic O6---H6 and imide O5 along the a-axis (Fig. 3). In addition, there are significant C---H···O hydrogen bonds (Desiraju & Steiner 1999; Desiraju 2002; Desiraju 2007) within nitrofurantoin molecules, which lead to ribbons running along a-axis and support the key hydrogen bonding synthon (Fig. 4). It has structural reminiscences with anhydrous nitrofurantoin (β-form), where the packing is stabilized by imide catemer of N---H···O interactions (Pienaar et al., 1993b; Bertolasi et al., 1993). Here, however, it is replaced with N---H···O---H···O catemer type of heterosynthon by retaining a two fold screw axis. Recently, we have noted an identical synthon in a 1:1 co-crystal involving nitrofurantoin and phenolic co-former (4-hydroxybenzoic acid) (Vangala et al., 2011). Hence, supramolecularly methnolic O--H interacted similar to what phenolic O--H is able to do in the reported co-crystal. The overall crystal packing of the title pseudopolymorph is further assisted by weak C---H···O interactions to give a herringbone type of pattern (Fig. 5). Further analysis showed that this herringbone pattern was comparable to that of a crystal structure of nitrofurantoin dimethyl sulfoxide monosolvate (Tutughamiarso et al., 2011). Experimental {#experimental} ============ The title psuedopolymorph was obtained by evaporative crystallization during attempts to co-crystallize a commercially available (purchased from Aldrich) nitrofurantoin (β-form, 119 mg, 0.5 mmol) with fumaric acid (58 mg, 0.5 mmol) in methanol (25 ml) at ambient conditions. The yellow needle shaped crystals suitable for single-crystal X-ray diffraction were obtained in three days. Refinement {#refinement} ========== All H atoms bonded to C, N, O atoms were located in a difference map and allowed to ride on their parent atoms in the refinement cycles. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A perspective view showing the molecular structures of nitrofurantoin and methanol, with atom labels and 50% probability displacement ellipsoids for non-H atoms. The dashed line shows the N---H···O hydrogen bond. ::: ![](e-67-0o550-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### TGA traces showed that there was a weight loss of 11.6% (w/w), which can be attributed to a methanol solvate. ::: ![](e-67-0o550-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A partial packing diagram of the title pseudopolymorph is viewed down b-axis, showing formation of the N---H···O---H···O synthon along a-axis. Notice the strong C---H···O hydrogen bonds within nitrofurantoin molecules to support the solid-state structure. ::: ![](e-67-0o550-fig3) ::: ::: {#Fap4 .fig} Fig. 4. ::: {.caption} ###### A partial packing diagram of the title pseudopolymorph is viewed down b-axis, showing ribbons running along a-axis. Notice the methanol monosolvate showed in space filled style. ::: ![](e-67-0o550-fig4) ::: ::: {#Fap5 .fig} Fig. 5. ::: {.caption} ###### Crystal packing of the title pseudopolymorph is viewed down the a-axis, showing a herringbone pattern. Notice also the methanol monosolvate showed in space filled style. ::: ![](e-67-0o550-fig5) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e239 .table-wrap} ------------------------- --------------------------------------- C~8~H~6~N~4~O~5~·CH~4~O D~x~ = 1.591 Mg m^−3^ M~r~ = 270.21 Melting point: 547 K Monoclinic, P2~1~/c Mo Kα radiation, λ = 0.71073 Å a = 6.4084 (13) Å Cell parameters from 2901 reflections b = 6.5941 (13) Å θ = 1.5--31.2° c = 26.705 (5) Å µ = 0.14 mm^−1^ β = 91.70 (3)° T = 110 K V = 1128.0 (4) Å^3^ Block, yellow Z = 4 0.13 × 0.11 × 0.11 mm F(000) = 560 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e373 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Rigaku Saturn 70 CCD area-deterctor diffractometer 3299 independent reflections Radiation source: fine-focus sealed tube 2849 reflections with I \> 2σ(I) graphite R~int~ = 0.048 ω scans θ~max~ = 31.2°, θ~min~ = 3.2° Absorption correction: multi-scan (CrystalClear; Rigaku, 2008) h = −6→9 T~min~ = 0.983, T~max~ = 0.985 k = −8→9 17441 measured reflections l = −37→37 ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.071 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.129 All H-atom parameters refined S = 1.24 w = 1/\[σ^2^(F~o~^2^) + (0.033P)^2^ + 0.7077P\] where P = (F~o~^2^ + 2F~c~^2^)/3 3299 reflections (Δ/σ)~max~ \< 0.001 212 parameters Δρ~max~ = 0.24 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ----- ------------ ------------- ------------- -------------------- -- x y z U~iso~\/U~eq~ O6 0.9997 (2) −0.1389 (2) 0.22463 (5) 0.0263 (3) C9 0.9409 (4) −0.0216 (3) 0.18136 (8) 0.0278 (4) H9C 0.997 (4) 0.115 (4) 0.1824 (10) 0.042 (7)\ H9B 0.990 (4) −0.085 (4) 0.1496 (10) 0.039 (7)\* H9A 0.786 (4) −0.017 (4) 0.1807 (10) 0.047 (8)\* H6 1.134 (5) −0.139 (4) 0.2267 (10) 0.046 (8)\* O3 0.6808 (2) 0.3602 (2) 0.58168 (5) 0.0284 (3) N3 0.5389 (2) 0.0501 (2) 0.36110 (6) 0.0215 (3) O2 0.4103 (2) 0.4243 (2) 0.62695 (5) 0.0295 (3) C7 0.5011 (3) −0.0753 (3) 0.28106 (7) 0.0215 (4) N2 0.5159 (3) 0.1188 (2) 0.40903 (6) 0.0215 (3) N4 0.7053 (3) −0.0642 (3) 0.29543 (6) 0.0221 (3) C4 0.3538 (3) 0.3193 (3) 0.54700 (7) 0.0217 (4) C8 0.3751 (3) −0.0024 (3) 0.32458 (7) 0.0212 (4) C1 0.2822 (3) 0.2104 (3) 0.47230 (7) 0.0210 (4) C6 0.7351 (3) 0.0089 (3) 0.34419 (7) 0.0218 (4) C3 0.1432 (3) 0.3112 (3) 0.54369 (8) 0.0250 (4) C2 0.0962 (3) 0.2407 (3) 0.49475 (8) 0.0238 (4) C5 0.3262 (3) 0.1396 (3) 0.42254 (7) 0.0214 (4) H5 0.208 (3) 0.109 (3) 0.4017 (8) 0.016 (5)\* H2 −0.034 (4) 0.218 (3) 0.4794 (9) 0.027 (6)\* H8B 0.284 (4) −0.114 (4) 0.3365 (9) 0.028 (6)\* O1 0.4459 (2) 0.2587 (2) 0.50437 (5) 0.0212 (3) H4 0.807 (4) −0.098 (4) 0.2753 (10) 0.039 (7)\* H3 0.053 (4) 0.348 (4) 0.5693 (9) 0.034 (7)\* H8A 0.292 (4) 0.116 (4) 0.3134 (9) 0.038 (7)\* O5 0.4315 (2) −0.1331 (2) 0.24050 (5) 0.0259 (3) O4 0.9013 (2) 0.0278 (2) 0.36653 (5) 0.0281 (3) N1 0.4910 (3) 0.3720 (2) 0.58760 (6) 0.0226 (3) ----- ------------ ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1153 .table-wrap} ---- ------------- ------------- ------------- ------------- ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ O6 0.0204 (7) 0.0356 (8) 0.0228 (7) 0.0026 (6) 0.0015 (6) 0.0021 (6) C9 0.0291 (11) 0.0273 (10) 0.0269 (10) −0.0001 (8) 0.0004 (8) 0.0039 (8) O3 0.0195 (7) 0.0364 (8) 0.0294 (7) −0.0017 (6) 0.0000 (6) −0.0018 (6) N3 0.0171 (8) 0.0272 (8) 0.0200 (7) −0.0002 (6) 0.0007 (6) −0.0018 (6) O2 0.0340 (8) 0.0333 (8) 0.0216 (7) −0.0004 (6) 0.0075 (6) −0.0031 (6) C7 0.0192 (9) 0.0216 (9) 0.0236 (9) 0.0011 (7) −0.0004 (7) 0.0016 (7) N2 0.0243 (8) 0.0214 (8) 0.0186 (7) −0.0018 (6) 0.0003 (6) 0.0005 (6) N4 0.0176 (8) 0.0279 (8) 0.0208 (8) 0.0013 (6) 0.0019 (6) 0.0001 (6) C4 0.0229 (9) 0.0212 (9) 0.0211 (8) 0.0006 (7) 0.0037 (7) −0.0008 (7) C8 0.0179 (9) 0.0240 (9) 0.0215 (9) 0.0005 (7) −0.0014 (7) −0.0014 (7) C1 0.0189 (9) 0.0205 (9) 0.0236 (9) −0.0006 (7) −0.0003 (7) 0.0020 (7) C6 0.0184 (9) 0.0242 (9) 0.0228 (9) −0.0016 (7) 0.0000 (7) 0.0027 (7) C3 0.0229 (10) 0.0254 (10) 0.0269 (10) 0.0021 (8) 0.0058 (8) 0.0014 (7) C2 0.0187 (9) 0.0250 (9) 0.0276 (10) 0.0004 (7) −0.0003 (8) 0.0025 (7) C5 0.0185 (9) 0.0214 (9) 0.0241 (9) −0.0001 (7) −0.0012 (7) 0.0003 (7) O1 0.0196 (7) 0.0246 (7) 0.0195 (6) 0.0005 (5) 0.0015 (5) −0.0007 (5) O5 0.0235 (7) 0.0324 (8) 0.0217 (7) 0.0007 (6) −0.0016 (5) −0.0036 (5) O4 0.0186 (7) 0.0390 (8) 0.0267 (7) −0.0029 (6) −0.0004 (5) 0.0026 (6) N1 0.0246 (9) 0.0215 (8) 0.0219 (8) −0.0017 (6) 0.0026 (6) 0.0013 (6) ---- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1532 .table-wrap} ---------------- ------------- ---------------- ------------- O6---C9 1.432 (2) N4---H4 0.88 (3) O6---H6 0.86 (3) C4---C3 1.351 (3) C9---H9C 0.97 (3) C4---O1 1.358 (2) C9---H9B 1.00 (3) C4---N1 1.419 (3) C9---H9A 1.00 (3) C8---H8B 1.00 (2) O3---N1 1.234 (2) C8---H8A 0.99 (3) N3---N2 1.370 (2) C1---C2 1.365 (3) N3---C6 1.375 (2) C1---O1 1.372 (2) N3---C8 1.454 (2) C1---C5 1.444 (3) O2---N1 1.234 (2) C6---O4 1.212 (2) C7---O5 1.220 (2) C3---C2 1.411 (3) C7---N4 1.355 (2) C3---H3 0.94 (2) C7---C8 1.513 (3) C2---H2 0.93 (2) N2---C5 1.286 (3) C5---H5 0.95 (2) N4---C6 1.396 (2) C9---O6---H6 107.0 (19) N3---C8---H8A 112.7 (15) O6---C9---H9C 112.9 (16) C7---C8---H8A 108.3 (15) O6---C9---H9B 112.2 (15) H8B---C8---H8A 111.3 (19) H9C---C9---H9B 106 (2) C2---C1---O1 110.68 (17) O6---C9---H9A 105.6 (16) C2---C1---C5 130.44 (18) H9C---C9---H9A 110 (2) O1---C1---C5 118.88 (16) H9B---C9---H9A 109 (2) O4---C6---N3 128.06 (18) N2---N3---C6 119.80 (15) O4---C6---N4 126.05 (18) N2---N3---C8 127.60 (15) N3---C6---N4 105.89 (16) C6---N3---C8 112.43 (15) C4---C3---C2 104.99 (17) O5---C7---N4 126.39 (18) C4---C3---H3 125.3 (16) O5---C7---C8 126.25 (17) C2---C3---H3 129.7 (16) N4---C7---C8 107.36 (16) C1---C2---C3 106.88 (18) C5---N2---N3 115.25 (16) C1---C2---H2 124.4 (15) C7---N4---C6 112.76 (16) C3---C2---H2 128.8 (15) C7---N4---H4 122.4 (17) N2---C5---C1 120.33 (17) C6---N4---H4 124.8 (17) N2---C5---H5 124.0 (13) C3---C4---O1 113.05 (17) C1---C5---H5 115.7 (13) C3---C4---N1 130.92 (18) C4---O1---C1 104.40 (14) O1---C4---N1 115.98 (16) O2---N1---O3 124.47 (17) N3---C8---C7 101.52 (15) O2---N1---C4 116.97 (16) N3---C8---H8B 112.3 (14) O3---N1---C4 118.54 (16) C7---C8---H8B 110.1 (14) ---------------- ------------- ---------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1894 .table-wrap} ------------------ ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N4---H4···O6 0.88 (3) 1.88 (3) 2.755 (2) 170 (3) O6---H6···O5^i^ 0.86 (3) 1.93 (3) 2.787 (2) 172 (3) C5---H5···O4^ii^ 0.95 (2) 2.22 (2) 3.155 (2) 169.2 (18) C3---H3···O3^ii^ 0.94 (2) 2.42 (2) 3.176 (3) 138 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- ---------- ---------- ----------- ------------- N4---H4⋯O6 0.88 (3) 1.88 (3) 2.755 (2) 170 (3) O6---H6⋯O5^i^ 0.86 (3) 1.93 (3) 2.787 (2) 172 (3) C5---H5⋯O4^ii^ 0.95 (2) 2.22 (2) 3.155 (2) 169.2 (18) C3---H3⋯O3^ii^ 0.94 (2) 2.42 (2) 3.176 (3) 138 (2) Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.906845	2011-2-02	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052167/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o550-o551", "authors": [ { "first": "Venu R.", "last": "Vangala" }, { "first": "Pui Shan", "last": "Chow" }, { "first": "Reginald B. H.", "last": "Tan" } ] }
PMC3052168	Related literature {#sec1} ================== For the synthesis, see: Bossio et al. (1985[@bb2]); Shestakov et al. (2006[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~13~N~5~M ~r~ = 239.28Triclinic,a = 8.2836 (4) Åb = 9.6135 (5) Åc = 16.5694 (8) Åα = 92.121 (1)°β = 96.100 (1)°γ = 112.597 (1)°V = 1206.94 (10) Å^3^Z = 4Mo Kα radiationμ = 0.09 mm^−1^T = 295 K0.30 × 0.20 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometer13373 measured reflections5550 independent reflections4124 reflections with I \> 2σ(I)R ~int~ = 0.019 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.044wR(F ^2^) = 0.136S = 1.015550 reflections345 parameters4 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e444} Data collection: APEX2 (Bruker, 2005[@bb3]); cell refinement: SAINT (Bruker, 2005[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb4]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb4]); molecular graphics: X-SEED (Barbour, 2001[@bb1]); software used to prepare material for publication: publCIF (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006507/hg5003sup1.cif](http://dx.doi.org/10.1107/S1600536811006507/hg5003sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006507/hg5003Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006507/hg5003Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg5003&file=hg5003sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg5003sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg5003&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG5003](http://scripts.iucr.org/cgi-bin/sendsup?hg5003)). We thank Manchester Metropolitan University, Baku State University and the University of Malaya for supporting this study. Comment ======= The reported synthesis involves the reaction of 4,6-dimethylpyrimidin-2-ylcyanamide with o-phenylenediamine, and it illustrates the type of heterocycles that are formed by the reaction of cyanamides with N,N-binucleophiles (Shestakov et al., 2006). The unsubstituted compound was reported earlier (Bossio et al., 1985). The present synthesis is a more convenient synthesis that uses acetylacetone as one of the reactants. An amino N atom in the approximately planar C~13~H~13~N~5~ molecule is connected to a benzimidazoyl fused-ring and a pyrimidyl ring; the amino N atom of the fused ring forms an intramolecular N--H···O hydrogen bond to a pyridmidyl N atom (Scheme I, Fig. 1). There are two independent molecules; each molecule is connected to an inversion-related molecule by an N--H···O hydrogen bond. Experimental {#experimental} ============ 1H-Benzo\[d\]imidazol-2-yliminomethanediamine (0.05 mol) and acetylacetone (0.10 mol, approx.10 ml) along with several drops of acetic acid were heated at 473 for 1 h. The solid that formed on cooling was collected and recrystallized from ethanol to give the title compound in 80% yield; m.p. 623 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C--H 0.93 to 0.96 Å; U(H) 1.2 to 1.5U(C)\] and were included in the refinement in the riding model approximation. The amino H-atoms were located in a difference Fourier map, and were refined with a distance restraint of N--H 0.86±0.01 Å; their temperature factors were refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the two independent molecules of C13H13N5 at the 50% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o719-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e136 .table-wrap} ------------------------- --------------------------------------- C~13~H~13~N~5~ Z = 4 M~r~ = 239.28 F(000) = 504 Triclinic, P1 D~x~ = 1.317 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 8.2836 (4) Å Cell parameters from 4428 reflections b = 9.6135 (5) Å θ = 2.3--27.4° c = 16.5694 (8) Å µ = 0.09 mm^−1^ α = 92.121 (1)° T = 295 K β = 96.100 (1)° Prism, colorless γ = 112.597 (1)° 0.30 × 0.20 × 0.20 mm V = 1206.94 (10) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e269 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII diffractometer 4124 reflections with I \> 2σ(I) Radiation source: fine-focus sealed tube R~int~ = 0.019 graphite θ~max~ = 27.5°, θ~min~ = 1.2° φ and ω scans h = −10→10 13373 measured reflections k = −12→12 5550 independent reflections l = −21→21 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e367 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.044 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.136 H atoms treated by a mixture of independent and constrained refinement S = 1.01 w = 1/\[σ^2^(F~o~^2^) + (0.0736P)^2^ + 0.1933P\] where P = (F~o~^2^ + 2F~c~^2^)/3 5550 reflections (Δ/σ)~max~ = 0.001 345 parameters Δρ~max~ = 0.25 e Å^−3^ 4 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e526 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ N1 0.66435 (17) 0.61916 (15) 0.45010 (8) 0.0480 (3) N2 0.80016 (16) 0.45944 (14) 0.43969 (8) 0.0470 (3) N3 0.94151 (17) 0.67635 (15) 0.53228 (8) 0.0498 (3) N4 1.11489 (17) 0.88346 (14) 0.61816 (8) 0.0491 (3) N5 0.83527 (16) 0.86534 (14) 0.55242 (8) 0.0477 (3) N6 0.98905 (15) 1.11808 (14) 0.92502 (8) 0.0453 (3) N7 0.72463 (16) 1.09201 (14) 0.86230 (8) 0.0452 (3) N8 0.74067 (16) 0.92463 (15) 0.96388 (8) 0.0485 (3) N9 0.52809 (16) 0.73369 (14) 1.01630 (8) 0.0477 (3) N10 0.44770 (16) 0.87329 (14) 0.91397 (8) 0.0464 (3) C1 0.5574 (2) 0.50529 (17) 0.39234 (9) 0.0453 (3) C2 0.3985 (2) 0.48064 (19) 0.34608 (11) 0.0570 (4) H2 0.3415 0.5464 0.3516 0.068\ C3 0.3283 (2) 0.3542 (2) 0.29138 (11) 0.0648 (5) H3A 0.2219 0.3343 0.2590 0.078\* C4 0.4132 (2) 0.2562 (2) 0.28378 (11) 0.0646 (5) H4 0.3630 0.1726 0.2458 0.077\* C5 0.5706 (2) 0.27942 (19) 0.33104 (10) 0.0566 (4) H5 0.6258 0.2122 0.3261 0.068\* C6 0.64326 (19) 0.40638 (17) 0.38613 (9) 0.0446 (3) C7 0.80551 (19) 0.58625 (16) 0.47531 (9) 0.0433 (3) C8 0.96246 (19) 0.81387 (17) 0.56914 (9) 0.0444 (3) C9 1.1398 (2) 1.01836 (18) 0.65380 (10) 0.0502 (4) C10 1.0141 (2) 1.07950 (19) 0.64206 (10) 0.0541 (4) H10 1.0317 1.1723 0.6684 0.065\* C11 0.8619 (2) 0.99939 (18) 0.59025 (10) 0.0492 (4) C12 1.3142 (2) 1.1021 (2) 0.70528 (13) 0.0679 (5) H12A 1.3969 1.0598 0.6921 0.102\* H12B 1.2994 1.0930 0.7618 0.102\* H12C 1.3577 1.2069 0.6949 0.102\* C13 0.7188 (2) 1.0572 (2) 0.57189 (12) 0.0638 (5) H13A 0.6895 1.0528 0.5140 0.096\* H13B 0.7591 1.1600 0.5946 0.096\* H13C 0.6163 0.9959 0.5953 0.096\* C14 1.01079 (19) 1.22562 (16) 0.86868 (9) 0.0423 (3) C15 1.1636 (2) 1.33597 (18) 0.84877 (10) 0.0510 (4) H15 1.2738 1.3468 0.8743 0.061\* C16 1.1476 (2) 1.42941 (19) 0.78990 (10) 0.0563 (4) H16 1.2488 1.5041 0.7758 0.068\* C17 0.9839 (2) 1.41438 (19) 0.75126 (10) 0.0569 (4) H17 0.9777 1.4789 0.7117 0.068\* C18 0.8299 (2) 1.30521 (19) 0.77048 (10) 0.0525 (4) H18 0.7199 1.2954 0.7451 0.063\* C19 0.84684 (19) 1.21133 (16) 0.82922 (9) 0.0433 (3) C20 0.81693 (18) 1.04241 (16) 0.91841 (9) 0.0417 (3) C21 0.56341 (18) 0.84116 (16) 0.96416 (9) 0.0433 (3) C22 0.3584 (2) 0.64850 (18) 1.01769 (10) 0.0489 (4) C23 0.2285 (2) 0.67368 (19) 0.96860 (11) 0.0554 (4) H23 0.1101 0.6147 0.9705 0.066\* C24 0.27647 (19) 0.78683 (18) 0.91699 (10) 0.0494 (4) C25 0.3156 (2) 0.5228 (2) 1.07291 (12) 0.0647 (5) H25A 0.4053 0.5504 1.1191 0.097\* H25B 0.3105 0.4326 1.0439 0.097\* H25C 0.2036 0.5048 1.0911 0.097\* C26 0.1440 (2) 0.8194 (2) 0.86077 (12) 0.0683 (5) H26A 0.1696 0.9257 0.8660 0.102\* H26B 0.0280 0.7643 0.8746 0.102\* H26C 0.1495 0.7889 0.8056 0.102\* H1 0.653 (2) 0.6974 (15) 0.4721 (10) 0.062 (5)\* H3 1.0279 (19) 0.647 (2) 0.5423 (11) 0.067 (5)\* H7 0.6096 (12) 1.0539 (19) 0.8546 (11) 0.063 (5)\* H8 0.811 (2) 0.902 (2) 0.9979 (9) 0.059 (5)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1311 .table-wrap} ----- ------------- ------------- ------------- ------------ ------------- ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ N1 0.0468 (7) 0.0444 (7) 0.0547 (8) 0.0227 (6) −0.0035 (6) 0.0018 (6) N2 0.0440 (7) 0.0451 (7) 0.0521 (7) 0.0199 (6) −0.0010 (6) −0.0007 (6) N3 0.0447 (7) 0.0479 (7) 0.0585 (8) 0.0243 (6) −0.0064 (6) −0.0042 (6) N4 0.0465 (7) 0.0477 (7) 0.0525 (7) 0.0203 (6) −0.0013 (6) −0.0007 (6) N5 0.0470 (7) 0.0495 (7) 0.0504 (7) 0.0239 (6) 0.0032 (6) 0.0015 (6) N6 0.0374 (6) 0.0460 (7) 0.0527 (7) 0.0178 (5) −0.0004 (5) 0.0092 (5) N7 0.0379 (6) 0.0476 (7) 0.0497 (7) 0.0186 (6) −0.0035 (5) 0.0055 (5) N8 0.0357 (6) 0.0484 (7) 0.0606 (8) 0.0167 (5) −0.0021 (6) 0.0146 (6) N9 0.0400 (6) 0.0491 (7) 0.0567 (8) 0.0203 (6) 0.0054 (6) 0.0072 (6) N10 0.0383 (6) 0.0493 (7) 0.0498 (7) 0.0179 (5) −0.0032 (5) −0.0003 (6) C1 0.0457 (8) 0.0438 (8) 0.0443 (8) 0.0157 (6) 0.0015 (6) 0.0101 (6) C2 0.0526 (9) 0.0554 (9) 0.0616 (10) 0.0228 (8) −0.0072 (8) 0.0119 (8) C3 0.0567 (10) 0.0670 (11) 0.0595 (10) 0.0173 (9) −0.0133 (8) 0.0074 (9) C4 0.0641 (11) 0.0588 (10) 0.0566 (10) 0.0128 (9) −0.0057 (8) −0.0046 (8) C5 0.0571 (10) 0.0504 (9) 0.0582 (10) 0.0182 (8) 0.0030 (8) −0.0021 (7) C6 0.0438 (8) 0.0451 (8) 0.0438 (8) 0.0160 (6) 0.0047 (6) 0.0079 (6) C7 0.0415 (7) 0.0440 (8) 0.0456 (8) 0.0189 (6) 0.0020 (6) 0.0058 (6) C8 0.0442 (8) 0.0441 (8) 0.0458 (8) 0.0187 (6) 0.0041 (6) 0.0032 (6) C9 0.0507 (9) 0.0489 (8) 0.0486 (8) 0.0178 (7) 0.0029 (7) 0.0017 (7) C10 0.0586 (10) 0.0495 (9) 0.0560 (9) 0.0245 (8) 0.0055 (8) −0.0047 (7) C11 0.0523 (9) 0.0510 (8) 0.0501 (8) 0.0259 (7) 0.0095 (7) 0.0035 (7) C12 0.0601 (11) 0.0584 (10) 0.0767 (12) 0.0205 (9) −0.0115 (9) −0.0104 (9) C13 0.0617 (11) 0.0672 (11) 0.0729 (12) 0.0382 (9) 0.0051 (9) −0.0016 (9) C14 0.0429 (7) 0.0425 (7) 0.0427 (7) 0.0196 (6) 0.0004 (6) 0.0015 (6) C15 0.0464 (8) 0.0503 (9) 0.0527 (9) 0.0161 (7) 0.0018 (7) 0.0046 (7) C16 0.0619 (10) 0.0485 (9) 0.0538 (9) 0.0158 (8) 0.0094 (8) 0.0069 (7) C17 0.0740 (11) 0.0530 (9) 0.0490 (9) 0.0308 (9) 0.0052 (8) 0.0115 (7) C18 0.0580 (9) 0.0567 (9) 0.0482 (9) 0.0306 (8) −0.0026 (7) 0.0052 (7) C19 0.0472 (8) 0.0428 (8) 0.0418 (7) 0.0218 (6) −0.0007 (6) −0.0004 (6) C20 0.0381 (7) 0.0419 (7) 0.0466 (8) 0.0193 (6) −0.0016 (6) 0.0028 (6) C21 0.0370 (7) 0.0434 (8) 0.0503 (8) 0.0181 (6) 0.0009 (6) −0.0005 (6) C22 0.0431 (8) 0.0494 (8) 0.0560 (9) 0.0194 (7) 0.0101 (7) 0.0004 (7) C23 0.0370 (8) 0.0599 (10) 0.0646 (10) 0.0145 (7) 0.0051 (7) 0.0024 (8) C24 0.0372 (7) 0.0552 (9) 0.0527 (9) 0.0176 (7) −0.0023 (6) −0.0058 (7) C25 0.0547 (10) 0.0660 (11) 0.0781 (12) 0.0242 (9) 0.0201 (9) 0.0210 (9) C26 0.0422 (9) 0.0854 (13) 0.0718 (12) 0.0228 (9) −0.0082 (8) 0.0089 (10) ----- ------------- ------------- ------------- ------------ ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1956 .table-wrap} ---------------------- -------------- ----------------------- -------------- N1---C7 1.3535 (18) C5---H5 0.9300 N1---C1 1.377 (2) C9---C10 1.380 (2) N1---H1 0.86 (1) C9---C12 1.502 (2) N2---C7 1.3176 (19) C10---C11 1.376 (2) N2---C6 1.3960 (19) C10---H10 0.9300 N3---C7 1.3689 (19) C11---C13 1.499 (2) N3---C8 1.3756 (19) C12---H12A 0.9600 N3---H3 0.87 (1) C12---H12B 0.9600 N4---C9 1.336 (2) C12---H12C 0.9600 N4---C8 1.3396 (19) C13---H13A 0.9600 N5---C8 1.3343 (18) C13---H13B 0.9600 N5---C11 1.340 (2) C13---H13C 0.9600 N6---C20 1.3183 (18) C14---C15 1.385 (2) N6---C14 1.3917 (19) C14---C19 1.397 (2) N7---C20 1.3558 (18) C15---C16 1.380 (2) N7---C19 1.383 (2) C15---H15 0.9300 N7---H7 0.87 (1) C16---C17 1.388 (2) N8---C20 1.3650 (19) C16---H16 0.9300 N8---C21 1.3771 (19) C17---C18 1.383 (2) N8---H8 0.87 (1) C17---H17 0.9300 N9---C22 1.3310 (19) C18---C19 1.384 (2) N9---C21 1.3367 (19) C18---H18 0.9300 N10---C21 1.3352 (18) C22---C23 1.380 (2) N10---C24 1.3481 (19) C22---C25 1.498 (2) C1---C2 1.382 (2) C23---C24 1.372 (2) C1---C6 1.396 (2) C23---H23 0.9300 C2---C3 1.378 (3) C24---C26 1.496 (2) C2---H2 0.9300 C25---H25A 0.9600 C3---C4 1.384 (3) C25---H25B 0.9600 C3---H3A 0.9300 C25---H25C 0.9600 C4---C5 1.382 (2) C26---H26A 0.9600 C4---H4 0.9300 C26---H26B 0.9600 C5---C6 1.386 (2) C26---H26C 0.9600 C7---N1---C1 106.87 (13) C9---C12---H12C 109.5 C7---N1---H1 120.2 (12) H12A---C12---H12C 109.5 C1---N1---H1 132.8 (12) H12B---C12---H12C 109.5 C7---N2---C6 104.12 (12) C11---C13---H13A 109.5 C7---N3---C8 126.91 (13) C11---C13---H13B 109.5 C7---N3---H3 115.8 (13) H13A---C13---H13B 109.5 C8---N3---H3 117.0 (13) C11---C13---H13C 109.5 C9---N4---C8 115.66 (13) H13A---C13---H13C 109.5 C8---N5---C11 116.23 (13) H13B---C13---H13C 109.5 C20---N6---C14 104.20 (12) C15---C14---N6 129.94 (13) C20---N7---C19 106.69 (12) C15---C14---C19 119.88 (14) C20---N7---H7 121.9 (12) N6---C14---C19 110.18 (13) C19---N7---H7 131.3 (12) C16---C15---C14 118.09 (15) C20---N8---C21 127.59 (13) C16---C15---H15 121.0 C20---N8---H8 116.5 (13) C14---C15---H15 121.0 C21---N8---H8 115.9 (12) C15---C16---C17 121.51 (16) C22---N9---C21 116.15 (13) C15---C16---H16 119.2 C21---N10---C24 115.57 (14) C17---C16---H16 119.2 N1---C1---C2 132.25 (15) C18---C17---C16 121.25 (15) N1---C1---C6 105.39 (13) C18---C17---H17 119.4 C2---C1---C6 122.37 (15) C16---C17---H17 119.4 C3---C2---C1 116.96 (16) C17---C18---C19 116.95 (15) C3---C2---H2 121.5 C17---C18---H18 121.5 C1---C2---H2 121.5 C19---C18---H18 121.5 C2---C3---C4 121.27 (16) N7---C19---C18 132.51 (14) C2---C3---H3A 119.4 N7---C19---C14 105.17 (12) C4---C3---H3A 119.4 C18---C19---C14 122.32 (15) C5---C4---C3 121.77 (16) N6---C20---N7 113.75 (13) C5---C4---H4 119.1 N6---C20---N8 122.52 (13) C3---C4---H4 119.1 N7---C20---N8 123.73 (13) C4---C5---C6 117.67 (16) N10---C21---N9 127.34 (13) C4---C5---H5 121.2 N10---C21---N8 118.60 (14) C6---C5---H5 121.2 N9---C21---N8 114.06 (12) C5---C6---C1 119.94 (14) N9---C22---C23 120.91 (15) C5---C6---N2 130.14 (14) N9---C22---C25 117.17 (14) C1---C6---N2 109.91 (13) C23---C22---C25 121.90 (15) N2---C7---N1 113.70 (13) C24---C23---C22 119.11 (14) N2---C7---N3 123.06 (13) C24---C23---H23 120.4 N1---C7---N3 123.24 (14) C22---C23---H23 120.4 N5---C8---N4 126.91 (14) N10---C24---C23 120.91 (14) N5---C8---N3 118.65 (13) N10---C24---C26 116.69 (15) N4---C8---N3 114.42 (13) C23---C24---C26 122.39 (15) N4---C9---C10 121.78 (15) C22---C25---H25A 109.5 N4---C9---C12 116.46 (14) C22---C25---H25B 109.5 C10---C9---C12 121.74 (15) H25A---C25---H25B 109.5 C11---C10---C9 118.16 (15) C22---C25---H25C 109.5 C11---C10---H10 120.9 H25A---C25---H25C 109.5 C9---C10---H10 120.9 H25B---C25---H25C 109.5 N5---C11---C10 121.22 (14) C24---C26---H26A 109.5 N5---C11---C13 116.37 (15) C24---C26---H26B 109.5 C10---C11---C13 122.40 (15) H26A---C26---H26B 109.5 C9---C12---H12A 109.5 C24---C26---H26C 109.5 C9---C12---H12B 109.5 H26A---C26---H26C 109.5 H12A---C12---H12B 109.5 H26B---C26---H26C 109.5 C7---N1---C1---C2 −179.49 (17) C20---N6---C14---C15 −179.64 (15) C7---N1---C1---C6 0.26 (16) C20---N6---C14---C19 0.28 (16) N1---C1---C2---C3 178.38 (17) N6---C14---C15---C16 −179.89 (15) C6---C1---C2---C3 −1.3 (2) C19---C14---C15---C16 0.2 (2) C1---C2---C3---C4 0.4 (3) C14---C15---C16---C17 0.0 (2) C2---C3---C4---C5 0.7 (3) C15---C16---C17---C18 0.2 (3) C3---C4---C5---C6 −0.9 (3) C16---C17---C18---C19 −0.6 (2) C4---C5---C6---C1 0.0 (2) C20---N7---C19---C18 −179.50 (16) C4---C5---C6---N2 −178.51 (16) C20---N7---C19---C14 0.38 (16) N1---C1---C6---C5 −178.65 (14) C17---C18---C19---N7 −179.37 (15) C2---C1---C6---C5 1.1 (2) C17---C18---C19---C14 0.8 (2) N1---C1---C6---N2 0.17 (17) C15---C14---C19---N7 179.52 (13) C2---C1---C6---N2 179.95 (14) N6---C14---C19---N7 −0.42 (16) C7---N2---C6---C5 178.13 (16) C15---C14---C19---C18 −0.6 (2) C7---N2---C6---C1 −0.53 (16) N6---C14---C19---C18 179.48 (14) C6---N2---C7---N1 0.72 (17) C14---N6---C20---N7 −0.03 (17) C6---N2---C7---N3 −179.09 (14) C14---N6---C20---N8 179.56 (13) C1---N1---C7---N2 −0.64 (18) C19---N7---C20---N6 −0.23 (17) C1---N1---C7---N3 179.17 (14) C19---N7---C20---N8 −179.82 (14) C8---N3---C7---N2 176.24 (14) C21---N8---C20---N6 177.63 (14) C8---N3---C7---N1 −3.6 (3) C21---N8---C20---N7 −2.8 (3) C11---N5---C8---N4 −1.6 (2) C24---N10---C21---N9 0.1 (2) C11---N5---C8---N3 179.66 (14) C24---N10---C21---N8 179.65 (13) C9---N4---C8---N5 0.2 (2) C22---N9---C21---N10 0.6 (2) C9---N4---C8---N3 179.02 (13) C22---N9---C21---N8 −178.95 (13) C7---N3---C8---N5 3.8 (2) C20---N8---C21---N10 1.4 (2) C7---N3---C8---N4 −175.12 (15) C20---N8---C21---N9 −179.03 (14) C8---N4---C9---C10 1.5 (2) C21---N9---C22---C23 −1.1 (2) C8---N4---C9---C12 −176.69 (15) C21---N9---C22---C25 177.35 (14) N4---C9---C10---C11 −1.8 (3) N9---C22---C23---C24 1.0 (2) C12---C9---C10---C11 176.30 (16) C25---C22---C23---C24 −177.42 (16) C8---N5---C11---C10 1.2 (2) C21---N10---C24---C23 −0.3 (2) C8---N5---C11---C13 −179.73 (14) C21---N10---C24---C26 −179.39 (14) C9---C10---C11---N5 0.4 (3) C22---C23---C24---N10 −0.2 (2) C9---C10---C11---C13 −178.64 (16) C22---C23---C24---C26 178.81 (16) ---------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3158 .table-wrap} ------------------ ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1···N5 0.86 (1) 2.05 (2) 2.664 (2) 128 (2) N3---H3···N2^i^ 0.87 (1) 2.05 (1) 2.912 (2) 170 (2) N7---H7···N10 0.87 (1) 2.10 (2) 2.695 (2) 125 (2) N8---H8···N6^ii^ 0.87 (1) 2.05 (1) 2.908 (2) 170 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+2, −y+2, −z+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- ---------- ---------- ----------- ------------- N1---H1⋯N5 0.86 (1) 2.05 (2) 2.664 (2) 128 (2) N3---H3⋯N2^i^ 0.87 (1) 2.05 (1) 2.912 (2) 170 (2) N7---H7⋯N10 0.87 (1) 2.10 (2) 2.695 (2) 125 (2) N8---H8⋯N6^ii^ 0.87 (1) 2.05 (1) 2.908 (2) 170 (2) Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.910416	2011-2-26	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052168/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o719", "authors": [ { "first": "Shaaban Kamel", "last": "Mohamed" }, { "first": "Mahmoud A. A.", "last": "El-Remaily" }, { "first": "Atash V.", "last": "Gurbanov" }, { "first": "Ali N.", "last": "Khalilov" }, { "first": "Seik Weng", "last": "Ng" } ] }
PMC3052169	Related literature {#sec1} ================== For the preparation of the title compound see: Lamani et al. (2009[@bb8]). For the biological activity of benzisoxazole derivatives, see: Priya et al. (2005[@bb11]). For the use of five-membered heterocyclic ring 1,3,4-thiadiazoles in the design of compounds, see: Katritzky (1984)[@bb7]; Diamond & Sevrain (2003a [@bb3],b [@bb4]); Nakao et al. (2002a [@bb9],b [@bb10]). For related structures, see: Sun & Zhang (2009[@bb13]). For hydrogen-bond motifs, see: Bernstein et al. 1995[@bb1]) Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~11~ClN~4~OSM ~r~ = 366.83Monoclinic,a = 38.419 (7) Åb = 5.7761 (10) Åc = 14.772 (3) Åβ = 108.004 (5)°V = 3117.5 (10) Å^3^Z = 8Mo Kα radiationμ = 0.39 mm^−1^T = 123 K0.18 × 0.16 × 0.16 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD detector diffractometerAbsorption correction: multi-scan Bruker Smart Apex T ~min~ = 0.933, T ~max~ = 0.9408822 measured reflections3379 independent reflections2587 reflections with I \> 2σ(I)R ~int~ = 0.051 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.053wR(F ^2^) = 0.185S = 1.313379 reflections226 parametersH-atom parameters constrainedΔρ~max~ = 0.74 e Å^−3^Δρ~min~ = −0.58 e Å^−3^ {#d5e523} Data collection: SMART (Bruker, 1998[@bb2]); cell refinement: SAINT-Plus (Bruker, 1998[@bb2]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb12]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb12]); molecular graphics: ORTEP-3 (Farrugia, 1997[@bb5]) and CAMERON (Watkin et al., 1996)[@bb14]; software used to prepare material for publication: WinGX (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004582/gw2098sup1.cif](http://dx.doi.org/10.1107/S1600536811004582/gw2098sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004582/gw2098Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004582/gw2098Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gw2098&file=gw2098sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gw2098sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gw2098&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GW2098](http://scripts.iucr.org/cgi-bin/sendsup?gw2098)). NSB is thankful to the University Grants Commission (UGC), India, for financial assistance and the Department of Science and Technology, (DST), India, for the data-collection facility under the IRHPA--DST program. Comment ======= Imidazo\[2,1-b\]\[1,3,4\]thiadiazole derivatives are reported to possess diverse pharmacological properties such as anticancer, antitubercular, antibacterial, antifungal, anticonvulsant, analgesic and antisecretory activities. Moreover, the are known to possess important biological activities (Priya et al., 2005) and are useful in different therapies. Amongst them, five membered heterocyclic ring 1,3,4-thiadiazoles find wide application in designing compounds possessing useful properties (Katritzky et al., 1984; Diamond & Sevrain, 2003a,b; Nakao et al., 2002a,b). Due to the increasing importance of these heterocycles in biological and pharmaceutical fields, new chemical entities were synthesized by incorporating active pharmacophores in a single molecular frame work so as to enhance their biological activities.In the title compound, the benzisoxazole (O1/N4/C3/C13--18) and imidazothiadiazole (S1/N1---N3/C1/C4---C6) rings are individually planar similar to those reported earlier (Sun & Zhang, 2009) with maximum deviations of 0.038 (3)Å for C1 and 0.016 (3)Å for C3 respectively. The mean planes of the benzisoxazole and imidazothiadiazole are inclined at an angle 23.81 (7)° with each other. The imidazothiadiazole and chlorophenyl rings make a dihedral angle of 27.34 (3)°. The thiadiazole moiety displays differences in the bond lengths between S1---C1/S1---C4 \[1.756 (3)/1.736 (3)\]. This can be attributed to the resonance effects of the imidazole ring which is stronger than that due to thiadiazole group. The crystal structure is stabilized by intermolecular C---H···N, C---H···O and S···N interactions. The C---H···N interaction generates chain like pattern along c axis. The C---H···O interaction forms centrosymmetric head-to-head dimers about inversion centers corresponding to R22(26) graph set motif (Bernstein et al., 1995). The C---H···N interaction along with S···N \[3.206 (4) Å\]interaction results in a ring motif with a graph set R(7). The molecular packing is further stabilized by π-π stacking interactions between thiadiazole rings (Cg3: centroid of S1/C1/N2/N3/C4) with the shortest centroid---centroid distance 3.497 (3) Å. In addition, π-ring interactions of the type C---H···Cg (Cg being the centroids of rings C7---C12 and C13---C18) are also observed in the crystal structure; details have been given in Table 1. Experimental {#experimental} ============ The title compound was synthesized by following the procedure reported earlier (Lamani et al., 2009). Refinement {#refinement} ========== The H atoms were placed at calculated positions in the riding model approximation with aromatic C---H = 0.93Å and methylene C---H = 0.97 Å, and U~iso~(H) = 1.2U~eq~(N/C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### ORTEP (Farrugia, 1997) view of the title compound, showing 50% probability ellipsoids and the atom numbering scheme. ::: ![](e-67-0o617-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A unit cell packing of the title compound depicting the C---H···N, C---H···O and S···N intermolecular interactions with dotted lines. H-atoms not involved in hydrogen bonding have been excluded. ::: ![](e-67-0o617-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e158 .table-wrap} ------------------------ --------------------------------------- C~18~H~11~ClN~4~OS F(000) = 1504 M~r~ = 366.83 D~x~ = 1.563 Mg m^−3^ Monoclinic, C2/c Mo Kα radiation, λ = 0.71073 Å Hall symbol: -C 2yc Cell parameters from 3379 reflections a = 38.419 (7) Å θ = 2.2--27.0° b = 5.7761 (10) Å µ = 0.39 mm^−1^ c = 14.772 (3) Å T = 123 K β = 108.004 (5)° Block, yellow V = 3117.5 (10) Å^3^ 0.18 × 0.16 × 0.16 mm Z = 8 ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e283 .table-wrap} ----------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD detector diffractometer 3379 independent reflections Radiation source: fine-focus sealed tube 2587 reflections with I \> 2σ(I) graphite R~int~ = 0.051 ω scans θ~max~ = 27.0°, θ~min~ = 2.2° Absorption correction: multi-scan Bruker Smart Apex h = −46→48 T~min~ = 0.933, T~max~ = 0.940 k = −6→7 8822 measured reflections l = −18→14 ----------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e394 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.053 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.185 H-atom parameters constrained S = 1.31 w = 1/\[σ^2^(F~o~^2^) + (0.0894P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 3379 reflections (Δ/σ)~max~ \< 0.001 226 parameters Δρ~max~ = 0.74 e Å^−3^ 0 restraints Δρ~min~ = −0.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e548 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The compound was synthesized by following the procedure given in Lamani et al., (2009) Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e656 .table-wrap} ----- ------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.19871 (8) 0.2236 (5) 0.1424 (2) 0.0151 (6) C2 0.16451 (8) 0.1564 (5) 0.1657 (2) 0.0183 (7) H2A 0.1565 0.0071 0.1366 0.022\ H2B 0.1711 0.1355 0.2341 0.022\* C3 0.13263 (8) 0.3171 (5) 0.1363 (2) 0.0166 (7) C4 0.25323 (8) 0.4023 (5) 0.1246 (2) 0.0160 (7) C5 0.28417 (8) 0.0835 (6) 0.1177 (2) 0.0167 (6) H5 0.2910 −0.0704 0.1157 0.020\* C6 0.30436 (8) 0.2790 (5) 0.1142 (2) 0.0149 (6) C7 0.34193 (8) 0.2930 (5) 0.1098 (2) 0.0148 (7) C8 0.35464 (9) 0.4896 (5) 0.0746 (2) 0.0181 (7) H8 0.3389 0.6139 0.0527 0.022\* C9 0.39034 (9) 0.5024 (5) 0.0718 (2) 0.0192 (7) H9 0.3986 0.6340 0.0484 0.023\* C10 0.41322 (8) 0.3176 (6) 0.1039 (2) 0.0183 (7) C11 0.40183 (9) 0.1192 (6) 0.1396 (2) 0.0206 (7) H11 0.4178 −0.0038 0.1616 0.025\* C12 0.36610 (8) 0.1082 (6) 0.1418 (2) 0.0178 (7) H12 0.3580 −0.0244 0.1649 0.021\* C13 0.07777 (9) 0.4766 (5) 0.1117 (2) 0.0176 (7) C14 0.04157 (9) 0.5159 (6) 0.1076 (2) 0.0209 (7) H14 0.0292 0.6519 0.0834 0.025\* C15 0.02526 (9) 0.3370 (6) 0.1424 (2) 0.0219 (7) H15 0.0010 0.3519 0.1407 0.026\* C16 0.04440 (8) 0.1336 (6) 0.1800 (3) 0.0212 (7) H16 0.0326 0.0188 0.2036 0.025\* C17 0.08036 (8) 0.1001 (6) 0.1828 (2) 0.0178 (7) H17 0.0928 −0.0352 0.2074 0.021\* C18 0.09718 (8) 0.2764 (5) 0.1474 (2) 0.0166 (7) O1 0.09977 (6) 0.6281 (4) 0.08271 (17) 0.0222 (5) N1 0.28445 (7) 0.4813 (4) 0.11762 (19) 0.0161 (6) N2 0.22129 (7) 0.0628 (5) 0.13533 (19) 0.0171 (6) N3 0.25177 (7) 0.1673 (4) 0.12454 (19) 0.0158 (6) N4 0.13496 (7) 0.5207 (5) 0.1006 (2) 0.0208 (6) S1 0.21240 (2) 0.51078 (13) 0.13431 (6) 0.0182 (2) Cl1 0.45843 (2) 0.33439 (15) 0.10073 (6) 0.0267 (3) ----- ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1135 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0141 (14) 0.0126 (15) 0.0175 (16) 0.0005 (12) 0.0032 (13) 0.0015 (12) C2 0.0170 (15) 0.0154 (16) 0.0248 (18) 0.0016 (12) 0.0095 (14) 0.0034 (13) C3 0.0197 (15) 0.0141 (15) 0.0155 (16) −0.0028 (12) 0.0049 (13) −0.0002 (12) C4 0.0202 (15) 0.0121 (15) 0.0152 (16) 0.0008 (12) 0.0047 (13) −0.0006 (12) C5 0.0152 (14) 0.0138 (15) 0.0214 (16) 0.0032 (12) 0.0062 (13) 0.0002 (13) C6 0.0131 (14) 0.0162 (16) 0.0153 (16) −0.0011 (12) 0.0042 (13) 0.0011 (12) C7 0.0137 (14) 0.0156 (16) 0.0159 (16) −0.0034 (12) 0.0054 (12) −0.0023 (12) C8 0.0206 (16) 0.0157 (16) 0.0191 (17) 0.0021 (12) 0.0078 (14) 0.0006 (12) C9 0.0252 (17) 0.0161 (17) 0.0176 (17) −0.0052 (13) 0.0086 (14) −0.0021 (12) C10 0.0142 (14) 0.0231 (17) 0.0179 (17) −0.0048 (12) 0.0051 (13) −0.0056 (13) C11 0.0231 (16) 0.0177 (17) 0.0220 (18) 0.0049 (13) 0.0084 (14) −0.0019 (13) C12 0.0193 (15) 0.0169 (16) 0.0178 (17) 0.0012 (13) 0.0067 (13) 0.0014 (13) C13 0.0190 (16) 0.0158 (16) 0.0204 (17) −0.0004 (12) 0.0096 (14) 0.0009 (13) C14 0.0194 (16) 0.0200 (17) 0.0220 (18) 0.0035 (13) 0.0042 (14) 0.0000 (13) C15 0.0177 (16) 0.0283 (19) 0.0209 (18) −0.0017 (13) 0.0077 (14) −0.0013 (14) C16 0.0149 (15) 0.0216 (17) 0.0276 (19) −0.0029 (13) 0.0075 (14) 0.0010 (14) C17 0.0172 (15) 0.0163 (16) 0.0202 (17) 0.0005 (12) 0.0060 (13) 0.0023 (13) C18 0.0136 (14) 0.0178 (16) 0.0183 (16) 0.0011 (12) 0.0049 (13) −0.0003 (13) O1 0.0200 (11) 0.0167 (12) 0.0325 (14) 0.0044 (9) 0.0120 (11) 0.0055 (10) N1 0.0114 (12) 0.0167 (14) 0.0206 (14) 0.0006 (10) 0.0054 (11) −0.0008 (11) N2 0.0127 (12) 0.0178 (14) 0.0211 (15) −0.0055 (10) 0.0059 (11) 0.0001 (11) N3 0.0174 (13) 0.0115 (13) 0.0189 (15) −0.0012 (10) 0.0059 (11) 0.0013 (10) N4 0.0147 (13) 0.0244 (16) 0.0251 (16) 0.0015 (11) 0.0087 (12) 0.0010 (12) S1 0.0184 (4) 0.0124 (4) 0.0257 (5) −0.0008 (3) 0.0096 (4) −0.0007 (3) Cl1 0.0177 (4) 0.0329 (5) 0.0318 (5) −0.0021 (3) 0.0110 (4) −0.0057 (4) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1603 .table-wrap} ----------------------- ------------ ---------------------- ------------ C1---N2 1.297 (4) C9---C10 1.371 (4) C1---C2 1.508 (4) C9---H9 0.9300 C1---S1 1.756 (3) C10---C11 1.387 (5) C2---C3 1.490 (4) C10---Cl1 1.755 (3) C2---H2A 0.9700 C11---C12 1.384 (4) C2---H2B 0.9700 C11---H11 0.9300 C3---N4 1.304 (4) C12---H12 0.9300 C3---C18 1.440 (4) C13---O1 1.374 (4) C4---N1 1.316 (4) C13---C14 1.392 (4) C4---N3 1.358 (4) C13---C18 1.389 (4) C4---S1 1.736 (3) C14---C15 1.387 (5) C5---C6 1.380 (4) C14---H14 0.9300 C5---N3 1.369 (4) C15---C16 1.406 (5) C5---H5 0.9300 C15---H15 0.9300 C6---N1 1.406 (4) C16---C17 1.383 (4) C6---C7 1.468 (4) C16---H16 0.9300 C7---C12 1.398 (4) C17---C18 1.392 (4) C7---C8 1.398 (4) C17---H17 0.9300 C8---C9 1.387 (4) O1---N4 1.436 (3) C8---H8 0.9300 N2---N3 1.370 (3) N2---C1---C2 119.1 (3) C12---C11---C10 118.5 (3) N2---C1---S1 116.7 (2) C12---C11---H11 120.7 C2---C1---S1 124.0 (2) C10---C11---H11 120.7 C3---C2---C1 117.9 (3) C11---C12---C7 121.1 (3) C3---C2---H2A 107.8 C11---C12---H12 119.4 C1---C2---H2A 107.8 C7---C12---H12 119.4 C3---C2---H2B 107.8 O1---C13---C14 125.8 (3) C1---C2---H2B 107.8 O1---C13---C18 109.8 (3) H2A---C2---H2B 107.2 C14---C13---C18 124.4 (3) N4---C3---C18 112.3 (3) C13---C14---C15 115.0 (3) N4---C3---C2 121.8 (3) C13---C14---H14 122.5 C18---C3---C2 125.9 (3) C15---C14---H14 122.5 N1---C4---N3 112.7 (3) C14---C15---C16 121.9 (3) N1---C4---S1 138.5 (3) C14---C15---H15 119.1 N3---C4---S1 108.8 (2) C16---C15---H15 119.1 C6---C5---N3 104.3 (3) C17---C16---C15 121.6 (3) C6---C5---H5 127.8 C17---C16---H16 119.2 N3---C5---H5 127.8 C15---C16---H16 119.2 C5---C6---N1 111.2 (3) C16---C17---C18 117.5 (3) C5---C6---C7 128.2 (3) C16---C17---H17 121.3 N1---C6---C7 120.6 (3) C18---C17---H17 121.3 C12---C7---C8 118.3 (3) C17---C18---C13 119.7 (3) C12---C7---C6 120.2 (3) C17---C18---C3 136.7 (3) C8---C7---C6 121.5 (3) C13---C18---C3 103.7 (3) C9---C8---C7 121.1 (3) C13---O1---N4 107.6 (2) C9---C8---H8 119.4 C4---N1---C6 103.5 (2) C7---C8---H8 119.4 C1---N2---N3 108.1 (3) C10---C9---C8 118.8 (3) C4---N3---N2 118.5 (3) C10---C9---H9 120.6 C4---N3---C5 108.4 (3) C8---C9---H9 120.6 N2---N3---C5 133.0 (3) C9---C10---C11 122.1 (3) C3---N4---O1 106.6 (2) C9---C10---Cl1 118.8 (2) C4---S1---C1 87.82 (14) C11---C10---Cl1 119.1 (2) N2---C1---C2---C3 −155.9 (3) O1---C13---C18---C3 −0.9 (3) S1---C1---C2---C3 30.1 (4) C14---C13---C18---C3 179.8 (3) C1---C2---C3---N4 −7.1 (5) N4---C3---C18---C17 −177.9 (4) C1---C2---C3---C18 176.2 (3) C2---C3---C18---C17 −0.9 (6) N3---C5---C6---N1 −0.8 (3) N4---C3---C18---C13 1.6 (4) N3---C5---C6---C7 177.9 (3) C2---C3---C18---C13 178.6 (3) C5---C6---C7---C12 −22.8 (5) C14---C13---O1---N4 179.2 (3) N1---C6---C7---C12 155.8 (3) C18---C13---O1---N4 0.0 (3) C5---C6---C7---C8 157.7 (3) N3---C4---N1---C6 −0.8 (3) N1---C6---C7---C8 −23.7 (4) S1---C4---N1---C6 178.9 (3) C12---C7---C8---C9 −0.3 (5) C5---C6---N1---C4 1.0 (3) C6---C7---C8---C9 179.2 (3) C7---C6---N1---C4 −177.8 (3) C7---C8---C9---C10 0.2 (5) C2---C1---N2---N3 −173.3 (3) C8---C9---C10---C11 −0.3 (5) S1---C1---N2---N3 1.1 (3) C8---C9---C10---Cl1 −179.8 (2) N1---C4---N3---N2 177.4 (3) C9---C10---C11---C12 0.5 (5) S1---C4---N3---N2 −2.5 (3) Cl1---C10---C11---C12 180.0 (2) N1---C4---N3---C5 0.3 (4) C10---C11---C12---C7 −0.7 (5) S1---C4---N3---C5 −179.5 (2) C8---C7---C12---C11 0.6 (5) C1---N2---N3---C4 0.9 (4) C6---C7---C12---C11 −179.0 (3) C1---N2---N3---C5 177.1 (3) O1---C13---C14---C15 −179.3 (3) C6---C5---N3---C4 0.3 (3) C18---C13---C14---C15 −0.1 (5) C6---C5---N3---N2 −176.1 (3) C13---C14---C15---C16 0.9 (5) C18---C3---N4---O1 −1.7 (4) C14---C15---C16---C17 −1.1 (5) C2---C3---N4---O1 −178.8 (3) C15---C16---C17---C18 0.4 (5) C13---O1---N4---C3 1.1 (3) C16---C17---C18---C13 0.4 (5) N1---C4---S1---C1 −177.4 (4) C16---C17---C18---C3 179.8 (4) N3---C4---S1---C1 2.4 (2) O1---C13---C18---C17 178.7 (3) N2---C1---S1---C4 −2.1 (3) C14---C13---C18---C17 −0.6 (5) C2---C1---S1---C4 172.1 (3) ----------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2426 .table-wrap} -------------------------------------------------------------------------------- Cg1 and Cg2 are the centroids of the C7--C12 and C13--C18 rings, respectively. -------------------------------------------------------------------------------- ::: ::: {#d1e2430 .table-wrap} --------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A C9---H9···O1^i^ 0.93 2.39 3.232 (4) 150 C2---H2B···N1^ii^ 0.97 2.49 3.352 (4) 148 C5---H5···N1^iii^ 0.93 2.60 3.478 (4) 157 C17---H17···Cg1^iv^ 0.93 2.78 3.470 (4) 131 C11---H11···Cg2^iv^ 0.93 2.93 3.548 (4) 126 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1/2, −y+3/2, −z; (ii) −x+1/2, y−1/2, −z+1/2; (iii) x, y−1, z; (iv) −x+1/2, y+1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 and Cg2 are the centroids of the C7--C12 and C13--C18 rings, respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- --------- ------- ----------- ------------- C9---H9⋯O1^i^ 0.93 2.39 3.232 (4) 150 C2---H2B⋯N1^ii^ 0.97 2.49 3.352 (4) 148 C5---H5⋯N1^iii^ 0.93 2.60 3.478 (4) 157 C17---H17⋯Cg1^iv^ 0.93 2.78 3.470 (4) 131 C11---H11⋯Cg2^iv^ 0.93 2.93 3.548 (4) 126 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::	PubMed Central	2024-06-05T04:04:18.917327	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052169/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o617-o618", "authors": [ { "first": "Afshan", "last": "Banu" }, { "first": "Mohamed", "last": "Ziaulla" }, { "first": "Noor Shahina", "last": "Begum" }, { "first": "Ravi S.", "last": "Lamani" }, { "first": "I. M.", "last": "Khazi" } ] }
PMC3052170	Related literature {#sec1} ================== For metal complexes with phosphoryl donor ligands, see: Gholivand et al. (2010[@bb4]). For a polyoxometalate-based inorganic--organic compound containing a phosphoryl ligand, see: Niu et al. (1996[@bb6]). For phosphoric triamide compounds having a C(=O)NHP(=O) skeleton, see: Pourayoubi & Sabbaghi (2009[@bb7]) and references cited therein. For bond lengths in related structures, see: Sabbaghi et al. (2010[@bb8]). For hydrogen-bond motifs, see: Etter et al. (1990[@bb3]); Bernstein et al. (1995[@bb1]). For the synthesis of the starting material, CClF~2~C(O)NHP(O)Cl~2~, see: Iriarte et al. (2008[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~21~ClF~2~N~3~O~2~PM ~r~ = 415.80Triclinic,a = 10.3059 (9) Åb = 10.5030 (9) Åc = 10.9473 (9) Åα = 71.743 (2)°β = 67.294 (2)°γ = 63.265 (2)°V = 962.15 (14) Å^3^Z = 2Mo Kα radiationμ = 0.32 mm^−1^T = 120 K0.28 × 0.22 × 0.15 mm ### Data collection {#sec2.1.2} Bruker SMART 1000 CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 1998[@bb9]) T ~min~ = 0.916, T ~max~ = 0.9549258 measured reflections4148 independent reflections3359 reflections with I \> 2σ(I)R ~int~ = 0.025 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.049wR(F ^2^) = 0.111S = 1.004148 reflections247 parametersH-atom parameters constrainedΔρ~max~ = 0.39 e Å^−3^Δρ~min~ = −0.37 e Å^−3^ {#d5e534} Data collection: SMART (Bruker, 1998[@bb2]); cell refinement: SAINT-Plus (Bruker, 1998[@bb2]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb10]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005423/lh5205sup1.cif](http://dx.doi.org/10.1107/S1600536811005423/lh5205sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005423/lh5205Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005423/lh5205Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5205&file=lh5205sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5205sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5205&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5205](http://scripts.iucr.org/cgi-bin/sendsup?lh5205)). Support of this investigation by Islamic Azad University--North Tehran Branch is gratefully acknowledged. Comment ======= Phosphoryl donor ligands have been used to prepare coordination complexes (Gholivand et al., 2010) and polyoxometalate-based inorganic-organic hybrid compounds (Niu et al., 1996). The structure determination of title compound was performed as a part of a project on the synthesis of new potential phosphoric triamide ligands having a C(═O)NHP(═O) skeleton (Pourayoubi & Sabbaghi, 2009). In the title compound, C~18~H~21~ClF~2~N~3~O~2~P, the phosphoryl group and NH unit are syn to each other and the phosphorus atom has a slightly distorted tetrahedral configuration (Fig. 1). The P atom adopts a slightly distorted tetrahedral environment and the N atoms of the tertiary amine groups are bonded in an essentially planar geometry (see Table 1). The P═O bond length is comparable to those in similar compounds e.g. in P(O)\[NHC(O)C~6~H~4~(4-NO~2~)\]\[NHC~6~H~11~\]~2~ (Sabbaghi et al., 2010). In the (CClF~2~)C(O) unit, the O---C---C---F dihedral angles showing the orientation of flourine atoms relative to carbonyl group are 17.7 (3) and 137.1 (2)° and the O---C---C---Cl dihedral angle is -101.9 (2)°. The phosphoryl is a better H-acceptor relative to the carbonyl counterpart (Pourayoubi & Sabbaghi, 2009); so, the hydrogen atom of the C(═ O)NHP(═ O) group is involved in an intermolecular --P═O···H---N-- hydrogen bond (see Table 2) to form a centrosymmetric dimeric aggregate \[graph set: R~2~^2^(8) (Etter et al., 1990; Bernstein et al., 1995)\], Fig. 2. Experimental {#experimental} ============ Synthesis of CClF~2~C(O)NHP(O)Cl~2~: CClF~2~C(O)NHP(O)Cl~2~ was prepared according to procedure reported by Iriarte et al. (2008) from a reaction between phosphorus pentachloride (16.91 mmol) and CClF~2~C(O)NH~2~ (16.91 mmol) in dry CCl~4~ at 358 K (3 h) and then the treatment of formic acid (16.91 mmol) at ice bath temperature; then removing of solvent in vacuum to yield CClF~2~C(O)NHP(O)Cl~2~. Synthesis of title compound: To a solution of CClF~2~C(O)NHP(O)Cl~2~ (1.04 mmol) in dry CHCl~3~, a solution of N-methylbenzylamine (4.16 mmol) in dry CHCl~3~ was added dropwise and stirred at 273 K. After 4 h, the solvent was removed at room temperature. The solid was washed with H~2~O. The product was obtained after recrystallization from a methanol/n-heptane mixture (4:1) after a slow evaporation at room temperature. IR (KBr, cm^-1^): 3066, 2886, 1729 (C═O), 1592, 1481, 1359, 1286, 1218, 1150, 1009, 965, 863, 809, 698. ^19^F NMR (470.59 MHz, DMSO-d6, 300 K, CFCl~3~): -63.69 p.p.m. (s). ^31^P{^1^H} NMR (202.46 MHz, DMSO-d6, 300 K, 85% H~3~PO~4~): 12.80 p.p.m. (s). ^1^H NMR (500.13 MHz, DMSO-d6, 300 K, TMS): 2.48 (s, 3H, CH~3~), 2.50 (s, 3H, CH~3~), 4.16 (m, 4H, CH~2~), 7.25--7.38 (m, 10H, Ar--H), 10.60 p.p.m. (s, 1H, NH). ^13^C NMR (125.76 MHz, DMSO-d6, 300 K, TMS): 33.16 (d, ^2^J(P,C) = 4.6 Hz, 2 C, CH~3~), 51.78 (d, ^2^J(P,C) = 5.1 Hz, 2 C, CH~2~), 118.08 (dt, 1C, CClF~2~), 127.17 (s), 127.96 (s), 128.32 (s), 137.68 (d, ^3^J(P,C) = 3.9 Hz, 2 C, C~ipso~), 159.81 p.p.m. (t, ^2^J(F,C) = 35.0 Hz, 1 C, C═O). Refinement {#refinement} ========== H atoms were placed in calculated postions with C---H = 0.95 - 0.99Å and N---H = 0.87Å and were included in the refinement with U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(C~methyl~). The U~iso~(H) value of the H atom bonded to N3 was refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with displacement ellipsoids at the 50% probability level. ::: ![](e-67-0o663-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the H-bonded (dashed lines) centrosymmetric dimer (symmetry code: (A) 1-x, 1-y, -z). ::: ![](e-67-0o663-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e381 .table-wrap} --------------------------- --------------------------------------- C~18~H~21~ClF~2~N~3~O~2~P Z = 2 M~r~ = 415.80 F(000) = 432 Triclinic, P1 D~x~ = 1.435 Mg m^−3^ Hall symbol: -P 1 Mo Kα radiation, λ = 0.71073 Å a = 10.3059 (9) Å Cell parameters from 3946 reflections b = 10.5030 (9) Å θ = 2.3--29.1° c = 10.9473 (9) Å µ = 0.32 mm^−1^ α = 71.743 (2)° T = 120 K β = 67.294 (2)° Prism, colourless γ = 63.265 (2)° 0.28 × 0.22 × 0.15 mm V = 962.15 (14) Å^3^ --------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e521 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART 1000 CCD area-detector diffractometer 4148 independent reflections Radiation source: fine-focus sealed tube 3359 reflections with I \> 2σ(I) graphite R~int~ = 0.025 φ and ω scans θ~max~ = 27.0°, θ~min~ = 2.1° Absorption correction: multi-scan (SADABS; Sheldrick, 1998) h = −13→13 T~min~ = 0.916, T~max~ = 0.954 k = −13→13 9258 measured reflections l = −13→13 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e638 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.049 Hydrogen site location: mixed wR(F^2^) = 0.111 H-atom parameters constrained S = 1.00 w = 1/\[σ^2^(F~o~^2^) + (0.0309P)^2^ + 1.6759P\] where P = (F~o~^2^ + 2F~c~^2^)/3 4148 reflections (Δ/σ)~max~ \< 0.001 247 parameters Δρ~max~ = 0.39 e Å^−3^ 0 restraints Δρ~min~ = −0.37 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e795 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e894 .table-wrap} ------ -------------- -------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ P1 0.24133 (6) 0.55399 (6) 0.07097 (5) 0.01766 (13) Cl1 0.40224 (7) 0.93801 (7) −0.06620 (6) 0.03255 (16) F1 0.45008 (15) 0.79512 (15) 0.15810 (14) 0.0304 (3) F2 0.25207 (16) 0.99322 (15) 0.16926 (15) 0.0346 (3) O1 0.37544 (16) 0.44767 (15) −0.00684 (15) 0.0207 (3) O2 0.09472 (17) 0.85802 (17) 0.16326 (17) 0.0290 (4) N1 0.11179 (19) 0.66717 (19) −0.00324 (17) 0.0194 (4) N2 0.1560 (2) 0.47741 (19) 0.21311 (17) 0.0205 (4) N3 0.3102 (2) 0.66075 (19) 0.09736 (18) 0.0197 (4) H3N 0.4088 0.6297 0.0731 0.039 (8)\ C1 −0.0432 (3) 0.6755 (3) 0.0358 (2) 0.0300 (5) H1A −0.0678 0.6791 −0.0435 0.045\* H1B −0.1129 0.7630 0.0751 0.045\* H1C −0.0534 0.5902 0.1021 0.045\* C2 0.1497 (3) 0.7723 (2) −0.1223 (2) 0.0232 (4) H2A 0.2436 0.7795 −0.1257 0.028\* H2B 0.0671 0.8685 −0.1125 0.028\* C3 0.1726 (2) 0.7347 (2) −0.2540 (2) 0.0215 (4) C4 0.1249 (2) 0.8454 (2) −0.3561 (2) 0.0241 (5) H4A 0.0693 0.9420 −0.3396 0.029\* C5 0.1583 (3) 0.8152 (3) −0.4825 (2) 0.0281 (5) H5A 0.1265 0.8912 −0.5521 0.034\* C6 0.2378 (3) 0.6744 (3) −0.5067 (2) 0.0299 (5) H6A 0.2612 0.6537 −0.5929 0.036\* C7 0.2835 (3) 0.5633 (3) −0.4041 (2) 0.0293 (5) H7A 0.3371 0.4666 −0.4204 0.035\* C8 0.2511 (3) 0.5929 (2) −0.2784 (2) 0.0254 (5) H8A 0.2825 0.5165 −0.2088 0.030\* C9 0.0398 (3) 0.5614 (2) 0.3182 (2) 0.0254 (5) H9A −0.0450 0.5282 0.3573 0.038\* H9B 0.0031 0.6641 0.2790 0.038\* H9C 0.0839 0.5478 0.3885 0.038\* C10 0.2044 (3) 0.3195 (2) 0.2526 (2) 0.0235 (4) H10A 0.2779 0.2738 0.1736 0.028\* H10B 0.1151 0.2927 0.2808 0.028\* C11 0.2766 (2) 0.2604 (2) 0.3657 (2) 0.0217 (4) C12 0.4040 (3) 0.2854 (2) 0.3528 (2) 0.0249 (5) H12A 0.4465 0.3391 0.2720 0.030\* C13 0.4683 (3) 0.2321 (2) 0.4577 (2) 0.0263 (5) H13A 0.5547 0.2497 0.4485 0.032\* C14 0.4077 (3) 0.1535 (2) 0.5757 (2) 0.0267 (5) H14A 0.4521 0.1177 0.6473 0.032\* C15 0.2827 (3) 0.1271 (2) 0.5896 (2) 0.0279 (5) H15A 0.2415 0.0723 0.6702 0.034\* C16 0.2175 (3) 0.1812 (2) 0.4847 (2) 0.0250 (5) H16A 0.1309 0.1635 0.4948 0.030\* C17 0.2317 (2) 0.7958 (2) 0.1275 (2) 0.0213 (4) C18 0.3323 (3) 0.8782 (2) 0.1073 (2) 0.0242 (5) ------ -------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1556 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ P1 0.0166 (3) 0.0174 (3) 0.0179 (3) −0.0063 (2) −0.0047 (2) −0.0021 (2) Cl1 0.0383 (3) 0.0335 (3) 0.0279 (3) −0.0217 (3) −0.0053 (2) −0.0007 (2) F1 0.0315 (7) 0.0306 (7) 0.0366 (8) −0.0135 (6) −0.0154 (6) −0.0052 (6) F2 0.0362 (8) 0.0289 (7) 0.0408 (8) −0.0132 (6) −0.0024 (6) −0.0182 (6) O1 0.0184 (7) 0.0203 (7) 0.0230 (8) −0.0061 (6) −0.0055 (6) −0.0059 (6) O2 0.0209 (8) 0.0242 (8) 0.0371 (9) −0.0052 (7) −0.0030 (7) −0.0108 (7) N1 0.0179 (8) 0.0201 (9) 0.0189 (9) −0.0076 (7) −0.0057 (7) −0.0004 (7) N2 0.0197 (9) 0.0193 (9) 0.0186 (8) −0.0077 (7) −0.0038 (7) 0.0002 (7) N3 0.0167 (8) 0.0188 (9) 0.0237 (9) −0.0056 (7) −0.0065 (7) −0.0044 (7) C1 0.0195 (11) 0.0406 (14) 0.0272 (12) −0.0104 (10) −0.0092 (9) −0.0002 (10) C2 0.0294 (11) 0.0194 (10) 0.0213 (11) −0.0098 (9) −0.0103 (9) 0.0008 (8) C3 0.0211 (10) 0.0259 (11) 0.0195 (10) −0.0124 (9) −0.0057 (8) −0.0013 (8) C4 0.0208 (10) 0.0270 (11) 0.0239 (11) −0.0105 (9) −0.0070 (9) −0.0005 (9) C5 0.0277 (12) 0.0373 (13) 0.0210 (11) −0.0146 (10) −0.0114 (9) 0.0023 (9) C6 0.0314 (12) 0.0449 (14) 0.0208 (11) −0.0212 (11) −0.0062 (9) −0.0060 (10) C7 0.0321 (12) 0.0300 (12) 0.0285 (12) −0.0155 (10) −0.0046 (10) −0.0079 (10) C8 0.0282 (11) 0.0242 (11) 0.0246 (11) −0.0125 (9) −0.0084 (9) 0.0001 (9) C9 0.0250 (11) 0.0295 (12) 0.0173 (10) −0.0114 (9) −0.0016 (9) −0.0023 (9) C10 0.0275 (11) 0.0203 (10) 0.0243 (11) −0.0116 (9) −0.0102 (9) 0.0016 (8) C11 0.0236 (10) 0.0171 (10) 0.0237 (11) −0.0063 (8) −0.0084 (9) −0.0025 (8) C12 0.0253 (11) 0.0253 (11) 0.0236 (11) −0.0119 (9) −0.0055 (9) −0.0020 (9) C13 0.0222 (11) 0.0258 (11) 0.0317 (12) −0.0078 (9) −0.0096 (9) −0.0054 (9) C14 0.0273 (11) 0.0249 (11) 0.0264 (11) −0.0042 (9) −0.0125 (9) −0.0051 (9) C15 0.0308 (12) 0.0236 (11) 0.0241 (11) −0.0102 (10) −0.0080 (9) 0.0026 (9) C16 0.0242 (11) 0.0245 (11) 0.0268 (11) −0.0116 (9) −0.0092 (9) 0.0013 (9) C17 0.0235 (11) 0.0205 (10) 0.0192 (10) −0.0088 (9) −0.0054 (8) −0.0025 (8) C18 0.0249 (11) 0.0205 (10) 0.0261 (11) −0.0072 (9) −0.0055 (9) −0.0068 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2156 .table-wrap} -------------------- -------------- ----------------------- -------------- P1---O1 1.4769 (15) C5---H5A 0.9500 P1---N2 1.6241 (18) C6---C7 1.391 (3) P1---N1 1.6308 (18) C6---H6A 0.9500 P1---N3 1.7093 (18) C7---C8 1.387 (3) Cl1---C18 1.768 (2) C7---H7A 0.9500 F1---C18 1.345 (3) C8---H8A 0.9500 F2---C18 1.336 (2) C9---H9A 0.9800 O2---C17 1.215 (3) C9---H9B 0.9800 N1---C1 1.453 (3) C9---H9C 0.9800 N1---C2 1.471 (3) C10---C11 1.512 (3) N2---C9 1.469 (3) C10---H10A 0.9900 N2---C10 1.469 (3) C10---H10B 0.9900 N3---C17 1.353 (3) C11---C16 1.387 (3) N3---H3N 0.8700 C11---C12 1.399 (3) C1---H1A 0.9800 C12---C13 1.387 (3) C1---H1B 0.9800 C12---H12A 0.9500 C1---H1C 0.9800 C13---C14 1.383 (3) C2---C3 1.517 (3) C13---H13A 0.9500 C2---H2A 0.9900 C14---C15 1.379 (3) C2---H2B 0.9900 C14---H14A 0.9500 C3---C4 1.393 (3) C15---C16 1.391 (3) C3---C8 1.394 (3) C15---H15A 0.9500 C4---C5 1.394 (3) C16---H16A 0.9500 C4---H4A 0.9500 C17---C18 1.543 (3) C5---C6 1.384 (4) O1---P1---N2 112.34 (9) C7---C8---C3 120.0 (2) O1---P1---N1 117.13 (9) C7---C8---H8A 120.0 N2---P1---N1 107.02 (9) C3---C8---H8A 120.0 O1---P1---N3 105.06 (9) N2---C9---H9A 109.5 N2---P1---N3 110.57 (9) N2---C9---H9B 109.5 N1---P1---N3 104.38 (9) H9A---C9---H9B 109.5 C1---N1---C2 114.36 (17) N2---C9---H9C 109.5 C1---N1---P1 126.21 (15) H9A---C9---H9C 109.5 C2---N1---P1 119.42 (14) H9B---C9---H9C 109.5 C9---N2---C10 115.45 (17) N2---C10---C11 113.28 (18) C9---N2---P1 121.56 (14) N2---C10---H10A 108.9 C10---N2---P1 122.42 (15) C11---C10---H10A 108.9 C17---N3---P1 127.29 (15) N2---C10---H10B 108.9 C17---N3---H3N 117.5 C11---C10---H10B 108.9 P1---N3---H3N 114.0 H10A---C10---H10B 107.7 N1---C1---H1A 109.5 C16---C11---C12 118.6 (2) N1---C1---H1B 109.5 C16---C11---C10 120.9 (2) H1A---C1---H1B 109.5 C12---C11---C10 120.59 (19) N1---C1---H1C 109.5 C13---C12---C11 120.2 (2) H1A---C1---H1C 109.5 C13---C12---H12A 119.9 H1B---C1---H1C 109.5 C11---C12---H12A 119.9 N1---C2---C3 114.05 (17) C14---C13---C12 120.4 (2) N1---C2---H2A 108.7 C14---C13---H13A 119.8 C3---C2---H2A 108.7 C12---C13---H13A 119.8 N1---C2---H2B 108.7 C15---C14---C13 120.1 (2) C3---C2---H2B 108.7 C15---C14---H14A 120.0 H2A---C2---H2B 107.6 C13---C14---H14A 120.0 C4---C3---C8 119.4 (2) C14---C15---C16 119.6 (2) C4---C3---C2 119.3 (2) C14---C15---H15A 120.2 C8---C3---C2 121.15 (19) C16---C15---H15A 120.2 C3---C4---C5 120.3 (2) C11---C16---C15 121.2 (2) C3---C4---H4A 119.8 C11---C16---H16A 119.4 C5---C4---H4A 119.8 C15---C16---H16A 119.4 C6---C5---C4 120.1 (2) O2---C17---N3 127.4 (2) C6---C5---H5A 120.0 O2---C17---C18 118.39 (19) C4---C5---H5A 120.0 N3---C17---C18 114.16 (18) C5---C6---C7 119.7 (2) F2---C18---F1 107.18 (18) C5---C6---H6A 120.1 F2---C18---C17 110.49 (18) C7---C6---H6A 120.1 F1---C18---C17 111.98 (17) C8---C7---C6 120.5 (2) F2---C18---Cl1 108.70 (15) C8---C7---H7A 119.8 F1---C18---Cl1 109.06 (15) C6---C7---H7A 119.8 C17---C18---Cl1 109.35 (15) O1---P1---N1---C1 115.12 (19) C6---C7---C8---C3 −0.1 (3) N2---P1---N1---C1 −12.0 (2) C4---C3---C8---C7 1.2 (3) N3---P1---N1---C1 −129.24 (19) C2---C3---C8---C7 −173.7 (2) O1---P1---N1---C2 −64.27 (18) C9---N2---C10---C11 −61.8 (2) N2---P1---N1---C2 168.61 (15) P1---N2---C10---C11 109.64 (19) N3---P1---N1---C2 51.38 (17) N2---C10---C11---C16 122.1 (2) O1---P1---N2---C9 167.42 (16) N2---C10---C11---C12 −57.4 (3) N1---P1---N2---C9 −62.69 (18) C16---C11---C12---C13 −0.2 (3) N3---P1---N2---C9 50.40 (19) C10---C11---C12---C13 179.2 (2) O1---P1---N2---C10 −3.55 (19) C11---C12---C13---C14 0.2 (3) N1---P1---N2---C10 126.34 (17) C12---C13---C14---C15 0.3 (3) N3---P1---N2---C10 −120.57 (16) C13---C14---C15---C16 −0.6 (3) O1---P1---N3---C17 158.89 (18) C12---C11---C16---C15 −0.1 (3) N2---P1---N3---C17 −79.68 (19) C10---C11---C16---C15 −179.6 (2) N1---P1---N3---C17 35.1 (2) C14---C15---C16---C11 0.6 (4) C1---N1---C2---C3 −75.1 (2) P1---N3---C17---O2 13.3 (3) P1---N1---C2---C3 104.32 (19) P1---N3---C17---C18 −164.20 (15) N1---C2---C3---C4 143.87 (19) O2---C17---C18---F2 17.7 (3) N1---C2---C3---C8 −41.2 (3) N3---C17---C18---F2 −164.59 (18) C8---C3---C4---C5 −1.5 (3) O2---C17---C18---F1 137.1 (2) C2---C3---C4---C5 173.5 (2) N3---C17---C18---F1 −45.2 (2) C3---C4---C5---C6 0.7 (3) O2---C17---C18---Cl1 −101.9 (2) C4---C5---C6---C7 0.4 (3) N3---C17---C18---Cl1 75.8 (2) C5---C6---C7---C8 −0.6 (4) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3051 .table-wrap} ------------------ --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N3---H3N···O1^i^ 0.87 1.91 2.772 (3) 174 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −x+1, −y+1, −z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond angles (°) ::: --------------- ------------- O1---P1---N2 112.34 (9) O1---P1---N1 117.13 (9) N2---P1---N1 107.02 (9) O1---P1---N3 105.06 (9) N2---P1---N3 110.57 (9) N1---P1---N3 104.38 (9) C1---N1---C2 114.36 (17) C1---N1---P1 126.21 (15) C2---N1---P1 119.42 (14) C9---N2---C10 115.45 (17) C9---N2---P1 121.56 (14) C10---N2---P1 122.42 (15) --------------- ------------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ --------- ------- ----------- ------------- N3---H3N⋯O1^i^ 0.87 1.91 2.772 (3) 174 Symmetry code: (i) . :::	PubMed Central	2024-06-05T04:04:18.922846	2011-2-19	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052170/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o663-o664", "authors": [ { "first": "Akbar", "last": "Raissi Shabari" }, { "first": "Mehrdad", "last": "Pourayoubi" }, { "first": "Anahid", "last": "Saneei" } ] }
PMC3052171	Related literature {#sec1} ================== For similar complexes of the type \[RuCl~2~(DMSO)(arene)\], see: Ogata et al. (1970[@bb8]) (arene = benzene); Chandra et al. (2002[@bb5]) (arene = p-cymene); Beasley et al. (1993[@bb2]) (arene = 1,4,9,10-tetrahydroanthracene); Haquette et al. (2008[@bb7]) (arene = 9,10-dihydroanthracene); Sadler et al. (2005[@bb9]) (arene = 2-chloro-N-(2-phenylethyl)acetamide). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[RuCl~2~(C~9~H~12~)(C~2~H~6~OS)\]M ~r~ = 370.28Monoclinic,a = 8.1184 (4) Åb = 22.9372 (13) Åc = 8.3417 (4) Åβ = 116.443 (3)°V = 1390.82 (12) Å^3^Z = 4Mo Kα radiationμ = 1.64 mm^−1^T = 100 K0.24 × 0.15 × 0.09 mm ### Data collection {#sec2.1.2} Stoe IPDS 2T diffractometerAbsorption correction: multi-scan (Blessing, 1995[@bb3]) T ~min~ = 0.630, T ~max~ = 0.9949737 measured reflections2935 independent reflections2753 reflections with I \> 2σ(I)R ~int~ = 0.051 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.017wR(F ^2^) = 0.044S = 1.042935 reflections150 parametersH-atom parameters constrainedΔρ~max~ = 0.42 e Å^−3^Δρ~min~ = −0.71 e Å^−3^ {#d5e448} Data collection: X-AREA (Stoe & Cie, 2001[@bb11]); cell refinement: X-AREA; data reduction: X-RED (Stoe & Cie, 2001[@bb11]); program(s) used to solve structure: SIR92 (Altomare et al., 1993[@bb1]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb10]); molecular graphics: DIAMOND (Brandenburg, 2007[@bb4]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100314X/kj2168sup1.cif](http://dx.doi.org/10.1107/S160053681100314X/kj2168sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100314X/kj2168Isup2.hkl](http://dx.doi.org/10.1107/S160053681100314X/kj2168Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?kj2168&file=kj2168sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?kj2168sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?kj2168&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [KJ2168](http://scripts.iucr.org/cgi-bin/sendsup?kj2168)). Routine data collection was performed by the XRD service department (Dr K. Harms, G. Geiseler, R. Riedel) of the Chemistry Department, Philipps University, and is gratefully acknowledged. Comment ======= Complexes of the type \[{RuCl~2~(arene)}~2~\] are valuable starting materials for the preparation of ruthenium(II) complexes because they allow facile ligand substitution. During our investigations concerning the arene substitution behaviour of such complexes, we found that \[{RuCl~2~(C~6~H~3~Me~3~)}~2~\] readily reacts with dimethylsulfoxide, yielding the monomeric title compound \[RuCl~2~(DMSO)(C~6~H~3~Me~3~)\]. Similar reactivity has been reported for the corresponding benzene and p-cymene complexes (Ogata et al., 1970; Chandra et al., 2002). The overall complex geometry of the title compound is best described as a piano-stool configuration. Another possible description is that of an octahedral d^6^ low-spin complex with the arene ligand occupying three fac-oriented coordination sites. The angles between the monodentate chloro and DMSO ligands are thus close to 90° (Table 1). The planar, η^6^-bound mesitylene ligand shows almost equal Ru--C distances of 2.1978 (15) to 2.2219 (16) Å. Dimethylsulfoxide is coordinated via sulfur as usual for complexes without sufficient steric bulk to force O-coordination. All numerical parameters concerning the molecular geometry are similar to those observed for the corresponding p-cymene complex (Chandra et al., 2002). Experimental {#experimental} ============ \[{RuCl~2~(C~6~H~3~Me~3~)}~2~\] (175 mg, 0.30 mmol) was dissolved in DMSO (12 ml). The solution was heated to 100 °C for 45 min and a small amount of ruthenium black was removed by filtration. The dark red solution was concentrated in vacuo until the formation of crystals was observed. The product was isolated by filtration and dried in vacuo. A second crop of material was obtained from the mother liquor by layering with toluene. Yield: 150 mg (68%) of red crystals. Crystals suitable for X-ray diffraction were obtained by slow evaporation of a saturated DMSO solution. Refinement {#refinement} ========== Hydrogen atoms were placed on idealized positions and refined using a riding model with U~iso~(H) = 1.2 × U~eq~(C) (1.5 for methyl groups) and C--H bond lengths of 0.95 Å for aromatic protons and 0.98 Å for methyl groups. Reflexes 0 1 1 and -1 1 1 were omitted from the refinement because they were effected by the diffractometer\'s beamstop. Reflex -5 0 3 was also omitted because of its exceptionally large deviation from the calculated intensity. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound. Displacement ellipsoids are shown for 50% probability. ::: ![](e-67-0m319-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e192 .table-wrap} ------------------------------------ ---------------------------------------- \[RuCl~2~(C~9~H~12~)(C~2~H~6~OS)\] F(000) = 744 M~r~ = 370.28 D~x~ = 1.768 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 16004 reflections a = 8.1184 (4) Å θ = 1.9--27.2° b = 22.9372 (13) Å µ = 1.64 mm^−1^ c = 8.3417 (4) Å T = 100 K β = 116.443 (3)° Block, light red V = 1390.82 (12) Å^3^ 0.24 × 0.15 × 0.09 mm Z = 4 ------------------------------------ ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e326 .table-wrap} ---------------------------------------------------- -------------------------------------- Stoe IPDS 2T diffractometer 2935 independent reflections Radiation source: fine-focus sealed tube 2753 reflections with I \> 2σ(I) graphite R~int~ = 0.051 Detector resolution: 6.67 pixels mm^-1^ θ~max~ = 26.7°, θ~min~ = 2.9° rotation method scans h = −10→10 Absorption correction: multi-scan (Blessing, 1995) k = −28→29 T~min~ = 0.630, T~max~ = 0.994 l = −9→10 9737 measured reflections ---------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e441 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.017 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.044 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.0208P)^2^ + 0.742P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2935 reflections (Δ/σ)~max~ = 0.002 150 parameters Δρ~max~ = 0.42 e Å^−3^ 0 restraints Δρ~min~ = −0.71 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e598 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. Anal. calc. for C~11~H~18~Cl~2~ORuS (370.29 g/mol) C 35.68, H 4.90%; found C 35.42, H 4.98%. ^1^H NMR (250 MHz, DMSO-d~6~, 300 K) δ = 2.14 (s, 9H, CH~3~), 2.54 (s, 6H, DMSO), 5.46 (s, 3H, CH) p.p.m.; ^13^C NMR (75 MHz, DMSO-d~6~, 300 K) δ = 18.2 (CH~3~), 40.4 (DMSO), 82.0 (CH), 104.8 (CCH~3~) p.p.m.. IR (neat, ATR) ν = 3063 w, 3024 m, 2963 w, 2931 w, 1525 m, 1447 m, 1408 m, 1377 m, 1303 m, 1286 m, 1105 s, 1034 m, 1008 versus, 983 s, 971 m, 932 m, 905 m, 887 m, 721 m, 680 m, 641 m, 507 w, 415 s cm^-1^. Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e758 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.1365 (2) 0.08700 (8) −0.1389 (2) 0.0176 (4) C2 0.2204 (2) 0.03526 (7) −0.0475 (2) 0.0172 (3) H2 0.2639 0.0074 −0.1039 0.021\ C3 0.2406 (2) 0.02437 (7) 0.1282 (2) 0.0168 (3) C4 0.1758 (2) 0.06592 (7) 0.2106 (2) 0.0162 (3) H4 0.1889 0.0588 0.3279 0.019\* C5 0.0910 (2) 0.11842 (7) 0.1211 (2) 0.0161 (3) C6 0.0741 (2) 0.12862 (7) −0.0535 (2) 0.0168 (3) H6 0.0201 0.1639 −0.1137 0.020\* C7 0.1190 (3) 0.09819 (10) −0.3227 (2) 0.0283 (4) H7A 0.2138 0.0762 −0.3392 0.042\* H7B 0.1348 0.1399 −0.3369 0.042\* H7C −0.0030 0.0858 −0.4122 0.042\* C8 0.3318 (3) −0.03050 (8) 0.2244 (3) 0.0257 (4) H8A 0.3877 −0.0238 0.3539 0.039\* H8B 0.4273 −0.0420 0.1891 0.039\* H8C 0.2400 −0.0616 0.1930 0.039\* C9 0.0139 (2) 0.16108 (8) 0.2056 (3) 0.0244 (4) H9A −0.1136 0.1506 0.1753 0.037\* H9B 0.0174 0.2004 0.1609 0.037\* H9C 0.0875 0.1602 0.3359 0.037\* C10 0.5260 (2) 0.16583 (7) 0.5447 (2) 0.0178 (3) H10A 0.5907 0.1970 0.6298 0.027\* H10B 0.6034 0.1309 0.5755 0.027\* H10C 0.4105 0.1570 0.5500 0.027\* C11 0.7007 (2) 0.21278 (7) 0.3628 (2) 0.0169 (3) H11A 0.6939 0.2315 0.2544 0.025\* H11B 0.7841 0.1793 0.3935 0.025\* H11C 0.7470 0.2408 0.4618 0.025\* O1 0.35990 (15) 0.24130 (5) 0.28238 (15) 0.0164 (2) S1 0.47771 (5) 0.188752 (16) 0.32416 (5) 0.01120 (8) Cl1 0.65955 (5) 0.066716 (17) 0.30769 (5) 0.01704 (9) Cl2 0.50102 (5) 0.159381 (18) −0.04032 (5) 0.01767 (9) Ru1 0.364774 (16) 0.110410 (5) 0.124893 (15) 0.01033 (5) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1237 .table-wrap} ----- -------------- -------------- -------------- --------------- -------------- --------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0100 (8) 0.0246 (9) 0.0132 (8) −0.0059 (6) 0.0007 (6) −0.0026 (6) C2 0.0133 (8) 0.0158 (7) 0.0200 (8) −0.0048 (6) 0.0052 (6) −0.0089 (6) C3 0.0126 (7) 0.0115 (7) 0.0229 (8) −0.0046 (6) 0.0048 (6) −0.0011 (6) C4 0.0138 (8) 0.0175 (8) 0.0167 (8) −0.0050 (6) 0.0062 (6) 0.0005 (6) C5 0.0102 (8) 0.0152 (7) 0.0219 (8) −0.0033 (6) 0.0063 (7) −0.0044 (6) C6 0.0075 (7) 0.0165 (8) 0.0200 (8) −0.0007 (6) 0.0003 (6) 0.0032 (6) C7 0.0219 (10) 0.0449 (11) 0.0126 (8) −0.0066 (8) 0.0029 (7) −0.0010 (8) C8 0.0215 (9) 0.0144 (8) 0.0358 (10) −0.0009 (7) 0.0079 (8) 0.0028 (7) C9 0.0184 (9) 0.0226 (9) 0.0368 (10) −0.0024 (7) 0.0165 (8) −0.0075 (8) C10 0.0231 (9) 0.0162 (8) 0.0126 (7) −0.0017 (7) 0.0067 (7) −0.0004 (6) C11 0.0140 (8) 0.0169 (8) 0.0189 (8) −0.0046 (6) 0.0065 (6) −0.0047 (6) O1 0.0164 (6) 0.0114 (5) 0.0179 (5) 0.0031 (4) 0.0044 (5) −0.0005 (4) S1 0.01161 (18) 0.00975 (17) 0.01084 (17) −0.00026 (13) 0.00373 (14) −0.00063 (13) Cl1 0.01246 (19) 0.01451 (18) 0.01854 (19) 0.00243 (14) 0.00185 (15) −0.00313 (14) Cl2 0.01695 (19) 0.0227 (2) 0.01450 (18) −0.00450 (15) 0.00802 (15) −0.00160 (14) Ru1 0.00945 (8) 0.00984 (7) 0.01029 (8) −0.00034 (4) 0.00314 (5) −0.00124 (4) ----- -------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1577 .table-wrap} --------------------- -------------- ---------------------- -------------- C1---C2 1.411 (2) C7---H7C 0.9800 C1---C6 1.413 (3) C8---H8A 0.9800 C1---C7 1.498 (2) C8---H8B 0.9800 C1---Ru1 2.2209 (15) C8---H8C 0.9800 C2---C3 1.423 (2) C9---H9A 0.9800 C2---Ru1 2.2162 (15) C9---H9B 0.9800 C2---H2 0.9500 C9---H9C 0.9800 C3---C4 1.407 (2) C10---S1 1.7807 (16) C3---C8 1.499 (2) C10---H10A 0.9800 C3---Ru1 2.2219 (16) C10---H10B 0.9800 C4---C5 1.423 (2) C10---H10C 0.9800 C4---Ru1 2.2097 (16) C11---S1 1.7792 (17) C4---H4 0.9500 C11---H11A 0.9800 C5---C6 1.420 (2) C11---H11B 0.9800 C5---C9 1.496 (2) C11---H11C 0.9800 C5---Ru1 2.2160 (17) O1---S1 1.4806 (11) C6---Ru1 2.1978 (15) S1---Ru1 2.3399 (4) C6---H6 0.9500 Cl1---Ru1 2.4097 (4) C7---H7A 0.9800 Cl2---Ru1 2.3963 (4) C7---H7B 0.9800 C2---C1---C6 119.41 (15) S1---C10---H10A 109.5 C2---C1---C7 120.01 (17) S1---C10---H10B 109.5 C6---C1---C7 120.56 (17) H10A---C10---H10B 109.5 C2---C1---Ru1 71.28 (9) S1---C10---H10C 109.5 C6---C1---Ru1 70.47 (9) H10A---C10---H10C 109.5 C7---C1---Ru1 129.03 (12) H10B---C10---H10C 109.5 C1---C2---C3 120.71 (15) S1---C11---H11A 109.5 C1---C2---Ru1 71.64 (9) S1---C11---H11B 109.5 C3---C2---Ru1 71.52 (9) H11A---C11---H11B 109.5 C1---C2---H2 119.6 S1---C11---H11C 109.5 C3---C2---H2 119.6 H11A---C11---H11C 109.5 Ru1---C2---H2 129.7 H11B---C11---H11C 109.5 C4---C3---C2 119.20 (15) O1---S1---C11 106.80 (8) C4---C3---C8 120.71 (16) O1---S1---C10 107.79 (8) C2---C3---C8 120.09 (16) C11---S1---C10 99.56 (8) C4---C3---Ru1 71.02 (9) O1---S1---Ru1 116.76 (5) C2---C3---Ru1 71.09 (9) C11---S1---Ru1 114.32 (6) C8---C3---Ru1 129.33 (12) C10---S1---Ru1 110.09 (6) C3---C4---C5 121.05 (16) C6---Ru1---C4 67.42 (6) C3---C4---Ru1 71.97 (10) C6---Ru1---C5 37.53 (6) C5---C4---Ru1 71.49 (10) C4---Ru1---C5 37.50 (6) C3---C4---H4 119.5 C6---Ru1---C2 67.06 (6) C5---C4---H4 119.5 C4---Ru1---C2 66.92 (6) Ru1---C4---H4 129.6 C5---Ru1---C2 79.51 (6) C6---C5---C4 118.76 (15) C6---Ru1---C1 37.29 (7) C6---C5---C9 120.37 (16) C4---Ru1---C1 79.38 (6) C4---C5---C9 120.83 (16) C5---Ru1---C1 67.47 (6) C6---C5---Ru1 70.54 (9) C2---Ru1---C1 37.08 (6) C4---C5---Ru1 71.01 (9) C6---Ru1---C3 79.68 (6) C9---C5---Ru1 132.43 (12) C4---Ru1---C3 37.01 (6) C1---C6---C5 120.86 (15) C5---Ru1---C3 67.42 (6) C1---C6---Ru1 72.24 (9) C2---Ru1---C3 37.40 (6) C5---C6---Ru1 71.93 (9) C1---Ru1---C3 67.33 (6) C1---C6---H6 119.6 C6---Ru1---S1 107.34 (5) C5---C6---H6 119.6 C4---Ru1---S1 103.51 (4) Ru1---C6---H6 128.6 C5---Ru1---S1 91.13 (4) C1---C7---H7A 109.5 C2---Ru1---S1 170.04 (5) C1---C7---H7B 109.5 C1---Ru1---S1 141.22 (5) H7A---C7---H7B 109.5 C3---Ru1---S1 135.20 (5) C1---C7---H7C 109.5 C6---Ru1---Cl2 98.80 (5) H7A---C7---H7C 109.5 C4---Ru1---Cl2 165.32 (4) H7B---C7---H7C 109.5 C5---Ru1---Cl2 132.05 (5) C3---C8---H8A 109.5 C2---Ru1---Cl2 103.74 (5) C3---C8---H8B 109.5 C1---Ru1---Cl2 86.49 (5) H8A---C8---H8B 109.5 C3---Ru1---Cl2 138.75 (5) C3---C8---H8C 109.5 S1---Ru1---Cl2 85.030 (14) H8A---C8---H8C 109.5 C6---Ru1---Cl1 166.37 (4) H8B---C8---H8C 109.5 C4---Ru1---Cl1 103.89 (4) C5---C9---H9A 109.5 C5---Ru1---Cl1 138.64 (5) C5---C9---H9B 109.5 C2---Ru1---Cl1 100.16 (5) H9A---C9---H9B 109.5 C1---Ru1---Cl1 132.98 (5) C5---C9---H9C 109.5 C3---Ru1---Cl1 87.19 (4) H9A---C9---H9C 109.5 S1---Ru1---Cl1 84.567 (14) H9B---C9---H9C 109.5 Cl2---Ru1---Cl1 88.636 (15) C6---C1---C2---C3 0.8 (2) C9---C5---Ru1---Cl1 86.88 (18) C7---C1---C2---C3 179.05 (15) C1---C2---Ru1---C6 29.22 (10) Ru1---C1---C2---C3 54.15 (14) C3---C2---Ru1---C6 −103.49 (11) C6---C1---C2---Ru1 −53.39 (13) C1---C2---Ru1---C4 103.39 (11) C7---C1---C2---Ru1 124.90 (15) C3---C2---Ru1---C4 −29.32 (10) C1---C2---C3---C4 0.0 (2) C1---C2---Ru1---C5 66.34 (10) Ru1---C2---C3---C4 54.18 (13) C3---C2---Ru1---C5 −66.37 (10) C1---C2---C3---C8 −179.36 (15) C3---C2---Ru1---C1 −132.71 (15) Ru1---C2---C3---C8 −125.15 (15) C1---C2---Ru1---C3 132.71 (15) C1---C2---C3---Ru1 −54.21 (14) C1---C2---Ru1---Cl2 −64.65 (10) C2---C3---C4---C5 −0.1 (2) C3---C2---Ru1---Cl2 162.64 (9) C8---C3---C4---C5 179.26 (15) C1---C2---Ru1---Cl1 −155.73 (9) Ru1---C3---C4---C5 54.15 (14) C3---C2---Ru1---Cl1 71.55 (9) C2---C3---C4---Ru1 −54.21 (13) C2---C1---Ru1---C6 −132.10 (15) C8---C3---C4---Ru1 125.12 (15) C7---C1---Ru1---C6 114.0 (2) C3---C4---C5---C6 −0.6 (2) C2---C1---Ru1---C4 −65.58 (10) Ru1---C4---C5---C6 53.79 (13) C6---C1---Ru1---C4 66.52 (10) C3---C4---C5---C9 176.92 (15) C7---C1---Ru1---C4 −179.48 (19) Ru1---C4---C5---C9 −128.72 (15) C2---C1---Ru1---C5 −102.83 (11) C3---C4---C5---Ru1 −54.37 (14) C6---C1---Ru1---C5 29.27 (10) C2---C1---C6---C5 −1.4 (2) C7---C1---Ru1---C5 143.28 (19) C7---C1---C6---C5 −179.70 (15) C6---C1---Ru1---C2 132.10 (15) Ru1---C1---C6---C5 −55.19 (13) C7---C1---Ru1---C2 −113.9 (2) C2---C1---C6---Ru1 53.77 (13) C2---C1---Ru1---C3 −28.92 (10) C7---C1---C6---Ru1 −124.51 (15) C6---C1---Ru1---C3 103.18 (11) C4---C5---C6---C1 1.3 (2) C7---C1---Ru1---C3 −142.81 (19) C9---C5---C6---C1 −176.18 (15) C2---C1---Ru1---S1 −163.99 (8) Ru1---C5---C6---C1 55.34 (13) C6---C1---Ru1---S1 −31.89 (13) C4---C5---C6---Ru1 −54.01 (13) C7---C1---Ru1---S1 82.11 (19) C9---C5---C6---Ru1 128.48 (15) C2---C1---Ru1---Cl2 118.42 (10) C1---C6---Ru1---C4 −102.51 (11) C6---C1---Ru1---Cl2 −109.48 (9) C5---C6---Ru1---C4 29.64 (9) C7---C1---Ru1---Cl2 4.53 (17) C1---C6---Ru1---C5 −132.15 (14) C2---C1---Ru1---Cl1 33.57 (12) C1---C6---Ru1---C2 −29.07 (10) C6---C1---Ru1---Cl1 165.67 (8) C5---C6---Ru1---C2 103.08 (11) C7---C1---Ru1---Cl1 −80.32 (19) C5---C6---Ru1---C1 132.15 (14) C4---C3---Ru1---C6 −66.00 (10) C1---C6---Ru1---C3 −65.95 (10) C2---C3---Ru1---C6 65.54 (10) C5---C6---Ru1---C3 66.20 (10) C8---C3---Ru1---C6 179.40 (18) C1---C6---Ru1---S1 159.72 (9) C2---C3---Ru1---C4 131.54 (14) C5---C6---Ru1---S1 −68.13 (9) C8---C3---Ru1---C4 −114.6 (2) C1---C6---Ru1---Cl2 72.21 (10) C4---C3---Ru1---C5 −28.87 (9) C5---C6---Ru1---Cl2 −155.64 (9) C2---C3---Ru1---C5 102.67 (11) C1---C6---Ru1---Cl1 −50.2 (2) C8---C3---Ru1---C5 −143.47 (18) C5---C6---Ru1---Cl1 81.9 (2) C4---C3---Ru1---C2 −131.54 (14) C3---C4---Ru1---C6 103.26 (11) C8---C3---Ru1---C2 113.9 (2) C5---C4---Ru1---C6 −29.67 (9) C4---C3---Ru1---C1 −102.85 (11) C3---C4---Ru1---C5 132.92 (14) C2---C3---Ru1---C1 28.69 (10) C3---C4---Ru1---C2 29.61 (9) C8---C3---Ru1---C1 142.55 (18) C5---C4---Ru1---C2 −103.31 (11) C4---C3---Ru1---S1 38.27 (12) C3---C4---Ru1---C1 66.25 (10) C2---C3---Ru1---S1 169.81 (8) C5---C4---Ru1---C1 −66.67 (10) C8---C3---Ru1---S1 −76.33 (18) C5---C4---Ru1---C3 −132.92 (14) C4---C3---Ru1---Cl2 −157.62 (8) C3---C4---Ru1---S1 −153.33 (9) C2---C3---Ru1---Cl2 −26.08 (13) C5---C4---Ru1---S1 73.75 (9) C8---C3---Ru1---Cl2 87.78 (17) C3---C4---Ru1---Cl2 82.2 (2) C4---C3---Ru1---Cl1 117.67 (9) C5---C4---Ru1---Cl2 −50.7 (2) C2---C3---Ru1---Cl1 −110.79 (9) C3---C4---Ru1---Cl1 −65.67 (9) C8---C3---Ru1---Cl1 3.07 (16) C5---C4---Ru1---Cl1 161.41 (8) O1---S1---Ru1---C6 −11.73 (8) C4---C5---Ru1---C6 131.39 (14) C11---S1---Ru1---C6 −137.40 (8) C9---C5---Ru1---C6 −113.8 (2) C10---S1---Ru1---C6 111.55 (8) C6---C5---Ru1---C4 −131.39 (14) O1---S1---Ru1---C4 −81.94 (7) C9---C5---Ru1---C4 114.8 (2) C11---S1---Ru1---C4 152.39 (8) C6---C5---Ru1---C2 −65.82 (10) C10---S1---Ru1---C4 41.34 (8) C4---C5---Ru1---C2 65.57 (10) O1---S1---Ru1---C5 −46.16 (7) C9---C5---Ru1---C2 −179.61 (18) C11---S1---Ru1---C5 −171.83 (8) C6---C5---Ru1---C1 −29.10 (10) C10---S1---Ru1---C5 77.11 (8) C4---C5---Ru1---C1 102.29 (11) O1---S1---Ru1---C1 7.87 (9) C9---C5---Ru1---C1 −142.89 (19) C11---S1---Ru1---C1 −117.80 (9) C6---C5---Ru1---C3 −102.88 (10) C10---S1---Ru1---C1 131.14 (9) C4---C5---Ru1---C3 28.51 (10) O1---S1---Ru1---C3 −104.49 (8) C9---C5---Ru1---C3 143.33 (19) C11---S1---Ru1---C3 129.85 (9) C6---C5---Ru1---S1 117.62 (9) C10---S1---Ru1---C3 18.79 (9) C4---C5---Ru1---S1 −110.99 (9) O1---S1---Ru1---Cl2 85.96 (6) C9---C5---Ru1---S1 3.83 (17) C11---S1---Ru1---Cl2 −39.71 (6) C6---C5---Ru1---Cl2 33.29 (11) C10---S1---Ru1---Cl2 −150.77 (6) C4---C5---Ru1---Cl2 164.69 (7) O1---S1---Ru1---Cl1 175.05 (6) C9---C5---Ru1---Cl2 −80.50 (18) C11---S1---Ru1---Cl1 49.39 (6) C6---C5---Ru1---Cl1 −159.32 (8) C10---S1---Ru1---Cl1 −61.67 (6) C4---C5---Ru1---Cl1 −27.93 (12) --------------------- -------------- ---------------------- -------------- ::: Table 1 ::: {.caption} ###### Selected geometric parameters (Å, °) ::: ::: {#d32e520 .table-wrap} ----------- ------------- C1---Ru1 2.2209 (15) C2---Ru1 2.2162 (15) C3---Ru1 2.2219 (16) C4---Ru1 2.2097 (16) C5---Ru1 2.2160 (17) C6---Ru1 2.1978 (15) S1---Ru1 2.3399 (4) Cl1---Ru1 2.4097 (4) Cl2---Ru1 2.3963 (4) ----------- ------------- ::: ::: {#d32e568 .table-wrap} ----------------- ------------- S1---Ru1---Cl2 85.030 (14) S1---Ru1---Cl1 84.567 (14) Cl2---Ru1---Cl1 88.636 (15) ----------------- ------------- :::	PubMed Central	2024-06-05T04:04:18.929270	2011-2-12	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052171/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m319", "authors": [ { "first": "Benjamin", "last": "Oelkers" }, { "first": "Lars Hendrik", "last": "Finger" }, { "first": "Jörg", "last": "Sundermeyer" } ] }
PMC3052172	Related literature {#sec1} ================== For general background to N-acyl-N′,N′-disubstituted thiourea, see: Koch (2001[@bb10]); Sosa-Albertus & Piris (2001[@bb17]); Pérez et al. (2008a [@bb14]). For related structures, see: Arslan et al. (2003[@bb1]); Bolte & Fink (2003[@bb3]); Pérez et al. (2008b [@bb15]); Gomes et al. (2010[@bb9]). For details of the synthesis, see: Nagasawa & Mitsunobu (1981[@bb12]); Che et al. (1999[@bb4]). For graph-set notation, see: Bernstein et al. (1995[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~12~N~2~OSM ~r~ = 208.28Monoclinic,a = 10.8602 (9) Åb = 5.5590 (6) Åc = 18.6864 (10) Åβ = 102.768 (5)°V = 1100.24 (16) Å^3^Z = 4Mo Kα radiationμ = 0.26 mm^−1^T = 294 K0.26 × 0.13 × 0.13 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: gaussian (Coppens et al., 1965[@bb5]) T ~min~ = 0.943, T ~max~ = 0.9697078 measured reflections2282 independent reflections1762 reflections with I \> 2σ(I)R ~int~ = 0.041 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.120S = 1.052282 reflections133 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.27 e Å^−3^ {#d5e499} Data collection: COLLECT (Enraf--Nonius, 2000[@bb6]); cell refinement: SCALEPACK (Otwinowski & Minor 1997[@bb13]); data reduction: DENZO (Otwinowski & Minor 1997[@bb13]) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb16]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb16]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[@bb7]) and Mercury (Macrae et al., 2006[@bb11]); software used to prepare material for publication: WinGX (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005137/gk2336sup1.cif](http://dx.doi.org/10.1107/S1600536811005137/gk2336sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005137/gk2336Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005137/gk2336Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2336&file=gk2336sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2336sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2336&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2336](http://scripts.iucr.org/cgi-bin/sendsup?gk2336)). The authors thank the Grupo de Cristalografia, IFSC, USP, Brazil, for allowing the X-ray data collection. The authors acknowledge financial support from the PhD Cooperative Program - ICTP/CLAF. RSC thanks FAPESP for a fellowship. Comment ======= N-Acyl-N\',N\'-disubstituted thiourea derivatives have been a subject of investigations due to their ability to form stable metal complexes (Koch et al., 2001). The crystal structure analysis of the title compound was undertaken as a continuation of our interest in these N\',N\'-disubstituted acylthiourea derivatives as intermediates towards novel heterocycles and for the systematic study of their bioactivity and complexation behavior (Pérez et al., 2008a). On the other hand, the crystal structure determination of this compound helps to confirm its most stable molecular conformation, previously predicted by theoretical methods (Sosa-Albertus & Piris, 2001) in order to explain the behavior of polydentate systems in alkylation reactions. The main bond lengths of the title compound are within the ranges obtained for similar compounds (Pérez et al., 2008b; Arslan et al., 2003). The C--S and C--O bonds both show the expected double-bond character. However, the C--N bonds of acylthioureido fragment are intermediate between those expected for single and double C--N bonds (1.47 and 1.27 Å, respectively). These results can be explained by the existence of resonance in this part of the molecule. The conformation with respect to the thiocarbonyl and carbonyl groups is twisted, as reflected by the torsion angles O1/C1/N1/C2 and C1/N1/C2/N2 of -2.6 (3) and 57.9 (2)°. The dihedral angle between the O1/C1/N1 and S1/C2/N2 planes is 55.3 (2)°, while that between the O1/C1/N1 plane and the benzene ring is 35.8 (2)°. Compared to the diethyl analog (Bolte & Fink, 2003) and its monoclinic polymorph (Gomes, et al., 2010), the molecular confomation of the title molecule is significantly less twisted, as reflected by the corresponding torsion angles O/C/N/C \[12.48 (4)°, in Bolte & Fink (2003); 7.58 (17)° in Gomes et al. (2010) and C/N/C/N (-80.79 (3)° in Bolte & Fink (2003); -71.44 (14)° in Gomes et al. (2010)\]. The dihedral angle between the O/C/N and S/C/N planes is also smaller than those of the diethyl analog \[(73.9 (2)° in Bolte & Fink (2003); 67.3 (1)° in Gomes et al. (2010)\]. In the crystal structure (Fig. 2), an N---H···S(-x + 1,-y + 2,-z + 1) hydrogen bond links the molecules into R^2^~2~(8) centrosymetric dimers (Bernstein et al., 1995) across the crystallographic centre of symmetry at (1/2, 0, 1/2). The molecules are also linked by weak C---H···O hydrogen bonds (Table 1). Experimental {#experimental} ============ N-Benzoyl-N\',N\'-dimethylthiourea was prepared using the standard procedure previously reported in the literature (Nagasawa & Mitsunobu, 1981) by the reaction of benzoyl chloride with KSCN in anhydrous acetone, and then condensation with dimethylamine. The synthesis of title compound was previously reported (Che et al., 1999). Recrystallization from acetone/water solution (1:1, v/v) yielded colourless crystals (1.6 g, 7.5 mmol, 75%). m.p. 448 K. Analysis calculated for C~10~H~12~N~2~OS: C 57.67, H 5.80, N 13.45, S 15.40%. Found: C 57.88, H 5.92, N 13.60, S 15.19%. Refinement {#refinement} ========== H atoms bonded to C atoms were included in calculated positions and refined as riding, with C--H = 0.93 or 0.96 Å and with U~iso~(H) = 1.2Ueq(C) or 1.5Ueq(C). H atom bonded to N atom was located in difference Fourier synthesis and was refined isotropically. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o647-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The R22(8) centrosymmetric dimer lying across the centre of symmetry at (1/2,0, 1/2). Hydrogen bonds are shown as dashed lines \[symmetry code (i) -x + 1, -y + 2, -z + 1\]. ::: ![](e-67-0o647-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e211 .table-wrap} ------------------------- --------------------------------------- C~10~H~12~N~2~OS F(000) = 440 M~r~ = 208.28 D~x~ = 1.257 Mg m^−3^ Monoclinic, P2~1~/n Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 1912 reflections a = 10.8602 (9) Å θ = 3.5--26.7° b = 5.5590 (6) Å µ = 0.26 mm^−1^ c = 18.6864 (10) Å T = 294 K β = 102.768 (5)° Prism, colourless V = 1100.24 (16) Å^3^ 0.26 × 0.13 × 0.13 mm Z = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e339 .table-wrap} -------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 1762 reflections with I \> 2σ(I) ω scan R~int~ = 0.041 Absorption correction: gaussian (Coppens et al., 1965) θ~max~ = 26.7°, θ~min~ = 3.5° T~min~ = 0.943, T~max~ = 0.969 h = −13→13 7078 measured reflections k = −6→7 2282 independent reflections l = −22→23 -------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e445 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ 0 restraints Least-squares matrix: full H atoms treated by a mixture of independent and constrained refinement R\[F^2^ \> 2σ(F^2^)\] = 0.043 w = 1/\[σ^2^(F~o~^2^) + (0.0587P)^2^ + 0.1899P\] where P = (F~o~^2^ + 2F~c~^2^)/3 wR(F^2^) = 0.120 (Δ/σ)~max~ \< 0.001 S = 1.05 Δρ~max~ = 0.17 e Å^−3^ 2282 reflections Δρ~min~ = −0.27 e Å^−3^ 133 parameters ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e596 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e616 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- x y z U~iso~\/U~eq~ C1 0.55382 (16) 0.7917 (3) 0.35288 (9) 0.0475 (4) C2 0.38501 (16) 0.6859 (3) 0.41573 (8) 0.0459 (4) C3 0.69073 (16) 0.8469 (3) 0.36576 (9) 0.0484 (4) C4 0.7314 (2) 1.0217 (4) 0.32357 (10) 0.0638 (5) H4 0.6731 1.103 0.2878 0.077\ C5 0.8583 (2) 1.0756 (5) 0.33449 (13) 0.0778 (6) H5 0.8853 1.1951 0.3067 0.093\* C6 0.9442 (2) 0.9537 (5) 0.38608 (14) 0.0822 (7) H6 1.0296 0.9899 0.393 0.099\* C7 0.90569 (19) 0.7787 (5) 0.42771 (14) 0.0785 (6) H7 0.965 0.6965 0.4627 0.094\* C8 0.77898 (18) 0.7235 (4) 0.41797 (11) 0.0608 (5) H8 0.7529 0.6042 0.4463 0.073\* C9 0.3971 (3) 0.3391 (4) 0.33595 (14) 0.0806 (7) H9A 0.4844 0.3341 0.3609 0.121\* H9B 0.3906 0.3891 0.2861 0.121\* H9C 0.3607 0.182 0.3366 0.121\* C10 0.19432 (19) 0.4648 (5) 0.36413 (12) 0.0753 (6) H10A 0.1503 0.6153 0.3619 0.113\* H10B 0.1803 0.373 0.4051 0.113\* H10C 0.1636 0.3765 0.3196 0.113\* N1 0.51125 (13) 0.7326 (3) 0.41555 (8) 0.0485 (4) N2 0.32963 (14) 0.5100 (3) 0.37299 (8) 0.0557 (4) O1 0.48381 (12) 0.7991 (3) 0.29255 (6) 0.0623 (4) S1 0.31430 (4) 0.84543 (10) 0.47135 (3) 0.0602 (2) H1 0.5514 (19) 0.802 (4) 0.4545 (11) 0.066 (6)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e966 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0508 (9) 0.0491 (10) 0.0440 (8) 0.0049 (7) 0.0133 (7) −0.0020 (7) C2 0.0449 (9) 0.0501 (10) 0.0416 (8) −0.0028 (7) 0.0073 (6) 0.0012 (7) C3 0.0505 (9) 0.0528 (10) 0.0452 (8) 0.0041 (7) 0.0176 (7) −0.0013 (7) C4 0.0672 (12) 0.0686 (13) 0.0596 (11) 0.0016 (10) 0.0228 (9) 0.0091 (9) C5 0.0744 (14) 0.0826 (15) 0.0854 (14) −0.0127 (12) 0.0369 (12) 0.0106 (13) C6 0.0530 (12) 0.0933 (18) 0.1055 (17) −0.0082 (11) 0.0288 (12) 0.0052 (15) C7 0.0476 (11) 0.0905 (16) 0.0961 (16) 0.0084 (11) 0.0130 (11) 0.0168 (13) C8 0.0541 (11) 0.0630 (12) 0.0669 (11) 0.0047 (9) 0.0170 (9) 0.0115 (9) C9 0.0980 (17) 0.0543 (12) 0.0940 (16) −0.0025 (11) 0.0312 (14) −0.0231 (11) C10 0.0614 (12) 0.0833 (16) 0.0749 (13) −0.0227 (11) 0.0017 (10) −0.0145 (11) N1 0.0435 (8) 0.0610 (9) 0.0410 (7) −0.0033 (6) 0.0093 (6) −0.0038 (7) N2 0.0561 (9) 0.0519 (9) 0.0582 (8) −0.0062 (7) 0.0106 (7) −0.0106 (7) O1 0.0590 (8) 0.0824 (10) 0.0436 (7) 0.0056 (6) 0.0075 (6) 0.0021 (6) S1 0.0504 (3) 0.0722 (4) 0.0626 (3) −0.0118 (2) 0.0222 (2) −0.0184 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1252 .table-wrap} ------------------- -------------- -------------------- -------------- C1---O1 1.2133 (19) C6---H6 0.93 C1---N1 1.390 (2) C7---C8 1.382 (3) C1---C3 1.485 (2) C7---H7 0.93 C2---N2 1.321 (2) C8---H8 0.93 C2---N1 1.396 (2) C9---N2 1.464 (3) C2---S1 1.6759 (17) C9---H9A 0.96 C3---C4 1.384 (3) C9---H9B 0.96 C3---C8 1.388 (3) C9---H9C 0.96 C4---C5 1.381 (3) C10---N2 1.464 (2) C4---H4 0.93 C10---H10A 0.96 C5---C6 1.364 (3) C10---H10B 0.96 C5---H5 0.93 C10---H10C 0.96 C6---C7 1.368 (3) N1---H1 0.85 (2) O1---C1---N1 122.28 (16) C7---C8---C3 119.70 (19) O1---C1---C3 122.89 (15) C7---C8---H8 120.1 N1---C1---C3 114.83 (14) C3---C8---H8 120.1 N2---C2---N1 116.90 (15) N2---C9---H9A 109.5 N2---C2---S1 123.85 (14) N2---C9---H9B 109.5 N1---C2---S1 119.21 (12) H9A---C9---H9B 109.5 C4---C3---C8 119.31 (17) N2---C9---H9C 109.5 C4---C3---C1 119.15 (16) H9A---C9---H9C 109.5 C8---C3---C1 121.52 (16) H9B---C9---H9C 109.5 C5---C4---C3 120.14 (19) N2---C10---H10A 109.5 C5---C4---H4 119.9 N2---C10---H10B 109.5 C3---C4---H4 119.9 H10A---C10---H10B 109.5 C6---C5---C4 120.0 (2) N2---C10---H10C 109.5 C6---C5---H5 120 H10A---C10---H10C 109.5 C4---C5---H5 120 H10B---C10---H10C 109.5 C5---C6---C7 120.5 (2) C1---N1---C2 123.76 (14) C5---C6---H6 119.7 C1---N1---H1 114.1 (14) C7---C6---H6 119.7 C2---N1---H1 113.5 (14) C6---C7---C8 120.3 (2) C2---N2---C10 120.48 (16) C6---C7---H7 119.9 C2---N2---C9 123.91 (17) C8---C7---H7 119.9 C10---N2---C9 115.48 (17) O1---C1---C3---C4 34.5 (3) C4---C3---C8---C7 0.8 (3) N1---C1---C3---C4 −144.94 (17) C1---C3---C8---C7 179.32 (19) O1---C1---C3---C8 −144.04 (19) O1---C1---N1---C2 −2.6 (3) N1---C1---C3---C8 36.5 (2) C3---C1---N1---C2 176.89 (15) C8---C3---C4---C5 −1.3 (3) N2---C2---N1---C1 57.9 (2) C1---C3---C4---C5 −179.87 (19) S1---C2---N1---C1 −124.37 (16) C3---C4---C5---C6 1.1 (3) N1---C2---N2---C10 −173.79 (17) C4---C5---C6---C7 −0.4 (4) S1---C2---N2---C10 8.6 (2) C5---C6---C7---C8 −0.1 (4) N1---C2---N2---C9 10.6 (3) C6---C7---C8---C3 −0.1 (4) S1---C2---N2---C9 −167.03 (16) ------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1700 .table-wrap} --------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N1---H1···S1^i^ 0.85 (2) 2.65 (2) 3.4335 (17) 154.2 (18) C9---H9A···N1 0.96 2.43 2.778 (3) 101 C9---H9B···O1 0.96 2.49 2.902 (3) 106 C10---H10C···O1^ii^ 0.96 2.38 3.265 (3) 153 --------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1/2, y−1/2, −z+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A --------------------- ---------- ---------- ------------- ------------- N1---H1⋯S1^i^ 0.85 (2) 2.65 (2) 3.4335 (17) 154.2 (18) C10---H10C⋯O1^ii^ 0.96 2.38 3.265 (3) 153 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.936147	2011-2-16	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052172/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o647", "authors": [ { "first": "Hiram", "last": "Pérez" }, { "first": "Rodrigo S.", "last": "Corrêa" }, { "first": "Ana María", "last": "Plutín" }, { "first": "Anislay", "last": "Álvarez" }, { "first": "Yvonne", "last": "Mascarenhas" } ] }
PMC3052173	Related literature {#sec1} ================== For isophthalic acid, see: Bhogala et al. (2005[@bb1]); Derissen (1974[@bb5]). For the use of the title compound in crystal engineering, see: Zhang et al. (2010[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~8~H~5~FO~4~M ~r~ = 184.12Monoclinic,a = 3.7736 (8) Åb = 16.292 (4) Åc = 6.2753 (14) Åβ = 91.871 (5)°V = 385.60 (14) Å^3^Z = 2Mo Kα radiationμ = 0.14 mm^−1^T = 297 K0.22 × 0.20 × 0.15 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 2003[@bb6]) T ~min~ = 0.969, T ~max~ = 0.9792201 measured reflections743 independent reflections603 reflections with I \> 2σ(I)R ~int~ = 0.018 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.041wR(F ^2^) = 0.161S = 1.04743 reflections64 parametersH-atom parameters constrainedΔρ~max~ = 0.16 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e398} Data collection: APEX2 (Bruker, 2003[@bb4]); cell refinement: SAINT (Bruker, 2001[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb7]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb7]); molecular graphics: SHELXTL (Sheldrick, 2008[@bb7]) and DIAMOND (Brandenburg, 2005[@bb2]); software used to prepare material for publication: SHELXTL. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004004/go2002sup1.cif](http://dx.doi.org/10.1107/S1600536811004004/go2002sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004004/go2002Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004004/go2002Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?go2002&file=go2002sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?go2002sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?go2002&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GO2002](http://scripts.iucr.org/cgi-bin/sendsup?go2002)). The authors gratefully acknowledge the Jiangsu Province Outstanding Science and Technology Innovation Team and Changzhou University for financial support. Comment ======= As an analogue of isophthalic acid (Bhogala et al. 2005; Derissen, 1974), 5-fluoroisophthalic acid has been seldom used in the crystal engineering of organic or inorganic-organic systems (Zhang et al. 2010). The fluorinated group may participate in hydrogen-bonding and may also induce luminescence properties. Herein we report the crystal structure of the title compound, C~8~H~5~FO~4~, to further investigate the supramolecular interactions involving the fluorine atom. The structure of the title compound, is shown below. The molecule presents C~2~symmetry with the fundamental unit lying on a C~2~-axis at \[x, 3/4, z\]. Intermolecular O---H···O interactions between adjoining centrosymmetry-related carboxylic groups form a hydrogen-bonded ribbon running along the \[010\] direction. C---H···F interactions connect the ribbons into a two-dimensional supramolecular array. Experimental {#experimental} ============ 5-Fluoroisophthalic acid and solvents for synthesis and analysis were commercially available and used as received. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of the methanol solution of the title compound. Refinement {#refinement} ========== Benzene H atoms were assigned to calculated positions with C---H = 0.93 Å, and refined using a riding model, with Uiso(H) = 1.2Ueq(C). H atoms bound to carboxylic O atoms were located in difference maps and refined as riding with U~iso~(H) = 1.5 U~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound drawn with 30% probability ellipsoids. ::: ![](e-67-0o590-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Two-dimensional hydrogen-bonded layer of the title compound. Hydrogen bonds are indicated as dashed lines. ::: ![](e-67-0o590-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------- --------------------------------------- C~8~H~5~FO~4~ F(000) = 188 M~r~ = 184.12 D~x~ = 1.586 Mg m^−3^ Monoclinic, P2~1~/m Mo Kα radiation, λ = 0.71073 Å Hall symbol: -P 2yb Cell parameters from 1020 reflections a = 3.7736 (8) Å θ = 2.5--28.0° b = 16.292 (4) Å µ = 0.14 mm^−1^ c = 6.2753 (14) Å T = 297 K β = 91.871 (5)° Block, colourless V = 385.60 (14) Å^3^ 0.22 × 0.20 × 0.15 mm Z = 2 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} --------------------------------------------------------------- ------------------------------------- Bruker APEXII CCD diffractometer 743 independent reflections Radiation source: fine-focus sealed tube 603 reflections with I \> 2σ(I) graphite R~int~ = 0.018 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.5° Absorption correction: multi-scan (SADABS; Sheldrick, 2003) h = −4→4 T~min~ = 0.969, T~max~ = 0.979 k = −17→19 2201 measured reflections l = −7→5 --------------------------------------------------------------- ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e387 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.161 H-atom parameters constrained S = 1.04 w = 1/\[σ^2^(F~o~^2^) + (0.1244P)^2^\] where P = (F~o~^2^ + 2F~c~^2^)/3 743 reflections (Δ/σ)~max~ \< 0.001 64 parameters Δρ~max~ = 0.16 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e541 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e586 .table-wrap} ---- ------------ -------------- ------------ -------------------- -- x y z U~iso~\/U~eq~ C1 0.6268 (4) 0.59855 (9) 0.8588 (3) 0.0524 (5) C2 0.7105 (4) 0.67633 (9) 0.7484 (2) 0.0487 (5) C3 0.8602 (4) 0.67563 (10) 0.5486 (3) 0.0529 (5) H3 0.9107 0.6265 0.4806 0.063\ C4 0.9312 (5) 0.7500 0.4549 (3) 0.0540 (6) C5 0.6370 (5) 0.7500 0.8476 (3) 0.0477 (6) H5 0.5379 0.7500 0.9813 0.057\* F1 1.0787 (4) 0.7500 0.2629 (2) 0.0744 (6) O1 0.7073 (4) 0.53205 (8) 0.7622 (2) 0.0775 (6) H1 0.6348 0.4905 0.8205 0.116\* O2 0.4837 (4) 0.60037 (7) 1.0328 (2) 0.0722 (6) ---- ------------ -------------- ------------ -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e755 .table-wrap} ---- ------------- ------------- ------------- ------------- ------------ ------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0490 (9) 0.0612 (10) 0.0474 (10) −0.0023 (6) 0.0088 (7) −0.0080 (7) C2 0.0385 (8) 0.0652 (11) 0.0424 (9) −0.0012 (6) 0.0022 (6) −0.0051 (6) C3 0.0420 (9) 0.0726 (12) 0.0441 (10) −0.0006 (6) 0.0027 (7) −0.0087 (7) C4 0.0426 (11) 0.0852 (16) 0.0346 (11) 0.000 0.0069 (9) 0.000 C5 0.0400 (10) 0.0642 (14) 0.0395 (11) 0.000 0.0072 (8) 0.000 F1 0.0745 (10) 0.1105 (12) 0.0393 (8) 0.000 0.0190 (7) 0.000 O1 0.1022 (11) 0.0610 (8) 0.0715 (10) −0.0050 (6) 0.0359 (8) −0.0121 (6) O2 0.0938 (10) 0.0622 (9) 0.0628 (9) −0.0038 (6) 0.0355 (7) −0.0032 (5) ---- ------------- ------------- ------------- ------------- ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e940 .table-wrap} ------------------- -------------- ---------------------- -------------- C1---O2 1.235 (2) C3---H3 0.9300 C1---O1 1.2826 (19) C4---F1 1.343 (2) C1---C2 1.483 (2) C4---C3^i^ 1.377 (2) C2---C5 1.3841 (18) C5---C2^i^ 1.3841 (19) C2---C3 1.392 (2) C5---H5 0.9300 C3---C4 1.377 (2) O1---H1 0.8201 O2---C1---O1 123.73 (15) C2---C3---H3 121.1 O2---C1---C2 119.91 (13) F1---C4---C3 118.37 (11) O1---C1---C2 116.35 (15) F1---C4---C3^i^ 118.36 (11) C5---C2---C3 120.34 (15) C3---C4---C3^i^ 123.3 (2) C5---C2---C1 118.83 (15) C2---C5---C2^i^ 120.3 (2) C3---C2---C1 120.83 (14) C2---C5---H5 119.9 C4---C3---C2 117.89 (16) C2^i^---C5---H5 119.9 C4---C3---H3 121.1 C1---O1---H1 113.5 O2---C1---C2---C5 2.3 (3) C1---C2---C3---C4 179.97 (14) O1---C1---C2---C5 −178.51 (16) C2---C3---C4---F1 179.40 (14) O2---C1---C2---C3 −177.68 (14) C2---C3---C4---C3^i^ −0.3 (3) O1---C1---C2---C3 1.5 (3) C3---C2---C5---C2^i^ 0.3 (3) C5---C2---C3---C4 0.0 (3) C1---C2---C5---C2^i^ −179.72 (12) ------------------- -------------- ---------------------- -------------- ::: Symmetry codes: (i) x, −y+3/2, z. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1178 .table-wrap} ------------------- --------- --------- ----------- --------------- D---H···A D---H H···A D···A D---H···A O1---H1···O2^ii^ 0.82 1.81 2.625 (2) 174 C5---H5···F1^iii^ 0.93 2.52 3.404 (2) 160 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −x+1, −y+1, −z+2; (iii) x−1, y, z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ---------------- --------- ------- ----------- ------------- O1---H1⋯O2^i^ 0.82 1.81 2.625 (2) 174 C5---H5⋯F1^ii^ 0.93 2.52 3.404 (2) 160 Symmetry codes: (i) ; (ii) . :::	PubMed Central	2024-06-05T04:04:18.939912	2011-2-09	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052173/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o590", "authors": [ { "first": "Jin-Ling", "last": "Mi" }, { "first": "Le", "last": "Chen" }, { "first": "Ming-Yang", "last": "He" } ] }
PMC3052174	Related literature {#sec1} ================== For background to chalcone synthesis and the biological activity of pyrazole derivatives, see: Bekhit et al. (2008[@bb2]); Ono et al. (2007[@bb12]); Cottineau et al. (2002[@bb6]); Gadakh et al. (2010[@bb8]); Hall et al. (2008[@bb9]); Hoepping et al. (2007[@bb10]); Mikhaylichenko et al. (2009[@bb11]); Park et al. (2005[@bb13]) Souza et al. (2002[@bb15]); Xie et al. (2008[@bb18]). For related structures, see; Chantrapromma et al. (2009[@bb4]); Suwunwong et al. (2009[@bb17]). For the stability of the temperature controller used in the data collection, see Cosier & Glazer (1986[@bb5]). For bond-length data, see: Allen et al. (1987[@bb1]). For puckering parameters, see: Cremer & Pople (1975[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~19~BrN~4~SM ~r~ = 403.34Triclinic,a = 6.9153 (1) Åb = 9.5122 (1) Åc = 15.1545 (2) Åα = 72.196 (1)°β = 80.941 (1)°γ = 69.845 (1)°V = 889.48 (2) Å^3^Z = 2Mo Kα radiationμ = 2.44 mm^−1^T = 100 K0.55 × 0.32 × 0.31 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Bruker, 2005[@bb3]) T ~min~ = 0.349, T ~max~ = 0.52028456 measured reflections7823 independent reflections6784 reflections with I \> 2σ(I)R ~int~ = 0.023 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.028wR(F ^2^) = 0.073S = 1.057823 reflections227 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.96 e Å^−3^Δρ~min~ = −0.50 e Å^−3^ {#d5e545} Data collection: APEX2 (Bruker, 2005[@bb3]); cell refinement: SAINT (Bruker, 2005[@bb3]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[@bb14]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009[@bb16]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006106/rz2558sup1.cif](http://dx.doi.org/10.1107/S1600536811006106/rz2558sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006106/rz2558Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006106/rz2558Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2558&file=rz2558sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2558sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2558&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2558](http://scripts.iucr.org/cgi-bin/sendsup?rz2558)). TS thanks the Graduate School, Prince of Songkla University for partial financial support. The authors thank the Prince of Songkla University for financial support through the Crystal Materials Research Unit and also thank Universiti Sains Malaysia for the Research University Grant No. 1001/PFIZIK/811160. Comment ======= The pyrazole moiety is one of the core structures in a number of natural products (Xie et al., 2008). Numerous compounds which contain the pyrazole moiety are known to exhibit a wide range of biological properties such as antihypertensive (Mikhaylichenko et al., 2009), analgesic (Hall et al., 2008), anti-inflammatory (Bekhit et al., 2008), antipyretic (Souza et al., 2002), antimicrobial (Gadakh et al., 2010), hypoglycemic (Cottineau et al., 2002), sedative-hypnotic (Hoepping et al., 2007) and antitumor activities (Park et al., 2005). Our on going research on biological activities of pyrazole derivatives led us to synthesize the title compound by cyclization of the chalcone derivative (Ono et al., 2007) with excess thiosemicarbazide. Herein we report the crystal structure of the title compound. The molecular structure of the title compound is twisted. The central pyrazole ring adopts a flattened envelope conformation with puckering parameter Q = 0.1775 (11) Å and φ = 75.9 (3)° (Cremer & Pople, 1975), with the slightly puckered C9 atom having the maximum deviation of 0.1120 (11) Å. The pyrazole ring is coplanar with the 4-bromophenyl whereas inclined to the 4-dimethylaminophenyl rings with dihedral angles of 1.68 (6) and 85.12 (6)°, respectively. The dihedral angle between the two phenyl rings being 86.56 (6)°. The dimethylamino group is slightly twisted from the attached benzene ring with the torsion angles C16--N3--C13--C14 = 8.9 (2)° and C17--N3--C13--C12 = 8.4 (2)°. The carbothioamide is slightly twisted from the pyrazole ring as indicated by the torsions angles N4--C18--N2--N1 = 5.51 (14)° and S1--C18--N2--N1 = -172.28 (7)°. The bond distances agree with the literature values (Allen et al., 1987) and are comparable to those observed in related structures (Chantrapromma et al., 2009; Suwunwong et al., 2009). In the crystal structure (Fig. 2), the molecules are linked by intermolecular N---H···S hydrogen bonds (Table 1) into chains along the \[2 1 0\] direction. The crystal is further stabilized by C---H···π interactions (Table 1). Experimental {#experimental} ============ The title compound was synthesized by dissolving (E)-1-(4-bromophenyl)-3-(4-(dimethylamino)phenyl)prop-2-en-1-one (Ono et al., 2007) (0.33 g, 1.0 mmol) in a solution of KOH (0.06 g, 1.0 mmol) in ethanol (20 ml). An excess thiosemicarbazide (0.14 g, 1.5 mmol) in ethanol (20 ml) was then added, and the reaction mixture was vigorously stirred and refluxed for 7 h. The yellow solid of the title compound obtained after cooling of the reaction mixture was filtered off under vacuum. Pale yellow block-shaped single crystals of the title compound suitable for X-ray structure determination were recrystalized from acetone/ethanol (1:1 v/v) by slow evaporation of the solvent at room temperature after several days. M.p. 481--482 K. Refinement {#refinement} ========== The amino H atoms were located in difference Fourier map and refined isotropically. The remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with d(C---H) = 0.93 Å for aromatic, 0.97 Å for CH~2~ and 0.96 Å for CH~3~ atoms. The U~iso~ values were constrained to be 1.5U~eq~ of the carrier atom for methyl H atoms and 1.2U~eq~ for the remaining H atoms. A rotating group model was used for the methyl groups. The highest residual electron density peak is located at 0.75 Å from Br1 and the deepest hole is located at 0.56 Å from Br1. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids. ::: ![](e-67-0o701-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound viewed along the a axis. Hydrogen bonds are drawn as dashed lines. ::: ![](e-67-0o701-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e188 .table-wrap} ----------------------- --------------------------------------- C~18~H~19~BrN~4~S Z = 2 M~r~ = 403.34 F(000) = 412 Triclinic, P1 D~x~ = 1.506 Mg m^−3^ Hall symbol: -P 1 Melting point = 481--482 K a = 6.9153 (1) Å Mo Kα radiation, λ = 0.71073 Å b = 9.5122 (1) Å Cell parameters from 7823 reflections c = 15.1545 (2) Å θ = 2.4--35.1° α = 72.196 (1)° µ = 2.44 mm^−1^ β = 80.941 (1)° T = 100 K γ = 69.845 (1)° Block, pale yellow V = 889.48 (2) Å^3^ 0.55 × 0.32 × 0.31 mm ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e323 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD area-detector diffractometer 7823 independent reflections Radiation source: sealed tube 6784 reflections with I \> 2σ(I) graphite R~int~ = 0.023 φ and ω scans θ~max~ = 35.1°, θ~min~ = 2.4° Absorption correction: multi-scan (SADABS; Bruker, 2005) h = −11→10 T~min~ = 0.349, T~max~ = 0.520 k = −15→15 28456 measured reflections l = −24→24 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e440 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.028 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.073 H atoms treated by a mixture of independent and constrained refinement S = 1.05 w = 1/\[σ^2^(F~o~^2^) + (0.0344P)^2^ + 0.3232P\] where P = (F~o~^2^ + 2F~c~^2^)/3 7823 reflections (Δ/σ)~max~ = 0.003 227 parameters Δρ~max~ = 0.96 e Å^−3^ 0 restraints Δρ~min~ = −0.50 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e597 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e702 .table-wrap} ------ --------------- ---------------- --------------- -------------------- -- x y z U~iso~\/U~eq~ Br1 1.641401 (17) −0.173962 (13) 0.169443 (10) 0.02713 (4) S1 0.08981 (4) 0.61386 (3) 0.083129 (18) 0.01668 (5) N1 0.62104 (13) 0.27982 (10) 0.13070 (6) 0.01465 (14) N2 0.44511 (13) 0.40189 (10) 0.14121 (6) 0.01404 (14) N3 −0.0497 (2) 0.25372 (15) 0.52890 (9) 0.0346 (3) N4 0.31575 (15) 0.37031 (12) 0.02111 (7) 0.01857 (16) C1 1.02110 (17) 0.05782 (12) 0.12650 (8) 0.01819 (18) H1A 0.9213 0.0544 0.0933 0.022\ C2 1.21950 (17) −0.04510 (13) 0.12460 (9) 0.02047 (19) H2A 1.2534 −0.1179 0.0908 0.025\* C3 1.36736 (16) −0.03752 (12) 0.17431 (8) 0.01850 (18) C4 1.32036 (16) 0.06853 (12) 0.22612 (8) 0.01758 (18) H4A 1.4208 0.0711 0.2593 0.021\* C5 1.12052 (15) 0.17132 (12) 0.22782 (7) 0.01604 (17) H5A 1.0873 0.2432 0.2623 0.019\* C6 0.96924 (15) 0.16730 (11) 0.17801 (7) 0.01418 (16) C7 0.76209 (15) 0.27851 (11) 0.17797 (7) 0.01395 (15) C8 0.69425 (15) 0.40713 (12) 0.22566 (7) 0.01553 (16) H8A 0.7585 0.4870 0.1952 0.019\* H8B 0.7266 0.3671 0.2904 0.019\* C9 0.45956 (15) 0.47007 (11) 0.21552 (7) 0.01428 (16) H9A 0.4135 0.5839 0.1937 0.017\* C10 0.33157 (15) 0.41586 (12) 0.30181 (7) 0.01506 (16) C11 0.40552 (17) 0.27201 (13) 0.36660 (8) 0.01809 (18) H11A 0.5411 0.2104 0.3590 0.022\* C12 0.28225 (18) 0.21843 (14) 0.44205 (8) 0.0221 (2) H12A 0.3371 0.1226 0.4842 0.027\* C13 0.07487 (19) 0.30739 (14) 0.45555 (8) 0.0219 (2) C14 0.00187 (17) 0.45394 (14) 0.39134 (8) 0.01970 (19) H14A −0.1332 0.5167 0.3988 0.024\* C15 0.12813 (16) 0.50602 (13) 0.31725 (7) 0.01712 (17) H15A 0.0761 0.6039 0.2765 0.021\* C16 −0.2680 (2) 0.3366 (2) 0.53468 (10) 0.0324 (3) H16A −0.3276 0.3493 0.4785 0.049\* H16B −0.2880 0.4370 0.5428 0.049\* H16C −0.3334 0.2786 0.5866 0.049\* C17 0.0361 (3) 0.1144 (2) 0.60089 (12) 0.0443 (4) H17A 0.1564 0.1203 0.6219 0.067\* H17B 0.0737 0.0256 0.5768 0.067\* H17C −0.0645 0.1046 0.6519 0.067\* C18 0.29283 (15) 0.45225 (12) 0.08212 (7) 0.01415 (16) H1N4 0.211 (3) 0.386 (2) −0.0067 (13) 0.028 (4)\* H2N4 0.414 (3) 0.287 (2) 0.0245 (12) 0.027 (4)\* ------ --------------- ---------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1281 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ Br1 0.01316 (5) 0.01906 (5) 0.05023 (9) −0.00079 (4) −0.00226 (5) −0.01560 (5) S1 0.01295 (10) 0.01764 (10) 0.01829 (11) −0.00210 (8) −0.00309 (8) −0.00530 (8) N1 0.0112 (3) 0.0157 (3) 0.0161 (4) −0.0029 (3) −0.0005 (3) −0.0046 (3) N2 0.0112 (3) 0.0159 (3) 0.0149 (3) −0.0024 (3) −0.0014 (3) −0.0059 (3) N3 0.0276 (6) 0.0347 (6) 0.0316 (6) −0.0095 (5) 0.0114 (5) −0.0020 (5) N4 0.0150 (4) 0.0224 (4) 0.0189 (4) −0.0026 (3) −0.0039 (3) −0.0088 (3) C1 0.0155 (4) 0.0180 (4) 0.0224 (5) −0.0042 (3) −0.0027 (3) −0.0078 (4) C2 0.0165 (4) 0.0178 (4) 0.0284 (5) −0.0035 (3) −0.0014 (4) −0.0102 (4) C3 0.0125 (4) 0.0140 (4) 0.0282 (5) −0.0032 (3) −0.0008 (3) −0.0060 (4) C4 0.0128 (4) 0.0158 (4) 0.0251 (5) −0.0044 (3) −0.0029 (3) −0.0061 (4) C5 0.0131 (4) 0.0150 (4) 0.0210 (4) −0.0046 (3) −0.0012 (3) −0.0060 (3) C6 0.0112 (4) 0.0140 (4) 0.0170 (4) −0.0044 (3) −0.0005 (3) −0.0034 (3) C7 0.0120 (4) 0.0142 (4) 0.0153 (4) −0.0043 (3) −0.0001 (3) −0.0035 (3) C8 0.0122 (4) 0.0167 (4) 0.0194 (4) −0.0043 (3) −0.0012 (3) −0.0073 (3) C9 0.0124 (4) 0.0153 (4) 0.0164 (4) −0.0046 (3) −0.0016 (3) −0.0055 (3) C10 0.0133 (4) 0.0168 (4) 0.0161 (4) −0.0038 (3) −0.0011 (3) −0.0068 (3) C11 0.0154 (4) 0.0189 (4) 0.0185 (4) −0.0033 (3) 0.0000 (3) −0.0059 (3) C12 0.0207 (5) 0.0216 (5) 0.0194 (5) −0.0046 (4) 0.0007 (4) −0.0023 (4) C13 0.0208 (5) 0.0256 (5) 0.0199 (5) −0.0086 (4) 0.0040 (4) −0.0078 (4) C14 0.0147 (4) 0.0244 (5) 0.0204 (5) −0.0041 (4) 0.0008 (3) −0.0100 (4) C15 0.0142 (4) 0.0195 (4) 0.0173 (4) −0.0027 (3) −0.0017 (3) −0.0072 (3) C16 0.0234 (6) 0.0522 (9) 0.0273 (6) −0.0184 (6) 0.0087 (5) −0.0162 (6) C17 0.0419 (9) 0.0417 (8) 0.0351 (8) −0.0142 (7) 0.0126 (7) 0.0035 (6) C18 0.0124 (4) 0.0167 (4) 0.0131 (4) −0.0051 (3) −0.0005 (3) −0.0032 (3) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1816 .table-wrap} --------------------- -------------- ----------------------- -------------- Br1---C3 1.8976 (10) C7---C8 1.5091 (14) S1---C18 1.6896 (10) C8---C9 1.5391 (14) N1---C7 1.2927 (13) C8---H8A 0.9700 N1---N2 1.3901 (12) C8---H8B 0.9700 N2---C18 1.3518 (13) C9---C10 1.5155 (14) N2---C9 1.4917 (13) C9---H9A 0.9800 N3---C13 1.3759 (16) C10---C11 1.3972 (15) N3---C17 1.441 (2) C10---C15 1.3990 (14) N3---C16 1.4450 (19) C11---C12 1.3893 (16) N4---C18 1.3404 (14) C11---H11A 0.9300 N4---H1N4 0.842 (19) C12---C13 1.4113 (17) N4---H2N4 0.841 (19) C12---H12A 0.9300 C1---C2 1.3859 (15) C13---C14 1.4090 (17) C1---C6 1.4049 (15) C14---C15 1.3848 (16) C1---H1A 0.9300 C14---H14A 0.9300 C2---C3 1.3945 (16) C15---H15A 0.9300 C2---H2A 0.9300 C16---H16A 0.9600 C3---C4 1.3848 (15) C16---H16B 0.9600 C4---C5 1.3926 (14) C16---H16C 0.9600 C4---H4A 0.9300 C17---H17A 0.9600 C5---C6 1.3999 (14) C17---H17B 0.9600 C5---H5A 0.9300 C17---H17C 0.9600 C6---C7 1.4583 (14) C7---N1---N2 107.84 (8) N2---C9---C8 100.12 (8) C18---N2---N1 119.42 (8) C10---C9---C8 114.94 (8) C18---N2---C9 127.78 (8) N2---C9---H9A 110.4 N1---N2---C9 112.61 (8) C10---C9---H9A 110.4 C13---N3---C17 120.35 (12) C8---C9---H9A 110.4 C13---N3---C16 120.36 (12) C11---C10---C15 117.01 (10) C17---N3---C16 119.29 (12) C11---C10---C9 122.25 (9) C18---N4---H1N4 117.0 (13) C15---C10---C9 120.66 (9) C18---N4---H2N4 120.0 (12) C12---C11---C10 121.88 (10) H1N4---N4---H2N4 119.5 (17) C12---C11---H11A 119.1 C2---C1---C6 120.68 (10) C10---C11---H11A 119.1 C2---C1---H1A 119.7 C11---C12---C13 120.90 (10) C6---C1---H1A 119.7 C11---C12---H12A 119.6 C1---C2---C3 118.82 (10) C13---C12---H12A 119.6 C1---C2---H2A 120.6 N3---C13---C14 121.54 (11) C3---C2---H2A 120.6 N3---C13---C12 121.30 (11) C4---C3---C2 121.77 (10) C14---C13---C12 117.15 (10) C4---C3---Br1 119.03 (8) C15---C14---C13 121.01 (10) C2---C3---Br1 119.19 (8) C15---C14---H14A 119.5 C3---C4---C5 119.05 (10) C13---C14---H14A 119.5 C3---C4---H4A 120.5 C14---C15---C10 122.00 (10) C5---C4---H4A 120.5 C14---C15---H15A 119.0 C4---C5---C6 120.47 (10) C10---C15---H15A 119.0 C4---C5---H5A 119.8 N3---C16---H16A 109.5 C6---C5---H5A 119.8 N3---C16---H16B 109.5 C5---C6---C1 119.21 (9) H16A---C16---H16B 109.5 C5---C6---C7 120.05 (9) N3---C16---H16C 109.5 C1---C6---C7 120.72 (9) H16A---C16---H16C 109.5 N1---C7---C6 121.29 (9) H16B---C16---H16C 109.5 N1---C7---C8 113.61 (8) N3---C17---H17A 109.5 C6---C7---C8 124.98 (9) N3---C17---H17B 109.5 C7---C8---C9 102.52 (8) H17A---C17---H17B 109.5 C7---C8---H8A 111.3 N3---C17---H17C 109.5 C9---C8---H8A 111.3 H17A---C17---H17C 109.5 C7---C8---H8B 111.3 H17B---C17---H17C 109.5 C9---C8---H8B 111.3 N4---C18---N2 116.40 (9) H8A---C8---H8B 109.2 N4---C18---S1 122.21 (8) N2---C9---C10 110.17 (8) N2---C18---S1 121.35 (8) C7---N1---N2---C18 164.20 (9) C7---C8---C9---N2 −16.35 (9) C7---N1---N2---C9 −11.12 (11) C7---C8---C9---C10 101.64 (9) C6---C1---C2---C3 −0.38 (17) N2---C9---C10---C11 82.45 (11) C1---C2---C3---C4 0.78 (18) C8---C9---C10---C11 −29.71 (13) C1---C2---C3---Br1 −178.27 (9) N2---C9---C10---C15 −94.19 (11) C2---C3---C4---C5 −0.65 (17) C8---C9---C10---C15 153.64 (9) Br1---C3---C4---C5 178.40 (8) C15---C10---C11---C12 1.39 (16) C3---C4---C5---C6 0.12 (16) C9---C10---C11---C12 −175.37 (10) C4---C5---C6---C1 0.25 (16) C10---C11---C12---C13 0.81 (18) C4---C5---C6---C7 −178.15 (10) C17---N3---C13---C14 −170.94 (15) C2---C1---C6---C5 −0.12 (16) C16---N3---C13---C14 8.9 (2) C2---C1---C6---C7 178.27 (10) C17---N3---C13---C12 8.4 (2) N2---N1---C7---C6 −177.42 (9) C16---N3---C13---C12 −171.79 (13) N2---N1---C7---C8 −1.24 (11) C11---C12---C13---N3 178.51 (13) C5---C6---C7---N1 178.25 (10) C11---C12---C13---C14 −2.16 (18) C1---C6---C7---N1 −0.12 (15) N3---C13---C14---C15 −179.34 (12) C5---C6---C7---C8 2.53 (15) C12---C13---C14---C15 1.33 (17) C1---C6---C7---C8 −175.85 (10) C13---C14---C15---C10 0.88 (17) N1---C7---C8---C9 12.11 (11) C11---C10---C15---C14 −2.23 (16) C6---C7---C8---C9 −171.88 (9) C9---C10---C15---C14 174.59 (10) C18---N2---C9---C10 81.36 (12) N1---N2---C18---N4 5.51 (14) N1---N2---C9---C10 −103.80 (9) C9---N2---C18---N4 −179.96 (9) C18---N2---C9---C8 −157.18 (10) N1---N2---C18---S1 −172.28 (7) N1---N2---C9---C8 17.65 (10) C9---N2---C18---S1 2.25 (15) --------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2660 .table-wrap} ----------------------------------------------------------------------------------- Cg1 and Cg2 are the centroids of the C1--C6 and C10--C15 rings, respectively. ----------------------------------------------------------------------------------- ::: ::: {#d1e2669 .table-wrap} ----------------------- ---------- ---------- ------------- --------------- D---H···A D---H H···A D···A D---H···A N4---H1N4···S1^i^ 0.84 (2) 2.54 (2) 3.3679 (11) 170.8 (17) C5---H5A···Cg2^ii^ 0.93 2.72 3.5462 (12) 149 C16---H16B···Cg2^iii^ 0.96 2.71 3.6676 (18) 154 C17---H17C···Cg1^iv^ 0.96 2.74 3.5990 (19) 149 ----------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −x, −y+1, −z; (ii) x+1, y, z; (iii) −x, −y+1, −z+1; (iv) −x+1, −y, −z+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) Cg1 and Cg2 are the centroids of the C1--C6 and C10--C15 rings, respectively. ::: D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------------- ---------- ---------- ------------- ------------- N4---H1N4⋯S1^i^ 0.84 (2) 2.54 (2) 3.3679 (11) 170.8 (17) C5---H5A⋯Cg2^ii^ 0.93 2.72 3.5462 (12) 149 C16---H16B⋯Cg2^iii^ 0.96 2.71 3.6676 (18) 154 C17---H17C⋯Cg1^iv^ 0.96 2.74 3.5990 (19) 149 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009. [^2]: § Additional correspondence author, e-mail: suchada.c@psu.ac.th. Thomson Reuters ResearcherID: A-5085-2009.	PubMed Central	2024-06-05T04:04:18.941954	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052174/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o701-o702", "authors": [ { "first": "Hoong-Kun", "last": "Fun" }, { "first": "Thitipone", "last": "Suwunwong" }, { "first": "Suchada", "last": "Chantrapromma" } ] }
PMC3052175	Background ========== WHO defined palliative care as \'\'the active total care of patients whose disease is not responsive to curative treatment\' \[[@B1]\]. In Belgium, palliative care relies on this definition and is provided in different settings: home care, residential units or hospices. These 51 residential units have 379 palliative beds, i.e. an insufficient number of beds in view of the palliative care demand. Therefore, every acute hospital is subsidized for an intramural palliative support team. Recently, 6 day centres have been created in Belgium. All these services are specialized in the care of palliative patients with more complex needs. The patients not treated in these services are treated in classic structures providing palliative care but not specialized in palliative care (general hospital wards, home care nursing services, general practitioners, nursing homes\...) \[[@B2]\]. Beside the specialised palliative services, the country is divided into 25 areas, called palliative networks, each covering around 300.000 inhabitants. These networks coordinate the intervention of palliative care services and integrate them into the health care system. Each network has its own home care team. Even though more than 70% of Belgian population would prefer to be treated at home, a large number of deaths occur in hospital \[[@B3]\]. A considerable amount of information regarding palliative inpatients is available and the place of death and its determinants in this specific context have been extensively investigated \[[@B4]\]. Van den Block et al. reported on the institutionalised nature of the final phase of life and concluded that clinical condition, expression of preferences, and characteristics of healthcare organisation seem to be associated with the transfer of such patients to the hospital \[[@B5]\]. However, the wider use of the hospital setting in providing palliative care has been less frequently considered. Most of the previous studies have been limited to specific diagnoses (e.g., cancer), age groups (e.g., the elderly), or settings (e.g., specialist palliative care services). Although some surveys have included the number of palliative inpatients, they do not give a global overview as they were all conducted in one single or in a university hospital \[[@B6]-[@B10]\]. Furthermore, two of them have focused only on terminally ill patients and another study was specifically interested in the need for specialist inpatient palliative care \[[@B6],[@B7],[@B10]\]. The purpose of this study was to assess the overall population of hospital palliative inpatients who should benefit from palliative care and to describe their main demographic and medical characteristics. Methods ======= The study was prospective and data was collected by interviews conducted with medical and nursing staff. The literature shows that the proportion of cancer patients among palliative inpatients varies around 50% \[[@B6]\]. The sample size was computed to detect a 25% difference between the proportions of cancer and non cancer patients. With a hypothesis of type I error equal to 0.05 and a power equal to 0.80, the sample size should be 364 palliative patients. In order to estimate the number of beds to include, we chose a proportion of palliative patients of 10% as this proportion varies between 5% and 15% in the literature \[[@B6],[@B9]\]. This would lead to investigate 364/0.10 = 3640 inpatients. Taking an occupation rate of 0.75 entails that 4842 beds should be checked. Fourteen hospitals were randomly selected from all Belgian hospitals, taking into account the type (academic/non academic; acute/non acute), the size (\< 300 beds, 300-500 beds and \>500 beds), and the geographical location (Brussels, Flanders and Wallonia). Twelve categories were created based on these hospital\'s characteristics and each Belgian hospital was allocated to a single category. The hospital sample was built by a random selection of one hospital in each category. Finally, a university hospital from Flanders and another from Wallonia were added to the sample. Two non university hospitals refused to participate and were replaced by 2 other hospitals randomly selected in the corresponding categories. All hospital beds were included (4746 beds), except obstetrics and psychiatry as such wards are only rarely involved in palliative care. Intensive care units were also excluded although these units present a high death rate and in spite of innovative and specific palliative care programs \[[@B11]\]. Indeed the survey design was not adapted to this type of patients and treatments (prognostic uncertainties, specific life-sustaining treatment\...). Paediatric and neonatology units were also not eligible due to their specific care plans. As we intended to measure the frequency of patients who could be considered as palliative and therefore should benefit from a palliative care program, the palliative units were not included in this survey. All patients hospitalised in an eligible unit for at least 48 hours (i.e. enough time for the physicians and the nurses to know the patient) were included in the study. Patients undergoing in-hospital transfer during the same stay were included only once. The Ethics Committee of St Luc Hospital-UCL gave a positive opinion to the protocol which was registered in the National Federal Experimentation Data Bank of the National Ethics Committee under the number B40320084090. The study was performed according the different Belgian laws concerning confidentiality and private life (2002), patients\' rights (2002) and experimentation on human beings (2004). This study was a sub-project of a larger one which was asked by the promoter, the Belgian Health Care Knowledge (KCE). Three specifically appointed nurses conducted the survey in 2008, over a 3-month period. After hospital approval, the caregivers of each ward included in the survey were interviewed once on a certain day fixed in advance. In small hospitals with few wards, all interviews were conducted in a single day. Larger hospitals with a greater number of wards to be surveyed required more time. Only 3 physicians refused to participate, i.e. less than 1% of the physicians contacted. The study nurses interviewed the nurses and physicians who were in charge of the patients and had daily contact with them. Firstly, the nurses and physicians were separately asked to assess whether that patient met the definition of a palliative patient. In 2002, the World Health Organisation defined palliative care as \"an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness through the prevention and relief of suffering by means of early identification, impeccable assessment and treatment of pain and other problems physical psychosocial and spiritual\" \[[@B12]\]. This definition is broader than the one given by the World Health Organisation in (1990): \"Palliative care is the active total care of patients whose disease is not responsive to curative treatment\"\[[@B1]\]. In Belgium, even though the notion of palliative patient is not officially defined, preferential reimbursement rate are granted to the patient having a \'palliative\' status. As mentioned by Keirse et al. and by Pastrana et al., there is no current consensus about the definition of palliative patient \[[@B13],[@B14]\]. Therefore within the context of our survey we used the following definition: \"a patient suffering from an incurable, progressive, life-threatening disease, with no possibility of obtaining remission, stabilization or improvement of this illness\". The term \"incurable\" excluded illnesses for which there is a chance of complete cure; the term \"progressive\" eliminated chronic, incurable but stable disease; the terms \"no possibility of obtaining remission, stabilization or improvement of the illness\" highlighted the ineffectiveness of specific therapeutics to control the disease \[[@B15]\]; and the term \"life-threatening disease\" introduced a notion of survival prediction and fatal outcome. This last notion could not be defined in a more precise way due to the difficulty in giving an accurate prognosis except when the patient is very close to death \[[@B16]\]. This definition of \"palliative patient\" does not include any criterion based on patient needs because we considered this aspect too difficult to define precisely, as it would have required taking into account many other factors deemed by the caregivers to be related to palliative care \[[@B17]\]. The second part of the study was carried out in respect of those patients who met these four criteria. The study nurses made an interview of the same caregivers using a structured questionnaire. The questionnaire collected data relating to the patient\'s socio-demographic characteristics, diagnoses, prognosis, and care plan. The questionnaire can be found in annex (File [1](#S1){ref-type="supplementary-material"}: English version; File [2](#S2){ref-type="supplementary-material"}: French version). In order to avoid any (mis)interpretation of the palliative patient\'s definition, the term \'palliative\' was not used during the interview of the caregivers. The interviewer presented to the caregivers a paper mentioning the 4 abovementioned criteria of our definition. Then the caregivers reviewed if the patient met each of the four criteria presented. Before the beginning of the hospital survey, the questionnaire was first tested in 2 hospitals not included in the survey\'s sample. Then, the study nurses performed in one hospital under the supervision of the survey\'s designer. Finally, during the survey, regular meetings were organised between the study nurses and the survey\'s designer. Univariate and multivariate statistics were performed to analyse the data. Pearson\'s chi square test was used to detect statistical differences between groups as the data were primarily categorical. Comparisons of age between groups were made using the Wilcoxon\'s test. Multivariate logistic regression was also used to test the effects of various factors on the intention to prolong life. The covariates introduced in the model were age, sex, pathology, prognosis and type of bed. The analysis was made with SAS version 9.1 and a p-value equal or less than 0.05 was considered as significant. Results ======= Prevalence of palliative patients --------------------------------- Two-hundred and forty-nine in-patients were identified as \"palliative\" by the medical and nursing staff, comprising 9.4% of the total in-patient population. Table [1](#T1){ref-type="table"} shows that the prevalence of palliative patients was significantly less in surgical and rehabilitation beds than in medical and geriatric beds. The prevalence also varied significantly among regions. One Brussels\' hospital had a particularly high prevalence value. After exclusion of this \'outlier\', there were no significant differences in the prevalence of palliative patients between university and other hospitals, private or public institutions, and hospitals with or without a palliative care unit. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Prevalence of palliative inpatients ::: N Palliative Patients Non Palliative Patients p-value ---------------------- ---------------- ------ --------------------- ------------------------- ------------ Type of beds Surgery 727 16 (2.2%) 711(97.8%) p ≤ 0,001 Rehabilitation 488 22 (4.5%) 466 (95.5%) Medicine 1015 134 (13.2%) 881 (86.8%) Geriatric 409 77 (18.8%) 332 (81.2%) Region Flanders 624 49 (7.9%) 575 (92.1%) p ≤ 0,001 Wallonia 692 56 (8.1%) 636 (91.9%) Brussels 534 85 (15.9%) 449 (84.1%) Palliative care unit With 1614 166 (10.3%) 1448 (89.7%) p = 0.0610 Without 1025 83 (8.1%) 942 (91.9%) Social status Public 1111 96 (8.6%) 1005 (91.4%) p = 0.2338 Private 1528 153 (10.0%) 1375 (90.0%) ::: Patients\' characteristics -------------------------- Of the 249 palliative patients, 55% (136/249) were female and the mean age was 72 years with a range of 21 to 99. The majority of patients were older than 65 years (175/249) with a considerable number older than 80 (93/249). About half of the patients were married (112/239) and the others were widowed (79), divorced (14) or single (34). Seventy percent of patients (174/249) had been admitted from home and 30% from another residence, such as a nursing home. The primary diagnoses are shown in Table [2](#T2){ref-type="table"}. Approximately half of the patients had a primary diagnosis of cancer. The most common non-cancer diagnoses were dementia, stroke, and cardiac, respiratory or hepatic failure. Cancer patients were significantly younger than the non-cancer patients (68 ± 14 versus 77 ± 13 years, p \< 0.0001) and mainly hospitalised in medical beds (81/128). Patients suffering from dementia and stroke were significantly older than the other palliative patients (82 ± 9 years versus 70 ± 15 years, p \< 0.0001) and were largely hospitalised in geriatric beds (34/49) (Figure [1](#F1){ref-type="fig"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Distribution of primary diagnoses ::: Cancer diagnoses 128 (51.4%) ------------------------- ------------- Solid tumour 108 (43.4%) Haematological cancer 19 (7.6%) Non-cancer diagnoses 121 (48.6%) Dementia 32 (12.9%) Stroke 17 (6.8%) Organ system failure 50 (20.0%) Cardiac failure 16 (6.4%) Respiratory failure 16 (6.4%) Hepatic failure 13 (5.2%) Renal failure 5 (2.0%) Other diseases 40 (16.0%) Neurological diseases 8 (3.2%) Vascular diseases 6 (2.4%) Infectious diseases 2 (0.8%) Others 6 (2.4%) Total 249 (100%) ::: ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Age distributions of palliative patients by diagnostic group. The first bar represents the distribution of age of all palliative patients whatever the disease. The others display the distribution of age for the most frequent underlying diseases. ::: ![](1472-684X-10-2-1) ::: For almost one third of patients (71/242), the diagnosis had been established 3 months before the current hospitalisation and for half of them (112/242), it had been established during the year prior to the study. As illustrated in Table [3](#T3){ref-type="table"} the estimated life expectancy varied from less than 7 days to more than 5 years. One third of patients had a life expectancy of three months or less and, from the primary diagnosis, one half of patients would be expected to still be alive after six months (Figure [2](#F2){ref-type="fig"}). The prognosis was less than 1 year for 88% of cancer patients and for 56% of non-cancer patients (p \< 0.0001). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Distribution of estimated life expectancy ::: \< 7 days 10 (4.1%) 79 (32.5%) ---------------------- ------------ ------------ \> 3 and ≤ 6 months 40 (16.5%) 97 (40.0%) \> 6 and ≤ 12 months 57 (23.5%) \> 1 and ≤ 5 years 62 (25.5%) 67 (27.5%) \> 5 years 5 (2.0%) Total 243 (100%) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Survival prognosis according to disease. The first bar represents the distribution of life expectancy of all palliative patients whatever the disease. The others display the distribution of survival prognosis for the most frequent underlying diseases. ::: ![](1472-684X-10-2-2) ::: Patients\' treatment -------------------- The caregivers had already established a treatment plan for 220 of the 249 patients (88%) before the interview. The plan had been discussed by physicians and nurses in 191 cases (77%) and by physicians alone in 27 cases (11%). These percentages were independent of the pathology, survival prognosis, or expectations of the treatment plan. When analysing the expectations of the treatment plan, it appears that the goal of physicians and nurses was to improve patient comfort rather than prolonging life. Multivariate logistic regression analysis showed that treatment expectations depended mainly on the patient\'s prognosis (OR = 1.760, CL = 1.360 - 2.279). For the 79 patients with a survival prognosis less than 3 months, an expectation of prolonging life was reported in just 6.3% of cases (5/79), while for the 67 patients with a prognosis of at least 1 year, the expectation of prolonging life was reported in 41.8% of cases. No significant differences in expectations were observed comparing cancer to non-cancer patients (Table [4](#T4){ref-type="table"}); however, the caregivers more frequently reported an expectation to prolong life in patients with stroke (6/17) or organ system failure (20/50) than in patients with dementia (1/32). ::: {#T4 .table-wrap} Table 4 ::: {.caption} ###### Physicians\' expectations from the treatment plan ::: -------------------------------------------------------------------------------------- Life prolongation\ Improvement of comfort\ n = 65 (100%) n = 179 (100%) ----------- ------------- -------------------- ------------------------- ------------- Age \< 75 years 37 (56.9%) 72 (40.2%) p = 0.0204 ≥ 75 years 28 (43.1%) 107 (59.8%) Prognosis ≤ 3 months 5 (7.7%) 73 (40.8%) p \< 0.0001 \> 3 months 56 (86.2%) 104 (58.1%) ≤ 1 year 33 (50.8%) 141 (78.8%) p = 0.0019 \> 1 year 28 (43.1%) 36 (20.1%) -------------------------------------------------------------------------------------- ::: The type of treatment was generally clearly documented and defined by the professional caregivers. Cardiac resuscitation was excluded for 71% of patients (177/249). Antibiotics, transfusions, treatments specific to the causative pathology (e.g., chemotherapy for cancer patients), artificial nutrition, and transfer to the intensive care unit were being considered, had been planned, or were ongoing in 90% (224/249), 78% (195/249), 57% (142/249), 50% (124/249) and 33% (81/249) of patients, respectively. These interventions were administered in order to control symptoms in 66% (149/224), 74% (144/195), 56% (80/142), 45% (56/124) and 25% (20/81) of the cases, respectively. Table [5](#T5){ref-type="table"} shows the proportion of patients for which treatments were excluded depending on their prognosis. In case of very poor prognosis, cardiac resuscitation and transfer to intensive care unit were excluded for all patients. These 2 treatments were excluded for more than half of patients whatever their prognosis. ::: {#T5 .table-wrap} Table 5 ::: {.caption} ###### Prognosis and treatment excluded ::: Prognosis --------------------------------------------- ----------- ------- ------- ------- ------- ------- Cardiac resuscitation 100% 91.7% 81.8% 72.5% 63.2% 67.2% Transfer to intensive care unit 100% 95.5% 72.7% 57.9% 58.2% 56.5% Treatment specific to the causative disease 90.0% 52.2% 54.8% 30.8% 28.6% 33.3% Artificial nutrition 90.0% 73.9% 47.6% 54.1% 40.0% 36.1% Antibiotics 80.0% 30.4% 4.4% 0 1.8% 3.1% Transfusion 80.0% 54.2% 20.5% 13.5% 9.1% 5.0% ::: Discussion ========== Several limitations should be mentioned when interpreting these results. The first is a possible bias in the recruitment of patients. The initial sample size calculations gave an estimate of at least 3640 beds to recruit 364 palliative patients. The final sample size was smaller, i.e. 249 patients, for two reasons. The mean bed occupation rate was lower than expected; the study excluded patients with a length of stay less than 48 hours (25% of patients in some acute hospitals). The second limitation is related to the fact that only the health care providers were interviewed and therefore, the survey inaccurately reflects patient treatment preferences. The third limitation concerns the method of patient selection. We quantified the palliative in-patient population on just one day. Visiting the same hospitals more than once would have provided a more precise measure. Nevertheless, this is the first survey to explore the number and characteristics of palliative inpatients at a national level. Slightly less than one out of ten inpatients was identified as palliative. Similar percentages have been reported from other surveys but these were conducted in just one institution. Morize et al included all patients with advanced or terminal stage life-threatening illness who were hospitalised in a large French university hospital \[[@B6]\]. These authors reported that 13% of the inpatients were palliative patients. A similar percentage (12%) was observed by Edmonds et al. and by Billings et al in an English and an American academic hospital, respectively \[[@B7],[@B8]\]. In a study by Gott and colleagues, the prevalence of palliative patients was higher (22%), but the inclusion criteria in this study were based on need for supportive and palliative care \[[@B9]\]. Similarly, Skilbek et al. concentrated on specialist palliative care services and observed that 4% of in-patients were considered suitable for referral to a palliative care unit \[[@B10]\]. As expected, the largest numbers of palliative in-patients were admitted to geriatric beds. Metropolitan hospitals also had greater number of palliative patients, supporting the findings of Houtekkier et al. who concluded that palliative patients died in hospital more often in Brussels than in other parts of country \[[@B18]\]. As mentioned in the section \'method\', one hospital was considered as an \'outlier\'. This hospital holds 22% of Brussels\' palliative beds and was the pioneer of in-hospital palliative care in the country. The higher proportion of palliative patients observed in this hospital could be due to a different culture about palliative care. The second aim of the present study was to describe the demographic and clinical characteristics of the palliative inpatients. Our results show that the palliative inpatient population is complex. A large number of cancer and non-cancer pathologies are represented, contrary to what is usually described in specialist palliative care services \[[@B19],[@B20]\]. As in previous reports, cancer was the leading diagnosis in our study but nearly half the patients had a non-malignant disease \[[@B6],[@B9]\]. Despite their typically insidious onset, prolonged disease trajectory and difficulty in predicting life expectancy, chronic illnesses are major causes of death in developed countries today \[[@B21]-[@B23]\]. Moreover, persons dying from chronic illness tend to have frequent exacerbations requiring hospitalisation. There is evidence suggesting that these patients may require palliative care, just as those who suffer from malignant disease \[[@B24]\]. In view of these findings, palliative care in hospital cannot be confined to one patient group and professional caregivers need to acquire sufficient expertise to meet the common but also the specific needs of cancer and non-cancer patients \[[@B13]\]. Even if a correct estimation of the patient\'s prognosis remains quite difficult, our results show considerable variation in the life-expectancy of our palliative population \[[@B16]\]. One third of the palliative inpatients had a life expectancy of 3 months or less. These patients can be considered \"terminally ill patients\" as they are referred to in the current literature. For approximately another one third of patients, the physicians and nurses considered the survival prognosis to be more than one year. Nevertheless, in 70% of all the palliative patients, the treatment plan aimed at improving symptoms rather than at prolonging life. As other researchers, we noted that when caregivers considered using potentially life-prolonging interventions, their decision was significantly associated with a long-term survival prognosis \[[@B25]\]. However, we found no difference between patients with and those without cancer, as reported by Van den Block et al \[[@B26]\]. In summary, in contrast to Becker and colleagues who noted that comfort-focused care concerned less than one dying patient out of two, our results indicate that the Belgian physicians and nurses are willing to limit aggressive treatments and to plan comprehensive palliative care \[[@B27]\]. Our results also indicate that the caregivers seem to be in agreement with the World Health Organisation\'s recommendation and tend to integrate palliative care as soon as possible into the course of illness, as reported by the majority of European medical oncologists \[[@B1],[@B12],[@B28]\]. Another striking finding of our study was that antibiotics, blood transfusions, specific treatments for primary disease, artificial nutrition, and transfer to the intensive care unit were considered for, or given, to about 90%, 80%, 60%, 50% and 33% of the patients, respectively. Several authors have already noted that in an acute care hospital, such therapeutic interventions, considered as comfort care, were continued for the majority of dying patients \[[@B26],[@B29],[@B30]\]. However, as these studies were retrospective charts reviews, the detailed reasons for the therapeutic procedures could not be clearly determined. In our survey, the treatment objective was generally clearly noted by the health care providers: transfusions and antibiotics were used largely to alleviate symptoms; whereas admission to the intensive care unit, artificial nutrition, and specific disease-related treatments were used more to prolong life. Undoubtedly, interventions such as antibiotics may contribute to a better management of distressing symptoms \[[@B31]\]. Furthermore, the long-term prognosis of some patients and uncertainty about the short-term prognosis in others may encourage a mixed management strategy and an interaction between a curative and palliative approach. Nevertheless, in a setting where priority is given to life-supporting and life prolonging activities, some of these interventions may be considered invasive and futile \[[@B32]\]. Van Leeuwen et al, who observed oncology multidisciplinary meetings discussing potentially life prolonging treatments, came to the conclusions that before making a decision, healthcare professionals should gather extensive information about gains that may be expected from an intervention \[[@B33]\]. If case of doubt about whether or not to start or continue treatment, the patient\'s wish could be a decisive consideration. Unfortunately, the purpose of our study was not to assess whether the decisions of the interviewed healthcare professionals were medically and ethically appropriate. Conclusions =========== The ability of health care providers to recognise the patient as \"palliative\" and their readiness to limit aggressive treatment and plan palliative care is essential to improve palliative care for hospitalised patients. The main result of this article is that physicians and nurses identified 10% of inpatients as \"palliative\" patients and that they adopted a comfort care plan in 70% of cases. Our results highlight that the palliative inpatient population is multifaceted and that therapeutic procedures are varied and complex. These findings may help in planning the organisation of palliative care in health care systems. Models of care that embrace all end-of-life paths and meet the common but also the specific needs of every disease must be developed. Medical and nursing staff also need to be educated and supported in provision of care so that palliative patients can live with comfort and dignity whatever their primary diagnosis or their life expectancy. Another challenge is to determine how many and which of the 10% of palliative in-patients should have access to specialised palliative care services. These issues are important and require careful consideration if high quality of care is to be provided to all patients at the end of life. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MSD conceived of the study, participated in its design and coordination and helped to the draft of the manuscript. YLK participated to the data analysis. CMB participated in the acquisition of data, statistical analysis and drafted the manuscript. All authors read and approved the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1472-684X/10/2/prepub> Supplementary Material ====================== ::: {.caption} ###### Additional file 1 Questionnaire (English version). This file contains the questionnaire used by the study nurses when interviewing the caregivers. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 Questionnaire (French version). This file contains the questionnaire used by the study nurses when interviewing the caregivers. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ We would like to thank Sylvie Roels, Pierre Fontaine and Ann Cardinael for data collection. These individuals were compensated as study personnel. We are also indebted to Chantal Doyen and Annie Drowart who tested the questionnaire. We also thank the reviewers for their constructive remarks.	PubMed Central	2024-06-05T04:04:18.947450	2011-3-2	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052175/", "journal": "BMC Palliat Care. 2011 Mar 2; 10:2", "authors": [ { "first": "Marianne S", "last": "Desmedt" }, { "first": "Yolande L", "last": "de la Kethulle" }, { "first": "Myriam I", "last": "Deveugele" }, { "first": "Emmanuel A", "last": "Keirse" }, { "first": "Dominique J", "last": "Paulus" }, { "first": "Johan J", "last": "Menten" }, { "first": "Steven R", "last": "Simoens" }, { "first": "Paul J", "last": "vanden Berghe" }, { "first": "Claire M", "last": "Beguin" } ] }
PMC3052176	Background ========== Slowed muscle relaxation due to persistent electrical discharges is the hallmark of myotonia \[[@B1]-[@B4]\]. Myotonia occurs naturally in several species (humans, goats, mice) as a result of genetic deficiency of the skeletal muscle CLC-1 channel, a disease which in humans is termed myotonia congenita \[[@B1]-[@B13]\]. It can also be produced experimentally by blocking muscle Cl^-^channels of normal muscle, for example with 9-anthracene carboxylic acid (9-AC), p-chloro-phenoxy-propionic acid, or 2,4-dichlorphenoxyacetate \[[@B4],[@B14]-[@B16]\]. Muscle from humans and animals with myotonia congenita has physiological, structural and biochemical alterations which transcend the loss of CLC-1 channels, including hypertrophy (goats, most humans) or atrophy (mice), alterations in fiber type composition (in particular loss of type IIB fibers, seen in most species with myotonia congenita), and altered amounts of parvalbumin \[[@B1],[@B5],[@B7],[@B9],[@B11]-[@B13],[@B17],[@B18]\]. These downstream changes may contribute to the complex abnormalities in contractile performance found in CLC-1 deficient muscle, in particular changes that occur during the contractile phase of the contraction-relaxation cycle, such as impaired force production and alterations in rate of fatigue during isometric contractions \[[@B19]\]. Humans with myotonia experience limb muscle stiffness which interferes particularly with the initiation of movements \[[@B3],[@B20]-[@B22]\]. Involvement of respiratory muscles may lead to \"breathing difficulties\", dyspnea, sleep apnea, and daytime alveolar hypoventilation \[[@B23]-[@B26]\]. For many subjects the myotonia has an adverse effect on their ability to engage in sports \[[@B2],[@B21]-[@B23]\]. The extent of myotonia, however, dissipates with repetitive contractions, the so-called warm-up phenomenon \[[@B2]-[@B4],[@B16],[@B21]\]. This has been examined in the context of a short series of low intensity contractions reducing myotonia during subsequent low intensity contractions \[[@B7],[@B16],[@B20],[@B27]\] rather than in the context of repetitive contractions of sufficient severity to produce fatigue, such as might occur during athletic activities. The general purpose of the present study was therefore to examine myotonia during fatigue-inducing stimulation. Based on previous studies examining the decline of myotonia in response to non-fatiguing contractions, the specific hypotheses of the present study were that a) myotonia declines more rapidly than force during fatigue-inducing stimulation, and b) the rate of decline of the myotonia during fatigue-inducing stimulation is affected by the frequency of stimulation producing fatigue (specifically higher stimulation frequencies augment the rate of dissipation). In order to avoid the effects of downstream structural and biochemical changes (eg., alterations in fiber type composition and atrophy or hypertrophy \[[@B1],[@B5],[@B7],[@B9],[@B11]-[@B13],[@B17],[@B18]\]) resulting from genetic CLC-1 channel deficiency that can affect muscle fatigue properties in manners apart from the myotonia itself, the present study utilized Cl^-^channel blockade with 9-AC to produce myotonia in otherwise normal muscle rather than testing muscle that is genetically deficient in Cl^-^channels. Muscles pertinent to breathing (diaphragm), fast twitch movements (EDL), and slow twitch movements (soleus) were tested to determine whether 9-AC has varying effects on muscles with different fiber type compositions. Methods ======= Studies were performed using adult male Sprague-Dawley rats (n = 35, weight = 390 ± 15 grams). All protocols were approved by the Institutional Animal Care and Use Committee and conformed to animal care guidelines established by the National Institutes of Health. Rats were well-anesthetized using a rodent anesthetic cocktail (initial dose, ketamine 21-30 mg/kg, xylazine 4.3-6.0 mg/kg and acepromazine 0.7-1.0 mg/kg, with supplemental smaller doses given as needed to produce and maintain a deep level of anesthesia). The EDL and soleus muscles were removed from the legs with intact tendons, and the diaphragm muscles were removed with intact rib origins and central tendon insertions. Contractile studies were performed in physiological solution consisting of (in mM): 135 NaCl, 5 KCl, 2.5 CaCl2, 1 MgSO4, 1 NaH2PO4, 15 NaHCO3, and 11 glucose, with the pH adjusted to 7.35-7.45 at 37°C while being aerated with 95% O~2~-5%CO~2~. The diaphragm muscle was cut into small strips parallel to the fiber direction keeping origin and insertion intact (strip width \~5 mm), and mounted vertically in a double-jacketed chamber while the temperature was maintained at 37°C. The soleus and EDL muscles were similarly mounted in the same chamber by the attached tendons, except that they were left whole and not cut into strips like the diaphragm. A pair of platinum electrodes was placed parallel to the diaphragm muscle strips or limb muscles, and supramaximal voltages were delivered with a pulse width of 1 ms. The lengths of the muscle samples were adjusted until the twitch force was maximized (optimal length), and kept at this length for the duration of the contractile study. Ten minutes after the diaphragm muscle or limb muscle (at optimal length) had equilibrated to the Kreb\'s solution, three twitch contractions were recorded 10 seconds apart to determine the baseline force of the muscle. Three minutes thereafter, another three twitches were recorded 10 seconds apart to verify stability of the muscle sample (defined as \<5% variability in force between first and second set of twitches). Subsequently 1 ml Kreb\'s solution containing 9-AC was added to half of the muscle samples to obtain a bath concentration of 100 μM, and to the other half of the muscle samples 1 ml of the Kreb\'s solution without 9-AC was added. Twenty minutes later repetitive train stimulation was initiated. This consisted of intermittent 20-Hz or 50-Hz train stimulations, with a train length of 0.33 s and one train every three seconds. The relatively long inter-train interval was needed due to the markedly slowed rate of relaxation in the presence of 9-AC, as this allowed time for muscle force to return back to baseline prior to the subsequent train. Due to the slow isometric kinetics of the soleus muscle, contractions have a high degree of fusion during 50 Hz stimulation, impairing the ability to measure contraction and relaxation times. Therefore soleus was only studied during 20 Hz stimulation. Muscle contractile performance was assessed with respect to four parameters (Figure [1](#F1){ref-type="fig"}), and in all instances this was relative to baseline passive tension. Peak force was defined as the largest value that occurred during the portion of the contraction while the muscle was being electrically stimulated (and thus did not include mechanical myotonia even if mechanical myotonia exceeded force during active electrical stimulation). These force values were normalized relative to twitch force before drug addition to factor out the effects of variability among muscle samples in absolute force related to variability in animal size and muscle sample size, similar to previous studies of a similar nature \[[@B11],[@B15],[@B19],[@B22]\]. Contraction time was defined as the time from the onset of force production to the top of the first peak of the non-fused contraction; values for contraction time are not presented in those instances in which a distinct first peak was not discernable (which was the case for 50 Hz stimulation for the diaphragm). Half-relaxation time was the time required for force to decrease from the peak value at the end of electrical stimulation to 50% of this value. Late relaxation time was the time for force to decline from 50% of peak to 10% of peak. These four values were quantified for a total duration of six minutes. All data presented are means and SD. Statistical analysis of paired data was performed with a paired t-test. Statistical analysis of data obtained during repetitive stimulation was performed with analysis of variance for repeated measures followed by the Newman-Keuls post-hoc test in the event of significance by analysis of variance. The level for statistical significance was set at P \< 0.05 (two tailed). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Parameters measured for a diaphragm myotonic contraction at 20 Hz. The baseline is passive force related to stretching the muscle to optimal length, and all other active force values were quantified relative to baseline. ::: ![](1472-6793-11-5-1) ::: Results ======= Diaphragm --------- The effects of 9-AC on diaphragm force, contraction time, half relaxation time and late relaxation time at the outset of repetitive stimulation are listed in Table [1](#T1){ref-type="table"}. 9-AC increased force and contraction time during 20 Hz but not 50 Hz stimulation. Half relaxation and late relaxation times increased during both 20 Hz and 50 Hz stimulation, reaching values in the hundreds of milliseconds. Furthermore, values were generally longer for late relaxation (\~1 to 1.5 seconds) than for the half-relaxation time (\~0.5 to 1 second). None of these parameters changed at the outset of repetitive stimulation in the control muscle samples which were not treated with 9-AC. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### The outset of repetitive stimulation during 20 Hz and 50 Hz stimulation. ::: Stimulation Measurement Frequency Stimulation Before Krebs After Krebs Before 9-AC After 9-AC ------------------------------- ----------------------- -------------- ------------- ------------- ------------------ Peak force (% of initial) 20 Hz 138 ± 8 142 ± 10 155 ± 21 315 ± 53\* 50 Hz 319 ± 65 345 ± 91 293 ± 47 356 ± 58 Contraction time (ms) 20 Hz 23.7 ± 2.3 23.8 ± 1.2 23.2 ± 2.8 44.8 ± 6.7\* 50 Hz 20.1 ± 0.9 20.6 ± 1.3 20.0 ± 0.7 20.7 ± 1.2 Half relaxation time (ms) 20 Hz 26.0 ± 4.4 26.5 ± 1.7 29.2 ± 5.0 883.5 ± 296.0\* 50 Hz 26.4 ± 1.6 27.9 ± 2.6 28.6 ± 3.2 421.7 ± 308.3\* Late relaxation time (ms) 20 Hz 45.5 ± 11.8 51.4 ± 10.4 73.6 ± 50.8 1324.4 ± 339.2\* 50 Hz 32.0 ± 6.0 34.5 ± 3.9 28.6 ± 8.0 1142.6 ± 504.9\* The effect of Kreb\'s solution and 9-AC on diaphragm muscle at the outset of repetitive stimulation on peak force, contraction time, half relaxation time, and late relaxation time during 20 Hz and 50 Hz stimulation. Values are means ± SD. Asterisks indicate significant differences between before and after 9-AC data. ::: Force values for diaphragm during repetitive 20 and 50 Hz stimulation are depicted in Figure [2A](#F2){ref-type="fig"}. During 20 Hz repetitive stimulation, force declined rapidly in muscles that were treated with 9-AC after the initial 9-AC-induced augmentation. At one minute into the fatigue-inducing stimulation and all points thereafter, force values were equivalent in 9-AC treated and untreated muscles. In contrast, force values did not differ for drug-treated and untreated diaphragm at any time during 50 Hz stimulation. Contraction time also was prolonged by 9-AC during 20 Hz stimulation (Figure [2B](#F2){ref-type="fig"}) and not measurable during 50 Hz stimulation because successive stimulation was 20 ms apart and contraction time was greater than 20 ms. This prolongation waned with repetitive fatigue-inducing stimulation, but did not fully dissipate over the course of six minutes. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in diaphragm muscle during repetitive 20 Hz and 50 Hz train stimulation. Contraction time was not measurable at 50 Hz. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-2) ::: Both the half relaxation time (Figure [2C](#F2){ref-type="fig"}) and the late relaxation time (Figure [2D](#F2){ref-type="fig"}) were prolonged substantially by 9-AC, but eventually declined to normal or near-normal values during fatigue-inducing stimulation. The decline was more precipitous for the early compared to the late phase of relaxation as well as during 50 Hz compared with 20 Hz stimulation. The rate at which myotonia resolved was much faster than the rate at which force decreased, in that myotonia was almost completely resolved over the first 60 seconds of stimulation whereas force continued to decline for the full duration of stimulation (compare Figures [2C](#F2){ref-type="fig"} and [2D](#F2){ref-type="fig"} with Figure [2A](#F2){ref-type="fig"}). Furthermore, during 50 Hz stimulation the mechanical myotonia was substantially resolved before there was any appreciable force loss. Limb Muscles ------------ Soleus muscle did not demonstrate myotonia in response to 9-AC (data shown for 20 Hz stimulation in Figure [3](#F3){ref-type="fig"}). There was a mild increase in force (Figure [3A](#F3){ref-type="fig"}), but contraction time (Figure [3B](#F3){ref-type="fig"}), half relaxation time (Figure [3C](#F3){ref-type="fig"}) and late relaxation time (Figure [3D](#F3){ref-type="fig"}) were unaffected. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### The effect of 9-AC on peak force, contraction time, half relaxation time, and late relaxation time in the soleus muscle during repetitive 20 Hz train stimulation. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-3) ::: In contrast, the response of EDL was similar in most respects to that of the diaphragm. Peak EDL force increased during 20 Hz but only minimally so during 50 Hz stimulation (Figure [4A](#F4){ref-type="fig"}), and for 20 Hz stimulation this waned over time with repetitive stimulation. However, contraction time was not altered by 9-AC at either stimulation frequency (Figure [4B](#F4){ref-type="fig"}). Both half-relaxation time (Figure [4C](#F4){ref-type="fig"}) and late relaxation time (Figure [4D](#F4){ref-type="fig"}) of the EDL were prolonged by 9-AC. All relaxation times prolonged by 9-AC normalized rapidly during repetitive stimulation, and this occurred faster than the rate at which force declined, in that myotonia was almost completely resolved over the first 30 seconds of stimulation whereas force continued to decline for the full duration of stimulation (compare Figures [4C](#F4){ref-type="fig"} and [4D](#F4){ref-type="fig"} with Figure [4A](#F4){ref-type="fig"}). As seen with the diaphragm, during 50 Hz stimulation the mechanical myotonia was substantially resolved before there was any appreciable force loss. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in the EDL (extensor digitorum longus) muscle during repetitive 20 Hz and 50 Hz train stimulation. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-4) ::: Discussion ========== The inability of muscles to relax normally after voluntary contractions is characteristic of the disease myotonia. The results of this study showed that mechanical myotonia decreases rapidly during fatigue-inducing stimulation. Furthermore, myotonia was found to decrease faster than force in both the diaphragm and EDL muscles. The normalization of relaxation times was slightly faster at a higher frequency (50 Hz) than a lower frequency (20 Hz) in the diaphragm muscle; however this may have been due to the effects of myotonia being less during 50 Hz than 20 Hz stimulation. Furthermore, the resolution of myotonia was also slightly faster in the EDL muscle than the diaphragm muscle, although again possibly because of differences in the magnitude of the myotonia. Both the diaphragm and EDL muscles had much larger degrees of myotonia than the soleus in response to 9-AC. In addition, force production increased at the lower stimulation frequency (20 Hz) in the diaphragm and EDL, and increased slightly in the soleus at this frequency, but did not increase at the higher frequency (50 Hz) in any of the three muscles with 9-AC. Contraction time increased only in the diaphragm during 20 Hz stimulation. Myotonia, whether genetically- or drug-induced, decreases during repeated contractions, this resolution being termed the \"warm up\" phenomenon. This has been described in clinical reports of humans with myotonia congenita and is also apparent when observing the behavior of genetically myotonic mice \[[@B2],[@B3],[@B21]\]. Physiological manifestations when tested experimentally include improved rate of muscle relaxation and diminution of the duration and intensity of persistent electromyographic activity following repetitive muscle activation. One of the early experimental studies of the warm up phenomenon was that performed by Senges and Rudel \[[@B16]\] in a model of myotonia induced by 2,4-dichlorphenoxyacetate. They examined the effects of a conditioning tetanus preceding a test contraction by 0.5, 1, 2 and 4 seconds. The shortest time interval virtually abolished myotonia, with the effect diminishing markedly as the time interval increased. The warm up phenomenon was described by Heller et al.\[[@B7]\] in the original report of genetically myotonic mice. This was demonstrated based on electromyographic recordings from affected muscle in response to direct peripheral nerve stimulation rather than on measurements of muscle force. Heller and colleagues \[[@B7]\] described the myotonia as declining with repeated trials at 10 second intervals, but recovering when the muscle has rested for one minute. The warm-up phenomenon was also studied by Heimann et al \[[@B27]\]. EDL muscles from myotonic ADR mutants and ADR-MDX double mutants were shown to have similar degrees of myotonia as quantified by the myotonia index \[[@B28]\] (myotonia index of 0.49 vs. 0.57, respectively). Furthermore, they had similar degrees to which the myotonia improved when contractions were preceded by a series of single twitches and incomplete tetanic stimulations. However, the study also found that myotonia symptoms were more pronounced in ADR than ADR-MDX muscle, but ADR-MDX mice had higher levels of weight reduction and premature death. In contrast, for the soleus the ADR mutant had a significantly higher myotonia index than the ADR-MDX mutant (myotonia index of 0.90 vs. 0.61). Data for the warm up phenomenon were not depicted for the soleus. Van Beekvelt et al. \[[@B21]\] studied three humans with myotonia and defined the warming-up phenomenon as the force recovery phase after initial paresis during a sustained voluntary contraction. This study hypothesized that warming-up was due to the enhanced activation of Na+-K+-ATPase during exercise, and used ouabain (a Na+-K+-ATPase inhibitor) to test this. However, it was found that ouabain infusion did not prevent recovery from transient paresis. Therefore, it was concluded that the warm-up phenomenon was not due to Na+-K+-ATPase. Taken together, the above studies provide a comprehensive picture of the manner in which myotonia improves following brief contractions, but these studies had not examined changes in myotonia during the course of repetitive fatigue-inducing contractions. The latter issue has been examined to a limited extent in a previous study from our lab in which we examined isotonic contractions of diaphragm muscle from genetically myotonic mice \[[@B19]\]. Diaphragm from these mice had lesser degrees of myotonia than seen in the diaphragm of the present study. Total relaxation time during a singe train contraction ranged from \~0.2 to 0.6 seconds in contrast to values exceeding 2 seconds with 9-AC in the present study. In the genetically myotonic mice, repetitive train stimulation at a frequency of 50 Hz resulted in a rapid reduction in relaxation time over the course of 30 seconds, with minimal changes thereafter during the subsequent 30 seconds. The present study expands on our previous findings \[[@B19]\] in several manners. We found that the reduction of myotonia during fatigue-inducing contractions occurs during isometric as well as isotonic contractions, and in the drug-induced myotonia model as well as genetic myotonia. Furthermore, the present study indicates that the resolution of myotonia varies as a function of the frequency of muscle stimulation. In addition the extent of drug-induced myotonia differed among the three muscles studied, with the slow fiber type predominance of the soleus appearing to have had a protective effect. Finally, the present data indicate that the time course of the warm-up phenomenon is much faster than that of force loss during fatigue-inducing contractions. One of the limitations of the present study is that the studies were done in vitro, under conditions in which there is no blood flow and thus no delivery of nutrients and/or impaired removal of potentially adverse metabolites. Thus the development of fatigue may have occurred faster in the drug-induced myotonia model than would occur in vivo in humans or animals with genetic CLC-1 chloride channel deficient myotonia. A second limitation is that the genetic muscle diseases that cause myotonia are a heterogeneous group which include not only two variants of CLC-1 deficient myotonia but also myotonic dystrophy. Several of these disorders have features in addition to the myotonia, which for some includes muscle weakness. Among these additional features, muscle weakness in particular may impact the rate at which fatigue develops, thereby changing the temporal relationship between the improvement of the myotonia and the reduction of force in response to repetitive vigorous contractions. Conclusions =========== Fatigue-inducing contractions were shown to dissipate the amount of mechanical myotonia induced by the chloride channel blocker 9-AC. However the rate at which this occurred was considerably faster than the drop in force over time, consistent with different mechanisms accounting for the warm up phenomenon and the production of fatigue. From a clinical perspective this suggests that subjects with myotonia need not warm up to a sufficiently large extent to produce muscle fatigue in order for the myotonia to dissipate, but nonetheless suggest a role for vigorous rather than more modest contractions as a means for resolving the muscle myotonia more quickly. Abbreviations ============= 9-AC: 9-anthracene carboxylic acid. Authors\' contributions ======================= EvL conceived of, and designed the study, participated in statistical analysis, and helped to draft the manuscript. SS participated in the design of the study, collection of data, statistical analysis, and helped to draft the manuscript. MM participated in the design of the study, collection of data, and statistical analysis. All authors read and approved the final manuscript. Acknowledgements ================ This study was supported in part by funding from the Department of Veterans Affairs Medical Research Service.	PubMed Central	2024-06-05T04:04:18.951290	2011-2-28	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052176/", "journal": "BMC Physiol. 2011 Feb 28; 11:5", "authors": [ { "first": "Erik", "last": "van Lunteren" }, { "first": "Sarah E", "last": "Spiegler" }, { "first": "Michelle", "last": "Moyer" } ] }
PMC3052177	Background ========== Cognition-focused interventions are becoming increasingly popular techniques for older adult populations. These interventions are typically grouped into one of three categories - cognitive training, cognitive rehabilitation and cognitive stimulation. Interventions may vary in terms of the degree to which the program is individualised, the content of the activity and the nature of the facilitation (e.g. one-to-one, group, computer based) (see \[[@B1]\] for a review). Cognitive stimulation therapy (CST) has been recommended as the treatment of choice for individuals in the early stages of dementia (Mini Mental State Examination - MMSE, score ≥ 20) \[[@B2]\]. This type of intervention emphasises the benefits of group activities which, dependent on the target population, can range from education, discussion and debate, and problem solving to reality orientation, reminiscence and validation therapy. In a multi-centred randomised controlled trial (RCT), Spector and colleagues \[[@B3]\] allocated 201 participants with dementia to either a CST group or a no treatment control. People in the intervention demonstrated improved cognitive and quality of life scores. A Cochrane review of reminiscence therapy concluded that whilst there was a need for more rigorous trials, there were promising indications that this form of intervention was of potential benefit to patients and their carers \[[@B4]\]. The cost effectiveness of CST has also been established \[[@B5]\] and manuals operationalised \[[@B6]\]. CST has traditionally been implemented in group settings such as day centres and residential facilities and co-ordinated by trained facilitators. Some interventions have also adopted multi-modal programs targeting cognition and well being in the patient with dementia and addressing the coping abilities and needs of the family member/care-giver with positive results (e.g. \[[@B7]\]). However there is a paucity of research that has utilised cognitive stimulation techniques in a manner easily adopted for the home environment and implemented by the carer/family member. Quayhagen and Quayhagen \[[@B8]\] had spousal caregivers apply cognitive stimulation techniques and found that improvements in memory, as well as additional aspects of cognition, could be achieved, with a home-based program. This study, however, was limited to spouses and a research team modelled the programme in the home of the dyad. For those patients who are widowed or single, access to a carer or companion may be limited to less contact hours. The feasibility of having instructors/team members provide one-to-one instruction may also restrict the availability of this type of facilitation. We have designed a single-blind, randomized trial of an intervention drawing on principles of cognitive stimulation. The activities and intervention were selected with regard to suitability for older adults with mild Alzheimer\'s disease (AD) and designed in a manner that could be readily adapted for use in the home environment and implemented by a companion. The study aims to determine if a program of cognitive activity (CA) that includes both people with AD living in the community and a companion has better cognitive outcomes over six months for participants with dementia than a CA program delivered to companions only. Secondary outcomes for this trial include the quality of life and well being of people with AD and their companions. Methods/Design ============== Background ---------- The Promoting Healthy Ageing with Cognitive Exercise for the treatment of mild Alzheimer\'s Disease (PACE-AD) study is a randomised clinical trial that commenced recruitment of participants in October 2009. In 2007, our group developed a cognitive activity intervention program which was well received by older adults with mild cognitive impairment \[[@B9]\]. In early 2009, this program was modified for its suitability for participants with mild AD. Nine relatives of individuals with mild AD were invited to attend a morning education and activity session regarding the proposed study. Feedback from the relatives regarding the nature of the study was overwhelmingly positive, though the length of the proposed sessions, coupled with the complexity of the program content, were areas identified as requiring further consideration. After collating the verbal and written feedback, additional minor modifications were made to the study protocol and recruitment began. Study Design and Setting ------------------------ PACE-AD is a six-month, single blind randomised trial of a CA intervention delivered to older adults with mild AD and companions compared with companions alone. Ethics ------ The Human Research Ethics Committees of Royal Perth Hospital (RPH), Mercy Hospital and Bentley Hospital have approved the study protocol and procedures, and the study is being conducted according to the Declaration of Helsinki. Recruitment and Selection of participants ----------------------------------------- Recruitment for this trial is currently ongoing. Participants are community dwelling volunteers, recruited mainly from local memory clinics. Potentially suitable participants are approached via mail and receive a follow up telephone call. Interested volunteers are screened with a semi-structured telephone interview and invited to visit the Mercy Hospital for a more detailed screening assessment (clinic screen) and to provide written informed consent. ### Inclusion and Exclusion Criteria The defining feature of participants included in the PACE-AD study is a diagnosis of Alzheimer\'s disease (probable or possible) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer\'s Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer\'s Criteria. Participants need to have a Mini Mental State Examination (MMSE) score between 18-26 inclusive (i.e., mild severity), at the time of screening and be fluent in written and spoken English. Mild AD participants with a prevalent psychiatric disorder (e.g. depressive episode), current history of hazardous or harmful alcohol consumption (Alcohol Use Disorders Identification Test - AUDIT - score ≥15 \[[@B10]\]), or who do not have an available companion are excluded. Those individuals with a current medical condition preventing participation in the study tasks (such as severe sensory impairment) or associated with reduced survival over a six-month period (e.g. advanced cancer) are also excluded. ### Telephone Interview Volunteers are initially screened via a telephone interview to ascertain suitability for the study. Those without a suitable companion (someone who spends at least ten hours per week with the person, including time at their home) are immediately excluded. All individuals are asked about their general health (past and current), education, English literacy skills and current alcohol and cigarette consumption. Telephone interviews range from 10 to 20 minutes in length and those meeting provisional inclusion criteria are invited to a face-to-face assessment (clinic screen). ### Clinic Screen After obtaining written consent from volunteers with mild AD and their companions each person\'s eligibility for the study is established according to the following criteria: #### Mild AD • Mini Mental State Examination score ranging between 18-26 inclusive \[[@B11]\] • Patient Health Questionnaire (PHQ-9) score \<15 \[[@B12]\] #### For the companion of the volunteer with mild AD • MMSE total score of 26 or above \[[@B11]\] • PHQ-9 score \<15 \[[@B12]\] [The MMSE]{.underline}\[[@B11]\] is a brief test of mental status and cognitive function commonly used to screen for dementia and to monitor cognitive decline. It produces a total score that can range from 0 to 30. Scores lower than 24 are reliably associated with the diagnosis of dementia or other organic mental disorders. The present study also used the MMSE to exclude companions with cognitive impairment. The [PHQ-9]{.underline}\[[@B12]\] is a widely used scale to establish the presence of clinically significant depression amongst community-dwelling adults. Scores range from 0 to 27, with scores of 15 or greater indicative of clinically significant depression. In addition to the cognitive and mood screen, a self-reported medical history questionnaire is completed by each individual, which includes details regarding their medication usage. This information is also collected at the final assessment. The screening assessment of both volunteers takes approximately 30 minutes to complete and any pertinent clinical information is reported to the relevant treating physician with the consent of the study participant. If both volunteers meet criteria for the study, they proceed to undertake the baseline assessment. Outcome Measures and Assessment Procedures ------------------------------------------ ### Baseline and Follow-up Assessments Baseline assessments are completed immediately after the clinic screen, 1-2 weeks prior to the first intervention session and randomisation. Post-intervention assessments are undertaken within two weeks of program completion and the final assessment is completed 26 weeks after the baseline assessment (see Figure [1](#F1){ref-type="fig"}). All assessments take between 90 to 120 minutes to complete (including the provision of short breaks) and consist of the following series of tests and questionnaires (see also Table [1](#T1){ref-type="table"}). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Baseline assessment ::: ![](1745-6215-12-47-1) ::: ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Outline of the primary and secondary outcome measures used in the PACE-AD trial ::: Assessment Tool Participant with mild AD Companion -------------------- -------------------------- ----------- ADAS-COG X RBMT-3 X ToL X COWAT X MMSE X X PHQ-9 X X DEMQOL-version 4 X X Short-Form IQ CODE X X IADL X NPI-Q X AUDIT X SF-12 X The X indicates who completed the respective assessments (participant with mild AD or companion). All measures were given at baseline, 13 and 26 weeks. ADAS-COG = Alzheimer Disease Assessment Scale-Cognitive; RBMT-3 = Rivermead Behavioural Memory Test-Third Edition; ToL = Tower of London; COWAT = Controlled Oral Word Association Test; MMSE = Mini Mental State Examination; PHQ-9 = Patient Health Questionnaire - Nine Item; Short-Form IQ CODE = Modified Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly; IADL = The Lawton Instrumental Activities of Daily Living; NPI-Q = The Neuropsychiatric Inventory Questionnaire; AUDIT = World Health Organisation\'s Alcohol Use Disorders Identification Test; SF-12 = Short-Form 12-Item Health Survey. ::: ### Primary outcome measure Alzheimer Disease Assessment Scale-Cognitive (ADAS-COG)\[[@B13]\] is a frequently used measure of global cognitive functioning and assesses cognitive domains including orientation, memory, language, and praxis; common areas of impairment present in AD. It provides sub-scale scores as well as a global score out of 70, with higher scores indicating lower levels of cognitive functioning. A four-point change on the ADAS-COG over a six month period is considered a clinically relevant difference \[[@B14],[@B15]\]. ### Secondary Outcome Measures #### Measures completed by participants with mild AD The Rivermead Behavioural Memory Test-Third Edition (RBMT-3)\[[@B16]\] comprises a series of memory tasks analogous to those faced in everyday situations. Sensitive to changes in memory functioning over time and well validated with patient groups \[[@B16]\], a parallel version also reduces the confounds of practice effects. Three subtests from the RBMT-3 are performed with mild AD participants at all assessment time points, with the parallel version administered at the post intervention assessment. The Tower of London (ToL) \[[@B17]\] consists of ten problems of increasing difficulty designed to assess executive planning abilities. The participant is required to manipulate three coloured beads across three pegs on a wooden board to mirror the examiner\'s board. Participants are instructed to solve the problem in as few moves as possible while adhering to two specific rules, within a two minute time limit. In the current trial this test is administered with minor modifications, in order to minimise frustration for participants with mild AD. The Controlled Word Association Test (COWAT) \[[@B18]\] requires the participant to generate as many words as possible with a given letter of the alphabet, within a one-minute time period, excluding proper nouns and the same word with a different suffix. This test is used as an indicator of executive functioning for participants with mild AD. #### Measures completed by participants with mild AD and their companions We use the MMSE total score and the PHQ-9 total score, as previously described, to monitor changes in cognition and mood of all participants throughout the trial. DEMQOL-version 4\[[@B19]\] is a 28-item self-reported, interviewer administered questionnaire assessing participants\' perceptions of their health related quality of life in the past week. It assesses five domains: daily activities/self care, health and well-being, cognitive functioning, social relationships, and self-concept. The DEMQOL has been demonstrated to show high reliability (internal consistency and test-retest) and moderate validity in people with mild to moderate dementia. In this trial, participants with mild AD are given the questions verbally with the aid of visual response options. Companions\' quality of life is also assessed with this measure. Modified Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (Short-Form IQ Code) \[[@B20]\] is an informant based, brief cognitive screening questionnaire for individuals with dementia. It assesses an individual\'s cognitive abilities as they apply to everyday situations and consists of 16 items. The original version asks the informant to judge the extent to which the patient\'s level of functioning has changed in the past ten years. Subsequent versions have used different time frames to allow for informants who might not have known the patient for very long. In this trial only AD participants\' current level of functioning will be assessed, to allow direct comparison at follow-up testing. #### Measures completed by companions The Lawton Instrumental Activities of Daily Living (IADL) \[[@B21]\] scale is an informant based questionnaire which assesses the patient\'s current ability to perform eight independent activities of daily living. These include using the telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, taking medications and handling finances. The Neuropsychiatric Inventory Questionnaire (NPI-Q)\[[@B22]\] is a brief screening instrument assessing the frequency and severity of twelve neuropsychiatric behavioural disturbances common in dementia. The companion is asked to rate the presence, change and severity of symptoms in the AD patient in the past month along with associated caregiver distress. The NPI-Q is considered to be a reliable and valid tool for assessing psychopathology in dementia patients and is sensitive to treatment effects. The World Health Organisation\'s Alcohol Use Disorders Identification Test (AUDIT) \[[@B10]\] is used to screen for risky, hazardous or harmful drinking. There are 10 items and supplementary questions, with questions scored on a scale of 0 to 4. Scores of 16 or above suggest \"high-risk\" or \"harmful level\" of drinking behaviour. This questionnaire is monitoring the companion\'s alcohol usage throughout the trial. Short-Form 12-Item Health Survey (SF-12) \[[@B23]\] is a self-report questionnaire consisting of twelve questions from the SF-36 Health Survey \[[@B24]\] and assesses an individual\'s perception of their general physical/health functioning, bodily pain, vitality, social functioning, general mental health, psychological wellbeing, and role limitations due to physical or emotional issues. This questionnaire is used to monitor change in the companion\'s mental and physical components of quality of life throughout the trial. ### DNA Collection Participants with mild AD are asked to provide a saliva sample for the extraction of DNA to assess the influence of common genetic polymorphisms (e.g., apolipoprotein E4 genotype) on the outcomes of the study. The samples are collected and processed by the Department of Clinical Pathology and Biochemistry at the RPH and stored at -80°C. All material is batched and will only be processed at the end of the trial. Intervention ------------ Following the baseline assessment, dyads (person with mild AD and companion) are randomised to one of two intervention groups. The intervention consists of a twelve-week CA program. Sessions are run by facilitators experienced in conducting research with older adults. The two groups are exposed to the same length of intervention, social interaction and contact with the program facilitators. The program was developed by a qualified Neuropsychologist (MV) and a manual produced. All of the sessions are delivered in a structured way for consistency, and audio-taped for subsequent fidelity assessment. Research assistants (RAs) blinded to group allocation conduct all assessments. RAs are provided with strict instructions to avoid any potential opportunity for disclosure regarding intervention participation. Following completion of the trial, RAs undertaking data collection will be asked to identify the group membership of participants, to determine the effectiveness of the blinding procedures that were put in place for this project. A brief summary of each intervention group is provided below. Participants with mild AD and their companions (Group 1): Each group consists of a maximum of five dyads taking part in 90-minute sessions once a week for seven weeks. Session One introduces the nature of the program and develops familiarity within the group, with personal introductions and sharing of background information and experiences. Sessions Two to Six focus on defining attention, processing speed, memory, language and executive functions. These sessions outline how these cognitive abilities are affected in AD and provide participants with strategies and techniques for managing declining capacity in each of these domains. Regular opportunity for supervised practice of such techniques and examples of activities to strengthen abilities occurs in all sessions. Dyads are also provided with an hour of home activities, to reinforce material learnt in the sessions. Sessions Seven to Eleven are completed by the participant with mild AD and their companion together in their own environment. Participants are provided with a workbook containing instructions and examples, along with phone calls from the facilitator once per week to address any questions and to monitor task completion. The final session (Session 12) offers an overview and discusses strategies to maximise participation. Companions of participants with mild AD alone (Group 2): This group consists of a maximum of five companions presented with the same session information and materials as Group 1. The only difference is that the companions attend the sessions with other companions, and are instructed to convey what is learnt during the sessions to the participant with mild AD during their home activities. Randomisation ------------- Randomisation is performed according to a random list of numbers generated by computer and undertaken in random blocks of 8 or 10 with no more than five dyads allocated to each group. The allocation list is handled by an independent investigator (OPA) who has no contact with study participants and is not involved in the supervision of staff responsible for the collection of data. The allocation table is then passed on to the facilitator running the intervention, who invites eligible participants to join the relevant groups. RAs undertaking the follow-up assessments remain blinded to group allocation. Sample Size and Power Calculation --------------------------------- This trial aims to recruit 128 participants with mild AD and their carers, with 64 patients being allocated to each study group. A study of this size will have 80% power to detect between group differences on the ADAS-COG associated with moderate effect size (Cohen\'s d = 0.5) and alpha of 5%. Analysis of the Data -------------------- Changes in the ADAS-COG score from baseline are the primary outcome of interest in the study. We will model these changes at 2 time points: 13 (immediately after the intervention comes to an end) and 26 weeks. We will use mixed effects models to analyse the data. This approach will enable us to take into account the cognitive performance of participants at baseline, as well as the intra-person correlation generated from repeated measures. Intention-to-treat (ITT) analyses will be based on the use of imputation by chain equations (ICE), which will precede the use of the mixed-effects model. The ITT will be the primary analysis of the study. Discussion ========== Cognition-focussed interventions are increasingly being adopted for the treatment of cognitive decline in older adults, with CST recently recommended as the treatment of choice for individuals with mild dementia \[[@B2]\]. However, the efficacy, sustainability of effect, and cost-effectiveness of involving and training a carer/companion to deliver cognitive tasks, and the degree to which cognitive changes can be maintained over time using this form of delivery, is yet to be established. This trial has been designed according to CONSORT guidelines and has been structured to enable its reproduction in both research and clinical settings. We expect to complete recruitment by December 2011 and anticipate that the results of this study will have implications for health care policy and resourcing and facilitate improvements in the management of people with mild AD. The results of this study will enable us to determine, for the first time, if a CA intervention delivered to companions alone is as effective at promoting changes in cognitive function as an intervention involving both the person with dementia and his/her companion. These results will have important implications for the design of sustainable cost-effective health services for people with mild AD. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= All authors are members of the PACE-AD project group. MV acts as guarantor of the data; she has designed the intervention and supervises research staff. MV and OPA designed the study, which is funded by a grant from ANZ Trustees Limited to OPA. JS is responsible for data collection and contributed to drafting the paper together with MV. OPA and LF reviewed the manuscript critically. All authors have approved the submission of the present paper to Trials. Acknowledgements ================ We are most grateful to all volunteers taking part in the study and to our research staff (Joanna Eaton, Rachel Lowry, Kendall Sharpe and Natalie Di Renzo). The staff at the WACHA as well as Bentley, Mercy and Royal Perth Hospitals have been instrumental in their assistance with recruiting patients. This project is supported by an unrestricted grant from ANZ Trustees Limited.	PubMed Central	2024-06-05T04:04:18.953487	2011-2-17	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052177/", "journal": "Trials. 2011 Feb 17; 12:47", "authors": [ { "first": "Mandy R", "last": "Vidovich" }, { "first": "Josephine", "last": "Shaw" }, { "first": "Leon", "last": "Flicker" }, { "first": "Osvaldo P", "last": "Almeida" } ] }
PMC3052178	Background ========== The placebo-controlled trial is a widely accepted design for evaluating pharmacological and device interventions. There has, however, been considerable debate in the literature about the ethical acceptability of including a placebo in procedures such as surgery. Whilst the use of a placebo in surgical trials is not new \[[@B1]-[@B8]\] the concept remains highly controversial. Several commentators have argued that placebo procedures are ethical for certain trials of surgery \[[@B9]\], but others have argued strongly that the use of surgical placebos cannot be justified as any surgical procedure carries risks of harm that are greater than those associated with no surgery \[[@B10],[@B11]\]. The term \"placebo\" is commonly used to describe any substance or procedure a patient accepts as medicine or therapy, but which has no known mechanism other than a patient\'s belief in its value \[[@B12]\]. The aim of any placebo is to maximise the mimic of the active intervention (and its benefits) whilst minimising the risks associated with it \[[@B13],[@B14]\]. A range of interventions, from dummy pills to surgical techniques, have been used as placebos \[[@B14]\]. Within a surgical context, however, no surgical placebo can be completely without the possibility of harm. This leads to particularly complex issues when trying to design a surgical placebo-controlled trial. In this paper we report on a study (the KORAL study) conducted to assess the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage (washing out of the knee space under general anaesthetic) for the management of people with osteoarthritis of the knee in the UK. Whilst the primary focus was on arthroscopic lavage (and was written up in a separate monograph \[[@B15]\]), the study highlighted a range of wider issues relevant to the design and conduct of surgical placebo-controlled trials in general, and it is those that we focus on in this paper. The KORAL study --------------- Our group was commissioned by the UK National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme to design and conduct a placebo-controlled trial to assess the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. The purpose of the trial was to confirm or refute the findings of an earlier study conducted in the US by Moseley and colleagues \[[@B16]\]. In the Moseley trial, patients had been randomised to arthroscopic lavage, arthroscopic debridement or placebo procedure and had found that whilst all groups improved, no significant difference was observed at follow-up between the placebo group and either \'active\' surgery group; the conclusion being that observed benefit was due to the placebo effect. Whilst the Moseley trial had been conducted with methodological rigour, it had been conducted in a single US centre by a single surgeon and the generalisability of the results had been questioned by a number of authors \[[@B17]-[@B19]\]. Given that it was unclear whether an acceptable placebo could be designed and delivered in a feasible manner, the project first explored in an in-depth manner issues around the design, acceptability and feasibility of a surgical placebo for this trial (it is this in-depth study that is presented in this paper). This study, which was known as KORAL (Knee Osteoarthritis: Role of Arthroscopic Lavage) had the following research questions (RQs) that were addressed in a staged way in a series of sub-studies: RQ1. Is there a need for a further placebo-controlled trial of arthroscopic lavage for osteoarthritis of the knee? If yes, RQ2. Can an appropriate surgical and anaesthetic placebo be designed for such a trial? If yes, RQ3. Would key stakeholders find the proposed placebo-controlled trial design acceptable? If yes, RQ4. Would conducting such a multi-centre surgical placebo-controlled trial be feasible in the UK? Methods ======= The research was conducted in two main phases. Firstly, an in-depth qualitative and quantitative exploration of possible placebo designs and their acceptability to key stakeholder groups (addressing RQs1-3) was conducted. Secondly a formal pilot of the proposed trial design to test feasibility (RQ4) was undertaken. Multi-centre Research Ethics Committee (MREC) approval was received separately for the two phases. Full details of the methods used in this study were given in the clinical monograph \[[@B15]\], however, brief details are provided below. Exploration of possible placebo designs and the acceptability of a placebo-controlled trial to key stakeholder groups --------------------------------------------------------------------------------------------------------------------- In the first phase, we particularly addressed: a) the perceived scientific merit of further evaluation of arthroscopic lavage (including by placebo-controlled trial); b) the choice of the placebo procedure, both surgical and anaesthetic; and c) the likely acceptability of different placebo-controlled trial designs to key stakeholder groups including surgeons, anaesthetists, potential participants and chairs of ethics committees. We conducted focus groups with, and postal surveys of, surgeons and anaesthetists; focus groups and interviews with people with osteoarthritis (potential trial participants); and interviews with Chairs of MRECs (Table [1](#T1){ref-type="table"}). Focus group discussions were informed by a presentation from the project team on background rates of arthroscopic lavage, details of the Moseley trial (including the design, results and perceived criticisms) and the project brief. Focus group discussions and interviews were audio-tape recorded and transcribed. Transcripts were analysed thematically using a modified Framework approach \[[@B20]\]. Within the focus groups and interviews we used the term \"placebo surgery\" (rather than possible alternatives such as \"sham\" or \"dummy\" surgery) as early on in the research we found that the choice of word could lead to different perceptions, despite the rationale behind their use being the same \[[@B15]\]. The term \"placebo surgery\" was adopted in an attempt to describe as accurately as possible the intention behind the procedure ie, to maximise the mimic, whilst minimising the risk. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Details of those who contributed to the focus groups, interviews and surveys ::: Study component Number who participated ----------------------------------------------------------------------------------------------- ------------------------- Focus groups with health professionals: • two surgeon focus groups at the 2005 British Orthopaedic Association meeting 16 surgeons • one regional surgeon focus group 25 surgeons • plenary discussion at the 2005 British Society of Orthopaedic Anaesthetists meeting 130 anaesthetists • detailed focus group at the 2005 British Society of Orthopaedic Anaesthetists meeting 8 anaesthetists • two regional focus groups with anaesthetists 50 anaesthetists Focus group and interviews with people with osteoarthritis: • two focus groups with members of the patient organisation Arthritis Care 7 people • telephone interviews with patients on consultant waiting lists from two UK regional centres 15 people Interviews with Chairs of UK MRECs: • telephone interviews with MREC Chairs 6 MREC Chairs Surveys of health professionals: • postal survey of all members of the British Association of Surgeons of the Knee 382 surgeons • postal survey of all members of the British Society of Orthopaedic Anaesthetists 398 anaesthetists Note: 12 of the 13 UK MRECs which were in existence at the time of the research were invited to take part in the research. (To preserve their independence with regard to any future ethics decisions about KORAL, the MREC that approved this part of the study was excluded from this component) ::: All members of the British Association of Surgeons of the Knee and members of the British Association of Orthopaedic Anaesthetists were surveyed for their opinion. Permission was received from both Societies for only a single mailing to members. Responses to the surveys were summarised using simple descriptive statistics. The final output of this first phase was the template for a preferred trial design. Formal pilot of the proposed trial design to test feasibility ------------------------------------------------------------- The second phase was a formal pilot of the preferred trial design that had been developed in Phase One. The formal pilot was conducted in two centres. Analysis of the pilot data consisted primarily of descriptive statistics including proportion of eligible patients randomised, and reasons for refusing to take part in the trial. Results ======= Need for proposed further evaluation of arthroscopic lavage ----------------------------------------------------------- From the focus groups and interviews, there was broad acceptance across all stakeholder groups of the need to find out more about the effects of arthroscopic lavage. Surgeons expressed uncertainty about the overall effectiveness of lavage. On the one hand some indicated that there was some evidence to suggest that lavage might offer at least short-term pain relief: \"if \... you end up washing the knee out, sometimes the symptoms do improve and make it pseudo-working. We had a lady recently, and she had a defect, and she\'s a lot better since we washed the knee out, that\'s three weeks ago now.\" (Surgeon 1, Group C) However, others commented that they often observed their patients \"all coming back\" with continuing problems after the procedure, thus raising concerns about the longer term and overall effectiveness of the technique. People with osteoarthritis of the knee also expressed the need to find out definitively whether arthroscopic lavage was effective. For example, one mentioned the scientific uncertainty surrounding the effectiveness of arthroscopic lavage, and another highlighted the need for research into the long-term effectiveness of such surgical procedures: \"Well, we have got to find out, you know, it has been going on for years and years and no one has ever found a complete answer so things have got to be tried, you know\... If you want to advance that is what you have to do.\"(Participant 1) \"I certainly think it \[a trial of arthroscopic lavage\] is worthwhile because at the end of the day \...I don\'t think that people should undergo surgery unless it was having some long term benefit to them \... it should only be done when it is going to have a positive effect and a long lasting effect.\" (Participant 2) Although all the groups accepted there was a need to find out more about the effects of arthroscopic lavage, there was variation in opinion about howresearchers should investigate this and about whether it would be acceptable to investigate the effectiveness of arthroscopic lavage using placebo surgery. This is discussed below. Design of a surgical placebo ---------------------------- Discussion within the surgeons\' focus groups concentrated mainly on the ways in which a placebo could mimic arthroscopic lavage (the active surgery), whilst ensuring that any risks of harm were minimised. The consensus emerged fairly readily that three superficial skin incisions were needed, that these should only pierce the epidermis, and that any penetration of the knee capsule should be avoided. \"No, you don\'t have to do the dermis \... just enough to make it bleed\" (Surgeon 8, Group B) Ensuring that penetration of the knee capsule did not occur was promoted for two primary reasons: a) that it would reduce the risk of any infection and b) it would ensure that no form of lavage was inadvertently performed: \"If you put the scope in you introduce fluid therefore technically it becomes a lavage even if it\'s a tiny amount, doesn\'t it?\" \[several yes\'s round the table\] (Surgeon 7, Group C) Within the anaesthetists\' focus groups, the question about the most appropriate form of anaesthesia to incorporate within a placebo procedure was more contentious. Some anaesthetists objected to the ethics of conducting any research that involved a placebo (see acceptability section below), and did not feel comfortable discussing the design of an anaesthetic for such a procedure. However, a consensus eventually emerged that the patients in both trial groups should receive the same anaesthetic, and that this should be the regimen the individual anaesthetists who participated in the trial would customarily use for a simple arthroscopic procedure (i.e. a general anaesthetic). They believed that this would not only maximise the mimic of the active surgery but would also minimise the risks to participants. As they had more experience with general anaesthesia in these cases, they believed it would be safer than a technique using a combination of sedatives and analgesics as used in the Moseley trial (on the premise that it was less risky for their patients), but was felt to be less familiar and therefore less safe by our respondents: \"Hasn\'t the starting point got to be, you should do the same \[as for the active surgery group\] unless there is a really good reason not to? And if the really good reason is all about risk then you have to show that their \[the sedation procedure used by the Moseley trial, on the grounds that it was of lower risk to patients\] intervention has less risk than the standard full anaesthetic. I am convinced that that is not the case. So therefore you should do the standard straightforward general anaesthetic\" (Anaesthetist 5, Group B) \"Statistically, \[the sedation procedure used by the Moseley trial\], is more dangerous than a general anaesthetic \[on the grounds that it was of lower risk to patients\]\" (Anaesthetist 6, Group A) Assuming that general anaesthesia was to be adopted, the anaesthetists within the focus groups agreed that inclusion should be restricted to low risk patients, as defined by those who were American Society of Anesthesiologists (ASA) grades 1 or 2 \[[@B21],[@B22]\] - that is \"normal healthy patients\" or \"patients with mild systemic disease\" who had no other contraindication to anaesthesia. Acceptability of a surgical placebo-controlled trial ---------------------------------------------------- ### Views expressed by health professionals Although none of the surgeons who took part in the focus groups disputed the need for further investigation of the effectiveness or otherwise of arthroscopic lavage, there was extensive debate within the groups about whether a placebo-controlled trial was necessary to generate new knowledge, and whether it was acceptable. For example: \"It would be more ethically correct to compare doing nothing to a lavage first and then look at the results and see\"\... You don\'t need to know the benefits of the placebo, it\'s irrelevant. When you make a clinical decision, you have to decide whether it\'s lavage or not. And so all you need to know is benefit from lavage and benefit from not doing anything and if the benefit from the lavage is marginal, then you don\'t do lavage and that\'s all that you need to do\...\"(Surgeon 3, Group C) \"What you need to do first is a decent study to actually look at conservative versus operative \[management\] and then once you\'ve done that decent study, can you consider putting people at risk of placebo operations\" (Surgeon 10, Group C) Other surgeons disagreed, however, arguing that there was a methodological need for a placebo surgical trial because: a) a placebo component is needed to detect a small difference between the groups; and b) that a placebo is needed to attempt to disentangle what (if any) aspect of the arthroscopic lavage procedure is having a positive effect. Overall, the health professionals tended to be split between: a) those who were strongly opposed to the inclusion of a placebo surgical arm on the grounds that it could lead to potential harm among individuals who could expect no personal benefit; and b) those who were in favour as that they believed the small risks that relatively few people in a placebo surgery trial arm would be exposed to were justified (because they were outweighed by the potential benefit to future patients and broader society of helping to ensure either that a demonstrably effective surgical procedure was used or that a demonstrably ineffective procedure was stopped). Those opposed to the inclusion of a placebo surgical arm expressed strong personal views on their perceived ethics of such an approach: \"As an anaesthetist I would not anaesthetise someone for sham surgery. I just couldn\'t! I just think it\'s immoral and unethical \... I mean it\'s as simple as that, you wouldn\'t do it\". (Anaesthetist 1, Group A) \"The number who will do this willingly will be very, very small, most of my colleagues would say - no you\'re joking\"\...(Anaesthetist 6, Group A) On the other hand, those in favour pointed to the benefit to future patients and the desire to let patients rather than clinicians decide what was best for them: \"If the patient is prepared to accept the risk in order to have the operation and they are prepared to enter the trial on the understanding that they might not have an operation, are we all being a bit precious \[ie, overly protective\]?\" (Anaesthetist 4, Group B) \"34,000 people \... per year are having a procedure which has no proof to it. So you\'re already doing the ladies with the \[weak\] hearts, putting the tourniquets up, giving them the drugs for absolutely no proven evidence\... at the moment if there are 34,000 of these procedures being done and we are exposing that number of patients to all the risks of anaesthesia then we need to know the answer\" (Anaesthetist 5, Group A) Some individuals who were personally in favour of using a placebo were concerned that professional regulators would not be (with consequent implications for their potential participation): \"Interesting though \... I accept \[it\] is completely logical that the needs of the many outweigh the needs of the few but the GMC \[General Medical Council\] doesn\'t see that do they? The GMC make it very specific in their guidance to us that it is the needs of the individual which is your primary concern\" (Anaesthetist 4, Group B) One hundred and seventy three (43%) members of the British Association of Surgeons of the Knee responded to the survey as did 136 (34%) members of the British Society of Orthopaedic Anaesthetists (Table [2](#T2){ref-type="table"}). Findings from the surveys supported the insights observed in the focus groups. The surveys showed that a sizeable percentage of health professionals (51% of surgeons and 40% of anaesthetists) were supportive of a trial with a placebo arm being mounted. The survey also showed that 43% of surgeons would personally consider taking part in such a trial as would 47% of anaesthetists. It was interesting to note that although some anaesthetists were personally not in favour of a placebo arm being involved they would, however, consider taking part if their surgeon colleagues wished to take part. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Attitudes of surgeons and anaesthetists to a placebo controlled trial ::: Surgeons Anaesthetists --------------------------------------------------------------------------------------------- --------------- --------------- Number of questionnaires despatched 382 398 Number (%) of questionnaire returned 173 (45%) 136 (34%) *Potential trial of arthroscopic lavage vs placebo surgery vs conservative management:* n/N (%) n/N (%) • Supportive of trial with placebo arm being mounted 85/168 (50.6) 54/135 (40.0) • Would consider taking part in a trial with a placebo arm 71/166 (42.8) 63/134 (47.0) • Would encourage a friend or family member to sign up for a trial with a placebo arm 67/168 (39.9) 48/135 (35.6) ::: As part of the survey we also asked surgeons and anaesthetists for their views on the appropriate randomisation ratio for any potential trial. The majority favoured an allocation ratio of 1:1:1 to arthroscopic lavage, placebo surgery or non-operative management (60% of surgeons, 46% anaesthetists) or had no preference (25% surgeons, 41% anaesthetists), rather than a 2:1:1 ratio (10% surgeons, 10% anaesthetists) or some other ratio (5% surgeons, 3% anaesthetists). ### Views expressed by people with osteoarthritis In their focus groups and interviews, people with osteoarthritis echoed the need to find out more about the effects of arthroscopic lavage, and many of our sample indicated that they would consider taking part in a placebo-controlled trial. Two participants also discussed how, from a research point of view, including a placebo surgical component could be very useful. They drew on the information presented by the interviewers and explained that a placebo arm would help check whether any perceived benefit from arthroscopic lavage was due to a placebo effect. For example: \"\... I would say it is important to have the placebo in it because if there is a sort of mind set that it does help to heal you, I mean it has been proven over the years that placebos do benefit in certain things.\" (Participant 1) \"\... I think the placebo group is a very good idea because it can almost fool somebody into thinking they have had a procedure when they haven\'t and basically prove to some people that you think you are better because you think you have had this procedure but in fact you didn\'t have any treatment done at all.\"(Participant 2) However, a few people in our sample thought involvement in a placebo-controlled trial would not be appropriate for them: \"if I was informed then that I had had the placebo and I realised that I had still got the pain I would be so furious\...so angry\" (Participant 14) Those who were willing to take part openly acknowledged the risks of general anaesthetic and endorsed the need for anaesthetists to select only those at low risk. For example: \"\... there is always, albeit I think it is quite small, risk of complications with anaesthesia \... there can be problems but they are very few and far between and if the right patients are selected then I don\'t think there would be any problems.\" (Participant 2) ### Views expressed by Chairs of Ethics Committees The Chairs of Ethics Committees highlighted a range of issues that should be addressed in any ethics application, eg, justifying the need for the placebo and the general anaesthetic, plans for minimising risks to patients, etc. Whilst they acknowledged that a surgical placebo-controlled trial would not simply be dismissed on principle, they predicted a \"rough journey\" through the ethics process for any such proposal: \"\... I would have to think extremely laterally to envisage that this would get through without a very rough journey on the way \... We have one committee in particular which anything placebo \... is evaluated with a fine tooth comb and there we\'re talking little white tablets\... The prospect of using a surgical approach I think raises the stakes enormously\" (MREC 3) \"\...I would think that in conclusion it\'s probably the general anaesthesia that will cause ethics committees the most problems because then they will say now is this really too much of a risk to be giving somebody a general anaesthetic for nothing\... I can see everybody say, \'Oh oh no way, not general anaesthetics\'\" (MREC 1) \" \... I\'d want a very robust justification for tackling the equipoise in this rather risky, in this potentially risky way. I think any self-respecting Committee that is the question they would ask. I would certainly be weighed by what risks our anaesthetic colleagues thought fair. I mean you\'ve got to, you can\'t negate the risk\... If the study is going ahead, there is a risk, you can\'t negate it. I think I\'d want evidence that the risks had been fully considered and minimised\... my experience is \[that\] anaesthetists are a very ethical lot indeed\... and they serve as a very useful counterbalance to the surgeons \...I can see the surgeons are faced with people in awful, intractable pain and they want to do something about it\" (MREC 4) Development of a preferred design to take to pilot study -------------------------------------------------------- The final output of the exploratory phase was to develop a preferred trial design to take forward to a formal pilot. The preferred design was developed from the insights gained from the exploratory work undertaken with surgeons anaesthetists and potential participants. The finalised design was agreed with the funder and was as follows - patients were to be eligible for inclusion if they were: adults aged 18 years or older with radiological evidence of osteoarthritis of the knee who might be considered for arthroscopic lavage; at low risk for general anaesthesia - ASA grades 1 and 2; and able to give informed consent. Following consent, patients would be randomly allocated to: arthroscopic lavage (with or without debridement as deemed clinically necessary); placebo surgery; or non-operative management (fuller details of the three intervention arms are presented in Figure [1](#F1){ref-type="fig"}). No change in treatment (other than in analgesia use) was to be allowed in any of the randomised groups for a period equivalent to three months after randomisation. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Schematic of pilot. ::: ![](1745-6215-12-50-1) ::: For those randomised to some form of surgery, the type of surgery (whether arthroscopic lavage or placebo) was not to be revealed until the patient had been anaesthetised and was in the operating theatre. After surgery, discussions with patients would follow a pre-agreed approach: \"you know that I cannot tell you whether you had the active surgery or the placebo, but I can tell you that the procedure went well and we will now need to see how well this helps your knee\". This approach was to be maintained during follow-up clinic appointments. Feasibility of the proposed placebo-controlled design ----------------------------------------------------- ### Ethics approval Gaining ethics approval for the pilot study was difficult and took nine months. The initial application for the pilot phase was rejected. Two main concerns were raised: a) the potential inclusion of surgeons who would not routinely offer arthroscopic lavage; and b) the potential inclusion of centres where arthroscopic lavage was being phased out and was no longer a routine treatment choice. We appealed against this decision on the counter-arguments that: a) surgeons who would neverconsider arthroscopic lavage would not agree to take part in the trial, so one could assume that all patients recruited from surgeons who agreed to participate in the trial would have a possibility (albeit sometimes low) of having been offered lavage had the trial not been in place; and b) it could have been uncertainty of effectiveness of arthroscopic lavage rather than certainty about the lack of effectiveness that led centres to stop undertaking routinearthroscopic lavage. Thus including those centres where surgeons who still wished to find out whether lavage was truly effective was a further justification for the research, rather than an ethical objection to it. The second MREC which heard our appeal approved the pilot, subject to our considerably extending the patient information leaflet (which we duly did). ### Local authorisations Despite ethics committee approval, the pilot subsequently required major discussion and negotiation at each individual centre before local clinical approvals could be obtained. Some of the arguments discussed at the ethics committee were raised again at local level and the fact that ethics approval had been granted did not mean that clinicians would automatically accept that the process was ethical. There were also concerns about who would pay for any placebo procedure and about indemnity arrangements. Despite extensive negotiations full local approval was not achieved for one of the two pilot centres within the four-month timeframe of the pilot study (a number, but not all, of the authorisations were successfully in place). In the centre where the pilot did receive approval, the local authorisation process also led to caveats being placed on the delivery of the trial locally (eg, the restriction that only consultant anaesthetists take part). ### Delivery of the pilot design Eight clinics were held over the course of the pilot phase, drawing patients identified as potentially eligible for the trial by screening referral letters sent by the patients\' General Practitioners (GPs). Forty nine patients were invited to attend. Of the 40 patients who attended, 13 were eligible and nine consented to take part (Figure [2](#F2){ref-type="fig"}). Six were randomised to some form of surgery and three to non-operative management. Two of the six patients randomised to surgery subsequently withdrew from the pilot prior to surgery. Both cited anxieties about the possibility of receiving placebo rather than active surgery among their reasons for withdrawal. One also highlighted concerns about Methicillin-resistant Staphylococcus Aureus(MRSA). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Feasibility checklist for surgical placebo controlled trials. ::: ![](1745-6215-12-50-2) ::: The three patients randomised to non-surgical management were reassessed by the treating clinician on the same day as the recruiting clinic, following randomisation. All three were advised on analgesic use. Two participants were given lifestyle modification advice and exercise information. The use of a walking stick was suggested to one participant but this was declined. Two participants were advised to use an elastic knee brace and one on the use of heat or ice. One surgical session took place which involved one active and one placebo procedure (the two remaining surgical patients were managed outwith the framework of the pilot - see below). The patient allocated to active procedure underwent arthroscopic lavage with three litres of saline (debridement was not required) and the procedure was completed as per protocol. The placebo surgery was also undertaken successfully as per protocol. The surgeon and anaesthetist reported that the practicalities of both active and placebo surgery presented no major problems. Operating theatre staff did, however, express some concern when it was revealed that a patient was to receive placebo surgery (despite the fact that they had previously been fully informed of the nature of the trial). Through the two month follow-up questionnaire, neither patient reported that they thought they had undergone placebo surgery. ### Decision whether to progress to a large-scale trial Towards the planned end of the pilot, the funders reviewed our study findings to decide whether to continue seamlessly into the conduct of a full-scale trial. They concluded that a surgical placebo for arthroscopic lavage could be successfully designed, was generally acceptable to the range of stakeholder groups (although a few held strong views against the use of a surgical placebo under any circumstances), but faced considerable feasibility barriers when trying to conduct the trial in practice. In the light of these findings, the funders decided that the anticipated time, energy and cost required to bring multiple centres on board to recruit sufficient numbers (approximately 800 would be required) to a definitive large-scale trial over a sustained period of time was not justified (especially against a background of a gradual, albeit slow, decline in arthroscopic lavage \[[@B23]\]). As two of the pilot patients were still awaiting their surgery at the time of this decision, and it was as yet unclear if this was to be active or placebo surgery, it was deemed inappropriate to continue their management under pilot conditions and their management was reviewed outside the pilot framework. Discussion ========== Our study illustrated that a surgical placebo for arthroscopic lavage could be designed that was acceptable to a sizeable proportion of people across the range of stakeholder groups (although a few held strong views against the use of a surgical placebo under any circumstances), but conducting such a trial in practice would face considerable feasibility issues. Our study also illustrated well the opposing and often strongly held opinions that are held about placebos in surgery, the ethical issues that underpins this controversy, and the challenges of mounting such a trial that exist even when ethics committee approval has been granted. Issues of ethical and scientific acceptability of a placebo design in surgery ----------------------------------------------------------------------------- There was widespread acceptance in our study that further investigation was required into the effectiveness of arthroscopic lavage. Whether that investigation should or should not include a placebo-controlled design generated much wider discussion. Commentators agree that the ethical principles appropriate to all clinical research must be satisfied as a minimum when considering a placebo-controlled design. These principles are that the study must: a) have scientific merit, b) be acceptable to participants in terms of the risk-to-benefit ratio of participation and c) respect the autonomy of participants by enabling them to determine whether they should participate \[[@B24]\]. In the qualitative components of our study participants raised and discussed these factors for the case of arthroscopic lavage. The scientific merit of the proposed study and the need for informed consent were readily accepted. Whether the proposed study design provided an acceptable balance of risks and potential benefits for participants generated much wider debate. The discussion of an acceptable risk-to-benefit ratio in a placebo-controlled study is not straightforward. As Horng and Miller \[[@B25]\] argue, the risks must be considered in the context of alternative study designs to answer the research question - could an evaluation of arthroscopic lavage be conducted without the use of a placebo control and without compromising scientific rigour? The subjective measurement of the primary outcome in our study (patient reported pain) was recognised to be prone to bias in an open trial design (ie, when people would know which intervention they had been randomised to) \[[@B26]\], and it was considered impossible to maintain an open trial sufficiently long for any placebo effect to have dissipated, and as such the inclusion of a placebo control was deemed to maximise scientific rigour. An additional consideration in the risk-to-benefit ratio for participants is the nature of the proposed placebo - how \"risky\" the proposed placebo is perceived to be. A placebo must be able to mimic the intervention under evaluation, but minimise the risks to those who might take part in the trial. Edwards et alsuggest that perceptions of acceptability of placebo are likely to vary depending on the nature of the placebo in question \[[@B27]\]. In our study, agreement of the choice of placebo surgical procedure proved easier than the method of anaesthesia. The surgical approach chosen (three small skin incisions) was both a satisfactory mimic and had low intrusiveness and thus required little debate. However, the use of general anaesthesia, while an excellent mimic, was more intrusive and as such generated much greater discussion, and was the factor that caused most discussion with local decision-makers when seeking formal approval to conduct the pilot. It is interesting to note, however, that the content experts (ie, the anaesthetists) contended that the use of a general anaesthetic would be safer (because this is the technique which they used routinely and with which they have the greatest experience) than a supposedly less intrusive alternative, such as a form of analgeso-sedative regimen, with which they were less familiar. The wider literature supports this, suggesting that the success of a procedure is directly related to the number of procedures undertaken by that individual \[[@B28]\]. Further evidence of the controversial nature of the placebo design was the need to go to an appeal before the pilot trial received ethics committee approval, despite evidence of support from a range of surgeons, anaesthetists and potential participants. In response to the ethical debate raised by the Moseley trial \[[@B16]\], the American Medical Association produced a set of principles under which a placebo-controlled trial in surgery would be considered ethical \[[@B29]\]. These principles outlined: that surgical \"placebo\" controls should be used only when no other trial design will yield the requisite data; that particular attention must be paid to the informed consent process when enrolling participants in such trials; that the use of surgical \"placebo\" controls may be justified when an existing, accepted surgical procedure is being tested for efficacy (but that it was not justified when testing the effectiveness of an innovative surgical technique that represents only a minor modification of an existing, accepted surgical procedure); and that when a new surgical procedure is developed with the prospect of treating a condition for which no known surgical therapy exists, using surgical \"placebo\" controls may be justified, but must be evaluated in light of whether the current standard of care includes a non-surgical treatment and the benefits, risks and side-effects of that treatment. Our experience suggests that these principles remain relevant; but, for a placebo-controlled trial to be conducted successfully, it is clear that it must not only be an ethicallyand scientificallyacceptable course of action but must also be a feasiblecourse of action. Issues around feasibility of a placebo-controlled trial in surgery ------------------------------------------------------------------ Randomised controlled trials in surgery are well-known to be difficult to design and often suffer from recruitment problems \[[@B30],[@B31]\] and adding a placebo component to the design adds to this complexity. Our study also faced a number of practical hurdles before it commenced recruitment and it proved impossible to surmount all of these in one of the two pilot centres within the four-month timeframe of the pilot. We found that: a) stakeholders in each trial centre needed to be fully briefed and any ethical and practical concerns resolved prior to trial commencement; b) that arrangements needed to be put in place to cover the costs of the placebo before the trial could go ahead; and that c) appropriate indemnity arrangements needed to have been instituted. The crucial importance of local stakeholders and gatekeepers has been outlined by a number of authors and the need to develop explicit recruitment and communication strategies identified \[[@B32],[@B33]\]. Our study confirmed that recruitment to a surgical placebo-controlled trial is achievable - nine of 13 eligible patients approached agreed to join the trial - and the study also demonstrated that blinding of participants receiving surgery was successfully maintained. However, two of the six allocated to surgery subsequently withdrew before surgery citing concerns about the possibility of receiving placebo surgery and risks associated with hospitalisation as reasons. This raises questions about the potential influence of a placebo arm on retention rates in surgical trials. This range of feasibility issues is likely to be faced by anyone considering a placebo-controlled surgical trial, and a checklist of appropriate issues that trialists should consider is presented in Figure [2](#F2){ref-type="fig"}. Strengths and weaknesses of the study ------------------------------------- Surgical placebos are controversial and this is one of the few studies to have explored empirically the attitudes and perceptions of stakeholders on this important issue. In addition it sought to reflect the perspectives of a wide range of stakeholders including surgeons, anaesthetists, potential participants and ethics committee chairs. It also ensured UK-wide coverage of opinions through the professional surveys (although response rates were, like those for other surveys among health professionals, quite low), and this provides reassurance that the results are reflective of the current range of opinion on the issue of surgical placebos in general. Similarly the involvement of multiple centres in the research was a strength, as previous studies of placebos have often been conducted in a single centre setting. This was one of the key criticisms of the Moseley trial as it only involved a single surgeon in a single centre. We recognise, however, that our study concentrated on a relatively minor surgical procedure and that the results may have been different if we had been trying to design a placebo for a more invasive procedure which would have required a larger surgical incision or more complex anaesthetic or a higher risk of major complications. We anticipate that in those circumstances consensus on both the design and acceptability of the placebo would have been harder to achieve and that recruitment to the study may have been lower. In addition, the number of patients recruited to the pilot study was small; limiting the conclusions we can draw from their responses. However, we are confident that the range of issues which require to be considered when planning a placebo-controlled trial in surgery were encountered in this study. Conclusions =========== Our study showed in principle, a placebo-controlled trial of arthroscopic lavage could be conducted in the UK, albeit with difficulty. It highlighted well that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. In the light of our experience, the place of placebo-controlled surgical trials seems likely to be very limited. Our study suggests that the following conditions would need to be satisfied: a\) alternative designs would provide inferior (and potentially biased) results, particularly where the primary outcome is of a subjective nature and blinding cannot be sustained beyond the time of any placebo effect; b\) a placebo surgical procedure and type of anaesthesia can be devised which adequately mimic the active intervention with a level of intrusiveness and risk that is acceptable to the surgeons and anaesthetists who would take part in the trial, and to ethics committees, research governance assessors and potential participants; c\) appropriate practical arrangements can be instituted in local centres to ensure that the delivery of such a design would be feasible; d\) sufficient numbers of potential participants (after assessment of clear descriptions and careful explanations in patient information leaflets of the advantages and disadvantages of taking part) judge for themselvesthat the risk-to-benefit ratio of participation is acceptable to them; and e\) levels of compliance with the allocation are sufficiently high to sustain scientific rigour. Those who would rule out the use of surgical placebos in these circumstances come up against two difficult questions: 1) What about the apparent acceptability of the methodology to potential participants? and 2) What do we tell people with this painful, chronic and progressive condition why a procedure that is unproven is being offered or why a potentially effective intervention has been discarded? Abbreviations ============= ASA: American Society of Anesthesiologists; GMC: General Medical Council; GP: General Practitioner; HTA: Health Technology Assessment; KORAL: Knee Osteoarthritis: Role of Arthroscopic Lavage; MREC: Multi-centre Research Ethics Committee; MRSA: Methicillin-resistant Staphylococcus Aureus; NCCHTA: National Coordinating Centre for Health Technology Assessment; NIHR: National Institute for Health Research; RQ: Research Question; UK: United Kingdom; US: United States. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MC was the principal grant applicant, led on the development of the study protocol, led the writing of the manuscript, was responsible for the overall conduct of the study and is guarantor of the study. VE contributed to the development of the study design, led on the design of the qualitative component of the study, and contributed to the writing of the manuscript. BC contributed to the development of the study design, led on all anaesthetic and other clinical aspects of the study and contributed to the writing of the manuscript. ZS contributed to the development of the study design, was responsible for the day-to-day management of the qualitative component of the study, and contributed to the writing of the manuscript. AS and contributed to the development of the study design, led on all surgical aspects of the study and contributed to the writing of the manuscript. AMcD contributed to the design of the study materials, to the organisation of study authorisations and assisted in the preparation of the manuscript. JN contributed to the design and conduct of the study and assisted in the preparation of the manuscript. RC contributed to the design and conduct of the study, provided expert guidance on ethical arguments and the place of placebos within these frameworks and contributed to the writing of the manuscript. SB contributed to the design and conduct of the pilot at a local level and contributed to the preparation of the manuscript. The KORAL Study Group - Seonaidh Cotton, Angela Donaldson, Ray Fitzpatrick, Adrian Grant, Alastair Gray, James Hutchison, Marie Johnston, David Murray, Craig Ramsay, David Rowley, Luke Vale and Carlos Wigderowitz - were all members of the KORAL Project Management Group, advising on the design and conduct of the study, and commenting on drafts of the manuscript. All authors have seen and approved the final version of the manuscript. Acknowledgements ================ The authors wish to thank Nelda Wray and Carol Ashton for their invaluable insights into the design and co-ordination of the Moseley trial and for their guidance and contribution to the design of this study. The authors also wish to thank Paul Dieppe for his excellent insights into the feasibility of placebo-controlled studies and his advice in the field of osteoarthritis. The authors also wish to thank the following individuals for their assistance in the co-ordination and practical outworking of the study: Gladys McPherson for database and programming support; Alastair Chambers, Julie Downie, Nicola Maffulli, Ian Dos Remedios, Iain Smith, Lynne Swan and Gayle Walley for their contributions to the pilot phase of the study and Kathleen McIntosh for secretarial support. The authors would also like to thank all those who took part in the various aspects of this project - the focus groups, interviews, surveys and pilot study - for their time and detailed consideration of the issues. The authors would also like to thank the members of both MRECs who were involved in the assessment of this study and for their thoughtful consideration of the ethical issues raised by this project. The authors are also indebted to the staff of the National Coordinating Centre for Health Technology Assessment (NCCHTA) for their invaluable advice on the practical coordination of this study and especially Jon Nicholl for his expert guidance through the decision-making stages of the project. The study was funded by the NIHR HTA Programme (03/48/01). The funder had no role in the design, conduct or analysis of the study. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorates. The views expressed are those of the authors alone. \* The KORAL study group are: Seonaidh Cotton, Angela Donaldson, Ray Fitzpatrick, Adrian Grant, Alastair Gray, James Hutchison, Marie Johnston, David Murray, Craig Ramsay, David Rowley, Luke Vale and Carlos Wigderowitz.	PubMed Central	2024-06-05T04:04:18.955808	2011-2-21	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052178/", "journal": "Trials. 2011 Feb 21; 12:50", "authors": [ { "first": "MK", "last": "Campbell" }, { "first": "VA", "last": "Entwistle" }, { "first": "BH", "last": "Cuthbertson" }, { "first": "ZC", "last": "Skea" }, { "first": "AG", "last": "Sutherland" }, { "first": "AM", "last": "McDonald" }, { "first": "JD", "last": "Norrie" }, { "first": "RV", "last": "Carlson" }, { "first": "S", "last": "Bridgman" } ] }
PMC3052179	Background ========== Obesity is one of the main determinants of avoidable disease burden \[[@B1]-[@B3]\]. In lieuof affordable, non-invasive, effective obesity treatment over the long-term, and because the adverse effects of obesity on health status are not fully reversible, a stronger focus on the prevention of obesity has been advocated \[[@B4]\]. Since overweight status and obesity in adulthood are predicated on childhood and adolescent weight, obesity prevention should start early in life. One important target group is the child of school-age i.e. the age-group around adolescence \[[@B5]\]. Although genetic factors may influence the susceptibility of individuals to weight gain \[[@B6]\], there is a consensus that changes in lifestyle activities have driven the current obesity epidemic \[[@B7]\]. Therefore, obesity prevention among school children should target dietary habits as well as physical activity and sedentary behaviour \[[@B4]\]. The school environment is regarded as a good setting for the promotion of health interventions among children because no other institution has as much contact time with the target population \[[@B8]\]. Schools provide an environment where almost all children can be reached repeatedly and continuously, and where health education can be combined with health promoting environmental changes \[[@B5]\]. The development of personal skills and coping practices involves the promotion of healthier behaviour, particularly with respect to nutrition and physical activity, and this can be achieved by health education. Health education attempts to provide information regarding healthy diets and physical activity by means of active participation of the target population and, in soliciting a response, to promote health as the process of enabling people to increase control over, and to improve, their health \[[@B9]\]. Officially, teachers are preoccupied with academic activities and an option may be to involve young students from medical and health science departments of the local university who, as part of their new curriculum, receive health education oriented towards school-based interventions. Although some school-based interventions have had positive effects on overweight and/or obesity \[[@B10]-[@B12]\] most, particularly those involving large cohorts \[[@B13]-[@B15]\], have not. The effects of a long-term school-based intervention on improving diet and increasing physical activity and reducing obesity in the north-west Mediterranean area are, as-yet, unknown. Our hypothesis is that a regular systematic educational intervention in primary school improves lifestyle choices and reduces obesity. As such, the aims of the study are: 1) To evaluate the effects of a 3-year school-based program of lifestyle improvement, including diet and physical activity, on the prevalence of obesity; 2) To design a health promotion program for implementation by university students acting as \"health promoting agents\" (HPA) in primary schools. Methods/Design ============== University program ------------------ The training focuses on promoting a healthy lifestyle via activities designed to reduce obesity, and to prepare the HPA to implement these educational interventions in schools. The intervention approach combines constructs from education- and nutrition-based evidence. Two courses are proposed: Course \#1: Methodology for the promotion of health in schools Description of the course Bases of health education and health behaviour Theory and program planning: A study of determinants of health behaviour, factors influencing health behaviour, health behaviour theories and application of methodology are examined. Health education curriculum and instruction: Research methods in health education; principles of evidence-based nutrition. 12 lectures of 1 h duration each, delivered over 15 weeks per academic year. Eight topics in nutrition are chosen for scientific evidence to improve consumption of some foods. Increased physical activity and healthy habits such as teeth-brushing and hand-washing are highlighted. The objectives are: 1\. Healthy lifestyle. Taste (knowledge of previously-unknown food items) 2\. Healthy drinks 3\. Vegetables and legumes 4\. Candies and pastry vs. nuts 5\. Healthy habits: timetable (home meals preferably) and physical activity 6\. Fruits 7\. Dairy products 8\. Fish Course \#2. Interdisciplinary implementation of health education in schools This course provides a careful examination of strategies of design, implementation, and health program evaluations, including training and standardisation of each activity as well as the performance of these activities in schools. In the activity training, the primary school teachers are included in the jury to assess the performance of the HPA in the primary schools. 4 lectures of 1 h duration each; in 12 h for training and standardisation and 12 activities (1 h/activity/classroom) over 15 weeks per academic year Schools ------- The school-based lifestyle modification program is designed as an interdisciplinary health promotion program performed by HPA. All strategies are focused on children aged between 7 and 8 years. The program targets the whole school community including parents, pupils, staff and teachers within the school environment. The schools for the program needed to be representative of the child population. We offered the program to all schools whether public (funded by the government and termed \"charter\" schools) or private. To maintain independence between intervention and control schools, we selected schools from Reus (a town with about 100,000 citizens) to represent the intervention group, with Cambrils, Salou and Vilaseca (3 towns on the outskirts of Reus with about 70,000 citizens in total) to represent the control group. There are very good communications between schools within each town and, hence, to avoid cross influence between control schools that were masked with respect to intervention, the towns themselves were the units for randomisation. The coordinating Centre developed a randomization scheme in which the schools in Reus (designated as group A) and the schools in the three others towns of Cambrils, Salou and Vilaseca (designated as group B) had similar pupil populations. Randomisation defined A group as the intervention and B as the control group. In our area of Spain, each classroom contains approximately 25 children (at most 27 children and, occasionally, 20-22 children). When the numbers of children exceed the state-recommended level, a new classroom at the same education level is opened in the school. Thus, there could be 2 or more classrooms for any specific level; some schools may even have 3 classrooms per level with 25-27 children per classroom. All classes are co-educational Participating intervention institutions consist of 24 schools involving 36 classrooms (97% public or state funded \"charter\" schools and 3% private) involving at least 700 pupils in Reus. Participating control institutions consist of 14 schools involving 39 classrooms (96% public or state funded \"charter\" and 4% private) involving at least 700 pupils in the 3 surrounding towns of Cambrils, Salou and Vilaseca. The ethnic origin of control and intervention pupils are: 83.2% of Western European descent (mainly from Catalunya) and 16.8% are non- European; 7.8% from Latin America, 5% of North-African Arab descent, 3% recent immigrants from Eastern Europe (mainly Rumanian) and from other countries from the Asian Far East (such as China). For a school to be included in the study, at least 50% of the children in the classrooms needed to have volunteered to participate. In the intervention group, all children of the selected classroom are exposed to the intervention. For logistics reasons, the first scholastic group was enrolled in 2006 and followed-up for 3 years (2006-2009), and a second scholastic group was enrolled in 2007 and also followed-up for 3 years. Thus the final measures are performed in the year 2010. The data are collected on all the children, but only the data from individuals (and their parents) who provided informed consent are included in the final analyses. Name, gender, date and place of birth are recorded at the start of the program, while weight, height, body mass index (BMI) and waist circumference variables (identified set of anthropometric measures) are recorded in each of the 3 years of the study. The measurements were performed in May of the years 2006, 2007, 2008, 2009, and 2010. Body weight was measured to the nearest 0.05 kg using a standard beam balance (Tanita TBF-300 Body Composition Analyzer, Brooklyn NY, USA). The set of anthropometric measurements was performed three times each academic year. The mean values were used in all subsequent statistical analyses. To assess intra-observer variability, the anthropometric measurements were repeated in 20 children (10 boys and 10 girls). To assess inter-observer variability, all 5 observers conducted the 5 anthropometric measurements in 10 children. The standardisation of observers was performed in each year of the study \[[@B16]\]. If the child is lost to follow-up (the child is relocated to a different school, or the parents move to a different area) we are able to contact the child/parents via the name and date of birth; data that are held in the records of the local education authority. If the child moves to a school that is participating in the study, he/she is identified and followed-up within the new school. If, instead, the children move to another city outside the study area, they are lost to the study and are not replaced. We anticipate a loss of about 20% of pupils which, by chance, would be similar in intervention and control schools. The assumption would be that all losses are, also, by chance and the statistical methods used are robust enough to accommodate for randomly-produced missing values. Questionnaires regarding eating habits (Krece-Plus) developed by Serra-Majem et al \[[@B17]\] and physical activity as well as the level of parental education and their habits \[[@B18]\] are filled-in by the parents at the start and conclusion of the study. Intervention program -------------------- The intervention program consisted of three components: 1\. Classroom practice by HPA to highlight healthy lifestyle habits 2\. Teaching practice by HPA using books designed to include the nutritional objectives 3\. Parental activities included with their children In each of 12 activities (1 h/activity), the classroom practice consisted of three components: 1\. Experimental development of activities regarding each healthy lifestyle habit 2\. Assessment of activity performed in classroom 3\. An activity developed for use at home Approval -------- This study was approved by the Clinical Research Ethical Committee of the Hospital Universitari Sant Joan of Reus, Universitat Rovira i Virgili (Catalan ethical committee registry \#20; ref: 08-07-24/07aclproj1). The protocol conformed to the Helsinki Declaration and Good Clinical Practice guides of the International Conference of Harmonization (ICH GCP). This trial is registered with International Standard Randomised Controlled Trial Register, number ISRCTN29247645. Statistical Analyses -------------------- We estimated that with a sample of 700 pupils per group, the study would have 83.5% power to detect a difference of 5 percentage points between the intervention and control schools (9%-14%), with respect to the primary outcome (prevalence of obesity), setting the bilateral level of statistical significance at 5%. Descriptive data are presented as means ±SD (95%CI) or percentages. Generalised linear mixed models were used to analyse differences between the intervention and control pupils with respect to the primary outcome. Measurements were conducted at baseline when the pupils are 2^nd^-3^rd^graders (6 or 7 year olds) and at the end of the study when they are 4^th^-5^th^graders (9 or 10 year olds). Primary outcomes include obesity (BMI ≥95^th^percentile) and overweight (BMI ≥85^th^percentile) based on the 1988 BMI tables of Hernandez \[[@B19]\]. We analysed obesity and overweight and a measure of thinness according to the Cole criteria \[[@B20],[@B21]\] as well as other measures of adiposity such as BMI z score and waist circumference. The numbers of subjects having a particular dietary habit are expressed as percentages of the total number of individuals being evaluated. Discussion ========== Developing personal skills and coping practices involving the promotion of healthier behaviours or habits can be induced by health education, particularly with respect to nutrition and physical activity. Nutrition and health education programs attempt to inculcate nutritional values or healthy diets by means of active participation of the target population, often involving person-to-person interactions. Although genetic factors may influence the susceptibility of individuals to weight gain \[[@B6]\], there is growing awareness that recent changes in lifestyle habits underlie the current obesity epidemic \[[@B7]\]. We chose BMI as the measure of obesity and the changes in BMI as the effectiveness of the education program. Although waist circumference (WC) or skin-fold thickness, particularly tricipital, or BMI z score can be used as the measure of obesity, BMI values are acceptable. We proposed 3 evaluation methods based on the tables of Hernández et al and Cole et al \[[@B18],[@B19]\] and the EnKid study of 2003 \[[@B22]\] because each one has advantages and inconveniences. Hernandez is the oldest, and the values of BMI are the lowest corresponding to data before the increase in prevalence of overweight and obesity. The Enkid study contains BMI values from 1998-2000, which are ten years more recent than that of Hernández \[[@B18]\], and describe the increase in BMI in a youth population. Obesity is defined as BMI ≥95^th^percentile and overweight by BMI ≥85^th^percentile in order to compare the results of United States guidelines \[[@B23]\]. The tables from Cole et al \[[@B19],[@B20]\] enable comparisons to be made with European studies. We standardised intra- and inter-observer variation to assure quality in the anthropometric measurements. The results expected are the reduction of obesity prevalence based on improving lifestyle habits. Wang et al \[[@B24]\] had proposed that 1% increase/year in childhood obesity in Mediterranean Europe would induce an estimated 11.5% obesity and 30.2% overweight prevalence by the year 2010 and, as such, increase in prevalence of obesity and overweight will have an important health effect. The lifestyle interventions in the program implemented by the university students being trained as HPA include experimental activities using natural food in the habitual diet, and increasing physical activity in the schools. Multi-component foods, physical education, class curricula, behavioural knowledge and skills, communications and social marketing, and the acceptability of healthy behaviour have been proposed as means of reducing BMI. However, the efficacy observed has been inconsistent. Evidence for effectiveness on anthropometrical obesity-related measures is lacking \[[@B25]\]. The challenge is to identify and to develop a cohesive hypothesis which combines educational and health promotion, to examine the effects of the intervention with valid and reliable measurements of the outcomes. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MG participated in the conception and design of the study and its final approval, drafting and revising the manuscript. RA participated in designing the study, drafting and revising the manuscript. DM participated in designing the biostatistical methods of the study, drafting and revising the manuscript. RS participated in designing the study, drafting and revising the manuscript. Acknowledgements ================ This research project has been supported by Reddis Private Foundation (Spain) \[Fundació Privada Reddis\]; the Municipality of Reus, Spain \[Ajuntament de Reus\], the Ministry of Health of the Autonomous Government of Catalunya, Spain \[Conselleria de Salut de Generalitat de Catalunya\], Central Market of Reus, Spain \[Mercat Central de Reus\], Protected Designation of Origin Siurana, Spain \[DOP Siurana\], La Morella Nuts, S.A. Spain; Nutrition and Health Technology Centre CT09-1-0019, Spain \[Centre Tecnològic de Nutrició i Salut\]. We express our appreciation to the university medical and health science students of the Facultat de Medicina i Ciències de la Salut, Universitat Rovira I Virgili(Reus, Spain) as well as the staff and parents of the pupils of the primary schools of Reus, Cambrils, Salou and Vilaseca for their enthusiastic support in this study	PubMed Central	2024-06-05T04:04:18.960547	2011-2-27	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052179/", "journal": "Trials. 2011 Feb 27; 12:54", "authors": [ { "first": "Montse", "last": "Giralt" }, { "first": "Rosa", "last": "Albaladejo" }, { "first": "Lucia", "last": "Tarro" }, { "first": "David", "last": "Moriña" }, { "first": "Victoria", "last": "Arija" }, { "first": "Rosa", "last": "Solà" } ] }
PMC3052180	1. Public Health and Economic Costs Associated with Salmonella ================================================================ Salmonellais an important foodborne pathogen world-wide. A recent study estimated that approx. 93.8 (95% Confidence Interval: 61.8-163.6) million human cases of gastroenteritis and 155 000 (95% Confidence Interval: 39 000 - 303 000) deaths occur due to Salmonellainfection around the world each year \[[@B1]\]. In the USA alone, Salmonellacauses an estimated 1.4 million human cases, 15 000 hospitalizations and more than 400 deaths annually \[[@B2],[@B3]\]. However, only a fraction of cases is reported, and in the USA, only an estimated 1-5% of cases are laboratory confirmed and reported to the Centers for Disease Control and Prevention (CDC) \[[@B4]\]. In 2006, the national case rate in the USA equaled 13.6 reported cases per 100 000 population per year \[[@B4]\]. Rates varied considerably by geographic region, with estimates particularly high in the Mid-Atlantic and New England States. This heterogeneity is likely in part due to differences in reporting. Differences in salmonellosis case rates between geographically and socio-economically similar USA states have been documented, with rates differing by as much as 200% between neighboring states \[[@B4]\]. Similarly, of the 168 929 human cases reported in the European Union (EU) during 2005, 31% stemmed from Germany even though less than 20% of the EU\'s population resides in Germany, again suggesting reporting differences \[[@B5],[@B6]\]. In 1999, non-typhoidal Salmonellainfections in the USA were estimated to contribute 10% of foodborne human illnesses, 26% of hospitalizations, and 31% of deaths attributable to infections by known foodborne pathogens, thereby ranking first among all bacterial foodborne pathogens in hospitalizations and deaths and second after Campylobacterin the number of illnesses \[[@B3]\]. In 2009, Salmonellawas the most commonly reported bacteriological agent of human foodborne disease in the USA, causing approx. 44% of confirmed foodborne bacterial infections \[[@B7]\]. More than 20% of human clinical Salmonellaisolates in the USA are obtained from children under the age of 5 years, emphasizing the great importance of this age group \[[@B8],[@B9]\]. Approx. 1% of Salmonellacases are thought to require hospitalization \[[@B10]\]. However, due to the high prevalence of Salmonellainfections, the Economic Research Service of the United States Department of Agriculture (USDA) \[[@B11]\] estimated the annual cost inflicted on the USA economy to equal approx. 2.5 billion US dollar, thereby clearly exceeding the annual economic cost attributable to human infections by Escherichia coli(\$460 million) or Listeria monocytogenes(\$2 billion) \[[@B12]\]. 2. SalmonellaEpidemiology and Transmission Dynamics ===================================================== Salmonellaserotypes can be divided into host restricted, host specific, and generalists serotypes, with important implications for epidemiology and public health \[[@B13]\]. Host specific serotypes, for instance serotypes Paratyphi A, Gallinarum biovars Gallinarum and Pullorum, or Typhi only cause disease in one host species \[[@B13],[@B14]\]. In contrast, host restricted serotypes are predominantly associated with one host species, but can cause disease in other species as well \[[@B13]\]. SalmonellaDublin, for example, is adapted to cattle but infections in small ruminants, pigs and humans have also been documented, and serotype Choleraesuis is adapted to swine but has also been isolated from a range of other host species \[[@B15],[@B16]\]. Generalist serotypes such as SalmonellaTyphimurium commonly cause disease in a broad range of hosts, even though a narrow host range has been described for certain subtypes, for instance Typhimurium subtypes DT2 and DT99, which appear to be adapted to pigeons \[[@B17]\]. Serotypes with broad and narrow host range seem to differ in clinical manifestation even though other factors such as host species, age, and concomitant disease affect the clinical manifestation as well (see \[[@B17]\] for a comprehensive review). Infections with generalist serotypes are often characterized by high morbidity but low mortality, and gastro-intestinal symptoms are the predominant clinical manifestation \[[@B13],[@B17]\]. On the contrary, infections with host adapted or restricted serotypes, such as Choleraesuis, Abortusequi, Gallinarum biovar Gallinarum, or Gallinarum biovar Pullorum, are typically characterized by low morbidity and high mortality, and systemic disease is common \[[@B13],[@B17]\]. Salmonellaserotypes clearly seem to differ in their pathogenic potential for humans and serotype distributions often vary vastly between human and animal populations as well as among different animal populations in the same geographic area (see Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). For instance, approximately 40% of all known Salmonellaserotypes are predominantly associated with reptiles or amphibians, yet less than 1% of human salmonellosis cases are caused by these reptile-associated serotypes. The molecular determinants of serotype-specific host range differences have so far largely remained elusive. However, serotype-specific differences in virulence have been characterized in some cases. For instance, in competition experiments with SalmonellaTyphimurium, reptile-associated SalmonellaArizonae and Diarizonae showed a significantly reduced ability to colonize and persist in the intestine of BALB/c mice, clearly suggesting virulence differences \[[@B18]\]. Majowicz et al. \[[@B1]\] recently estimated that approx. 80.3 of 93.8 million human Salmonella-related gastroenteritis cases that are estimated to occur globally each year are foodborne, thus representing approx. 86% of human salmonellosis cases. Another study based on formal elicitation of expert opinion estimated that approx. 55% (range 32-88%) of human Salmonellacases are foodborne, 14% (range 3-26%) are travel-related, 13% (range 0-29%) are acquired through environmental sources, 9% (range 0-19%) occur due to direct human-to-human transmission and 9% (range 0-19%) are attributable to direct animal contact \[[@B5],[@B19]\]. Yet another study, based on surveillance data, estimated that 95% of non-typhoidal human Salmonellacases in the USA are foodborne, emphasizing the complexity and controversy of the subject matter \[[@B3]\]. Food products derived from the animal species discussed in this review can also serve as sources of human infection, and such products have been implicated in numerous human outbreaks. However, as this review focuses on animal-acquired infection, foodborne infections will not be further discussed here. Several excellent reviews of foodborne salmonellosis have been published in recent years, and the reader is referred to these publications for further details regarding infections associated with the consumption of meat, eggs, dairy products, vegetables, reptile products, and other foods (see for instance \[[@B10],[@B20]-[@B29]\]). The comparison of Salmonellaoutbreak and surveillance data across geographic regions or from different time periods represents a considerable challenge. The advent of novel molecular subtyping methods has noticeably improved discriminatory power, with important impacts on sensitivity and specificity \[[@B30]\]. The impacts of differences in public health infrastructure, disease surveillance sampling plans, public health legislation etc. are difficult to measure, but differences in apparent prevalence between states or countries are clearly noticeable. Case and outbreak definitions are also variable. For clarity, we will henceforth define \"case\" to refer to any instance where strong epidemiological or molecular evidence suggests an animal source of human infection, while trying to point out instances where such conclusions are solely based on serotype data or circumstantial epidemiological links. Furthermore, we will define an outbreak as an event where two or more human cases are presumably linked to the same source. We acknowledge that the epidemiological definition of an outbreak differs from this definition, but due to the large amount of underreporting and the problem of attributing cases with broad host-range serotypes to animal sources we chose this definition. As some serotypes are strongly associated with specific animal species and some case definitions utilize serotype data to define for instance reptile-acquired cases (see for instance \[[@B31],[@B32]\]), serotype-dependent differences in case detection are likely. Similarly, unusual exposures, such as those attributable to newly acquired or exotic pets, visits to animal exhibits, or contacts with clinically sick animals, are more likely to be recalled than routine exposures (see for instance \[[@B33]-[@B36]\]). In addition, small outbreaks are probably less likely to be reported in the peer-reviewed literature. Animal acquired infections are therefore probably strongly underreported, and the data is potentially biased towards larger outbreaks, uncommon serotypes, certain animal species, and unusual exposures. 3. Mammals as Source of Human Infection ======================================= 3.1. Mammalian livestock species and Salmonella ------------------------------------------------- ### 3.1.1. The global distribution and economic importance of mammalian livestock The estimated number of mammals farmed for agricultural purposes around the world exceeds 4 billion animals \[[@B37]\]. In 2006, approx. 20% of the world\'s population, equaling approx. 1.3 of 6.55 billion people, were employed in the livestock sector, and livestock accounted for approx. 40% of global agricultural output \[[@B38]\]. An estimated 1 billion pigs and 2 billion small ruminants are farmed worldwide \[[@B39]\]. The global cattle population is believed to equal approx. 1.3 billion animals, and 181 million buffaloes as well as approx. 24.7 million camels are farmed for commercial purposes around the world \[[@B37]\]. The relative and absolute abundance of livestock differs considerably by country and geographic area. For instance, the USA is the world\'s largest producer of beef and the third-largest producer of pork, while large numbers of cattle and pigs are also farmed in the EU \[[@B37]\]. Australia is a leading producer of wool and sheep meat, and India is an important producer of goat, buffalo and cow milk and a leading producer of goat and buffalo meat. Africa as well as parts of Western Asia are major producers of camel and goat products \[[@B37]\]. ### 3.1.2. Cattle and Salmonella #### 3.1.2.1. The clinical and economic importance of Salmonellainfections among cattle Abortions attributable to Salmonellainfection are possible but rare in cattle, thus economic losses in cattle operations are primarily due to increased mortality, performance losses, and direct and indirect costs associated with treatment and infection control (see \[[@B40]\] for a review of the topic). Mortality rates attributable to Salmonellainfection are particularly high in young animals, which also generally require the greatest amount of treatment. Significant weight losses in calves due to Salmonellainfection have been reported in numerous studies, even though surviving calves seem to regain the weight after recovery (see \[[@B40]\]). In addition, Salmonellainfection often leads to increased feed costs due to diminished feed conversion \[[@B40]\]. Clinically, Salmonellainfection in cattle is typically manifested as watery or bloody diarrhea, and often associated with fever, depression, anorexia, dehydration and endotoxemia. Less common clinical manifestations include abortion and respiratory disease, and mortality rates can be high. Particularly in adult animals Salmonellafrequently causes subclinical disease, and is known to persist on infected farms for months or years \[[@B41]-[@B44]\]. Individual animals shed Salmonellaintermittently, over variable periods of time, and infections with host adapted serotypes such as SalmonellaDublin may potentially result more frequently in the development of asymptomatic shedders than infections with broad host-range serotypes \[[@B45]\]. One recent study estimated the median duration of shedding in dairy cattle to equal 50 days, with a maximum duration of 391 days, and the results appear comparable to previous reports \[[@B46],[@B47]\]. However, the duration of Salmonellapersistence in herds exceeds maximum shedding durations observed for individual animals, and is believed to be largely attributable to endemic Salmonellainfections within the herd \[[@B47]\]. Several studies report isolating Salmonellaat high rates from farm environments, a likely important Salmonellareservoir \[[@B43],[@B47]-[@B50]\]. Salmonellawithin- and between-herd prevalence estimates vary considerably, with between-herd point prevalence estimates for cattle operations ranging from 2-42% and within-herd estimates for these operations ranging from 0-37% \[[@B47],[@B51]-[@B57]\]. In addition, herds with clinically sick animals are generally characterized by higher within-herd prevalence than herds where clinical salmonellosis is absent, and serotype distribution may differ between herds with and without clinical cases \[[@B58]-[@B63]\]. Large herd size represents an important risk factor for salmonellosis, and the risk of Salmonellashedding seems to vary by production system, housing type, general hygiene level, management type and animal age, although the results reported in the literature have been somewhat contradictory \[[@B64]\]. Calves, heifers, and periparturient cows generally appear to be at a particular risk of infection, and one study found heifers and periparturient cows to be the most likely cattle to become asymptomatic carriers \[[@B47],[@B65],[@B66]\]. The distribution of Salmonellaserotypes among cattle varies greatly over time, and differs among geographic regions, age groups, clinical manifestation, and production systems. The United States National Veterinary Service Laboratory (NVSL), for instance, reported that serotypes Typhimurium, Newport, Orion, Montevideo, and Agona were the serotypes most frequently isolated from clinically sick cattle in 2005 and 2006, while serotypes Cerro, Kentucky, Anatum, Newport, Montevideo, and Orion were the serotypes most frequently isolated from clinically healthy cattle in the same time period \[[@B67]\]. In 2007, serotypes Cerro, Kentucky, Montevideo, Muenster, Meleagridis, Mbandaka and Newport were the serotypes most commonly isolated from healthy dairy cattle in the USA, while serotypes Montevideo, Meleagridis, Cerro, Mbandaka, Typhimurium, Anatum, Give, Kentucky, Muenchen and Senftenberg had been the serotypes most commonly isolated from healthy USA dairy cattle in 1996 \[[@B68]\]. In comparison, serotypes Montevideo, I 6,7:k:-, Braenderup, Meleagridis, Newport and I 3,10:-:1, were the serotypes most commonly isolated from USA beef cattle in 2007/2008, and serotypes Typhimurium, Anatum, Dublin, Montevideo, and Newport were the serotypes most commonly isolated from USA beef herds in 1999 \[[@B69],[@B70]\]. The implications of these differing serotype distributions for human health, however, are currently difficult to assess. #### 3.1.2.2 The public health importance of Salmonellainfection among cattle Cattle play a paramount role as source of foodborne infection, and a considerable number of serotypes frequently isolated from humans have been isolated from sick or clinically healthy cattle (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Some human cases have also been linked to direct cattle exposure (Table [1](#T1){ref-type="table"}). For instance, in 2002 and 2004, human SalmonellaNewport outbreaks in Michigan were linked to cattle contact in a public setting; in 2001, SalmonellaNewport was transmitted to humans during a farm visit, even though the consumption of contaminated raw milk may have been a contributing factor; and in 2000, serotype Typhimurium was transmitted to children at a farm camp. In several instances, attribution of human cases to cattle exposure is further complicated by simultaneous consumption of raw milk or cheese from the same farm, as illustrated by recent outbreaks of SalmonellaNewport and Dublin (Table [1](#T1){ref-type="table"}). Nail biting, contact with manure, thumb sucking, eating, or having soiled hands and shoes have been identified as risk factors for animal-acquired E. coliinfections, and a similar role for Salmonellaappears likely \[[@B71]\]. Much less is known about the Salmonellarisk posed to humans by indirect animal contacts, especially through environmental contamination. Further studies, especially on spatial clustering of human cases around livestock premises, are needed to assess the indirect risks posed by livestock operations. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Documented reports of Salmonellatransmissions from mammals to humans available in the peer-reviewed literature or otherwise published by public health agencies ::: Outbreak source Year Salmonellaserotype Type of contact Human cases Country Reference --------------------------------------------- -------------- ---------------------- ------------------------------------------------------------------------- ------------- -------------- --------------------- Livestock Cattle 2005^a^ Stanley occupational (dead calf delivery); pustular dermatitis 1 UK \[[@B36]\] Cattle 2004 Newport public setting 6 USA \[[@B35]\] Cattle 2003 Newport public setting 3 USA \[[@B35]\] Cattle 2002 Newport public setting 6 USA \[[@B35]\] Cattle 2001 Newport farm visit; potentially raw milk consumption 4 USA \[[@B35]\] Cattle 2000 Typhimurium farm day camp 1 USA \[[@B35],[@B304]\] Cattle 1998 Typhimurium household or farm environment 1 USA \[[@B305]\] Cattle 1990 Virchow occupational (dead calf delivery); dermatitis 2 Netherlands \[[@B306]\] Cattle 1983 Newport farm environment, nocosomial, feed-borne 1 USA \[[@B307]\] Cattle 1979 Dublin farm environment, nocosomial, potentially raw milk n/a USA \[[@B307]\] Cattle 1976 Heidelberg farm environment, secondary perinatal &nocosomial n/a USA \[[@B307]\] Cattle 1975 Dublin occupational (dead calf delivery); pustular dermatitis; 3 cases 3 UK \[[@B308]\] Cattle 1973 Saintpaul occupational (dead calf delivery); folliculitis 3 Canada \[[@B309]\] Cattle 1973 Typhimurium farm environment, animal feed pot. source n/a USA \[[@B307]\] Cattle 1972 Typhimurium occupational, farm environment n/a USA \[[@B307]\] Cattle 1969 Dublin occupational (dead calf delivery); pustular dermatitis 1 UK \[[@B308]\] Cattle 1965 Typhimurium farm environment, cow and newborn calf 2 Canada \[[@B310]\] Cattle 1948 Typhimurium farm environment, household, well water 7 Canada \[[@B311]\] Cattle/Pigs 2001 Typhimurium farm or household (contaminated clothes) 1 Netherlands \[[@B37]\] Pigs 2005 Typhimurium public setting; potentially environmental 19 USA \[[@B35]\] Sheep 1998-2003^b^ Brandenburg occupational, household, prob. secondary dogs n/a New Zealand \[[@B97]\] Sheep/Cattle 1991-1993 Typhimurium occupational, household, farm environment 9 UK \[[@B73]\] Sheep 1975 Typhimurium occupational, farm environment, secondary dog infected 1 UK \[[@B72]\] Livestock 2000 Typhimurium petting zoo, animal source unclear 18 US \[[@B303]\] Livestock 1991 Typhimurium science fair, animal source unclear 5 US \[[@B303]\] Equines Horse 2001 Newport state fair, horse clinically sick 2 USA \[[@B35]\] Horse 1995/1996 Typhimurium occupational, veterinary hospital, secondary ruminants 2 USA \[[@B145],[@B312]\] Horse 1976 Typhimurium occupational, veterinary hospital, secondary dog 1 USA \[[@B313]\] Horse 1967/1968 Typhimurium occupational, veterinary hospital, complex epidemiology 2 - 14\* UK \[[@B314]\] Horse 1936 Abortusequi occupational, gynecological exam, developed abscess 1 Japan \[[@B315]\] Canines & Felines Cat 1999 Typhimurium occupational, veterinary clinic 10 USA \[[@B316]\] Cat 1999 Typhimurium household, secondary daycare contact, shelter cats 7 USA \[[@B316]\] Cat 1999 Typhimurium occupational, veterinary clinic, secondary environmental 3 USA \[[@B316]\] Cat/Dog 2003 Typhimurium occupational, veterinary clinic, household infections 7 USA \[[@B317]\] Cat/wild birds 1999 Typhimurium household, prob. complex transmissions n/a Sweden \[[@B318]\] Cat/Dog 1973 Typhimurium household, dog and cat breeder, common food source 4 Canada \[[@B319]\] Dog 1974 Enteritidis household 1 USA \[[@B148]\] Dog 1952 Paratyphi B household 1 UK \[[@B320]\] Dog 1938 Glostrup household, pot. common food source 6 Denmark \[[@B321],[@B322]\] Dog 1937 Paratyphi B^1^ household 6 Norway \[[@B322],[@B323]\] Dog 1938 Paratyphi B household, caused abortion in bitch 4 Sweden \[[@B322],[@B324]\] Pet food & Treats Dry pet food 2006-2008 Schwarzengrund household 70 USA \[[@B325]\] Pet treats 2004/2005 Thompson household 9 USA & Canada \[[@B326]\] Pet treats 2002 Newport household 5 Canada \[[@B327]\] Pet treats 1999 Infantis household, dogs potential shedders 12 Canada \[[@B328]\] Rodents Guinea pig 2000 Oranienburg household, guinea pig soft-tissue abscess and died 1 USA \[[@B329]\] Guinea pig 1967 Enteritidis breeding colony in household 3 Canada \[[@B330]\] Rodents 2005/2006 Typhimurium classroom or household, snakes fed frozen rodents 7 - 21\* USA \[[@B331]\] Rodents 2003/2004 Typhimurium household, sick pet rodents, secondary household 15 - 28\* USA \[[@B332]\] Non-traditional mammalian pets/wildlife Hedgehogs 2002 Typhimurium household, potentially eggs 6 Australia \[[@B333]\] Hedgehogs 2000/2001 Typhimurium unclear, wild animals, potentially contaminated produce 37 Norway \[[@B192]\] Hedgehogs 1996 Typhimurium unclear, wild animals, potentially contaminated produce, 2 outbreaks 28 - 65\* Norway \[[@B192]\] Hedgehogs 1995-1997 Tiliene household, pet hedgehogs, multiple outbreaks, interspecies transmission 9 Canada \[[@B334]\] Hedgehogs 1994/1995^c^ Typhimurium household, pet hedgehog 1 Canada \[[@B196]\] Hedgehogs 1994 Tiliene household, pet hedgehog, indirect contact, breeding herd in household 1 USA \[[@B335]\] Sugar glider 1995 Tiliene household 1 Canada \[[@B334]\] Wallaby 2003 Enteritidis farm environment, traveling petting zoo 17 USA \[[@B35]\] ^1^identical to serotype Abortuscanis ^a^estimated time of outbreak, exact time not specified; ^b^estimated time period for prolonged nationwide outbreak; ^c^exact time of outbreak not specified more precisely; \* exact number of cases unclear; n/a exact number of cases not specified ::: In conclusion, the studies summarized above show that direct cattle contacts represent a potential human health risk. Clinically sick animals probably pose the greatest risk to humans because they are more likely to shed Salmonella, and at higher concentration, than apparently healthy animals. However, even asymptomatic carriers can shed Salmonellafor long periods of time, and increased stress, as often experienced during exhibitions, represents an important risk factor for shedding. In addition, herds with clinical signs of Salmonellahave higher within-herd prevalence than those without clinical signs, Salmonellaprevalence is correlated with animal age as well as management-related factors, and environmental contamination can play an important epidemiologic role. Clinically affected herds and certain management systems may therefore pose an increased risk to the public. Several additional management practices may mitigate the human health risk associated with cattle contacts, for instance strict enforcement of good hygiene practices, the prevention of contact with manure, or targeted education of vulnerable human subpopulations. Several Salmonellainfections have been attributed to occupational livestock contact (see for instance \[[@B36],[@B72],[@B73]\]). Surprisingly, a considerable number of cutaneous infections among veterinarians have been reported as results of obstetric manipulations, reinforcing the need for good hygiene practices and adequate protective equipment (Table [1](#T1){ref-type="table"}). However, quantitative estimates of the occupational risks are scarce. One study reported Salmonella-specific antibodies in 60% of poultry workers and nearly 10% of workers in meat-packaging plants in Russia, with highest prevalence among those handling sick poultry or pathological material (or consuming raw meat sausages) \[[@B74]\]. Similarly, occupational transmission of SalmonellaTyphimurium to a slaughterhouse employee has been reported by Molbak et al. \[[@B75]\]. Another study found nearly 9% of poultry workers and 6% of duck workers were Salmonellacarriers, with intermittent clinical symptoms \[[@B76]\]. Conversely, another study of SalmonellaMuenster reported no occupational transmission in an affected dairy herd, but the study relied exclusively on self-reporting of clinical disease in farm personnel, and sample size as well as observational period were limited \[[@B77]\]. Future studies are therefore clearly needed to understand the magnitude and specific nature of the risks associated with occupational exposure. ### 3.1.3. Small ruminants and Salmonella #### 3.1.3.1. The clinical and economic importance of Salmonellainfections among small ruminants The severity and clinical manifestation of Salmonellainfection in small ruminants differs by age group and serotype \[[@B78]\]. Acute enteric salmonellosis is common in adult sheep, leading to fever, anorexia, depression, and diarrhea, while septicemia is common in young animals \[[@B79],[@B80]\]. However, asymptomatic carriage, chronic gastro-enteritis, and abortion have also been described \[[@B80],[@B81]\]. Late term abortion, mortality in ewes, and high calf mortality can lead to extensive economic losses in sheep operations, making Salmonellaabortion one of the economically most important diseases of small ruminants \[[@B40]\]. Abortion due to infection with serotypes such as Typhimurium or Dublin has been reported, but abortion is most frequently caused by SalmonellaAbortusovis, an ovine-adapted serotype that also occasionally infects goats, and abortion generally occurs in the last weeks before parturition \[[@B78],[@B82]-[@B84]\]. Infections of ewes with serotype Abortusovis can also lead to stillbirth, metritis, placental retention, or peritonitis, and infected ewes may present with fever, anorexia, and depression prior to abortion \[[@B85]\]. Mortality rates in ewes are highly variable, and mortality is often associated with the occurrence of secondary diseases such as placental retention. Neonatal mortality in affected herds is usually high. Lambs carried to term frequently die of septicemia \[[@B78]\]. While neonates often die within hours of birth, lambs can in some cases survive for weeks, and in these instances disease is often manifested as polyarthritis, pneumonia, and severe diarrhea. Salmonella Abortusovis infection in non-pregnant ewes and rams appears to be predominantly asymptomatic and venereal infection have been described in some instances \[[@B86]\]. The prevalence of Salmonellaamong small ruminants seems to vary considerably between serotypes, herds, and geographic regions. Large outbreaks of SalmonellaAbortusovis among sheep have been reported repeatedly, for instance in Switzerland, where infections with serotype Abortusovis seem to have contributed up to 70% of lambing losses between 2003 and 2007 \[[@B87]\]. The prevalence of serotype Abortusovis within herds can be high, and within-herd prevalence estimates of between 20 and 50% have been reported \[[@B82],[@B87]\]. Animals that survive infection with SalmonellaAbortusovis usually develop robust immunity, so that infections tend to be associated with primigravide animals \[[@B82]\]. SalmonellaDiarizonae is the causative agent of winter dysentery, a disease of sheep that is also associated with abortion and stillbirth. Serotype Diarizonae represents another common, sheep-adapted serotype. The prevalence of serotype Diarizonae in Norwegian sheep herds, for instance, has been estimated at approx. 12%, with within-herd prevalence in the range of 0-45%, even though the samples were collected at the abattoir and increased stress may have contributed to the high observed prevalence \[[@B88]\]. Other studies have also reported a high prevalence of various Salmonellaserotypes including for instance serotypes Typhimurium, Anatum, or Saintpaul, in goats and sheep at slaughterhouses in different countries, with prevalence estimates generally in the range of 17-60%, even though a considerably lower prevalence among slaughtered goats and sheep in India and Ethiopia has been reported in some studies \[[@B81],[@B89]-[@B93]\]. The prevalence of Salmonellaamong healthy goats and sheep on farms generally appears to be considerably lower, with reported prevalence estimates often in the range of 0-4% \[[@B94],[@B95]\]. However, environmental contamination on farms is potentially high, and Edrington et al. \[[@B96]\], for instance, reported isolating Salmonellafrom 50% of wool samples but only 7% of fecal samples collected from feedlot sheep in the USA, indicating a potentially important epidemiological role of environmental reservoirs. ### 3.3.2. The human public health importance of Salmonellainfections among small ruminants A limited number of zoonotic transmissions from sheep to humans have been reported in the literature, mostly associated with occupational exposures (Table [1](#T1){ref-type="table"}). For instance, occupational sheep exposure was found to be significantly associated with human SalmonellaBrandenburg infections in New Zealand \[[@B97]\]. In addition, human outbreaks have repeatedly been linked to occupational contacts on farms in the UK, reiterating the potential public health importance of sheep and goat contacts \[[@B73]\]. In conclusion, Salmonellainfections represent an economic and potential public health risk on sheep and goat farms, but considerable differences between the serotypes exist. Infections with serotype Abortusovis are responsible for large economic losses, but carry little health hazards for humans. However, several other serotypes such as Typhimurium can cause similar clinical disease in ewes, with potentially important implications for human health. Good hygiene practices and personal protective clothing are crucial to prevent occupational infections, especially during lambing or obstetrical intervention. Secondary transmissions to family members after occupational exposure have also been documented, reinforcing the importance of good hygiene practices on farms to reduce the human health risk \[[@B73]\]. Animals with clinical signs of gastro-intestinal disease or septicemia may pose the highest risk for humans, but asymptomatic shedding at relatively high prevalence has been documented at slaughter, indicating that clinically healthy animals may also pose a considerable risk. Salmonellacarriage among healthy animals on farms appears to be relatively rare, but environmental contamination likely contributes to the infection risk. In conclusion, contacts with small ruminants pose a potential health risk to occupationally exposed subpopulations as well as the general public, but the risk depends strongly on the serotype involved. 3.4. Salmonellaand pigs ------------------------- ### 3.4.1. The clinical and economic importance of Salmonellainfections among pigs A variety of clinical manifestations have been observed in Salmonellainfected pigs, ranging from asymptomatic to peracute disease. Infections with generalist serotypes such as Typhimurium usually cause mild or no disease, and infected animals may shed Salmonellafor considerable periods of time. For instance, piglets experimentally inoculated with SalmonellaTyphimurium developed mild gastro-intestinal disease and were found to shed bacteria in their feces for several days \[[@B98]\]; however, systemic disease and mortality associated with broad host-range serotypes has also been reported \[[@B99]\]. In contrast, infection with host adapted serotype Choleraesuis generally causes severe systemic disease with high mortality (see \[[@B99]\] for a recent review). All age groups are susceptible to Salmonellainfection, but disease is most commonly observed among weaned pigs more than eight weeks of age, and asymptomatic carriers are thought to represent the most important source of Salmonellaintroduction onto pig farms. A variety of clinical manifestations have been documented among Salmonella-infected pigs, including enteritis, septicemia, pneumonia, meningitis, and arthritis. Fever, diarrhea, inappetence, depression, respiratory distress, lameness, edema, and hypoxia in the extremities are common symptoms in clinically sick pigs, and mortality rates in such instances are high. Schofield \[[@B100]\], for instance, reported salmonellosis outbreaks among pigs manifested as ataxia, fever, depression, diarrhea, and necrotic enteritis, which resulted in approx. 17% mortality. Salmonellaprevalence estimates for pig farms seem to differ considerably by production and management type, with average between-herd estimates in the USA equaling 53% in 2006 and exceeding 80% for some farrow-to-finish production systems, while within-herd estimates range from 3.5 to 28% \[[@B58]-[@B63]\]. High Salmonellaprevalence on pig breeding farms and considerably lower prevalence on replacement gilt development farms have been described in one study \[[@B58]\]. However, another study reported high prevalence among replacement gilts and finishing gilts, suggesting variability between herds and studies \[[@B60]\]. Surprisingly, Davies et al. \[[@B101]\] reported a higher Salmonellaprevalence in all-in-all-out than continuous flow management systems, and distinct Salmonellaserotype populations in breeding herds, nursery and finishing herds from the same farrow-to-finish system have been reported \[[@B101]\]. Breeding herds or nurseries therefore seem to represent epidemiologically relatively unimportant sources of infection in finishing herds, and environmental contamination may play an important role in maintaining endemic infections. In fact, Dahl et al. \[[@B102]\] demonstrated that Salmonellafree finishing herds can be produced from endemically infected herds if pigs are strategically moved to clean stalls as they move through the farrow-to-finish system. Reducing the prevalence of Salmonellais particularly important because Salmonellaprevalence at slaughter tends to be considerably higher than on farm \[[@B64]\]. Indeed, one study reported 7-fold higher Salmonellaprevalence in pigs sampled at the abattoir than in animals from the same herds sampled on farm, indicating an important effect of stress or other transportation-related factors \[[@B103]\]. In addition to host adapted serotype Choleraesuis, serotypes Typhimurium, Derby, Agona and Anatum are frequently isolated from sick and clinically healthy pigs, indicating a potential risk for human health (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### *Distribution of the 20 most common human Salmonellaserotypes\[[@B7]\]among animals, based on US data from 2006. SalmonellaTyphi was excluded from this analysis as it represents a host-restricted serotype adapted to humans and non-human primates. ::: ![](1297-9716-42-34-1) ::: #### 3.1.4.2. The human public health importance of Salmonellainfections among pigs On few occasions, likely zoonotic transmissions of Salmonellafrom pigs to humans have been described (Table [1](#T1){ref-type="table"}). For instance, in 2005, a Typhimurium outbreak among humans in Wisconsin was linked to indirect pig contact in a public setting \[[@B34]\]. Similarly, in 2001 occupational exposure to pigs likely led to human infection, even though in this case the possibility of a transmission from calves could not be conclusively eliminated \[[@B36]\]. In conclusion, Salmonellarepresents an occupational hazard for those working with pigs, especially since asymptomatic carriage of broad host-range serotypes appears to be relatively common. Environmental reservoirs appear to play an important role in maintaining endemic infections, and contaminated clothing has been implicated in the transmission of Salmonellafrom pigs or calves to the son of a farmer, indicating the paramount importance of good hygiene practices \[[@B36]\]. Stress probably represents a major reason for the increased Salmonellaprevalence among pigs at slaughter relative to that observed on farms, and a similarly increased prevalence of shedding during exhibitions or at other public venues appears likely. Contact with pigs on farms, at the slaughterhouse, or in the scope of public exhibitions therefore likely represents a risk to occupationally exposed population subgroups and the general population. 3.2. Companion animals and Salmonella* --------------------------------------- ### 3.2.1. The changing role of companion animals in the 20^th^century The keeping of animals as pets has a long tradition, but historically, companion animals were foremost held for labor \[[@B104],[@B105]\]. Dogs served as guard dogs, hunting companions, or were used for herding, while cats were kept to catch rodents. Dogs and cats were rarely kept in homes, even pet animals \[[@B104]\]. During the 19^th^century engine-powered machines replaced horses as sources of labor. Simultaneously, the public\'s attitude towards animals changed, manifested in the foundation of animal welfare organizations such as the British Royal Society for the Prevention of Cruelty to Animals (RSPCA) in 1824 \[[@B104],[@B105]\]. The number of pet animals held for companionship increased drastically after World War II \[[@B104]\]. Currently, an estimated 63% of households in the USA own at least one pet; approximately 83.2 million households own dogs or cats, and roughly 4.3 million households own horses \[[@B106]\]. Similarly, in the United Kingdom, an estimated 26% of households own cats and 31% of households own dogs, amounting to approximately 10.3 million cats and 10.5 million dogs \[[@B85]\]. Today, dogs and cats primarily live indoors, share living spaces with their owners, and assume integral roles as companions, family members, or service animals \[[@B104],[@B107]\]. In one recent survey 95% of USA dog owners reported petting their animals, 67% reported playing with them, and 30% reported sharing their beds with their dogs \[[@B108]\]. Companion animals are also increasingly used in therapeutic settings, for instance in psychotherapy, or to support AIDS patients, children with disabilities, orthopedic and cardiac patients, Alzheimer patients, or the elderly \[[@B109]-[@B114]\]. The potential risks associated with such contacts, particularly for young children or immune-compromised patients, are difficult to quantify. In some parts of the world, companion animals still fulfill functional roles as source of food or labor, and may be allowed to roam around freely \[[@B115]\]. ### 3.2.2. Salmonellainfections in horses and humans #### 3.2.2.1. The clinical and economic importance of Salmonellainfections among horses Salmonellosis is an important disease of horses. Equine mortality rates vary depending on host age, predisposing factors and potentially the Salmonellaserotype involved \[[@B116]\]. Mortalities as high as 40 to 60% have been reported, but in general, mortality appears to be considerably lower \[[@B117],[@B118]\]. In most cases, animals present with profuse, watery and malodorous diarrhea, frequently associated with abdominal pain and endotoxemia. Fever, dehydration and depression are common, and in severe cases these symptoms are accompanied by colic, gastric reflux, cardiovascular shock or coagulopathies. However, the severity of disease can vary considerably and, in animals of the same age group, may range from severe to asymptomatic \[[@B119]\]. Both peracute and chronic forms of disease are common, and convalescent carriers may shed Salmonellafor months, but a carrier state does not appear to develop in all instances \[[@B118],[@B120],[@B121]\]. Disease may also manifest without gastrointestinal signs. Some serotypes appear to result more frequently in systemic disease than others, but the underlying mechanisms are still incompletely understood \[[@B122]\]. Respiratory forms are comparably frequent, and systemic forms of infection are commonly associated with arthritis, osteomyelitis, or soft-tissue abscesses \[[@B123],[@B124]\]. Foals, pregnant mares, and immune compromised horses are at a heightened risk of infection and, among foals, Salmonella-associated meningoencephalitis has been described \[[@B125],[@B126]\]. Abortions due to Salmonellacause important economic losses on stud farms \[[@B127]-[@B129]\]. Numerous studies have focused on horses in equine hospitals, with apparent prevalence estimates ranging from 1.8 to 18%; Anderson and Lee, however, report isolating Salmonellafrom 26.6% of slaughter horses \[[@B125],[@B130]-[@B135]\]. The prevalence among healthy horses on farms or in riding schools appears to be considerably lower, in the range of 1 to 2% \[[@B117],[@B131],[@B135],[@B136]\]. Asymptomatic carriers shed Salmonellaintermittently. Increased shedding has been associated with antibiotic treatment and stressful situations such as transportation, horse competitions, co-morbid disease, or surgery \[[@B125],[@B133],[@B137]-[@B140]\]. High population density is thought to be another predisposing factor. The epidemiological significance of environmental contamination remains difficult to assess, but good environmental hygiene practices have been efficient in controlling hospital outbreaks \[[@B132],[@B141]-[@B143]\]. Numerous serotypes have been isolated from clinically healthy or sick horses, and a considerable number of outbreaks involving a variety of medically important serotypes have occurred in large animal hospitals (Table [1](#T1){ref-type="table"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). #### 3.2.2.2. The public health importance of Salmonellainfection among horses Zoonotic transmission in large animal veterinary hospitals and private veterinary clinics is thought to occur frequently, even though only a small number of human cases associated with such transmissions have been documented (Table [1](#T1){ref-type="table"}) \[[@B144],[@B145]\]. Salmonellatransmission to humans at a state fair has also been reported (Table [1](#T1){ref-type="table"}) \[[@B34]\]. In conclusion, horse contacts clearly represent a risk to humans. However, clinically healthy horses in riding schools or on farms, especially if held under optimal conditions, seem to pose a comparably low risk. The risk at competitions, state fairs or other public venues might be considerably higher due to increased stress, whereas pregnant mares, foals and hospitalized horses clearly represent a high risk. Salmonella-infected horses often present with no or atypical clinical symptoms, emphasizing the need for strict quarantine, environmental contamination control, and good hygiene practices. Due to the high Salmonellaprevalence, high risk population subgroups may choose to refrain from entering equine hospitals or stud farms, or take particular precautionary measures. ### 3.2.3. Salmonellainfections in dogs, cats and humans #### 3.2.3.1. The veterinary importance of Salmonellainfections among dogs and cats A considerable number of Salmonellaserotypes have been isolated from domestic dogs and cats around the world (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). The majority of infections are asymptomatic \[[@B146]\]. However, gastrointestinal disease manifested as enterocolitis and endotoxemia can occur and is often associated with fever, vomiting, anorexia, dehydration and depression \[[@B147]-[@B149]\]. Abortion, stillbirth, meningoencephalitis, respiratory distress and conjunctivitis have also been described \[[@B150],[@B151]\]. Salmonellaprevalence among dogs and cats appears variable and probably depends on a variety of factors. One study analyzed the apparent Salmonellaprevalence among greyhounds on race tracks and found 43.5% of dogs were shedders, while another study described the apparent prevalence among racing Alaskan sled dogs at approx. 60%, and the prevalence among stray dogs is likely equally high \[[@B147],[@B152]-[@B154]\]. In general, however, the rate of shedding is thought to be much lower, and a number of studies on non-racing client-owned dogs and client-owned cats report shedding rates in the range of 1-5% \[[@B155]-[@B160]\]. Ingestion of contaminated food is thought to be the predominant risk factor. Salmonellahas been isolated at high frequency from raw dog food on greyhound race tracks, and asymptomatic carriers developed after experimental oral inoculation, with shedding observed for periods of up to four weeks \[[@B161],[@B162]\]. Dogs fed raw food diets appear to be at particular risk. Finley et al. \[[@B163]\] report that, in the absence of clinical signs, 50% of dogs fed contaminated raw food diets shed Salmonellain their feces, while none of the control dogs fed Salmonella-free diets shed Salmonella. In another, longitudinal study, Joffe et al. \[[@B164]\] isolated Salmonellaat least once from the feces of 80% of client-owned dogs fed a common bone and raw food (BARF) diet. Surprisingly, Salmonellawas also isolated on one or more occasions from 30% of client-owned controls, which were fed commercial dog food. Some serotypes such as SalmonellaTyphimurium, Heidelberg, and Kentucky appear to be predominantly isolated from dogs fed raw food diet, and one study estimated the odds of shedding Salmonellato be approx. 23 times greater for dogs fed raw food diets than commercial diets \[[@B165]\]. Asymptomatic carriers shed Salmonellaintermittently, and longitudinal studies provide evidence for multiple coinfections during relatively short time periods \[[@B166]\]. #### 3.2.3.2. The public health risk associated with Salmonellainfection among dogs and cats A number of medically important serotypes for humans have been isolated from domestic dogs and cats (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1), and several studies have reported the isolation of multidrug-resistant isolates (see \[[@B167]\] for a comprehensive review of the topic). Human Salmonellacases have been attributed to contact with infected dogs or cats at home or in veterinary clinics (Table [1](#T1){ref-type="table"}). For instance, in 1938 the family dog was implicated as source of a human SalmonellaGlostrup outbreak and in 1952 a human case of Paratyphi B was linked to direct dog contacts at home. In 1999 human outbreaks of SalmonellaTyphimurium in Idaho and Washington were linked to contact with clinically ill kittens in veterinary clinics, and a human outbreak in Minnesota was linked to contact with cats from a shelter. A 2003 outbreak of SalmonellaTyphimurium among humans in New York was also linked to a small animal veterinary clinic, but the index animal was not clearly identified. A recent case-control study of childhood salmonellosis in Michigan identified cat exposure, as well as reptile contacts, as risk factor for Salmonellainfection, emphasizing the potential risk \[[@B168]\]. The risk posed to humans by indirect contact, for instance with excrement, is currently not clear. Infected humans also represent a possible source of infection for their animals. In addition, animal-to-animal spread occurs readily and has been clearly documented during a Salmonellaoutbreak in a military dog kennel \[[@B169]\]. In this instance, the index case acquired Salmonellathrough feed. Together, these data indicate that contacts with dogs and cats in homes, veterinary clinics and shelters clearly represent potential threats to human health. Raw food diets are associated with a significantly higher prevalence of Salmonellathan other pet food diets, and since asymptomatic shedding is common it appears that animals on such diets might be suspected of Salmonellashedding regardless of clinical symptoms. Especially if some household members are at a heightened risk of infection, or if animals are introduce into therapeutic settings, other feed types may be preferable. Salmonellarepresents a clear occupational hazard. Good hygiene practices, environmental infection control, strict quarantine procedures, personal protective equipment, and other biosecurity measures are therefore crucial to reduce the risk wherever dogs or cats are kept in large groups or subjected to high levels of stress. ### 3.2.4. Commercial pet food and treats as sources of infection Salmonellacontamination in pet foods and treats varies considerably by food type. Commercial raw food diets, representing combinations of raw meat, vegetables, grain and eggs or fruit, are available fresh or frozen in a large number of pet stores and veterinary clinics, and a recent Canadian study estimated Salmonellaprevalence in these feeds to equal approx. 21% \[[@B170]\]. Several Salmonella-related recalls of raw foods have been reported in recent years, for instance of frozen cat food in the USA in 2007. Contamination rates in dry or canned foods are thought to be considerably lower, and to our knowledge Salmonellahas not been isolated from canned dog food, but the number of available studies is very limited \[[@B8],[@B9]\]. Dry dog food has recently been linked to a large human salmonellosis outbreak, and dog and cat vitamins have been recalled due to Salmonellacontamination, but prevalence data is currently scarce \[[@B9],[@B171]\]. Dried pigs ears and a variety of other dried animal parts are commercially available as dog treats. Contamination rates in these commodities appear to be high. For instance, in 2001 a Canadian study reported isolating Salmonellafrom 50% of pig ears and other animal-derived pet treats, and a 2003 study found 41% of animal derived pet treats sold commercially in the USA contaminated with Salmonella\[[@B172],[@B173]\]. Isolates included SalmonellaTyphimurium, Heidelberg, Anatum, Infantis, and Derby, and a considerable number of samples contained more than one serotype (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Voluntary preventive measures implemented by the pet treat industry appear to have led to a considerable reduction in contamination rates, but a disease risk remains \[[@B174]\]. For instance, in December 2009, pig ears and beef hoof products were recalled in the USA because of a potential Salmonellacontamination. Exposure to commercial pet food and animal derived pet treats has also repeatedly led to human outbreaks (Table [1](#T1){ref-type="table"}). For instance, in 2007 the CDC identified a multi-state outbreak of SalmonellaSchwarzengrund linked to commercial dry pet foods, which affected dogs and their owners in 18 states of the USA and led to a nation-wide product recall. In 1999, pig ear treats contaminated with SalmonellaInfantis led to a human outbreak of salmonellosis in Canada, and in 2002, pet treats contaminated with SalmonellaNewport were responsible for human Salmonellainfections in Canada. Salmonellaoutbreaks among humans have also been linked to rodents commercially sold as pet food, but these are more appropriately described in the section regarding rodents. In conclusion, pet feeds represent a direct and indirect threat to human and animal health. The choice of pet food and treats can considerably influence the Salmonellarisk for animals and humans, and might be of particular importance if high-risk human population subgroups are exposed at home or in therapy settings, or if animals are exposed to stressful situation such as in kennels, veterinary clinics or shelters. However, good hygiene practices such as hand washing before and after feeding, appropriate cleaning of bowls and contact surfaces, and adequate storage can probably decrease the direct risk for humans considerably. 3.3. Rodents, rabbits and Salmonella -------------------------------------- ### 3.3.1. The clinical and environmental importance of Salmonellainfections among rodents and rabbits Salmonellahas repeatedly been isolated from wild mice and rats, which represent important reservoir hosts on farms and in food production environments (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Prevalence estimates for wild or captive rodents are relatively scarce, variable among geographic regions, and the numbers of studies as well as the prevalence seem to have decreased over time. In general, Salmonellashedding rate estimates are in the range of 1 to 15% \[[@B175]-[@B179]\]. Salmonellaprevalence among captive rodents is low, and environmental reservoirs may play a paramount epidemiologic role \[[@B180]\]. Salmonellahas also been isolated from pet rabbits, indicating a potential risk associated with this animal species \[[@B181]\]. However, the available prevalence data, especially for pet rabbits, is currently very scarce. Salmonellamight to be fairly common in intensive rabbit meat production systems, with one study reporting that as many as 30% of intensive rabbit farms in Italy were positive for Salmonella\[[@B182]\]. However, a low prevalence of Salmonellaamong rabbit carcasses in Spanish slaughterhouses has also been reported, indicating that Salmonellaprevalence among commercially farmed rabbits is probably variable \[[@B183]\]. Salmonellainfection can cause severe disease in rabbits, which is sometimes associated with high mortality \[[@B182]\]. Clinical symptoms include enteritis, metritis and abortion, but striking differences in pathogenic potential seem to exist among different Salmonellaserotypes \[[@B182]\]. In contrast, the majority of infections in mice and rats are asymptomatic. However, clinical disease among rodents has also been described, for instance during large outbreaks among laboratory rodents, which were associated with high mortality rates (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Indeed, SalmonellaTyphimurium and Enteritidis have been widely used as rodenticide in the first half of the 20^th^century and continue to be used in some countries despite the public health risk \[[@B184],[@B185]\]. Systemic disease appears to be the most common clinical manifestation in mice and rats, and mortality is predominantly attributable to septicemia \[[@B186]\]. Pathogenicity is age and host strain dependent, with the highest mortality rates observed in young animals under three weeks of age \[[@B187]\]. A number of serotypes with importance for humans have been isolated from wild, laboratory or pet rodents (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Clinical Salmonellaoutbreaks among guinea pigs and hamsters, associated with conjunctivitis and soft tissue abscesses, have also been described \[[@B188],[@B189]\]. ### 3.3.2. The public health importance of Salmonellainfection among rodents and rabbits In recent years, human outbreaks have repeatedly been associated with captive rodents sold in the USA as snake feed or pets (Table [1](#T1){ref-type="table"}). For instance, in 2004 a large multi-state outbreak of SalmonellaTyphimurium among humans was associated with hamsters, rats and mice sold in pet shops across the USA. Similarly, in 2005 and 2006, a multi-state outbreak of SalmonellaTyphimurium among humans was linked to frozen rodents sold as commercial snake feed. Sporadic human cases have also been linked to rodent contact, for instance a human case of SalmonellaOranienburg attributable to contact with a clinically sick guinea pig. In conclusion, rodent contacts represent a direct and indirect threat to human health. Wild rodents can serve as source of human infection by contaminating feeds, food, water or the environment, and they can conceivably infect dogs, cats or other animals if ingested. Salmonellosis represents an occupational hazard for exterminators, rodent breeders, and others that professionally handle rodents. Rodents often show no or atypical signs of salmonellosis, thus clinical symptoms in animals are of limited diagnostic value. To our knowledge, data on zoonotic transmissions from rabbits is not available at the point of writing, likely at least in part due to underreporting of human salmonellosis cases. Contacts with sick or clinically healthy rodents or rabbits can potentially lead to human exposures, and the enforcement of good hygiene practices is important to minimize the risk for humans. 3.4. The role of non-traditional mammalian pets and wildlife ------------------------------------------------------------ Non-traditional pets are captive-bred or wild-caught, endogenous or exotic animals held as pets that have not reached wide-spread popularity among pet owners and are therefore not commonly bred for human companionship \[[@B190]\]. Apart from reptiles, amphibians, and fish, non-traditional pets include a variety of mammalian species such as non-human primates, African pygmy hedgehogs, ferrets, prairie dogs, and sugar gliders \[[@B190],[@B191]\]. Lack of husbandry expertise often results in stress, malnutrition or abandonment, and bites or scratches pose a considerable risk to pet owners \[[@B191]\]. ### 3.4.1. Exotic pets, wildlife and Salmonella Little is known about the prevalence, pathogenicity, and distribution of Salmonellaamong non-traditional mammalian pets or their wild relatives, but Salmonellahas been isolated from a large number of wild mammals or their feces, including opossums, squirrels, woodchucks, raccoons, foxes, mink, cougars, tigers, wild boars, hippopotami, rhinoceroses, seals and whales (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Serotypes with particular importance for human health have also been isolated from white-tailed deer feces in Nebraska, even though Salmonellaprevalence in this species is believed to be quite low (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). One Norwegian study of Salmonellain feral hedgehogs reported prevalence estimates between 0 and 41%, which varied considerably by geographic area \[[@B192]\]. High prevalence corresponded to human outbreaks in the same region, and isolates with identical PFGE patterns were isolated from wild hedgehogs and humans, potentially indicating an epidemiological link, which is also supported by an independent Danish study \[[@B193]\]. Salmonellaprevalence among captive hedgehogs, sugar gliders and other non-traditional pets is currently unknown. Clinical disease associated with Salmonellainfection has been described in sugar gliders and hedgehogs, but a large number of cases are believed to be asymptomatic \[[@B194],[@B195]\]. Several human cases and outbreaks of serotypes Typhimurium and Tielene have been linked to pet hedgehog contacts (Table [1](#T1){ref-type="table"}), and SalmonellaEnteritidis and Sofia have also been isolated from hedgehogs kept as pets (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). SalmonellaTielene represents a very rare serotype. Human cases are strongly associated with hedgehog exposure, and children appear to be at heightened risk of infection \[[@B195]\]. SalmonellaTielene was first isolated in the USA in 1994 during a human outbreak associated with an African pygmy hedgehog breeding colony \[[@B195]\]. In Canada the geographic distribution of human Tielene cases starkly resembles that of pet hedgehogs, emphasizing the epidemiological role of this pet species \[[@B196]\]. Human Tielene outbreaks have also been linked to sugar glider exposure, indicating a role of this exotic pet in SalmonellaTielene epidemiology \[[@B196]\]. In conclusion, wildlife and exotic pets clearly represent potential sources of human infection, but relevant data is so far scarce. Salmonellacan cause disease in these animals, but asymptomatic carriers appear to be common and likely also pose a considerable infection risk. Good hygiene practices and measures that reduce stress, such as adequate housing, nutrition and care, can likely reduce the risks associated with captive animals. 4. Avian Sources of Human Salmonellosis ======================================= 4.1. Overview of Salmonellainfections in birds ------------------------------------------------ World-wide, birds are held for meat or egg production, companionship, sports, scientific or educational purposes. In 2007, an estimated 17.9 billion chickens, 1.1 billion ducks, 447 million turkeys and 343 million geese and guinea fowl were farmed world-wide \[[@B39]\]. Of these, approx. 9.4 billion chickens, 997 million ducks, 14 million turkeys and 307 million geese were farmed in Asia alone. In addition, a considerable number of animals are held as pets, with 6.4 million households in the USA alone owning pet birds \[[@B106]\]. 4.2. Salmonellainfections among galliform birds ------------------------------------------------- Chickens, turkeys, quails, pheasants and other gamebirds are members of the order galliformes. Salmonellais common in galliform birds, and has been isolated at high rates from commercially reared chicken, turkeys, and other poultry (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Apart from the associated foodborne risk, farms may represent a direct risk to public health, even though relevant studies are so far missing and high biosecurity standards in most commercial poultry productions probably minimize the risk. The clinical symptoms associated with Salmonellainfection vary considerably by age group and serotype \[[@B197]\]. Infections with generalist serotypes rarely cause clinical disease in galliform birds and most animals become asymptomatic carriers, even though severe clinical disease with high mortality has been observed in some instances, particularly during infections of young birds \[[@B198],[@B199]\]. Infections with the host adapted serotype Gallinarum biovars Gallinarum and Pullorum, however, cause severe disease with high mortality and immense economic losses on chicken and turkey farms (see \[[@B200]\] for a review of the topic). SalmonellaGallinarum biovar Pullorum causes \"Pullorum disease\" in young animals, which is associated with septicemia and high mortality that can exceed 85% in some instances \[[@B197]\]. SalmonellaGallinarum biovar Pullorum infections of adult birds are generally mild or asymptomatic, even though decreases in fertility and egg production as well as increased mortality have been observed in some instances. Adult animals can develop a carrier state, and transovarian transmission is thought to be the primary rout of transmission to young birds, even though rodents and other vectors are also thought to play an important epidemiologic role (see for instance \[[@B201]\]). Clinical symptoms include anorexia, diarrhea, dehydration, decreased hatching, and high mortality. SalmonellaGallinarum biovar Gallinarum causes \"fowl typhoid\" in young and particularly adult birds \[[@B200]\]. Clinical symptoms are very similar to those observed during infections with biovar Pullorum, and economic losses during outbreaks can be very high. Both Gallinarum biovars Gallinarum and Pullorum are host restricted and therefore pose a negligible risk to human health. In contrast, infections with SalmonellaEnteritidis are typically asymptomatic in adult birds but can cause systemic disease in young birds, and transovarian transmission of serotype Enteritidis has also been described \[[@B202]\]. Infections with SalmonellaEnteritidis pose a considerable human health risk, and have been estimated to inflict costs of approx. 1 billion US dollar per year on the USA economy \[[@B203]\]. Salmonellaprevalence varies considerably by poultry type, differs between serotypes and biovars, and intestinal carriage often appears to be lower than isolation rates from egg shells, dead birds, and environmental samples \[[@B204],[@B205]\]. Salmonellaprevalence in hatcheries is estimated between 0 and 17% for chickens, compared to approx. 25% for geese, and 20-60% for ducks \[[@B204],[@B205]\]. SalmonellaGallinarum biovars Pullorum and Gallinarum have been eradicated in commercial poultry productions in the developed world, but are still important in backyard flocks as well as the developing world \[[@B197]\]. It is conceivable that serotype Enteritidis filled the ecologic niche left by the eradication of serotype Gallinarum biovar Gallinarum, since a considerable increase in Enteritidis prevalence co-incided with the eradication of biovar Gallinarum in the 1960s (see \[[@B206]\] for a review of the subject). In fact, mathematical modeling results have suggested a potential role of competitive exclusion between serotypes Enteritidis and Gallinarum biovar Gallinarum in poultry \[[@B207]\]. SalmonellaEnteritidis, as well as serotypes Typhimurium, Kentucky, and Heidelberg, are commonly detected among clinically healthy as well as sick chickens and turkeys, indicating a potentially important risk for human health (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). A number of people raise chickens and other poultry in their backyards for meat, egg production or as pets \[[@B208]\]. In addition to household exposure, human cases have been linked to poultry contact on farms, in agricultural feed stores, and at country fairs \[[@B209]\]. Young hatchlings pose a particularly high risk for humans, and remarkably often infect children (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). The number of human outbreaks increases strikingly around Easter, when chicken or duck hatchlings are especially popular pets. Such outbreaks have been documented every few years since the 1950s (see for example \[[@B209]-[@B211]\]). To reduce the risk associated with hobby farming, the sale of poultry for meat or egg production at feed stores is prohibited in all USA states \[[@B212]\]. In addition, the USA CDC and some state health departments work to increase public awareness and to promote customer education at the store level. Some USA states have passed additional regulations, such as legislations restricting the minimum age of animals at sale or the maximum number of animals purchased per person \[[@B212]\]. However, enforcement of these laws is difficult and legislation varies among states \[[@B213]\]. The USA CDC has published recommendations regarding pet poultry, including that no children under the age of 5 handle baby poultry \[[@B214]\]. In conclusion, the human health hazards posed by pet poultry, and young hatchlings in particular, are substantial, but fairly well understood. The laws and recommendations provided by the USA CDC and comparable institutions can successfully mitigate the risks. However, public awareness and collaboration between governmental agencies, related industries, special interest groups, and the veterinary community is crucial to assure sustainable results. The risks of direct transmission to humans that are associated with commercial poultry productions are less well understood. Salmonellacertainly poses an occupational risk to farmers, veterinarians and slaughterhouse employees, but whether commercial poultry farming poses direct risks to the general population remains yet to be determined. 4.3. Salmonellainfections among anseriform birds -------------------------------------------------- Ducks, geese and swans belong to the order Anseriformes. The majority of Salmonellainfections in ducks appear to be asymptomatic, but severe clinical disease with high mortality has also been described \[[@B215]\]. Clinical disease is predominantly observed in young animals, and seems to generally be associated with environmental or management stressors. Common symptoms include anorexia, depression, diarrhea, dehydration, ataxia, opistothotonus, arthritis, and synoviatis, and decreases in fertility and hatching have also been reported \[[@B215]\]. The prevalence of Salmonellashedding appears to be species and age group dependent. Salmonellashedding is comparably common among commercially raised ducks and geese, yet highly variable across age groups. SalmonellaTyphimurium, for instance, has been isolated from 40% of hatchlings and 1% of older ducklings in Taiwan, even though clear host species specific differences were also detected \[[@B216]\]. The prevalence of Salmonellashedding among wild birds appears to be quite variable (see for instance \[[@B217]\] for a review). Mitchell and Ridgwell, for instance, reported isolating Salmonellafrom approx. 4% of bird droppings in London \[[@B218]\]. Conversely, Cizec et al. reported isolating Salmonellafrom 19% of wild gulls sampled in the Czech Republic \[[@B219]\]. However, lower prevalence estimates among gulls have also been reported in the literature, in the range of 3-13%, and considerable differences between bird species and age groups seem to exist \[[@B219]-[@B221]\]. A number of human outbreaks have been linked to duckling exposure, and often both ducklings and chicken hatchlings are involved in the same outbreak, indicating great similarities in transmission and epidemiology (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). Analogous to chicken farms, it remains yet to be determined whether commercial duck and geese farms represent a substantial direct risk to human health. Similarly, the potential role of wild ducks and geese for human health is still subject to debate and conclusive evidence for or against an important role has yet to be presented (see \[[@B217]\] for a review of the subject). In conclusion, the risk associated with pet ducklings is high, but relatively well understood and bears great similarities to that observed for young chicken. Commercially reared or wild anseriform birds might conceivably pose a substantial risk to human health, but more data is needed before the subject can be evaluated conclusively. 4.4. Salmonellainfections among columbiform birds --------------------------------------------------- Doves and pigeons belong to the order of columbiform birds. Upon Salmonellainfection, most adult birds show no or mild signs of disease, but severe paratyphoid disease with high mortality has been reported among young birds \[[@B222]\]. Clinical manifestations are variable and include gastro-enteritis, growth retardation, anorexia, depression, fever, torticollis, opisthotonos, oophoritis or orchitis, arthrosynovitis, and abscesses. While a variety of serotypes have been isolated from pigeons and doves, SalmonellaTyphimurium var. Copenhagen phage types 2 and 99 are the most commonly isolated subtypes \[[@B223]\]. Intriguingly, the Typhimurium isolates from pigeons differ biochemically and antigenically from other Typhimurium isolates, likely indicating host adaptation of these Typhimurium subtypes to pigeons \[[@B217],[@B222],[@B223]\]. Salmonellaappears to be a relatively common pathogen among pigeons and doves, but the prevalence seems to differ by serotype and habitat (see \[[@B217]\] for a review of the subject). Petersen \[[@B224]\], for instance, compared Salmonellaprevalence in wild pigeons from urban areas and dairy farms in Colorado, and detected Salmonellain approx. 8% of samples from dairy-exposed pigeons but not in samples from pigeons in urban areas. However, the isolation of various Salmonellaserotypes from wild pigeons in urban areas in Japan has also been reported, indicating a potential risk for human health \[[@B225]\]. Endemic infections among domestic pigeons in lofts have been described, and prevalence estimates of 25-30% within individual lofts have been reported \[[@B217]\]. SalmonellaTyphimurium var. Copenhagen phage types 2 and 99 seem to be the predominant serotypes among domestic pigeons, but other serotypes have also been isolated \[[@B217]\]. In conclusion, Salmonellaappears to be relatively common among pigeons. However, most infections seem to be due to host adapted subtypes of Typhimurium, and therefore likely only pose a limited risk to humans. In fact, to our knowledge, no zoonotic transmission from pigeons to humans has been documented in the literature, even though underreporting of human cases likely contributed to this lack of observation. Salmonellacan also be found in wild doves, probably mostly at low prevalence. Broad-spectrum serotypes have been isolated from wild pigeons and environmental contamination appears to represent an important risk factor for shedding in doves and pigeons, indicating that such birds may represent potentially important vectors on livestock premises and possibly carry some direct risk for humans. 4.5. Salmonellainfections among passerine birds, psittacine birds, and other non-domesticated birds ----------------------------------------------------------------------------------------------------- Passerine birds are commonly referred to as songbirds, while psittacine birds include parrots, cockatoos and parakeets. Both passerine and psittacine species are not only important wild bird species, but also represent popular pets and are often kept in zoological exhibits. Numerous Salmonellaserotypes have been isolated from a variety of captive birds held as pets (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Acute and chronic infections have been reported, which range from asymptomatic to clinically severe and can manifest as diarrhea, anorexia, dehydration, depression, crop stasis, septicemia or osteomyelitis \[[@B226]-[@B228]\]. For instance, Salmonellahas been isolated from pet shop and household birds in Trinidad, imported finches, lories and parakeets in Japan, a variety of captive birds imported into Britain, numerous psittacine species held in Brazil, psittacine pet birds in Texas, Tennessee and Kansas, and captive as well as free-ranging parrots in Bolivia (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Salmonellaoutbreaks with high bird mortalities have been described in zoologic exhibits, captive bird colonies and falcon collections \[[@B229]-[@B231]\]. Captive birds can also pose a Salmonellarisk to humans, even though only a very limited number of cases have been documented (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). For instance, parakeets were involved in the transmission of SalmonellaTyphimurium to a human infant and a cat, even though the exact transmission routes were not clearly determined \[[@B232]\]. Asymptomatic Salmonellacarriage in wild birds is thought to be high, and wild birds have repeatedly been implicated as vehicles on farms and in feed mills \[[@B233]-[@B236]\]. Around the world, a variety of serotypes, including those frequently isolated from humans, have been isolated from free-ranging songbirds, parrots and parakees, with clinical manifestations ranging from asymptomatic to peracute death (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Stress increases the risk of shedding, and in songbirds salmonellosis commonly peaks in winter months, likely due to crowding and increased contact rates at bird feeders \[[@B237]\]. Salmonellaprevalence among birds at feeders is commonly higher than in the general population, and epidemics have been reported repeatedly, for example during the winter of 1997/98, when an epidemic affected songbirds across the eastern parts of North America \[[@B237]-[@B239]\]. Wild songbirds have also been repeatedly implicated as source of human infection (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). For instance, during the winter of 2000, Typhimurium isolates with identical Pulsed Field Gel Electrophoresis (PFGE) patterns were associated with a Salmonellaoutbreak among wild birds as well as human cases in New Zealand, and an epidemiologic link, potentially due to contaminated water, appears plausible \[[@B239],[@B240]\]. Evidence also suggests that a large number of human Typhimurium cases in Norway were associated with wild bird contacts \[[@B241]\]. Other non-domesticated birds also potentially pose a risk to human health. In 2001 an elementary school Typhimurium outbreak involving at least 40 human cases was linked to dissecting owl pellets collected from captive owls, and more recently another outbreak in Massachusetts was also linked to owl pellets \[[@B242]\]. In conclusion, contacts with wild or captive birds pose a possible threat to human health, even though many epidemiological details remain to be understood. Birds, bird droppings, pellets, and feathers, as well as contaminated water and environments represent a potential risk. 5. Reptiles, Amphibians and Fish as Sources of Human Infection ============================================================== Contact with reptiles, amphibians or pet fish also represents an important source of Salmonellainfection (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptiles, amphibians and fish have become popular pets in many countries. For example, approx. 3% of households in the USA own one or more reptiles as pets, resulting in a total of approx. 7.3 million reptiles \[[@B106]\]. The number of pet turtles has doubled in recent years, and in the USA approx. 2 million turtles are now kept in over 1 million households. More than 400 000 USA households keep snakes and in excess of 700 000 households own lizards \[[@B106]\]. Pet fish are present in an estimated 15 million USA households, with approx. 0.8 million households owning salt water fish tanks \[[@B191]\]. An estimated 1.3 million reptiles and 203 million fish were imported legally into the USA in 2005 alone, and a considerable number of pets are imported illegally each year \[[@B191]\]. Imports include captive-bred as well as wild-caught animals and the exotic pet trade poses a potential public health threat \[[@B191]\]. 5.1. Reptiles and Salmonella ------------------------------ ### 5.1.1. Salmonellaprevalence and serotype diversity among reptiles Salmonellaoccurs naturally in the gastrointestinal tract of many reptiles, is commonly shed by these animals, and around the world a large number of serotypes have been isolated from feral and captive reptiles as well as their eggs (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Clinical disease, including septicemia, osteomyelitis, salpingitis, nephritis, dermatitis and abscesses, seems to be occasionally associated with Salmonellainfection in snakes, turtles, and lizards, but the overwhelming majority of infections in reptiles are undoubtedly asymptomatic; clinical salmonellosis in reptiles is rare, appears to be associated with underlying disease or other stressors, and a causal relationship between Salmonellainfection and disease is generally difficult to establish conclusively \[[@B243]-[@B245]\]. Whether Salmonellainfection causes diarrhea in reptiles is still subject to debate, and might depend on a variety of factors including host species and ambient temperature during infection \[[@B246],[@B247]\]. For instance, links between a case of necrotizing gastritis in a snake and Salmonellainfection or between atrophic gastritis in a tortoise and Salmonellahas been suggested, but so far reports are predominantly anecdotal (see for instance \[[@B248]\] for a review). Prevalence estimates in free-ranging reptiles vary widely, and a few studies report the absence of Salmonellain their study populations \[[@B249],[@B250]\]. Prevalence estimates in other studies range from 6 to 100% in turtles, from 30 to 76% in lizards and from 54 to 100% in snakes \[[@B251]-[@B257]\]. It has been estimated that as many as 90% of all captive reptiles carry Salmonella, including a large number of \'reptile-associated\' as well as \"broad host-range\" serotypes \[[@B196],[@B246]\]. Some studies have investigated the efficacy of antimicrobial treatments, sometimes combined with physical treatments, in reducing reptile Salmonellacarriage, and initial laboratory experiments proved promising \[[@B258]-[@B260]\]. However, the routine treatment of reptiles, eggs, or pond water on commercial farms is complicated by farming conditions, intermittent Salmonellashedding, transovarian infections, coprophagy, and environmental reservoirs, and these treatments appear to be associated with a heightened risk of antibiotic resistance \[[@B261]-[@B264]\]. Salmonellahas been isolated from commercially raised turtles, crocodiles, alligators, and iguanas, their meat, or the farm environment, and contamination levels appear to be substantial, with prevalence estimates for farmed turtles as high as 40% (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). The stress of transportation and the close physical contact during transport may further contribute to Salmonellashedding, especially among baby turtles and lizards. ### 5.1.2. The risk associated with contacts to reptiles Human salmonellosis attributable to reptile exposure was first documented in the 1940s, and a large number of case reports have since described zoonotic transmissions of Salmonellafrom reptiles to humans (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). The exact number of reptile-associated salmonellosis cases among humans is difficult to determine, but one study estimated that in the USA, reptile exposure contributes approx. 70 000 human cases each year \[[@B265]\]. This represents 6% of all sporadic human cases, and reptile-associated cases are estimated to contribute 11% of sporadic human cases in the population \< 21 years of age \[[@B265]\]. In the European Union, apparent prevalence estimates vary considerably among member states and over time \[[@B266]\]. In Sweden, for instance, 339 human reptile associated cases have been reported between 1990 and 2000, equaling approx. 5% of reported human cases \[[@B266],[@B267]\]. This number increased markedly in subsequent years until a public education campaign was launched in 1997 \[[@B267]\]. A large number of human salmonellosis cases have been linked to contact with turtles, terrapins, snakes, and lizards such as iguanas, bearded dragons, geckos, and chameleons (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptile-associated Salmonellainfections in humans tend to be more likely associated with systemic disease than foodborne infections. Especially among children, the elderly or pregnant women, septicemia, meningitis, arthritis, soft-tissue abscesses, osteomyelitis, pericarditis, myocarditis, peritonitis and urinary tract infections have been repeatedly described, leading to severe disease and comparably high mortality rates (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). However, frequently only a single person or household is affect, and many reported cases involve children and infants. The reasons for the high prevalence among infants and children are not clear and might include biological, immunological and behavioral determinants \[[@B268],[@B269]\]. Few reptile owners are aware of the disease risk. In the USA, the CDC recently reported that only approx. 20% of interviewed human cases were aware of the link between reptiles and Salmonella\[[@B269]\]. Good hand hygiene, which has been shown to be a very effective measure to prevent infection, may therefore not be strictly enforced \[[@B270]\]. Salmonellasurvives over long time periods in the environment, and a number of human outbreaks have been attributed to indirect reptile contact (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptile-associated salmonellosis occurs frequently in small children, which are rarely allowed direct contact with snakes or lizards, strongly suggesting indirect exposure routes (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). In fact, a case-control study found presence of reptiles in the home to be a highly significant risk factor for salmonellosis in infants \< 1 year of age, strongly suggesting a predominant role of indirect transmission \[[@B271],[@B272]\]. In other cases, the evidence is even more compelling. For instance, in 1996 a human Salmonellaoutbreak with at least 65 cases was linked to contact with a wooded barrier around a Komodo dragon habitat in the Colorado zoo \[[@B270]\]. In 1994, hospitalized infants were infected with SalmonellaKintambo \[[@B271]\]. One infant\'s family owned a lizard which shed Kintambo and the infant\'s mother reported diarrheal illness shortly before giving birth, potentially indicating prior infection. In 2001, SalmonellaNima was isolated from a sick infant and a boa at the school where the infant\'s father worked \[[@B273]\]. The father reported carefully washing his hands after handling the snake or its container, but frequently draped the snake around his arm and did not change his clothes before handling the infant. In 2004, SalmonellaTyphimurium was isolated from an 80 year old woman and the bowl in which her daughter\'s turtle was kept \[[@B274]\]. The women had no direct contact with the turtle or its bowl, but the bowl was cleaned in the kitchen sink. Given the large number of indirect transmissions, the USA CDC recommends that households with young children (i.e. \< 5 years of age) do not own reptiles and that reptiles are not introduced into school settings. Several organizations have published information materials and recommendations concerning pet reptiles. In the USA, these include for instance governmental organizations such as the CDC and FDA, as well as professional organizations such as the American Veterinary Medical Association, the Association of Reptile and Amphibian Veterinarians, and the National Association of State Public Health Veterinarians (NASPHV). However, despite intense efforts awareness has remained limited. Given the high prevalence of Salmonellaamong feral alligators, crocodiles, turtles, and lizards, contamination of surface water, ponds and other natural surfaces also represents a potential public health concern, but quantitative risk estimates are currently not available \[[@B275]-[@B279]\]. At least two human cases have been linked to reptile-contaminated surface water. In this instance, pet turtles were allowed to swim in a non-chlorinated in-ground pool frequented by the two human case patients \[[@B269]\]. In conclusion, direct or indirect exposures to reptiles clearly represent a substantial risk to human health. Infants and young children are at a particularly high risk, and severe clinical manifestations seem common. A considerable fraction of cases occur due to indirect contacts. Moreover, the prevalence of Salmonellashedding among captive reptiles is high, and clinical symptoms are rare. Large parts of the general population may therefore be affected. Legislative efforts have achieved substantial successes in reducing the risk of reptile-acquired infection. However, regulations have to be integrated with public education to achieve maximum compliance. Governmental agencies and several stakeholder groups work to increase consciousness. However, despite long-standing efforts, awareness of the Salmonellarisk has remained comparably low. A number of alternative exposure routes can also lead to reptile-associated infections, and should be taken into consideration as appropriate. ### 5.1.3. Salmonella -related regulations of pet turtle commerce Up to the 1970s, pet turtles represented a major source of salmonellosis in the USA, annually contributing an estimated 14 to 23% of salmonellosis cases among children \[[@B280],[@B281]\]. This prompted numerous state governments to mandate certification of Salmonellafree status for all locally sold pet turtles, and since 1972 the USA FDA required similar certifications for all pet turtles sold in interstate commerce \[[@B281]\]. When these measures proved ineffective, the FDA posed a nation-wide ban on the sale and distribution of turtle eggs and small turtles with shells less than 4 inches (10.2 cm) in diameter in 1975 \[[@B281]\]. This legislation markedly decreased the number of reptile-associated cases, and has been estimated to prevent approx. 100 000 cases of salmonellosis, predominantly among young children, each year \[[@B281]\]. However, the ban did not prevent the sale of young turtles in all cases. Turtles less than 4 inches were still allowed to be sold for scientific, educational and exhibitional purposes, for export, or for purposes other than business, and the ban did not include marine turtles. In addition, small turtles were still illegally sold in pet stores and at unregulated vendors such as flea markets, and small turtles with shell diameters below 4 inches were still implicated in a considerable number of reptile-associated salmonellosis cases after the sale ban was enacted in 1975 (see for example \[[@B269],[@B282]\]). In 2007, Louisiana Congressmen proposed the \"Domestic Pet Turtle Market Access Act of 2007\" to the US Senate, which aimed to overrule the sales ban if the seller met certain regulations regarding licensing, sanitization and consumer information. The specified reasons included the fact that the sale of lizards, snakes, frogs and other amphibians and reptiles as pets is not regulated by the FDA, even though they are known to carry Salmonella, and that Salmonellatreatment technologies have advanced since the ban was initiated in 1975. The bill was referred to the Senate committee on agriculture, nutrition and forestry, but had no action taken and never passed. 5.2. Amphibians and Salmonella -------------------------------- The prevalence of Salmonellaamong amphibians seems to vary considerably by host species, even though the number of studies that analyze Salmonellashedding by amphibians is quite limited. Salmonellahas frequently been isolated from frogs and toads, in which Salmonellainfection seems to be predominantly asymptomatic (see for instance \[[@B253],[@B283],[@B284]\]). The prevalence of Salmonellaamong salamanders and newts appears to be lower than among frogs and toads, but the available data is currently relatively limited \[[@B283]\]. Contacts with toads or frogs clearly pose a potential risk to humans. In 2009, for instance, an outbreak of SalmonellaTyphimurium, which affected people in more than 30 USA states, was associated with African dwarf frogs (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3) \[[@B285]\]. Implicated frogs were traced back to a breeder in California, and Typhimurium isolates with PFGE patterns matching the outbreak strain were isolated from several environmental samples taken in the implicated breeding facility. In 2001 an outbreak of SalmonellaJaviana in Mississippi was epidemiologically linked to contact with frogs and toads, even though the Salmonellaserotype was not isolated from amphibians sampled during the outbreak investigation \[[@B286]\]. In 2000, frogs were epidemiologically implicated as the source of water contamination at a construction site in Australia, but no microbiological investigations of the frogs were performed \[[@B287]\]. Moreover, a case-control study estimated that the odds of Salmonellaserogroup B or D infection among people \< 21 years of age were 2.9 (95% Confidence Interval: 1.5-5.8) times higher if amphibians were present in the household, again indicating a potential risk posed by these animal exposures \[[@B265]\]. 5.3. Fish and Salmonella -------------------------- Some studies have investigated the prevalence of Salmonellaamong wild, pet or farmed fish in different ecological niches, sometimes with somewhat conflicting results. Gaetner et al. \[[@B288]\], for instance, reported isolating Salmonellafrom 17-33% of fish sampled in the San Marcos river in Texas and Miruka et al. \[[@B289]\] isolated Salmonellafrom approx. 31% of fish samples collected in Lake Victoria, Kenya. Broughton and Walker \[[@B290]\], however, estimated the Salmonellaprevalence among farmed fresh-water fish in China at approx. 5%, and estimates for fish in retail markets in India have ranged from 10-28% \[[@B291]\]. Clinical disease associated with Salmonellainfected fish have been described, mainly manifested as septicemia \[[@B292]\]. Yet, fish can also shed Salmonellain the absence of clinical signs, and after experimental inoculation of silver carp, shedding has been observed for periods of up to 14 days \[[@B293]\]. Fish feed appears to represent a considerable source of Salmonellainfection in commercial aquacultures, and frequent bacterial carriage in raw materials paired with insufficient heat treatment appears to be the major driver \[[@B294]\]. ### 5.3.1. The risk associated with contacts to fish A variety of Salmonellaserotypes have been isolated from free-ranging or captive fish (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1), and Salmonellais common in wild and, probably to a lesser extent farmed, fish. Occupational infections have been linked to contacts with contaminated fish, and ornamental fish tanks have also been linked to human Salmonellaoutbreaks (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). An Australian study, for instance, reported that 82% of human cases during a SalmonellaJava outbreak had been directly or indirectly exposed to exotic fish tanks, and the outbreak strain was detected in implicated tanks \[[@B295]\]. Surprisingly, clinical disease in fish was observed in a large number of tanks, indicating a high pathogenic potential in the fish \[[@B295]\]. In conclusion, exposure to pet, wild or farmed fish represents a potential risk to humans, but the data available regarding infections acquired through contact with fish is currently scarce. 6. Invertebrates and Salmonella ================================= Salmonellahas been isolated from a large number of insects and worms including ants, flies, cockroaches, mealworms and mosquitoes (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). However, almost nothing is known about the pathogenic potential of Salmonellain invertebrates. Salmonella-induced mortality in butterflies and Caenorhabditis eleganshas been described, and it appears likely that Salmonellacan induce disease in other invertebrates \[[@B296],[@B297]\]. Whether Salmonellacan survive metamorphosis is equally unclear and results might be partially serotype, environment, and host dependent (see \[[@B298]\] for a review of the topic). In general, Salmonellaintestinal carriage decreases sharply during pupation, likely due to major changes in the gut environment, and competition with other gut microorganisms such as Proteushas been shown to effectively suppress Salmonellagrowth in flies \[[@B298]\]. The public health relevance of insects might therefore depend on the life stage, the breeding environment and the insect species, and some insects apparently represent more competent hosts than others \[[@B298]\]. Insects and worms have been proposed as disease vectors for Salmonellaon farms, agricultural fields and in households; invertebrates have been associated with Salmonellatransmissions between animal feeds; biting mites have been shown to efficiently transmit Salmonellato chickens, and house flies have been implicated as Typhoid fever vectors in military camps (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Moreover, insects can represent reservoir hosts, and therefore may play pivotal roles in Salmonellapersistence. 7. Animal Contact in Public Settings as Source of Human Infection ================================================================= 7.1. Human outbreaks linked to animal contacts in public settings ----------------------------------------------------------------- Salmonellahas repeatedly been isolated from captive and domestic animals held in public settings. For instance, a Korean study sampling clinically health zoo animals reported isolating Salmonellafrom approx. 6% of animals, including 30% of reptiles, 7% of birds and 1% of mammals \[[@B299]\]. Other studies report the isolation of SalmonellaDublin from a clinically healthy tiger at a zoo in the UK, from large cats and rodents in a zoo in India, from rhinoceroses in an animal park in the USA, from a newborn moose and an iguana in a zoo in Canada, from approx. 6.5% of animals in a zoo in Trinidad and from two animals in Swiss petting zoos (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Salmonellahas also been isolated from environmental surfaces in zoological gardens \[[@B300]\]. The health threat is aggravated by risky behaviors. For instance, one recent study found that 87% of visitors in Tennessee petting zoos had contact with potentially contaminated surfaces, and 74% had direct animal contact, but only 38% used hand sanitizer, while 49% had hand-to-face contacts with 22% eating or drinking in animal contact areas \[[@B301]\]. Animal contact in public settings therefore represents another source of human infection, and direct or indirect animal contacts in petting zoos, zoological parks, country fairs, or other settings represent threats to public health \[[@B190]\]. As mentioned above, in 1996, for instance, 65 children became sick after visiting the Denver zoo, due to indirect contact with a Komodo dragon \[[@B270]\]. In 1991, a visit to a science center in Washington was associated with 5 human salmonellosis cases, in 2000, at least 18 people were affected by a Salmonellaoutbreak linked to a petting zoo in Ohio, in 2001, at least 19 salmonellosis cases were linked to animal contact at an agricultural exhibit in Alberta, Canada, in 2003, at least 17 human Salmonellacases were linked to contact with a wallaby in a public setting in Michigan, and in 2005, 19 human cases were linked to direct or indirect contact with pigs in a public setting in Wisconsin \[[@B34],[@B302],[@B303]\]. In conclusion, animal contacts in public settings represent a Salmonellarisk to occupationally exposed subpopulations as well as the general public, but management practices can effectively reduce the risk. To minimize risks, several governmental agencies have passed legislations governing animal exhibitions, and governmental as well as professional organizations have published related recommendations. 7.2. Current legislation and recommendations: case study USA ------------------------------------------------------------ Minimizing the risk of disease transmission in public settings is a major concern for governments and professional organizations around the world. As one example, recommendations and legislation in the USA will be described in the following passage. The USA National Association of State Public Health Veterinarians (NASPHV), in conjunction with the CDC, published recommendations to prevent disease outbreaks in public settings, which are regularly updated. The recommendations are addressed to governmental agencies, educational settings, exhibit managers, veterinarians, caregivers, and visitors at particular risk of infection. The main focuses are on disseminating information, enhancing oversight and outbreak investigations, encouraging good hygiene practices, improving facility design, implementing disease monitoring and prevention systems, and prohibiting high risk contacts. To further address the threat, the CDC, the Association for Professionals in Infection Control and Epidemiology, the Animal-assisted Interventions Working Group and the NASPHV published a number of additional recommendations and the Association for Zoos and Aquariums has developed a certification program. Depending on the animal species, animal exhibits may also be subject to USDA inspections under the Animal Welfare act, but human disease risks are not explicitly addressed in these inspections. In addition, some states have passed additional legislations. For instance, North Carolina requires all animal exhibits with public access to obtain a license, Pennsylvania mandates minimum standards for exhibit sanitation, and Virginia requires a permit for the exhibition of wild animals. The relative effectiveness of these diverse mitigation strategies largely remains to be determined. 8. Conclusions ============== In conclusion, contact with animals is responsible for a number of human salmonellosis cases each year. A number of transmissions occur in the home, but others are occupational or related to public exposures in zoological gardens, schools, or state fairs. Infected animals can present with a great variety of clinical symptoms, and risk factors for transmission to humans clearly differ by animal species, age groups, animal purpose, and geographic region. However, some commonalities are clearly evident. Stress, concomitant disease, and contaminated feed represent universal risk factors for animal infection. Conversely, public awareness and proper hygiene practices are efficient measures to mitigate risks. In fact, frequent hand washing alone could likely prevent a substantial number of human infections each year. However, awareness of the risks is low and the collaboration between governmental agencies, professional organizations and special interest groups is necessary to resolve the problem. In some instances, new legislations or public awareness campaigns have led to dramatic decreases in Salmonellaincidence. Yet, much remains to be done to safeguard public health and many aspects of Salmonellaepidemiology remain to be discovered. Salmonellaserotypes differ in host range and distribution among host species, but our understanding of the molecular and evolutionary determinants of these host range differences is still limited and the public health implications are currently difficult to assess. In summary, the risks associated with animal contacts are diverse and much remains to be uncovered, but we already posses important clues to manage the risks. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= KH, MW and AIMS conceived and outlined the study. KH and AIMS reviewed the pertinent scientific literature and collated references and tables. KH drafted the manuscript. All authors have read and approved the final manuscript. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 Table S1. Overview of Salmonellaserotypes isolated from animals in different geographic regions. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 Table S2. Documented reports of Salmonella transmission from birds to humans available in the peer-reviewed literature or otherwise published by public health agencies. Table S3. Documented reports of Salmonellatransmission from reptiles, amphibians fish to humans available in the peer-reviewed literature or otherwise published by public health agencies. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ We thank Dr Kevin Cummings, Cornell University, for helpful comments and suggestions. Support for this project was provided by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract N01-AI-30054-ZC-006-07. K Hoelzer was supported by Morris Animal Foundation Fellowship Training Grant D08FE-403.	PubMed Central	2024-06-05T04:04:18.962435	2011-2-14	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052180/", "journal": "Vet Res. 2011 Feb 14; 42(1):34", "authors": [ { "first": "Karin", "last": "Hoelzer" }, { "first": "Andrea Isabel", "last": "Moreno Switt" }, { "first": "Martin", "last": "Wiedmann" } ] }
PMC3052181	Introduction ============ Mastitis is the first cause of economical loss in milk production worldwide \[[@B1]\] and is a major concern in milk transformation \[[@B2]\]. The problem is however currently hard to tackle for mastitis in dairy cows, sheep and goats. Especially, S. aureusmastitis is typically refractory to antibiotic treatment. Prophylactic measures, including the development of an effective vaccine, have so far proven unsuccessful for the control of the disease. S. aureusis well-known to produce a large variety of virulence factors (including numerous proteins like toxins or adhesins). Consequently, it induces a large panel of infections, and the clinical acuteness of each infection type may also be variable. For example, S. aureusmastitis in dairy sheep ranges from subclinical mastitis to lethal gangrenous mastitis. Such variability relies on staphylococcal virulence factors as well as host factors. Until now, no study has been performed to identify the transcripts and proteins commonly or specifically produced in vivo by S. aureusstrains during mastitis. To obtain such information using direct transcriptomic or proteomic approaches upon S. aureussamples collected within the infection site stumbles on technical bottlenecks such as the low amounts of S. aureuscells and the difficulty to localize the infection site within the udder. Serological proteome analysis (SERPA) is a promising technique that can be used to shed light on the host\'s immune response to staphylococcal infection. This technique was used to mine new antigen candidates for vaccine development in human infections \[[@B3]\]. SERPA has also been used to identify proteins produced in vivo, during infection \[[@B4]\]. In combination with whole genome shotgun sequencing, SERPA is a powerful tool to identify immunoreactive proteins produced by S. aureusduring the infection \[[@B5]\]. Genotyping studies indicated that S. aureusstrains isolated from dairy sheep farms in the south east of France were clonally related and are predominantly represented by a single pulse-field gel electrophoresis (PFGE) type OV/OV\' \[[@B6],[@B7]\]. Such close phylogenetic relationship was recently confirmed at the global scale using Multi Locus Sequence Typing and comparative genome hybridization \[[@B8],[@B9]\]. Among strains in this OV/OV\' PFGE profile, one was isolated from subclinical mastitis (O46) and another one from gangrenous mastitis (O11). Few genetic differences were identified \[[@B10]\] and their role in the development of mastitis with such different severity has not yet been determined. Moreover identification of the proteins produced by S. aureusin mastitis with different severity is an important step to better understand the host-pathogen interactions and to provide targets for the development of efficient prevention or treatment strategies against mastitis. Therefore, we applied SERPA to identify proteins that are produced by both S. aureusstrains O11 and O46 (core seroproteome) and the ones specifically produced by each strain (\"accessory\" seroproteome). Materials and methods ===================== Bacterial strains, growth conditions and preparation of protein samples ----------------------------------------------------------------------- S. aureusstrains used in this study are presented in Table [1](#T1){ref-type="table"}. S. aureusO46 was isolated from a case of ovine subclinical mastitis and O11 from a gangrenous lethal mastitis \[[@B10]\]. Genetic and genotypic background of S. aureusO46 and O11 are well-documented. They share the same pulsotype (OV/OV\') and are representative of the major lineage found associated to ewe mastitis in south east of France \[[@B6],[@B7]\]. Growth conditions and preparation of protein extracts were as described in Le Maréchal et al. 2009 \[[@B11]\]. Briefly, overnight cultures in BHI were diluted 1:1000 in fresh RPMI 1640 medium (Sigma, Saint Quentin Fallavier, France). RPMI was extemporaneously depleted of iron (and hereafter referred to as iron-depleted RPMI) by adding deferoxamine (0.15 mM) (Sigma). Growth conditions in which there is restriction in the bioavailability of iron can indeed lead to an increase of the expression of virulence factors which are normally expressed in vivo \[[@B12]\]. S. aureusstrains were grown in 500 mL flasks under agitation (150 rpm) at 37 °C (a flask-to-broth volumetric ratio of 5), for aerobic conditions, or in falcon tubes (50 mL) completely filled with medium and incubated at 37 °C without agitation for anaerobic conditions. Protein samples for supernatant, cell wall or total fraction were prepared exactly as previously described \[[@B11]\]. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Staphylococcus aureusstrains used in this study ::: Strain Type of mastitis Origin Isolated in: ----------- ------------------ ------------------- ------------------ O11\* gangrenous south east France 2002 1628 gangrenous south east France 2010 1624 clinical south east France 2003 1625 clinical south east France 2008 1626 clinical south east France 2008 1536 clinical south west France 1998 O46\* subclinical south east France 2002 1627 subclinical south east France 2008 O55 subclinical south east France 2003 O117 subclinical Corsica. France 2001 1535 subclinical south west France 1998 O82 subclinical south east France 2003 \: O11 and O46 were used for experimental infections and their genome was fully sequenced (see Materials and Methods). ::: Genome sequencing of O11 and O46 strains ---------------------------------------- To facilitate the analysis of SERPA results, the genome of the two strains used in experimental infection was fully sequenced using the Solexa technology (P Mayer, L Farinelli, and E Kawashima, 1997. Patent application WO98/44151) according to the manufacturer\'s protocol (Illumina, San Diego, CA, USA). Briefly, genomic DNA was physically fragmented by nebulization into 50- to 500-bp fragments. After end repair and ligation of the bar-coded paired-end adaptors, the products were purified on agarose gel to recover products with inserts of \~200 bp. Quality control was performed by cloning an aliquot of the library into a TOPO plasmid and capillary sequencing eight clones per library. The samples were then used to generate DNA colonies using one channel of a paired-end flow cell at dilutions of 4 pM. The flow cell was then submitted to 2 × 74 cycles of sequencing on the genome analyzer. Base calling was performed using the GAPipeline 1.4.0 software; a total of 27.6 million reads (pass filter) were obtained. After bar code selection, 13.9 and 11.8 million reads of 71 bases in length were obtained for the strains O11 and O46 respectively. The pool of sequences obtained was analyzed and assembled using the Edena assembler \[[@B13]\], which resulted in a set of 87 and 96 contigs for O11 and O46, respectively. The gene content of each strain (2787 and 2822 Coding Sequences -CDSs- for O11 and O46, respectively) was thus established and used in protein identification after SERPA. Detailed genome analysis of these strains is described elsewhere (Le Maréchal et al., submitted). 2-Dimensional Electrophoresis (2-DE) ------------------------------------ Samples (200 μg of proteins for Coomassie blue staining and 50 μg for Western blotting) were precipitated with 2D clean up kit (GE Healthcare, Orsay, France) according to the manufacturer\'s instructions. Pellets were solubilised in sample solution containing 7 M urea, 2 M thio-urea, 25 mM dithiothreitol (DTT), 4% (w/v) 3-\[(3-Cholamidopropyl)dimethylammonio\]-1-propane-sulfonate (CHAPS) and 2% (w/v) ampholyte containing buffer (IPG-Buffer 4-7 or 3-10 NL, GE Healthcare). Isoelectric focusing was carried out using pH 4 to 7 (Cell wall and total proteins) or 3 to 10 NL (exoproteins) 13 cm Immobiline Dry Strips on a Multiphor II electrophoresis system (Amersham Biosciences; GE Healthcare, Orsay, France) for a total of 60 kVh using a standard procedure described previously \[[@B14]\]. The second dimensional separation was performed on the Ettan™ DALTtwelve electrophoresis system (GE Healthcare) using 14% acrylamide separating gels without a stacking gel at a voltage of 50 V for 1 h and 180 V for about 7 h. Kaleidoscope Prestained Standards (Biorad) were used as standard. Gels were transferred onto membrane or stained with R250 Coomassie blue (Serva, Heildelberg, Germany) or MS-compatible silver nitrate (Sigma) \[[@B15]\]. Intramammary challenge with S. aureusin ewes ---------------------------------------------- Experimental mastitis was performed according to the Regional Committee for Animal Use and Care (Côte d\'Azur, France) and is recorded under reference NCA/2008-14/12-09. Healthy lactating primiparous ewes of Lacaune breeds were selected based on the absence of intramammary infections and milk somatic cell counts below 100 000 cells/mL. Repeated full bacteriological analysis of milk from the two quarters that were going to be infected showed that the ewes were negative for Staphylococcussp. and Mycoplasmasp. Absence of nasal carriage for staphylococci was also checked after enrichment and culturing of swab samples of the nares of ewes on selective media, as described previously \[[@B6]\]. At D0, 12 ewes were divided into 2 groups and urethral catheters (Portex^®^Jackson Cat Catheter, Coveto, France) were inserted into the teat canal after a thorough disinfection of the teat orifice with 70% ethanol. 1 mL PBS containing 20 CFU of S. aureus(O11 or O46) was injected through the catheter, which was removed afterwards. Six ewes were thus infected by strain O11 (group O11) and six by strain O46 (group O46). Severity of the mastitis induced in ewes was estimated according to criteria presented in Additional file [1](#S1){ref-type="supplementary-material"}, Table S1. Mastitis was classified as subclinical, clinical, pyogenic and gangrenous. Classification was based on clinical symptoms, presence of S. aureuscells and Somatic Cell Count (SCC) in milk. Sample processing ----------------- Sera from ewes were prepared from blood samples collected aseptically from the jugular vein of the animals at D0, D7, D14, D21 and D28 post inoculation (pi). Briefly, blood samples were kept for 2 h at room temperature before centrifugation. Sera were then stored at -20°C. Milk samples were taken 24 and 36 h pi for bacteriological examination and determination of SCC. Milk was 1/10 diluted and 100 μL of this dilution was plated on selective Rabbit Plasma Fibrinogen Baird-Parker medium to confirm S. aureuspresence in the mammary gland. SCC was measured with the Fossomatic method \[[@B16]\] to follow the onset of the infection. Western blot analysis --------------------- Total cell lysates were prepared as previously described \[[@B11]\]. Total protein extracts of S. aureusstrains O11 and O46 were separated by SDS-PAGE on 12% acrylamide separating slab gels (70 × 100 × 0.5 mm), with a 4% acrylamide stacking gel on a mini-protean III gel system (BioRad, Ivry sur Seine, France) according to Laemmli \[[@B17]\]. Protein migration was performed for 2 h at room temperature at constant 80 V voltage. Samples were diluted in sample buffer and denatured at 100 °C for 3 min. Gels were transferred onto a PVDF membrane (GE Healthcare) at constant 250 mA amperage in Towbin transfer buffer \[[@B18]\] using a Trans-Blot cell (Biorad) for 1.25 h. Membranes were washed three times with Tris Buffered Saline (TBS) at pH 7.5 and saturated in blocking solution (3% non-fat dry milk in TBS with 0.3% Tween 20 (TBS-T)) at 4 °C overnight. After saturation in blocking solution, membranes were washed 3 × 10 min with TBS-T and exposed to the different ewe sera used as primary antibody for 4 h at room temperature. After washing, membranes were incubated with alkaline phosphatase conjugated anti-sheep IgG (Sigma) diluted 1:15,000 in 25 mL blocking solution for 1 h and finally BCIP/NBT (Sigma) was used to visualize immunoreactive proteins, according to the manufacturer\'s instructions. Selection of the hyper-immune sera ---------------------------------- Sera samples were analysed by western blotting as described above. Sera sampled on D0, D7, D14, D21 and D28 pi were compared using the mini-protean II Multiscreen apparatus (Biorad) (600 μL of serum diluted 1:10,000 in blocking solution). Immunostained Western blots were scanned using an Image Scanner II (Amersham biosciences) and further analyzed using Image- Quant 1D software. The number, volume and area of bands were taken into account for the analysis. Optimal dilution for the selected sera was determined as described above. Sera and dilutions yielding the best ratio signal/background were selected. Identification of immunoreactive proteins ----------------------------------------- Bacterial proteins separated by 2-DE were transferred onto a PVDF membrane (GE Healthcare) as described above. Series of four gels were migrated and treated in parallel. Three gels were used for immunoblotting, and the fourth one was Coomassie blue-stained for spot matching and further identification. After saturation in blocking solution the membranes were treated with selected sera in blocking solution during 4 h. Then, the membranes were washed with TBS-T and incubated with alkaline phosphatase conjugated anti-sheep IgG (Sigma) diluted 1:15 000 in 25 mL blocking solution for 1 h. Finally BCIP/NBT (Sigma) was used to visualize immunoreactive proteins, according to the manufacturer\'s instructions. Membranes were scanned using an Image Scanner II (Amersham biosciences) and further analyzed using Image- Master 2D software. Immunoblot profiles for 2-DE-separated proteins were reproducible in at least two individual experiments. Images of the 2D electrophoresis gels and the BCIP-NBT treated membranes were compared to detect immunoreactive proteins. Spots that were absent or had a significantly different intensity in one strain were considered as proteins that differed between O11 and O46. Spots corresponding to proteins of interest were excised and identified using Nano-Liquid Chromatography (Nano-LC) MS/MS analysis. Nano-LC MS/MS analysis ---------------------- Proteins were identified by tandem mass spectrometry (MS/MS) after an in-gel trypsin digestion adapted from Shevchenko \[[@B19]\]. Briefly, gel pieces were excised from the gel, washed with acetonitrile and ammonium bicarbonate solution, and then dried under vacuum in a SpeedVac concentrator (SVC100H-200; Savant, Thermo Fisher Scientific, Waltham, MA, USA). In-gel trypsin digestion was performed overnight at 37 °C and stopped with spectrophotometric-grade trifluoroacetic acid (TFA) (Sigma-Aldrich). The supernatants containing peptides were then vacuum dried in a Speed-Vac concentrator and stored at -20 °C until mass spectrometry analysis. Nano-LC experiments were performed using an on-line liquid chromatography tandem mass spectrometry (MS/MS) setup using a Dionex U3000-RSLC nano-LC system fitted to a QSTAR XL (MDS SCIEX, Ontario, Canada) equipped with a nano-electrospray ion source (ESI) (Proxeon Biosystems A/S, Odense, Denmark). Samples were first concentrated on a PepMap 100 reverse-phase column (C18, 5 μm, 300-μm inner diameter (i.d.) by 5 mm length) (Dionex, Amsterdam, The Netherlands). Peptides were separated on a reverse-phase PepMap column (C18, 3 μm, 75 μm i.d. by 150 mm length) (Dionex) at 35 °C, using solvent A (2% (vol/vol) acetonitrile, 0.08% (vol/vol) formic acid, and 0.01% (vol/vol) TFA in deionized water) and solvent B (95% (vol/vol) acetonitrile, 0.08% (vol/vol) formic acid, and 0.01% (vol/vol) TFA in deionized water). A linear gradient from 10 to 50% of solvent B in 40 min was applied for the elution at a flow rate of 0.3 μL/min. Eluted peptides were directly electrosprayed into the mass spectrometer operated in positive mode. A full continuous MS scan was carried out followed by three data-dependent MS/MS scans. Spectra were collected in the selected mass range 400 to 2 000 m/zfor MS and 60 to 2 000 m/zfor MS/MS spectra. The three most intense ions from the MS scan were selected individually for collision-induced dissociation (1+ to 4+ charged ions were considered for the MS/MS analysis). The mass spectrometer was operated in data-dependent mode automatically switching between MS and MS/MS acquisition using Analyst QS 1.1 software. The instrument was calibrated by multipoint calibration using fragment ions that resulted from the collision-induced decomposition of a peptide from β-casein, β-CN (193-209). The proteins present in the samples were identified from MS and MS/MS data by using MASCOT v.2.2 software for search into two concatenated databases: (i) a homemade database containing all the predicted proteins of the S. aureusstrains O11 and O46 used in this study and (ii) a portion of the UniProtKB database corresponding to the S. aureustaxonomic group \[[@B20]\]. Search parameters were set as follows. A trypsin enzyme cleavage was used, the peptide mass tolerance was set to 0.2 Da for both MS and MS/MS spectra, and two variable modifications (oxidation of methionine and deamidation of asparagine and glutamine residues) were selected. For each protein identified in NanoLC-ESI-MS/MS, a minimum of four peptides with MASCOT score corresponding to a Pvalue below 0.05 or an Exponentially Modified Protein Abundance Index \[[@B21]\] greater than 0.4 were necessary for validation with a high degree of confidence. For automatic validation of the peptides from MASCOT search results, the 1.19.2 version of the IRMa software was used \[[@B22]\]. Intramammary infection with S. aureusin mice ---------------------------------------------- The animal study was conducted according to current Good Scientific Practice-principles (2000) and approved by the Ethical Committee of the Faculty of Veterinary Medicine, Ghent University (Belgium). Sixteen CD-1 lactating female mice (Harlan Laboratories Inc., Horst, The Netherlands) were used 12-14 days after birth of the offspring. The pups were removed 1 to 2 h before bacterial inoculation of mammary glands and a mixture of ketamine/xylazine was used for anesthesia of the lactating mice. The orifice of both L4 (on the left) and R4 (on the right) abdominal mammary glands was exposed by a small cut at the near end of the teat. 100 μL PBS without (n= 2) or with 150 CFU of S. aureusstrain O11 (n= 7) or O46 (n= 7) was injected slowly with a 32-gauge blunt needle through the teat canal. Rectal body temperature of the mice was measured at 0 h and 18 h pi. At 18 h pi mice were anesthetized with ketamine/xylazine to collect blood by cardiac puncture and serum was obtained after clotting at 37 °C and cold centrifugation. After cardiac puncture, mice were euthanized by cervical dislocation and mammary glands were isolated. Glands of six mice of each group were homogenated and bacterial CFU was quantified by plating serial logarithmic dilutions in PBS. Lysates from the homogenates were prepared in 1% NP40-based buffer. Serum and mammary gland lysates were quantified for IL-1β, IL-6, TNF, KC and MCP-1 using BD^™^Cytometric Bead Array technology. Mammary glands (inoculated and PBS control glands) of 4 mice (2 from each group) were embedded and used for further histopathological analysis (Vetopath, Antibes, France). Statistical analyses -------------------- A Fisher test was used with a risk α = 10% to determine the difference between the ewes infected with S. aureusO11 and the ewes infected with strain O46. Differences in rectal body temperature and cytokine levels in the mouse mastitis model were analyzed with the unpaired T-test. P\< 0.05 was considered statistically significant. Results ======= Ewes infected with O11 or O46 S. aureusstrains developed mastitis with different severities --------------------------------------------------------------------------------------------- Although O11 and O46 strains share the same genotype and are highly genetically similar \[[@B10]\], they were isolated from dramatically different ewe mastitis episodes. One can thus wonder whether the clinical signs associated with O11 and O46 infection were or not related to strains characteristics or a fortuitous matter of sampling time (mastitis can indeed evolve from subclinical to severe clinical or even gangrenous within a few days). To check this, two groups of ewes were infected either with O11 or O46 S. aureusstrains, as described in the previous section. Onset of the symptoms was followed up during the course of the experiment. All animals became infected and signs of mastitis were evident in most ewes as soon as 24 h pi. The animals shed the S. aureusstrains over the sampling period and remained infected for the duration of the experiment. Shedding from the infected glands varied and S. aureusload in milk ranged from 10 CFU/mL to 3.16 × 10^8^CFU/mL, depending on the individual ewe, and on the day pi (not shown). Symptoms evoked by intramammary inoculation varied among ewes. In group O11, five out of six ewes developed a gangrenous mastitis, the last one developed a pyogenic mastitis according the criteria defined in Additional file [1](#S1){ref-type="supplementary-material"}, Table S1. In group O46, symptoms were more heterogeneous and mastitis cases were classified in subclinical mastitis (n= 1), pyogenic mastitis (n= 2), mild clinical mastitis (n= 2) and gangrenous mastitis (n= 1). Subclinical mastitis was determined with the presence of bacteria (250 CFU/mL of milk 36 h pi), a raise in SCC (\> 200 000 cells/mL in each milk sample after 24 h) and absence of fever or symptoms. Except for the ewe with subclinical mastitis, bacteria were detected in all milk samples and reached more than 10^6^CFU/mL 36 h pi. All animals had fever (above 40 °C 36 h pi) and SCC increased quickly and was above 10^6^cells/mL at 36 h pi. The proportion of the gangrenous mastitis was significantly higher in the group of ewes infected with O11 strain compared to the group infected with O46 (p= 0.08) (Additional file [2](#S2){ref-type="supplementary-material"}, Figure S1). S. aureusO11 and O46 induce dramatically different clinical features in infected mice. To confirm our observation that S. aureusstrains O11 or O46 induce different types of mastitis, the mouse mastitis model was employed in the current study. Strains O11 and O46 grew equally well in the infected mouse mammary glands and induced mastitis, as determined by temperature measurement (hypothermia in O11 group and hyperthermia in O46 group, 24 h pi; Additional file [3](#S3){ref-type="supplementary-material"}, Figure S2) and histopathological analysis: polymorphonuclear neutrophils (PMN) infiltration was observed only in infected (either with O11 or O46 strains) mammary gland tissue (not shown). To analyse the role of each strain in the development of mastitis, cytokine profile of the serum and mammary gland tissue lysates of mice infected with O11 strain was compared to those infected with O46 strain. The results of cytokine quantification showed that mice infected with S. aureusO46 had significantly higher IL-1β and TNF levels in the mammary gland lysates and significantly higher systemic (serum) levels of IL-1β and MCP-1 (Additional files [4](#S4){ref-type="supplementary-material"} and [5](#S5){ref-type="supplementary-material"}, Figures S3 and S4). Altogether, these results demonstrate that despite their close genetic relationships, S. aureusO11 and O46 reproducibly induced mastitis with significantly different clinical signs. Antibody production in response to infection of ewes with S. aureusstrains O11 or O46 --------------------------------------------------------------------------------------- To compare the relative level of antibodies developed in response to S. aureuspresence in the mammary gland, serum sampled on D0, D7, D14, D21 and D28 pi were analysed by Western blotting using either O46 or O11 total bacterial extracts as described in the previous section. The number of bacterial proteins recognised by sera and signal intensity increased from D0 to D28 for both O11 and O46 samples (Figure [1](#F1){ref-type="fig"}). The intensity of the signal revealed with sera collected on D0 was low and much weaker compared to those obtained with sera collected on D21 or D28. Western blots membranes were analysed as described in the previous section. Sera collected either on D21 or D28 were selected for further analysis. Sera yielding the best signals in each group (one sample for each of the six ewes) were pooled to be used in SERPA experiments. Two pools were thus obtained: sera from ewes infected with O11 and sera from ewes infected by O46, hereafter referred to as group O11 sera and group O46 sera, respectively. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Western blot analysis of total lysates of S. aureusO11 (left panel) or S. aureusO46 (right panel) using D0, D7, D14, D21, D28 diluted 1:10,000 sera of ewes infected by O11 and O46. Bacteria were grown in iron-depleted RPMI without aeration to late exponential phase. Protein samples were prepared from total cell, submitted to 1-DE, western blotted on PVDF membrane and revealed using each of the 6 serum samples collected on ewes infected in each group. One representative example is given for each group of infected ewes (with O11 or O46). ::: ![](1297-9716-42-35-1) ::: Detection and identification of immunogenic staphylococcal proteins by SERPA ---------------------------------------------------------------------------- Protein samples were prepared from O11 and O46 strains grown in conditions that best mimic the mastitis context \[[@B11]\]. Each fraction (total, cell wall and supernatant) of O11 and O46 culture was immunoblotted using either group O11 or group O46 sera. Altogether, 89 proteins were identified as immunoreactive (Table [2](#T2){ref-type="table"}). Comparison of SERPA results (see Figure [2](#F2){ref-type="fig"}, and Additional files [6](#S6){ref-type="supplementary-material"} and [7](#S7){ref-type="supplementary-material"}, Figures S5 and S6) on the three fractions analyzed showed that immunoreactive proteins were mainly identified in supernatant samples prepared from aerobic and anaerobic cultures (Figure [2](#F2){ref-type="fig"} and Additional file [7](#S7){ref-type="supplementary-material"}, Figure S6) and cell wall samples (Additional file [6](#S6){ref-type="supplementary-material"}, Figure S5, upper panels) whereas total protein samples were poorly recognized (Additional file [6](#S6){ref-type="supplementary-material"}, Figure S5, lower panels). A vast majority of the immunoreactive proteins are thus found in supernatant and cell wall fractions (88.7%), and only 11.3% are found in the total fractions (Figure [3A](#F3){ref-type="fig"}). Of note, secreted and surface proteins are expected to be exposed to the host immune system. The predicted location of the proteins (according to the SurfG+ analysis of O11 and O46 genome sequences) \[[@B23]\], showed that the immunoreactive proteins were mainly predicted cytoplasmic (52.8%) (Figure [3A](#F3){ref-type="fig"}). Proteins were classified into categories based on functional annotation (Figure [3B](#F3){ref-type="fig"}). Most immunogenic proteins identified here are found in various functional categories involved in cellular machinery and metabolism; while 20% were virulence factors and virulence associated proteins. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Proteins identified in this study. ::: Description^1^ Spots^2^ O11 CDS^3^ O46 CDS^3^ ED133 CDS^3^ pI^4^ Mass (Da)^5^ Score^6^ Cov.^7^ \#pep.^8^ EmPAI^9^ Comp.^10^ Loc.^11^ Immun.^12^ ------------------------------------------------------------------------- --------------------------------------------------------------- --------------- --------------- ----------------- ---------- -------------- ------------- ----------- ----------- ----------- ----------- ---------- ------------------------------------------------------------ Metabolism* *Energy production and conversion* formate acetyltransferase 81, 83, 82 011\_0041 046\_0511 SAOV\_0163 5,31 84808 1301,60 34,31 22 1,57 CW C ldh L-lactate dehydrogenase 82, 99, 81, 83, 95 011\_0136 046\_0198 SAOV\_2646c 4,80 34389 1749,37 63,64 26 21,75 CW C \[[@B82]\] L-LACTATE DEHYDROGENASE (O11) 64 011\_0021 046\_0531 SAOV\_0178 5,00 34548 745,83 50,79 14 2,59 S C \[[@B82]\] bifunctional acetaldehyde-CoA/alcohol dehydrogenase 79 011\_0796 046\_0709 SAOV\_0095 5,68 94945 2090,64 45,45 33 2,26 CW C D-3-phosphoglycerate dehydrogenase 100 011\_0585 046\_1131 SAOV\_2344 5,32 34652 717,85 43,53 11 1,72 CW C atpD F0F1 ATP synthase subunit beta 62, 90 011\_2064 046\_0898 SAOV\_2144c 4,68 51368 631,03 30,21 10 0,98 S,CW C \[[@B83]\] *Nucleotide transport and metabolism* adk adenylate kinase 9 011\_0510 046\_1206 SAOV\_2266c 4,80 23375 531,72 42,38 9 2,80 S C \[[@B84]\] deoD purine nucleoside phosphorylase 9 011\_1051 046\_0577 SAOV\_2178 4,85 25892 470,94 53,39 8 1,97 S C \[[@B4]\] guaB inositol-monophosphate dehydrogenase 102, 129 011\_0077 046\_0960 SAOV\_0412 5,61 52818 1237,95 54,30 20 3,52 CW,T C \[[@B4]\] *Carbohydrate transport and metabolism* gpmA 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 131 011\_1952 046\_0264 SAOV\_2463c 5,23 26663 271.65 30.26 5 0.80 S,T C eno enolase 2-phosphoglycerate dehydratase 62, 88, 90, 96, 137 011\_2336 046\_2241 SAOV\_0818 4,55 47088 1868,52 63,59 25 7,09 S,CW,T C \[[@B4],[@B52],[@B85]-[@B87]\] fda fructose-1,6-bisphosphate aldolase 107, 94, 72, 91, 95 011\_0131 046\_0202 SAOV\_2650 5,06 32878 852,09 46,62 13 2,48 CW,S C \[[@B85]-[@B88]\] gap glyceraldehyde-3-phosphate dehydrogenase 99, 57, 81, 82, 83 011\_2340 046\_2237 SAOV\_0814 4,89 36258 940,06 46,13 13 3,04 CW,S C \[[@B82],[@B86],[@B87],[@B89],[@B90]\] putative translaldolase 9 011\_1872 046\_2451 SAOV\_1765 4,72 25689 554,11 46,84 10 3,32 S C tpiA triosephosphate isomerase 9 011\_2338 046\_2239 SAOV\_0816 4,81 27271 1396,16 76,28 21 16,78 S C \[[@B4],[@B91],[@B92]\] atl autolysin 23, 31 011\_1991 046\_0320 SAOV\_0999c 9,59 136983 2567,68 42,14 42 1,87 S S \[[@B52],[@B76],[@B93]\] pyk pyruvate kinase 105 011\_1282 046\_0580 SAOV\_1685 5,23 63067 271,45 11,62 5 0,29 CW C \[[@B94]\] *Lipid metabolism* fabZ 3R-hydroxymyristoyl ACP dehydratase 126 011\_2356 046\_1839 SAOV\_2140c 5,71 16071 86,65 13,70 2 0,47 T C acetoin reductase 106 011\_1332 046\_1393 SAOV\_0074 5,04 27199 566,84 40,31 7 1,82 CW C *Amino acid transport and metabolism* dipeptidase PepV 62 011\_1904 046\_1329 SAOV\_1737 4,56 52762 235.33 10.66 4 0,27 S C CYSTEINE SYNTHASE (O11) 64 011\_1382 046\_2402 SAOV\_0535 5,38 32955 266.80 28.71 5 0,61 S C Information storage and processing *Translation, ribosomal structure and biogenesis* fus elongation factor G 95 011\_0401 046\_1769 SAOV\_0582 4,80 76564 2173,77 68,11 30 4,11 CW C \[[@B3],[@B90]\] prs 50S ribosomal protein L25/general stress protein Ctc 94 011\_1370 046\_2414 SAOV\_0523 4,39 23773 384,17 34,56 6 2,26 CW,S C \[[@B95]\] rplC 50S ribosomal protein L3 131 011\_0531 046\_1185 SAOV\_2287c 9,72 22648 482,78 42,11 9 2,95 T C \[[@B95]\] rpsA 30S ribosomal protein S1 137, 62, 121, 171 011\_2142 046\_1743 SAOV\_1482 4,51 43252 1555,46 71,36 23 6,25 S,CW,T C \[[@B39],[@B95]\] rpsD 30S ribosomal protein S4 139 011\_1260 046\_1365 SAOV\_1706 10,02 22999 428,22 40,50 8 1,96 T C \[[@B95]\] rplB 50S ribosomal protein L2 91 011\_0528 046\_1188 SAOV\_2284c 10,77 30136 239,93 25,27 5 0,69 CW C \[[@B95]\] tsf elongation factor Ts 100, 64 011\_0909 046\_0755 SAOV\_1259 5,05 32474 436,02 31,06 7 0,97 CW,S C \[[@B4],[@B86],[@B93],[@B96]\] tuf elongation factor Tu 90, 88, 96, 10, 122, 137, 149, 81, 82, 83, 95 011\_0402 046\_1768 SAOV\_0583 4,74 43077 2665,48 84,26 38 52,14 S,CW,T C \[[@B3],[@B52],[@B82],[@B85],[@B86],[@B90],[@B93],[@B96]\] yfiA ribosomal subunit interface protein 106 011\_2483 046\_1255 SAOV\_0789 5,25 21511 376,75 35,33 6 1,76 CW C aspS aspartyl-tRNA synthetase 63 011\_2454 046\_2303 SAOV\_1627 4,99 66584 233,90 7,65 4 0,21 S C alaS alanyl-tRNA synthetase 82 011\_2466 046\_2291 SAOV\_1616 5,00 98604 442,31 11,74 8 0,30 O C \[[@B97]\] *Transcription* nusA transcription elongation factor NusA 62 011\_0919 046\_0765 SAOV\_1268 4,60 43701 247,74 11,00 4 0,34 S C *DNA replication, recombination and repair* dnaN DNA polymerase III subunit beta 90 011\_1166 046\_1471 SAOV\_0002 4,66 41888 706,28 45,62 11 1,30 CW C nuc staphylococcal thermonuclease precursor 151, 108, 5, 153, 206, 207, 217 011\_2070 046\_2528 SAOV\_0832 9,20 25089 967,00 50,00 20 14,46 S,CW PSE \[[@B98]\] ruvA Holliday junction DNA helicase 66 011\_2442 046\_2315 SAOV\_1639 5,77 22249 137,72 17,00 3 0,52 S C *Posttranslational modification, protein turnover, chaperones* ahpC alkyl hydroperoxide reductase subunit C 67, 82, 83, 99, 95 011\_0085 046\_0968 SAOV\_0404c 4,88 20963 667,36 56,08 11 4,95 S,CW C \[[@B93]\] AhpF ALKYL HYDROPEROXIDE REDUCTASE SUBUNIT F (O11) 97, 86 011\_0086 046\_0969 SAOV\_0403c 4,68 54655 2242,14 67,06 34 9,91 CW C dnaK chaperone protein 96, 173, 137 011\_2230 046\_2216 SAOV\_1580 4,63 46021 2907,83 80,29 43 24,66 S,CW,T C \[[@B90],[@B96],[@B99]\] peptidyl-prolyl cis-isomerase 212, 1, 68, 91 011\_2089 046\_2477 SAOV\_1837 9,01 35602 574,32 31,56 11 1,66 S,CW PSE tig trigger factor 105 011\_1304 046\_0602 SAOV\_1664 4,34 48565 1061,87 61,43 17 2,25 CW C \[[@B94]\] TrxB THIOREDOXIN REDUCTASE (O11) 64 011\_2580 046\_2228 SAOV\_0801 5,21 33595 681,95 33,76 11 1,81 S C \[[@B93]\] Cellular processes *Cell envelope biogenesis, outer membrane* IsaA IMMUNODOMINANT ANTIGEN A (O46) 185, 8, 161, 186, 9, 164, 189 011\_0168 046\_0166 SAOV\_2614c 5,91 24219 1516,56 59,23 22 40,99 S S \[[@B3],[@B75]\] isdA iron-regulated cell wall-anchored protein 31, 27, 73, 74, 75, 83, 118, 79, 81, 82, 95 011\_1476 046\_1296 SAOV\_1125c 8,69 70445 2288,12 57,87 38 6,04 S,CW PSE \[[@B100]-[@B102]\] isdB cell surface transferrin-binding protein 212, 211, 210, 208, 193, 156, 138, 110, 70, 86, 131, 156, 193 011\_1477 046\_1295 SAOV\_1126c 9,54 39197 886,30 45,48 15 4,45 S,CW,T PSE \[[@B54],[@B100],[@B103]\] IRON-REGULATED SURFACE DETERMINANT PROTEIN H (O11) 55, 31 011\_1248 046\_1353 SAOV\_1717 5,05 100650 2209,72 42,11 37 2,58 S PSE \[[@B75]\] IsdD iron-regulated protein 15, 16 011\_1480 046\_1292 SAOV\_1128 8,51 41357 278,05 15,36 5 0,47 S PSE *Cell motility and secretion* N-acetylmuramoyl-L-alanine amidase 52, 51, 187 011\_1090 046\_1546 SAOV\_2693 5,87 69226 3097,93 71,57 43 16,52 S S \[[@B57],[@B75],[@B76]\] *Inorganic ion transport and metabolism* nasE assimilatory nitrite reductase 10 011\_1932 046\_0245 SAOV\_2445c 4,95 11430 126,05 23,08 2 0,70 S C mntC Manganese/iron transport system substrate-binding protein 94 011\_2274 046\_0062 SAOV\_0666c 8,68 34719 1183,08 51,46 20 10,68 S,CW PSE sirA iron-regulated lipoprotein 135, 64 011\_1345 046\_1405 SAOV\_0062 9,20 36735 609,79 35,45 11 1,58 S,T PSE \[[@B104]\] fhuD2 ferrichrome-binding protein 91 011\_0566 046\_1150 SAOV\_2323c 9,16 33990 406,75 30,13 8 1,10 CW PSE \[[@B105]\] ferrichrome ABC transporter lipoprotein 91 011\_1857 046\_1674 SAOV\_2224c 9,44 36751 600,45 38,41 11 1,57 CW PSE *Signal transduction mechanisms* SA1540 GAF domain-containing protein 10 011\_1261 046\_1366 SAOV\_1705 5,09 17042 139,34 22,73 3 0,72 S C Universal stress response protein 7, 123 011\_1269 046\_1374 SAOV\_1697 5,60 18463 973,68 78,31 12 19,34 S,CW C \[[@B106]\] Toxins and haemolysins beta-hemolysin 15, 19, 205 011\_1750 046\_2394 SAOV\_2040 8,75 37386 1308,79 61,03 20 4,92 S S \[[@B57],[@B107]\] hla alpha-hemolysin precursor 13, 1, 15, 19, 21, 68, 72, 107, 146, 153 011\_1514 046\_1259 SAOV\_1161c 8,87 36329 2238,72 76,71 34 44,90 S,CW,T S \[[@B93],[@B107]\] hlgC gamma-hemolysin component C 68, 1 011\_1956 046\_0268 SAOV\_2469 9,29 35562 765,07 31,43 12 1,90 S,CW S \[[@B57]\] Virulence/defence mechanisms Sbi IGG-BINDING PROTEIN SBI (O11) 216, 217, 212 011\_1954 046\_0266 SAOV\_2466 9,38 49998 984,16 41,74 18 2,80 S S \[[@B76]\] SspB CYSTEINE PROTEASE PRECURSOR (O11) 58, 57, 64, 182, 215 011\_2154 046\_0327 SAOV\_0993c 5,45 42714 2027,86 65,52 30 11,52 S S \[[@B4]\] SplF serine proteinase 4 011\_0672 046\_2496 SAOV\_1795 9,36 25638 255,88 23,01 5 0,84 S S \[[@B108]\] lukD leukotoxin D subunit 1 011\_0685 046\_2484 SAOV\_1812 9,14 36936 365,37 22,02 7 0,98 S S \[[@B109]\] lukE leukotoxin E subunit 1, 68 011\_0686 046\_2483 SAOV\_1813c 9,38 34126 451,11 17,65 7 1,77 S,CW S \[[@B109]\] leukocidin chain lukM precursor 68, 1, 120, 145, 177, 194, 201, 202, 94 011\_1215 046\_2777 SAOV\_1909 9,41 35054 2504,69 71,43 35 29,80 S,CW,T S \[[@B58],[@B110]\] leukocidin F subunit 16, 70 011\_1752 046\_1972 SAOV\_2041 8,29 38639 1154,65 45,27 19 11,64 S,CW S \[[@B58],[@B110]\] leukocidin S subunit 199, 5, 70, 108, 109, 197, 200, 211 011\_1753 046\_1973 SAOV\_2042 9,38 40379 1399,91 55,56 23 6,70 S,CW S \[[@B58],[@B110]\] Panton-Valentine leukocidin LukF-PV chain precursor 1, 68, 70, 15, 31, 119, 195, 203, 204, 10, 91 011\_1216 046\_2776 SAOV\_1908 9,16 36496 965,38 50,31 15 3,37 S,CW S \[[@B58],[@B110]\] plc 1-phosphatidylinositol phosphodiesterase 11, 12, 19 011\_1424 046\_1419 SAOV\_0049 7,12 37030 2759,20 71,95 44 84,00 S S \[[@B4]\] Aur ZINC METALLOPROTEINASE AUREOLYSIN (O11) 220, 63 011\_1083 046\_1553 SAOV\_2686c 4,98 54947 921,93 47,39 17 1,68 S C \[[@B76],[@B111]\] Opp1A OLIGOPEPTIDE TRANSPORTER SUBSTRATE BINDING PROTEIN (O11) 86 011\_2424 046\_2102 SAOV\_2517c 8,33 59224 1398,01 47,53 24 3,28 CW PSE SspA GLUTAMYL ENDOPEPTIDASE SERINE PROTEASE (O11) 56, 184, 214 011\_2155 046\_0325 SAOV\_0994c 4,68 32250 1575,55 69,26 24 24,18 S C \[[@B57]\] SECRETED VON WILLEBRAND FACTOR-BINDING PROTEIN (O11) 22 011\_2679 046\_0987 SAOV\_2051c 8,39 57935 1122,89 36,67 17 1,70 S S epidermal cell differentiation inhibitor B 208, 209, 193, 156, 4 011\_0489 046\_2741 9,51 27969 1385,18 69,32 22 22,31 S S Miscellaneous adhA alcohol dehydrogenase 100 011\_1554 046\_0086 SAOV\_0640 5,34 36025 1167,82 66,37 16 4,30 CW C \[[@B87],[@B93]\] exported secretory antigen precursor 67 011\_0584 046\_1132 SAOV\_2343 5,77 17388 397,17 33,13 5 1,43 S S lip triacylglycerol lipase precursor 31, 27 011\_1119 046\_1518 SAOV\_2721c 8,13 76637 1723,17 50,95 29 2,36 S S \[[@B93]\] mqo malate:quinone oxidoreductase 128 011\_0130 046\_0203 SAOV\_2651c 6,12 55964 1047,99 46,79 17 2,50 T C putative staphylococcal enterotoxin 151 011\_0097 046\_0981 SAOV\_0394 9,54 23311 173,20 18,72 4 0,71 S S Unknown HYPOTHETICAL PROTEIN (O11) 220 011\_0736 046\_1969 SAOV\_0454 4,89 56229 823,11 39,40 14 1,21 S S hypothetical protein (Similar to truncated map-w protein (91%)) 88, 10, 62 011\_1749 046\_2393 9,91 53686 899,64 34,52 18 2,09 S,CW S \[[@B112]\] hypothetical protein (Similar to beta-lactamase (84%)) 10 011\_0679 046\_2490 6,84 20800 726,52 47,15 10 7,09 S S HYPOTHETICAL PROTEIN (O46) 157, 160, 175, 189, 193 011\_0490 046\_2740 8,88 30854 2343,27 74,29 41 65,07 S S hypothetical protein (Similar to probable glutamyl-endopeptidase (76%)) 66 011\_0488 046\_2742 5,44 20552 741,93 47,62 12 5,11 S C SA0570 HYPOTHETICAL PROTEIN (O46) 219,154, 127 011\_2290 046\_0078 SAOV\_0649 9,17 18554 815,59 69,05 13 15,93 S,CW S SA0663 hypothetical protein 10, 164, 94 011\_2561 046\_2636 SAOV\_0742c 9,15 16047 457,11 35,62 8 3,63 S PSE SA0914 hypothetical protein 6 011\_2000 046\_0311 SAOV\_1008c 6,55 11338 522,48 57,14 8 13,10 S S pathogenicity island protein 55 011\_2741 046\_0985 SAOV\_0429 9,55 12071 204,61 19,64 3 1,12 S S SA1607 hypothetical protein 91 011\_1867 046\_2456 SAOV\_1770 6,04 34973 232,41 16,56 4 0,43 CW S SA1402 hypothetical protein 91 011\_2223 046\_2209 SAOV\_1573 5,60 35160 448,93 28,27 6 0,72 CW S Gene products of the accessory seroproteome are indicated in bold capital letters, (O11) indicates O11-specific proteins, (O46) indicates O46-specific proteins. All the other proteins belong to the core seroproteome ^1^: Proteins are classified in Gene Ontology functional classes. Names are given according to annotation of available S. aureussequence genomes. ^2^: Spot number (see figures) ^3^: Coding sequence numbers corresponding to the identified proteins in S. aureusO11, S. aureusO46, and ED133, respectively. ^4^: Theoretical isoelectric point as determined from the predicted protein sequence ^5^: Theoretical Mass as determined from the predicted protein sequence ^6^: Mascot standard score ^7^: % of the protein sequence covered by the peptides identified ^8^: number of peptides identified ^9^: exponentially modified protein abundance index ^10^: Subproteome compartment where the spot was identified. CW, cell wall; S, supernatant; T, total fraction ^11^: predicted protein localization. C, cytoplasmic; S, secreted; PSE, predicted surface exposed ^12^: reported as immunogen elsewhere ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### *Representative 2-DE gels and SERPA on supernatant fractions of S. aureusO11 (A) and S. aureusO46 (B). Supernatant samples were prepared from stationary phase cultures of S. aureusstrains grown anaerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 3-10; 14% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ![](1297-9716-42-35-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### (A) Distribution of the immunoreactive proteins based on their experimentally observed (upper panel) or predicted (lower panel) subcellular localization. (B) Distribution of the immunoreactive proteins based on their GO functional classes. (C) Venn diagram of immunoreactive proteins defining the core and the accessory seroproteomes. ::: ![](1297-9716-42-35-3) ::: Composition of the core and accessory seroproteomes --------------------------------------------------- SERPA revealed 74 proteins as being recognised by both group O11 and group O46 sera (Table [2](#T2){ref-type="table"}). These proteins defined the core seroproteome, i.e. a pool of staphylococcal proteins that are recognized by the host immune system in both S. aureusstrains (Figure [3C](#F3){ref-type="fig"}). Moreover, 15 proteins were differentially recognized by group O11 sera or by group O46 sera. These proteins defined the accessory seroproteome, i.e. a pool of strain-specific proteins that are recognized by the host immune system. Among these 15 proteins, 12 appeared to be immunogenic only in infections with O11 (Table [2](#T2){ref-type="table"}). These proteins include 7 virulence-associated proteins (Sbi, SspB, SspA, Aur, IsdH, Opp1A, and VWbp), 2 stress response proteins (AhpF, TrxB), 1 hypothetical protein (product of CDS O11\_0736 or O46\_1969 in O11 or O46), Ldh and a cysteine synthase. Of note, when considering the corresponding genes, all of these 12 genes are present and highly similar in O11 and O46 strains. Only ahpFand vwbppresent 2 and 1 non-synonymous single nucleotide polymorphisms (NS-SNPs), respectively. These results suggest that O11 produce these 12 proteins in vivo in a mastitis context whereas O46 does not, or to a much lesser extent. Three proteins appeared to be immunoreactive with group O46 sera only. Two of them are hypothetical proteins corresponding to SAOV0649 (CDS 011\_2290 and 046\_0078, in O11 and O46, respectively) encoding a probable esterase or lipase, and a gene 011\_0490/046\_2740 with no homology in ED133 genome sequence. The third protein is IsaA, a virulence-associated immunodominant antigen A. The genes encoding IsaA and the probable esterase or lipase are highly homologous in O11 and O46 with only 1 synonymous SNP found when comparing O11\_2290 and O46\_0078. Interestingly, the CDS O11-0490 in O11 genome shares homology with O46\_2740 in O46. However, sequence analysis reveals that O11-0490 corresponds to a truncated form of O46\_2740. This gene encodes a predicted protein that presents 59% identity and 76% homology with exfoliative toxin D \[[@B24]\]. Selected S. aureusimmunoreactive proteins are widely distributed among a panel of strains isolated from clinical vs. subclinical ewe mastitis ----------------------------------------------------------------------------------------------------------------------------------------------- In order to test the hypothesis that the seroproteomic variations identified by SERPA on the two S. aureusisolates were more widely distributed among isolates of a specific host- and clinical-association, we screened an additional 10 strains isolated from subclinical (n= 5) and severe (i.e. clinical or gangrenous mastitis; n= 5) cases of ewe mastitis for the presence of 2 selected proteins by proteome analysis of supernatant samples (i.e. 2-DE and Coomassie blue staining). The O11 (severe mastitis) protein selected was SspB, which belongs to a proteolytic cascade where a metalloprotease aureolysin (Aur) activates a serine protease zymogen proSspA, which in turn activates the SspB cysteine protease \[[@B25]\]. SspB and the two other proteins, SspA and Aur of the cascade, were recognized in O11 and yielded a very faint signal in O46 (Figure [4A](#F4){ref-type="fig"}). SspB, one element of this proteolytic cascade, was detected in the culture supernatant of strains isolated from clinical mastitis cases whereas it was not found in the strains isolated from subclinical mastitis (Figure [5A](#F5){ref-type="fig"}). The other protein tested was O46\_2740 gene product (with similarity to exfoliative toxin family), which was specifically recognized in O46 infections and did not yield any significant signal in O11 infections (Figure [4B](#F4){ref-type="fig"}). When considering its presence in the culture supernatant of other S. aureusstrains isolated from clinical or subclinical mastitis in ewes, we observed that it was only detected in the subclinical strains (100%) whereas it was undetectable in any of the strains isolated from clinical mastitis (Figure [5B](#F5){ref-type="fig"}). These results show that at least these tested proteins are differentially produced by S. aureusstrains isolated from clinical or subclinical mastitis cases. Whether these differences are involved or not in the onset and the acuteness of the subclinical vs. clinical mastitis remains to be demonstrated. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### SERPA of O11-specific (A) and O46-specific (B) immunoreactive proteins. Protein specific signals were zoomed in on Coomassie blue stained gels (CB) and membranes revealed using sera obtained from animals infected with O11 (Group1) or O46 (Group 2). Aur, aureolysin; SspA, glutamyl endopeptidase serine protease; SspB, staphopain B; O46-2740, gene product similar to exfoliative toxin family. ::: ![](1297-9716-42-35-4) ::: ::: {#F5 .fig} Figure 5 ::: {.caption} ###### Distribution of SspB (A) and O46-2740 product (B) in a panel of S. aureusstrains isolated from clinical (a) and subclinical (b) mastitis. Supernatant samples were prepared on stationary phase cultures of strains grown on iron-depleted RPMI. 2-DE gels were Coomassie blue stained. ::: ![](1297-9716-42-35-5) ::: Discussion ========== Two closely related S. aureusovine strains reproducibly induce distinct mastitis types in ewe and mouse models. Contrarily to Escherichia colimastitis, which severity is mainly determined by host factors and not by the strains features \[[@B26]\], it seems that in S. aureus, inter-strain variations exist in terms of virulence potential. Such variations have been experimentally observed but the involved staphylococcal factors have not been clearly identified yet \[[@B27]-[@B29]\]. S. aureuscontent in virulence factors reportedly varies from strain to strain and this may account for the large panel of symptoms encountered in ruminant mastitis \[[@B30]\]. It was also shown that some elements of the core genome could account for host adaptation in S. aureusruminant isolates \[[@B8]\]. Here, we show that two closely related S. aureusstrains are able to induce dramatically different mastitis outcomes in animal model. The experimental mastitis induced in ewes confirmed that strain O11, originally isolated from a gangrenous mastitis, induced more severe infections than strain O46 in ewes. To corroborate the finding of the diversity of the clinical signs caused by O11 and O46, the mouse model of mastitis was employed for further investigation \[[@B31]\]. Despite variable susceptibility to viral, fungal or bacterial infections among the different mouse lines \[[@B32]\], the mouse model was validated as an experimental approach to the study of bovine mastitis \[[@B33]\]. In this study, CD-1 mice infected with O11 or O46 revealed diverse clinical signs and showed different cytokine profiles: O46 induced higher IL-1β and TNF-α levels in the mammary gland lysates and higher serum levels of IL-1β and MCP-1. It has been shown that the cytokines play a pivotal role in the development of the mastitis \[[@B34]-[@B36]\]. Recent investigation revealed that the proinflammatory cytokines, TNF-α and IL-1β, increased the capacity of bovine endothelial cells to eliminate intracellular S. aureus\[[@B37]\]. Endothelial cells may so represent a functional and active defence barrier against bacteria invasion of infected quarters. Higher synthesis of proinflammatory cytokines in O46-infected mice might thus reflect a higher anti-staphylococcal response and may allow more effective elimination of strain O46. Further investigation has to be conducted to confirm this hypothesis. Altogether, our findings demonstrated that these two well-characterized strains reproducibly induce drastically different mastitis in terms of severity, and will prove useful tools to gain further insights into host-pathogen interactions. Inventory of mastitis-associated core and accessory seroproteomes in S. aureusreveals new mastitis-related antigens --------------------------------------------------------------------------------------------------------------------- This study reports the application of SERPA to determine the core and accessory seroproteomes resulting from experimental ewe mastitis induced by two different S. aureusstrains, isolated from a subclinical mastitis (O46) and a gangrenous mastitis (O11). To determine which proteins are recognized by the ewe immune system during mastitis with different severity, experimental infections were carried out on primiparous ewes using these two S. aureusstrains. By comparison of the SERPA profiles, this study allowed, for the first time, the determination of core and accessory seroproteomes for S. aureusin a mastitis context. Eighty nine proteins were immunogenic in ewe mastitis implying they were produced during the infection. Seventy four were found in both seroproteome profiles and composed a core seroproteome. Fifteen of them were found strain-specific and composed the accessory seroproteome. Among the 74 proteins belonging to the core seroproteome, only 44 (59.5%) had already been reported to be immunogenic in infections caused by S. aureusor other pathogens (e.g. Bacillus anthracis, Staphylococcus epidermidis, Clostridium perfringens, Schistosoma japonicum) (Table [2](#T2){ref-type="table"}). Among these previously described antigens, only 30S ribosomal S1 and LukM/LukF\'-PV were previously reported to be immunogenic in S. aureusbovine mastitis \[[@B38],[@B39]\]. These 44 proteins include most of the immunoreactive proteins categorized in Toxins-Haemolysins and Virulence/Defence mechanisms. The remaining 30 proteins (40.5%) are described for the first time as potential staphylococcal antigens in a mastitis context and, to our knowledge, were not described as immunogenic elsewhere. In the accessory seroproteome, 8 out the 15 proteins identified were already described as immunogenic elsewhere whereas 7 of them (AhpF, Opp1A, VVbp, Mqo, cysteine synthase and two hypothetical proteins) are described as such for the first time (Table [2](#T2){ref-type="table"}). A majority of the proteins identified here are thus reported as immunogenic for the first time in a mastitis context. Furthermore, 37 out of 89 proteins of the total seroproteome (\~42%) correspond to proteins described as staphylococcal antigens for the first time whatever the infection considered. Only four of these new antigens are categorized in Toxins-Haemolysins and Virulence/defense mechanisms. The other ones are mostly found in Metabolism (n= 9), Information storage (n= 7), and Unknown function (n= 13). Only a few studies previously analyzed S. aureusproteome and all of them were carried out on human isolates, which reportedly differ from ruminant isolates \[[@B8],[@B9],[@B40]\] and the strains were grown in laboratory culture conditions \[[@B4],[@B41]-[@B46]\]. Here we used two ovine isolates grown in culture conditions mimicking the mastitis context \[[@B11]\]. These two criteria might account for the abundance of new staphylococcal antigens identified in this study. Importance of secreted and exported proteins in seroproteomic patterns ---------------------------------------------------------------------- It is commonly assumed that surface exposed proteins play a role in host-pathogen interactions and that, because of their cellular localization, they are preferentially recognized by the host immune system. In this study, immunoreactive proteins were mainly identified in protein samples prepared from supernatant and cell wall fractions revealing, somehow, discrepancies between experimental (gels of total, cell wall and supernatant protein fractions) and theoretical localization (as determined in silico). Indeed, among the 47 immunoreactive proteins that were predicted cytoplasmic, only 10 were experimentally found in the total fraction and 37 were found in supernatant or cell wall fractions (Table [2](#T2){ref-type="table"}). Such discrepancies were observed in other studies as well \[[@B4],[@B47],[@B48]\]. Some proteins are multifunctional and found both intra- and extracellularly. For example, glyceraldehyde-3-phosphate dehydrogenase \[[@B49]\] and enolase \[[@B50]\] were shown to be both cytoplasmic and surface exposed. In addition to their metabolic role in the cytoplasm, they play a role as adhesins when exposed on the bacterial surface. Furthermore, a new mechanism of protein exportation in Gram positive bacteria was recently described and not included yet in prediction tools for protein localization. It has actually been demonstrated that S. aureus, like some Gram negative bacteria, secretes membrane vesicles, which contained at least 90 different proteins \[[@B51]\]. Twelve of the proteins identified here were found in the vesicle-secreted proteins identified by Lee et al. \[[@B51]\]. Whether the other immunoreactive proteins identified here are secreted through a membrane vesicle mechanism remains undetermined. The core seroproteome --------------------- Proteins belonging to the core seroproteome are immunogenic regardless the severity of the induced mastitis. These proteins are therefore good targets for the development of new strategies against S. aureusmastitis. Some of them have been tested as vaccine target to prevent staphylococcal infections e.g., Enolase (Eno) \[[@B52]\], IsdA (an iron-regulated cell wall-anchored protein) and IsdB (a cell surface transferrin-binding protein) \[[@B53],[@B54]\], GapC/B protein (glyceraldehyde-3-phosphate dehydrogenase) \[[@B55]\], Hla (alpha-hemolysin) \[[@B56]\]. These vaccines seem at least to limit infection damage (by notably decreasing mortality) but not to provide total effective protection. Well-known virulence factors, such as Hla, Hlb (beta-hemolysin), SspA (V8 serine protease), ScpA (Staphopain A), and Plc (phosphatidylinositol phosphodiesterase), were identified here in a mastitis context and were previously identified as immunogenic in human infections \[[@B4],[@B57]\]. Hla and leukotoxins were reportedly produced in vivo during mastitis \[[@B58]\] but to our knowledge this is the first time that the other proteins listed in Table [2](#T2){ref-type="table"} are shown to be produced in vivo during mastitis. These proteins deserve more attention to test their role in the mastitis onset and to check their potential use as target for vaccine development. Of note, we found 5 iron-related proteins (IsdA, IsdB, IsdH, MntC and SirA, 4 of which belonged to the core seroproteome) consistent with the culture conditions (iron depletion) and with a role in the physiologically important and difficult iron uptake in the mastitis conditions. The accessory seroproteome -------------------------- Some proteins were shown to be specifically produced by strain O11 or by strain O46 in infected ewes. None of 12 proteins specifically produced by O11 in vivo had previously been reported as produced during mastitis. Their role in mastitis is thus unknown. Nevertheless most of them have been described as immunogenic in S. aureusinfections in humans. Their function is mainly linked to resistance to host immune response like for IsdH \[[@B59]\], AhpF and TrxB, implied in oxidative stress responses \[[@B60]\] that may confer O11 resistance to neutrophils and so be an advantage compared to O46, Sbi that forms complexes with immunoglobulins Fc regions \[[@B61]\], Aur and SspB. Aureolysin is essential for activation of SspA \[[@B25]\], which in turn activates the SspB zymogen \[[@B62]\]. Aur, SspA and SspB seemed to be more produced in O11 than in O46. They can degrade conjunctive tissue \[[@B63]\]. Aureolysin has been shown to be involved in resistance to macrophage phagocytosis \[[@B64]\] and to significantly contribute to the activation of the fibrinolytic system \[[@B65]\]. It might thus reinforce the degradation of extracellular matrix in the mammary gland and promote bacterial spread and invasion. SspB can activate the chemoattractant chemerin, which results in a local inflammation of the tissue \[[@B66]\]. Moreover it induces the depletion of functional phagocytes at the site of infection by blocking phagocytosis by neutrophils and inhibiting their chemotactic activity \[[@B67]\]. SspB may so take part in the observed swelling of the mammary gland observed during gangrenous mastitis. Moreover, it has been shown that SspA and SspB play an important role in virulence in a mouse abscess model \[[@B68]\]. Opp1A was found to be produced by strain O11 in vivo. Opp proteins seem to take part in virulence in several infection models \[[@B69]\]. Although the role of Opp has not been clearly demonstrated until now, Opp proteins have also been reported to be involved in virulence in other Gram positive pathogens such as group A streptococci \[[@B70]\], Streptococcus agalactiae\[[@B71]\] or Listeria monocytogenes\[[@B72]\]. A variant of von Willebrand factor-binding protein gene has recently been located on the pathogenicity island SaPIov2, characteristic of small ruminant isolates \[[@B9]\]. Interestingly, besides being a coagulase, it is also an activator of pro-thrombin \[[@B73]\] that is present in cow milk \[[@B74]\]. Pro-thrombin activation in thrombin may have a pro-inflammatory effect during mastitis and thus take part in the symptoms observed in animals infected by O11. Whether and how these proteins are involved in the acuteness of the disease induced by O11 remains unknown. O46 specifically produced 3 immunoreactive proteins when compared to O11. IsaA has been reported to be immunogenic in many S. aureusinfections \[[@B3],[@B52],[@B57],[@B75]-[@B77]\]. It presents autolytic activity and is necessary for complete virulence \[[@B78]\] but its role in mastitis is not known. Interestingly, a protein (encoded by O46-2740) which shows similarity to exfoliative toxin D (ETD) was found produced by O46 and not by O11. Three amino-acids were shown to constitute the active site common to all the exfoliative toxins \[[@B79]\]. These amino-acids are present in O46\_2740 gene (O46 strain) product but one is missing in O11-0490 gene product. The corresponding gene is not found in the recently released sequence of ovine strain ED133 \[[@B9]\] although we found its product in the exoproteome of 5 additional S. aureusstrains isolated from subclinical mastitis. ETD is associated with cutaneous abscesses and furuncles \[[@B80]\]. Interestingly this toxin is also produced by Coagulase Negative Staphylococci species like Staphylococcus hyicus, Staphylococcus pseudintermediusand Staphylococcus chromogenes. CNS are highly prevalent in ovine subclinical mastitis \[[@B81]\]. Whether this particular toxin is specifically produced and plays a role during subclinical mastitis remains to be tested. Altogether, proteins differentially produced by O11 and O46 may be considered as potential marker of gangrenous or subclinical mastitis but this has still to be further demonstrated. Conclusion ========== To the best of our knowledge, this study provides the first comparative and comprehensive serological proteome analysis in a mastitis context. The proteins identified are immunogenic in ewes implying that they are also produced in the udder during infection. Many of them are found immunogenic for the first time and a great proportion was found in the supernatant and cell wall fractions even though they were predicted as cytoplasmic proteins. Whether or how these proteins are really involved in the mastitis infection and or the severity of the mastitis remains to be elucidated. This study provides a handful of interesting candidates for further investigations on their potential use as new targets for prophylactic or curative strategies such as vaccine or drug target as some appear to be involved in important virulence-associated functions (toxins, immune evasion, iron uptake). Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= CLM participated in the experimental mastitis in ewes, carried out the 2-DE analyses, participated in the identification of the immunoreactive proteins and drafted the manuscript. JJ and GJ participated in the identification of the immunoreactive proteins by mass spectrometry, SE, NB and RT participated in the design of the study and in the results analyses, CP, JMG and EV carried out the experimental mastitis in ewes, DD and EM carried out the experimental mastitis in mice, DH, PF and JS carried out the genome sequencing and genome sequence analyses, EV and YLL conceived the study, and participated in its design and coordination. All authors read and approved the final manuscript. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 Table S1: Criteria used to define the acuteness of mastitis symptoms ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 Figure S1: Dynamics of gangrenous mastitis onset in ewes infected by S. aureusO11 (argyles) and O46 (squares). ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 3 Figure S2: (A) Intramammary growth of S. aureusstrain O11 and O46 in CD-1 mice. Populations are the mean values of S. aureuscounts in homogenates of 12 mice mammary gland. (B) Temperature of infected mice 24h post-infusion. The mean value of the groups of mice infected with S. aureusO11 or O46 is given. The dashed line indicates the temperature of the animals at T0, before infection. Asterisks indicate statistically significant values. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 4 Figure S3: Quantification of IL1β, IL6, TNF, KC and MCP-1 in mammary gland lysates with BD^™^Cytometric Bead Array. Cytokines were quantified on homogenates of mammary glands infected by S. aureusO11 or O46. Quantities are the mean values of 6 homogenates for each group (O11 and O46) and are expressed in pg/20 μg of total protein. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 5 Figure S4: Quantification of IL1β, IL6, TNF, KC and MCP-1 in serum with BD^™^Cytometric Bead Array. Cytokines were quantified in sera collected on 12 mice infected by S. aureusO11 (6 sera) or O46 (6 sera). Quantities are the mean values of 6 sera for each group (O11 and O46) and are expressed in pg/mL. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 6 Figure S5: Representative 2-DE gels and SERPA on cell wall fraction (upper panels) and total proteins (lower panels) of S. aureusO11. Supernatant samples were prepared from late exponential phase cultures of S. aureusstrains grown anaerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 4-7; 12% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 7 Figure S6: Representative 2-DE gels and SERPA on supernatant fractions of S. aureusO46 (upper panels) and S. aureusO11 (lower panels). Supernatant samples were prepared from late exponential phase cultures of S. aureus*strains grown aerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 3-10; 12% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ Caroline Le Maréchal is the recipient of a PhD grant from the French National Institute for Agricultural Research (INRA) and the Agence Nationale de Sécurité Sanitaire (ANSES), IMISa Project. CLM received a 3-month grant from Université Européenne de Bretagne (UEB).	PubMed Central	2024-06-05T04:04:18.971325	2011-2-15	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052181/", "journal": "Vet Res. 2011 Feb 15; 42(1):35", "authors": [ { "first": "Caroline", "last": "Le Maréchal" }, { "first": "Julien", "last": "Jardin" }, { "first": "Gwenaël", "last": "Jan" }, { "first": "Sergine", "last": "Even" }, { "first": "Coralie", "last": "Pulido" }, { "first": "Jean-Michel", "last": "Guibert" }, { "first": "David", "last": "Hernandez" }, { "first": "Patrice", "last": "François" }, { "first": "Jacques", "last": "Schrenzel" }, { "first": "Dieter", "last": "Demon" }, { "first": "Evelyne", "last": "Meyer" }, { "first": "Nadia", "last": "Berkova" }, { "first": "Richard", "last": "Thiéry" }, { "first": "Eric", "last": "Vautor" }, { "first": "Yves", "last": "Le Loir" } ] }
PMC3052182	Introduction ============ Paramyxoviridaeis a large and diverse family whose members have been isolated from many species of avian, terrestrial, and aquatic animal species around the world \[[@B1]\]. Paramyxoviruses are pleomorphic, enveloped, cytoplasmic viruses that have a non-segmented, negative-sense RNA genome. The family is divided into two subfamilies, Paramyxovirinaeand Pneumovirinae, based on their structure, genome organization, and sequence relatedness \[[@B2]\]. The subfamily Paramyxovirinaecontains five genera: Respirovirus, Rubulavirus, Morbillivirus, Henipavirus, and Avulavirus, while the subfamily Pneumovirinaecontains two genera, Pneumovirusand Metapneumovirus\[[@B3]\]. All paramyxoviruses that have been isolated to date from avian species can be segregated into two genera based on the taxonomic criteria mentioned above: genus Avulavirus, whose members are called the avian paramyxoviruses (APMV), and genus Metapneumovirus, whose members are called avian metapneumoviruses. The APMV of genus Avulavirusare separated into nine serotypes (APMV-1 through -9) based on Hemagglutination Inhibition (HI) and Neuraminidase Inhibition (NI) assays \[[@B4]\]. Various strains of APMV-1, which is also called Newcastle disease virus (NDV), have been analyzed in detail by biochemical analysis, genome sequencing, and pathogenesis studies, and important molecular determinants of virulence have been identified \[[@B5]-[@B9]\]. As a first step in characterizing the other APMV serotypes, complete genome sequences of one or more representative strains of APMV serotypes 2 to 9 were recently determined, expanding our knowledge about these viruses \[[@B10]-[@B18]\]. APMV-1 comprises all strains of NDV and is the best characterized serotype because of the severity of disease caused by virulent NDV strains in chickens. NDV strains vary greatly in their pathogenicity to chickens and are grouped into three pathotypes: highly virulent (velogenic) strains, which cause severe respiratory and neurological disease in chickens; moderately virulent (mesogenic) strains, which cause mild disease; and non-pathogenic (lentogenic) strains, which cause inapparent infections. In contrast, very little is known about the comparative disease potential of APMV-2 to APMV-9 in domestic and wild birds. APMV-2 strains have been isolated from chickens, turkeys and wild birds across the globe \[[@B4],[@B19]-[@B22]\]. APMV-2 infections in turkeys have been found to cause mild respiratory disease, decreases in egg production, and infertility \[[@B23],[@B24]\]. APMV-3 strains have been isolated from wild and domestic birds \[[@B25]\]. APMV-3 infections have been associated with encephalitis and high mortality in caged birds \[[@B26]-[@B28]\]. APMV-4 strains have been isolated from chickens, ducks and geese \[[@B29]\]. Experimental infection of chickens with APMV-4 resulted in mild interstitial pneumonia and catarrhal tracheitis \[[@B30]\]. APMV-5 strains have only been isolated from budgerigars (Melopsittacus undulatus) and cause depression, dyspnoea, diarrhea, torticollis, and acute fatal enteritis in immature budgerigars, leading to very high mortality \[[@B31]\]. APMV-6 was first isolated from a domestic duck and was found to cause mild respiratory disease and drop in egg production in turkeys, but was avirulent in chickens \[[@B10],[@B30],[@B32]\]. APMV-7 was first isolated from a hunter-killed dove and has also been isolated from a natural outbreak of respiratory disease in turkeys. APMV-7 infection in turkeys caused respiratory disease, mild multifocal nodular lymphocytic airsacculitis, and decreased egg production \[[@B33]\]. APMV-8 was isolated from a goose and a feral pintail duck \[[@B34],[@B35]\]. APMV-9 strains have been isolated from ducks around the world \[[@B36],[@B37]\]. APMV types -2, -3, and -7 have been associated with mild respiratory disease and egg production problems in domestic chickens \[[@B33]\]. There are no reports of isolation of APMV-5, -8 and -9 from poultry \[[@B32]\]. But recent serosurveillance of commercial poultry farms in USA indicated the possible prevalence of all APMV serotypes excluding APMV-5 in chickens \[[@B38]\]. APMV-1 (NDV) is known to replicate in non-avian species including humans \[[@B39]-[@B44]\], although its only natural hosts are birds. APMV-1 infections in non-avian species are usually asymptomatic or mild. Clinical signs in human infections commonly involve conjunctivitis, which usually is transient and self-limiting. Presently, APMV-1 is being evaluated as a vaccine vector against human pathogens \[[@B45]\]. When administered to the respiratory tract of non-human primates, NDV is highly restricted in replication, but foreign antigens expressed by recombinant NDV vectors are moderately to highly immunogenic. One of the major advantages of this approach is that most humans do not have pre-existing immunity to APMV-1. Pre-existing immunity is a potential drawback to using vectors derived from common human pathogens, and also can be a concern for any vector if two or more doses are necessary to elicit protective immunity. Therefore, we are investigating APMV types 2 to 9, which are antigenically distinct from APMV-1, as alternative human vaccine vectors. Also, some of these additional APMV types likely will have differences in replication, attenuation, and immunogenicity compared to APMV-1 that may be advantageous. However, the replication and pathogenicity of APMV-2 to -9 in non-avian species has not been studied. As a first step, we have evaluated the replication and pathogenicity of APMV-2 to -9 in hamsters. In this study, groups of hamsters were infected with a prototype strain of each APMV serotype by the intranasal route and monitored for virus replication, clinical symptoms, histopathology, and seroconversion. Our results showed that each of the APMV serotypes replicated in hamsters without causing adverse clinical signs of illness, although histopathologic evidence of disease was observed in some cases, and also induced high neutralizing antibody titers. Materials and methods ===================== Viruses and cells ----------------- The following nine prototype strains of APMV serotypes 1 to 9 were used, APMV-1, NDV lentogenic strain LaSota/46; APMV-2, APMV-2/Chicken/California/Yucaipa/56; APMV-3, APMV-3/PKT/Netherland/449/75; APMV-4, APMV-4/duck/HongKong/D3/75; APMV-5, APMV-5/budgerigar/Kunitachi/74; APMV-6, APMV-6/duck/HongKong/18/199/77; APMV-7, APMV-7/dove/Tennessee/4/75; APMV-8, APMV-8/goose/Delaware/1053/76; APMV-9, APMV-9/duck/New York/22/1978. All of the viruses were grown in 9-day-old embryonated specific-pathogen-free (SPF) chicken eggs inoculated by the allantoic route, except for APMV-5, which was grown in African green monkey kidney (Vero) cells (ATCC, Manassas, VA, USA) \[[@B17]\]. The allantoic fluids from infected eggs were collected 96 h post-inoculation and virus titers were determined by hemagglutination (HA) assay with 0.5% chicken RBC except in the case of APMV-5, which was titrated by plaque assay on Vero cells. The APMV-5 samples were inoculated in triplicate onto 24-well plates of Vero cells at 80% confluency, incubated for 1 h, washed with PBS, overlaid with 0.8% methylcellulose, and observed for plaque production till 7 days post infection (dpi). The cells were fixed with methanol and stained with 1% crystal violet. Values for each tissue sample were based on average plaque count from three wells. Vero cells were grown in Earle\'s minimum essential medium (EMEM) with 10% fetal bovine serum (FBS). Chicken embryo fibroblast (DF-1) cells were grown in Dulbecco\'s minimal essential medium (DMEM) containing 10% FBS at 37°C with 5% CO~2~. Preparation of hyperimmune antisera against viral nucleocapsid (N) proteins in rabbits -------------------------------------------------------------------------------------- For each of the prototype strains, virions were purified on discontinuous sucrose gradients \[[@B12]\]. The viral proteins were denatured and reduced and were separated on 10% SDS-Polyacrylamide gels and negatively stained using E-Zinc ™reversible stain kit (Pierce, Rockford, IL, USA). Each serotype was analyzed on a separate gel to avoid cross contamination. The N protein bands were excised from the gels and destained with Tris-glycine buffer, pH 8. The excised gel bands were minced in a clean pestle and mixed with elution buffer (50 mM Tris-HCl buffer pH 8, 150 mM NaCl, 0.5 mM EDTA, 5 mM DTT and 0.1% SDS) and transferred to the upper chambers of Nanosep centrifugal device (Pall Life Sciences, Ann Arbor, MI, USA). The proteins were eluted by centrifugation at 13000 × gfor 5 minutes, and the eluted proteins were quantified and 200 μg of each protein was mixed in complete Freund\'s adjuvant and injected subcutaneously into a rabbit. After two weeks, a booster immunization was given with 200 μg of protein in incomplete Freund\'s adjuvant and two weeks later the hyperimmune sera were collected. The sera were tested by western blot and were found to recognize specifically the homologous N protein (data not shown). The sera were stored at -80°C until further use. Experimental infection of hamsters ---------------------------------- To study viral replication and pathogenicity, fifty seven 4-week-old Syrian golden hamsters (Charles River Laboratories Inc, Wilmington, MA, USA) were housed in negative-pressure isolators under Bio Safety Level (BSL)-2 conditions and provided feed and water ad libitum. The animals were cared for in accordance with the Animal Welfare Act and the Guide for Care and Use of Laboratory Animals and the protocols were approved by the institution\'s IACUC. Hamsters in groups of six were inoculated intranasally with 100 μL of infectious allantoic fluid containing 2^8^HAU of each individual APMV, except for APMV-5, which contained 3 × 10^3^PFU/mL, under isoflurane anesthesia. A group of three hamsters served as uninfected controls and were mock infected with normal allantoic fluid. The hamsters were observed three times daily for physical activity and for any clinical signs of illness, and were weighed on day 0, 5 and 14 dpi. Three hamsters from each group were euthanized at 3 dpi and the other three (as well as the three animals in the control group) at 14 dpi by rapid asphyxiation in a CO~2~chamber. Necropsies were performed immediately postmortem and the following tissue samples were collected for immunohistochemistry (IHC), histopathology, and virus isolation: brain, nasal turbinates, lung, spleen, kidney and small intestine. In addition serum samples were collected on 14 dpi immediately prior to euthanasia, and seroconversion was evaluated by HI assay \[[@B46]\]. Virus detection and quantification from tissue samples ------------------------------------------------------ Half of each tissue sample was used for virus titration. These samples were collected aseptically in 1 mL of DMEM in 10X antibiotic solution containing 2000 units/mL penicillin, 200 ug/mL gentamicin sulfate, and 4 ug/mL amphotericin B (Sigma chemical co., St. Louis, MO, USA). They were processed immediately to avoid any reduction in virus titers. Briefly, a 10% homogenate of the tissue samples were prepared by using a homogenizer and clarified by centrifugation at 420 × gfor 10 min. For all of the serotypes except APMV-5, the virus titers in the clarified supernatants were determined by end-point dilution on DF-1 cells. Tenfold dilutions of tissue supernatant were inoculated onto DF-1 cells in 96-well plates and incubated for three days. The plates were fixed in 10% formalin for 30 min and the cells were permeabilized using 2% Triton X-100 for 2 min. The plates were washed five times with PBS to remove any residual formalin in the wells. The cells were blocked using 2% normal goat serum for 60 min and the plates were washed twice with PBS- Tween-20 (PBS-T). The cells were incubated with primary rabbit antiserum raised against the N protein of the homologous APMV serotype at room temperature for 1 h. The plates were washed with PBS twice, 5 min each. The cells were incubated with anti rabbit FITC antibody as secondary antibody for 45 min and washed finally with PBS twice, 5 min each. The slides were visualized and the virus titers were determined by end point titration method using the Reed and Muench formula, and were photomicrographed using a fluorescent microscope (Zeiss Axioshop 2000, Zeiss, Göttingen, Germany) \[[@B47]\]. The virus titers in the supernatants of tissue homogenates from APMV-5 infected hamsters were determined by plaque assay in Vero cells as described above using 10-fold dilution series. Values for each tissue sample were based on average plaque count from three wells. Immunohistochemistry (IHC) and histopathology --------------------------------------------- The other half of each tissue sample was used for IHC and histopathology. The tissues were fixed in 10% neutral buffered formalin, held for approximately seven days, and processed for IHC and histopathology. Paraffin embedded 5-micron sections of all the tissue samples were prepared at Histoserve, Inc. (Maryland, MD, USA). The sections were stained with hematoxylin and eosin for histopathology. Sections were also immunostained to detect viral N protein using the following protocol. Briefly, the tissue sections were deparaffinized in two changes of xylene for 5 min each, hydrated in two changes of 100% ethanol for 3 min each, changes of 95% and 80% ethanol for 1 min each, and finally washed in distilled water. The sections were processed for antigen retrieval in a water bath containing sodium citrate buffer (10 mM citric acid, 0.05% Tween 20, pH 6.0), at 95-100°C for 40 min and then allowed to cool to room temperature for another 60 min. The sections were rinsed in PBS-Tween 20, twice for 2 min each. The sections were blocked with 2% BSA in PBS for 1 h at room temperature. The sections were then incubated with a 1:500 dilution of the homologous primary N-specific rabbit antiserum in PBS for 1 h in a humidified chamber. After three washes in PBS, the sections were incubated with the secondary antibody (FITC conjugated goat anti-rabbit antibody) for 30 min. After a further wash cycle, the sections were mounted with glycerol and viewed under an immunofluorescence microscope. Serological analysis -------------------- Sera were collected from all the hamsters on 14 dpi and evaluated for seroconversion by HI assay \[[@B46]\], except in the case of APMV-5. In addition, cross-HI tests were performed to investigate cross reactivity with other APMV serotypes. Since APMV-5 does not cause hemagglutination of chicken RBC, the antibody titer was determined by plaque reduction neutralization assay. Briefly, the sera were heat inactivated at 56°C for 30 min. Ten-fold dilutions of sera were made and mixed with a constant amount of APMV-5 (3 × 10^3^PFU), and incubated at room temperature for 1 h in a shaker. The antigen antibody mixtures were analyzed by plaque assay as described above. The serum titer that reduced plaque numbers by 70% was the end point titer. Results ======= Clinical disease and gross pathology ------------------------------------ Four-week-old hamsters in groups of six were inoculated by the intranasal route with 2^8^HA units of each of the APMV serotypes except APMV-5, which was administered at a dose of 3 × 10^3^PFU/mL. Three animals were sacrificed at day 3 and the remaining three animals were sacrificed on day 14; following sacrifice, the animals were processed for gross pathology, histopathology, IHC, quantitative virology, and seroconversion. Three uninfected animals served as controls and were sacrificed and processed on day 14. All of the animals were observed three times daily and weighed daily. None of the hamsters infected with any of the APMV serotypes showed any visible clinical signs of disease except those infected with APMV-9. All the six hamsters infected with APMV-9 serotype were dull and had rough skin coat at 3 dpi. They appeared weak and lost weight (Table [1](#T1){ref-type="table"}) till 5 dpi, but later gained body weight and appeared normal by 10 dpi. None of the hamsters died of disease. The uninfected control hamsters appeared healthy and normal. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Body weights (in grams) of hamsters infected with APMV serotypes 1 to 9, measured on 0, 5 and 14 days post inoculation (dpi). ::: APMV 0 dpi 5 dpi 14 dpi Body weight difference at 5 dpi --------- ------------- -------------- -------------- --------------------------------- Control 79 ± 0.58 83 ± 0.58 89 ± 0.58 +4.82 APMV-1 75.8 ± 0.17 71 ± 0.58 74.3 ± 1.20 -6.33 APMV-2 77 ± 1.15 75.3 ± 0.3 79.3 ± 0.67 -2.22 APMV-3 78.3 ± 1.2 77.3 ± 2.69 80 ± 2.89 -1.33 APMV-4 77.6 ± 0.88 80.6 ± 0.67 84.67 ± 0.33 +3.72 APMV-5 82.3 ± 1.45 83.33 ± 1.67 90 ± 1.15 +1.2 APMV-6 77 ± 0.56 72.33 ± 1.45 80.33 ± 0.33 -6.45 APMV-7 77 ± 0.58 72.67 ± 1.78 74 ± 1 -5.96 APMV-8 78.3 ± 1.20 72.33 ± 1.45 75.3 ± 1.45 -8.26 APMV-9 78 ± 1.15 66.33 ± 0.67 80 ± 2.89 -17.59 Mean values with standard error are shown. The values of the difference in body weight at 5 dpi are calculated relative to day 0 for the same group and are expressed in percentage gain (+) or loss (-). ::: Following sacrifice on days 3 and 14, the followings organs were removed and examined for gross pathology, histopathology, immunohistochemical analysis, and quantitative virology: brain, lungs, nasal turbinates, small intestine, kidney and spleen. Gross pathologic findings were limited to the lungs of hamsters inoculated with APMV-2 (Figure [1a](#F1){ref-type="fig"}) and APMV-3 (Figure [1b](#F1){ref-type="fig"}), and were observed only at 3 dpi. In APMV-2-infected hamsters, the entire pulmonary parenchyma was wet, glistening and edematous, with some areas of reddening due to congestion and hemorrhages. There were several diffuse small round shaped red foci on the lungs. Similar gross pathology was also seen in the lungs of APMV-3 infected hamsters, but with foci that were five times larger than those seen in APMV-2 infected hamsters. No such gross lesions were observed in the hamsters of the other infected groups at 3 dpi. There were no gross visceral pathologic lesions in any of the infected hamsters at 14 dpi. No lesions were detected in the uninfected control hamsters. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Gross pathology in lungs from hamsters 3 dpi with APMV-2 (a) and -3 (b). (a) Lungs from a hamster infected with APMV-2, showing multifocal mottling with petechial hemorrhages (black arrow). (b) Lungs from a hamster infected with APMV-3, showing multifocal areas of consolidation (white arrow) and ecchymotic hemorrhage (black arrow). (c) Lungs from a mock infected hamster (control). ::: ![](1297-9716-42-38-1) ::: Histopathology -------------- Histopathological lesions at 3 dpi were observed in the nasal turbinates and lungs in all of the infected groups (Figure [2](#F2){ref-type="fig"}, and data not shown). Figure [2e](#F2){ref-type="fig"} and [2f](#F2){ref-type="fig"} show representative examples of the nasal turbinates for APMV-9 and -3, respectively. The most predominant histopathological lesions observed in the nasal turbinates were multifocal necrotic/apoptotic epithelial cells and nuclear pyknosis. Along the nasal septum were areas of epithelial necrosis, accumulation of nuclear debris in the mucosal epithelium, vacuolation of epithelial cells, and blunting or loss of cilia. Small numbers of mononuclear cells and neutrophils multifocally infiltrated the nasal mucosa, with transcytosis and exocytosis into the nasal cavity. There were small accumulations of inflammatory cells and necrotic cellular debris in the nasal cavity. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Representative histopathologic lesions in sections of lung (a-d) and nasal turbinates (e, f) from hamsters 3 dpi with APMV-1 (a, b), APMV-2 (c), APMV-7 (d) and APMV-9 (e, f). Lungs (g) and nasal turbinates (h) from uninfected hamster. (hematoxylin and eosin staining, magnification, ×400). (a) Section of lung infected with APMV-1. The bronchiolar and bronchial epithelia are multifocally hyperplastic (yellow arrow) and contain sloughed cellular debris and inflammatory cells (black arrow). There are moderate numbers of necrotic cells in the bronchiolar epithelium and in areas of inflammation in alveoli. (b) Section of lung infected with APMV-1. There is multifocal infiltration and consolidation of the pulmonary interstitium by moderate numbers of lymphocytes, monocytes, and neutrophils (black arrow), with an accumulation of inflammatory cells in alveoli (yellow arrow). Multifocally, alveoli are lined by rows of hyperplastic epithelial cells (white arrows) that sometimes exhibit cellular atypia, including anisocytosis, anisokaryosis, and cytomegaly (atypical type II pneumocyte hyperplasia). (c) Section of lung infected with APMV-2. The pulmonary interstitium is multifocally infiltrated by moderate numbers of lymphocytes, monocytes, and neutrophils (white arrows). (d) Section of lung infected with APMV-7. The pulmonary interstitium is multifocally infiltrated and consolidated by moderate numbers of lymphocytes, monocytes, and neutrophils (black arrow), with accumulations of inflammatory cells in alveoli. Multifocally, alveoli are lined by rows of hyperplastic epithelial cells (white arrow), with some areas exhibiting cellular atypia, including anisocytosis, anisokaryosis, and cytomegaly (atypical type II pneumocyte hyperplasia). The bronchiolar and bronchial epithelia are multifocally hyperplastic (yellow arrow). There are moderate numbers of necrotic cells in bronchiolar epithelium and in areas of inflammation in alveoli. (e) Section of nasal turbinate infected with APMV-9. There is massive cell death and necrosis of the epithelial tissue lining the turbinate bone (white arrow). There is no appreciable level of inflammatory cells in the surrounding tissues. (f) Section of nasal turbinate infected with APMV-3, showing necrotic tissue, loss of ciliary tissue, and blunting of cilia (white arrow). (g) Section of lung from a mock infected hamster (control). (h) Section of nasal turbinate from a mock infected hamster (control). ::: ![](1297-9716-42-38-2) ::: Examples of lung tissue are shown for APMV-1 (Figure [2a](#F2){ref-type="fig"} and [2b](#F2){ref-type="fig"}), -2 (Figure [2c](#F2){ref-type="fig"}), and -7 (Figure [2d](#F2){ref-type="fig"}). All the lung samples from the infected groups exhibited interstitial bronchopneumonia of varying severity at 3 dpi. The inflammatory cell infiltrates were mixed populations of lymphocytes, macrophages, and neutrophils. Additionally, bronchiolar and type II pneumocyte hyperplasia in areas of inflammation with variable degrees of cellular atypia were noticed and the degree of cellular atypia was quite prominent. There were no histopathologic findings for any other organs (brain, small intestine, kidney, and spleen) from any infected hamsters on day 3, or for any of the hamsters at 14 dpi. Immunohistochemistry -------------------- Deparaffinized sections of the virus-infected and uninfected control tissue (brain, lungs, nasal turbinates, small intestine, kidney, and spleen) were immunostained using polyclonal antisera against the N protein of the homologous APMV serotypes. Remarkably, animals infected with APMV-5 did not show any positive immunofluorescence in any of the tissues examined at 3 or 14 dpi. In animals infected with any of the other APMV serotypes, virus-specific antigens were detected on 3 dpi in the lungs and nasal turbinates (Figure [3](#F3){ref-type="fig"}). In the nasal turbinates, virus-positive immunofluorescence was noticed throughout the nasal epithelium lining the turbinate bone, and the harderian gland located near the eye showed complete diffuse fluorescence throughout the organ. In the lungs, the viral antigens were mostly localized in the epithelium surrounding the medium and small bronchi. Viral N antigens were not detected in any additional organs of infected hamsters at 3 dpi, and were not detected in any of the organs of infected hamsters at 14 dpi. The organs of uninfected control hamsters were also negative by immunohistochemistry assay. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Immunofluorescence localization of viral N antigen in sections of nasal turbinates (a, b), harderian glands (c, d) and lungs (e, f) from hamsters 3 dpi with APMV-9 (a), APMV-1 (b), APMV-9 (c), APMV-8 (d), APMV-3 (e), and APMV-2 (f). Nasal turbinates (g) and lung (h) from a representative uninfected control hamster (magnification, ×400). (a) Section of nasal turbinate infected with APMV-9. Immunofluorescence was evident in the ciliated epithelium lining the turbinate bone (white arrows). (b) Section of nasal turbinate infected with APMV-1. Immunofluorescence was evident primarily at the apical surface of the ciliated epithelial cells and in the cytoplasm (white arrows). (c) Section of harderian gland infected with APMV-9. Immunofluorescence was evident primarily in the collecting ducts of the gland and also in the cytoplasm of the infected cells (white arrows). (d) Section of harderian gland and nasal turbinate infected with APMV-8. Immunofluorescence was evident primarily the cytoplasm of the infected cells in the harderian gland (white arrows) and in the epithelial cells lining the turbinates (yellow arrows). (e) Section of the lung infected with APMV-3. Immunofluorescence was evident around the bronchial epithelium (white arrows). (f) Section of lung infected with APMV-2. Immunofluorescence was mainly evident around the bronchiolar epithelium (white arrows). (g) Section of nasal turbinate from a mock infected hamster (control). (h) Section of lung from a mock infected hamster (control). ::: ![](1297-9716-42-38-3) ::: Virus isolation and titration in tissue samples ----------------------------------------------- To analyze sites of virus replication, several organs (brain, lungs, nasal turbinate, small intestine, kidney and spleen) were collected on 3 and 14 dpi, for virus isolation and titration. For all of the APMV serotypes except APMV-5, titration was performed in DF-1 cells and the titers were expressed in TCID~50~/g tissue; for APMV-5, titration was by plaque assay in Vero cells (Table [2](#T2){ref-type="table"}). Virus was detected for a number of APMV serotypes on 3 dpi; no virus was detected in any sample for any serotype on 14 dpi. APMV-1 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 1.7 × 10^3^and 1 × 10^3^, respectively. APMV-2 was isolated from lungs (3/3 animals) and nasal turbinates (2/3 animals), with mean titers of 4.1 × 10^3^and 5.3 × 10^3^, respectively. APMV-3 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 5.3 × 10^2^and 3.6 × 10^4^, respectively. APMV-4 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 1.7 × 10^2^and 4.2 × 10^3^, respectively, and from the kidneys of one animal (1 × 10^1^). APMV-6 was isolated from the lungs and nasal turbinates of all three animals, with mean titers of 2.6 × 10^3^and 7 × 10^1^, respectively, and from the spleen (1 animal, 3 × 10^1^) and small intestine (1 animal, 3 × 10^1^). APMV-9 was isolated from the nasal turbinates only from all three animals, with a mean titer of 2.5 × 10^5^. No virus was isolated from any tissues of the hamsters infected with APMV-5, -7 and -8. Also, no virus was isolated from the brain of any hamsters infected with APMV-1 to -9. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Virus titers in the indicated tissues from hamsters 3 dpi with APMV serotypes 1 to 9. ::: -------------------------------------------------------------------------------------------- Virus Hamster\ Nasal\ Lung Brain Spleen Kidney Small\ No. Turbinates Intestine -------- ---------- -------------- ------------- ------- ----------- ----------- ----------- APMV-1 1 3 × 10^3^ 2 × 10^3^ \-- \-- \-- \-- 2 2.4 × 10^3^ 3 × 10^3^ \-- \-- \-- \-- 3 4 × 10^3^ 1 × 10^2^ \-- \-- \-- \-- APMV-2 1 9.29 × 10^3^ 1.7 × 10^3^ \-- \-- \-- \-- 2 3.4 × 10^3^ 6.6 × 10^2^ \-- \-- \-- \-- 3 3.5 × 10^3^ ^-^ \-- \-- \-- \-- APMV-3 1 3 × 10^4^ 4 × 10^2^ \-- \-- \-- \-- 2 4.06 × 10^4^ 5.5 × 10^2^ \-- \-- \-- \-- 3 3.75 × 10^4^ 6.6 × 10^2^ \-- \-- \-- \-- APMV-4 1 2 × 10^3^ 3 × 10^2^ \-- \-- \-- \-- 2 2 × 10^3^ 1 × 10^1^ \-- \-- 1 × 10^1^ \-- 3 2 × 10^2^ 2 × 10^2^ \-- \-- \-- \-- APMV-5 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-6 1 1 × 10^2^ 3 × 10^3^ \-- \-- \-- 3 × 10^1^ 2 1 × 10^1^ 4 × 10^3^ \-- \-- \-- \-- 3 1 × 10^2^ 1 × 10^3^ \-- 3 × 10^1^ \-- \-- APMV-7 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-8 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-9 1 3 × 10^5^ \-- \-- \-- \-- \-- 2 1.5 × 10^5^ \-- \-- \-- \-- \-- 3 3.8 × 10^5^ \-- \-- \-- \-- \-- -------------------------------------------------------------------------------------------- The virus titer values are expressed in TCID~50~per gram of the indicated tissue sample ::: Serology -------- The virus replication in the hamsters infected with APMVs was further investigated by measuring seroconversion 14 dpi. Sera were analyzed by HI assay using chicken erythrocytes (Table [3](#T3){ref-type="table"}) in the case of all of the serotypes except APMV-5, which was analyzed by plaque reduction assay. The HI titers of the pre-infection hamsters were 2 or less. All HI titers greater than 8 were considered positive. Our results showed that all of the infected hamsters seroconverted at 14 dpi, indicating replication by all APMV serotypes. The mean HI titers in hamsters for APMV-1, -2, -3, -4, -6, -7, -8, -9 were 1:256, 1:512, 1:512, 1:32, 1:64, 1:64, 1:1024, 1:256, respectively. The mean serum antibody titer of APMV-5 as determined by virus plaque neutralization test was found to be 1:256. The antigenic relationship among APMV serotypes was evaluated by reciprocal HI tests using these sera, which represent convalescent sera obtained by a single infection of hamsters via the intranasal route. Each of the antisera exhibited very high HI titer against the homologous serotype and either no or very low HI titer against heterologous serotypes, with the exception of APMV -1 and APMV-9 (Table [3](#T3){ref-type="table"}). The antiserum specific for APMV-1 and APMV-9 exhibited substantial cross-reactivity, although the APMV-1-specific antiserum had a four-fold higher titer against APMV-1 than against APMV-9, and the APMV-9 specific antiserum had a two-fold higher titer against APMV-9 than against APMV-1. These reactions indicated the existence of antigenic relatedness between APMV-1 and APMV-9. ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Cross-reactivity of sera from hamsters infected with the indicated APMV serotype (top) against the indicated APMV serotype (left column)\. ::: ----------- -------- ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ SERUM* APMV-1 APMV-2 APMV-3 APMV-4 APMV-5 APMV-6 APMV-7 APMV-8 APMV-9 VIRUS APMV-1 1:256 0 0 0 0 0 0 0 1:128 APMV-2 0 1:512 0 0 0 0 0 0 0 APMV-3 0 0 1:512 0 0 0 0 1:8 1:4 APMV-4 1:8 0 0 1:32 0 0 0 0 1:4 APMV-5 0 0 0 0 1:256 0 0 0 0 APMV-6 0 0 0 0 0 1:64 0 0 0 APMV-7 0 0 0 0 0 0 1:64 0 0 APMV-8 0 0 0 0 0 0 0 1:1024 0 APMV-9 1:64 0 0 0 0 0 0 0 1:256 ----------- -------- ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ \* Sera were harvested 14 dpi. Cross-reactivity was measured by HI assay except when tested against APMV-5, in which case a plaque neutralization assay was used. HI titers represent the highest dilution that displayed HI activity, and are expressed in mean HI units. For APMV-5, the 70% plaque reduction titer is shown as the mean. ::: Discussion ========== APMVs are frequently isolated from a wide variety of avian species and are grouped into nine serotypes based on antigenic reactions \[[@B48]\]. APMV-1 (NDV) is the most extensively characterized member of the APMV serotypes. APMV-2 to -9 have been isolated from both wild and domestic birds, but their disease potential in wild or domestic birds is largely unknown. APMV-1 has also been shown to infect a number of non avian species \[[@B41]\] and presently is being evaluated as a potential human vaccine vector for human pathogens \[[@B45]\]. Therefore, there is a possibility that APMV -2 to -9 could also be used as human vaccine vectors for human pathogens. However, the ability of APMV-2 to -9 to replicate in mammalian hosts was unknown. Hence, we have investigated the replication and pathogenicity of APMV-1 to -9 in hamsters inoculated intranasally. The intranasal route was intended to resemble the natural route of APMV infection as well as a likely route for vaccine vector administration. In this study, hamsters were chosen as the mammalian animal model because they are widely used to study replication and pathogenesis of a variety of viruses such as adenovirus \[[@B49]\], herpes virus \[[@B50]\], Nipah virus \[[@B51]\], human RSV \[[@B52]\], human parainfluenza viruses, SARS virus \[[@B53]\], and Eastern equine encephalitis \[[@B54]\]. Clinical disease was not evident with most of the APMV serotypes, and was observed only in the case of APMV-9. All of the animals infected with APMV-9 exhibited clinical disease including weakness and substantial weight loss. Only APMV-2 and -3 produced gross pathological lesions in the lungs, whereas in hamsters infected with the other APMV serotypes the appearance of the lungs was unremarkable. No gross pathology was evident for any other organs with any of the serotypes. Virus was recovered from animals infected with APMV-1, -2, -3, -4, -6, and -9. In all cases, virus was isolated 3 dpi: no virus was detected in any samples for any serotype 14 dpi. The viral titers were moderate and were mostly restricted to the lungs and nasal turbinates; there were isolated incidences of isolation from the spleen (APMV-6), small intestine (APMV-6), or kidneys (APMV-4). No virus was recovered from any tissue from animals infected with APMV-5, -7 and -8. However, the lungs and nasal turbinate tissues from animals infected with APMV-7 and -8 were positive by IHC, indicating that these viruses infected and replicated at a level that was below detection by our assays for quantitative virology. Although APMV-5 was not detected by virus isolation or by IHC in any of the tissues, all of the animals that were inoculated with APMV-5 developed titers of APMV-5 specific antibodies detected by virus plaque reduction neutralization assay, indicating a low level of replication. By 14 dpi, no virus could be detected in any of the tissues in any the infected hamsters for any serotype, whether by histopathology, histochemistry, or virus isolation. This suggests that the virus was cleared from all tissues and disease was resolved, indicating the self-limited nature of the infections. Similar results have been obtained from chickens infected with APMV-2, -3 and -4, where no virus could be isolated at 14 dpi \[[@B30]\]. Using IHC, viral N antigen was detected in the same tissues that were positive by virus isolation. An interesting finding was the presence of large amounts of viral antigens at the epithelial cell linings, suggesting that these cells are highly permissive to APMV replication. In addition, the detection of viral antigens, and in most cases infectious virus, in nasal turbinates and lungs of the hamsters indicate that APMV replication is mostly restricted to the respiratory tract. These results show that all APMV serotypes are capable of infecting hamsters using a nasal route of infection and the extensive amount of virus replication in the respiratory tract was not accompanied by severe disease in hamsters. Serologic assays demonstrated a humoral response in all the hamsters inoculated with APMV serotypes -1 to -9, a further indication of successful virus replication. Our results show that all APMVs (except APMV-5, which does not hemagglutinate) produced HI antibody titers that varied between 1:32 to 1:1024. Based on the HI titers, APMV-8 (1:1024) produced maximum antibody titer and APMV-4 (1:32) produced the least. Paradoxically, while APMV-8 induced the highest titer of HI antibodies, the virus could not be isolated from any of the infected hamsters. Conversely, APMV-4 replicated efficiently in hamsters as observed by virus isolation in nasal turbinates, lungs and kidneys, but produced low levels of virus-specific HI antibodies. Whether these examples of incongruity between levels of replication and serum antibody responses are indicative of differences in the antigenicity of the respective HN proteins or to some other factor remains to be determined. Warke et al. \[[@B30]\] have also provided evidence of low HI titers in the case of APMV-4, in chickens, which was taken as evidence of a low level of replication of this virus in chickens. The HI test is the most commonly used method to diagnose APMV infections and also is used to measure the antibody response. But chicken antiserum against NDV cross-reacts in HI tests with several of the other APMV serotypes, thus questioning the specificity of HI test in field cases \[[@B55]\]. Warke et al. \[[@B38]\] indicated that the HI test lacks sensitivity for detecting infection with these APMV serotypes. They also observed that even in the case of a high infectious dose and observed microscopic changes in the infected organs, high HI titers were not observed in the infected birds. On the contrary in our study, most of the APMV serotypes replicated well in hamsters, producing mild respiratory pathology and high neutralizing antibody titers. Our results indicated that the antibody developed in hamsters against these serotypes were very specific and no cross reaction was observed between serotypes except between APMV-1 and -9. Cross-reactivity between these two serotypes is not completely unanticipated, since they share the highest level of genome nucleotide sequence identity (58%) among the APMV serotypes \[[@B12]\]. Hence, we conclude that the HI test with hamster serum is highly specific and can be used to diagnose different APMV serotypes in field cases. The replication of APMVs in hamsters produced mild rhinitis and mild pathology that was mainly restricted to the respiratory tract. There was a concern that APMVs may also replicate in the intestine and shed in feces, which might act as a source of infection for the other animals. But our results indicated that none of the APMVs replicate in the intestinal epithelial cells of hamsters. Importantly, our results also suggest that these viruses do not cross the blood-brain barrier and do not induce neurological symptoms. Also, our previous experimental studies of all the APMVs in chickens showed that they were avirulent. Taken together, these results show that the APMVs replicate moderately in hamsters and produce either mild or no clinical signs, and elicit substantial antibody responses. Therefore, it is possible that APMVs might replicate in other mammalian species including humans. In conclusion, this study is the first comparative report on the replication and pathogenicity of prototype strains of all 9 APMV serotypes in hamsters. Our results lay the foundation for a good laboratory animal model for testing the replication and pathogenicity of APMV strains. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= AS carried out the pathogenesis studies, carried out the immunoassays, performed the analysis, and drafted the manuscript. MS carried out the pathogenesis studies. HS participated in the analysis, interpretation of histopathological slides. PC and SKS, conceived the study, participated in its design and coordination. All authors read and approved the final manuscript. Acknowledgements ================ We thank Daniel Rockemann, Flavia Dias and all our laboratory members for their excellent technical assistance and help. \"This research was supported by NIAID contract no. N01A060009 (85% support) and NIAID, NIH Intramural Research Program (15% support). The views expressed herein do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.\"	PubMed Central	2024-06-05T04:04:18.983039	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052182/", "journal": "Vet Res. 2011 Feb 23; 42(1):38", "authors": [ { "first": "Arthur S", "last": "Samuel" }, { "first": "Madhuri", "last": "Subbiah" }, { "first": "Heather", "last": "Shive" }, { "first": "Peter L", "last": "Collins" }, { "first": "Siba K", "last": "Samal" } ] }
PMC3052183	1. Introduction =============== The parasitic protozoa of the genus Leishmaniacause a spectrum of diseases in humans, ranging from subclinical cutaneous infections to more serious disseminating diffuse cutaneous, mucocutaneous and visceral forms of the disease. Leishmaniosis is one of the most prevalent neglected tropical diseases affecting public health worldwide \[[@B1],[@B2]\]. It is transmitted by the bite of female sandflies. In developing countries it is associated with extreme poverty. It is estimated that at least 20 million people are infected with Leishmania. The visceral form is the most severe form of the disease. Annually, there are approximately 500 000 new cases of visceral leishmaniosis (VL) \[[@B3]\]. Leishmania donovaniis the primary cause of VL in the Indian subcontinent and East Africa, L. infantumin the areas surrounding the Mediterranean Sea where it is a zoonosis, and L. chagasiin the New World. The last two species are identical. Human beings are the only known reservoir of L. donovani, while canines provide the reservoir for L. infantumand L. chagasi\[[@B4]\]. However, since asymptomatic parasitemic injecting drug users who share injecting devices seem to be a suitable reservoir for L infantum, an artificial anthro-ponotic cycle would be completed. Needles and syringes would be the vectors and uninfected injecting drug users the receptors \[[@B5]\]. Also, L. infantumis known to cause opportunistic infections in patients with HIV/AIDS \[[@B6]\]. Canis familiarisis the major host for these parasites, and the main reservoir for human visceral infection \[[@B7]\]. The risk for reintroduction of VL and other vector-borne diseases in Europe as a consequence of global warming has recently been highlighted \[[@B8]\]. Indeed, VL appears not to be limited to the Mediterranean region and has now spread northwards \[[@B9]\]. Manifestations of VL can vary from asymptomatic infection to progressive fatal visceral disease. Disease progression is dependent on both the species of Leishmaniainvolved and the genetics and immune status of the host. Active VL is characterized by fever, weight loss, hypergammaglobulinemia, hepatosplenomegaly, anemia, thrombocytopenia, leukopenia and immunodepression \[[@B10],[@B11]\]. Also, the presence of parasite-specific antibodies forming immune complexes in the kidneys may lead to the development of glomerulonephritis \[[@B12],[@B13]\]. Leishmaniosis diagnosis and treatment are expensive. Despite considerable advances, there are still no efficient vaccines available against human leishmaniosis \[[@B14],[@B15]\]. Recently, a vaccine containing the fucose-mannose ligand has been industrialized and licensed for commercialization in Brazilian endemic areas under the name of Leishmune^®^(Fort Dodge Ltda, São Paulo, Brazil) to prevent canine VL. Unfortunately, the immune response induced by vaccination has not yet been fully investigated. Also, this vaccine is solely recommended for asymptomatic and seronegative dogs \[[@B16]-[@B19]\]. L. infantumhas a digenetic life-cycle (Figure [1](#F1){ref-type="fig"}), alternating between free-living, flagellated, promastigotes in phlebotomine sand flies and obligate, intracellular, aflagellated amastigotes, which preferentially multiply within macrophages or dendritic cells (DCs) of the vertebrate host \[[@B20],[@B21]\]. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **L. infantumlife cycle*. (1) During the bloodmeal from an infected vertebrate host, the female sandfly ingests free amastigotes, as well as intracellular amastigotes. In the midgut of the sandfly the amastigotes transform into procyclic promastigotes. (2) The procyclic promastigotes multiply and transform into metacyclic promastigotes, the infective stage, that migrate towards the buccal cavity of the sandfly. (3) A bite from the sandfly transmits Leishmaniapromastigotes to susceptible mammalian hosts (i.e., humans and dogs). (4) Promastigotes invade macrophages and DCs. Within these host cells, promastigotes transform into intracellular amastigotes and replicate to produce a large number of parasites. (5) Consequently, the infected cell ruptures and releases amastigotes into the circulation. (6) Free amastigotes can infect other mononuclear phagocytic cells of the blood, spleen, liver, lymph nodes and bone marrow, and the life cycle is repeated. ::: ![](1297-9716-42-39-1) ::: Several experimental models of VL have been developed, but none of these entirely reproduce the disease in humans \[[@B22]\]. Much of the literature from these models documents the immune parameters contributing to resistance against the visceralizing Leishmaniaspecies used in vaccine studies \[[@B23]\]. This contrasts with a limited number of studies which have been prompted to study pathological aspects related to VL. In this context, close attention should be given to the histopathological alterations. Humans, dogs and hamsters often exhibit severe clinical signs and symptoms during visceral infection \[[@B23]-[@B25]\], whereas mice generally show a few minor signs or no clinical signs at all, depending mainly on the size of the parasite inoculum \[[@B26]\]. Under experimental conditions, progression of visceral disease also depends on the route of infection together with the strain of Leishmaniaparasites used \[[@B22]\]. These factors make the choice of a suitable laboratory model difficult. Studies using experimental murine models of VL do not allow exact extrapolations to be made concerning susceptibility in dogs and humans, but increase the ease of identifying genes and predicting their functional roles, as well as investigating the immune mechanisms involved in human and canine leishmaniosis. This review will aim to provide a better understanding of a variety of pathological-immune responses that have been described to date in the most widely used experimental models of VL (Syrian hamsters and BALB/c mice). Combining research approaches at the immunological, pathological and genetic levels helps to advance our understanding of the mechanisms involved in visceral infection at different stages of the disease. 2. Syrian hamster model of VL: suitability of this experimental model ===================================================================== The usual routes of infection in the hamster model of VL are intracardiac and intraperitoneal. However, the administration of parasites by the saphenous vein in order to minimize stress on the hamsters has also been reported \[[@B27]\]. Experimental studies in L. infantumand L. donovani-infected Syrian hamsters (Mesocricetus auratus) often reveal several clinical signs of progressive VL (hypergammaglobulinemia, hepatosplenomegaly, anemia, cachexia and immunodepression) that closely mimic active canine and human disease \[[@B22],[@B23],[@B25],[@B28],[@B29]\]. Surprisingly, there are significant amounts of Th1 cytokines (IFN-γ, IL-2 and TNF-α) in the spleen, but there is little or no IL-4. However, to allow the parasites to multiply, deactivating Th2 cytokines (TGF-β and IL-10) may act on infected macrophages as well as anti-Leishmaniaantibodies (which have no protective role in leishmaniosis) that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver \[[@B30]\]. Interestingly, Syrian hamsters exhibit reduced expression of the gene encoding inducible nitric oxide synthase (iNOS) in response to IFN-γ, and this is thought to lead to a low nitric oxide (NO) generation, subsequently defaulting in parasite killing \[[@B10],[@B28],[@B31]\]. Furthermore, there is a lack of reagents for immunological analysis in the hamster model of VL. Taking these factors into account, we consider the Syrian hamster to be a suitable experimental model for the study of the pathological features of active VL (as described below), but it is not a suitable model for the evaluation of immunization strategies, as a result of the animal\'s high innate susceptibility. In Syrian hamsters, manifestations of VL can range from asymptomatic and oligosymptomatic infections to progressive fatal visceral disease \[[@B28]\]. The pathological features reported during VL include hypoplasia of the white pulp in the spleen, hepatic granulomas and the deposition of a secondary amyloid substance both in the spleen and the liver \[[@B32],[@B33]\]. Also, other studies of active VL have reported that infected hamsters develop glomerulonephritis associated with deposition of immunoglobulins and parasite antigens (immune complexes) in the kidneys. Finally, the disseminated amyloidosis and glomerulonephritis produce renal failure and nephrotic syndrome in infected hamsters \[[@B12],[@B34]\]. The visceral infection in hamsters also induces pathological alterations in hepatocytes, mainly in the endomembrane system and the peroxisomal compartment, leading to a disturbance of liver metabolism \[[@B35]\]. In a recent study \[[@B36]\], hamsters infected with L. infantumwere shown to develop analogous inflammatory myopathies to those observed in naturally infected dogs \[[@B37]\]. Taken together, all these factors probably contributed to the immune response disorders that resulted in the death of the animals \[[@B22],[@B33]\]. Pathological studies from our laboratory showed that after L. infantumintracardiac infection, hamsters exhibited severe histopathological alterations in both the spleen and liver at the peak of parasite burden. Among these alterations, we detected the apparition of granulomas in different maturation stages and giant cell granulomas with amastigotes in the liver (Figure [2A-D](#F2){ref-type="fig"}), as well as disruption of the splenic architecture accompanied by lymphoid depletion (Figure [2E-F](#F2){ref-type="fig"}). Interestingly, several months after intracardiac infection with 10^7^promastigotes of L. infantum, we found external mucocutaneous lesions localized in the snout, accompanied by ulcers on the back of the animals (Figure [3](#F3){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Liver and spleen histological sections from Syrian hamsters stained with H&E. (A) Uninfected hamsters show normal liver histological sections (×40). (B) Hamsters infected with 10^5^L. infantumparasites show granuloma reactions after three months pi (×40). Compare (A) with (B). (C) Granuloma formation. Initial parasitization of KCs (arrows) surrounded by a few inflammatory cells (lymphocytes and monocytes), showing the lack of organization after three months pi (×400). (D) Developing granuloma and giant cells containing few residual amastigotes after three months pi (×400). (E) Normal splenic architecture in control hamsters (×40). (F) Disruption of the splenic architecture accompanied with lymphoid depletion in hamsters infected with 10^7^L. infantumpromastigotes after three months pi (×40). Compare (E) with (F). Hamsters and BALB/c mice were purchased from Harlan Interfauna Ibérica S.A. (Barcelona, Spain). The animals were maintained under conventional conditions approved by the Ethical Committee for the Animal Experimentation of the Complutense University of Madrid. ::: ![](1297-9716-42-39-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### External lesions observed in Syrian hamsters infected with 10^7^L. infantumpromastigotes at seven months pi. (A-B) Mucocutaneous lesions localized in the snout. (C) Ulcers on the back of the hamsters. The isolate M/CAN/ES/96/BCN150 (zymodeme MON-1) of L. infantumwas used for infection experiments. This strain was maintained in our laboratory by passage in Syrian hamsters. ::: ![](1297-9716-42-39-3) ::: 3. Mouse model of VL: genetic control of susceptibility to L. infantuminfection ================================================================================= Genetic control studies of various host defense mechanisms in the mouse (Mus musculus) model during the course of progressive infection with visceralizing Leishmania spp. are summarized in Table [1](#T1){ref-type="table"}. These experiments made an important contribution in identifying genes involved in VL innate and acquired immunity. Identification of the Slc11a1gene aided our understanding of the susceptibility at early stages of infection in BALB/c mice, which reflects the strength of the innate immune response in controlling early parasite growth independently of acquired immune mechanisms. The Slc11agene also controls susceptibility to bacteria. Indeed, mutations in Slc11a1cause susceptibility to infection with Salmonella spp. \[[@B38]\] and Mycobacteria spp. \[[@B39]\]. Interestingly, iron is required for replication of pathogens such as Leishmaniaparasites in phagosomes. The Slc11a1gene encodes a protein expressed on the membrane of infected phagosomes that removes Fe^2+^and Mn^2+^ions from the intra-phagosomal compartment restricting intracellular Leishmaniamultiplication in iron-limited intracellular environments \[[@B40],[@B41]\]. Genetically resistant mouse strains (e.g., CBA) possess a functional Slc11a1gene which confers innate resistance to early Leishmaniaparasite growth. In contrast, susceptible mice strains (e.g., C57BL/6 and BALB/c) possess a non-functional Slc11a1gene and early parasite growth in the liver cannot be controlled \[[@B42]\]. However, most susceptible mouse strains, including BALB/c, develop acquired immune mechanisms to control hepatic parasite growth at later stages of infection (as previously reviewed \[[@B43],[@B44]\]). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Genes that control the immune response to L. donovani/L. infantuminfection. ::: Host defense mechanism(s) Locus or gene Chromosome Reference(s) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------- ------------ ------------------- Innate intraphagosomal control of infection in the spleen and the liver Slc11a1* 1 \[[@B40]-[@B44]\] Influences antigen presentation during the acquired immune response in the splen, the liver and the bone marrow H2 17 \[[@B43],[@B45]\] Formation of hepatic granulomas. Acquired immune response Ir2 2 \[[@B43]\] Influences resistance to parasites in the spleen. C57BL/6J bg/bg mice expressed deficient natural killer cell activity and failed to eliminate L. donovaniamastigotes Lyst/Beige 13 \[[@B46]\] ::: The parasite load in the liver at later stages of infection, which probably reflects the strength of the acquired immune response, was found to be controlled by the H2and Ir2loci. The haplotype at the H2genomic region on chromosome 17 is involved in antigen presentation through the major histocompatibility complex (MHC). Genetic polymorphism in the MHC influences the response to numerous antigens. Several MHC haplotypes have not only been associated with resistance to leishmaniosis, but also with resistance to many other infections \[[@B45]\]. Differences between the H-2^b^and H-2^d^haplotypes were observed in the BALB/c background, where H-2^b^resulted in lower parasite numbers in the liver than H-2^d^. In addition to the liver, the H2region influences parasite numbers in the spleen and bone marrow \[[@B43]\]. Histopathological analysis revealed that the Ir2locus in mice promoted fewer granulomas that were smaller in size, due to an efficient anti-parasite response. The parasite burden in the spleen was also found to be controlled by the Lyst/Beigegene on chromosome 13. Indeed, homozygous C57BL/6J bg/bg (beige) mice expressed deficient natural killer (NK) cell activity and failed to eliminate L. donovaniamastigotes \[[@B46]\]. 4. BALB/c mouse model of VL: organ-specific immune responses ============================================================ The variations in the susceptibility to VL in different strains of mice were first described nearly 40 years ago \[[@B47]\]. In BALB/c mice, the immune response to L. infantumand L. donovaniinfection can vary markedly between different organs (liver and spleen) within the same animal. In the liver, the infection can resolve with subsequent immunity to re-infection, whereas in the spleen, Leishmaniaparasites can persist \[[@B48]\]. A schematic view of the organ-specific immune responses after experimental infection with L. infantumin susceptible BALB/c mice is shown in Figures [4](#F4){ref-type="fig"} and [6](#F6){ref-type="fig"}. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### *A schematic view of the immune responses in BALB/c mice livers after experimental infection with L. infantum**. After intravenous inoculation, the parasites enter the liver and invade macrophages and DCs. (A) During the hepatic acute phase (up to two weeks pi), Leishmaniaamastigotes multiply in the absence of both IL-12 production and activated T-cells. Consequently, the number of parasites in the liver reaches a peak. (B) Two weeks pi, Leishmania-specific T lymphocytes migrate to the liver from the spleen and the acquired hepatic immune response is initiated. The interaction of Leishmania-specific T cells with infected KCs and DCs provides the proinflammatory (Th1) environment required for efficient granuloma formation, resulting in the resolution of hepatic infection. (C) The kinetics of parasite burden and different stages of granuloma maturation in the liver after L. infantuminfection. Infected KCs with no granulomatous reaction and immature granulomas were observed in high numbers at 14 days pi but these initial stages of granuloma formation decreased in number during the course of infection, developing mature and sterile granulomas. Significantly, by 56 days pi, the number of sterile granulomas, in which the amastigotes were killed, increased and consequently, the Leishmaniaparasite burden decreased. Finally, the infection in the liver of BALB/c mice was resolved. ::: ![](1297-9716-42-39-4) ::: ::: {#F5 .fig} Figure 5 ::: {.caption} ###### The liver granuloma reaction after L. infantuminfection. (A) The histology of the liver and cellular infiltrates in infected mice at 28 days pi (×40). Compare (A) with the detail in the lower right corner of the image (non-infected mice showing normal histological appearance, ×40). Liver granuloma evolution: (B) immature granulomas. Early parasitization of KCs (arrows) with initial cell recruitment (×400), at 14 days pi. (C) Mature granuloma assembly at infected KCs, resulting in the attraction of lymphocytes and monocytes, at 28 days pi (×400). (D) Mature-sterile granuloma, free of amastigotes, at 56 days pi (×200). ::: ![](1297-9716-42-39-5) ::: ::: {#F6 .fig} Figure 6 ::: {.caption} ###### A schematic view of the immune responses in the BALB/c mice spleens after experimental infection with L. infantum**. (A) In the initial stage of infection, parasites from the blood invade macrophages and DCs into the splenic MZ. Also, DCs acquire parasite antigens in the MZ and subsequently migrate to the PALS. (B) DCs produce IL-12 and present parasite antigens to T cells in the PALS. (C) Leishmania-specific T-cells are activated in the PALS but a failure in the specific effector response prevents them from interacting with parasitized host cells in the MZ. Finally, chronicity of infection occurs in the spleen. (D) The kinetics of parasite burden and loss of germinal centers in the spleen after L. infantuminfection. The progressive loss of splenic germinal centers increased with time. Thus, in the spleen, a site of chronic infection, the high levels of depletion in the white pulp at 56 days pi correlated with the high Leishmaniaparasite burden. ::: ![](1297-9716-42-39-6) ::: 4.1. Liver: control of hepatic infection ---------------------------------------- ### 4.1.1. Development of an immune response to the early stage of infection After being inoculated into the lateral vein of the tail, the parasites enter the liver via the portal vein and invade macrophages and DCs. In both these types of host cell, promastigotes transform into amastigotes. At this point, the innate immune system constitutes its first line of defence against Leishmaniaparasites. The parasitized resident macrophages (Kupffer cells, KCs) secrete chemokines (CCL3, CCL2 and CXCL10) that stimulate the recruitment of monocytes and granulocytes \[[@B44]\]. Despite the activation of these mechanisms in mice, amastigotes survive during the hepatic acute phase (up to two weeks post-infection (pi)) in an environment with small quantities of inflammatory cytokines, in the absence of activated T cells. Consequently, the number of parasites in the liver reaches a peak (Figure [4A](#F4){ref-type="fig"}). Nevertheless, the parasite burden may decrease dramatically with the acquisition of the granulomatous response during the next stage of infection, as described below. ### 4.1.2. Development of an immune response to the later stage of infection: granuloma formation Recent research favours a model in which Leishmania-specific T lymphocytes are pre-activated in the spleen and then migrate to the liver \[[@B48]\]. Once there, activated T cells interact with parasitized DCs, serving as a critical source of IL-12 production, that then triggers the subsequent Leishmania-specific CD4^+^Th1 effector response during the later stage of infection \[[@B21]\]. Interestingly, activated DCs can also trigger NK cell cytotoxicity and the production of IFN-γ \[[@B49]\]. In contrast to DCs, the production of IL-12 is blocked in infected macrophages. Consequently, the parasite-carrying macrophages are incompetent at priming CD4^+^T cells or stimulating antigen-specific CD4^+^T cells \[[@B50]\]. Therefore, the interaction of Leishmania-specific CD4^+^T cells with infected DCs in the liver provides the proinflammatory (Th1) environment required for efficient granuloma formation (Figure [4B](#F4){ref-type="fig"}), which includes IL-12, IFN-γ, TNF-α and IL-2 production \[[@B10],[@B48],[@B51]-[@B53]\]. It is at this stage of infection (weeks 2-4 pi) that the acquired hepatic immune response is initiated. Simultaneously, the fusion of infected KCs to form multinucleated cells also contributes to inflammatory cytokine production during granuloma formation \[[@B54],[@B55]\]. In BALB/c mice, acquired hepatic resistance to L. infantumclearly depends upon granuloma development. Thus, the structure of a mature tissue granuloma consists of a core of fused, parasitized KCs with an encircling mononuclear cell mantle containing blood monocytes and both CD4^+^and CD8^+^T cells. In some instances, B cells, plasma cells and granulocytes are also attracted. In immunologically active granulomas, antigen-presenting DCs and cytokine-secreting T cells are required for antimicrobial activity \[[@B54]\]. The formation of a granuloma is not always associated with parasite control, and the effectiveness of hepatic granulomas to kill parasites depends on their degree of maturation \[[@B52],[@B54]\]. It appears that the TNF family of cytokines are not involved in the formation of granulomas but instead are involved in their maturation, as well as the maintenance of splenic architecture \[[@B42]\]. Granulomas become fully evolved by 2-4 weeks pi. The overall antimicrobial efficacy of the granulomatous response appears to be variable, and only mature granulomas develop efficient leishmanicidal mechanisms to kill parasites. In contrast, developing granulomas have been reported to be less efficient at killing Leishmaniaparasites. Among other factors, granuloma development has been found to vary depending on the initial inoculum size. Indeed, higher numbers of mature and sterile granulomas are observed in mice infected with a low-inoculum size than in those infected with a high-inoculum size \[[@B26]\]. In structurally mature hepatic granulomas, the elaboration of leishmanicidal reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates (RNIs) is essential for parasite killing within infected KCs and DCs \[[@B44],[@B54]\]. There are various classification schemes for granulomatous inflammation in VL. Murray et al. \[[@B54]\] reported a summary of liver granuloma structure-function relationships in experimental VL. To score the progression of the granulomatous response, Stager et al. \[[@B56]\] also classified the infected focus as follows: (1) an infected KC with no associated cellular infiltrate, (2) an early granuloma comprising an infected KC surrounded by a few inflammatory cells, with no organization, (3) a mature granuloma with an organized structure, or (4) a sterile granuloma, in which amastigotes had been killed as a result of effective antileishmanial immunity. Following the above criteria our laboratory data also revealed that the resolution of disease in the livers of mice infected with L. infantumcorrelates with granuloma development (Figure [4C](#F4){ref-type="fig"} and Figure [5A](#F5){ref-type="fig"}). Early in the course of infection, granulomas at various stages of maturation are apparent \[[@B44]\]. Thus, relatively mature granulomas can be readily detected alongside infected KCs that have no associated cellular infiltrate at around four weeks pi (Figure [4C](#F4){ref-type="fig"}). Infected KCs exhibiting no granulomatous reaction and immature granulomas (Figure [5B](#F5){ref-type="fig"}) were observed in high numbers at two weeks pi, but their numbers decreased during the course of infection as mature (Figure [5C](#F5){ref-type="fig"}), sterile (Figure [5D](#F5){ref-type="fig"}) granulomas developed, in which the amastigotes were killed. After eight weeks pi, sterile granulomas gradually dissembled in an involution process \[[@B54]\]. Although sterile cure is never achieved in the liver, parasite growth is controlled without inducing pathology and it is resistant to secondary infections with L. infantum\[[@B44]\]. It is possible that parasite persistence might mediate long-term immunity in the liver in a similar manner to that seen in the cutaneous leishmaniosis model caused by low-dose infection with L. major\[[@B57]\]. Studying the granulomatous response is important because granuloma development has been associated with Leishmaniainfection in the liver, as demonstrated in rodent models. Moreover, enhanced granuloma maturation represents a good marker of successful vaccination against VL \[[@B58]\]. 4.2. Spleen: visceralizing Leishmaniaparasites persist and destroy the splenic architecture --------------------------------------------------------------------------------------------- In contrast to the liver, the spleen and bone marrow become chronically infected in mice \[[@B44]\]. The immune response to L. infantumin the spleen (Figure [6A-C](#F6){ref-type="fig"}) can be separated into two phases: acute and chronic. ### 4.2.1. The acute phase of infection Following intravenous experimental infection in mice, L. infantumpromastigotes enter the spleen via the splenic artery and are rapidly removed from the circulation in the spleen by marginal zone (MZ) macrophages and rarely by DCs. It is likely that the majority of DCs acquire Leishmaniaantigens by phagocytosis of infected macrophages or their remnants in the MZ \[[@B44],[@B59]\]. Within these cells, promastigotes replicate intracellularly as amastigotes. In the spleen, MZ macrophages phagocytose \> 95% of intravenously administered L. infantumparasites, where \> 50% of the initial parasite inoculum is killed within 24 h of infection \[[@B48]\]. It appears that DCs acquire parasite antigens within the MZ (Figure [6A](#F6){ref-type="fig"}) and subsequently migrate to the periarteriolar lymphoid sheath (PALS). Once in the PALS, DCs secrete IL-12 \[[@B60]\] and present parasite antigens to T and NK cells, resulting in the activation of these effector cells (Figure [6B](#F6){ref-type="fig"}). Interestingly, L. infantuminfection stimulates IL-12 production by splenic DCs within the PALS, but not infected macrophages within the MZ \[[@B61]\]. As described above, evidence suggests that Leishmania-specific T lymphocytes are primed in the spleen during the acute stage of infection (\< 4 weeks) and then migrate to the liver to initiate a granulomatous response \[[@B42],[@B44],[@B48],[@B62]\]. ### 4.2.2. The chronic phase of infection During the chronic stage of infection (\> 4 weeks) in the spleen, failure to resolve L. infantuminfection occurs (Figure [6C](#F6){ref-type="fig"}) and the splenic architecture breaks down. There are at least three possible explanations for the failure of the specific effector response \[[@B48]\]: (1) assuming that the priming of T and NK cells by DCs occurs at the PALS, a site that is anatomically segregated from the MZ, infected macrophages fail to produce chemoattractants to bring effector cells into their vicinity. (2) Infected macrophages are unable to activate intrinsic leishmanicidal mechanisms following exposure to cytokines and ligands from T and NK cells. It has been reported that L. infantum-infected macrophages fail to produce IL-12 and also have a reduced capacity to generate both ROIs and NO, which are important microbicidal molecules for killing intracellular pathogens \[[@B44],[@B54],[@B61]\]. (3) Failure in the development of the efficient granulomatous immune effector response occurs in the spleen. Together, the low expression levels of MHC class II on L. infantummacrophages and their intrinsic defects in the generation of an antileishmanial response (see above), contribute to failure to form inflammatory foci around infected MZ macrophages \[[@B48]\]. Any of these three possibilities may contribute to the failure of the spleen to resolve murine VL. Paradoxically, the spleen is an initial site for the generation of cell-mediated immune responses, but ultimately becomes a site of parasite persistence, with associated immunopathological changes \[[@B44]\]. ### 4.2.3. Pathological changes in the spleen In the spleen, L. infantumparasite persistence is accompanied by a failure of granuloma formation, splenomegaly and other pathological changes, such as the disruption of splenic microarchitecture, including the disintegration of the white pulp accompanied by the destruction of follicular DCs, and the absence of germinal centres \[[@B10],[@B22],[@B24],[@B42],[@B48],[@B61],[@B63]\]. Interestingly, there is evidence that high levels of TNF mediate the destruction of MZ macrophages, while IL-10 promotes impaired DC migration into T-cell areas with subsequent ineffective T-cell priming \[[@B44]\]. Data from our laboratory showed that during the acute stage of infection (\< 4 weeks), parasite burden and the level of splenic disruption increases with time (Figure [6D](#F6){ref-type="fig"}). Previously, we have reported that the intensity of lymphoid depletion can vary depending on the initial inoculum size. Indeed, higher numbers of lymphoid-depleted BALB/c mice were observed when a high-inoculum size was used compared with a low-inoculum size \[[@B26]\]. In agreement with previous studies \[[@B44]\], our findings revealed the progressive development of splenic pathology in mice infected with L. infantum, including disruption of tissue anatomy accompanied by the loss of germinal centers (Figure [7](#F7){ref-type="fig"}). ::: {#F7 .fig} Figure 7 ::: {.caption} ###### Changes in splenic anatomy after L. infantuminfection. (A) Non-infected mice showed normal histological appearance (×40). (B) After 56 days pi, the splenic architecture showed a significant loss of germinal centers (arrow) in the white pulp (×40). Compare (A) with (B). ::: ![](1297-9716-42-39-7) ::: 5. Remarks and discussion ========================= The experimental murine model of L. infantuminfection mimics many of the features of canine and human infections. Syrian hamsters also exhibit severe clinical signs and symptoms that are similar to those observed in naturally infected dogs and humans \[[@B23],[@B24],[@B36]\]. However, the absence of iNOS expression \[[@B10],[@B28],[@B31]\] and the suppression of lymphoproliferative responses \[[@B64],[@B65]\] observed, lead us to argue that the hamster is a more suitable model for pathological studies of VL than for the evaluation of vaccine candidates. However, to date, most researchers have elected to use the BALB/c mouse model for investigating disease pathogenesis of VL, as well as for vaccine studies \[[@B26],[@B44],[@B54],[@B66]-[@B68]\]. In mice, the susceptibility to visceralizing Leishmaniaspecies is mainly determined by the Slc11a1gene that encodes a phagosomal component that confers the ability to control the early infection (as described above). Even so, BALB/c mice, lacking this gene, are able to control the infection at a later stage \[[@B42],[@B69]\]. In this context, BALB/c mice provide a better model of self-healing or subclinical infection than of disseminated visceral disease \[[@B10]\]. Paciello et al. \[[@B36]\] reported that susceptible mouse strains do not reproduce progressive disease as observed in human active VL. Furthermore, the intensity of pathological changes in the visceral organs of BALB/c mice can vary depending on the initial inoculum size, as described above. Indeed, we proposed that infecting mice with a large inoculum constitutes a suitable model for the study of the pathological changes of VL \[[@B26]\]. Infection with L. infantum, either intravenously or intradermally, leads to organ-specific immune responses that are important determinants of disease outcome in BALB/c mice \[[@B10],[@B48]\]. Apparently, the intravenous route of inoculation does not mimic natural infection by the sandfly \[[@B22]\]. However, during natural infection, the blood-sucking action of the vector on the skin of the host may result in both intravenous and intradermal administration of the parasite \[[@B26]\]. Subsequently, parasites multiply rapidly for the first few weeks in the liver. Curiously, the spleen is the initial site of generation of specific T effector cells with the ability to move to the liver. Once in the liver, the development of cell-mediated immune responses is essential for the clearance of L. infantumparasites. In contrast, the spleen ultimately becomes the site of parasite persistence \[[@B26],[@B44],[@B66],[@B70]\], suggesting that the spleen is more susceptible to L. infantum*infection than the liver \[[@B71]\]. Interestingly, the leishmanicidal efficacy of hepatic granulomas is dependent on their degree of maturation \[[@B26],[@B51],[@B56]\]. Therefore, determining the degree of maturation of hepatic granulomas constitutes an effective tool for selecting VL vaccine candidates and for monitoring disease progression. In summary, it is reasonable to suppose that understanding the development of acquired parasite-specific immunity in the liver and the reasons for effector splenic response failure in VL, may lead to the development of effective strategies for parasite clearance in host target organs during VL and new treatments for canine and human leishmaniosis. 6. Competing interests ====================== The authors declare that they have no competing interests. 7. Authors\' contributions ========================== AN performed the histopathological analyses and participated in the design of the study. GDB, JAO, RDF and NME participated in the design and the discussion section of this paper. JC conceived of the study, carried out the experiments and wrote the paper. All authors read and approved the final manuscript. 8. Acknowledgements =================== This research was support in part by a grant from the Spanish Ministry of Education and Science (MEC) (AGL2007-62207). Francisco Javier Carrión Herrero is an investigator of the \"Juan de la Cierva\" program (JCI-2009-04069) from the Spanish Ministry of Science and Innovation (MICINN).	PubMed Central	2024-06-05T04:04:18.986467	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052183/", "journal": "Vet Res. 2011 Feb 23; 42(1):39", "authors": [ { "first": "Ana", "last": "Nieto" }, { "first": "Gustavo", "last": "Domínguez-Bernal" }, { "first": "José A", "last": "Orden" }, { "first": "Ricardo", "last": "De La Fuente" }, { "first": "Nadia", "last": "Madrid-Elena" }, { "first": "Javier", "last": "Carrión" } ] }
PMC3052184	Introduction ============ Neospora caninumis an obligate intracellular parasite that is phylogenetically related to Toxoplasma gondiiand causes neuromuscular disease in dogs and abortion in cattle, although it can infect other host species \[[@B1],[@B2]\]. Neosporosis is currently recognised as one of the main causes of infectious bovine abortion worldwide \[[@B1]\]. Previous studies have demonstrated that differences occur in the genetic and biological characteristics of N. caninumisolates. Thus, genetic diversity among N. caninumisolates has been detected using different polymorphic markers \[[@B3]\], including those that are based on microsatellite sequences, which were demonstrated to be the most suitable for typing N. caninumisolates \[[@B4]-[@B8]\]. Importantly, N. caninumisolates exhibit differences in their capacity to produce pathology in cerebral mouse models \[[@B9]-[@B12]\], and in their efficacy to be transmitted from dams to offspring \[[@B13]-[@B16]\]. Genetic and biological intra-specific diversity of N. caninumisolates may influence their capacity to produce disease in the natural host, and the clinical presentation and epidemiology of neosporosis. Very little information is known about the inherent factors of this parasite that contribute to its intra-specific pathogenicity, but the capacity to produce pathology has been associated with the behaviour of different N. caninumisolates in the host. The dissemination capacity, the parasite burdens that are reached in target tissues, the ability to avoid the immune response produced against the infection by the host and the rate of tachyzoite-bradyzoite conversion in the host may all contribute to the different levels of pathogenicity that are caused by different isolates \[[@B11]-[@B13],[@B16],[@B17]\]. Previous in vitro studies have reported that the growth \[[@B18],[@B19]\] and bradyzoite conversion rates \[[@B14],[@B20],[@B21]\] are variable among different N. caninumisolates. Additionally, the low pathogenicity levels of the Nc-Spain 1 H isolate in mice and cattle have been attributed to the low viability rate and tachyzoite yield of this isolate in cell cultures \[[@B14],[@B15]\]. Therefore, similar to T. gondii, the inherent pathogenicity of different N. caninumisolates may be directly related to specific virulence traits, which include the migration capacity, the ability to cross barriers and the cell invasion and intracellular proliferation efficiencies \[[@B22]-[@B25]\]. In this work, we investigated the association between the in vitro phenotypes that were displayed by N. caninumisolates and their pathogenicity. Specifically, we examined the invasion efficiencies and the intracellular proliferation kinetics of eleven N. caninumisolates, including the naturally attenuated NcSpain-1 H isolate and the highly pathogenic Nc-Liverpool isolate, which showed profound differences in their vertical transmission characteristics and their capacities to induce pathology in pregnant cattle \[[@B14],[@B26]\]. Materials and methods ===================== Cell cultures, parasites and preparation of N. caninumisolates for in vitro assays ------------------------------------------------------------------------------------ The N. caninumisolates that were used in this study are shown in Table [1](#T1){ref-type="table"}. The Spanish N. caninumisolates and the Nc-Liverpool (Nc-Liv) isolate were routinely maintained in a monolayer culture of the MARC-145 monkey kidney cell line after reactivation from cryovials, as described previously \[[@B5]\]. The Nc-Liv isolate was previously passaged in a mouse and re-isolated in MARC-145 cell cultures as described previously \[[@B16]\], to minimise the occurrence of potential alterations in its biological characteristics due to prolonged cell culture maintenance, as has been previously reported \[[@B27]\]. The N. caninumisolates that were used in these in vitro assays were subjected to a limited number of culture passages (Table [1](#T1){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Neospora caninumisolates included in the in vitro assays. ::: ---------------------------------------------------------------------------------------------------------------------------------------------------------- Isolate\* Host origin\\ Geographical origin^&^ Passages number^§^ Neonatal morbidity\ Neonatal mortality\ Vertical\ (%)^\#^ (%)^\#^ transmission rate\ (%)^\#^ ---------------- -------------------------- ------------------------ -------------------- --------------------- --------------------- -------------------- Nc-Spain 1H^a^ 2-day-old healthy calf Madrid 12-18 0^L^ 5^L^ 5^L^ Nc-Spain 2H 2-day-old healthy calf Zaragoza 7-13 46.1^L^ 20.4^L^ 61.3^L^ Nc-Spain 3H^b^ 52-day-old healthy calf Navarra^1^ 19-25 10.6^L^ 7.7^L^ 89^H^ Nc-Spain 4H^b^ 22-day-old healthy calf Navarra^1^ 12-18 100^H^ 100^H^ 97.3^H^ Nc-Spain 5H 14-day-old healthy calf León 12-18 98.6^H^ 96^H^ 100^H^ Nc-Spain 6 30-day-old healthy calf País Vasco 20-26 34.5^L^ 29.8^L^ 57.6^L^ Nc-Spain 7 57-day-old healthy calf Navarra^2^ 17-23 98.3^H^ 95^H^ 79.1^L^ Nc-Spain 8 2-day-old healthy calf Navarra^1^ 8-14 4.7^L^ 1.1^L^ 56.4^L^ Nc-Spain 9 7-day-old healthy calf Navarra^2^ 9-15 39^L^ 32.5^L^ 52.6^L^ Nc-Spain 10^a^ 2-day-old affected calf? Madrid 21-27 25.5^L^ 17.9^L^ 65.5^L^ Nc-Liverpool 4-week-old affected dog UK 12R-19R^@^ 100^H^ 100^H^ 95.6^H^ ---------------------------------------------------------------------------------------------------------------------------------------------------------- Summary of name, genetic characterisation, host and geographical origin, passage number in cell culture, and their pathogenicity in a BALB/c pregnant mouse model determined in previous studies \[[@B14],[@B16]\]. \* Nc-Liv and Spanish isolates were genetically characterised by microsatellite analysis. Letters in superscript (^a^) and (^b^) indicate isolates with identical microsatellite profiles \[[@B4],[@B5],[@B14]\]. \\All Spanish isolates were obtained from asymptomatic calves from different cattle. Nc-Spain 10 was isolated from an affected calf, but its clinical signs could not be attributed to Neosporainfection \[[@B5],[@B14]\]. Nc-Liv was isolated from a clinically affected dog \[[@B50]\]. ^&^The geographical origin of Spanish isolates is indicated by province. Calves from Navarra originated from two dairy herds. Numbers in superscript (^1^) and (^2^) identify the dairy herd. Nc-Liverpool was isolated in the United Kingdom. ^§^The total number of cell culture passages of the N. caninumisolates included in these in vitro assays. (^@^) marks the total passages after re-isolation of Nc-Liv in cell culture from BALB/c nu/numice. ^\#^The percentages of neonatal morbidity and neonatal mortality and vertical transmission rates were determined in previous studies using a pregnant BALB/c mouse model \[[@B14],[@B16]\]. ^L,\ H^Isolates were categorised into lowly/moderately pathogenic (^L^) or highly pathogenic (^H^) groups according to the significant differences found in neonatal morbidity and mortality. Identical superscript letters denote highly (^H^) and lowly/moderately transmissible (^L^) isolates. ::: The tachyzoites that were used in the in vitro assays were recovered from 3.5-day growth cultures, when the majority of the parasites were still intracellular (at least 80% of the parasite vacuoles were undisrupted in the cell monolayer), and purified using PD-10 (Sephadex G-25) columns (GE-Healthcare, Buckinghamshire, UK) prior to cell monolayer inoculations \[[@B28]\]. The tachyzoite inoculation dose was previously optimised for the maintenance of each isolate to estimate the recovery of tachyzoites from infected cultures under optimal conditions (actively replicating) at 3.5 days post-inoculation (pi). Infected cell cultures were scraped with a plastic cell scraper, harvested by centrifugation at 1 350 gfor 10 min and suspended in Dulbecco Minimum Essential Medium (DMEM) supplemented with a 2% antibiotic-antimycotic solution (Gibco BRL, Paisley, UK), 10 mM HEPES and 2% heat-inactivated foetal bovine serum (FBS). The FBS employed in all in vitro assays was from the same production batch. Disrupted cell cultures were passed through 25 gauge needles, and tachyzoites were purified with PD-10 columns that had been previously equilibrated with the medium mentioned above. Tachyzoites were eluted from the columns with 5 mL of medium, and the number of tachyzoites was determined by trypan blue exclusion followed by counting in a Neubauer chamber. Tachyzoites were then resuspended at the required doses (2 × 10^5^tachyzoites/mL). Tachyzoite purification was performed at 4°C, and MARC-145 monolayers were inoculated within one hour of tachyzoite collection from flasks. In vitro invasion assays ------------------------ Host cell invasion was measured using a double (red/green) immunostaining probe that was described previously \[[@B28]\] and a laser scanning-cytometer-based assay that was previously described for T. gondii\[[@B29]\], with several modifications. All of the isolates were assayed in triplicate, and all of the assays were performed in three independent experiments. The Nc-Liv isolate was included as a control in each batch of experiments. Additionally, MARC-145 monolayers that were not inoculated were immunostained and included as negative controls in each assay. ### Double immunofluorescence staining Purified parasites (2 × 10^5^tachyzoites) were added onto MARC-145 monolayers that had grown to confluence on circular (13 mm diameter) glass coverslips and incubated at 37°C in a 5% CO~2~humidified incubator. At specific time periods (2 h, 4 h and 6 h pi), the coverslips were washed three times with 1 mL of phosphate buffered saline (PBS), fixed for 15 min in a 3% formaldehyde/0.05% glutaraldehyde solution and blocked with 3% bovine serum albumin (BSA) (Sigma-Aldrich, St. Louis, MO, USA) in PBS for 30 min. After blocking, the samples were labelled for 1 h with a 1:4000 dilution of a hyperimmune rabbit antiserum that was directed against N. caninumtachyzoites in PBS/0.3% BSA, washed three times with PBS and then labelled for 1 h with a 1:100 dilution of a secondary goat anti-rabbit IgG that was conjugated to PE-Cy5.5 (red, Invitrogen, Carlsbad, CA, USA). After washing, the samples were permeabilised with 0.25% Triton X-100 and blocked with PBS/3% BSA for 30 min. Parasites were then labelled with the rabbit anti-tachyzoite serum as described above, washed, and labelled with a 1:1000 dilution of a secondary goat anti-rabbit IgG conjugated to Alexa Fluor 488 (green, Molecular Probes, Eugene, OR, USA). Finally, the coverslips were washed, mounted on slides embedded with a 40% glycerol/2.5% 1,4-diazabicyclo\[2.2.2\]octane (Sigma-Aldrich) solution in PBS and analysed using a laser scanning cytometer. Polyclonal rabbit anti-N. caninumantiserum was raised in female New Zealand White rabbits (Harland Interfauna S.A., Barcelona, Spain) as described \[[@B30]\]. ### Laser scanning cytometry The coverslips were analysed on a CompuCyte laser scanning cytometer LSC (CompuCyte, Cambridge, MA, USA) equipped with a BX50 upright fluorescence microscope (Olympus America, Melville, NY, USA). A 60.8 mm^2^(4.4 mm radius) circular area was scanned with a 20× objective, an argon ion excitation laser (488 nm), and two detection filters (530/30 (green) and 650 LP (red)). Data were acquired and analysed using Wincyte 3.4 software (CompuCyte). ### Invasion rate determination The invasion rate (IR) was determined to be the number of green events (extracellular and intracellular parasites) minus the number of red events (extracellular parasites) per scanned field at specific times (2 h, 4 h and 6 h pi). Negative controls (the MARC-145 monolayer that was not inoculated) were included to eliminate potential fluorescent artefacts. No events were observed in the negative control samples. In vitro intracellular proliferation assays ------------------------------------------- Proliferation kinetics were determined by quantifying the number of tachyzoites at specific times (4 h, 8 h, 20 h, 32 h, 44 h, 56 h, and 68 h pi) by real-time PCR (qPCR). All of the isolates were assayed in triplicate, and all of the assays were performed in three independent experiments. The Nc-Liv isolate was included in each batch of experiments as mentioned above, and MARC-145 monolayers that were not inoculated were used as negative controls for PCR analyses. ### Culture conditions MARC-145 cells were grown to confluency in 24-well tissue culture plates. Purified N. caninumparasites (2 × 10^5^tachyzoites) were added to the monolayers at time 0 and incubated for 4 h at 37°C in 5% CO~2~. Next, the non-invading parasites were removed by washing the monolayer three times with DMEM/2% heat-inactivated FBS/2% antibiotic solution. The cultures were subsequently maintained at 37°C in 5% CO~2~for the time periods mentioned above. The samples were visualised by light microscopy to monitor parasite proliferation prior to their collection. Then, the media were removed and the cell cultures were recovered in 200 μL of PBS, 180 μL of lysis buffer and 20 μL of proteinase K (Qiagen, Hilden, Germany). The samples were transferred to Eppendorf tubes and were frozen at -80°C prior to DNA extraction. ### DNA extraction and real-time PCR Genomic DNA was extracted from cellular samples using the BioSprint 96 workstation and the BioSprint 96 DNA blood kit (Qiagen) according to the manufacturer\'s instructions. Genomic DNA was eluted in a final volume of 100 μL. Quantification of N. caninumDNA was performed by real-time PCR targeting the Nc-5 region as described previously \[[@B31]\]. A total of 5 μL (100 ng) DNA was used for the PCR amplifications. The number of N. caninumparasites was calculated by interpolating the corresponding Ct values (cycle threshold value, which represents the fractional cycle number reflecting a positive PCR result) on a standard curve that was generated in each real-time PCR run by assaying 10-fold serial dilutions of parasite DNA, which was equivalent to 10^-1^-10^5^tachyzoites. All of the tachyzoite quantifications were assessed from average values obtained from duplicate determinations. DNA extracted from the uninfected MARC-145 monolayer was also included as a negative PCR control in each batch of reactions. ### Proliferation rate, doubling time and tachyzoite yield determinations The proliferation rate (μ) and doubling time (Td) were assessed for each assay during the exponential multiplication period by applying non-linear regression analysis and an exponential growth equation using GraphPad Prism 5 Demo, v. 5.00 software (GraphPad, San Diego, CA, USA). The μ and Td for each isolate were defined as the average value obtained from all of the determinations that revealed a linear regression, R^2^≥ 0.95. The tachyzoite yield (TY~56h~) was defined as the average value of the number of tachyzoites quantified by qPCR at 56 h pi. Data statistics and correlation analysis ---------------------------------------- Differences between IRs determined over successive time points for each isolate were compared using the U Mann-Whitney test (2 h versus 4 h, 2 h versus 6 h, 4 h versus 6 h). The Kruskal-Wallis test was employed for comparisons among the IRs shown for the different isolates within each time point (2 h, 4 h, and 6 h pi). When statistically significant differences were found with the Kruskal-Wallis test, a Dunn\'s multiple-comparison test was applied to examine all of the possible pair-wise comparisons. A one-way ANOVA test, followed by the Tukey\'s multiple range tests, was employed to compare the Tds and TY~56h~s assessed for each isolate. Statistical analyses were carried out using a dataset composed of the values determined for each replicate obtained from the three independent experiments. The significance for these analyses was established at P\< 0.05. The Spearman\'s rank correlation coefficient (ρ) was applied to investigate the potential association between the in vitro parameters evaluated in this study (IR~2h~, IR~4h~, IR~6h~, Td, TY~56h~) and the neonatal morbidity, mortality and vertical transmission rates induced by these isolates in a well-established pregnant mouse model (Table [1](#T1){ref-type="table"}) \[[@B14],[@B16]\]. Statistical and correlation analyses were performed, and graphics were generated using GraphPad Prism 5 Demo, v. 5.00 software (GraphPad). Results ======= Invasion rate comparisons ------------------------- The IRs (the median number of intracellular events) of almost all isolates significantly increased from 2 h to 4 h pi or from 2 h to 6 h pi (P\< 0.05, UMann-Whitney test), with the exception of the Nc-Spain 9 isolate. However, no significant differences were found between the IRs of most of the isolates at 4 and 6 h pi. The IRs were only observed to significantly increase from 4 h to 6 h pi for the Nc-Spain 1 H and Nc-Spain 10 isolates. Significant differences were also found among the IRs of different isolates at 2 and 4 h pi (P\< 0.0001, Kruskal-Wallis test) (Figure [1A](#F1){ref-type="fig"} and B). At 2 h pi, the Nc-Spain 4 H, Nc-Spain 8 and Nc-Liv isolates exhibited the highest IRs (IR~2h~) in comparison to the IR~2h~s of the Nc-Spain 3 H, Nc-Spain 6 and Nc-Spain 10 isolates, which displayed the lowest values (by Dunn\'s test). At 4 h pi, the Nc-Spain 4 H and Nc-Liv isolates exhibited significantly higher IRs (IR~4h~) than the Nc-Spain 3 H and Nc-Spain 1 H isolates when they were analysed by the Dunn\'s test. Significant variations among the IRs of the isolates were also detected at 6 h pi (P= 0.046, Kruskal-Wallis test), although no differences were found in pair-wise analyses between the IRs of the different isolates (Figure [1C](#F1){ref-type="fig"}). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### *Box-plot graphs representing the maximum and minimum values, lower and upper quartiles and medians of invasion rate (IR) replicates from experiments performed in triplicate determined in vitro for each N. caninumisolate. IRs at 2 h pi (A). IRs at 4 h pi (B). IRs at 6 h pi (C). Error bars indicate the SD. (\\) marks the significantly higher IRs compared with all of those IRs that were significantly lower (\) according to the Kruskal-Wallis test and the Dunn\'s multiple-comparison test. ::: ![](1297-9716-42-41-1) ::: Proliferation kinetics, proliferation rate determination and doubling time comparisons -------------------------------------------------------------------------------------- The parasite proliferation kinetics of each N. caninumisolate was studied by plotting the numbers of tachyzoites, which were determined by qPCR, against the specific collection time periods (Figure [2A](#F2){ref-type="fig"}). After being inoculated onto MARC-145 cell monolayers, tachyzoites did not multiply for a specific period of time, which is known as the lag phase. The lag phase of the different isolates varied between the time periods of 8 h (Nc-Spain 10), 20 h (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 7, Nc-Spain 6 and Nc-Liv), 32 h (Nc-Spain 1 H, Nc-Spain 3 H and Nc-Spain 9) and 44 h (Nc-Spain 2 H, Nc-Spain 8) (Figure [2A](#F2){ref-type="fig"}). After the lag phase, an exponential proliferation phase was observed that persisted until 56 h pi for 3 of the 11 isolates (Nc-Spain 4 H, Nc-Spain 5 H and Nc-Spain 7 isolates) and until 68 h pi for the other 8 isolates (Figure [2B](#F2){ref-type="fig"}). Microscopic visualisation of the inoculated cultures prior to collection verified that some parasitophorous vacuoles with tachyzoite pairs were first observed for most of the isolates at 20 h pi. After 32 h, the number of tachyzoites from the N. caninumisolates that were undergoing endodyogeny inside of parasite vacuoles increased with increasing time. Between 56 and 68 h pi, non-synchronous rupture of the host cells and egression of the tachyzoites were observed in the cell monolayers infected with 7 of the 11 isolates (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 6, Nc-Spain 7, Nc-Spain 9, Nc-Spain 10, and Nc-Liv). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Plot graphs representing the proliferation kinetics over time, as assessed by real-time PCR (A), and the linear regression of the average numbers of tachyzoites (ln-transformed) determined by real-time PCR against the time of the exponential phase (B) for each isolate included in this study (see graph legend). The average number of tachyzoites for each time in plot graphs A and B is representative of all of the individual experiments with an R^2^\> 0.95, and the error bars indicate the SD. Line slopes in plot graph B define the proliferation rate (μ) and doubling time (Td, Ln 2/μ). For all isolates, R^2^\> 0.98. ::: ![](1297-9716-42-41-2) ::: The μ and the Td were determined for the exponential phase, excluding the lag and egression periods, for each replicate performed for each isolate with an R^2^\> 0.95. The average Td values for different isolates ranged from a minimum of 9.84 ± 1.516 h (Nc-Spain 6) to a maximum of 14.15 ± 2.364 h (Nc-Spain 4H) (Figure [3](#F3){ref-type="fig"}). When the Td values assessed for different isolates were compared, significant differences were detected (Figure [3](#F3){ref-type="fig"}). The Td value of the Nc-Spain 4 H isolate was significantly higher than the Td values of the Nc-Spain 5 H, Nc-Spain 6 and Nc-Liv isolates (P= 0.0016 by 1-way ANOVA, followed by Tukey\'s test). ::: {#F3 .fig} Figure 3 ::: {.caption} ###### *A column graph representing the average doubling time (Td) values of replicates from experiments performed in triplicate determined in vitro for each N. caninumisolate. Error bars indicate the SD. (\\) marks the significantly higher Tds compared with all of those Tds that were significantly lower (\) according to the ANOVA test followed by the Tukey\'s test. ::: ![](1297-9716-42-41-3) ::: Evaluation of tachyzoite yield ------------------------------ The TY~56\ h~was assessed to determine the number of tachyzoites produced during the same intracellular period after invasion, but prior to complete tachyzoite egression from cell monolayers. The TY~56\ h~values were significantly different between isolates (P\< 0.0001 by 1-way ANOVA, followed by Tukey\'s test) and varied from 1 731 (Nc-Spain 8) to 36 170 tachyzoites (Nc-Spain 7) (Figure [4](#F4){ref-type="fig"}). At 56 h pi, the isolates that were already undergoing exponential proliferation from 20 h pi (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 6, Nc-Spain 7, Nc-Spain 10 and Nc-Liv) had significantly higher TY~56\ h~values than the other four isolates (Nc-Spain 1 H, Nc-Spain 2 H, Nc-Spain 3 H, and Nc-Spain 8), which began to exponentially proliferate after 20 h pi (Figure [4](#F4){ref-type="fig"}). ::: {#F4 .fig} Figure 4 ::: {.caption} ###### *A column graph representing the average tachyzoite yield (TY~56h~) values of replicates from experiments performed in triplicate determined in vitro for each N. caninumisolate. Error bars indicate the SD. (\\) marks the significantly higher TY~56\ h~values compared with all those TY~56\ h~values that were significantly lower (\) according to the ANOVA test followed by the Tukey\'s test. ::: ![](1297-9716-42-41-4) ::: Correlation analysis -------------------- Previous studies using a well-established pregnant BALB/c mouse model demonstrated that extensive variability exists in the pathogenicity and transmissibility of the N. caninumisolates included in this study \[[@B14],[@B16]\]. Wide ranges in the morbidity, mortality and vertical transmission rates were observed (Table [1](#T1){ref-type="table"}), suggesting a relevant role of the implicated isolate in the outcome of infection in pregnant mice. Because the in vitro IRs, Td and TY~56\ h~values also varied significantly within this population of isolates, Spearman correlation analyses were applied to determine whether a potential association existed between the in vitro characteristics of isolates and their ability to be vertically transmitted and produce disease in mice. No correlations could be discerned between the Td or IR~2\ h~values and vertical transmission, neonatal morbidity or neonatal mortality rates. Additionally, no correlation could be established between the vertical transmission rates and the IR~4\ h,~IR~6\ h~or TY~56\ h~values. However, a significant correlation was found between the IR~4\ h,~IR~6\ h~and TY~56\ h~values and neonatal morbidity and mortality rates based on the Spearman\'s rho coefficient (Table [2](#T2){ref-type="table"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Spearman correlation analyses of the invasion rate at 2 h pi (IR~2h~), 4 h pi (IR~4h~), 6 h pi (IR~6h~), doubling time (Td), and the tachyzoite yield at 56 h pi (TY~56h~) that were determined in vitro for each isolate in this study. ::: IR~2h~ IR~4h~ IR~6h~ Td TY~56h~ -------------------------------- -------- -------- -------- ------- --------- ------- ------ ---- -------- -------- Neonatal morbidity N.C. \- 0.7107 0.018 0.7016 0.020 N.C. \- 0.7614 0.0065 Neonatal mortality N.C. \- 0.6287 0.044 0.7198 0.016 N.C. \- 0.7198 0.016 Vertical transmission rate N.C. \- N.C. \- N.C. \- N.C. \- N.C. \- \* Spearman rho coefficient. ^\#^Pvalue (two-tailed). N.C. No correlation. ::: Discussion ========== The apicomplexan parasite N. caninumis an obligate intracellular parasite. The processes of parasite invasion, adaptation to new intra-cytoplasmatic conditions, intracellular proliferation, and egress from host cells constitute successive steps involved in the lytic cycle of N. caninumand other apicomplexa \[[@B32]-[@B34]\]. These processes are required for the maintenance and multiplication of the parasite in vitro and for parasite survival and propagation in the course of animal infection in vivo. As a result of a primo-infection or the reactivation of a Neosporainfection in a chronically infected animal, tachyzoites rapidly disseminate throughout the body of the host, invade cells of different organs and cause cell death. Cell death results in the release of parasites, which develop new lytic replication cycles, thus allowing the infection to spread and cause disease \[[@B1]\]. Therefore, the processes involved in parasite invasion and intracellular proliferation are crucially important for understanding the pathogenesis of disease and for the development of protective vaccines and effective drug therapies. Recently, different studies have been performed to understand the precise mechanisms involved in the processes of the N. caninumlytic cycle, which includes parasite invasion \[[@B28],[@B35],[@B36]\] and egress \[[@B37]\]. However, intraspecific differences related to the efficiency of the lytic cycle processes, such as invasion and proliferation, and their association with isolate pathogenicity in vivo have been poorly investigated. The most detailed study in this regard was performed by Schock et al. \[[@B19]\], which revealed that differences occurred in the growth rates of six N. caninumisolates, although their potential correlation with virulence was not examined. Moreover, the isolates in this previous study were maintained by an undetermined number of culture passages, which could modify the original growth rate and pathogenicity of the isolates \[[@B27]\]. Attenuation of virulence, accompanied by faster multiplication in vitro has been previously demonstrated in N. caninumand T. gondiiparasites maintained for extended periods in cell cultures, which may have been due to adaptation of the isolates to cell cultivation \[[@B27],[@B38]\]. In this study, we comparatively examined the in vitro invasion efficiencies and proliferation kinetics of the active tachyzoite stage of eleven different N. caninumisolates, which were maintained with limited passages in cell cultures from their original isolation \[[@B5],[@B14]\]. The IRs determined in this study demonstrated that the tachyzoites from most of the N. caninumisolates penetrated cell monolayers 2 to 4 h pi. In previous studies, tachyzoites from the Nc-1 N. caninumisolate penetrated bovine aorta endothelial cell cultures 45-60 min after inoculation \[[@B28]\]. After the initial penetrations, an insignificant increase in the number of invading tachyzoites was detected from 4 to 6 h pi. This slight increase was likely due to the loose invasion capacity of the remaining tachyzoites that had not invaded that monolayer at 4 h pi \[[@B28],[@B35]\]. These results were similar to the results reported by Hemphill et al. \[[@B28]\], who observed that maintaining Nc-1 tachyzoites extracellularly at 37°C for time periods longer than 4-6 h resulted in decreased infectivity of the parasite. The observed differences in the invasion time periods of N. caninumtachyzoites may also have been influenced by the experimental conditions and the host cell types used in each experiment. N. caninumcan be maintained in vitro in a wide variety of well-established cell cultures, and thus, this parasite can invade a wide range of cell cultures, although N. caninumtachyzoites from different isolates may have different affinities for specific cell types. Based on this theory, the failure to isolate parasites in CV-1 and M617 cells from a clinically affected KO mouse can be attributed to the limited invasion and growth characteristics of the specific isolate in these cell lines \[[@B39]\]. This theory may also explain the natural host range and the tissue tropism displayed by N. caninumduring infection. Moreover, in previous studies, substantial differences were observed in the cell invasion processes of the closely related N. caninumand T. gondiiparasites, which could explain their dissimilar host preferences \[[@B35]\]. However, different N. caninumisolates, including those that were assayed in this study, could all be adapted to the MARC-145 cell line through a limited number of cell passages \[[@B5],[@B14],[@B18]\]. Therefore, the significant differences in the invasion efficiencies observed in this study could be attributed to the biological diversity of these N. caninumisolates. Throughout the experiments, the IRs determined for the Nc-Spain 4 H and Nc-Liv isolates were significantly higher than the IR of the Nc-Spain 3 H isolate. Furthermore, the IRs determined for the Nc-Spain 4 H and Nc-Liv isolates were significantly higher than the IR of the Nc-Spain 1 H isolate at 4 h pi (Figure [1](#F1){ref-type="fig"}). The intracellular proliferation kinetics also varied between the isolates that were analysed. Significant differences in the lag period, which ranged from 8 to 44 h pi, were observed between the isolates. Additionally, after the exponential proliferation period, the egress period, which occurred 56 to 68 h pi, was only detected in some of the isolates. Furthermore, we did not microscopically visualise parasitophorous vacuoles containing two or more tachyzoites until 20 h pi, and the cellular rupture releasing the tachyzoites was observed for some of the isolates from 56 h pi. The exponential proliferation period is delimited by the lag phase and the tachyzoite egress phase for each isolate. The Td values, which signify the μ, also varied from approximately 10 to 14 h, and significant differences in the values were detected between the isolates. Our results were similar to the results previously obtained for the Nc-1 isolate, which displayed a lag period of 10-12 h and a Td of 14-15 h using human foreskin fibroblasts \[[@B40]\]. However, we must consider, as we did for the IRs, that the proliferation kinetics may have been influenced by the host cell lines used in these assays \[[@B39]\]. In fact, previous studies on T. gondiihave demonstrated that differences in tachyzoite multiplication occur based on the cell lines used as hosts \[[@B41]\]. Variations in the IR, Td (proliferation rate) and the exponential proliferation period will determine the number of tachyzoite division cycles reached and the tachyzoite yield attained in vitro and in vivo. Significant differences in the TY~56\ h~values were apparent between the isolates based on comparative analysis, and the isolates clearly grouped into two populations: \"highly prolific\" and \"less prolific\" (Figure [4](#F4){ref-type="fig"}). Interestingly, the severity of histopathological lesions and clinical signs have been directly related to the parasite burdens in the brains of experimentally infected mice \[[@B11],[@B12],[@B42]-[@B45]\] and to the spread of the parasite in foetal and placental tissues from infected pregnant cattle \[[@B1],[@B15],[@B26],[@B32],[@B46]\]. Furthermore, an association between the severity of histological lesions and parasite burdens was established in studies performed in bovine foetuses that were naturally aborted during different periods of pregnancy \[[@B47]\]. Therefore, the high dissemination rate, the ability to cross biological barriers (blood-brain barrier and placenta) and the enhanced invasion and proliferation rates of different N. caninumisolates may contribute to host tissue damage and to the severity of clinical signs in vivo. In support of this hypothesis, we observed that the isolates with the highest IRs (Nc-Spain 4 H and Nc-Liv) caused the highest morbidity in dams and the highest morbidity and mortality in neonates (100% succumbed to infection), while the isolates with the lowest IRs (Nc-Spain 1 H and Nc-Spain 3H) induced lower neonatal mortality in a pregnant mouse model \[[@B14],[@B16]\]. Furthermore~,~the \"highly prolific\" and \"less prolific\" isolate populations contained isolates that displayed the highest (Nc-Spain 5 H and Nc-Spain 7) and lowest (Nc-Spain 2 H and Nc-Spain 3H) parasite burdens and the levels of histopathological lesions in the brain during the chronic phase of infection in a cerebral mouse model, respectively \[[@B12]\]. Interestingly, this system of ordering grouped the isolates that had the highest and lowest capacities to produce disease in the pregnant mouse model together (Table [1](#T1){ref-type="table"}) \[[@B14],[@B16]\]. Based on these observations, the association between the in vitro IRs and TY~56\ h~values for these isolates and the neonatal morbidity, mortality and vertical transmission rates produced by these isolates in mice was investigated through a correlation analysis. A direct correlation between the IR~4\ h~and IR~6\ h~values when invasion was completed, as well as the TY~56\ h~value and their pathogenicity in mice was established, suggesting that the in vitro invasion and proliferation rate traits are related to the in vivo virulence of the N. caninumisolates, at least in the pregnant BALB/c mouse model. Moreover, the Nc-Spain 1 H isolate (a \"less prolific\" and less invasive isolate in this study) had a limited ability to induce foetal death in a pregnant bovine model \[[@B15]\]. High growth rates due to a higher reinvasion capacity, but not due to significant variations between isolate-specific Tds, have also been recognised as a virulence trait in T. gondii\[[@B25]\], though pathogenesis in toxoplasmosis has mainly been found to be related to the inflammatory immune response against infection by specific T. gondiitypes \[[@B22],[@B48]\]. However, virulence factors, such as the ROP18 and ROP16 rhoptry proteins, have recently been identified in T. gondii, and the ability of ROP18 to increase the intracellular proliferation of this parasite has been specifically suggested to cause enhanced virulence of the parasite \[[@B23],[@B25],[@B49]\]. Because the outcome of N. caninuminfection is affected by a combination of host, parasite, and external factors, these factors need to be considered collectively when establishing direct associations between the in vitro and in vivo behaviour of N. caninumisolates. Various parasite factors, which include the efficacy of disseminating and crossing host barriers, may also be different between N. caninumisolates, as described for T. gondiiisolate types I, II and III \[[@B22],[@B23]\]. Therefore, differences may also exist between N. caninumisolates in the number of parasites that are able to spread throughout the host and colonise target organs (brain and placenta) and, consequently, the tachyzoite yield reached in the target tissues, the outcome of an infection and the transmission of the parasite to foetuses in pregnant animals. These differences may explain the lack of a correlation found between the IRs and TY~56\ h~values with vertical transmission rates. Interestingly, the genetically identical Nc-Spain 1 - Nc-Spain 10 and Nc-Spain 3 H - Nc-Spain 4 H isolates displayed significant differences in their in vitro behaviour, as well as in their pathogenicity in mice \[[@B14],[@B16]\]. Both pairs of isolates were obtained from the same dairy herd, but from different calves, and therefore, they could be considered as different isolates that may include genetic variations in other locithat were not examined. In summary, this study showed that there is intraspecific diversity in the invasion rate and proliferation kinetics of different N. caninumisolates. More interestingly, the correlation found between the in vitro characteristics of the isolates with their in vivo pathogenicity in pregnant mice and their offspring confirms that invasion and proliferation rates are virulence traits in N. caninum. Within apicomplexan parasites, host cell invasion and intracellular proliferation are tightly regulated processes that involve the sequential secretion of components from specialised organelles (micronemes, rhoptries and dense granules). A large number of these secreted elements and their interactions have already been identified in T. gondii\[[@B24]\]. Some of these elements, such as the ROP18 and ROP16 proteins, are virulence factors in T. gondii\[[@B23],[@B25],[@B49]\]. In contrast to T. gondii, the role of orthologous microneme, roptry and dense granule proteins in N. caninumis still unclear. In addition, cell culture-based approaches have demonstrated significant differences between T. gondiiand N. caninumspecies \[[@B32],[@B35]\]. Further studies are necessary to identify the molecular mechanisms within N. caninumthat are directly involved in mediating the differences observed between various isolates. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= JRC carried out in vitro assays, conceived the study, participated in its design, and drafted the manuscript. MGB participated in invasion assays, in its design and helped to draft the manuscript. IS performed invasion and proliferation assays. GA participated in the design of the study and coordination. GAG participated in proliferation assays and performed the statistical analysis. IP carried out real-time PCR determinations. LMO also conceived the study, participated in the design of the study and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript. Acknowledgements ================ This work was supported by the INIA project RTA04-047-C2. We thank Diana Williams (Liverpool School of Tropical Medicine, Liverpool, UK), who kindly provided us with the Nc-Liv isolate. We also thank the Flow Cytometry and Confocal Microscopy Unit of the Complutense University of Madrid for their technical support and Ricardo García de la Mata from the Complutense University of Madrid for statistical analyses.	PubMed Central	2024-06-05T04:04:18.989889	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052184/", "journal": "Vet Res. 2011 Feb 23; 42(1):41", "authors": [ { "first": "Javier", "last": "Regidor-Cerrillo" }, { "first": "Mercedes", "last": "Gómez-Bautista" }, { "first": "Itsaso", "last": "Sodupe" }, { "first": "Gorka", "last": "Aduriz" }, { "first": "Gema", "last": "Álvarez-García" }, { "first": "Itziar", "last": "Del Pozo" }, { "first": "Luis Miguel", "last": "Ortega-Mora" } ] }
PMC3052185	Introduction ============ Neuropathic pain is a chronic condition that affects millions of people worldwide. It is characterized by pain hypersensitivity, including spontaneous ongoing or intermittent burning pain, an exaggerated response to painful stimuli, and pain in response to normally innocuous stimuli. Because the mechanisms of neuropathic pain induction and maintenance are far more complicated than previously assumed, current treatments can be ineffective or produce potentially severe adverse effects. Understanding molecular mechanisms of this disorder may allow improvement of its treatment. It is generally believed that neuropathic pain is caused by changes in expression and function of receptors, enzymes, and voltage-dependent ion channels in peripheral nerves and dorsal root ganglion (DRG) neurons, as well as at synapses in the nociceptive pathway in the central nervous system \[[@B1],[@B2]\]. DRG neurons express many kinds of ion channels/receptors. These channels and receptors have at least three functions (Figure [1](#F1){ref-type="fig"}): 1) Transduction (e.g., transient receptor potential channels, sodium channels, acid-sensing ion channels, and ATP-sensitive receptors that are expressed in the peripheral terminals of DRG neurons transduce noxious stimuli into electric impulses), 2) Conduction (e.g., sodium and potassium channels are involved in the propagation of action potentials), and 3) Modulation of synaptic transmission (e.g., voltage-gated calcium channels and glutamate receptors that are expressed on presynaptic terminals of the primary afferents in dorsal horn regulate the release of neurotransmitters). After nerve injury, injured and uninjured DRG neurons become more excitable and exhibit ectopic firing \[[@B3],[@B4]\]. It is reasonable to conclude that this abnormal spontaneous activity might be related to nerve injury-induced changes in the density, distribution, and functional activities of voltage-gated sodium channels in the DRG neurons. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Involvement of dorsal root ganglion (DRG) channels and receptors in the induction and modulation of pain. A variety of DRG channels and receptors are involved in the transduction of noxious stimuli into electric impulses at the peripheral terminals of DRG neurons \[e.g., transient receptor potential (TRP) channels, voltage-sensitive sodium (Na^+^) channels, ATP-sensitive receptors, acid sensing ion channels\], in the conduction of action potentials along the axons \[e.g., voltage-sensitive Na^+^channels and potassium (K^+^) channels\], and in the modulation of neurotransmitter release at presynaptic terminals of primary afferents in the dorsal horn \[e.g., voltage-gated calcium (Ca^2+^) channels, GABA receptors, and glutamate receptors\]. ::: ![](1744-8069-7-16-1) ::: To date, at least nine subtypes of sodium channel have been cloned and identified on mammalian cells. All sodium channels consist of a central α-subunit and two auxiliary β-subunits. Nine α-subunits (Nav1.1-Nav1.9, also referred to as channels) and four β-subunits have been identified in mammals. The pore-forming α-subunit determines the primary function of sodium channels, but the kinetics and voltage-dependence of channel gating are in part modified by the β-subunits. The α-subunits form four homologous domains (I-IV), each of which contains six transmembrane α helices (S1-S6) and an additional pore loop located between the S5 and S6 segments. Voltage sensors of sodium channels are located in the highly conserved S4 transmembrane segments. Membrane depolarization produces changes in the transmembrane electric field and causes the S4 segment to spiral outward. This conformational change opens the pore. Following activation, sodium channels quickly inactivate to prevent further ion flow through the pore and to allow repetitive action potential firing of cells. Most voltage-gated sodium channels can be blocked by nanomolar concentrations of tetrodotoxin (TTX) and thereby are termed TTX-sensitive channels. These TTX-sensitive channels show rapidly activating and inactivating sodium currents. In contrast, Nav1.5, Nav1.8, and Nav1.9 are relatively resistant to this toxin and show sodium currents that are TTX-resistant \[[@B5]\]. Voltage-gated sodium channels can be modulated by receptors coupled to intracellular signaling molecules (Figure [2](#F2){ref-type="fig"}). The modulation can occur through phosphorylation of specific residues on the α-subunit after the activation of cytoplasmic protein kinases. Two protein kinases, protein kinase A and protein kinase C, have been shown to target voltage-gated sodium channels. Both are activated by G-protein-coupled second messenger systems. The specific amino acid residues that are phosphorylated by these two kinases are located primarily on the linker between domains 1 and 2. The phosphorylation of voltage-gated sodium channels alters their function \[[@B6]\]. Moreover, the expression of voltage-gated sodium channels can be up-regulated by neurotrophins, including nerve growth factor, brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) (Figure [3](#F3){ref-type="fig"}) \[[@B7]-[@B9]\]. Interestingly, intrathecal injection of neurotrophin-3 causes significant decreases in the levels of Nav1.8 and Nav1.9 in L5 DRGs ipsilateral and contralateral to chronic constriction injury (CCI) of sciatic nerve \[[@B10]\]. In addition, inflammatory cytokines such as tumor necrosis factor α (TNFα) up-regulate the expression of Nav1.3, Nav1.8, and Nav1.9 and increase both TTX-sensitive and -resistant currents in the DRG neurons \[[@B11],[@B12]\]. These effects of neurotrophins and pronociceptive cytokines on sodium channel expression might be mediated through regulation of intracellular downstream signaling pathways of their receptors, including p38 and ERK1/2 mitogen-activated protein kinase (Figure [3](#F3){ref-type="fig"}) \[[@B11],[@B13]\]. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Schematic representation of signaling pathways that modulate Na^+^channels (Nav). The activation of G-protein-coupled receptors (GPCR) by their ligands activates adenylyl cyclase (AC) and phospholipase C (PLC), which produce cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), respectively. cAMP then activates cAMP-dependent protein kinase (PKA), whereas DAG activates protein kinase C (PKC). Both PKA and PKC phosphorylate (P) the Na^+^channel to regulate its function. ::: ![](1744-8069-7-16-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Potential mechanisms by which sodium channel (Nav) expression is regulated. Neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) bind to their respective receptors: tyrosine kinase receptor (Trk) A, TrkB, and Ret; receptor stimulation then activates the Ras/MEK/MAPK pathway. Activated MAPK promotes expression of sodium channels at the levels of mRNA and protein through unknown mechanisms (indicated by the red dashed arrows). An inflammatory cytokine, tumor necrosis factor α (TNFα), also up-regulates expression of sodium channels through activation of the TRAF2/MEK/MAPK pathway. In contrast, neurotrophin-3 (NT-3) down-regulates the expression of sodium channels through TrkA-mediated inhibition of the Ras/MEK/MAPK pathway (indicated by the blue dashed arrows). MAPK: mitogen-activated protein kinases; MEK: MAPK kinase; TNFR1: tumor necrosis factor receptor 1; TRAF2: TNF receptor-associated factor 2. ::: ![](1744-8069-7-16-3) ::: Most sodium channels (except for Nav1.4, which is predominantly expressed in adult skeletal muscle \[[@B14]\] and Nav1.5, which is expressed in cardiac tissue) have been identified in adult DRGs \[[@B15]\]. Their expression level and the cell types to which they are localized in the DRG are distinct under normal conditions. Unexpectedly, preclinical studies indicate that peripheral nerve injury down-regulates most pain-associated voltage-gated channels in the injured DRG. Whether and how voltage-gated channels participate in nerve injury-evoked ectopic firing in the DRG neurons is still not unclear. In this review, we describe the expression and distribution of each sodium channel subtype in the DRG. We also review evidence regarding changes that occur in channel expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. Finally, we discuss their potential involvement in this disorder. Nav1.1 ------ Nav1.1 is a TTX-sensitive sodium channel \[[@B16],[@B17]\], but the current properties of Nav1.1 have not been characterized in DRG neurons. In situ hybridization histochemistry has shown that Nav1.1 mRNA expression in DRGs is high in large-diameter neurons, moderate in medium-diameter neurons, and low in small-diameter neurons \[[@B18],[@B19]\]. Approximately 25-33% of DRG neurons in naïve rats are positive for Nav1.1 mRNA \[[@B20]\]. Double immunostaining has shown that most Nav1.1-labeled cells are positive for NF200 (a marker for myelinated A-fibers), and that 79.2% of NF200-positive neurons express Nav1.1 mRNA. Research also has shown that 65.0% of Nav1.1-positive cells co-express neurotrophin-3 receptor tyrosine kinase C (TrkC; a marker for non-nociceptive mechanosensors) and that 51.6% of TrkC-labeled DRG cells are positive for Nav1.1 \[[@B21]\]. These findings indicate that Nav1.1 is expressed predominantly in the large-diameter A-fiber DRG neurons and that it might participate mainly in proprioceptive transmission (Table [1](#T1){ref-type="table"}). It should be noted that approximately 11% of Nav1.1 mRNA-positive DRG neurons are positive for IB4 (a marker for small non-peptidergic nociceptive neurons), suggesting that Nav1.1 in these small-diameter DRG neurons may participate in nociceptive transmission and modulation \[[@B20]\]. Indeed, mutations in SCN1A (the gene for Nav1.1) have been associated with inherited epileptic syndromes \[[@B22]\] and familial hemiplegic migraine in humans \[[@B23]\]. Interestingly, preclinical studies showed that the level of Nav1.1 mRNA was decreased in the injured DRG after peripheral spinal nerve ligation (SNL) or spared nerve injury (SNI) \[[@B24],[@B25]\]. Thus, whether and how DRG Nav1.1 is involved in neuropathic pain development is still elusive and remains to be further studied. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Summary of sodium channel distribution and potential involvement in pain conditions ::: Channel Distribution in normal DRG Inflammatory pain Neuropathic pain Effect of manipulation on behavioral consequences Human disorders --------- ----------------------------------------- ------------------------------------------ ------------------------------ --------------------------------------------------- -------------------------------------------------------------------------- ------------------------------------------------ ------------------------------------------------------------------------- --------------------------------------------------------------------------------------- 1.1 High in large cells, low in small cells Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A Migraine, epilepsy 1.2 Very low in most conditions Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A Epilepsy 1.3 Extremely low in adult DRG Increased (carrageenan) Increased (carrageenan) Increased (SNI, SNL) Increased (SNI, SNL) Effective on SCI and CCI, but no effect on SNI No effect on acute, inflammatory, or neuropathic pain Accumulates in neuromas of human painful neuropathy 1.6 High in large cells, low in small cells Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A N/A 1.7 Predominantly in small cells Increased (carrageenan, CFA) Increased (carrageenan, CFA) Decreased (SNI, SNL) Decreased (SNA, SNI, and SNL) Effective on CFA Effective on acute and inflammatory pain; no effect on neuropathic pain Decreased in human injured DRG; accumulates in neuromas; mutations: PE, PEPD, and CIP 1.8 Exclusively in small cells Increased (carrageenan) Increased (carrageenan) Decreased (SNI, SNL) Decreased in L5 DRG (SNL, SNI) but increased in L4 DRG and sciatic nerve Effective on CFA, SNL, and CCI Effective on inflammatory pain; no effect on neuropathic pain Accumulates in neuromas of human painful neuropathy 1.9 Selectively expressed in small cells Increased (CFA), unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNA, SNI, and SNL) Decreased (SNA, SNI, and SNL) No effect on SNL Effective on inflammatory pain; no effect on neuropathic pain N/A Abbreviations: CCI, chronic constrictive injury; CFA, complete Freund\'s adjuvant; CIP, channelopathy-associated insensitivity to pain; DRG, dorsal root ganglion; N/A, not applicable; PE, primary erythermalgia; PEPD, paroxysmal extreme pain disorder; SCI, spinal cord injury; SNA, sciatic nerve axotomy; SNI, spared nerve injury; SNL, spinal nerve ligation. ::: Nav1.2 ------ Nav1.2 is one of the predominant sodium channels in the central nervous system; it is localized on dendrites, unmyelinated axons, and premyelinated axons \[[@B26]\]. The level of Nav1.2 mRNA expression in the adult DRG is very low \[[@B18]\], although its expression is moderate in early developmental stages. Peripheral nerve injury and inflammation do not alter the levels of Nav1.2 mRNA or protein in the DRG \[[@B19],[@B24],[@B25]\]. The evidence suggests that DRG Nav1.2 is unlikely to be involved in the development of neuropathic pain (Table [1](#T1){ref-type="table"}). Nav1.3 ------ Although Nav1.3 is expressed abundantly in DRG neurons during fetal and neonatal periods, it is normally undetectable in adult naïve DRG neurons \[[@B27]\]. However, it can be up-regulated in the injured DRG and ipsilateral dorsal horn after peripheral nerve injury. Approximately 37.5% of DRG neurons are Nav1.3-positive in the L5 DRG after sciatic nerve lesion and 15.8% after sural axotomy \[[@B28]\]. In situ hybridization histochemistry showed that, after L5 SNL, 40.7-47.2% of DRG neurons were Nav1.3 mRNA-positive cells, most of which were medium or large in size \[[@B20]\]. A recent study indicated that L5 ventral root transection produces a TNFα-dependent increase in Nav1.3 at both the mRNA and protein levels in the L4 and L5 DRGs \[[@B12]\]. Nav1.3 protein was also found to accumulate in neuromas of patients with painful neuropathy \[[@B29]\] and to up-regulate in second-order dorsal horn neurons after CCI \[[@B30]\]. These findings suggest that an increase in Nav1.3 in DRG and dorsal horn might be involved in nerve injury-induced pain hypersensitivities. Despite the accrued evidence, the role of Nav1.3 in neuropathic pain behavior is still controversial. Hains et al. \[[@B31]\] reported that knockdown of DRG Nav1.3 via intrathecal administration of Nav1.3 antisense oligodeoxynucleotides (ASO) attenuated pain hypersensitivities induced by spinal cord injury and sciatic nerve CCI. In contrast, Lindia et al. \[[@B28]\] found that intrathecal administration of Nav1.3 ASO did not attenuate SNI-induced mechanical or cold allodynia, although it did significantly block the SNI-induced increase in DRG Nav1.3. In addition, neuropathic pain development remained intact in both conventional and conditional Nav1.3 knockout mice \[[@B32]\]. Furthermore, ectopic discharges from the injured nerves were unaffected in the absence of Nav1.3 in conventional knockout mice \[[@B32]\]. These results suggest that Nav1.3 is unlikely to be a key player in the induction of abnormal spontaneous activity in injured neurons (Table [1](#T1){ref-type="table"}). Nav1.6 ------ Nav1.6 is predominantly located in the Nodes of Ranvier of both motor and sensory axons in the peripheral and central nervous systems \[[@B33]\]. In adult DRG, the cellular distribution pattern of Nav1.6 is similar to that of Nav1.1. That is, it is highly colocalized with NF200 \[[@B20]\], indicating that Nav1.6 is an A-fiber-specific channel (Table [1](#T1){ref-type="table"}). Nerve injury alters expression of DRG Nav1.6. Its mRNA is down-regulated in the injured L5 DRG following SNL and SNI \[[@B25]\]. However, in a rat model of infraorbital nerve injury, the level of Nav1.6 protein was found to be significantly increased proximal to the lesion site \[[@B34]\], suggesting that it might be transported quickly to the peripheral terminals under neuropathic pain conditions. Whether this increase participates in the generation of abnormal spontaneous activity in the injured DRG neurons remains to be further studied. Nav1.7 ------ Nav1.7 is widely expressed in sensory, sympathetic, and myenteric neurons \[[@B18],[@B35],[@B36]\]. In the DRG, Nav1.7 is distributed predominantly in small-diameter neurons \[[@B18],[@B19]\]. Double-labeling studies have shown that most NF200-negative neurons (\>99%) express Nav1.7 mRNA \[[@B20]\] (Table [1](#T1){ref-type="table"}). Nav1.7, as well as Nav1.6, Nav1.8, and Nav1.9, is present in most intra-epidermal free nerve endings \[[@B37]\], suggesting that these sodium channels are poised to participate in amplification of generator potentials, and sets the gain on nociceptors. Nav1.7 displays slow closed-state inactivation \[[@B38]\]. As a result of this characteristic, Nav1.7 is unable to respond during high-frequency stimulation, but it responds to small depolarizing stimuli close to the resting membrane potential \[[@B38]\]. Nav1.7 may be physiologically coupled to Nav1.8 within DRG neurons. It serves to boost subthreshold stimuli, resulting in the activation of Nav1.8, which recovers rapidly from inactivation and produces high-frequency action potentials \[[@B39]\]. The evidence indicates that Nav1.7 is expressed mainly on C- and Aδ-nociceptive fibers, contributes to amplification of generator potentials, and sets the gain on nociceptors \[[@B40],[@B41]\]. Indeed, data from animal studies have indicated that Nav1.7 plays a crucial role in nociception. Nav1.7 mRNA and protein are up-regulated in DRG after peripheral inflammation induced by carrageenan or complete Freund\'s adjuvant (CFA) \[[@B19],[@B42]\]. In addition, knockdown of DRG Nav1.7 significantly prevents the development of hyperalgesia in response to CFA \[[@B43]\]. Nav1.7 knockout mice also fail to develop hyperalgesia in several inflammatory pain models (Table [1](#T1){ref-type="table"}) \[[@B44]\]. In humans, mutations in the SCN9A gene (which encodes Nav1.7) are associated with three known pain disorders: channelopathy-associated insensitivity to pain (CIP), paroxysmal extreme pain disorder (PEPD), and primary erythermalgia (PE) \[[@B45],[@B46]\]. Patients with CIP lose normal response to painful insults such as puncture wounds, bone fracture, biting, or contact with hot surfaces, although other sensory responses are normal \[[@B47]\]. PEPD is characterized by severe burning pain in the rectal, ocular, and submandibular regions, and PE by burning pain and redness of the extremities \[[@B48]\]. The evidence indicates that DRG Nav1.7 plays a key role in acute and inflammatory pain. In contrast to its role in acute and inflammatory pain, whether Nav1.7 is involved in nerve injury-induced neuropathic pain is still unclear. Nav1.7 protein and current are both increased in the DRG in a rat model of painful diabetic neuropathy \[[@B49],[@B50]\], whereas the amount of Nav1.7 protein is reduced in the injured DRG after SNL, SNI, and sciatic nerve axotomy in animals \[[@B25],[@B51]\]. The level of Nav1.7 protein is also decreased in the injured DRG of humans after peripheral axotomy or traumatic central axotomy \[[@B52]\], but Nav1.7 protein has been observed to accumulate in painful neuromas of amputees with phantom limb pain \[[@B29],[@B53]\]. Interestingly, a mouse behavioral study showed that conditional knockout of DRG Nav1.7 did not affect SNL-induced development of mechanical allodynia \[[@B54]\]. Thus, it remains questionable whether DRG Nav1.7 has a role in the development of neuropathic pain. Nav1.8 ------ Nav1.8 is a sensory neuron-specific voltage-gated sodium channel that is expressed exclusively in small-diameter nociceptive DRG neurons \[[@B55]\]. Double-labeling studies have shown that 60.0% of Nav1.8-positive DRG neurons are IB4-positive \[[@B20]\]. Nav1.8 mRNA and protein are increased in DRG neurons of rodents following injection of carrageenan into a hind paw \[[@B19],[@B56],[@B57]\]. Knockdown of DRG Nav1.8 reduces the mechanical allodynia caused by intraplantar injection of CFA \[[@B58]\]. Furthermore, Nav1.8 knockout mice display impaired thermal and mechanical pain hypersensitivity in response to carrageenan-induced inflammation \[[@B59]\]. These results indicate that Nav1.8 in DRG plays a key role in inflammatory pain (Table [1](#T1){ref-type="table"}). In contrast to inflammatory insult, peripheral nerve injury down-regulates Nav1.8 mRNA and protein expression in the small-diameter neurons of the injured DRG \[[@B25],[@B60]-[@B62]\]. This down-regulation might be related to epigenetic gene silencing. Peripheral nerve injury up-regulates neuron-restrictive silence factor (NRSF) expression in the DRG and promotes NRSF binding to the neuron-restrictive silencer element within the Nav1.8 gene, thereby silencing its expression \[[@B63]\]. Interestingly, an increase in Nav1.8 protein was observed in the large-diameter neurons of the uninjured L4 DRG after L5 SNL \[[@B25],[@B64]\]. After L5 SNL, Nav1.8 immunoreactivity was also strikingly increased in the uninjured C-fibers of sciatic nerves \[[@B62]\]. Moreover, intrathecal administration of Nav1.8 ASO prevented the nerve injury-induced increase in Nav1.8 in the sciatic nerve \[[@B62]\]. TNFα might participate in this increase because inhibition of TNFα synthesis and knockout of TNFα strongly inhibited nerve injury-induced up-regulation of DRG Nav1.8 \[[@B12]\]. In patients with chronic neuropathic pain, Nav1.8 channel expression was reported to be increased in the nerves proximal to injury sites \[[@B29]\]. These results suggest that peripheral nerve injury might trigger TNFα-dependent translation of Nav1.8 in uninjured DRG neurons and promote the transportation of Nav1.8 from the uninjured DRG cell bodies to their axons. The elevated Nav1.8 in uninjured DRG neurons and their axons might account, at least in part, for the abnormal spontaneous activity and behavioral tactile allodynia observed after nerve injury. Behavioral studies appear to support this conclusion. Intrathecal administration of Nav1.8 ASO attenuated nerve injury-induced mechanical and thermal hyperalgesia \[[@B62]\], although it failed to reduce mechanical allodynia in vincristine-induced neuropathic pain \[[@B58]\]. Small interfering RNAs that specifically target Nav1.8 were able to reverse mechanical allodynia in a rat CCI model when administered intrathecally \[[@B65]\]. Additionally, a Nav1.8 blocker, A-803467, dose-dependently attenuated mechanical allodynia in rat neuropathic pain models of SNL and sciatic nerve injury \[[@B66]\]. Interestingly, neuropathic pain develops normally in the Nav1.8 knockout mouse \[[@B59],[@B67]\]. Moreover, the use of diphtheria toxin to selectively delete most nociceptors (\> 85%) that predominantly express Nav1.8 (as well as Nav1.7 and Nav1.9) in mouse DRG did not affect nerve injury-induced mechanical or thermal pain hypersensitivities \[[@B68]\]. These conflicting results indicate that the role of DRG Nav1.8 in neuropathic pain development is still uncertain and needs to be investigated further. Nav1.9 ------ Nav1.9 is selectively expressed in small-diameter (\<30 μm) DRG neurons. Sixty-two percent of Nav1.9-positive DRG neurons are IB4-positive \[[@B20]\]. DRG Nav1.9 is also highly co-localized with TRPV1, purinergic P2X3 receptor, and B2 bradykinin receptor \[[@B69]\]. Although carrageenan injection does not alter the expression of Nav1.9 mRNA or protein in DRG \[[@B19]\], the level of Nav1.9 mRNA in DRG neurons is significantly increased in the CFA model \[[@B70]\]. Nav1.9 knockout mice exhibit blunted pain behaviors in response to formalin, carrageenan, CFA, and prostaglandin E2 \[[@B71]\]. Similar to Nav1.7 and Nav1.8, DRG Nav1.9 may be required for the development of inflammatory pain (Table [1](#T1){ref-type="table"}). In contrast to its involvement in inflammatory pain, DRG Nav1.9 might not contribute to the development of neuropathic pain. The levels of Nav1.9 mRNA and protein, as well as its current density, are reduced in the DRG after sciatic nerve axotomy \[[@B60],[@B72]\], SNL, and SNI \[[@B25],[@B61]\]. In addition, intrathecal administration of Nav1.9 ASO has no effect on SNL-induced neuropathic pain \[[@B64]\]. Intact mechanical and thermal pain hypersensitivities were observed in Nav1.9 knockout mice after SNI and partial ligation of the sciatic nerve \[[@B69],[@B71]\]. Current preclinical evidence does not support a role for DRG Nav1.9 in the development of neuropathic pain. Conclusion ========== Voltage-gated sodium channels conduct sodium ion influx and control action potential generation. It has been assumed that DRG voltage-gated sodium channels participate in induction of neuropathic pain. However, as summarized in Table [1](#T1){ref-type="table"}, most voltage-gated sodium channels in DRG (with the exception of Nav1.3) are down-regulated after peripheral nerve injury. This down regulation is in contrast to the increased expression that is observed under persistent inflammatory pain conditions. The mechanisms that underlie the expression changes in neuropathic pain are still unclear. As discussed above, neurotrophins (e.g., BDNF and GDNF) and cytokines modulate voltage-gated sodium channel expression (Figure [3](#F3){ref-type="fig"}). Up-regulation of the neurotrophic factors and the release of cytokines cannot explain the down-regulation of voltage-gated sodium channels in the DRG under neuropathic pain conditions \[[@B73],[@B74]\]. More importantly, most behavioral findings from animal models do not support a role for DRG voltage-gated sodium channels in neuropathic pain (Table [1](#T1){ref-type="table"}). Interestingly, the use of sodium channel blockers (such as lidocaine) in patients can effectively inhibit a variety of neuropathic pain syndromes \[[@B75]\], although they also produce significant side effects. Inconsistent results between clinical and laboratory observations necessitate careful consideration of the differences between human and animal models and the methods for pain assessment. Therefore, a possible role for DRG voltage-gated sodium channel function in neuropathic pain cannot be excluded and remains to be further investigated. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= WW and YXT participated in the drafted manuscript. JG, YQL, and YXT contributed to critical review of the manuscript. All authors have read and approved the final manuscript. Acknowledgements ================ This work was supported by the Blaustein Pain Research Fund, Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund, and the Brain Science Institute at the Johns Hopkins University; NIH Grant NS 058886; the National Natural Science Foundation of China (30771133, 30971123, 31010103909); the National Program of Basic Research of China (G2006CB500808); and the Innovation Research Team Program of Ministry of Education of China (31010103909). The authors thank Claire F. Levine, MS, for her editorial assistance.	PubMed Central	2024-06-05T04:04:18.993470	2011-2-23	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052185/", "journal": "Mol Pain. 2011 Feb 23; 7:16", "authors": [ { "first": "Wei", "last": "Wang" }, { "first": "Jianguo", "last": "Gu" }, { "first": "Yun-Qing", "last": "Li" }, { "first": "Yuan-Xiang", "last": "Tao" } ] }
PMC3052186	Background ========== Ventricular assist devices (VAD) are mechanical pumps that replace or augment left and/or right ventricular function in cases of refractory cardiogenic shock. A number of approaches are currently taken related to the indications of these devices: VAD can be used as a bridge to heart transplantation, as a bridge to myocardial recovery leading in some cases to their prolonged use with meaningful survival and improved quality of life \[[@B1]\]. Recently VAD have also begun to be used as a \"bridge to destination\" that is, they are the final plan for the patient, being used for many years, until the patient succumbs. Fundamental differences regarding cardiac output and systemic circulation distinguish two main types of VAD: pulsatile and continuous-flow VAD. The main advantages of continuous-flow VAD being the self-contained nature, not requiring a pneumatic driver, longevity, lack of bearing contacting with blood and absence of artificial valves with theoretically smaller thrombogenic surface \[[@B2]\]. However, the effects of non-pulsatile perfusion on end-organ function remain controversial \[[@B3]-[@B5]\]. Pulsatile circulation and its effects on systemic vascular resistances have been related to the improvement of microcirculation and endothelial integrity \[[@B6],[@B7]\]; reduction in splanchnic perfusion and reduction of intestinal edema \[[@B8]\]; improvement of the cerebral haemodynamics and cerebrospinal fluid drainage \[[@B2]\] and the maintenance of neuro-endocrine cascades, specifically within the renin-angiotensine system and catecholamine release \[[@B5]\]. Despite the use of pulsatile VADs, non-homogeneous output is often generated as pulsatile VADs eject once the pre-established filling volume (stroke volume) has been reached. Therefore, the VAD ejection rate varies depending on preload and systemic resistance. Frequently there is a variable degree of persistent native cardiac contractibility, leading to asynchrony, and irregularities in arterial blood pressure waveform (Figure [1](#F1){ref-type="fig"}). In such situations of circulatory irregularity, end-organ perfusion such as cerebral blood flow may require an intact autoregulation to ensure stable microcirculation. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Real time, beat-to-beat traces of arterial blood pressure (BP) and cerebral blood flow velocity (CBFV) with a ventricular assist device (VAD). Upper channel: arterial BP waveform in a patient supported with a VAD, showing irregular fluctuations; middle channel: CBFV (insonated at the level of middle cerebral artery) with fluctuations transmitted from arterial BP; lower channel: electrocardiogram (ECG). ::: ![](1471-2253-11-4-1) ::: Cerebral autoregulation is the mechanism by which cerebral blood flow (CBF) is maintained despite changes in cerebral perfusion pressure (CPP). Cerebral autoregulation mediates states of hyperemia and ischemia to avoid vasogenic edema or infarction respectively \[[@B9]\]. Impaired autoregulation has been regarded as a risk factor associated with adverse neurological outcome after cardiac surgery \[[@B10],[@B11]\]. As a dynamic phenomenon, cerebral autoregulation may respond to spontaneous and induced changes in arterial blood pressure (BP) such as those occurring with pulsatile VADs \[[@B12],[@B13]\]. Cerebral autoregulation has been extensively studied using transcranial Doppler (TCD) which measures cerebral blood flow velocities (CBFV) as a surrogate of CBF \[[@B14],[@B15]\] using a variety of methods \[[@B16]\]. From all described methods, transfer function analysis (TFA) enables the analysis of phase shift, gain and coherence between two signals (arterial BP as input and CBFV as output) at a range of frequencies, and has the advantage of being applicable for continuous and non-invasive testing of cerebral autoregulation at the bedside. Rider and coworkers assessed cerebral autoregulation in patients supported with non-pulsatile VADs, by exposing them to dynamic maneuvers such as head-up tilting and measuring the change in CBFV. They found that cerebral autoregulation was impaired, suggesting that circulatory pulsatility is crucial for the maintenance of cerebral autoregulation \[[@B17]\]. However, their study occurred during the acute phase of the disease, after the insertion of a non-pulsatile VAD and prior to any myocardial \"modeling\" \[[@B18]\] could have occurred. Some authors have demonstrated that even with the use of non-pulsatile VAD, if a recovery time is allowed, CBF shows recovery of its pulsatility \[[@B2]\], attributing this finding to overall myocardial recovery and specifically right ventricular recovery. Whilst previous study examined the effects of non-pulsatile VAD on the regulation of steady state CBF, this study is the first to investigate the effects of pulsatile VAD, which generates irregular pressure waveform patterns, on the dynamic cerebral pressure-flow relationship by applying the cross-spectral TFA technique. Methods ======= Institutional Ethics Committee approval for the performance of the study was granted. All patients or their next of kin gave informed consent prior to enrolment in the study. A convenience sample of five patients supported with a pulsatile Thoratec VAD (Thoratec corporation, Pleasenton, CA, US) was compared with five control patients, matched for age, comorbidities, current diagnosis and cardiac output state (Table [1](#T1){ref-type="table"}). All cases were supported with a left ventricular pulsatile VAD and inotropic drugs for an average of 7 days. All patients were in their acute phase of their disease. Control subjects were in a low output state requiring inotropic or vasopressor support but without the support of VAD. Although their mean arterial blood pressure (MAP) was similar to the VAD cases, their native left ventricular ejection fraction (LV EF) was better. All patients in the control group survived, whereas 2 of the VAD cases died (Table [2](#T2){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Demographics and patients\' characteristics ::: VAD Age (years) Pathology comorbidities day of admission --------- ------------- ----------- --------------- ------------------ VAD1 52 MI none day 2 VAD2 43 MI hypertension day 29 VAD3 25 OHCA + MI none day 25 VAD4 35 OHCA hypertension day 7 VAD5 63 OHCA hypertension day 25 Control C1 64 MI none day 5 C2 65 MI hypertension day 4 C3 69 OHCA + MI hypertension day 3 C4 55 OHCA hypertension day 3 C5 50 OHCA hypertension day 2 MI: Myocardial infarct; OHCA: Out of hospital cardiac arrest; ::: ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Therapy and clinical variables ::: VAD Support therapy MAP (mmHg) CBFV (cm/s) PCO~2~(mmHg) LV EF (%) Outcome ----------- ----------------- ------------ ------------- -------------- ----------- --------------------- VAD1 VAD 82 38 36 35 Survived VAD2 VAD 96 47 40 30 Survived VAD3 VAD + DPM + NA 60 101 42 20 Intrahospital death VAD4 VAD 74 45 40 20 Survived VAD5 VAD + DPM 70 39 32 15 Intrahospital death Mean ± SD 76 ± 14 54 ± 26 38 ± 4 24 ± 8 Control C1 DPM 79 36 42 40 Survived C2 DPM 90 43 35 25 Survived C3 DPM + DBT 70 53 48 30 Survived C4 DPM + NA 75 39 41 30 Survived C5 DPM 80 42 37 40 Survived Mean ± SD 79 ± 7 43 ± 6 41 ± 5 33 ± 7 P 0.74 0.36 0.39 0.09 VAD: Ventricular Assist Device; MAP: Mean Arterial Pressure; CBFV: cerebral blood flow velocity (mean values are given); LV EF: Left Ventricular Ejection Fraction; NA: Noradrenaline; DPM: Dopamine; DBT: Dobutamine. ::: We recorded at least 5 minutes of data under resting conditions in all subjects. Simultaneous beat-to-beat recordings of BP and cerebral blood flow velocity (CBFV) waveforms were sampled using a data acquisition unit (ADInstruments, Australia). The BP waveform was acquired from an intra-arterial catheter; CBFV of middle cerebral artery (MCA) was measured using a transcranial Doppler device with a 2 MHz probe and a power of 100 mW/cm^2^(DWL, Germany). CBFV of middle cerebral arteries (MCAs) were measured using TCD following referenced criteria at the temporal acoustic window \[[@B15]\]. Both MCAs were insonated and the side with best acoustic characteristics chosen for study. Intra-patient variability was minimized by using only one investigator formally trained in TCD \[[@B16]\]. Stability of the insonated vessel diameter was assumed by maintaining a stable partial pressure of arterial carbon dioxide (pCO~2~) during measurements. Therapeutic and clinical variables were recorded at the moment of data acquisition. This study was merely observational and did not interfere with the treating physician\'s management plan. Spectral Analysis ----------------- For the assessment of cerebral autoregulation, this study used TFA based on frequency domain cross-spectral analysis. TFA assesses the relationship between two signals in the frequency domain and yields three interpretable parameters (i.e. gain, phase, and coherence). Gain is the indicator of the magnitude with which the change of output signal (i.e. CBFV) is caused by the change of input signal (i.e. BP). In the context of cerebral autoregulation analysis, a small gain indicates that cerebral blood flow does not change significantly when blood pressure changes, indicating that the cerebral autoregulatory mechanisms are intact. Phase shift relates to the temporal lag between BP and CBFV at each frequency. Zero phase lag signifies synchronous fluctuations, whilst positive phase suggests CBFV leading BP, and negative phase suggests BP leading CBFV. The gain and phase metrics, however, need to be interpreted in the context of the cross-spectral coherence, which is an estimation of the linear correlation between the input and output signals at particular frequencies. Coherence varies between 0 and 1; where 0 indicates no linear relationship and 1 indicates perfect linear relationship. It has been suggested that an increase in coherence may be indicative of a blunted cerebral autoregulation \[[@B21]\]. A low coherence, however, can be interpreted as presence of external noise/input, or nonlinear/lack of relationship between input and output. In this study, spectral analysis was performed on 5 min artifact-free segments of continuous CBFV and BP signals. Signals were downsampled to 1 Hz after appropriate anti-aliasing lowpass filtering, with any slow trend removed by cubic spline detrending. The frequency spectra and transfer function were obtained using the Welch method \[[@B21]\]. This involved subdividing the signal into 120s segments with 75% overlap (resulting in 7 segments), multiplying each segment with a Hanning window, then performing a Fast Fourier Transform (FFT), and finally averaging to give the spectra. Defining the autospectra of BP and CBFV as S~xx~(f) and S~yy~(f) (with fdenoting frequency), the cross-spectrum of BP and CBFV, S~xy~(f), was computed as the product of S~xx~\(f) and S~yy~(f) (asterisk denotes the complex conjugate). The transfer function from BP to CBFV was computed as H(f) = S~xy~(f)/S~xx~(f), and the gain magnitude and phase angle of the transfer function was obtained accordingly. The magnitude-squared coherence function was computed as γ^2^(f) = \\|S~xy~(f)\\|^2^/S~xx~(f)S~yy~(f), for detecting linear correlation between the spectral components in the two signals. Coherence ranged from 0 (lack of linear correlation) to 1 (perfect linear relationship). The spectral powers of BP and CBFV and the mean values of the transfer function gain, phase and coherence were calculated in the very low frequency (VLF, 0.02-0.07 Hz), low frequency (LF, 0.07-0.20 Hz) and high frequency (HF, 0.20-0.35 Hz) ranges as previously defined \[[@B22]\]. Unpaired Student\'s t-test was performed to compare the variables between the VAD and the control groups. P\< 0.05 was considered statistically significant. Results ======= The patient characteristics are presented in table [1](#T1){ref-type="table"} and [2](#T2){ref-type="table"}. No significant difference in MAP, pCO~2~and LVEF was found between the VAD and the control groups. The levels of pCO~2~were maintained within normal ranges and stable throughout the study, thus the effect of CO~2~on cerebral vessel was minimised. LVEF was generally lower for the VAD cases, whichwas expected as these were patients with baseline refractory cardiogenic shock who required a VAD for life support. However the difference did not reached statistical significance. The results from spectral and cross-spectral transfer function analysis of MAP and CBFV were presented in table [3](#T3){ref-type="table"} and [4](#T4){ref-type="table"}. Display of gain, phase and coherence for a representative case and control are shown in figures [2](#F2){ref-type="fig"} and [3](#F3){ref-type="fig"} respectively. No significant difference was found between the VAD and the control groups, apart from a significantly higher LF coherence between MAP and CBFV in the VAD cases (P= 0.04). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Power spectrum analysis of mean arterial pressure (MAP) and mean cerebral blood flow velocity (CBFV) in ventricular assist device (VAD) cases and controls ::: VAD VLF LF HF ------------- ------------- ------------- ------------- ------------- ------------- ------------- VAD1 0.80 2.77 0.28 0.48 0.94 0.47 VAD2 2.34 7.94 2.41 3.77 0.32 1.46 VAD3 1.06 3.22 0.20 0.94 8.88 3.72 VAD4 3.26 6.55 4.42 3.67 2.15 1.79 VAD5 2.97 2.61 0.49 1.14 5.44 2.24 Mean ± SD 2.09 ± 1.11 4.62 ± 2.46 1.56 ± 1.84 2.00 ± 1.59 3.55 ± 3.58 1.94 ± 1.19 Control* VLF LF HF pMAP pCBFV pMAP pCBFV pMAP pCBFV C1 0.47 1.12 1.55 0.80 3.80 0.56 C2 1.52 4.92 0.08 0.61 2.44 1.42 C3 2.43 6.93 0.10 0.43 2.55 1.69 C4 0.95 2.72 0.23 0.65 0.17 0.25 C5 0.24 1.20 0.70 1.42 1.98 3.23 Mean ± SD 1.12 ± 0.88 3.38 ± 2.51 0.53 ± 0.62 0.78 ± 0.38 2.19 ± 1.31 1.43 ± 1.17 P 0.17 0.45 0.27 0.13 0.45 0.52 VLF, very low frequency (0.02-0.07 Hz); LF, low frequency (0.07-0.2 Hz); HF, high frequency (0.2-0.35 Hz). pMAP (in mmHg^2^) and pCBFV (in (cm/s)^2^) are spectral powers of MAP and mean CBFV respectively. \*P\< 0.05 from t-test between VAD and Control. ::: ::: {#T4 .table-wrap} Table 4 ::: {.caption} ###### Transfer function analysis (TFA) of mean arterial pressure (MAP) and mean cerebral blood flow velocity (CBFV) in ventricular assist device (VAD) cases and controls ::: VAD VLF LF HF ------------- ------------- ------------- -------------- ------------- ------------- ------------- ------------- ------------- ------------- VAD1 0.67 1.35 1.00 0.65 1.20 -0.38 0.67 0.75 0.51 VAD2 0.76 1.82 0.98 0.79 1.25 -0.08 0.68 1.96 0.30 VAD3 0.20 0.95 0.32 0.45 1.52 0.27 0.54 1.13 0.21 VAD4 0.44 0.89 0.90 0.82 0.83 0.51 0.74 0.79 0.16 VAD5 0.45 0.63 1.04 0.56 1.18 0.72 0.77 0.72 0.00 Mean ± SD 0.50 ± 0.22 1.13 ± 0.47 0.85 ± 0.30 0.65 ± 0.16 1.20 ± 0.25 0.21 ± 0.44 0.68 ± 0.09 1.07 ± 0.52 0.24 ± 0.19 Control VLF LF HF Coh Gain Phase Coh Gain Phase Coh Gain Phase C1 0.13 0.55 0.73 0.65 0.65 0.62 0.74 0.36 -0.09 C2 0.61 1.43 0.63 0.21 1.71 -0.24 0.32 2.29 0.27 C3 0.72 1.33 0.33 0.30 1.89 0.07 0.34 2.24 -0.15 C4 0.46 1.12 -0.27 0.25 1.07 -0.40 0.28 1.02 -0.18 C5 0.25 1.15 -1.71 0.51 1.18 0.76 0.91 1.28 0.21 Mean ± SD 0.43 ± 0.25 1.12 ± 0.34 -0.06 ± 1.00 0.38 ± 0.19 1.30 ± 0.50 0.16 ± 0.51 0.52 ± 0.29 1.44 ± 0.83 0.01 ± 0.21 P 0.65 0.96 0.089 0.039\* 0.69 0.88 0.26 0.42 0.11 VLF, very low frequency (0.02-0.07 Hz); LF, low frequency (0.07-0.2 Hz); HF, high frequency (0.2-0.35 Hz). Coh, gain (in cm/s/mmHg) and phase (in rad) are the transfer function coherence, gain and phase from MAP to mean CBFV. \*P\< 0.05 from t-test between VAD and Control. ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Transfer function analysis (TFA) of mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) in a patient with ventricular assist device (VAD). The gain, phase and coherence spectra of a representative case with VAD were shown. ::: ![](1471-2253-11-4-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Transfer function analysis (TFA) of mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) in a control patient. The gain, phase and coherence spectra of a representative control were shown. ::: ![](1471-2253-11-4-3) ::: Discussion ========== In this study, the cross-spectral transfer function analysis technique was applied to study the dynamic relationship between systemic BP and CBFV in patients using pulsatile VAD. The rationale was to describe any potential alteration of cerebral autoregulation function associated with the use of VAD, as the long term use of VAD may lead to impaired cerebral autoregulation and worse neurological outcomes. The key finding of the study was the higher coherence between MAP and CBFV in the VAD patients compared with the controls, at the LF range. A low coherence between MAP and CBFV (\<0.5)indicates a lack of linear relationship between pressure and flow at the particular frequency range, and can be attributed to the presence of an intact cerebral autoregulation that introduces nonlinearity relationship \[[@B21],[@B22]\]. It has been suggested that the complex nonlinear behavior of the cerebral vasculature might be responsible for the low coherences at the VLF and LF ranges \[[@B24]-[@B26]\]. The augmented LF coherence in the VAD patients, on the other hand, might suggest a lower degree of cerebral autoregulation, possibly due to disruption of autoregulatory mechanisms by the use of VAD. However, one potential limitation to this interpretation was that, although no significant difference in the MAP power was observed between the two groups, the two VAD patients with the highest coherence (\~0.8) also had much higher spectral power in MAP than the rest of the group. It has been suggested that an increased input pressure change might lead to an increase in coherence, via an improved \"signal-to-noise\" ratio \[[@B27]\]. This effect might contribute in part to the higher coherence in the VAD group. The lack of differences in TFA gain and phase between the VAD and the control group also raised questions whether there was significant disruption of cerebral autoregulation by the use of pulsatile VAD. Alterations in cerebral autoregulation function by pathological conditions (such as stroke and autonomic failure \[[@B28],[@B29]\]) are typically associated with changes in gain and/or phase, which were not observed in the current study. Neverthelss, it appeared that the highpass filtering property of the cerebral circulation, characterised by smaller gain at the lower frequencies (VLF) and an increase in gain towards the higher frequencies (HF) \[[@B21],[@B27]\], was more apparent in the control group compared with the VAD group. It would therefore still be possible that gain properties of cerebral autoregulation might have changed in the VAD patients, although the interpretation of the gain parameter would have been limited somewhat by the low coherences in the control patients. Methodological considerations and limitations --------------------------------------------- In this study, direct assessment of CBF was not feasible as the use of non-imaging TCD does not facilitate the measurement of the cerebral vessel cross-sectional area. Instead, there is a global consensus supporting the use of CBFV as a surrogate for CBF, provided the vessel diameter remains stable during the study \[[@B30]\]. Among all factors intervening in changes of vessel diameter and therefore determining CBF \[[@B23]\], pCO~2~is directly related with vessel diameter and was maintained stable and within normal values, during patient recruitment. For TCD recordings, only the MCA with better acoustic properties was recorded and analyzed. Although spatial heterogeneity of cerebral perfusion as well as interhemispheric differences has been described \[[@B30]\]; the endpoint in this study was to ensure the best transcranial Doppler recordings in order to minimize the signal-to-noise ratio and increase data reliability \[[@B30]\]. No significant change in gain and phase was found between the two groups in this study, but the small population recruited could have contributed to the lack of statistical significance, thus further studies with larger sample size would be desirable. Conclusion ========== The use of pulsatile VAD affected the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range, thus whether there was any significant disruption of cerebral autoregulation mechanism was not clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed. Given the absence of all conditions that define autoregulation, these results should be regarded as preliminary data, and further studies, employing bigger samples, are warranted. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= JB and JFF conceived and designed the study; JB undertook patient screen and data acquisition; JB drafted the manuscript which was reviewed and amended by all other authors. GC and Y-C T undertook data analysis and contributed to its interpretation. AGB undertook statistical analysis. KRD conceived and designed the technical components of the study, also reviewed revised the manuscript. RB and PA reviewed and amended the manuscript. All authors read and approved the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1471-2253/11/4/prepub> Acknowledgements ================ We acknowledge Dr Daniel Mullany for ensuring patients\' availability during study recruitment. This research was supported by a research grant from the Royal Brisbane Hospital Research Foundation (Protocol 2007/076). Additional funding was provided by the Prince Charles Hospital Research Foundation.	PubMed Central	2024-06-05T04:04:18.995985	2011-2-22	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052186/", "journal": "BMC Anesthesiol. 2011 Feb 22; 11:4", "authors": [ { "first": "Judith", "last": "Bellapart" }, { "first": "Gregory S", "last": "Chan" }, { "first": "Yu-Chieh", "last": "Tzeng" }, { "first": "Philip", "last": "Ainslie" }, { "first": "Adrian G", "last": "Barnett" }, { "first": "Kimble R", "last": "Dunster" }, { "first": "Rob", "last": "Boots" }, { "first": "John F", "last": "Fraser" } ] }
PMC3052187	Background ========== Reverse transcription quantitative PCR (RT-qPCR) is rapidly becoming a valuable tool for mRNA biomarker quantification in clinical diagnostics. There has been a proliferation of RT-qPCR assay formats and platforms in recent years due to wider applications of this technology, coupled with improvements in sensitivity, specificity and accuracy of measurements of gene expression. However, there is one intrinsic limitation to the current qPCR platforms, namely lack of controls for cross-platform comparison. Although the manufacturers have developed platform-specific quality controls, they are often not adequate for cross-platform comparisons, particularly for the evaluation and standardization of transcriptomic data due to differences in protocols, data processing and analysis methods. Thus, development of universal RNA standards offers great potential in the validation of data obtained from different RT-qPCR methods. In the present investigation, we have compared the performance of Fluidigm^®^BioMark™ Integrated microfluidic (henceforth referred to as BioMark) dynamic arrays with the widely used ABI 7900HT real-time PCR platform (henceforth called ABI 7900HT system) using generic RNA standards. Pre-amplification of RNA or cDNA facilitates the investigation of a large number of genes when the starting material is limiting, such as with tissue biopsies and archival formalin-fixed paraffin-embedded (FFPE) samples \[[@B1],[@B2]\]. Pre-amplification methods used generally include either linear amplification of RNA or exponential (PCR-based) amplification of cDNA \[[@B3]-[@B5]\]. However, concerns have been raised as to whether pre-amplification of samples by exponential amplification introduces bias in expression levels between genes \[[@B6]\]. For the BioMark microfluidic PCR system, each sample in the 48 × 48 dynamic array is distributed amongst 48 different reaction chambers, therefore pre-amplification is recommended for certain applications. However the limit of detection (LOD) of using pre-amplified vs. non-amplified cDNA samples, and its impact on the technical performance of the PCR array have not been fully characterized. Exogenous RNA controls produced by in vitrotranscription are ideal materials for investigating different RT-qPCR kits and methodologies \[[@B7]\]. Recently a panel of RNA controls have been developed for use in gene expression applications by the External RNA Controls Consortium (ERCC), an ad hocgroup of 70 members from private, public and academic organizations led by the National Institute of Standards (NIST) \[[@B8],[@B9]\]. It is hoped that standards developed from these sequences will aid in comparisons of gene expression data generated from various platforms such as microarray, RT-qPCR and next generation sequencing, and also provide quality control of gene expression measurements in the clinical laboratory \[[@B10]\]. Multigene biomarker measurements are at the forefront of a new class of medical devices using in vitrodiagnostic multivariate assays, such as MammaPrint and Oncotype Dx in the area of breast cancer prognosis \[[@B11]\]. Since gene expression biomarkers typically encompass a range of transcript abundances and differential expression ratios, it is more appropriate to use multiple RNA standards as quality controls for standardizing such measurements, as opposed to a single transcript at a fixed concentration. In the current study, we used a sub-set of the 96 ERCC RNA standards (Additional File [1](#S1){ref-type="supplementary-material"}) in order to characterize their performance on a nanofluidic PCR system, the BioMark 48 × 48 dynamic arrays, against a conventional qPCR platform, the ABI 7900HT system. We also investigated the impact of pre-amplification of cDNA samples on the linear range and precision of measurements by nanofluidic qPCR. Two prototype panels were constructed with selected RNA standards containing varying copy number within each panel, and varying ratios between them for mimicking non-differentially and differentially expressed mRNA biomarkers as represented in normal and disease states. The expression profile of the RNA standards was measured using both platforms and the accuracy and precision of their detection were compared. Results ======= Linear range of dynamic arrays ------------------------------ One advantage of the BioMark arrays is the capability to analyse a large number of genes in a single sample. In order to facilitate this, up to \~ 2 μL of sample is loaded into each sample inlet of the chip and further distributed in the channels of the microfluidic chip as 48 separate 9 nL reactions using the integrated fluidic circuit (IFC). Thus the original sample is diluted more than 200-fold prior to the PCR reaction. In order to ensure that there are sufficient copies of target molecules in each reaction, Fluidigm^®^recommends using either RNA samples that do not have a concentration lower than 250 ng total RNA/μL or that a pre-amplification stage is included, whereby the cDNA sample undergoes 14-18 cycles of amplification with a mix of up to 100 different primer pairs (Fluidigm Advanced Development Protocols 3, 5 and 8). In order to further investigate the requirement for pre-amplification, RNA standards were spiked into human total RNA at different concentrations (for sample composition, see Additional File [2](#S2){ref-type="supplementary-material"}) with the aim of mimicking a range of physiological abundances, from highly abundant mRNA transcripts (10^6^copies/ng total RNA; equivalent to 10^4^copies per cell) to transcripts only expressed in a sub-population of cells (1 copy/ng total RNA; equivalent to 0.01 copies per cell), based on the RNA content of a cell estimated as 26 pg \[[@B12]\]. A single RT reaction was performed for each RNA sample followed by 3 independent qPCR runs, with replicate assay measurements for each ERCC standard. Figure [1](#F1){ref-type="fig"} compares the results of real-time PCR with cDNA samples (equivalent to 1 ng total RNA) or pre-amplified cDNA on the BioMark arrays with non-amplified cDNA using the ABI 7900HT system. The linear range in terms of transcript copy numbers for the pre-amplified cDNA samples on the BioMark arrays was similar to the non-amplified cDNA samples on the ABI 7900HT system, covering five orders of magnitude between 10 and 10^6^copies/ng total RNA. Although the linear range of both platforms was similar, the Ct values from BioMark were over 10 units lower than those observed for ABI 7900HT system. This could be due to the higher concentration of the template in the 9 nL nanofluidic reaction chambers of BioMark arrays compared to the standard 20 μL volume used on the ABI 7900HT system, such that the fluorescence output of the PCR reaction exceeds the threshold level at an earlier cycle (personal communication: A. Meliss, Fluidigm, September 2009). For the RT-PCRs performed with non-amplified cDNA samples on BioMark arrays, the linear detection range covered only two orders of magnitude between the transcript numbers of 10^4^and 10^6^copies/ng. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Linear range of RT-qPCR platforms. Example plot showing detection of an ERCC RNA standard (ERCC-42) across a range of transcript copy numbers from 1 to 10^6^copies per ng total RNA with cDNA (triangles) or pre-amplified cDNA (diamonds) as the template on (A) BioMark (B) ABI 7900HT system. Data-points are displayed as individual qPCR replicates. Dotted line indicates linear detection range. ::: ![](1471-2164-12-118-1) ::: LOD of dynamic arrays --------------------- Unlike hybridization-based technologies such as microarrays, the LOD cannot be ascribed for RT-qPCR using a baseline for sample blanks, as a Ct value is not obtained for zero control samples. Therefore, the incidence of failed PCR reactions (undetermined Ct value) across the range of transcript abundances was also compared for conventional and nanofluidic PCR platforms with pre- or non-amplified cDNA as the template (Figure [2](#F2){ref-type="fig"}). As in Figure [1](#F1){ref-type="fig"}, a high percentage of PCR failures was observed at 1 copy/ng total RNA for both pre-amplified cDNA on the BioMark arrays and cDNA using the ABI 7900HT system. The rate of failures was slightly lower on the BioMark arrays as the projected template concentration per 9 nL reaction was 6 copies (assuming 100% efficiency of RT and pre-amplification), whilst it was only 1 RNA copy per ABI 7900HT reaction. For non-amplified cDNA, high reaction failure rates with BioMark arrays were observed below 10^3^copies/ng, which equates to 2 copies per 9 nL reaction. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Limit of detection of ERCC RNA standards. Incidence of failed PCR reactions on ABI 7900HT system or BioMark using cDNA or pre-amplified cDNA as the template. Mean percentage of failed PCR reactions ± SD are displayed based on data from 8 different RNA standards from 3 independent qPCR experiments across a range from 1 to 10^6^copies ERCC standard per ng total RNA. ::: ![](1471-2164-12-118-2) ::: qPCR accuracy and precision --------------------------- The accuracy and precision of qPCR detection across the above noted linear range was assessed by linear regression, comparing the slope and R^2^of the data from three independent dynamic arrays (Table [1](#T1){ref-type="table"}). Pre-amplification of cDNA samples resulted in a significant improvement in the slope of the linear regression of copy number against Ct value (p\< 0.05), with the mean slope within 6% of the ideal slope of 1. The pre-amplified cDNA samples demonstrated greater precision of the instrument over the linear detection range (Figure [1](#F1){ref-type="fig"}) than cDNA (p\< 0.05) (Table [1](#T1){ref-type="table"}). The accuracy and precision of pre-amplified cDNA detection on the BioMark arrays were comparable to those of the ABI 7900HT where non-amplified cDNA was used as the template (Table [1](#T1){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Accuracy and precision of linear detection range of PCR platforms ::: -------------------------------------------------------------------------------------------------------------------- Slope R^2^ -------------- -------------------- ---------------- -------------------- -------------------- ---------- ---------- Platform Dynamic arrays ABI 7900HT Dynamic arrays ABI 7900HT Template Pre-amplified\ cDNA cDNA Pre-amplified\ cDNA cDNA cDNA cDNA ERCC- 13 -1.06 -1.08 -1.06 0.999 0.993 0.997 42 -1.07 -1.11 -1.06 0.998 0.970 0.995 81 -1.02 -1.07 -1.04 0.998 0.976 0.998 84 -1.03 -1.07 -1.01 0.998 0.973 0.996 95 -1.07 -1.12 -1.08 0.997 0.975 0.998 99 -1.06 -1.06 -1.05 0.998 0.985 0.997 113 -1.06 -1.15 -1.04 0.998 0.971 0.997 171 -1.12 -1.13 -1.08 0.998 0.982 0.996 All -1.06 -1.10 -1.05 0.999 0.978 0.997 -------------------------------------------------------------------------------------------------------------------- Linear regression was performed with Ct values vs. log~2~(ERCC RNA copy number) for each PCR platform across the linear range marked in Figure 1. The mean slope and R^2^values from three independent qPCR experiments reflect the accuracy and precision of the detection of the 10-fold differences in copy numbers between samples. ::: Precision of qPCR detection as a function of transcript copy number for the two platforms is shown in Figure [3](#F3){ref-type="fig"}. For concentrations of RNA standards above 10^4^copies/ng (using cDNA with the ABI 7900HT system or pre-amplified cDNA for the BioMark arrays), and above 10^6^copies/ng (with non-amplified cDNA for the BioMark arrays), Ct standard deviation values are below 0.1 units, corresponding to less than 7% variation \[[@B13]\]. As RNA copy numbers decrease, variation between replicate qPCR measurements increases, with maximum average standard deviation values corresponding to 46% and 66% variation at 10 copies/ng for the BioMark arrays (pre-amplified cDNA) and ABI 7900HT system respectively (Figure [3](#F3){ref-type="fig"}). ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Precision of real-time PCR platforms. Within-run qPCR precision across a range of transcript abundance levels (copies per ng total RNA) are displayed for cDNA or pre-amplified cDNA quantified using ABI 7900HT system or BioMark. Mean variation (SD) of Ct values ± SD is displayed based on data from eight different RNA standards from three independent qPCR experiments. ::: ![](1471-2164-12-118-3) ::: RNA biomarker panels -------------------- The accuracy of nanofluidic dynamic PCR for detection of multiple genetic biomarkers was further tested using two panels of RNA standards. With the aim of mimicking \'normal\' and \'disease\' states where some biomarkers are differentially expressed whilst others remain unchanged in their expression, standards were spiked at different ratios (1.0, 1.5, 2.0, 5.0, 10.0 and 20-fold differences) over a range of transcript copy numbers (Table [2](#T2){ref-type="table"}). Three independent RT experiments, each containing two replicate RT reactions, were performed in order to investigate how technical noise associated with the whole RT-qPCR process impacts on the detection of differential or non-differential transcript expression levels. The resulting cDNA was quantified on the ABI 7900HT system or pre-amplified and measured on the BioMark. Fold change values were calculated using ΔCt values and the results of pair-wise comparison of the expression levels of each ERCC standard in the two panels displayed in Figure [4](#F4){ref-type="fig"}. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Concentrations and ratios of ERCC RNA standards in simulated \'normal\' and \'disease\' panels ::: ERCC standard Copies/ng total RNA Ratio B/A --------------- --------------------- ------------- ------ 13 1 × 10^5^ 1 × 10^5^ 1.0 25 1 × 10^2^ 1.5 × 10^2^ 1.5 42 1 × 10^4^ 5 × 10^3^ 0.5 51 5 × 10^0^ 1 × 10^2^ 20.0 81 1 × 10^2^ 1 × 10^2^ 1.0 84 1 × 10^2^ 5 × 10^2^ 5.0 95 1 × 10^3^ 1 × 10^3^ 1.0 99 8 × 10^3^ 1.2 × 10^4^ 1.5 113 1 × 10^1^ 1 × 10^1^ 1.0 171 1 × 10^1^ 1 × 10^2^ 10.0 10 ERCC RNA standards were spiked in a background of Universal Human Reference RNA at different concentrations and ratios in order to create simulated \'normal\' and \'disease\' panels, A and B. ::: ::: {#F4 .fig} Figure 4 ::: {.caption} ###### Accuracy of fold change detection. Two panels (A and B) containing different ratios of RNA standards across a range of copy numbers were quantified using (A) cDNA with the ABI 7900HT system or (B) pre-amplified cDNA with BioMark 48 × 48 dynamic arrays. Expected fold change values (see the tables below the Figures) are compared to the mean of measured fold changes from RT-qPCR reactions performed on six pairs of samples. The error bars represent standard error. ::: ![](1471-2164-12-118-4) ::: Overall, fold change estimation was found to be accurate for both ABI 7900HT system and BioMark arrays (Figures [4A](#F4){ref-type="fig"} and [4B](#F4){ref-type="fig"}), with the observed fold change values overlapping with the expected fold change measurements for all standards. For ERCC standards mimicking low abundance transcripts, the technical noise associated with the resulting fold change measurement was considerably greater than higher abundance RNA species. For example, a 20-fold increase in expression level at 5 copies/ng (ERCC-51) is associated with 16-fold and 10-fold difference in the minimum and maximum fold changes detected by the BioMark arrays and ABI 7900HT system respectively. For non-differential expression at low copy numbers (fold change = 1.0; ERCC-113), fold change measurements spanned a range of over 50% and 150% of the expected value on the BioMark and ABI 7900HT system respectively. At levels of abundance exceeding 100 copies/ng, mean fold change measurements were accurate to within 10% of expected values. Discussion ========== In this study we sought to demonstrate the utility of RNA standards for characterisation of a new platform, the BioMark, where PCR reactions are performed in volumes over a 1000-fold lower than on a conventional RT-qPCR instrument (ABI 7900HT system). The requirement for sample pre-amplification for this technology contrasts with standard two-step RT-qPCR approach, therefore the impact of this methodology was also evaluated. Dilutions of RNA standards across a wide physiological range demonstrated that the linear detection range of the BioMark arrays is similar to the ABI 7900HT real-time PCR system, when pre-amplified cDNA is used as the template (Figure [1](#F1){ref-type="fig"}). The precision of replicate measurements within the array also compared favourably to the intra-run standard deviation of Ct values for the ABI 7900HT system (Figure [3](#F3){ref-type="fig"}). At copy numbers mimicking medium to high abundance transcripts, the precision of the BioMark arrays is in a similar range to the minimum variation of \~ 0.1 units observed for another nanofluidic PCR array, the OpenArray format \[[@B14]\]. However, when non-amplified cDNA is quantified using the nanofluidic BioMark arrays, the linear range is severely limited, to only two orders of magnitude (Figure [1](#F1){ref-type="fig"}). At the lower detection limit of 10^4^RNA copies per reaction (Ct \~ 27), the variation between measurements increases significantly (Figure [3](#F3){ref-type="fig"}), whilst below this level of abundance, the rate of PCR failures increases rapidly (Figure [2](#F2){ref-type="fig"}). Pre-amplification of template cDNA using a preliminary PCR step of 14 cycles improves both the accuracy and precision of the transcript quantification using the dynamic arrays (Table [1](#T1){ref-type="table"}). The improved detection of the 10-fold differences in RNA copy numbers between sample series (resulting in an average slope within 6% of expected value) also indicates that the pre-amplification process does not introduce bias into the detection of transcripts which cover a wide dynamic range. Relative expression measurements are central to gene expression analysis by RT-qPCR and for determining whether a panel of biomarkers has predictive power for disease diagnosis and prognosis \[[@B15]\]. Therefore, we developed two panels of RNA standards in order to further investigate the accuracy of detecting gene expression ratios using the new type of PCR array compared to an established system. The standards were spiked at varying ratios between panels in order to obtain information on how well the methodologies can discriminate between differentially and non-differentially expressed candidate genes at different transcript abundance levels (Figure [4](#F4){ref-type="fig"}). Our results show good accuracy of observed vs. expected values for both platforms, which is in agreement with previous studies demonstrating good concordance of fold change measurements between the BioMark arrays and the ABI 7900HT system \[[@B16]\]. The precision of the fold change estimation varied according to the abundance of the transcripts, demonstrating increased variation in the observed values for lower concentrations of standards for both nanofluidic and standard real-time PCR approaches. This suggests that the sensitivity of the technique to correctly detect the expected fold change is reduced at low copy numbers (10 RNA copies or less per reaction on the ABI 7900HT system). Dixon et al. \[[@B14]\] also found that the sensitivity of the OpenArray platform was lower for Ct values corresponding to lower copy numbers, resulting in an increased number of false negative results. The increased variation in fold change detection at low copy numbers is likely to arise due to decreased efficiency at RT stage and increased stochastic variation in the PCR reaction for low target numbers \[[@B17]\]. We also found that both qPCR platforms were able to accurately detect a 1.5-fold change in mRNA expression, below the 2-fold cut-off which has been cited as a limit to the resolving power of conventional PCR, as it constitutes a difference of less than a single cycle \[[@B18]\]. The BioMark dynamic arrays were recently shown to be able to detect a 1.25-fold difference in DNA copy number by qPCR, with greater levels of precision achievable with the larger number of technical replicates possible with this high-throughput approach \[[@B19]\]. Since assay and sample loadings are in separate inlets on 48 × 48 dynamic arrays, it is possible to increase technical replication by using multiple assay inlets and/or multiple sample inlets. However, it should be noted that replication only at the assay level does not substitute for true sampling variation by the process of taking a sample from a population of molecules. The use of gene-specific oligonucleotide standards for inter-run and cross-platform calibration has been demonstrated to improve the accuracy of class prediction based on panels of biomarkers \[[@B15]\]. Although ERCC RNA standards do not directly provide information on the performance of biomarker-specific assays, a panel of multiple standards, such as that used here provides a robust means of evaluating platform performance by minimizing confounding effects resulting from differences in assay performance due to individual primer and probe specificity. RNA standards could also serve as calibrator samples between experiments where different sets of potential biomarkers genes are investigated, as well as in the context of a diagnostic assay where the expression of the same panel of genes is quantified. In addition to target gene normalization using a reference gene or panel of reference genes \[[@B20]\], normalization to an ERCC RNA standard or multiple RNA standards may be a useful control for elucidating technical variation due to RT and qPCR steps \[[@B21]\]. Conclusions =========== We conclude that universal RNA standards can provide robust information on the performance characteristics of different RT-qPCR platforms and methodologies. The results obtained using panels of multiple RNA standards indicate that the linear detection range, precision and accuracy of nanofluidic BioMark dynamic arrays are similar to those of an established real-time PCR instrument, the ABI 7900HT system, when pre-amplified cDNA is used as the template. The standards also provide reference values for the range of transcript abundance over which it would be possible to measure non-amplified cDNA on the nanofluidic BioMark high-throughput arrays. Carefully constructed panels of ERCC RNA standards have the potential to act as benchmarks for the calibration and interpretation of biomarker measurements in drug discovery and clinical diagnostics. Further evaluation of these standards is required for potential incorporation into a \'quality metrics\' toolkit for assessing their suitability for cross-platform comparisons. Methods ======= Preparation of in vitrotranscribed RNA and samples ---------------------------------------------------- In vitrotranscribed ERCC RNA standards were produced from ERCC plasmid DNA (courtesy of Dr. Marc Salit, NIST, USA). Plasmid DNA from standards ERCC-13, 25, 42, 51, 81, 84, 95, 99, 113 and 171 was cleaved into a single linear molecule using BamHI restriction endonuclease (New England Biolabs, UK). 500 ng of plasmid DNA was used for each sample and digested by adding 40 U of BamHI enzyme in NEB3 buffer provided by the manufacturer. The digestion mixture was incubated at 37°C for 2 hours followed by purification using QiaQuick PCR purification kit with an elution volume of 32 μl. In vitrotranscription was carried out with 8 μl digested plasmid DNA using MEGAscript^®^T7 Kit (Applied Biosystems/Ambion, UK) followed by DNasetreatment and clean-up using RNeasy columns (Qiagen, UK). RNA concentration and insert sizes were estimated using the Nanodrop 1000 spectrophotometer (Thermo Scientific, UK) and 2100 Bioanalyzer (Agilent Technologies, USA) respectively. RNA standards were diluted in nuclease free-water and spiked into Universal Human Reference RNA (Stratagene, UK) (final concentration 100 ng/μl). For experiments investigating the linear range of platform detection, standards were spiked at 10-fold intervals between 1 and 10^6^copies/ng total RNA (Additional File [2](#S2){ref-type="supplementary-material"}). For the simulated \'normal\' and \'disease\' panels, standards were spiked at various copy numbers and ratios (Table [2](#T2){ref-type="table"}). Reverse transcription and pre-amplification of cDNA --------------------------------------------------- RNA samples were reverse-transcribed using the TaqMan^®^Reverse Transcription Reagents kit (Applied Biosystems, UK) in 40 μL reactions containing 400 ng total RNA and oligo(dT) primers according to manufacturer\'s instructions. cDNA samples were diluted to a concentration of 0.5 ng/μL (total RNA equivalent) with nuclease-free water. For experiments investigating the linear range of platform detection (Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}), a single RT reaction was performed for each RNA sample whilst for the simulated \'normal\' and \'disease\' panels (Figure [4](#F4){ref-type="fig"}), 6 replicate RT reactions were performed. A single aliquot of each cDNA sample, equivalent to 12.5 ng RNA, was pre-amplified with assays corresponding to all 10 standards in a 25 μL volume reaction using TaqMan^®^PreAmp Mastermix (Applied Biosystems, UK) according to manufacturer\'s protocol. Following pre-amplification, the samples were diluted 1:5 (v/v) in TE buffer, pH 8.0. Real-time PCR ------------- Further information on sample preparation and real-time PCR validation complying with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines \[[@B22]\] is available in Additional Files [2](#S2){ref-type="supplementary-material"} and [3](#S3){ref-type="supplementary-material"} (MIQE Additional Information and Checklist). Custom-designed primers and TaqMan^®^FAM-TAMRA probes for each ERCC standard (Additional File [1](#S1){ref-type="supplementary-material"}) were supplied by Applied Biosystems and a 20 × assay mix was prepared containing 18 μM primer and 5 μM probe (final concentration 900 nM primer and 250 nM probe). qPCR assays were tested initially using a serial dilution of ERCC cDNA and PCR efficiencies calculated (see Additional Data Table 2: MIQE Additional information). All 10 assays were found to have PCR efficiencies of greater than 86%. BioMark arrays were prepared according to the manufacturer\'s instructions. TaqMan^®^assays were diluted 1:1 (v/v) with DA Assay Loading Reagent (Fluidigm^®^) and 5 μL was added to each assay inlet of the array. Also, 5 μL reaction mix was prepared by mixing 2 × TaqMan^®^Universal Mastermix (Applied Biosystems), DA Sample Loading Reagent and nuclease-free water containing 2 μL of cDNA or pre-amplified cDNA. The samples were loaded into each sample inlet as per manufacturer\'s recommendations. Following loading of the assays and samples into the chip by the IFC controller, PCR was performed with the following reactions conditions: 50°C for 2 minutes, 95°C for 10 minutes, followed by 45 cycles of 95°C for 15 seconds and 60°C for 60 seconds. Data was processed by automatic global threshold setting with the same threshold value for all assays and linear baseline correction using BioMark Real-time PCR Analysis software (version 2.1.1). The quality threshold was set at the default setting of 0.65. For experiments investigating the linear range of platform detection (Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}), 8 qPCR reactions consisting of 4 assay inlet and 2 sample inlet replicates were performed for each cDNA or pre-amplified cDNA sample. For the simulated \'normal\' and \'disease\' panels (Figure [4](#F4){ref-type="fig"}), 12 qPCR reactions consisting of 4 assay inlet and 3 sample inlet replicates were performed for each cDNA sample. Conventional real-time PCR was performed using ABI 7900HT system in 20 μL reaction volumes containing TaqMan^®^Universal PCR Master Mix and 2 μL of respective cDNA in optical 96-well plates (Applied Biosystems). Cycling conditions were as those used for the BioMark arrays. Triplicate qPCR reactions were performed for each cDNA sample for all experiments. The threshold fluorescence level was set manually for each plate using SDS software version 2.3 (Applied Biosystems). Following export of Cycle threshold (Ct) data, further data analysis for both platforms was performed in Microsoft^®^Excel 2003. Comparison of slope and R^2^values between pre-amplified and non-amplified cDNA, as a template on the BioMark arrays, was performed as paired t-test in Microsoft^®^Excel 2003. List of abbreviations ===================== ERCC: External RNA Controls Consortium; RT-qPCR: Reverse Transcription Quantitative PCR; LOD: limit of detection; FFPE: formalin-fixed paraffin-embedded; IFC: integrated fluidic circuit; RT: Reverse Transcription; PCR: polymerase chain reaction. Authors\' contributions ======================= AD performed RT-qPCR experiments, participated in the design of the study, performed data analysis and drafted the manuscript. RE participated in the design of the study and helped to draft the manuscript. CF conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Additional files ================ The following additional are available with the online version of this paper. Additional data file [1](#S1){ref-type="supplementary-material"} is a table detailing the primer and probe sequences used for qPCR assays. Additional files [2](#S2){ref-type="supplementary-material"} and [3](#S3){ref-type="supplementary-material"} are additional data and a checklist in compliance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 Taqman assays for ERCC RNA standards. Microsoft Word file detailing the sequences of primers and probes used for qPCR assays. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 MIQE Additional Information. Microsoft Excel file containing further information on RNA preparation, purity, PCR efficiency and negative control data complying with the MIQE guidelines. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 3 MIQE Checklist. Checklist in Microsoft Word format detailing information complying with MIQE guidelines. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ The work described in this paper was funded by the UK National Measurement System. We are grateful to Dr. Marc Salit (NIST, USA) for the provision of ERCC plasmid DNA. We would also like to thank Jesus Minguez (LGC) for statistical analysis and Dr. Bridget Fox (LGC) for assistance with the production of in vitrotranscribed RNA standards.	PubMed Central	2024-06-05T04:04:19.000675	2011-2-18	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052187/", "journal": "BMC Genomics. 2011 Feb 18; 12:118", "authors": [ { "first": "Alison S", "last": "Devonshire" }, { "first": "Ramnath", "last": "Elaswarapu" }, { "first": "Carole A", "last": "Foy" } ] }
PMC3052188	Background ========== In the last few years it has became increasingly evident that, among the multiple gene expression regulation mechanisms, eukaryotic genes expression level is also dependent on their location within the genome \[[@B1]\]. For example, a more or less strong tendency for colocalization in the same chromosomal regions has been described for genes expressed at very high levels \[[@B2]\], genes constitutively expressed in most tissues (housekeeping genes) \[[@B3]\], genes encoding proteins assigned to the same functional pathway \[[@B4]\] or genes simultaneously expressed (coexpressed) in a particular tissue or organ \[[@B5]\]. The coexpression of colocalized genes could be determined by the conformation of chromatin domains to which they belong, or by local sharing of regulatory (e.g., enhancer) elements, thus raising questions about the functional significance of clustering of coexpressed genes \[[@B1]\]. Alternatively, clustering of genes could be explained by coinheritance, a selective pressure to maintain a genetic linkage among genes that encode for functionally related products and that will tend to be inherited together or, finally, it could merely reflect the origin of functionally related genes via tandem duplication of genes \[[@B6],[@B7]\]. Further studies about the relationships between the expression of eukaryotic genes and their relative position in the genome are needed to clarify this biological issue. Such studies will take great advantage of the ever increasing amount of genomic-scale expression data obtained by serial analysis of gene expression (SAGE), gene expression microarrays or high-throughput RNA sequencing that are now made available in public databases. In fact, the transcriptome maps studies mentioned above showed the biological relevance of a global view of gene expression distribution by exploiting the availability of gene expression profile data obtained by the method of SAGE \[[@B2],[@B3],[@B5]\]. These studies contributed to challenge the traditional view that genes are randomly distributed along each chromosome in eukaryotic genomes. However, no computational biology tool for the generation and analysis of transcriptome maps was released to perform the algorithms described in these papers, with the exception of the web-based application \"Transcriptome Map\" \[[@B2],[@B8]\]. Nevertheless, this only supports a limited number of input data types (derived from a few species, and, for human, only derived from SAGE experiments or from three Affymetrix microchip platforms), normalization methods and visualization options. The application \"Caryoscope\" \[[@B9]\] is a Java-based program, able to generate a graphical representation of microarray data in a genomic context. However, it is not intended to process input data (that must come from one single source, already containing all localization information for each element), or to perform any test of statistical significance on the resulting plot. The lack of software dedicated to constructing and analyzing transcriptome maps was already pointed out in 2006 \[[@B10]\], emphasizing that up until then, only algorithms or scripts had been presented and these were often tailored to specific uses (e.g., the study of a particular organism or the analysis of data derived from a single type of experimental platform). In addition, the tools that are available typically accept only gene lists as input and are not able to represent and analyze the continuous change, along the chromosome, of expression intensity assigned to overlapping regions of desired size, on the basis of the mean expression value calculated across all genes located in that region. This representation better reflects the biological reality of the quantitative changes of regional gene activity, rather than a simple count of the enrichment in differentially expressed genes, which is however also a desirable additional parameter of analysis. These considerations underline the need for a general tool able to generate and analyze quantitative transcriptome maps from any source, provided that gene expression values for a certain gene set are available. Such a tool should also be capable of accepting and integrating data from multiple sources and be easily configurable for the investigation of any organism. Here we describe TRAM (Transcriptome Mapper), a user-friendly graphical interface software that may be run locally on personal computers (based on both Macintosh and Windows operating systems) and that meets and exceeds these specifications, by integrating original methods for parsing, normalizing, mapping and statistically analyzing expression data (Figure [1](#F1){ref-type="fig"}); in addition, it has the ability to easily generate maps showing differential expression between two sample groups, relative to two different biological conditions. The results of a test, using the hematopoietic progenitors CD34+ cells differentiation toward megakaryocytic cells (the large bone marrow cells whose fragments form platelets that are released into the blood) as a biological model, are also presented and discussed. This shows the ability of TRAM to identify chromosomal segments and gene clusters which are biologically relevant for the cell differentiation toward the megakaryocyte phenotype. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### General architecture of TRAM software. The user is guided step-by-step through import and analysis of any gene expression profile dataset in text format. The gene identifiers of any type are converted in official gene symbols/gene names, followed by intra-sample as well as inter-sample normalization of gene expression values. The expression is mapped along each chromosome and graphically displayed on the basis of mean value for all genes included in each segment of arbitrary length. Over- and under-expressed regions are determined following statistical analysis. ::: ![](1471-2164-12-121-1) ::: Results ======= Expression data import, parsing and normalization ------------------------------------------------- The software is composed of a set of 37 related database tables, with 118 relationships among them. Some tables are designed to convert gene identifiers associated with expression data, e.g. GenBank accession numbers and/or UniGene cluster identifiers, into official gene symbols. Gene identifier conversion tables may be loaded or updated by the user, or are provided pre-loaded for human, mouse and zebrafish organisms. In addition, the user may download genomic data from Entrez Gene (e.g. chromosome number, chromosome lengths and genomic coordinates for known mRNAs) relating to the organism investigated. These data files are then easily imported and processed by the software during the set up process. Three species-specific pre-loaded (pre-setup) versions are also distributed. In addition, TRAM makes fully original specific data management and analysis tools available, including a parser able to find the best and updated gene/RNA cluster name available to be assigned to a probe identifier. This is based on a converter of any RNA sequence accession number to the relative gene symbol, by searching an embedded parsed full UniGene updatable database table. For the human version, the parser locally resolves all 6,956,798 RNA sequence accession numbers, which are related to both known transcripts and to expression sequence tags (ESTs) included in H. sapiensUniGene build \#228, December 2010. This allows a better conversion of those sequence accession numbers listed in a platform that may have been registered in the past few years without the availability of the presently corresponding gene symbols. For example, in the commonly used GPL96 GEO platform (Affymetrix HG-U133A microarray), 597 probe identifiers, with unavailable gene symbols in the Affymetrix platform scheme, were successfully assigned to mapped gene symbols or UniGene clusters. A sample is defined as a homogeneous series of gene identifiers and their corresponding expression values, i.e. a list of values obtained in a single channel following a microarray hybridization experiment. To allow the comparison of expression data obtained from different samples, the absolute values of a sample may be converted into percentages of the mean (or median, or maximum) of all expression values within that sample. The software is also designed for the comparison between a sample (or a pool of samples) named \'A\' and another sample (or a pool of samples) named \'B\', each collected into specific tables. In this case, the ratio of \'A\' and \'B\' (named \'A/B\') expression for each locus will be analyzed. Although TRAM is a map-centred transcriptome analysis tool it can also summarize and allow the analysis of gene expression data of unmapped genes, exploiting its capability of parsing and normalization in order to highlight differential expression of single genes between two biological conditions even in the absence of data about genomic location of the gene. Scaled quantile normalization ----------------------------- We compared the correlation between sample datasets of the same pool but derived from different platforms, using the intra-sample normalization \'Mean\' method (by which each value is expressed as percentage of the mean gene expression value for that sample). Inter-sample scaled quantile normalization always gave analogous or better results compared to standard quantile normalization. For example, the correlation coefficient between two series of locus-matched values obtained by distinct Authors, using different microarray platforms (samples A1 and A3, respectively; see Table [1](#T1){ref-type="table"}), was 0.23 in absence of any inter-sample normalization, 0.34 following standard quantile normalization for all values and 0.41 following scaled quantile method. In the case of B10 and B12 samples, the quantile method worsened the correlation coefficient from 0.85 to 0.73, while this remained stable using scaled quantile normalization (0.83). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Samples selected for the biological model used to test TRAM software ::: TRAM ID GEO ID Sample GEO Platform Microarray Spots Ref. ---------------- ----------- ---------------------------- -------------- --------------------- -------- ------------ Pool \'A\' A1 GSM321577 Mk (BM) (n = pool) GPL96 Affymetrix U133A 22,283 \[[@B19]\] A2 GSM321578 Mk (BM) (n = pool) \" \" \" \" A3 GSM112277 Mk (PB) (n = 1, rep. 1) GPL887 Agilent 1A 22,575 \[[@B20]\] A4 GSM112278 Mk (PB) (n = 1, rep. 2) \" \" \" \" A5 GSM15648 Mk (BM) (n = 6) GPL96 Affymetrix U133A 22,283 \[[@B21]\] A6 GSM8649 Mk (BM) (n = 6) \" \" \" \" A7 GSM88022 Mk (PB) (n = 1) GPL887 Agilent 1A 22,575 \[[@B22]\] A8 GSM88014 Mk (PB) (n = 1) \" \" \" \" A9 GSM88034 Mk (PB) (n = 1) \" \" \" \" Pool \'B\' B1 GSM321567 CD34+ (BM) (n = pool) GPL96 Affymetrix U133A 22,283 \[[@B19]\] B2 GSM321568 CD34+ (BM) (n = pool) \" \" \" \" B3 GSM321569 CD34+ (CB) (n = pool) \" \" \" \" B4 GSM321570 CD34+ (CB) (n = pool) \" \" \" \" B5 GSM321571 CD34+ (PB) (n = pool) \" \" \" \" B6 GSM321572 CD34+ (PB) (n = pool) \" \" \" \" B7 GSM76923 CD34+ (BM) (n = 5) GPL96 Affymetrix U133A 22,283 \[[@B23]\] B8 GSM76924 CD34+ (BM) (n = 5) \" \" \" \" B9 GSM76925 CD34+ (BM) (n = 5) \" \" \" \" B10 GSM307288 CD34+ (BM) (n = 6, rep. 1) GPL7091 Agilent 22 k A 16,391 \- B11 GSM307289 CD34+ (BM) (n = 6, rep. 2) \" \" \" \- B12 GSM88023 CD34+ (PB) (n = 1) GPL887 Agilent 1A 22,575 \[[@B22]\] B13 GSM88003 CD34+ (PB) (n = 1) \" \" \" \" B14 GSM23407 CD34+ (BM) (n = 1) GPL201 Affymetrix HG-Focus 8,793 \[[@B24]\] B15 GSM23410 CD34+ (BM) (n = 1) \" \" \" \" B16 GSM23411 CD34+ (BM) (n = 1) \" \" \" \" B17 GSM23408 CD34+ (BM) (n = 1) \" \" \" \" B18 GSM23409 CD34+ (BM) (n = 1) \" \" \" \" B19 GSM23406 CD34+ (BM) (n = 1) \" \" \" \" Sample: Mk, megakaryocytic/megakaryoblast cells, obtained by in vitro differentiation of CD34+ cells; CD34+, undifferentiated CD34+ cells; (BM), (CB) or (PB): CD34+ cells derived from bone marrow, cord blood or peripheral blood, respectively. n = number of subjects from which the sample was derived (in some cases, where n = pool, the exact number of subjects included in a pool was not available). rep. = biological replicate. Microarray: U133A: Affymetrix Human Genome U133A Array; 1A: Agilent-012097 Human 1A Microarray (V2) G4110B; 22 k A: Agilent Human oligo 22 k A; HG-Focus: Affymetrix Human HG-Focus Target Array. When not directly provided, expression value was calculated as the median intensity value of a microarray feature minus the median background value. ::: In addition, we determined the standard deviation (SD, expressed as percentage of the mean) of measurements from different samples for housekeeping loci such as beta actin (ACTB) and a set of ribosomal proteins, using the intra-sample normalization \'Mean\' method. In the absence of any inter-sample normalization, the SD for ACTBwas 84.95 for pool \'A\' (26 data points) and 148.80 for pool \'B\' (60 data points). After applying quantile normalization to all available data, the SD became 35.36 and 78.91, and following the use of the scaled quantile method it changed into 51.44 and 54.75, for pool \'A\' and \'B\' respectively. Therefore, the scaled quantile method allowed both a decrease in the variability among the samples within a sample pool, and an increase in comparability between the \'A\' and \'B\' sample pools compared to a reference gene expected to be stably expressed in both pools. In the absence of any inter-sample normalization the SD for genes encoding small ribosomal proteins was 85.80 for pool \'A\' and 138.75 for pool \'B\' (mean of SD for 34 loci with \"RPS\" prefix, total data points were 402 for pool \'A\' and 830 for pool \'B\'). Following quantile normalization of all available data the SD changed to 66.01 and 78.25, and after using the scaled quantile method the SD decreased to 56.21 and 49.06, for pool \'A\' and \'B\' respectively, thus improving homogeneity within each sample pool as well as between the two sample pools. Generation and analysis of transcriptome maps --------------------------------------------- Two main types of analysis are available within TRAM: \'Transcriptome map - search for over/under-expressed segments\' (\'Map\') mode and \'Search for clusters of neighbouring over/under-expressed genes\' (\'Cluster\') mode. In \'Map\' mode, the software generates a graphical map of the transcriptome showing a vertical line representing each chromosome. An expression value for a selected area of a chromosome is calculated as the mean for all available expression data relating to the genes included in that segment. The mean expression level of the segment is represented by an horizontal bar next to the corresponding segment of the chromosome, the bar size being proportional to the segment expression level (Figure [2](#F2){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Screenshot of the \'Map\' graphical display of TRAM software (detail). The length of each horizontal bar is proportional to the mean gene expression within a chromosomal segment of 0.5 Mb. Consecutive bars are shifted by 250 kb. The vertical line represents human chromosome 4, from position 64,750,001 (start of the top segment) to position 76,750,000 (end of the bottom segment). The expression value on the left of each bar is derived from the analysis of the test set used (Table 1). Bars are colour-coded in proportion to their expression values. Segments, whose expression value is greater (or lower) than the chosen percentile threshold, are highlighted in the \"Over/Under\" field, which is only filled when they also include the user-defined minimum number of over/under-expressed genes that must be present in the segment. Statistical significance p- and q-values are calculated for these regions. ::: ![](1471-2164-12-121-2) ::: Bars representing expression values included within the highest/lowest (n) user-defined percent of all segment expression values are pinpointed, thus highlighting genomic regions globally over/under-expressed with respect to the desired threshold. To avoid artefacts due to very high or very low expression of single genes in the region, the minimum number of over/under-expressed genes that must be present in the segment can be defined. The threshold for a gene to be considered as over- or under-expressed is the inclusion of the gene expression value within the highest/lowest (n) user-defined percent of all gene expression values. The user may also set the \'Shift\' parameter that causes the window to slide along the chromosome at pre-arranged intervals. In this way the user obtains a set of partially overlapping segments thereby attaining better sensitivity because a rigid division in chromosome segments, always starting from the fixed position 1, may let neighbouring over- or under-expressed genes be assigned to different segments. The user maintains full control of the numerical data associated with each segment and may easily navigate among the map of the genes and gene expression values data tables. Segments may be explored and searched according to any desired criteria and sorted and processed like ordinary database records. Differential transcriptome maps, based on the ratio between corresponding gene expression values from two \'A\' and \'B\' samples or sample pools, relative to two different biological conditions, may be easily generated. The statistical significance of the over/under-expression of each segment fulfilling the criteria to be tagged as over/under-expressed is displayed, and it is calculated as described in the \"Statistical analysis\" Methods section. The user may choose to refer the statistical calculations to data sets within each chromosome rather than to the whole genome dataset, in order to retrieve domains regionally over- or under-expressed within each DNA molecule. Differences between the genome- and chromosome-centred types of analysis are graphically highlighted when both have been performed. Search for clusters of neighbouring over/under-expressed genes -------------------------------------------------------------- In \'Cluster\' mode, the software searches for a set of at least two successive genes, arranged according to the position indicated by their known transcription start site, and over/under-expressed in terms of inclusion of the gene expression value within the highest/lowest (n) user-defined percent of gene expression values. In this type of analysis, each horizontal bar represents the expression level of an individual gene (Figure [3](#F3){ref-type="fig"}). Gene clusters are then built starting from over/under-expressed individual loci, if other contiguous genes fulfil the criteria defined for inclusion in the cluster. This analysis is complementary to that performed in \'Map\' mode, which requires an arbitrary segment window. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Screenshot of the \'Cluster\' graphical display of TRAM software (detail). Two example clusters, identified by default analysis of the biological model (Table 1) described in the text, are shown. The length of each horizontal bar is proportional to the mean \'A\'/\'B\' ratio gene expression across all samples. Bar red colour indicates gene over-expression according to set criteria. Genes without associated expression values in the samples are shown but are not considered in the cluster construction. \'Gap\' parameter was set equal to 1, so a maximum of one not over-expressed gene (hot pink colour bar) may separate two consecutive over-expressed genes. The cluster mean expression value, derived from all genes included in each cluster, is shown. The number of data points from which each value was derived, p-, q-value and length for each over/under-expressed cluster are also calculated (not shown here). ::: ![](1471-2164-12-121-3) ::: The results of the analysis are displayed in the \'Cluster\' layouts, as clusters of genes over/under-expressed. Each gene is actually a record (row) of the database. The user can find and sort genes and gene clusters using any desired criteria. Specific buttons help to retrieve entries from online databases for the desired genes. Clusters of differentially expressed genes between two different biological conditions may be easily generated, based on the ratio between corresponding gene expression values from two defined \'A\' and \'B\' pools. Statistical significance of the over/under-expression of each gene cluster fulfilling the criteria to be tagged as over/under-expressed is displayed, and it is calculated as described in the \"Statistical analysis\" Methods section. In \'Cluster\' mode the user may choose if statistical calculations are to be performed separately for each chromosome as it is possible in \'Map\' mode. Moreover, the user may choose how many genes can be tolerated in the cluster between each gene pair counted in the cluster, even if they do not fulfil the user-set criteria. Biological model - Chromosomal segments --------------------------------------- We compared several options of the software in the analysis of differential expression of pool \'A\' (9 megakaryocyte cells (Mk) samples, including RNA from at least 21 different subjects) versus pool \'B\' (19 CD34+ cells samples, including RNA from at least 41 different subjects) (Table [1](#T1){ref-type="table"}). A total of 180,365 data points (gene expression values) from the pool \'A\' and 294,987 data points from the pool \'B\', relative to 17,676 distinct loci, for which an \'A\'/\'B\' ratio value was determinable, were included in the analysis. Results obtained by default analysis (according to the parameters described in the \"Methods\" section) included 18 significantly over- or under-expressed segments (\'Map\' mode, Table [2](#T2){ref-type="table"}) and 73 clusters (\'Cluster\' mode, Table [3](#T3){ref-type="table"}). The use of inter-sample normalization (scaled quantile method) improved the identification of significantly over/under-expressed genome segments versus absence of any inter-sample normalization (18 vs. 12). In addition, segments enriched in relevant genes known to be over- or under-expressed in megakaryocytes/platelets were not identified in the absence of inter-sample normalization. For example an over-expressed segment on chromosome 17 was found to contain, among others genes, ICAM2and PECAM1, as well as an under-expressed segment on 6p21.3 containing several HLA (human leukocyte antigen) system class II members. The differential expression of these genes is expected in the differentiation process studied in our model: ICAM2is a functional integrin ligand present on platelets surface \[[@B11]\] and PECAM1encodes platelet/endothelial cell adhesion molecule, while the down-regulated genes HLA-DRA, HLA-DRB1and HLA-DQA1are typically expressed in antigen presenting cells. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Genomic segments significantly over/under-expressed in Mk cells (pool \'A\') vs. CD34+ cells (pool \'B\') ::: Chr and Location Segment Start Segment End \'A\'/\'B\' Ratio q-value Genes in the segment ------------------ --------------- ------------- ------------------- --------- --------------------------------------------------------------------------------------------------------------------------------------------------------- chr2 2q23-q24 160,250,001 160,750,000 0.398 0.00024 *BAZ2B-MARCH7-CD302- LY75-* chr4 4q11-q12 57,500,001 58,000,000 0.421 0.00039 *HOPX- SPINK2-REST- C4orf14- POLR2B+IGFBP7-* chr4 4p15.32 15,500,001 16,000,000 0.427 0.00039 FBXL5-*BST1- CD38-FGFBP1- FGFBP2-PROM1-* chr6 6p21.3 32,250,001 32,750,000 0.434 0.00079 C6orf10+ BTNL2-*HLADRA- HLADRB1- HLADQA1-*HLADQB1- HLADQA2- HLADQB2- chrX Xp11.23 47,000,001 47,500,000 1.806 0.00505 NDUFB11+ RBM10+ UBA1+*INE1+USP11- ZNF157+ ZNF41+ ARAF+SYN1+ TIMP1+*CFP+ ELK1+ chr11 11q12.2 61,250,001 61,750,000 1.859 0.00573 C11orf66+ SYT7- DAGLA- C11orf9+ C11orf10+ FEN1+*FADS1+ FADS2+FADS3- RAB3IL1+ BEST1-FTH1+* chr16 16p12.1 28,500,001 29,000,000 1.877 0.00248 CLN3+ APOB48R+ IL27+*NUPR1+CCDC101- SULT1A2+SULT1A1+EIF3C- ATXN2L+ TUFM+ SH2B1-ATP2A1+RABEP2- CD19- NFATC2IP+ SPNS1+LAT+* chr17 17q23 62,000,001 62,500,000 1.957 0.00381 *CD79B-SCN4A-C17orf72+ ICAM2+ERN1+ TEX2+PECAM1+*C17orf60- POLG2+ DDX5+ chr6 6p21-1 43,500,001 44,000,000 2.196 0.00235 XPO5-*POLH+ GTPBP2+ MAD2L1BP+*MRPS18A+ VEGFA+ C6orf223+ chr5 5qter 178,750,001 179,250,000 2.367 0.00222 ADAMTS2-*RUFY1+HNRNPH1+ CANX+ MAML1+LTC4S+ MGAT4B+*SQSTM1+ chr11 11p15 5,000,001 5,500,000 2.384 0.00796 MMP26- OR51L1+ OR52J3+ OR52A1+ HBB+*HBD+ Hs.20205+ HBG1+*HBG2+ HBE1+ OR51B4+ OR51B2- OR51B6+ OR51M1- OR51I1+ OR51I2+ chr17 17p13.2 4,750,001 5,250,000 2.620 0.00796 MINK1+ CHRNE+*GP1BA+SLC25A11+ RNF167+PFN1+ENO3+ SPAG7+ CAMTA2+KIF1C+*GPR172B+ ZFP3- ZNF232- USP6+ ZNF594- RABEP1- chr4 4q13-q21 74,500,001 75,000,000 9.226 0.00000 IL8+ CXCL6+*PF4V1+ CXCL1+ PF4+ PPBP+CXCL5+CXCL3+PPBPL2+CXCL2+* Chr: chromosome; Segment Start/End: chromosomal coordinates for each segment. Bold and \'+\': over-expressed gene; bold and \'-\': under-expressed gene; \'+\' or \'-\': gene expression value higher or lower than the median value, respectively. Analysis was performed using default parameters (see \"Methods\" section). Segments are sorted by increasing \'A\'/\'B\' ratio. In the \'Map\' mode, TRAM displays UniGene EST clusters (with the prefix \"Hs.\" in the case of H. sapiens) only if they have an expression value. Five out of a total of 18 segments are not shown for simplicity, because their over-expressed genes are overlapping with those highlighted in the listed regions. The complete results for this model are available along with TRAM software. ::: ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Clusters of genes significantly over/under-expressed in Mk cells (pool \'A\') vs. CD34+ cells (pool \'B\') ::: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Chr and Location Cluster Start Cluster End\ \'A\'/\'B\' Ratio q-value Genes in the cluster (Cluster size) --------------------- --------------- ---------------------- ------------------- ----------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------- chr19 19p13.3 827,831 856,246 (28,416) 0.103 0.00011 *AZU1- PRTN3- ELANE-* chr4 4q11-q12 57,514,154 57,687,893 (173,740) 0.140 0.00084 *HOPX-Hs.630172 Hs.121443 Hs.673386 Hs.613041 Hs.677243 Hs.601479 Hs.44210 Hs.566128SPINK2-* chr10 10q23-q24 97,951,455 98,098,321 (146,867) 0.172 0.00084 *BLNK-Hs.716018 Hs.673979 Hs.444049 Hs.688648 Hs.679276DNTT-* chr1 1p36 26,644,411 26,647,014 (2,604) 0.192 0.00084 *CD52- Hs.597423-* chr1 1q21 153,330,330 153,363,549 (33,220) 0.212 0.00011 *S100A9- S100A12-LOC645900S100A8-* Chr6 6p21.3 32,407,647 32,611,429 (203,783) 0.217 0.00011 *HLADRA-LOC10028939 Hs.601001 Hs.544645 Hs.693189 Hs.654238 HLADRB5 Hs.664382 Hs.611927 Hs.606311HLADRB1-Hs.706474 Hs.625753 Hs.691818HLADQA-* chr8 8p23.1 6,835,171 6,875,816 (40,646) 0.233 0.00084 *DEFA1-DEFA1BDEFA3-* chr2 2p22.3 32,853,129 33,624,576 (771,448) 6.738 0.00084 *TTC27+Hs.616001 Hs.664352 Hs.639709 Hs.683829 Hs.678473 Hs.623026 LOC285045 LOC100271832LTBP1+* chr11 11q12.2-q13.1 61,567,097 61,634,825 (67,729) 7.059 0.00084 *FADS1+Hs.651782 Hs.621796 LOC100131326 Hs.667454FADS2+* chr17 17q21.32 42,422,491 42,466,873 (44,383) 7.976 0.00084 *GRN+Hs.602870 FAM171A2 LOC390800ITGA2B+* chr12 12p13.31 7,966,397 8,088,892 (158,906) 8.033 0.00084 *SLC2A14+Hs.664258 Hs.539507 Hs.668117 LOC100130582 Hs.662096SLC2A3+* chr11 11p15.5 5,254,059 5,271,087 (21,857) 8.722 0.00010 *HBD+ Hs.20205+Hs.295459 Hs.702082 Hs.702189HBG1+* chr12 12p13.3 6,058,040 6,347,427 (289,388) 10.492 0.00084 *VWF+Hs.605384 Hs.539512 Hs.712104CD9+* chr4 4q12-q21 74,719,013 74,964,997 (245,985) 11.289 0.00000 *PF4V1+ CXCL1+Hs.708652 LOC642958PF4+Hs.552264PPBP+CXCL5+ Hs.598417 Hs.603888 Hs.617230CXCL3+PPBPL2+ LOC643014 Hs.719458CXCL2+* ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Chr: chromosome; Cluster Start/End: chromosomal coordinates for each gene cluster. Bold and \'+\': over-expressed gene; bold and \'-\': under-expressed gene; \'+\' or \'-\': gene expression value higher or lower than the median value, respectively; gene name without \'+\' or \'-\' symbols: no expression value available in the investigated dataset. Analysis was performed using default parameters (see \"Methods\" section), choosing to list all colocalized known genes and mapped EST clusters, regardless of the availability of expression values for them in the investigated samples. Clusters are sorted by increasing \'A\'/\'B\' ratio. Only the 7 cluster with the highest and the 7 cluster with the lowest cluster mean gene expression are shown (out of a total of 31 significantly over- and 42 significantly under-expressed identified clusters). The complete results for this model are available along with TRAM software. ::: The higher expression ratio between Mk and CD34+ cells (9.23) was observed in the segment at coordinates 74,500,001-75,000,000 on chromosome 4 (4q13-q21). All 10 genes in this location showed expression values greater than the median, and 6 out of 10 showed values within the higher 2.5th percentile. While it was known that several genes in this region are sequence-related and form a structural cluster of members of the CXC chemokine gene family (CXCL1, CXCL5, CXCL3, CXCL2), this finding highlights the simultaneous very high activity of genes such as PF4V1(platelet factor 4 variant 1), PF4(platelet factor 4) and PPBP\[official name: pro-platelet basic protein (chemokine (C-X-C motif) ligand 7)\], previously known as beta-thromboglobulin \[[@B12]\], following differentiation of CD34+ cells in megakaryocytes. The second segment with highest expression was located on chromosome 6 and contained over-expressed genes such as GP1BA\[glycoprotein Ib (platelet), alpha polypeptide\], encoding the alpha chain of megakaryocyte- and platelet-specific surface membrane Glycoprotein Ib, and KIF1C(kinesin family member 1C). Over-expression of kinesin 1C, which is recruited in neural cells APP (amyloid precursor protein) transport vesicles, was not to date described in Mk cells. However, it is known that during the complex and poorly understood process by which Mks generate platelets, kinesin motors carry platelet-specific granules and organelles over microtubules into the pro-platelets \[[@B13]\]. The third over-expressed segment spans the cluster of haemoglobins on chromosome 11, highlighting the known common early origin of erythroid and Mk cells \[[@B14]\]. Under-expressed segments included genes encoding surface antigens whose expression is known to be restricted to leukocytes or leukocyte subpopulations (e.g., CD302, LY75/CD205, CD38 and HLA-DR; Table [2](#T2){ref-type="table"}), highlighting their down-regulation during differentiation of common CD34+ progenitors to megakaryocyte. Switching from \'Mean\' to \'Median\' intra-sample normalization (values expressed as a percentage of the median value for each array) globally decreased sensitivity from 18 significantly over- or under-expressed genome segments to 10. However, one segment was identified only with the \'Median\' mode. This segment includes MYOM1(myomesin 1/skelemin), MYL12A(myosin, light chain 12A, regulatory, non-sarcomeric) and MYL12B(myosin, light chain 12B, regulatory) and it went undetected with the \'Mean\' mode. Interestingly, myomesin 1 \[[@B15]\] and myosins \[[@B16]\] pathways have been involved in pro-platelet formation and platelet function. Some differences in the results while using different intra-sample normalization parameters are expected on the basis of the different distribution of the values for each sample. For example the sample mean value is greater than the sample median value if there is a tail of high values. Normalizing by median could uncover additional significantly over-expressed regions that were masked by the mean-based normalization. Concerning inter-sample normalization, the scaled quantile adjustment appeared to increase sensitivity in the identification of significantly over/under-expressed segments with respect to the standard quantile method (18 vs. 13). In particular, the quantile method was not able to detect any under-expressed segment, such as that containing the HLA class II genes typical of leukocytes that were identified by scaled quantile adjustment. Lowering or raising the threshold to define a gene and/or a segment as over/under-expressed makes the analysis more stringent or less stringent, respectively. We found that a good starting point is to use lower and upper 2.5th percentile, so that 5% of the data are included as positive results, which in a Gaussian distribution would roughly correspond to the percentage of values exceeding the mean by two standard deviations. The statistical test will compensate for the high number of segments or cluster marked as over/under-expressed obtained relaxing the threshold, by identifying which results are to be considered significant (Q \< 0.05). Biological model - Gene clusters -------------------------------- In the \'Cluster\' mode, the identified clusters included genes well known for being upregulated during megakaryocytopoiesis, as well as genes encoding leukocyte proteins expected to be down-regulated in the same context. For example, a cluster is composed by DNTT, encoding deoxynucleotidyl transferase, expressed in a restricted population of pre-B and pre-T lymphocytes, and BLNK, encoding B-cell linker, an adaptor protein that plays a critical role in B cell development (Table [3](#T3){ref-type="table"}). In this mode of use, the physical contiguity of at least two over/under-expressed genes is considered as the bond for cluster definition rather than an enrichment of such genes in a genomic region independently of their order. Results are in part similar and in part complementary to those obtained in the \'Map\' mode. In particular, the cluster with lowest \'A\'/\'B\' ratio mean value turned out to be the series of genes AZU1(azurocidin 1), PRTN3(proteinase 3) and ELANE(elastase, neutrophil expressed), located on chromosome 19 and known to be coordinately expressed in a granulocyte-specific fashion \[[@B17]\], which resulted to be significantly under-expressed only in this mode of analysis. On the other hand, an over-expressed cluster composed only by the two contiguous genes, encoding platelet-specific proteins VWF (Von Willebrand Factor, present in the alpha-granules of platelets) and CD9 (a specific platelet marker), was identified on chromosome 12 (Table [3](#T3){ref-type="table"}). This would have been undetected in the \'Map\' mode because the minimal number of over/under-expressed genes required to be present in a chromosomal segment was by default set equal to 3. Another over-expressed cluster included GATA1, encoding a major transcription factor for megakaryocytopoiesis. The modification of parameters used for \'Cluster\' mode analysis, such as those above listed for the \'Map\' mode, had analogous effects on the results. Some additional significant results were obtained by setting chromosome-specific thresholds for the analysis, rather than using the whole genome gene set as a reference. For example, the cluster of the two genes HIPK2(a nuclear kinase that interacts with homeodomain transcription factors, previously associated with megakaryocyte lineage) \[[@B18]\] and TBXAS1\[official name: thromboxane A synthase 1 (platelet), catalyzing the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation\] scored as significantly over-expressed on a local basis when the gene expression of chromosome 7 but not whole genome dataset was considered. In both \'Map\' and \'Cluster\' modes, TRAM displays EST clusters, in addition to known genes, mapped in the region of interest. In the case of \'Cluster\' mode this occurs independently of the availability of expression values for the loci within the cluster extension (Table [3](#T3){ref-type="table"}). The results for each mode of analysis of the presented test model, using default parameters, are available in the folder \'Biological\_Model\_Test\' of the TRAM distribution, allowing the user to explore the model following variation of analysis parameters. Individual gene expression values, summarized for each of the two pools \'A\' and \'B\', can be visualized and sorted in the \'Cluster\' results layout. Amongst the first 12 genes with the highest \'A\'/\'B\' ratio (PF4V1, PF4, GP1BA, PPBP, RGS18, CMTM5, SLC44A1, VWF, SH3BP5, HSPC159, ITGA2Band HBG1, ranging from 34.22 to 11.92 expression ratio, in this order, between CD34+ and Mk cells), 7 were placed in one significantly over-expressed segment or gene cluster by the transcriptome mapping analysis. The CD34gene was under-expressed in Mk cells compared to CD34+ cells, as expected (mean ratio across all samples was 0.29, within the lowest 2.5th percentile of \'A\'/\'B\' ratios). Discussion ========== Here, we have described an original software named TRAM, designed to create and analyze transcriptome maps for any organism, based on gene expression data in a general form and able to generate a relational, fully-indexed map database, usable on Macintosh and Windows operating systems-based computers. The \'Map\' mode allows the identification of chromosomal regions of defined size (with the possibility of using a sliding window) whose expression is defined as the gene expression average of the genes contained in the segment. This segment, also, must contain a specified number of loci transcribed beyond a desired threshold. The wide flexibility of the parameters required for the building of the Map (e.g., the independence of the threshold value chosen to consider each gene as over/under-expressed from the threshold value set to define a genomic segment as over/under-expressed) makes an open exploration of the expression data feasible at different levels; in addition, an estimate of statistical significance for the definition of a segment as over/under-expressed can then be obtained. This type of analysis considers the global expression of all genes in the region, regardless of their exact reciprocal position: in fact, it has been shown, for example for genes belonging to the same functional pathway, that clustering is loose and individual genes may be spread, despite remaining closer to each other than expected by chance \[[@B4]\]. In addition, we added a complementary mode of data visualization and analysis, the \'Cluster\' mode, where the window width is defined by a number of clustered genes rather than nucleotide range. This method can consider the gene-by-gene order in the region and can provide results about clusters of over/under-expressed genes that are adjacent or separated by a small user-defined number of not over/under-expressed genes within the cluster. All TRAM data and results tables are widely interconnected by simple navigation buttons, as well as linked to the relevant entries available on line (via automatic opening of the default web browser). The novelty of the tool is supported by several arguments. Firstly, the uniqueness of TRAM general basic architecture, which dynamically integrates an advanced and flexible relational database with parsing and meta-analysis capability, a map graphic displayer and a two-modes (\'Map\' and \'Cluster\') analyzer searching for significantly over/under-expressed genomic regions, starting from any source of global gene expression profiles data (Figure [1](#F1){ref-type="fig"}). The TRAM data model is also unique in two other aspects: users are given direct access to expression numerical values, which are always visualized near the horizontal expression bar used to visualize the expression intensity of chromosomal segments or clustered genes localized on the map; moreover, the users do not need to provide genomic coordinates for the investigated genes, whose location is resolved by the pre-setup gene database table. A series of buttons allows an easy, transparent tracking of gene expression measurements from raw input data to normalized values, up to expression intensity display on the map. In addition, TRAM makes original specific data management and analysis tools available such as: a parser which is able to find the best and updated gene/RNA cluster name suitable to be assigned to a probe identifier (e.g., the parser locally resolves all \~7 millions human RNA sequence accession numbers included in the latest available H. sapiensUniGene version); a novel effective method for the normalization of data derived from platforms with highly different number of probes (scaled quantile) which allows more samples to be included in a biologically homogeneous sample pool and maximizes gene expression information that may be extracted from each sample; the statistical analysis, based on individual chromosome data summary in addition to genome data summary, emphasizing local effects expected on the basis of the behaviour of single chromosomes with respect to chromatin organization and gene expression regulation. Finally, a powerful feature of TRAM is its ability to compare, within the same analysis, the transcriptome maps derived from two datasets (or two pools of datasets) related to different biological conditions (indicated as \'A\' and \'B\'), such as two tissues or cell types, two developmental stages, normal vs pathological cells or cells maintained in absence or in presence of a substance. The generation of a transcriptome map of the relative \'A\'/\'B\' ratio expression, allows the easy investigation of regional differential expression without the need to generate the results separately for the two datasets or pool of datasets and to devise additional calculations to compare them. TRAM was able to generate original results of relevant biological interest in the ab initiomodelling of differentiation from CD34+ stem cells to megakaryocyte (Mk) cells in a meta-analysis of a total of 28 publicly available microarray datasets obtained from different sources. Many genes with a fundamental role in Mk/platelet biology, known since early classical studies (see \"Results\" section), were shown to significantly colocalize in genome segments or in clusters of adjacent genes. Moreover, additional regions significantly over/under-expressed during megakaryocytopoiesis were identified (Table [2](#T2){ref-type="table"} and Table [3](#T3){ref-type="table"}). These results are original compared to the data analysis presented in the relative primary works from which expression data were derived \[[@B19]-[@B24]\]. This may be ascribed to the lack of data integration in the original studies (analysis was typically applied only to the datasets produced in the context of the work itself) \[[@B19]-[@B24]\], to the lack of a search for local enrichment of over/under-expressed genes \[[@B20]-[@B24]\], to the use of a different analysis pipeline when a localization study was performed (in particular, use of gene lists as a starting point rather than the actual mean expression value of the genes in a region) \[[@B19]\], or to the different biological model considered (when the study was not intended to investigate differential expression during differentiation of CD34+ cells toward Mk cells) \[[@B21],[@B23],[@B24]\]. EST clusters can be mapped to the region of interest in addition to known genes by exploiting an original integration between NCBI UniGene and UCSC Genome Browser data (Table [2](#T2){ref-type="table"} and Table [3](#T3){ref-type="table"}). This feature offers useful hints for the functional investigation of uncharacterized transcripts, on the basis of their presence, and in case of their over/under-expression, within genomic regions differentially expressed in a certain biological context. While feasibility of integration of gene expression profile data, obtained from different experimental platforms or investigators, is highly desirable to build transcriptome maps representing all information available for a certain biological condition, the occurrence of systematic errors associated with each experimental situation requires advanced methods of inter-sample data normalization, such as the widely accepted quantile normalization \[[@B25]\]. However, this method may cause loss of data due to the removal of all genes whose expression values are missing for any dataset in order to obtain a fully filled data matrix, representing each sample as a column and the values for each gene as a row (for an example of this filtering see \[[@B26]\]). Alternatively, some Authors retain all data values in quantile normalization by placing missing values at the end of each sorted column \[[@B27]\]. In such cases, all available data are analyzed but with an artefact due to the misalignment of values included in similar classes of expression level, compared to their sample of origin (Figure [4](#F4){ref-type="fig"}). The original method of scaled quantile we propose here in order to properly manage data derived from platforms with different number of analyzed genes, has proven to be effective, allowing maximization of information that can be extracted from all pertinent available data. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### Scaled quantile normalization: concept. If two data columns with different numbers of values, derived from two A1 and A2 samples, respectively, are individually sorted by magnitude of expression to obtain the mean value for all values with the same rank, i.e. in the same row (quantile normalization), the highest values in the sample A2 will be aggregate to the intermediate values in the sample A1. Proportional scaling of A2 ranks aligns them to A1 values located in analogous ordered positions with respect to each sample whole distribution (scaled quantile inter-sample normalization), allowing low, intermediate and high values to be aggregated with suited corresponding values from the other sample(s). ::: ![](1471-2164-12-121-4) ::: Interestingly, after selecting for the analysis only samples homogeneous with respect to the used experimental platform, a decrease in sensitivity was observed, thus showing the effectiveness and usefulness of analysis starting from multiple sources. For example, by performing the analysis only on the datasets obtained with commonly used Affymetrix U133A microarray (GPL96 GEO platform) among those listed in Table [1](#T1){ref-type="table"}, only 5 vs. 18 significantly over/under-expressed chromosomal segments, and 68 vs. 73 gene clusters were found, compared to the analysis integrating data from the whole available pool of samples. A variation of analysis parameters allows the exploration of data from different points of view. The final statistical significance test will provide the actual reliability of the corresponding results independently of the parameters selected to define the thresholds for considering segments and genes as over/under-expressed (selection performed at the start of the data analysis by descriptive statistics). For example, lowering the threshold to consider segments and genes as over/under-expressed will retrieve a larger number of differentially expressed regions but this will be taken into account during the calculation of the statistical significance of each result where only a minor fraction of these regions will have a q-value (p-value corrected for FDR) \< 0.05. It is noteworthy that, among the first 12 individual genes with the absolute highest \'A\'/\'B\' ratio between CD34+ and Mk cells, 7 were placed in one significantly over-expressed segment or gene cluster by the transcriptome mapping analysis. In addition, valuable information may also be extracted by using the capability of TRAM to numerically describe the normalized and summarized intensity of transcription along each chromosome. In this way a user could readily search, find and sort regions with no positive expression values despite containing known genes (\"expression deserts\"). Taken together, the described features of TRAM make it difficult to compare in details this tool with all other tools that, to our knowledge, are described in the literature as being capable of transcriptome mapping and analysis. This is because TRAM is actually a suite of different and strictly integrated data parsing and displaying as well as analysis tools. In particular, the existing software reviewed in the \"Background\" section, accept gene lists as an input (lists are to be obtained through different dedicated tools), so they cannot represent and analyze the gene expression level changing along the chromosome. Neither will they generate differential expression maps comparing two different biological conditions such as the one we have discussed in our biological model showing progression from CD34+ cells to megakaryocytes. The local differential gene expression between two conditions is a function offered by the \"R\" library MACAT \[[@B28]\], whose Authors used a set of publicly available microarray data \[[@B29]\] related to human T- (n = 43) and B-cell (n = 205) paediatric acute lymphoblastic leukaemias as biological test example. Only one chromosomal region in chromosome 6 was found to be differentially expressed between T- and B-leukaemia cells. This was a biologically meaningful finding since HLA genes are localized in this region and they are known to be under-expressed in T-cells vs. B-cells \[[@B28]\]. TRAM was able to replicate this result by using default analysis parameters. In addition, TRAM was able to individually list the loci under-expressed in T-cells present in this region (6p21.3, coordinates 32,2500,000-33,000,000, q-value \< 0.000002, under-expressed genes: HLA-DRA, HLA-DRB1, HLA-DQA1, HLA-DQB1, TAP2- involved in antigen presentation -, HLA-DMB, HLA-DMA). Moreover, TRAM has been able to identify three additional differentially expressed chromosomal regions, each of which contained several genes over-expressed in T-cells, one on chromosome 1 (1q22-q23, q-value = 0.000007, genes: CD1D, CD1A, CD1B, CD1E) and two on chromosome 11 (11q12.2, q-value \< 0.0007, genes: CCDC86, GPR44, a chemoattractant receptor homologous molecule expressed on T-helper type 2 cells, and CD5; 11q23, q-value \< 0.0007, genes: CD3E, CD3Dand CD3G). These regions are of remarkable biological and clinical interest because they contain clusters of genes related to CD1, CD5 and CD3, respectively; these are well known as main and universally used specific surface markers of T-cells. In the \"Cluster\" mode, TRAM identifies 35 gene clusters significantly over- (n = 16) or under-expressed (n = 19) in leukaemic T-cells compared to B-cells, including several other genes known to be T- or B-cell specific (data not shown). Finally, MACAT is limited to the analysis of Affymetrix microarray, further underlining the need for a tool open to all platforms as well as to cross-platform analysis. The batch effects are the systematic differences between batches (groups) of samples in microarray experiments due to technical reasons, such as variability in materials, protocols or operators, possibly introducing a bias able to confound true biological differences (recently reviewed by Luo and coll. \[[@B30]\]). The TRAM data model described appears to be intrinsically resistant to the influence of batch effects, for the following reasons: the TRAM locus-centred data model does not attempt to separate subgroups within a sample pool, because it is assumed that the samples come from the same biological condition (e.g. cell type, disease) for which only one aggregate value per locus is obtained and considered; the TRAM algorithm is non-parametric at different levels of normalization and analysis and this is expected to reduce the noise due to different value scales; the biological model discussed above deliberately used data from different platforms, protocols and operators, showing results coherent with the current biological knowledge and even better with respect to the results obtained analyzing data deriving from a single platform. However, if the user suspects that batch effects could confound the results, in particular if two single and distinct batches of samples are loaded as pool \'A\' and \'B\', respectively, it could be useful to attempt removing batch effects from the raw data using one of the existing tools \[[@B30]\] prior to importing data in TRAM. While this manuscript was being revised, two novel software were described in addition to those reviewed in the \"Background\" section, able to analyze local enrichment of over/under-expressed genes. CROC \[[@B31]\] also uses the hypergeometric distribution to find genomic regions or gene clusters enriched in over/under-expressed genes, and supports calculations based on both whole genome data and individual chromosome values. However, like the previously published REEF tool \[[@B10]\], it accepts gene name lists as an input and it is not designed to parse, normalize and map original expression data and to display the corresponding quantitative transcriptome maps. The Integrated Genome Browser \[[@B32]\] can load expression data and visualize them along an xaxis representing the chromosome sequence. However, it lacks any function of data integration, normalization and analysis (Figure [1](#F1){ref-type="fig"}), being essentially a graphical display tool for expression data, like the previously published program ChromoViz \[[@B33]\]. The large agreement of TRAM results, obtained without any a priorispecific assumptions, with classical biological knowledge about megakaryocytopoiesis, shows that TRAM can perform integrated analysis of expression data from multiple platforms producing high confidence lists of over/under-expressed chromosomal segments and clustered genes. In conjunction with our previous implementation of a GenBank format full parsing system \[[@B34]\] (currently undergoing complete redesigning within FileMaker Pro 7 architecture) and UniGene Tabulator \[[@B35]\], TRAM may also contribute to the building of a novel, relational, multi-purpose, user-friendly and modular platform for the large-scale integrated analysis of genomic and post-genomic data. Conclusions =========== We have here described a unique package able to create and analyze transcriptome maps by integrating gene expression profile data from multiple sources and generating a relational, fully-indexed database-structured map, usable on Macintosh as well as on Windows operating systems-based computers, features that are non commonly available in other applications. TRAM provides a simple and intuitive system for the display and analysis of gene expression data within a single solution, including built-in multiple gene identifier conversion modules, intra-sample and inter-sample data normalization, map comparison between two biological conditions, graphical display and highly flexible data analysis (by both descriptive and inferential statistics) that has proven to generate results of biological interest. The current release of TRAM software is freely available at TRAM home page \[[@B36]\]. We also distribute preconfigured implementations ready for analysis of Homo sapiens(human), Mus musculus(mouse) and Danio rerio(zebrafish) gene expression profiles. Methods ======= Database development -------------------- TRAM was developed within the FileMaker Pro environment. This is a database management system with a user-friendly graphical interface usable on Macintosh and Windows operating systems-based computers. All data import, expression analysis and results of graphical output functions are obtained combining FileMaker Pro scripts and calculated fields (i.e. fields automatically calculating their result processing value from other fields by a pre-defined formula). No additional plug-in or software are required. A specific advantage of this platform as a transcriptome map generator and analyzer is the relational database environment at its core. As a consequence, each dataset in any table (e.g. gene expression values, gene names, expression value of chromosomal segments or gene clusters) is structured as a series of records that may be easily sought according to the desired criteria and then sorted, exported, and possibly related to other database tables. In this way, the graphical display of the map allows the user to maintain full control over the original expression data values at the basis of the map. The freely distributed licensed runtime application allows full data import and export in several formats, as well as full record management and analysis script execution. Only for the creation of new fields, further calculation or additional relationship definition an original copy of FileMaker Pro version 10 (or higher) package is required. TRAM set up ----------- In order to link gene identifiers to the corresponding gene symbols/gene names, it is possible to import in TRAM any text data file containing essential description (e.g., probe identifiers list and matching gene symbols or GenBank sequence accession numbers) for each experimental platform used to assess gene expression level in the examined samples (Figure [1](#F1){ref-type="fig"}). A typical use is loading a GEO \[[@B37]\] Platform file, in order to parse expression datasets obtained using that platform. Pre set-up human, mouse and zebrafish versions are distributed following loading of the most used GEO Platforms for those organisms. In order to uniform the assignment of gene identifiers to standard gene symbols, in absence of an available official gene symbol or an Entrez Gene \[[@B38]\] name, the UniGene \[[@B39]\] Cluster identifier (UniGene ID) is used as the gene name, if available, while the GenBank accession number is used, if provided, in absence of any match to an Entrez Gene or UniGene entry (Figure [1](#F1){ref-type="fig"}). TRAM 1.0 distribution was set up using data available at January 2011, downloading from Entrez Gene the gene localization data and parsing from UniGene tables, allowing the conversion of any RNA or expression sequence tag (EST) GenBank accession number into the corresponding gene symbol \[[@B35]\]. In the case of human UniGene latest available version (build \#228), about 7 millions RNA and EST code data were imported in TRAM. In addition, localization of EST clusters, which are sequences not characterized as official genes but represented in the transcriptome, was derived from UCSC \"ESTs\" track in the UCSC Genome Browser \[[@B40]\], which is also imported and processed during the TRAM set-up. A relationship between UniGene and UCSC ESTs data allows to determine the minimal available start genomic coordinate and maximum available end genomic coordinate for each set of ESTs belonging to the same UniGene cluster. These coordinates are operatively considered the limits of the locus while constructing the transcriptome map. Clusters containing ESTs mapped on different chromosomes are not further considered in the building of the map, as well as those with ESTs mapping on very distant positions on the same chromosome. To this aim, we set a rather conservative limit of 250,000 bp for TRAM, considering that the Entrez Gene set of 27,018 human genes, that is the largest known, has a mean size of 46,210 bp and a standard deviation of 107,161 bp, therefore our limit is equivalent to considering a size range within mean plus or minus 2 SD (approximately 95% of values in a Gaussian distribution). This correction effectively removes approximately 3,000 transcripts, erroneously mapped to regions of several Mb or tens of Mb. The user retains the possibility to inspect the list of EST clusters with a genomic extension greater than 250 kb present in a given chromosome segment, even if they are not considered in the creation of the transcriptome map. Expression data import, parsing and normalization ------------------------------------------------- Each series of data related to a TRAM \'Sample\' is defined as a \'distinct biological sample\'. For example, a sample should be a single channel in the case of two channels experiment, each channel data being imported as a distinct data file. The expression data file may be any tabulated (tab-delimited) text file containing two columns separated by a \'TAB\' character (tabulator key, ASCII9): a gene identifier and a numerical expression value, respectively. Gene symbol, Entrez gene name, custom identifier, GEO Platform probe ID or GenBank accession number are accepted as gene identifiers: the first two by default, the others provided that the software has been appropriately set up. The expression value is usually the pre-processed intensity value (i.e., the value assigned to the spot as it has been processed by the software of the specific experimental platform used, for example, following background subtraction for a microarray spot). An internal utility interactively assists the user in the preparation of text files in the required format, starting from raw expression data. Batch import of a large number of data files is possible. Each sample or set composed of any number of samples may be imported in one of two pools, \'A\' or \'B\', relative to two different biological conditions that may be then easily compared. TRAM is able to perform some useful data normalization methods (Figure [1](#F1){ref-type="fig"}) to allow comparison of gene expression data obtained by different biological samples and/or by different experimental platforms. Intra-sample (e.g., intra-array) normalization works within each distinct sample data, while inter-sample (e.g., inter-array) normalization is simultaneously applied to the desired sample set. The user may select different combinations between these types of normalization. Intra-sample normalization methods are \'Mean\' or \'Median\' (each value is expressed as the percentage of the corresponding sample mean or median value, respectively; this is equivalent to the classic \"global normalization\" in the microarray data analysis \[[@B41]\]) and \'Max\' (each value is expressed as the percentage of the corresponding sample maximum value, equivalent to the classic \"scale normalization\"). These methods rescale values within each data set using a standard internal reference for each sample. Inter-sample normalization method is the commonly used \"quantile\" algorithm \[[@B25]\]. Implementation of this algorithm in the database structure at the core of TRAM is realized as follows: each intra-sample normalized value is given a rank following sample data sorting in ascendant order, then the mean value for all the values with the same rank across all samples is calculated. This mean value is assigned as the expression value to each gene with the same rank in each sample. An original variant of this method implemented in TRAM is described below. The inter-sample normalization methods rescale values across a whole sample set, allowing inter-sample comparison. The summary of gene expression values, under the current mode of normalization, may be viewed as an indexed database table summarizing all data points available in the sample pool for each locus. The mean value of the data points available for each locus is considered the expression value for the respective gene and it is used in the subsequent analysis. Scaled quantile normalization ----------------------------- The quantile method assumes that each sample has the same number of values. However, datasets obtained from different platforms used to assess the gene expression profile, may have highly different numbers of values. In this case, applying the quantile method to the matrix resulting after aligning and sorting values from each sample (represented as a column) gives raise to artefacts, in that the highest values of a sample are summarized with intermediate values of samples with a greater number of values (Figure [4](#F4){ref-type="fig"}). To correct for this artefact, we applied the following formula in TRAM: Scaled Rank = Rank \* Max Rank/Max Sample Rank, were \'Rank\' is the rank (position in the ranking) of the value in the sample data column sorted in ascendant order, \'Max Rank\' is the highest rank present in the whole sample dataset, and \'Max Sample Rank\' is the highest rank assigned within each considered sample. The result of the calculation is rounded to the nearest integer number. The adjusted rank is then used to calculate the mean value across all genes which had the same rank assigned (Figure [4](#F4){ref-type="fig"}). In the case that the experimental platforms have the same number of features, the scaled quantile is identical to quantile. Comparability of values is best attained if previous intra-sample normalization has been performed too. Generation and analysis of transcriptome maps --------------------------------------------- In the \'Map\' mode of analysis, TRAM will generate a graphical map of the transcriptome showing a vertical line representing each chromosome (Figure [2](#F2){ref-type="fig"}). An expression value is associated to each segment of the line, whose size is determined by a window (in bp) set by the user. A differentially coloured horizontal bar is displayed for each chromosomal segment, with a length proportional to the expression value assigned to the relative segment. This value is the mean for all available expression data related to genes included in each segment. The available settings for this analysis are: Window, which defines the length for a segment; Sliding window shift, which defines the overlapping region between a segment and the next one; Percent (segment), which defines the threshold required to consider a segment as over/under-expressed, in terms of inclusion of the segment expression value within the highest/lowest (n) percent of segment expression values; Percent (gene), which defines the threshold expression value to consider a gene as over/under-expressed, in terms of inclusion of the gene expression value within the highest/lowest (n) percent of gene expression values; Number of genes in the window, which defines the minimum number of over/under-expressed genes required to mark the segment with the tag of over/under-expressed, respectively. The calculation of statistical significance of the over/under-expression of the segment is performed as described in the \"Statistical analysis\" Methods section below. Search for clusters of neighbouring over/under-expressed genes -------------------------------------------------------------- In the \'Cluster\' mode of analysis, TRAM will search for sets of at least two contiguous/neighbouring genes, all expressed beyond a defined \'n\' threshold, i.e. with expression values higher than the (100 - \'n\') percentile or lower than the \'n\' percentile. In this mode, results are centred on individual differentially expressed loci without any bond about the length of the over/under-expressed region. The available settings for this analysis are: Percent (gene), which defines the thresholds required to consider a gene as over/under-expressed, in terms of inclusion of the gene expression value within the highest/lowest (n) percent of gene expression values; Gap, which defines the maximum number of non over/under-expressed genes allowed to be localized between two over/under-expressed genes in a cluster (if Gap = 0, only strictly contiguous genes will be considered to be in cluster); Gene Type, which defines if TRAM, while constructing the linear map of genes, will use only genes with an official gene symbol assigned, or will use also genes with at least an Entrez Gene identifier available, or will use any locus with at least a UniGene cluster identifier, even in absence of an official or Entrez Gene symbol. The statistical significance of the results is calculated as described in the \"Statistical analysis\" Methods section below. Statistical analysis -------------------- To assess the statistical significance of the results, TRAM uses the hypergeometric distribution to test the probability \'P\' that colocalization of over/under-expressed genes within the same chromosomal segment (\'Map\' analysis mode) or in the same cluster of contiguous genes (\'Cluster\' analysis mode) may be due to chance. To this aim, calculations are performed as previously described \[[@B10]\]. The \'P\' value needs to be corrected to account for False Discovery Rate (FDR) due to the high number of segments or genes in a genome. The \'Q\' field in TRAM displays the p-value corrected for FDR. Q (q-value) for each chromosomal segment or cluster of contiguous genes is defined as Q = (p\*N)/i, where \'p\' is the p-value of the segment or of the cluster, \'N\' is the total number of segments or cluster considered (i.e., all those tagged as over/under-expressed under the criteria defined by the user selected analysis settings) and \'i\' is the number of windows with a p-value not higher than \'p\' \[[@B10]\]. Results are considered statistically significant for Q \< 0.05. Depending on the type of analysis selected by the user, TRAM may perform statistical significance computation taking into account all genes in the genome or, in order to emphasize local chromosomal effects, taking into account only the genes located in the same chromosome the chromosomal segment or gene cluster belongs to. The results discussed above, regarding the outcome of the normalization methods implemented in TRAM, were obtained using descriptive statistical analysis functions of the software JMP 5 for Mac OS X (SAS Institute, Cary, NC). Biological model test --------------------- To test the software, we performed a meta-analysis of a dataset obtained by gene expression profiling of human hematopoietic progenitor cells, searching for up- or down-regulated chromosomal segments and gene clusters in human megakaryocyte (Mk) cells, the precursors of platelets, compared to CD34+ hematopoietic undifferentiated stem cells. After searching in the GEO database, we selected 9 human Mk samples and 19 human CD34+ cell samples, using the following criteria: homogeneity of cell type, derivation from different Authors works and representation of microarray platforms with different technology and number of spots (Table [1](#T1){ref-type="table"}) \[[@B19]-[@B24]\]. The default analysis parameters were: expression values normalized both intra-sample (by percentage of sample mean) and inter-sample (by scaled quantile method); 2.5th percentile upper and lower threshold to define over- or under-expression, for both segments and genes, with respect to whole genome gene set; requirement of at least 3 over/under-expressed genes to define a segment accordingly; window (segment) of 500,000 bp (with shift of 250,000 bp). The wideness of the window and the minimum number of over/under-expressed genes required to lie in the window (\'n\') should be reciprocally adjusted so that the mean number of all genes included in a segment (shown at the end of the Segment Map) would exceed \'n\'. In our human genes data set, setting a window to 500,000 bp led to segments containing a mean of 4.3 genes, while lowering the window to 250,000 bp led to a mean of 2.7 genes (segments with no gene value are ignored in the calculation of mean). In the \'Cluster\' mode, all available genes including UniGene clusters of transcripts were selected to construct the map, and the Gap was set equal to 1. The test was run on March 2010, using Entrez Gene and UniGene data available at the time (UniGene build \#222). Authors\' contributions ======================= SF, PS and LL conceived the software. PS and LL developed and tested the basic version of the software and wrote the software guide. PS conceived, built and analyzed the biological model used to test the software. FP and MG systematically tested the software, debugged the Windows version and revised and expanded the software guide. FFa, MCP, FFr and RC tested and improved the Macintosh version of the software and developed the organism-specific versions. LV tested the software and collaborated to the biological model test. SC tested the software and developed its graphical interface. SB and AC critically revised the software and the manuscript. GAD, GP and SF supervised the work and revised the whole manuscript. All authors drafted, critically discussed and approved the final manuscript as well as the software guide. Acknowledgements ================ This work was funded by a grant from the Italian Ministry of University and Research (PRIN2005050779). The biological model test was performed on the Apple Mac Pro \"Multiprocessor Server\" available at the Center for Research in Molecular Genetics \"Fondazione CARISBO\", Bologna, and funded by \"Fondazione CARISBO\". We are grateful to Dr. Francesco Ferrari for his useful discussion about the project; to Dr. Mariangela Casadei (SAS Institute Australia, Sidney, Australia) for her helpful advices about statistical analysis and for manuscript revision; to Dr. Francesco Noferini for his helpful discussion of statistical analysis; to Dr. John Kenny for his expert revision of the manuscript; to Prof. Pier Paolo Gatta for his valuable advices about the manuscript. PS wishes to dedicate this work to his father Giuseppe, who died in December 2009, that lovingly followed and strongly supported his scientific endeavours.	PubMed Central	2024-06-05T04:04:19.004482	2011-2-18	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052188/", "journal": "BMC Genomics. 2011 Feb 18; 12:121", "authors": [ { "first": "Luca", "last": "Lenzi" }, { "first": "Federica", "last": "Facchin" }, { "first": "Francesco", "last": "Piva" }, { "first": "Matteo", "last": "Giulietti" }, { "first": "Maria Chiara", "last": "Pelleri" }, { "first": "Flavia", "last": "Frabetti" }, { "first": "Lorenza", "last": "Vitale" }, { "first": "Raffaella", "last": "Casadei" }, { "first": "Silvia", "last": "Canaider" }, { "first": "Stefania", "last": "Bortoluzzi" }, { "first": "Alessandro", "last": "Coppe" }, { "first": "Gian Antonio", "last": "Danieli" }, { "first": "Giovanni", "last": "Principato" }, { "first": "Sergio", "last": "Ferrari" }, { "first": "Pierluigi", "last": "Strippoli" } ] }
PMC3052189	Background ========== Bovine viral diarrhea virus, a single-stranded RNA is found in cattle and other ruminants worldwide \[[@B1]-[@B4]\]. The presence of BVDV in other domestic species such as sheep or wild species such as whitetail deer might be relevant to the epidemiology other disease in cattle \[[@B5]\]. The BVDV infections range from clinically in apparent infections to severe disease involving one or more organ systems. Historically, BVDV was associated with digestive tract disease including high mortality. Currently, BVDV is associated more frequently with respiratory disease and fetal infections \[[@B2]\]. Raise skia deer already had hundreds years at present artificially in china and farmed populations had reached hundreds of thousands in recent year. However, bovine viral diarrhea (BVD) caused significantly losses in the deer population. It was reported that infections rates of BVDV for young deer reached 60%\~86.7% in some areas of china in recently years \[[@B6]\], which caused economic losses to sika deer industry due to the high morbidity and fetal infections associated with the disease. Thus, the isolation and identification of BVDV from sika deer, which is fundamental to prevent and control of BVDV in sika deer, becomes an urgent task to many researchers. The Bovine viral diarrhea virus (BVDV) belongs to the genus pestiviruswithin the family Flaviviridae. BVDV is closely related to the classical swine fever virus (CSFV) and the ovine border disease virus (BDV) \[[@B7]\]. The pestiviral genome consists of a single stranded positive sense RNA with a length of about 12.3 kb. It contains one larger open reading frame (ORF), which is flanked by nontranslated regions (NTR) on both genome termini. The single ORF is translated into one polyprotein, which is co-and post- translationally processed into the mature proteins N^pro^, C, E0 (gp48, also named E^rns^), E1, E2, NS2/3, NS4a, NS4b, NS5a and NS5b by viral and cellular proteases \[[@B8]-[@B10]\]. E0 protein, the main structural protein of BVDV, plays a very important role in inducing protective immunoreaction against BVDV and diagnosing virus \[[@B2]\]. Although BVDV from the skia deer has been seriously concerned, there are only a few articles with respect to the prevalence of BVDV investigations and BVDV clinical sign \[[@B6]\], Particular, lacking in articles with regard to the molecular virology, gene sequences and genetically engineering vaccine of local BVDV isolates in China due to BVDV from skia deer without isolation and identification. The purpose of our study was isolation and identification BVDV from skia deer by a series of methods, which contributes this disease control. Results ======= Isolation and identification ---------------------------- The significant cytopathic effects (CPE) were observed in MDBK cell infected with virus 24h-48h. The MDBK cells generate obvious cell lesion and net between cells in comparison to the control cells, which is consistent with CPE of BVDV on MDBK cell (Figure [1](#F1){ref-type="fig"}). The IPX assay showed that the well of positive serum appeared red-brown cytoplasmic staining, which suggested that new isolation virus might be BVDV. The negatively stained virus particles extracted from liver were approximately 40 nm-60 nm in diameter when examined by electron microscope (Figure [2](#F2){ref-type="fig"}), and displayed a typical BVDV morphology. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### The CPE of BVDV. A: The MDBK cell as negative control; B: The CPE of C~24~V strain as positive control. C: The CPE of CCSYD strain. ::: ![](1743-422X-8-83-1) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Negatively stained BVDV. ::: ![](1743-422X-8-83-2) ::: Amplification, sequencing and analysis of E0 gene ------------------------------------------------- The MDBK cell infected with CCSYD were positive by the RT-PCR assays, and the expected sizes of the PCR products, 706 bp for E0 of CCSYD, were observed as clear electrophoretic band (Figure [3](#F3){ref-type="fig"}). The obtained E0 genes segment by sequencing has been deposited in GeneBank under accession No. FJ55520. Alignment with other 9 strains of BVDV, 7 strains of CSFV and 3 strains of BDV in the world, showed that the homology were 98.6%-84.8%, 76.0%-74.7%, 76.6%-77.0% for nucleotide sequence, respectively (Table [1](#T1){ref-type="table"}), which shows that there is no significant deviation of CCSYD E0 with conventional BVDV. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### The amplified products by RT-PCR. Lan1 and Lan2: E0 gene from infected MDBK cell; Lan3: MDBK cell as negative control. ::: ![](1743-422X-8-83-3) ::: ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Homology of E0 gene sequence of different RHDV isolates ::: C~24~V R1935 naqdl SD-1 Bega Y546 CCSYD VEDEVAC ILLC OSLOSS ALD GPE Brescia SM C LN9912 JL BD31 BDVX818 C413 --------- -------- ------- ------- ------ ------ ------ ------- --------- ------ -------- ------ ------ --------- ------ ------ -------- ------ ------ --------- ------ C~24~V 99.5 91.5 92.7 88.4 88.6 84.9 84.6 85.6 85.2 75.5 75.4 74.5 75.5 76.0 75.8 75.2 77.1 77.0 76.6 R1935 0.6 91.5 92.7 88.6 88.9 85.2 84.8 85.8 85.2 75.5 75.4 74.6 75.5 76.0 75.8 75.3 77.1 77.0 76.5 naqdl 11.8 11.8 91.5 87.7 87.8 86.2 85.5 87.0 85.6 75.6 75.8 75.2 75.3 75.1 74.8 75.1 77.8 77.5 76.9 SD-1 10.0 10.0 11.8 88.1 88.6 84.8 84.7 85.7 85.7 75.1 74.9 74.0 74.9 75.4 75.2 74.7 78.9 78.0 76.7 Bega 16.9 16.5 18.0 17.4 95.1 85.8 85.8 87.4 86.4 74.8 74.9 74.9 74.9 74.5 74.5 76.3 77.7 77.6 76.9 Y546 16.6 16.2 17.9 16.5 6.5 85.5 85.4 86.7 86.5 74.5 74.6 74.7 74.4 73.9 73.9 76.2 79.1 78.2 76.3 CCSYD 22.8 22.4 20.5 23.2 21.2 21.8 98.6 92.7 95.1 76.0 76.1 75.1 75.8 74.7 74.9 75.5 76.6 76.7 77.0 VEDEVAC 23.5 23.1 21.8 23.4 21.2 22.1 1.8 93.4 95.8 76.2 76.3 75.1 76.0 74.9 74.9 75.8 76.9 76.7 77.4 ILLC 21.7 21.3 19.2 21.5 18.6 19.9 10.0 9.0 92.6 76.0 76.2 75.3 76.0 75.5 75.5 76.7 77.4 77.1 77.8 OSLOSS 22.6 22.6 21.6 21.5 20.2 20.0 6.5 5.5 10.3 76.1 76.2 75.2 76.0 75.2 75.2 76.1 77.3 76.6 77.1 ALD 40.9 40.9 40.8 42.3 42.7 43.6 40.1 39.4 39.9 39.6 99.3 94.7 98.6 96.6 96.6 88.2 79.2 79.1 77.6 GPE 41.2 41.2 40.4 42.6 42.4 43.2 39.8 39.1 39.3 39.3 0.9 94.1 97.9 96.1 96.1 88.5 79.4 79.4 77.7 Brescia 43.2 42.9 41.6 44.6 42.1 42.6 42.0 41.9 41.3 41.5 7.1 8.0 94.4 92.8 93.3 87.4 78.3 78.0 76.8 SM 40.9 40.9 41.6 42.6 42.3 43.7 40.5 39.8 39.8 39.7 1.8 2.7 7.5 96.4 96.6 88.3 79.2 79.1 77.3 C 39.8 39.8 42.2 41.4 43.7 45.1 43.3 42.5 41.0 41.8 4.4 5.2 9.8 4.7 99.5 86.8 78.9 78.7 77.8 LN9912 40.3 40.3 42.7 41.9 43.6 45.1 42.6 42.5 40.9 41.7 4.4 5.2 9.2 4.4 0.6 86.8 78.9 78.7 77.6 JL 41.6 41.3 42.0 43.0 38.8 39.1 41.0 40.3 38.1 39.4 17.3 16.7 18.5 17.0 19.7 19.7 78.5 79.0 76.7 BD31 37.2 37.2 35.8 33.5 36.0 33.0 38.3 37.6 36.6 36.8 33.7 33.5 35.6 33.8 34.5 34.5 34.8 92.3 77.4 BDVX818 37.4 37.4 36.5 35.4 36.3 35.0 38.1 38.2 37.2 38.5 33.9 33.4 36.4 33.9 34.9 35.0 33.9 10.6 76.7 C413 38.4 38.7 37.8 38.2 37.8 39.1 37.2 36.5 35.5 36.9 36.2 35.9 37.9 37.0 35.7 36.2 37.9 36.7 38.3 ::: Phylogenetic analysis --------------------- To better understand the relationship of CCSYD to other 9 strain of BVDV, 7 strains of CSFV and 3 strains of BDV variants co-circulating in the word, genetic sequences of Pestivirusfrom cattle, swine and ovine in GenBank were used to construct phylogenetic trees. Figure [4](#F4){ref-type="fig"} clearly showed that E0 genes of the CCSYD belonged to BVDV1b. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### Phylogenetic analysis of E0 protein sequence of different BVDV isolates. ::: ![](1743-422X-8-83-4) ::: Discussion ========== In the present study, CCSYD strain was isolated from skia deer in Changchun city. By employing a series of biochemical and biophysical methods, we have firstly identified that CCSYD might be BVDV. The BVDV can be classified into biotypes and genotypes \[[@B2]\]. Biotypes are based on the presence or absence of visible CPE in infected cell cultures, cytopathic (CP) or noncytopathic (NCP) \[[@B2]\]. Genotype classification is based on divergence in the viral genome sequences revealed by phylogenetic analysis \[[@B11]-[@B15]\]. Based on phylogenetic comparison, the virus can be classified into two genotypes: BVDV1 and BVDV2. Whereas BVDV1 has a world-wide distribution, BVDV2 appears to be highly prevalent only in North America \[[@B13],[@B16]\] and relatively rare in other continents \[[@B15],[@B17]\]. Moreover, recently the BVDV1 and BVDV2 genotypes have been further divided into subgenotypes BVDV1a, BVDV1b, BVDV2a, and BVDV2b in North American \[[@B18],[@B19]\]. Genetic and phylogenetic analysis showed that the virus belonged to BVDV1b. Similar strains contain the VEDEVAC strain isolated Hungary, with 98.7% homology for amino acid. Moreover, we have also successfully cloned NS2/3 genes of CCSYD strain, with 100% homology for amino acid and NS2/3 genes of VEDEVAC strain, which further showed that CCSYD strain and VEDEVAC strain belonged to BVDV1b. The protection conferred by conventional inactivated BVDV vaccines is strongly correlated with genetically and antigenically of specific BVDV strain. In addition to, an increasing frequency of skia deer with elevated antibody titers to BVDV suggests that exposure to field strains has not been diminished despite the use of both management and vaccine \[[@B6]\]. This suggests that current vaccine may be inadequate in conferring skia deer protection against the acute disease in skia deer. Design of efficacious vaccines must be based on specific BVDV strain about the immune responses critical to development of protection. Hence, it is appropriate to guide the selection of the vaccine strain according to the specific BVDV strain from local area and similar strain, which depend on further studies of BVDV from skia deer distribution and identification. There is currently no commercial skia deer BVDV vaccine used in China, and therefore, it is important to select the vaccine candidate strain from control BVD from skia deer. Inactivated CCSYD strain by a certain method might be employed in preventing and counterchecking the skia deer BVD in Jilin province. Moreover, selected E~0~protein of CCSYD construction a DNA vaccine might induce cellular immune response and antibody responses specific for BVD from skia deer. Therefore, isolation and identifcation of a skia deer bovine viral diarrhea virus (CCSYD) contributes development new BVDV vaccine to prevent and control of BVDV in sika deer. Conclusions =========== The present study described the isolation and identifcation of a skia deer bovine viral diarrhea virus (CCSYD) isolated from sick skia deer for the first time in China. This study provided a detailed analysis of the genetic and evolution of CCSYD which is likely to be helpful to guide efficient diagnostic, preventive and control strategies against BVD from skia deer in China. Materials and methods ===================== Virus isolation --------------- Field samples came from skia deer at field of Changchun (China), which might infected with BVDV according to clinical sign such as diarrhea and miscarriage and stillbirth. Skia deer liver was collected from an aborted fetus deer. A total of 1 g of fresh liver tissue was homogenized in 4 ml of phosphate-buffered saline (PBS, PH 7.2) and then repeated freeze thawed 3 times, and centrifuged at 5000 rpm for 30 min. A certain liver extract was then inoculated onto MDBK monolayer cultures, 25 cm flasks with a 1 ml inoculum (1:10 dilution of original samples) and the total volume was 5 ml. The MDBK cultures were observed for 6 days with presence or absences of CPE recorded. The cultures were frozen at 70°C, thawed and supernatants collected after centrifugation with subsequent storage at 70°C. Uninoculated cultures were included as negative controls and inoculated C~24~V as positive control. Identification of virus ----------------------- BVDV was detected by indirect immunoperoxidase test (IPX) and electron microscopy technique (EM). For IPX, the test was carried out on 96-well plates using low-passage MDBK cells. Serum (20 μl) was added to each of four wells before the addition of 100 μl of cell suspension. Positive and negative control sera were run on each plate. The test plates were incubated for 4 days in 5% CO~2~, 37°C. Plates were fixed and dried, then stained with immunoperoxidase as described by Meyling \[[@B20]\], using a polyclonal bovine anti-BVDV serum (BVD virus positive control serum, China) to detect the virus. The presence of red-brown cytoplasmic staining in any of the wells exposed to the specific anti-BVDV antibody denoted a positive result. For electron microscopy technique (EM), chloroform (1/10 of the volume of the liver extract) was added into the liver extract, and then the liver extract) was added into the liver extract, and then the mixture was incubated for 30 min at 4°C and then centrifuged at 12000 rpm for 30 min. The precipitate was resuspended in 0.005 M moderate phosphate buffered saline (PBS; PH 7.2), and negatively stained with 2% phosphotungstic acid. The specimens were examined with a transmission electron microscope (Hitachi-8100, Japan) at 80 kV. PCR amplification and sequencing -------------------------------- Total RNA was isolated from infected MDBK cell using TRIzol reagent (Invitrogen China) according to the manufacturer\'s protocol and as described in the online supplement. In short, 200 μl infected MDBK cell was incubated with 1 ml TRIzol for 5 min at room temperature (RT). Cell debris was removed by centrifugation (12,000 × g at 4°C for 10 min) and 0.4 ml chloroform was added. After vortexing the mix was incubated for 5 min at RT. The phases were separated by centrifugation (12,000 × g at 4°C for 15 min) and the aqueous phase was transferred to a new tube. 0.6 × volume of isopropyl alcohol and a 0.1 × volume of 3 M sodium acetate were added to this aqueous phase and incubated for 10 min at 4°C. The precipitated RNA was pelleted by centrifugation (12,000 × g at 4°C for 15 min) and after the removal of the supernatant the RNA pellet was washed twice with 70% ethanol. After drying, the RNA was resuspended in 30 μl DEPC-treated water. Using mRNA as template, single-stranded cDNAs were generated by Superscript II reverse transcriptase (Invitrogen) according to the manufacturer\'s directions. The E0 primer sequences were as follows: sense prime: 5\'-CCGGATCCACCATGGAAAACATAACACAGTGG-3\'; anti-sense prime: 5\'- GCCTCGAGTTAAGCGTATGCTCCAAACCACGT -3\'. The PCR conditions were 94°C for 3 min, followed by 30 cycles of DNA amplification (45s at 94°C, 1 min at 61°C, and 1 min 30s at 72°C) and 8 min incubation at 72°C. PCR products were separated by electrophoresis at a constant voltage (2 V/cm) in a 1.2% (w/v) agarose gel. The full-length E0 gene subjected to DNA sequencing. Analysis of sequence -------------------- The sequence data were analyzed with computer programs such as DNAMAN and DNASTAR. Phylogenetic analysis was done by the distance-based Neighbor-joining method using software EGA 4.1. (DNAStar Inc.). Abbreviations ============= BDV: Border Disease Virus; BVD: Bovine viral diarrhea; BVDV: Bovine Viral Diarrhea Virus;CPE: Cytopathic Effects; CSFV: Classical Swine Fever Virus; DNA: Deoxyribonucleic Acid; EM: Electron Microscopy; IPX: Indirect Immunoperoxidase; MDBK: Bovine Kidney; PCR: Polymerase Chain Reaction; RNA: Ribonucleic Acid. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= YG and PZ participated in the design and conducted the majority of the experiments in the study and drafted the manuscript. RD and SW contributed to the interpretation of the findings and revised the manuscript. QW and NW edited the manuscript. CS performed analyses of data. All authors read and approved the final manuscript. Acknowledgements ================ The authors gratefully acknowledge the financial support provided by China Postdoctoral Science Foundation (20090461042), Supported by Ministry of Science and Technology of China(2009GJB10031) and Supported by National Natural Science Foundation of China (30570185).	PubMed Central	2024-06-05T04:04:19.012872	2011-2-25	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052189/", "journal": "Virol J. 2011 Feb 25; 8:83", "authors": [ { "first": "Yugang", "last": "Gao" }, { "first": "Shijie", "last": "Wang" }, { "first": "Rui", "last": "Du" }, { "first": "Quankai", "last": "Wang" }, { "first": "Changjiang", "last": "Sun" }, { "first": "Nan", "last": "Wang" }, { "first": "Pengju", "last": "Zhang" }, { "first": "Lianxue", "last": "Zhang" } ] }
PMC3052190	Introduction ============ Almost 170-200 million of the world population is infected with HBV, leading to world\'s most common cancer \"Hepatocellular carcinoma (HCC)\", causing nearly one million deaths per year. Approximately, 20% of chronic HBV patients have eventually progressed to liver cirrhosis, and some infections have evolved into HCC in a substantial number of patients \[[@B1],[@B2]\]. The most common contradiction in diagnosis of HBV patients is the differentiation of chronic active cases from the inactive carriers, as they share same serological profile. Diagnosis of disease outcome in these patients with PCR and HBV DNA levels assay, and defining the state of infection with these tools is emerging during last decade \[[@B3]-[@B5]\]. However, in many countries and regions like United States, Western Europe and other high or middle income countries, ELISA is still used and majority of the positive tests are not confirmed by PCR. It is interesting to note that many HBeAg (-) patients showed presence of chronic active HBV in further screening by PCR and vice versa \[[@B6]\]. To differentiate active chronic HBV from inactive carrier state, an arbitrary serum HBV DNA level of 100000 copies/mL has been proposed by the United States national Institute of health (NIH) \[[@B7]\]. During HBV disease progression, after seroconversion (HBeAg (+) to HBeAg (-), HBeAg consists of two clinical forms; one known as chronic inactive with low persistant aminotransferase levels and HBV DNA levels (≤ 100,000 copies/ml) and second with no HBeAg, high ALT and HBV DNA levels (≥ 100,000 copies/ml). In low-income countries like Pakistan, many patients refused to do PCR and liver biopsy procedure due to poverty and cost of these tests. Beside these challenges, the growing concern is the early detection of viral hepatic disease and liver damage. For this purpose, in routine laboratory tests, elevated alanine aminotransferase (ALT) levels are used as indicators of liver cell injury and as non-invasive diagnostic tests \[[@B8]\]. Elevated AST levels are usually predominant in liver cirrhosis with increased ALT levels \[[@B9],[@B10]\]. During assessment of liver disease due to hepatitis, serum AST and ALT levels are most commonly used serum markers to detect acute and chronic hepatocytes cytotoxicity \[[@B11]-[@B13]\]. Now a days, the main emphasis of workers is early detection of liver damage due to chronic HBV, however, there is always questions about the effectiveness of these test because of their low sensitivity \[[@B14],[@B15]\]. Several studies in Italy, China, Korea and Hong Kong showed that ALT levels higher than the normal limits are strongly associated with an increased risk of liver cirrhosis in HBV infected patients \[[@B16]-[@B19]\]. Recent studies revealed that in patients with HBeAg (-), high ALT levels greater than 0.5x to the upper limit of normal (ULN) relate to advance fibrosis and ALT \> 30 IU/L and 19 IU/L in male and female respectively, with base line HBV DNA levels \> 100000 copies/ml; can better differentiate between active chronic HBV patients from inactive chronic carriers \[[@B11],[@B12],[@B20]-[@B22]\]. While, Degertekin et al.proposed HBV DNA cutoff values of 5000 copies/mL to differentiate between active chronic HBV patients from inactive chronic carriers \[[@B23]\]. These studies indicates ALT level as a reliable serum marker leading to fact that HBV natural history can vary from one population to another \[[@B24]\]. Therefore, we should determine more reliable cutoff value for serum ALT and AST levels to predict active HBV patients according to our population. The aim of our study was to assess the relationship between HBV DNA load, AST and ALT levels in HBeAg (-) patients, review the performance of serum ALT and HBV DNA levels as the screening tool for liver disease and to find whether new cutoff values of ALT and HBV DNA are able to predict HBV infection in Pakistani population. The need of PCR and invasive procedure liver biopsy may be eradicated if the serum biochemical marker ALT with high positive or negative predictive values of HBeAg (-) patients can be obtained and thus minimize the cost of PCR and therapy time. Material and methods ==================== Patients -------- Patients of this study were the native Pakistani people referred to Pathology department, Jinnah Hospital, Lahore, Pakistan, for biochemical and serological tests. This retrospective cross-sectional study was carried out from March 2008 to September 2009 with collaboration of National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. Blood samples (10 mL) collected from each patient tested for HBsAg and HBeAg by ELISA. All patients did not have any history about HBV vaccination or disease infection, and/or other type of hepatitis. The routine liver function tests (LFTs) were estimated for each patient in hospital laboratory. Patients with positive serology and/or positive test for HBV alone and no evidence of liver failure were included in this study. Informed consents were obtained from patients containing their bio data and lab results. This study was approved by the Institutional ethics committee. Laboratory assays ----------------- Test for HBsAg and HBeAg were done by using ELISA kits (Abbot Diagnostics). Serum ALT and AST levels were measured by using commercially available Hitachi-7600 series automatic analyzer. The normal limits considered for ALT was 40 IU/L and for AST 35 IU/L. Serum HBV DNA was evaluated by using commercially available polymerase chain reaction assay (Amplicor HBV Moniter test; Roche Diagnostic System, Inc., Branchburg, New Jersey) with lower limit of detection 80 copies/mL and accurate range 500-200,000 copies/mL according to manufacturer protocol. Selected patients were HBeAg (-) with base line ALT determined at first visit. Patients ALT levels were determined four times every three months. Patients were divided into two groups as inactive (A) and active (B) chronic carriers based on HBeAg absence, liver diagnosis by ultrsonography, persistent ALT levels and HBV DNA load. Patients with ≥ 100000 HBV DNA copies/mL and continual elevated ALT levels were considered as active chronic carriers. Statistical analysis -------------------- Statistical analysis was performed using the statistical package for social studies (SPSS) version 16 for windows. Student t-test and chi-square tests were applied to evaluate differences in proportions. Pvalue \<0.05 was considered significant. Univariate analysis includes the variables age, HBV DNA levels, ALT and AST. Gender and PCR results were taken as independent categorical factors. Spearman correlation was used to assess the association between two quantitative variables. The diagnostic validity of serum ALT, AST and HBV DNA load and their combination were tested for classification of HBeAg (-) patients into active and inactive chronic patients. ROC curves were drawn for predicting values of ALT, AST and ALT at specific cut off values. Cutoff values for AST and ALT were 40 and 35 IU/L for each respectively, while for HBV DNA cut off values were 2000, 5000, 20,000, 50,000 and 100,000 copies/mL, respectively. New cut off values with high sensitivity, specificity, PPV and NPV were also predicted. Results ======= Patient\'s clinical characteristics ----------------------------------- A total of 567 HBeAg (-) patients were selected for this study. Patient\'s data is given in Table [1](#T1){ref-type="table"}. The mean age of the patients was 32.20 ± 11.9. Of 567 patients, 228 were classified into HBeAg (-) chronic inactive, while remaining 339 were active. The age difference between both groups was not significant (P= 0.181). Male were dominant in both groups. Out of 228 inactive and 339 active patients, 58 and 114 were female respectively (P= 0.038). Among 170 chronic inactive male, 168 have ALT \< 30IU/L; while 51 chronic inactive female out of 58, have ALT \< 19 IU/L. Regarding AST levels, 225 inactive and 74 active carriers have their AST levels \< 35 IU/L. Baseline ALT and AST values were significantly higher in HBeAg (-) chronic active patients (P \< 0.05). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Clinical characteristics of HBsAg positive patients ::: Patients characteristics Inactive carriers n = 228 Active carriers n = 339 P-value -------------------------- --------------------------- ------------------------- ----------- M/F 170/58 225/114 0.038 Age 31.3 ± 12.1 32.75 ± 11.7 0.181 ALT (IU/L) 17.3 ± 4.3 70.3 ± 15.1 0.000 AST (IU/L) 15.9 ± 7.1 48.4 ± 22.6 0.000 HBV DNA (copies/mL) 4.9 × 10^3^ 6.5 × 10^8^ 0.000 ::: HBV DNA levels were five times elevated in active carriers (HBV DNA levels = 4.38 × 10^8^(± 1.04 × 10^9^) copies/mL vs6.9 × 10^4^(± 4.9 × 10^5^) copies/mL). More than 99% (n = 227) inactive carriers patients have HBV DNA levels less than 50, 000 copies/mL, and below undetected limits (\< 200 copies/mL) in 21 patients. Application of revised cutoff values ------------------------------------ Receiver operating characteristics (ROC) curves were drawn for ALT, AST and HBV DNA levels. All of them showed high area under the curve (AUC) to discriminate HBeAg (-) active carriers from inactive as mentioned in Table [2](#T2){ref-type="table"} (see also Figure [1](#F1){ref-type="fig"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### ROC curve analysis of serum AST, ALT and HBV DNA levels ::: Test Result Variable(s) Area SE P-value 95% C I ------------------------- ------- ------- ----------- --------- ------- AST 0.969 0.006 0.000 0.957 0.982 ALT 0.997 0.002 0.000 0.994 1.001 HBV DNA level 1.000 0.000 0.000 1.000 1.000 ::: ::: {#F1 .fig} Figure 1 ::: {.caption} ###### ROC curve of serum ALT, AST and HBV DNA levels for HBeAg (-) patients showed serum ALT, AST and HBV levels could better predict HBV chronic active carriers at given cutoff value. ::: ![](1743-422X-8-86-1) ::: We observed approximately same sensitivity and specificity for the HBV DNA level ≥ 50,000 and NIH described limits ≥100,000 copies/mL. This value was much better than HBV DNA value of 2000, 5000 and 20,000 copies/mL. In general cohort, ALT and AST ≤ 20 IU/L were observed in 200 and 191 patients, respectively. ALT ≤ 30 IU/L showed high sensitivity (99.1%) and specificity (97.4%), while normal AST value (≤ 35 IU/L) showed high sensitivity (98.6%) but low specificity (77.8%) to discriminate active and inactive chronic HBeAg (-) carriers, respectively. In combination, ALT and HBV DNA levels; if ALT value were ≥30 IU/L for male and ≥19 IU/L for female, and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers (Table [3](#T3){ref-type="table"}). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Validity of serum ALT, AST and HBV DNA levels for the differentiation of patients with HBeAg (-) inactive chronic hepatitisB from active chronic HBeAg (-) carriers ::: Lab tests Spe% Sen% PPV% NPV% Inactive carriers (n = 228) Chronic carriers (n = 339) ---------------------------------------------- ------ ------ ------ ------ ----------------------------- ---------------------------- ALT (IU/L) ≤ 20 99.1 87.7 99 92 200/28 2/337 ≤ 30 97.4 99.1 96 99.3 226/2 8/331 ≤ 35 96.6 99.6 96 99.6 227/1 9/330 ≤ 40 93.4 100 93 100 228/0 16/323 AST (IU/L) ≤ 20 93.5 83.7 82 89.5 191/37 40/317 ≤ 30 79.1 95.6 75.4 96.4 218/10 71/268 ≤ 35 77.8 98.6 75.2 98.8 225/3 74/264 ≤ 40 63.1 99.1 64.4 99.5 227/1 124/214 HBV DNA (Copies/mL) ≤ 2000 100 48.2 100 75 110/118 0/339 ≤ 5000 100 75.4 100 84 172/56 0/339 ≤ 20,000 100 95.1 100 95 217/21 0/339 ≤ 50,000 100 99.1 100 99 227/1 0/339 ≤ 100,000 100 100 100 100 228/0 0/339 ALT + HBV DNA (Our findings) ALT (30 M/19F) HBV DNA (≤ 100,000 copies/mL) 92 98 97 94 210/18 5/334 *ALT + HBV DNA (Assy et al.**\[[@B22]\]) ALT (30 M/19F) HBV DNA (≤ 100,000 copies/mL) 100 92 100 86 \- \- ::: A statistical significant correlation was found between HBV DNA levels and ALT in HBeAg (-) chronic active patients (r= 0.911, P \< 0.05). However, no such association was observed in case of ALT in chronic inactive patients and AST in both groups (Figure [2](#F2){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Correlation of ALT and AST with HBV DNA levels in HBeAg chronic inactive and active patients. A and C: association between ALT and AST with HBV DNA levels in chronic inactive carriers; B and D: association between ALT and AST with HBV DNA levels in chronic active carriers. ::: ![](1743-422X-8-86-2) ::: Discussion ========== In this study, we assess the performance of new cut off values for serum ALT levels in male and female to predict active HBV in HBeAg (-) patients. As high ALT levels are thought to be associated with chronic HBV, and are commonly used during evaluation of HBV \[[@B10],[@B25]-[@B28]\]. It is interesting to know that HBV evaluation depend on geographical association of the host and viral factors. Prati et al.proposed new cutoff value of ALT ≥ 30 IU/L in male and ≥19 IU/L in female \[[@B12]\], while Assy et al.2009 reported ALT ≥ 30 IU/L in male and ≥ 19 IU/L in female along with HBV DNA levels ≥ 100000 copies/mL can classify a patient into the active carrier state \[[@B22]\]. Although, serum AST levels are not thought to be incredibly useful predictor of HBV disease, we also evaluate their performance either they are useful or not for discriminating HBeAg (-) chronic active from inactive patients. Previous studies reported raised serum ALT levels from ULN can predict liver dysfunction with 90% specificity and 56% sensitivity \[[@B29]\], but according to Kim et al.prior testing of ELISA along with ALT level can better predict liver function as compared to only ALT levels \[[@B30]\]. This is particularly important because without performing PCR and liver biopsy, the decision as to predict HBeAg (-) chronic inactive is difficult. ROC curve analysis was performed to find out an accurate cutoff value for ALT, AST and HBV DNA load to guess HBeAg (-) inactive chronic patients from active (Table [2](#T2){ref-type="table"} and [3](#T3){ref-type="table"}). Serum ALT, AST and HBV DNA levels were found to be highly significant with immense AUROC. Their performance was assessed by using different cut off values irrespective of patient\'s gender. We observed same results as described by Prati et al.\[[@B12]\] and Assy et al.\[[@B23]\]. ALT ≤30 IU/L and HBV DNA load ≤ 100,000 copies/mL showed high sensitivity, specificity, PPV and NPV to differentiate HBeAg (-) inactive chronic patients from active. In combination (ALT and HBV DNA levels) we observed higher sensitivity (98%) and NPV (94%) than previously described \[[@B22]\] (92% and 86%, respectively) (Table [3](#T3){ref-type="table"}). Although Borg et al.found AST level as an important predictor during same circumstances \[[@B31]\], and in our study single AST value (≤ 20 IU/L) also showed high sensitivity and specificity, its prognostic ability was not better than serum ALT and HBV DNA. Our results are in agreement with Assay et al\[[@B22]\]. that the new baseline value for ALT levels (30 IU/L for male and 19 IU/L for female) notably perform well than AST as given in Table [3](#T3){ref-type="table"}. We detect HBV DNA in all patients. By using new cut off value of ALT, HBV DNA cut off values 50, 000 and 100,000 copies/mL showed same investigative performance and were better than 2000, 5000 and 20,000 copies/mL. These results indicate that NIH proposed HBV DNA levels limits are useful, and our findings are according to the study by Assy et al.\[[@B22]\] as given in Table [3](#T3){ref-type="table"}. As HBV DNA load and liver damage appears to be different in HBeAg (+) and negative patients. In HBeAg (+) patients, no correlation was found between severity of liver damage and HBV DNA load \[[@B32]-[@B34]\]. In recent study by Kim et al.*(2011) validate the performance of ALT and HBV DNA, and found that these markers may also used for discriminating patients with HBeAg (-) active carriers from inactive \[[@B35]\]. In our study, HBV DNA load was five times higher in chronic active patients. We also observed a positive significant correlation between HBV DNA levels and ALT in chronic active patients (Figure [2](#F2){ref-type="fig"}) leading to the conclusion that inflammation increases in patients with elevated HBV DNA levels as HBeAg has immunomodulatory action \[[@B36]\]. Recent studies showed that for HBeAg (-) patients, low HBV DNA levels are associated with less liver damage although some studies were unable to observe such relationship \[[@B37],[@B38]\]. These findings suggest that HBV DNA load and ALT are most convenient techniques to predict active chronic HBV in HBeAg (-) patients. Although, there are some limitations in our study like absence of liver biopsy data, HBV genotyping and/or a short period of follow up; yet the population size in this study is far larger than reported by others. In conclusion, we verified the new cut off value of ALT and found better results than previously described and also found AST as good predictor. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= BI, WA and FTJ contributed equally to this work. BI, WA, SG, FTJ and SH designed the study, analyze the data and wrote paper. They also checked the revised manuscript thoroughly and confirmed all the data given in manuscript. All work was performed under supervision of SH. We all authors read and approved the final manuscript. Authors\' information ===================== Bushra Ijaz (M Phil Molecular Biology), Waqar Ahmad (M Phil Chemistry) and Gull S (MSc Biochemistry) are Research Officer; Javed FT is Head Pathology Department Jinnah Hospital, Lahore; while Sajida Hassan (PhD Molecular Biology) is Principal Investigator at CEMB, University of the Punjab, Lahore Acknowledgements ================ Financial support by Prime Minister program for prevention of hepatitis (2005-10) is highly acknowledged.	PubMed Central	2024-06-05T04:04:19.015111	2011-2-27	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052190/", "journal": "Virol J. 2011 Feb 27; 8:86", "authors": [ { "first": "Bushra", "last": "Ijaz" }, { "first": "Waqar", "last": "Ahmad" }, { "first": "Fouzia T", "last": "Javed" }, { "first": "Sana", "last": "Gull" }, { "first": "Sajida", "last": "Hassan" } ] }
PMC3052191	Background ========== Aplastic anemia, acquire or congenital anemia associated with hypoplastic \"fatty or empty\" bone marrow and global dyshematopoiesis, has been first described by Paul Ehrlich in year 1888 \[[@B1]\]. The pathophysiology is believed to be idiopathic \[[@B2]\] or immune-mediated phenomenon with active destruction of haematopoietic stem cells \[[@B3]\]. The abnormal immune response may be elicited by environmental exposures, such as to chemicals, drugs, viral infections and endogenous antigens generated by genetically altered bone marrow cells \[[@B4]\]. A small fraction of the genes involved in pancytopenia has been represented by the congenital BM failure syndromes (relatively rare) which lately develop in clinical syndromes as Fanconi\'s anemia, Dyskeratosis Congenita, and Shwachman-Diamond syndrome \[[@B5],[@B6]\]. Hepatitis-associated aplastic anemia (HAAA) is a well recognized and distinct variant of clinical syndrome, acquired aplastic anemia, in which an acute attack of hepatitis leads to the marrow failure and pancytopenia \[[@B7]-[@B9]\]. HAAA has been first reported in two cases by Lorenz and Quaiser in 1955 \[[@B8]\] and the number of the cases increase up to value of 200 by the year 1975 \[[@B10]-[@B12]\]. However, this syndrome has been reported in 2-5% cases of west and 4-10% in area of more prevalent to hepatitis and Human Immunodeficiency Viruses (HIV) in the Far East \[[@B12],[@B13]\], it belongs to the area of low socioeconomic status \[[@B14],[@B15]\]. HAAA is not considered relative to age, sex and severity of hepatitis \[[@B14]\], predominantly it has been found in children \[[@B13]\], adolescent boys and in young aged men \[[@B10],[@B16]\]. The onset of syndrome, pancytopenia, usually takes two to three months \[62 days: ranging from 14 to 225) after attack of acute hepatitis \[[@B12],[@B14]\]. Hepatitis associated with aplastic anemia may be acute and chronic \[7\], mild and transient \[[@B16]\], self-limiting and fulminant and the development of AA is always fatal if not treated on time \[[@B7],[@B10]\]. Majority of the cases have been found as fulminant where the mortality rate reaches up to 85% \[[@B17]\]. Aetiology of the syndrome has been attributed to various agents and factors \[7\] which may include pathogenic viruses, autoimmune responses, liver transplantation procedure \[[@B18]\] bone marrow transplantation, radiation \[[@B19]\] and drugs administered to control the viral replication \[[@B14]\]. Aplastic anemia associated hepatitis viruses ============================================ Several hepatitis viruses such as Hepatitis A \[[@B20]\], B \[[@B21],[@B22]\], C \[[@B23]\], and E, G \[[@B24]\] have been anticipated to be associated with this set of symptoms \[[@B7]\]. No association has been found with blood transfusion, toxins and drugs \[[@B17]\]. In one study Safadi and co-workers (2001) found out that sera of eight of the patients had the existence of Hepatitis Bc IgG and/or anti-HBs antibodies which was suggested due to past exposure and immunizing effect and they were unable to establish any direct relation with acute hepatitis B \[[@B14]\]. As non-A, non-B hepatitis agents are usually responsible for the hepatitis associated aplastic anemia; the prevalence of anti-hepatitis C virus antibodies is similar in HAAA and aplasia of other origins \[[@B25]\]. HCV seropositivity has been observed in the patients developing cytopenia following non-A non-B hepatitis (NANBH). HCV viremia has been frequently observed without detecting anti-HCV antibodies in patients\' blood reflecting the transfusion associated HCV infection \[[@B25],[@B26]\]. However, it has also been reported that HCV is not generally implicated as a causative agent of hepatitis preceding aplastic anemia \[[@B27]\]. Hepatitis G virus (HGV) has been reported as a possible etiological agent of acute hepatitis, chronic liver dysfuntioning, and fulminant hepatitis and hepatitis associated aplastic anemia. A relation of Hepatitis G virus with hepatitis subsequently developing in the aplastic anemia has been seen in a 24 years old person by measuring the hematological, biochemical, serological and virological parameters and detecting HGV RNA in his serum by PCR and electro-immunoassay \[[@B24]\]. The development of aplastic anemia generally found to occur in hepatitis not caused by the hepatitis A and hepatitis B viruses commonly known as the non-A and non-B hepatitis associated aplastic anemia which were reported in above than 80% of the cases of hepatitis preceding severe cytopenia \[[@B28],[@B29]\]. Viruses other than hepatitis associated with aplastic anemia ============================================================ Viruses other than the hepatitis viruses have also been implicated as a causative agent of AA \[[@B1],[@B5]\] which include parvovirus B19 \[[@B19],[@B30],[@B31]\], Cytomegalovirus, Epstein bar virus \[[@B19],[@B31],[@B32]\], Echovirus 3 \[[@B33]\], GB virus-C \[[@B34]\], Transfusion Transmitted virus (TTV) \[[@B35]\], SEN virus and non-A-E hepatitis virus (unknown viruses) \[[@B7]\]. Parvovirus B19, an under recognized hepatotrophic virus, is documented as an offending agent of HAAA. Its infection cause hepatic manifestation ranging from abnormal liver functioning to Fulminant Hepatic failure and aplastic anemia \[[@B30]\]. The primary site of infection of this virus is erythroid progenitor cell in which it halts the erythropoises and leads to the anemia in immunocompromised hosts. The DNA of this virus has been detected in liver of fulminant hepatic failure manifested with bone marrow aplapsia and in the serum of fulminant hepatitis children of unknown origin \[[@B36],[@B37]\]. Association of Torque Teno virus, single stranded circular DNA has liver as a susceptible host as well as various other tissues including bone marrow. It has been firstly reported in 12 years old Japanese boy suffered from cytopenia following acute hepatitis by detecting Torque Teno virus DNA of genotype 1a and IgM antibodies against this virus in peripheral blood and bone marrow mononuclear cells which precludes that acute bone marrow failure majorly concerns with infection of TTV virus to haemopoietic progenitor cells. However, other studies have also been done on assessing the TTV as an etiological agent of HAAA \[[@B33],[@B38]\]. In a study a 6-year-old boy was experienced aplastic anemia two months after the onset of acute hepatitis associated with echovirus-3 \[[@B33]\]. As idiopathic aplastic anemia is associated with the increased level of secretion of INF-γ and TNF-α from T cells which inhibit the hematopoietic cell proliferation \[[@B39]\], similar increased level of serum INF-γ and TNF-α was found in the patient four weeks after the onset of aplastic anemia \[[@B33]\]. Similarly varying degrees of cytopenia has been related to the HIV infection and severe aplastic anemic conditions develop after subsequent attack of HSV-6 \[[@B17],[@B40]\]. Epstein Bar virus infection, involved in hepatitis, manifests the pathogenesis of marrow aplasia \[[@B40]\]. The pathogenic mechanism involve in the EBV infection is direct cytotoxity or mediates the immune response of host \[[@B7],[@B17],[@B14],[@B41]\]. Immunopathogenesis of HAAA ========================== Aplastic anemia can be acquired or congenital \[[@B1],[@B42]\]. As the aplastic anemia following the hepatitis has been elucidated as a severe bone marrow failure with an episode of acute hepatitis, following lymphocyte variations occur during the course of the syndrome: activation of circulating cytotoxic T cells increase, tend to accumulate in the liver, broad skewing patter of T cell reportrie in peripheral blood of the patient forms, a large number of T cell infiltration from liver parenchyma occurs \[[@B13],[@B26],[@B43],[@B44]\] defective monocyte to macrophage differentiation \[[@B45]\] and decreased circulating level of interleukin-1 occur \[[@B46]\]. Various Immunological abnormalities have been accountable for the development of aplastic anemia following hepatitis. The immunological abnormalities with HAAA show that CD8+ kupffer cells detecting by liver biopsies appear as a mediator of this syndrome. In a study it has been reported that patient showed a decreased ratio of CD4/CD8 cells and a high percentage of CD8 cells which can be cytotoxic and myleopoietic during the in vitro study of aplastic anemia \[[@B10],[@B20]\]. The residing of CD8 cells in bone marrow during HAAA produces a high level of interferon gamma (INF-γ) and cells derived from bone marrow locating in liver may activate these cytotoxic T cells causing their intrahepatic accumulation strongly affected by the Tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) causing the onlooker damage to liver cell of genetically modified mouse model. However, it has also been shown in several studies that increased level of soluble IL-2 receptor forms the major reason of non specific inflammation of HAAA \[[@B47],[@B48]\]. The pathogenesis of HAAA in children has been suggested to relate with the interruption in balance of lymphocyte sub-populations and T lymphocyte activation \[[@B49]\]. Genetic Vulnerability of HAAA ============================= Being an acquired disease, severe HAAA has also been presented as a Familial Bone Marrow Failure Syndrome (FBMFS) in a study while finding the family donor of HSCs transplant for treatment of idiopathic fulminant liver failure patient who has developed myelodysplastic syndrome after onset of severe aplastic anemia. The donor sibling also found to be developed the acute lymphoblastic leukemia after diagnosing the hypocelluarity of bone marrow. The event of finding these two familial cases shows the bone marrow failure syndrome to be inherited \[[@B50]\]. HAAA has not been clarified with any genetic tendency \[[@B18]\]. Mutation in genes of the telomere repair complex, TERC(the gene for the RNA component of telomerase) and TERT(the gene for the telomerase reverse transcriptase catalytic enzyme), reduce the marrow regenerative capacity, making genes mutation carriers susceptible to the development of aplastic anemia once it has been started \[[@B42]\]. Clinical features ================= Most of the clinical features relating to aplastic anemia following the hepatitis include: Pallor and multiple skin bleeding \[[@B11]\], lymphocytopenia, hypogammaglobulin \[[@B51]\] low number of CD8/T cell ratio \[[@B12]\] and increased number of cytotoxic cells \[[@B48]\] Neutropenia, fever \[[@B17]\]. Bacterial and fungal infection may emerge as secondary in presenting the disease \[[@B2]\]. Later complications may develop especially involving myelodysplasia \[[@B4]\]. The victims of severe aplastic anemia following the hepatitis experience a severe immune deficiency that might be either due to the hepatitis or aplastic anemia that is yet to be discovered \[[@B51]\]. Diagnosis of hepatitis associated aplastic anemia ================================================= On a course of HAAA, hepatitis can be detected on some of the following parameters: subsequent increase in serum Alanine Trasnaminase (ALT), Aspartate Transaminase (AST), by at least three times above the normal values which are 6 to 41U/l, 9-34U/l, 5-58U/L for ALT and AST respectively \[[@B12],[@B18],[@B30],[@B35],[@B36],[@B43],[@B52],[@B53]\], increase in serum Alkaline phosphatase (ALP), gamma glutaryl transferase (GGT) and billirubin (39-117U/l, 5-58 U/l, and 2-7 micromol/L, respectively). Peripheral blood count can be determined by Flow cytometry analysis with directly conjugated monoclonal antibodies for CD2, CD3, CD4, CD8, CD19 and HLA-DR, whereas haematopoietic failure with bone marrow hypocellularity can be elucidated in terms of absolute neutrophil count (less than 500 per mm^3^), Platelet count (less than 20,000 per mm3), Reticulocyte count (less than 60,000 per mm^3^) \[[@B53]\] and Protrombin Index (%): normal value 70-100% \[[@B24]\]. To establish the onset of pancytopenia following hepatitis, hypocelluarity of bone marrow below 50% might be obtained by bone marrow aspiration \[[@B14]\] and trephine biopsy \[[@B11]\]. Various virological and serological markers are available for the detection of hepatitis A, B, C, D, E, G, TTV and parvovirus. Among these tests, anti-HAV Ig total antibodies, HBsAg, HB core antigen, HBsIgG antibodies, various HCV recombinant antigens and hepatitis E virus IgM and IgG are being in use. However, to determine causative nature of all hepatitis viruses, RNA genome of RNA containing viruses such as HCV, HDV, HEV and HGV can be qualitatively detected by RT-PCR reaction and DNA of parvovirus B19 and TTV can be detected by Nested PCR \[[@B14],[@B53]\]. IgG antibody for Cytomegalovirus, EBV and parvovirus has been found a useful tool for the diagnostic purposes \[[@B18]\]. However, serological and virological parameters for hepatitis A, B, and C were found negative in majority of the HAAA cases reported in several studies \[[@B17],[@B23],[@B27]\]. Treatment ========= The standard therapy which is employed for the treatment of HAAA is allogenic bone marrow (BM) transplantation treatment from HLA matched siblings \[[@B13],[@B54]\]. HAAA is mostly occurring in children and it would be easier to find the HLA matched donor. As HAAA shows poor prognosis, most often it has been treated by hematopoietic stem cell transplantation \[[@B26],[@B55]\]. Immunosuppressive therapy has proved effective after BM transplantation. Various immunosuppressive drugs named Antithymocyte Globulin (ATG) and Cyclosporine have been administered without eliciting any acute side effects. Steroids such as Glucocorticoids have also been employed in combination with immunosuppressive medications for the treatment of the HAA patients \[[@B26]\]. A durable remission from HAA has been achieved by the administrating high dose of Cyclophosphamide (CY), a highly immunosuppressive, which elicits its effect by readily destroying the lymphocytes and committed myeloid cells. The haemopoietic stem cells are not susceptible to the toxic effects of the CY due to releasing the aldehyde dehydrogenase enzyme which inactivates the drug. However, restoration of haematopoesis process may achieved by high dose of CY which mediates autoimmune attack on haematopoiectic stem cells HSCs \[[@B13]\]. Patients irresponsive to the IST are prone to be cured by unrelated donor bone marrow transplantation \[[@B18]\]. Immunosuppressive therapy might have proved as a safe and alternative treatment for HAAA after of bone marrow or haemotopoietic stem cell transplantation \[[@B55]\]. Several studies showed that Parvovius induced aplastic anemia improves by the administration of retroviral therapy \[[@B21],[@B56]\]. Antiviral therapy for treating hepatitis B associated HAAA has been unknown yet; however it has been tested by administrating the nucleoside analogs, lamiviudine, against the aplastic anemic secondary to hepatitis B virus infection and remission occurs from the severe aplastic anemia accompanied with the hepatitis B viral infection. Interferon, an effective therapy for the hepatitis B and C viral infections, cannot be employed as a potential approach for the HAAA because of its mylosuppressive effects \[[@B21]\]. Acyclovir has been used for the treatment of aplastic anemia caused by the Epstein Bar virus \[[@B32]\]. The blood count comes to the normal range after five years of treatment \[[@B55]\], however, chances of recovery from hepatitis associated acquired aplastic anemia is rare \[[@B57]\]. Growth factors deficiencies have been found to be responsible for the majority of the aplastic anemic cases \[[@B1]\]. As these growth factors released by stromal cells are essential for the survival, proliferation and differentiation of hematopoietic stem cells \[[@B58],[@B59]\], a transient increase in granulocytes has been found effective in most aplastic anaemic trials by administrating the erythropoietin, growth factors, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, interleukin-3 \[[@B1]\] and androgens \[[@B5]\]. The limiting factors in success of immunosuppressive therapy are found to be the extent to which organ has been destructed, tissue regeneration capacity and most importantly pharmacology effect of drugs that is not sufficient for uncontrolled potent immune response \[[@B1]\]. The survival of the patients treated with hematopoietic cell transplantation and response rate to immunosuppressive therapy found to be 85% and 70% respectively \[[@B7]\]. Children response better than the adults to bone marrow transplantation and survival rate with Bone marrow transplantation from HLA matched donors is found to be similar as that for the non hepatitis associated aplastic anemia \[[@B14]\]. It has also been reported that parameters of liver dysfunctioning tend to improve when pancytopenia starts presenting itself \[[@B18],[@B28]\]. Although majority of the patients survives after aplastic anaemia tends to have complete recovery, the mortality rate is yet very high \[[@B52]\]. The mean survival rate after developing the severe bone marrow aplasia has been 2 months and fatality rate ranges from 78-88% \[[@B28],[@B60],[@B61]\]. Conclusion ========== HAAA is a well documented and diverse variant of clinical syndrome of aplastic anemia, in which an acute attack of hepatitis leads to the marrow failure and pancytopenia that may be acute or chronic. This disorder has been reported in 2-5% cases in West, 4-10% in Far East and high in area of low socioeconomic status. HAAA is not related to age, sex and severity of hepatitis, predominantly it has been found in children, adolesecent boys and in young aged men. A number of hepatitis viruses manifest the disease symptoms. Amongst the hepatitis viruses, HBV, HCV and HGV seropositivity has been mostly commonly observed in reported cases of HAAA. The causative agent of HAAA can be detected using hematological, biochemical, immunological and virological markers. The clinical features relating to HAAA are pallor and multiple skin bleeding, lymphocytopenia, hypogammaglobulin, low number of CD8/T cell ratio and increased number of cytotoxic cells, neutropenia and fever etc. For HAAA, immunosuppressive therapy is more effective after BM transplantation. Abbreviations ============= AA: Aplastic anemia; HAAA: hepatitis associated aplastic anemia; HCV: hepatitis C virus; NANBH: non-A non-B hepatitis; HGV: hepatitis G virus; HBV: hepatitis B virus; HAV: hepatitis A virus; HDV: hepatitis delta virus; HEV: hepatitis E virus; ELISA: enzyme linked immunosorbant assay; PCR: polymerase chain reaction; TTV: transfusion transmitted virus; INF-γ: interferon gamma; TNF-α: tumor necrosis factor alpha; Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= BR reviewed the literature, and wrote the manuscript. MI & SARS edited the manuscript. SB, AMB, AH, IR, MA, LA and SB helped BR in literature review. All the authors read and approved the final manuscript.	PubMed Central	2024-06-05T04:04:19.017300	2011-2-28	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052191/", "journal": "Virol J. 2011 Feb 28; 8:87", "authors": [ { "first": "Bisma", "last": "Rauff" }, { "first": "Muhammad", "last": "Idrees" }, { "first": "Shahida Amjad Riaz", "last": "Shah" }, { "first": "Sadia", "last": "Butt" }, { "first": "Azeem M", "last": "Butt" }, { "first": "Liaqat", "last": "Ali" }, { "first": "Abrar", "last": "Hussain" }, { "first": "Muhammad", "last": "Ali" } ] }
PMC3052192	Introduction ============ Retinitis pigmentosa (RP) is clinically characterized by loss of predominantly rod photoreceptor function as well as loss of peripheral vision. The classic clinical triad is considered to be the presence of bone spicule pigmentation in the peripheral retina, arteriolar attenuation, and waxy disc pallor. Cataracts, most commonly of the posterior subcapsular type, are often found in all forms of retinitis pigmentosa. Ectopia lentis and lens dislocation are known risk factors for those with RP, presumably secondary to zonular fiber weakness and vitreous degeneration \[[@B1],[@B2]\]. The post-operative complication of lens dislocation following cataract extraction in RP patients has also been documented \[[@B2]\]. In this report, we describe a spontaneous late posterior chamber intraocular lens subluxation secondary to severe capsular bag contraction in a patient with RP. Case presentation ================= A 58-year-old Hispanic woman presented to our clinic with blurred vision. She had been diagnosed with RP two years prior to presentation. Her best corrected visual acuity (BCVA) was 20/70 in the right eye and 20/25 in the left. Slit-lamp examination revealed anterior subcapsular as well as nuclear cataracts in both eyes, but worse in the right eye. No phacodonesis or iridodonesis was noted. Dilated fundus examination revealed bone spicule pigmentation in the retinal periphery, arteriolar attenuation, and optic disc pallor in both eyes, but which was more prominent in her right eye than in her the left. She had severe field loss of peripheral visual in the right eye (measured by Humphrey visual field. Humphrey Field Analyzer, Zeiss Ophthalmic, Dublin, CA, USA), leaving only the central 10°. Her left eye was found to have only mild loss of peripheral vision nasally. Electroretinography demonstrated an isoelectric potential in her right eye consistent with the diagnosis of RP. In her left eye, there was a generalized decrease in amplitude. She underwent an uncomplicated cataract extraction by phacoemulsification of the right eye. A continuous curvilinear capsulorrhexis was performed without any zonular stress observed. The capsulorrhexis was approximately 6 mm in diameter. A foldable acrylic intraocular lens (Tecnis Abbott Medical Optics Inc. Santa Ana, CA, USA) was inserted and observed to be well-centered at the end of the case. Post-operatively, her BCVA improved to 20/40 in the right eye. The intraocular lens was well-positioned within the capsular bag. However, three months after the surgery, she again presented to the clinic with blurry vision. She denied any history of trauma or fall. At this time her BCVA was 20/100 in the right eye and 20/25 in the left eye. On slit-lamp examination, the edge of the intraocular lens was displaced nasally and the capsular bag was displaced temporally (Figure [1](#F1){ref-type="fig"}). There were prominent capsular bag folds indicating severe bag contraction. Fundus examination again revealed changes from RP that were stable compared to previous examination. She was offered surgery, but declined it ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Capsular bag contraction and intraocular lens subluxation. ::: ![](1752-1947-5-65-1) ::: Discussion ========== There is a strong association between RP and zonular fiber weakness, anterior capsule contraction, and extensive vitreous degeneration \[[@B2],[@B3]\]. In one case study of a Korean patient with RP, intraocular lens dislocation into the anterior chamber occurred six years after phacoemulsification of the left eye and eight years after extracapsular cataract extraction of the right eye \[[@B4]\]. Hayashi, in a 2007 study, documented the possible predisposing factors for late in-the-bag or out-of-the-bag intraocular lens dislocation after intraocular lens placement \[[@B3]\]. RP was found to be associated with an increased incidence of in-the-bag lens dislocation. One case study reported a posterior lens dislocation in an RP patient one year following posterior Nd-YAG laser capsulotomy \[[@B5]\]. Although there is the possibility of zonular disruption having been inflicted during surgery in our patient, the lens was well-positioned and stable for more than 10 weeks post-operatively. Nonetheless, it is likely that the turbulent forces of the phacoemulsification process further disrupted an already weak set of zonular fibers. Dehiscence of these fibers and the fibrotic changes found in the anterior capsule are likely to have contributed to the development of severe capsule contraction and intraocular lens subluxation in this patient. Again, it is possible that a tear in the posterior capsule was created during surgery or from asymmetrical placement of the intraocular lens. However, no tear was detected visually and there was no prolapse of vitreous into the posterior chamber. Additionally, the correct placement of the intraocular lens was confirmed intra-operatively as well as on multiple post-operative visits. Thus, severe capsular contraction combined with anterior vitreous degeneration and zonular fiber weakness provides the most plausible mechanism of lens subluxation. Conclusion ========== Although the occurrence of posterior lens subluxation following phacoemulsification and intraocular lens placement is not a common event \[[@B3]\], it is a complication that should be discussed with patients with RP undergoing cataract surgery given its ability to cause dramatic consequences. Furthermore, careful slit-lamp examination is essential preoperatively to detect any zonular weakness or loss. If this weakness is present, consideration should be given as to the method of cataract extraction that would best preserve zonule fiber integrity and limit the risk of posterior capsule tears. For example, a chopping technique may be preferred to reduce zonular stress. In addition, gentle hydrodissection can also be employed to decrease stress on the zonules during surgery. Consideration should be given to using a capsular tension ring prophylactically in the fellow eye in order to help prevent a similar event. Consent ======= Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= DN gathered the data, performed the literature review, and edited the manuscript. FT and AI were major contributors in writing the manuscript. All authors read and approved the final manuscript.	PubMed Central	2024-06-05T04:04:19.019273	2011-2-14	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052192/", "journal": "J Med Case Reports. 2011 Feb 14; 5:65", "authors": [ { "first": "Dany M", "last": "Najjar" }, { "first": "Ann O", "last": "Igbre" }, { "first": "Frank F", "last": "Tsai" } ] }
PMC3052193	Introduction ============ Extremity casts are frequently applied for routine immobilization for many acute fractures. The period of immobilization varies according to the patient and the fracture. For example, a non-operatively treated tibial fracture is rarely immobilized for longer than six months. Total contact casting has been used in the treatment of Charcot\'s neuropathy for periods of up to one year \[[@B1]\]. We report a case of a below knee cast removal after 28 months. Case presentation ================= When she was 40 years old, a Caucasian woman underwent bunion surgery for pain whilst ambulating. The wounds healed without complication but she went on to develop mechanical allodynia, intermittent swelling and a bluish discoloration of the foot, consistent with a diagnosis of type 1 complex regional pain syndrome. She received many different treatments for continued pain over the subsequent years. Drug therapies using pregabalin, strong opiates and epidural analgesia were not fully successful and she was offered a below knee cast as a temporizing measure. There was no pre-existing psychiatric diagnosis but the patient developed a psychological dependence upon this cast. She was reluctant to have it removed, believing that her pain remained inadequately treated. She failed to attend several appointments at the pain clinic. When she did return, the anesthetists asked for orthopaedic assistance to remove her cast. By this point she was 45 years old and had spent the previous 28 months in the same below knee cast. She was no longer taking regular analgesia but was unable to tolerate anyone touching her leg and therefore received a general anesthetic to facilitate the cast removal. The cast was found to be intact, despite having been worn for such a long period. This can be explained by the fact that she had been using crutches and the plaster was reinforced with a heel stirrup. The resin surface was filthy (Figure [1](#F1){ref-type="fig"}). The toes were swollen and erythematous with thick scales in the web spaces; the toenails showed evidence of onychocryptosis and onychogryphosis and had not been cut. The deep cotton bandages were intact but appeared soiled on removal of the cast. The exposed leg was covered in thick yellow skin scales (Figure [2](#F2){ref-type="fig"}) which were easily exfoliated by hand (Figure [3](#F3){ref-type="fig"}). There were no significant areas of skin loss with integument intact over bony protuberances. Dense heel callosities were removed with a sharp blade. Closer inspection of the skin surface revealed small pitted ulcers 1-2 mm in diameter replacing the normal skin pores. Healthy pink granulation tissue was seen at the base of these ulcers which appeared clean and were not infected (Figure [4](#F4){ref-type="fig"}). They did not bleed on palpation and required no dressing. Some superficial telangiectasia were also noted on the anterior aspect of the ankle joint which were not present elsewhere on her limbs. There was no change in skin pigmentation. The leg circumferences were reduced by 5.5 cm at the calf and 1.5 cm at the ankle when compared to the normal leg. Passive dorsiflexion was symmetrically zero degrees. Passive plantar flexion was 30° in the cast leg and 40° in the normal leg. Her passive knee movements were normal. Doppler ultrasound showed good flow at the dorsalis pedis and posterior tibial pulses. Swabs, skin and toenails sent at time of the removal of the cast showed no growth of any organisms or fungal species. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Photograph of below knee cast prior to removal. ::: ![](1752-1947-5-74-1) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### Photograph demonstrating the appearance of leg after cast removal. ::: ![](1752-1947-5-74-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### Photograph showing yellow scales being exfoliated by hand. ::: ![](1752-1947-5-74-3) ::: ::: {#F4 .fig} Figure 4 ::: {.caption} ###### Photograph of showing small skin pits with pink granulation tissue following removal of scales. ::: ![](1752-1947-5-74-4) ::: She was later reviewed in the pain clinic. Her skin was healthy but her allodynia remained symptomatic. At this stage she was reluctant to pursue any further treatment. Discussion ========== Cast immobilization is a routine orthopedic treatment which is administered for short periods of time in order to limit its complications. Total contact casts are used for longer time periods but are changed quite often in order to monitor for complications \[[@B1]\]. A patient found to have been wearing the same cast for 28 months is extremely rare and there have been no previous cases reported in the literature. Patients who are known to be wear casts occasionally fail to attend for cast removal. In this scenario an awareness of the extent of potential complications is useful for this less compliant patient group. Halanski and Noonan \[[@B2]\] reviewing plaster cast complications describe joint stiffness, muscle atrophy, cartilage degradation, ligament weakening and disuse osteoporosis. Joint stiffness was present in this case but was relatively insubstantial with only 10° of relative reduction in passive plantar flexion. This finding suggests that any stiffness observed after cast removal may be attributable to capsular stretch pain. Muscle atrophy as a consequence of cast immobilization has been described \[[@B3]\] and was observed in this case where the leg circumference was substantially reduced. Research has attributed this change to an increase in both the resting inorganic phosphate concentration in skeletal muscle \[[@B4]\] and a change in the neural command of muscle contraction \[[@B5]\] with immobilization. Skin complications have been described following plaster cast immobilization. Ulceration occurs where there is insufficient padding over bony protuberances and excoriation is known to occur particularly in casts worn by children which have become soiled \[[@B6]\]. One case describes skin atrophy and hyperpigmentation thought to be a variant of stasis dermatitis \[[@B7]\]. In this case the skin under the dense scales was relatively healthy. The small and regularly distributed pitted ulcers occurred where each individual skin pore had become blocked. The tissue at the base of these pits was healthy. Conclusion ========== Prolonged cast immobilization is extremely rare and occurs in non compliant patients. This case demonstrates muscle atrophy which was anticipated. The stiffness of the ankle joint was not marked. Skin changes were minor with no substantial areas of ulceration or stasis dermatitis. Where patients choose to remain in their cast for prolonged duration the complications may only be minor. Competing interests =================== The authors declare that they have no competing interests. Consent ======= Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Authors\' contributions ======================= CFY and DWE reviewed the patient and performed the operation. SE researched for previous case reports and evidence. HI documented and described the findings. HI, SE and DWE contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript.	PubMed Central	2024-06-05T04:04:19.020013	2011-2-22	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052193/", "journal": "J Med Case Reports. 2011 Feb 22; 5:74", "authors": [ { "first": "Helen", "last": "Ingoe" }, { "first": "Sarah", "last": "Eastwood" }, { "first": "David W", "last": "Elson" }, { "first": "Claire F", "last": "Young" } ] }

PMC3052094

Related literature {#sec1} ================== For background literature concerning compounds of alkyl carboxylic acids and primary alkyl amines, see: Backlund *et al.* (1994[@bb3], 1997[@bb2]); Karlsson *et al.* (2000[@bb6], 2001[@bb7]); Kohler *et al.* (1972[@bb10]); Kohler, Atrops, *et al.* (1981[@bb8]); Kohler, Gopal, *et al.* (1981[@bb9]). For a description of the 'subcell' associated with the packing of the *n*-alkyl chains, see: Dorset (2005[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~24~N^+^·C~8~H~15~O~2~ ^−^*M* *~r~* = 301.50Monoclinic,*a* = 5.5526 (2) Å*b* = 44.489 (2) Å*c* = 8.0931 (4) Åβ = 100.788 (3)°*V* = 1963.90 (15) Å^3^*Z* = 4Mo *K*α radiationμ = 0.06 mm^−1^*T* = 180 K0.35 × 0.18 × 0.02 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (*SORTAV*; Blessing, 1995[@bb4]) *T* ~min~ = 0.773, *T* ~max~ = 1.0005524 measured reflections2233 independent reflections1438 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.053θ~max~ = 22.0° ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.051*wR*(*F* ^2^) = 0.128*S* = 1.022233 reflections202 parameters3 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.13 e Å^−3^Δρ~min~ = −0.17 e Å^−3^ {#d5e536} Data collection: *COLLECT* (Nonius, 1998[@bb12]); cell refinement: *SCALEPACK* (Otwinowski & Minor, 1997[@bb13]); data reduction: *DENZO* (Otwinowski & Minor, 1997[@bb13]) and *SCALEPACK*; program(s) used to solve structure: *SIR92* (Altomare *et al.*, 1994[@bb1]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb14]); molecular graphics: *Mercury* (Macrae *et al.*, 2008[@bb11]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005125/lh5207sup1.cif](http://dx.doi.org/10.1107/S1600536811005125/lh5207sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005125/lh5207Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005125/lh5207Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5207&file=lh5207sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5207sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5207&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5207](http://scripts.iucr.org/cgi-bin/sendsup?lh5207)). We thank the Department of Chemistry and the BP Institute for financial and technical assistance, and Dr John E. Davies for collecting the X-ray data. Comment ======= The combination of alkyl carboxylic acids and primary alkyl amines is of continuing interest both in the bulk and in adsorbed monolayers. There is mainly spectroscopic evidence that a number of stoichiometric complexes can form, depending upon the molecular structure: combinations AB (1 acid: 1 amine), A~2~B and A~3~B have been reported (Backlund *et al.*, 1994; Backlund *et al.*, 1997; Karlsson *et al.*, 2000; Karlsson *et al.*, 2001; Kohler, Atrops *et al.*, 1981; Kohler, Gopal *et al.*, 1981; Kohler *et al.*, 1972). Interestingly, similar complexes have not been reported on the amine-rich side of the phase diagram. The precise nature of the complexation is still a matter of debate, but hydrogen bonding between the species is obviously strongly implicated and different structures have been proposed on this basis. However, we are not aware of any single-crystal diffraction studies for these materials. The absence of reported single-crystal data for this class of complexes is probably attributable to difficulties in obtaining suitable crystals. Our various crystallization attempts have consistently failed, and our discovery of the crystal used for this study was serendipitous. The crystal was a thin plate that diffracted weakly, and data could be measured only to 0.95 Å resolution. Nonetheless, the data are adequate to localize the H atoms associated with the ammonium group, and these H atoms could be refined satisfactorily with restrained N---H bond lengths and individual isotropic displacement parameters. The C---O bond lengths of 1.269 (3) and 1.253 (3) Å are also consistent with proton transfer to yield a carboxylate anion. Both molecules adopt essentially fully extended conformations (*i.e.* the torsion angles along the main chain are all close to 180°), although the decylammonium chain is clearly disorted from planarity (Fig. 1). As a measure of this distortion, we note that the terminal C atom of the chain (C10) lies 1.43 (1) Å from the mean plane defined by atoms C1, C2 and C3. As might be expected, the crystal structure is layered, with the hydrophilic sections accommodated around the glide planes parallel to (010) at *y* = 1/4 and 3/4 (Fig. 2). The hydrogen bonding between the ammonium groups and carboxylate anions (Table 1) defines a 2-D network comprising 6-membered rings (Fig. 3). Projection along the *n*-alkyl chains of the molecules reveals an approximately orthorhombic \"subcell\" with approximate dimensions 5.1 × 7.3 Å (the third dimension being the translation of *ca* 2.54 Å along the *n*-alkyl chain). The plane through the C atoms of the *n*-alkyl chain of each octanoate anion lies almost perpendicular to the planes of the *n*-alkyl chains of the ammonium cations (Fig. 4). This is a common subcell arrangement for long-chain *n*-alkyl compounds (Dorset, 2005). The distortion from planarity of the *n*-alkyl chain in the decylammonium cation serves to accommodate it between two neighbouring octanoic acid molecules \[symmetry codes: 1 + *x*,0.5 - *y*,-1/2 + *z* and 1 + *x*,0.5 - *y*,1/2 + *z*\], optimizing dispersion interactions along the length of the *n*-alkyl chains within the constraints imposed by the hydrogen-bonding geometry. At the interface between layers (*i.e.* in the (020) planes of the structure) the methyl groups of the decylammonium cations meet the methyl groups of the octanoate anions to form C···C contacts of 3.972 (4) Å, with the H atoms approximately eclipsed. Experimental {#experimental} ============ Octanoic acid (99%) and decylamine (99.5%) were obtained from Sigma Aldrich and used without further purification. A number of solution and melt methods were attempted to grow a single-crystal of sufficient dimensions and quality, but all were unsuccessful. A crystal was finally obtained serendipidously by growth from the vapour when poorly sealed vessels containing each of the individual components were stored together inside a small container (1 litre volume) in a glove bag initially purged with N~2~ and left undisturbed for a number of weeks. Crystal growth was observed on most of the plastic surfaces inside the storage container but principally on the polypropylene cap of the decylamine bottle. Elemental analysis found for the bulk sample: C 72.4, H 13.1, N, 4.8%; calculated C 71.7, H 13.0, N 4.7%. Refinement {#refinement} ========== The crystal diffracted relatively weakly, and data were collected to a maximum θ of 22° (0.95 Å resolution). Approximately 65% of data were observed at the 2σ level to this limit. The data are adequate to support location and refinement of the H atoms associated with the ammonium group. These were refined with N---H distances restrained to 0.91 (1) Å, and with individual *U*~iso~ values refined in the range 0.061 (10)--0.064 (10) Å^2^. All other H atoms were placed geometrically and refined as riding with C---H = 0.99 (CH~2~) or 0.98 (CH~3~) Å, and with *U*~iso~(H) = 1.2 or 1.5*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure with displacement ellipsoids drawn at 50% probability for non-H atoms. ::: ![](e-67-0o655-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Projection along the c axis showing the layered structure. H atoms are omitted and the N atoms of the NH3+ groups are highlighted as spheres. ::: ![](e-67-0o655-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Section of the structure projected along the c axis, showing the hydrogen-bond topology (dashed lines). Only the C---CO2- and C---NH3+ groups are shown. All other C and H atoms are omitted. ::: ![](e-67-0o655-fig3) ::: ::: {#Fap4 .fig} Fig. 4. ::: {.caption} ###### Section of the structure projected approximately along the long axes of the n-alkyl chains, showing the orthorhombic \"subcell\" packing. The dimensions indicated for the subcell are approximate. The third dimension of the subcell refers to the translational repeat of ca 2.54 Å along the n-alkyl chain. See Dorset (2005). ::: ![](e-67-0o655-fig4) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e258 .table-wrap} --------------------------------- ---------------------------------------- C~10~H~24~N^+^·C~8~H~15~O~2~^−^ *F*(000) = 680 *M~r~* = 301.50 *D*~x~ = 1.020 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 29938 reflections *a* = 5.5526 (2) Å θ = 1.0--22.0° *b* = 44.489 (2) Å µ = 0.06 mm^−1^ *c* = 8.0931 (4) Å *T* = 180 K β = 100.788 (3)° Block, colourless *V* = 1963.90 (15) Å^3^ 0.35 × 0.18 × 0.02 mm *Z* = 4 --------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e398 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 1438 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.053 ω and φ scans θ~max~ = 22.0°, θ~min~ = 3.7° Absorption correction: multi-scan (*SORTAV*; Blessing, 1995) *h* = −5→5 *T*~min~ = 0.773, *T*~max~ = 1.000 *k* = −46→46 5524 measured reflections *l* = −8→8 2233 independent reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e514 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.051 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.128 H atoms treated by a mixture of independent and constrained refinement *S* = 1.02 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0647*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2233 reflections (Δ/σ)~max~ \< 0.001 202 parameters Δρ~max~ = 0.13 e Å^−3^ 3 restraints Δρ~min~ = −0.17 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e668 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e767 .table-wrap} ------ ------------- ------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ N1 0.6509 (4) 0.23800 (6) 0.6408 (3) 0.0368 (6) H1A 0.797 (3) 0.2475 (6) 0.635 (3) 0.064 (10)\* H1B 0.552 (4) 0.2520 (5) 0.681 (3) 0.061 (10)\* H1C 0.564 (4) 0.2308 (6) 0.540 (2) 0.063 (10)\* C1 0.7131 (5) 0.21366 (6) 0.7683 (3) 0.0376 (7) H1D 0.7889 0.2226 0.8776 0.045\* H1E 0.8346 0.2000 0.7330 0.045\* C2 0.4907 (5) 0.19598 (6) 0.7896 (3) 0.0443 (8) H2A 0.4128 0.1875 0.6794 0.053\* H2B 0.3712 0.2097 0.8271 0.053\* C3 0.5494 (5) 0.17059 (6) 0.9156 (3) 0.0453 (8) H3A 0.6910 0.1591 0.8902 0.054\* H3B 0.5984 0.1793 1.0296 0.054\* C4 0.3373 (5) 0.14915 (6) 0.9157 (3) 0.0479 (8) H4A 0.1991 0.1606 0.9465 0.057\* H4B 0.2827 0.1415 0.7999 0.057\* C5 0.3925 (5) 0.12257 (7) 1.0335 (3) 0.0469 (8) H5A 0.4359 0.1301 1.1504 0.056\* H5B 0.5369 0.1118 1.0077 0.056\* C6 0.1810 (5) 0.10059 (6) 1.0222 (3) 0.0466 (8) H6A 0.0387 0.1113 1.0520 0.056\* H6B 0.1335 0.0938 0.9042 0.056\* C7 0.2351 (5) 0.07329 (7) 1.1342 (4) 0.0511 (8) H7A 0.2901 0.0801 1.2516 0.061\* H7B 0.3725 0.0621 1.1009 0.061\* C8 0.0211 (5) 0.05205 (6) 1.1290 (4) 0.0505 (8) H8A −0.1158 0.0633 1.1630 0.061\* H8B −0.0345 0.0453 1.0114 0.061\* C9 0.0743 (6) 0.02465 (7) 1.2396 (4) 0.0648 (10) H9A 0.1386 0.0313 1.3563 0.078\* H9B 0.2044 0.0128 1.2015 0.078\* C10 −0.1459 (6) 0.00445 (7) 1.2403 (4) 0.0763 (11) H10A −0.0969 −0.0128 1.3145 0.114\* H10B −0.2086 −0.0027 1.1258 0.114\* H10C −0.2744 0.0158 1.2809 0.114\* O1 0.4243 (3) 0.28030 (4) 0.81491 (19) 0.0384 (5) O2 0.1023 (3) 0.26380 (4) 0.6328 (2) 0.0424 (5) C11 0.1952 (5) 0.27876 (6) 0.7601 (3) 0.0333 (7) C12 0.0316 (4) 0.29610 (6) 0.8566 (3) 0.0358 (7) H12A 0.0647 0.2891 0.9748 0.043\* H12B −0.1413 0.2912 0.8086 0.043\* C13 0.0628 (5) 0.33012 (6) 0.8553 (3) 0.0368 (7) H13A 0.2345 0.3353 0.9050 0.044\* H13B 0.0292 0.3374 0.7376 0.044\* C14 −0.1081 (5) 0.34575 (6) 0.9533 (3) 0.0400 (7) H14A −0.0733 0.3381 1.0702 0.048\* H14B −0.2785 0.3400 0.9038 0.048\* C15 −0.0940 (5) 0.37981 (6) 0.9594 (3) 0.0419 (8) H15A 0.0749 0.3859 1.0110 0.050\* H15B −0.1288 0.3877 0.8431 0.050\* C16 −0.2713 (5) 0.39370 (6) 1.0579 (3) 0.0447 (8) H16A −0.2394 0.3851 1.1728 0.054\* H16B −0.4400 0.3879 1.0041 0.054\* C17 −0.2585 (5) 0.42763 (6) 1.0715 (4) 0.0527 (8) H17A −0.2878 0.4363 0.9568 0.063\* H17B −0.0911 0.4335 1.1277 0.063\* C18 −0.4416 (5) 0.44107 (7) 1.1682 (4) 0.0704 (10) H18A −0.4233 0.4630 1.1721 0.106\* H18B −0.4115 0.4330 1.2830 0.106\* H18C −0.6084 0.4359 1.1119 0.106\* ------ ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1576 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ N1 0.0325 (15) 0.0405 (16) 0.0377 (16) −0.0004 (14) 0.0076 (13) −0.0051 (14) C1 0.0383 (16) 0.0406 (18) 0.0332 (15) 0.0040 (15) 0.0051 (12) 0.0004 (15) C2 0.0379 (17) 0.051 (2) 0.0441 (17) −0.0020 (16) 0.0070 (13) 0.0085 (16) C3 0.0410 (17) 0.052 (2) 0.0412 (17) −0.0032 (16) 0.0038 (14) 0.0024 (16) C4 0.0411 (17) 0.059 (2) 0.0427 (18) −0.0047 (17) 0.0053 (14) 0.0068 (17) C5 0.0435 (18) 0.052 (2) 0.0449 (17) −0.0015 (16) 0.0069 (14) 0.0087 (17) C6 0.0470 (18) 0.048 (2) 0.0448 (18) 0.0012 (16) 0.0081 (14) 0.0064 (16) C7 0.0499 (19) 0.049 (2) 0.0553 (19) 0.0005 (16) 0.0115 (15) 0.0081 (17) C8 0.0524 (19) 0.045 (2) 0.056 (2) −0.0044 (17) 0.0152 (15) 0.0033 (17) C9 0.067 (2) 0.056 (2) 0.076 (2) −0.001 (2) 0.0242 (18) 0.013 (2) C10 0.080 (3) 0.057 (2) 0.100 (3) −0.010 (2) 0.036 (2) 0.007 (2) O1 0.0247 (11) 0.0510 (13) 0.0390 (10) 0.0009 (9) 0.0048 (8) −0.0016 (10) O2 0.0360 (11) 0.0542 (14) 0.0364 (11) −0.0062 (10) 0.0049 (9) −0.0129 (11) C11 0.0300 (17) 0.0360 (18) 0.0349 (16) 0.0013 (15) 0.0084 (13) 0.0116 (16) C12 0.0306 (15) 0.0392 (18) 0.0381 (16) −0.0013 (14) 0.0080 (13) −0.0008 (14) C13 0.0333 (15) 0.0378 (18) 0.0392 (16) −0.0006 (14) 0.0065 (12) 0.0036 (14) C14 0.0389 (16) 0.039 (2) 0.0441 (16) 0.0028 (15) 0.0124 (13) 0.0000 (15) C15 0.0389 (17) 0.041 (2) 0.0472 (17) 0.0004 (15) 0.0105 (14) −0.0029 (15) C16 0.0452 (18) 0.040 (2) 0.0492 (18) 0.0021 (16) 0.0095 (14) −0.0030 (16) C17 0.0494 (19) 0.045 (2) 0.063 (2) 0.0036 (17) 0.0077 (16) −0.0066 (17) C18 0.065 (2) 0.059 (2) 0.088 (3) 0.0103 (19) 0.0179 (19) −0.015 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1975 .table-wrap} -------------------- ------------ ----------------------- ------------ N1---C1 1.491 (3) C9---H9A 0.990 N1---H1A 0.92 (1) C9---H9B 0.990 N1---H1B 0.93 (1) C10---H10A 0.980 N1---H1C 0.92 (1) C10---H10B 0.980 C1---C2 1.501 (3) C10---H10C 0.980 C1---H1D 0.990 O1---C11 1.268 (3) C1---H1E 0.990 O2---C11 1.253 (3) C2---C3 1.516 (3) C11---C12 1.515 (3) C2---H2A 0.990 C12---C13 1.524 (3) C2---H2B 0.990 C12---H12A 0.990 C3---C4 1.516 (3) C12---H12B 0.990 C3---H3A 0.990 C13---C14 1.515 (3) C3---H3B 0.990 C13---H13A 0.990 C4---C5 1.514 (4) C13---H13B 0.990 C4---H4A 0.990 C14---C15 1.517 (3) C4---H4B 0.990 C14---H14A 0.990 C5---C6 1.518 (3) C14---H14B 0.990 C5---H5A 0.990 C15---C16 1.510 (3) C5---H5B 0.990 C15---H15A 0.990 C6---C7 1.511 (4) C15---H15B 0.990 C6---H6A 0.990 C16---C17 1.514 (4) C6---H6B 0.990 C16---H16A 0.990 C7---C8 1.513 (4) C16---H16B 0.990 C7---H7A 0.990 C17---C18 1.517 (4) C7---H7B 0.990 C17---H17A 0.990 C8---C9 1.508 (4) C17---H17B 0.990 C8---H8A 0.990 C18---H18A 0.980 C8---H8B 0.990 C18---H18B 0.980 C9---C10 1.518 (4) C18---H18C 0.980 C1---N1---H1A 105.9 (17) C8---C9---H9B 108.7 C1---N1---H1B 108.7 (18) C10---C9---H9B 108.7 H1A---N1---H1B 107 (3) H9A---C9---H9B 107.6 C1---N1---H1C 111.8 (18) C9---C10---H10A 109.5 H1A---N1---H1C 116 (2) C18^i^---C10---H10A 53.7 H1B---N1---H1C 107 (2) C9---C10---H10B 109.5 N1---C1---C2 111.8 (2) C18^i^---C10---H10B 79.7 N1---C1---H1D 109.3 H10A---C10---H10B 109.5 C2---C1---H1D 109.3 C9---C10---H10C 109.5 N1---C1---H1E 109.3 H10A---C10---H10C 109.5 C2---C1---H1E 109.3 H10B---C10---H10C 109.5 H1D---C1---H1E 107.9 O2---C11---O1 123.2 (2) C1---C2---C3 112.9 (2) O2---C11---C12 120.0 (2) C1---C2---H2A 109.0 O1---C11---C12 116.8 (3) C3---C2---H2A 109.0 C11---C12---C13 115.0 (2) C1---C2---H2B 109.0 C11---C12---H12A 108.5 C3---C2---H2B 109.0 C13---C12---H12A 108.5 H2A---C2---H2B 107.8 C11---C12---H12B 108.5 C4---C3---C2 113.6 (2) C13---C12---H12B 108.5 C4---C3---H3A 108.9 H12A---C12---H12B 107.5 C2---C3---H3A 108.9 C14---C13---C12 111.7 (2) C4---C3---H3B 108.9 C14---C13---H13A 109.3 C2---C3---H3B 108.9 C12---C13---H13A 109.3 H3A---C3---H3B 107.7 C14---C13---H13B 109.3 C5---C4---C3 115.2 (2) C12---C13---H13B 109.3 C5---C4---H4A 108.5 H13A---C13---H13B 107.9 C3---C4---H4A 108.5 C13---C14---C15 116.2 (2) C5---C4---H4B 108.5 C13---C14---H14A 108.2 C3---C4---H4B 108.5 C15---C14---H14A 108.2 H4A---C4---H4B 107.5 C13---C14---H14B 108.2 C4---C5---C6 113.7 (2) C15---C14---H14B 108.2 C4---C5---H5A 108.8 H14A---C14---H14B 107.4 C6---C5---H5A 108.8 C16---C15---C14 113.0 (2) C4---C5---H5B 108.8 C16---C15---H15A 109.0 C6---C5---H5B 108.8 C14---C15---H15A 109.0 H5A---C5---H5B 107.7 C16---C15---H15B 109.0 C7---C6---C5 114.6 (2) C14---C15---H15B 109.0 C7---C6---H6A 108.6 H15A---C15---H15B 107.8 C5---C6---H6A 108.6 C15---C16---C17 114.8 (2) C7---C6---H6B 108.6 C15---C16---H16A 108.6 C5---C6---H6B 108.6 C17---C16---H16A 108.6 H6A---C6---H6B 107.6 C15---C16---H16B 108.6 C6---C7---C8 114.7 (2) C17---C16---H16B 108.6 C6---C7---H7A 108.6 H16A---C16---H16B 107.5 C8---C7---H7A 108.6 C16---C17---C18 113.8 (2) C6---C7---H7B 108.6 C16---C17---H17A 108.8 C8---C7---H7B 108.6 C18---C17---H17A 108.8 H7A---C7---H7B 107.6 C16---C17---H17B 108.8 C9---C8---C7 115.0 (2) C18---C17---H17B 108.8 C9---C8---H8A 108.5 H17A---C17---H17B 107.7 C7---C8---H8A 108.5 C17---C18---H18A 109.5 C9---C8---H8B 108.5 C17---C18---H18B 109.5 C7---C8---H8B 108.5 H18A---C18---H18B 109.5 H8A---C8---H8B 107.5 C17---C18---H18C 109.5 C8---C9---C10 114.3 (3) H18A---C18---H18C 109.5 C8---C9---H9A 108.7 H18B---C18---H18C 109.5 C10---C9---H9A 108.7 N1---C1---C2---C3 178.6 (2) O2---C11---C12---C13 −115.7 (3) C1---C2---C3---C4 −169.5 (2) O1---C11---C12---C13 64.4 (3) C2---C3---C4---C5 177.0 (2) C11---C12---C13---C14 179.6 (2) C3---C4---C5---C6 −176.4 (2) C12---C13---C14---C15 −179.6 (2) C4---C5---C6---C7 177.9 (2) C13---C14---C15---C16 179.4 (2) C5---C6---C7---C8 177.4 (2) C14---C15---C16---C17 178.3 (2) C6---C7---C8---C9 179.6 (2) C15---C16---C17---C18 178.9 (2) C7---C8---C9---C10 176.8 (3) -------------------- ------------ ----------------------- ------------ ::: Symmetry codes: (i) −*x*−1, *y*−1/2, −*z*+5/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2878 .table-wrap} -------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1B···O1 0.93 (1) 1.89 (1) 2.788 (3) 164 (2) N1---H1C···O1^ii^ 0.92 (1) 1.91 (1) 2.821 (3) 170 (2) N1---H1A···O2^iii^ 0.92 (1) 1.85 (1) 2.768 (3) 175 (3) -------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (ii) *x*, −*y*+1/2, *z*−1/2; (iii) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- ---------- ---------- ----------- ------------- N1---H1*B*⋯O1 0.93 (1) 1.89 (1) 2.788 (3) 164 (2) N1---H1*C*⋯O1^i^ 0.92 (1) 1.91 (1) 2.821 (3) 170 (2) N1---H1*A*⋯O2^ii^ 0.92 (1) 1.85 (1) 2.768 (3) 175 (3) Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.396533

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052094/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o655", "authors": [ { "first": "Andrew E.", "last": "Jefferson" }, { "first": "Chenguang", "last": "Sun" }, { "first": "Andrew D.", "last": "Bond" }, { "first": "Stuart M.", "last": "Clarke" } ] }

PMC3052095

Related literature {#sec1} ================== For related structures with an indane group linked to a pyridine derivative through a C---O---C bridge, see: Dinçer *et al.* (2004[@bb3]); Lifshits *et al.* (2008[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~13~BrN~2~O*M* *~r~* = 305.17Monoclinic,*a* = 11.3944 (18) Å*b* = 9.4515 (15) Å*c* = 12.438 (2) Åβ = 110.678 (2)°*V* = 1253.2 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 3.27 mm^−1^*T* = 100 K0.21 × 0.16 × 0.08 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2001[@bb1]) *T* ~min~ = 0.547, *T* ~max~ = 0.78023669 measured reflections2942 independent reflections2595 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.046 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.023*wR*(*F* ^2^) = 0.054*S* = 1.032942 reflections163 parametersH-atom parameters constrainedΔρ~max~ = 0.38 e Å^−3^Δρ~min~ = −0.30 e Å^−3^ {#d5e405} Data collection: *APEX2* (Bruker, 2007[@bb2]); cell refinement: *SAINT* (Bruker, 2007[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb5]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005332/rz2555sup1.cif](http://dx.doi.org/10.1107/S1600536811005332/rz2555sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005332/rz2555Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005332/rz2555Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2555&file=rz2555sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2555sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2555&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2555](http://scripts.iucr.org/cgi-bin/sendsup?rz2555)). Comment ======= The present study confirmed the expected structure of the title compound, the product of reaction between indan-1-yl methanesulfonate and 2-amino-5-bromopyridin-3-ol in the presence of caesium carbonate (Fig. 1). All C atoms of the indane fragment with the exception of C7 are coplanar within 0.03 Å; the latter atom is displaced by 0.206 (2) Å from the mean plane based on all the remaining atoms of the bicyclic system. The O1 atom deviates from this plane by 1.008 (2) Å in the same direction as the C7 atom. The central C2---O1---C6 bridge is in fact coplanar with the pyridine ring so that the N1/C1/C2/C3/C3/C4/C5/O1/C6 fragment is planar within 0.01 Å and its plane forms the dihedral angle of 57.6 (3)° with the above mentioned indane plane. It is noteworthy, that general conformations of a few other structurally studied molecules featuring indane group linked to pyridine derivatives through the C---O---C bridge (Dinçer *et al.*, 2004; Lifshits *et al.*, 2008) bear close resemblance to that of the molecule of the title compound. The N2---H2NA···N1^i^ bonds \[symmetry code (i): 2 - *x*, 1 - *y*, 2 - *z*\] (Table 1) link molecules in the crystal of the title compounds into centrosymmetric dimers (Fig. 2). One more intermolecular contact N2---H2NB···Br1^ii^ \[symmetry code (ii): *x* - 1/2, 1.5 - *y*, *z* - 1/2\] may also play certain role in the stability of the packing, although corresponding interaction seems to be too weak to be qualified as one more independent H-bond. Experimental {#experimental} ============ To a solution of 2-amino-5-bromopyridin-3-ol (1.640 g, 8.48 mmol) in 42 ml of DMF was added 2,3-dihydro-1*H*-inden-1-yl methanesulfonate (0.9 g, 4.24 mmol) and caesium carbonate (1.380 g, 4.24 mmol) and heated to 60°C overnight. The reaction mixture was quenched with water and the aqueous layer was extracted with EtOAc (3 *x* 20 ml). The organic layers were combined, dried over MgSO~4~, filtered and concentrated. The product was purified by flash chromatography (silica gel, 10--50% EtOAc/heptane) to give 525 mg (46%) 5-bromo-3-(2,3-dihydro-1*H*-inden-1-yloxy)pyridin-2-amine as a white solid. The colorless crystals were grown by slow cooling of the solution of the title compound in boiling dichloroetane. Refinement {#refinement} ========== All H atoms were placed in geometrically calculated positions (N---H 0.88 Å, C---H 0.95 Å, 0.99 Å and 1.00 Å for aromatic, methylene and methine groups respectively) and included in the refinement in the riding motion approximation. The *U*~iso~(H) were set to 1.2*U*~eq~ of the carrying atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound, showing 50% probability displacement ellipsoids. H atoms are drawn as circles of arbitrary small radius. ::: ![](e-67-0o650-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Packing diagram of the title compound viewed down the b axis. H-bonds are shown as dashed lines. ::: ![](e-67-0o650-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e157 .table-wrap} ------------------------- --------------------------------------- C~14~H~13~BrN~2~O *F*(000) = 616 *M~r~* = 305.17 *D*~x~ = 1.617 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 9797 reflections *a* = 11.3944 (18) Å θ = 2.8--27.7° *b* = 9.4515 (15) Å µ = 3.27 mm^−1^ *c* = 12.438 (2) Å *T* = 100 K β = 110.678 (2)° Block, colorless *V* = 1253.2 (3) Å^3^ 0.21 × 0.16 × 0.08 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e285 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2942 independent reflections Radiation source: fine-focus sealed tube 2595 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.046 φ and ω scans θ~max~ = 28.3°, θ~min~ = 2.1° Absorption correction: multi-scan (*SADABS*; Bruker, 2001) *h* = −15→14 *T*~min~ = 0.547, *T*~max~ = 0.780 *k* = −12→12 23669 measured reflections *l* = −16→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e402 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.023 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.054 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0191*P*)^2^ + 0.7815*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2942 reflections (Δ/σ)~max~ = 0.001 163 parameters Δρ~max~ = 0.38 e Å^−3^ 0 restraints Δρ~min~ = −0.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e559 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e658 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 1.235622 (16) 1.080477 (17) 1.070416 (15) 0.02063 (6) O1 0.95752 (11) 0.77404 (12) 0.71352 (10) 0.0192 (3) N1 1.06647 (13) 0.68706 (14) 1.01301 (12) 0.0179 (3) N2 0.95112 (15) 0.56292 (15) 0.84811 (13) 0.0227 (3) H2NA 0.9477 0.4894 0.8903 0.027\* H2NB 0.9150 0.5591 0.7729 0.027\* C1 1.01219 (16) 0.68247 (17) 0.89913 (14) 0.0163 (3) C2 1.01793 (15) 0.79884 (17) 0.82822 (14) 0.0165 (3) C3 1.08206 (16) 0.91835 (17) 0.87805 (15) 0.0171 (3) H3 1.0868 0.9979 0.8331 0.020\* C4 1.14048 (16) 0.91900 (16) 0.99797 (15) 0.0161 (3) C5 1.13089 (16) 0.80499 (17) 1.06228 (15) 0.0180 (3) H5 1.1704 0.8086 1.1435 0.022\* C6 0.95743 (16) 0.88611 (17) 0.63483 (14) 0.0168 (3) H6 1.0431 0.9283 0.6559 0.020\* C7 0.85977 (17) 1.00246 (18) 0.62819 (15) 0.0209 (4) H7A 0.8003 0.9696 0.6647 0.025\* H7B 0.9019 1.0892 0.6681 0.025\* C8 0.78992 (16) 1.03247 (17) 0.49914 (15) 0.0184 (3) H8A 0.6983 1.0385 0.4815 0.022\* H8B 0.8193 1.1220 0.4759 0.022\* C9 0.82218 (16) 0.90756 (16) 0.43914 (15) 0.0164 (3) C10 0.91601 (15) 0.82524 (17) 0.51553 (14) 0.0163 (3) C11 0.96492 (16) 0.70772 (17) 0.47841 (15) 0.0200 (4) H11 1.0284 0.6517 0.5316 0.024\* C12 0.91930 (17) 0.67388 (18) 0.36230 (16) 0.0225 (4) H12 0.9523 0.5947 0.3353 0.027\* C13 0.82497 (17) 0.75614 (19) 0.28514 (15) 0.0224 (4) H13 0.7942 0.7322 0.2059 0.027\* C14 0.77560 (17) 0.87233 (18) 0.32274 (15) 0.0204 (4) H14 0.7109 0.9272 0.2699 0.025\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1068 .table-wrap} ----- -------------- ------------- -------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.02147 (10) 0.01833 (9) 0.01970 (10) −0.00397 (7) 0.00432 (7) −0.00082 (6) O1 0.0247 (7) 0.0182 (6) 0.0125 (6) −0.0039 (5) 0.0038 (5) 0.0033 (4) N1 0.0195 (7) 0.0179 (7) 0.0156 (7) −0.0011 (6) 0.0055 (6) 0.0024 (5) N2 0.0298 (9) 0.0198 (7) 0.0140 (7) −0.0074 (6) 0.0021 (6) 0.0035 (6) C1 0.0150 (8) 0.0174 (7) 0.0168 (8) 0.0007 (6) 0.0058 (7) 0.0029 (6) C2 0.0149 (8) 0.0209 (8) 0.0137 (8) 0.0019 (6) 0.0052 (6) 0.0030 (6) C3 0.0178 (8) 0.0168 (8) 0.0172 (9) 0.0013 (6) 0.0070 (7) 0.0039 (6) C4 0.0141 (8) 0.0155 (7) 0.0184 (8) −0.0002 (6) 0.0053 (7) −0.0013 (6) C5 0.0187 (9) 0.0201 (8) 0.0145 (8) 0.0009 (7) 0.0049 (7) 0.0003 (6) C6 0.0195 (9) 0.0169 (7) 0.0140 (8) −0.0022 (6) 0.0057 (7) 0.0033 (6) C7 0.0257 (10) 0.0202 (8) 0.0161 (9) 0.0025 (7) 0.0067 (7) 0.0009 (7) C8 0.0184 (9) 0.0171 (8) 0.0180 (9) 0.0002 (6) 0.0045 (7) 0.0020 (6) C9 0.0170 (8) 0.0158 (7) 0.0166 (8) −0.0037 (6) 0.0062 (7) 0.0018 (6) C10 0.0159 (8) 0.0177 (8) 0.0158 (8) −0.0032 (6) 0.0061 (7) 0.0012 (6) C11 0.0179 (9) 0.0193 (8) 0.0225 (9) −0.0002 (7) 0.0067 (7) 0.0013 (7) C12 0.0233 (9) 0.0200 (8) 0.0262 (10) −0.0048 (7) 0.0113 (8) −0.0068 (7) C13 0.0256 (10) 0.0258 (9) 0.0154 (9) −0.0086 (7) 0.0066 (7) −0.0050 (7) C14 0.0213 (9) 0.0199 (8) 0.0169 (9) −0.0040 (7) 0.0028 (7) 0.0029 (7) ----- -------------- ------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1416 .table-wrap} ------------------ ------------- ----------------- ------------- Br1---C4 1.9044 (16) C7---C8 1.545 (2) O1---C2 1.368 (2) C7---H7A 0.9900 O1---C6 1.4419 (19) C7---H7B 0.9900 N1---C1 1.331 (2) C8---C9 1.510 (2) N1---C5 1.356 (2) C8---H8A 0.9900 N2---C1 1.361 (2) C8---H8B 0.9900 N2---H2NA 0.8800 C9---C10 1.391 (2) N2---H2NB 0.8800 C9---C14 1.395 (2) C1---C2 1.426 (2) C10---C11 1.393 (2) C2---C3 1.369 (2) C11---C12 1.388 (3) C3---C4 1.402 (2) C11---H11 0.9500 C3---H3 0.9500 C12---C13 1.397 (3) C4---C5 1.369 (2) C12---H12 0.9500 C5---H5 0.9500 C13---C14 1.388 (3) C6---C10 1.504 (2) C13---H13 0.9500 C6---C7 1.546 (2) C14---H14 0.9500 C6---H6 1.0000 C2---O1---C6 117.49 (13) C6---C7---H7A 110.4 C1---N1---C5 118.79 (14) C8---C7---H7B 110.4 C1---N2---H2NA 120.0 C6---C7---H7B 110.4 C1---N2---H2NB 120.0 H7A---C7---H7B 108.6 H2NA---N2---H2NB 120.0 C9---C8---C7 104.11 (13) N1---C1---N2 119.49 (15) C9---C8---H8A 110.9 N1---C1---C2 121.84 (15) C7---C8---H8A 110.9 N2---C1---C2 118.66 (15) C9---C8---H8B 110.9 O1---C2---C3 127.25 (15) C7---C8---H8B 110.9 O1---C2---C1 113.39 (14) H8A---C8---H8B 109.0 C3---C2---C1 119.35 (15) C10---C9---C14 119.63 (16) C2---C3---C4 117.53 (15) C10---C9---C8 111.25 (15) C2---C3---H3 121.2 C14---C9---C8 129.04 (16) C4---C3---H3 121.2 C9---C10---C11 121.40 (16) C5---C4---C3 120.80 (15) C9---C10---C6 110.97 (14) C5---C4---Br1 120.25 (13) C11---C10---C6 127.55 (15) C3---C4---Br1 118.94 (12) C12---C11---C10 118.81 (16) N1---C5---C4 121.67 (16) C12---C11---H11 120.6 N1---C5---H5 119.2 C10---C11---H11 120.6 C4---C5---H5 119.2 C11---C12---C13 120.06 (16) O1---C6---C10 108.27 (13) C11---C12---H12 120.0 O1---C6---C7 112.76 (14) C13---C12---H12 120.0 C10---C6---C7 104.49 (14) C14---C13---C12 120.92 (16) O1---C6---H6 110.4 C14---C13---H13 119.5 C10---C6---H6 110.4 C12---C13---H13 119.5 C7---C6---H6 110.4 C13---C14---C9 119.18 (16) C8---C7---C6 106.45 (14) C13---C14---H14 120.4 C8---C7---H7A 110.4 C9---C14---H14 120.4 ------------------ ------------- ----------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1844 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N2---H2NA···N1^i^ 0.88 2.10 2.975 (2) 178 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+2, −*y*+1, −*z*+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- --------- ------- ----------- ------------- N2---H2*NA*⋯N1^i^ 0.88 2.10 2.975 (2) 178 Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.402344

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052095/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o650", "authors": [ { "first": "Sujin", "last": "Cho-Schultz" }, { "first": "John C.", "last": "Kath" }, { "first": "Curtis", "last": "Moore" }, { "first": "Arnold L.", "last": "Rheingold" }, { "first": "Alex", "last": "Yanovsky" } ] }

PMC3052096

Related literature {#sec1} ================== For other inorganic--organic hybrid materials based on polyoxidometalates with organic cations, see: Alizadeh *et al.* (2008*a* [@bb3],*b* [@bb2]); Nikpour *et al.* (2009[@bb8], 2010[@bb7]). For details of (H~2~O)~*n*~ cluster analysis, see: Aghabozorg *et al.* (2010[@bb1]). For background to pseudopolymorphism, see: Desiraju (2003[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~6~H~12~N~5~O)~3~\[W~12~(PO~4~)O~36~\]·6H~2~O*M* *~r~* = 3495.88Orthorhombic,*a* = 14.616 (3) Å*b* = 15.213 (3) Å*c* = 26.735 (6) Å*V* = 5944 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 23.27 mm^−1^*T* = 100 K0.12 × 0.11 × 0.06 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2005[@bb4]) *T* ~min~ = 0.078, *T* ~max~ = 0.24659635 measured reflections12321 independent reflections9617 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.159 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.052*wR*(*F* ^2^) = 0.104*S* = 1.0012321 reflections446 parameters6 restraintsH-atom parameters constrainedΔρ~max~ = 2.80 e Å^−3^Δρ~min~ = −2.72 e Å^−3^Absolute structure: Flack (1983[@bb6]), 5544 Friedel pairsFlack parameter: −0.041 (19) {#d5e926} Data collection: *APEX2* (Bruker, 2005[@bb4]); cell refinement: *SAINT* (Bruker, 2005[@bb4]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003734/wm2435sup1.cif](http://dx.doi.org/10.1107/S1600536811003734/wm2435sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003734/wm2435Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003734/wm2435Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2435&file=wm2435sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2435sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2435&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2435](http://scripts.iucr.org/cgi-bin/sendsup?wm2435)). The Islamic Azad University, Quchan Branch, Quchan, Iran is gratefully acknowledged for financial support of this research paper. Comment ======= In continuation of our previous studies of inorganic-organic hybrid materials based on polyoxidometalates (Alizadeh *et al.*, 2008*a*,*b*; Nikpour *et al.*, 2009), we report here on the structure of the title compound, \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^6H~2~O, (I), as a pseudopolymorph (different number of crystal water molecules; Desiraju, 2003) of \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^5H~2~O as reported by us previously (Nikpour *et al.*, 2010). The structure of (I) consists of one discrete anion \[(PO~4~)W~12~O~36~\]^3-^, three \[C~6~H~12~N~5~O\]^+^ cations and six water molecules of crystallisation. (Fig. 1). The anion in the title compound is of the well-known α-Keggin type consisting of four groups of W~3~O~10~ units. Each WO~6~ octahedron in such a unit shares edges with its neighbours. Four W~3~O~10~ units are linked together *via* corner-sharing WO~6~ octahedra to form a cage with a P atom located in the tetrahedrally surrounded centre. There are four kinds of oxygen atoms in the heteropolyanion, *viz*. four O atoms (O1c, O5c, O9c, O13c) that are bonded to the P atom and to three W atoms, twelve corner-sharing atoms Oc atom that bridge the different W~3~O~13~ units, twelve edge-sharing atoms Ob that bridge within the W~3~O~13~ units, and twelve terminal oxygen atoms Ot. In the organic cation, the 1*H*-tetrazole ring and the methylcarbon atom lie approximately in the same plane and the morpholine ring is in a chair configuration. In (I), all bond lengths and angles are normal and comparable with those observed in the pseudopolymorph with 5 crystal water molecules (Nikpour *et al.*, 2010)). The three organic cations in (I) show only minor differences with respect to bond lengths and angles. The molecular entities are linked together *via* an extensive network of N---H···O, N---H···N, O---H···O and O---H···N hydrogen bonding interactions (Fig. 2). The charge-compensating cations \[C~6~H~12~N~5~O\]^+^ can be considered as the space-filling structural subunits and are connected to one side of the α-\[(PO~4~)W~12~O~36~\]^3-^ anion by the aforementioned multiple hydrogen-bonding interactions. Since \[C~6~H~12~N~5~O\]^+^ cations lie at one side of the anion, the inorganic anions are well-separated by \[C~6~H~12~N~5~O\]^+^ cations and by additional water molecules of crystallisation. In recent years, there has been increasing interest in the experimental and theoretical study of water clusters (H~2~O)*~n~* because these water assemblies might provide an insight into some of the unexplained properties of bulk water, namely into the processes that occur at the ice-liquid, ice-air, and liquid-air interfaces, and into the nature of water-water and water-solute interactions (Aghabozorg *et al.* 2010). In the network of (I), six uncoordinated water molecules increase the number of O---H···O hydrogen bonds and thus lead to the formation of (H~2~O)~∞~ clusters. Indeed, these units were found to act as a \'supramolecular glue\' in the aggregation of \[C~6~H~12~N~5~O\]~3~\[W~12~(PO~4~)O~36~\]^.^6H~2~O and hence support the consolidation of the three-dimensional network. Experimental {#experimental} ============ A solution of ((1*H*-tetrazole-5-yl)methyl)morpholine (0.14 g, 0.82 mmol) in 30 ml of distilled water was added with vigorous stirring to a solution of α-H~3~\[(PO~4~)W~12~O~36~\]^.^21H~2~O (0.50 g, 0.27 mmol) in 25 ml of distilled water. A colorless precipitate was formed after five hours. The solid was filtered off, washed with DMF and dried at room temperature. The precipitate was then re-dissolved in acetonitrile and the solution was cooled to ambient temperature; colorless block-shaped crystals were obtained, filtered off, washed several times with distilled water, and dried in air (yield 30% based on W) and characterized by spectroscopy and X-ray crystallography methods. ^1^H NMR in D~2~O:d 2.65 (t, 4H, (CH~2~)~2~N), 3.80 (t,4*H*, (CH~2~)~2~O), 4.15 (s, 2H, CH~2~-(N(CH~2~)~2~)).Anal. calcd. for C~18~H~45~N~15~O~49~PW~12~:*C*, 6.19; H, 1.30; N, 6.02; P, 0.90; W, 63.20. Found: C, 6.41; H, 1.41; N, 5.88; P, 0.85; W, 63.00. Refinement {#refinement} ========== Only heavy atoms (P and W) were refined anisotropically. Refinement in anisotropic approximation for all atoms was unstable due to the limited scattering powder of the crystal and absorption effects which could not be completely corrected. The highest peak and the deepest hole in the final Fourier map are 0.86 Å and 0.91 Å away from atoms W8 and W3, respectively. Positions of hydrogen atoms were calculated. All hydrogen atoms were treated in the riding model approximation with the *U*~iso~(H) parameters equal to 1.2 *U*~eq~(Ci), where *U*~eq~(C) are the equivalent temperature factors of the atoms to which corresponding H atoms are bonded. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of \[C6H12N5O\]3\[W12(PO4)O36\].6H2O, with displacement ellipsoids drawn at the 50% probability level. ::: ![](e-67-0m301-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of (I) in a projection along a, emphasizing the three-dimensional H-bonded network (dashed lines). ::: ![](e-67-0m301-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e472 .table-wrap} ------------------------------------------------- -------------------------------------- (C~6~H~12~N~5~O)~3~\[W~12~(PO~4~)O~36~\]·6H~2~O *F*(000) = 6224 *M~r~* = 3495.88 *D*~x~ = 3.906 Mg m^−3^ Orthorhombic, *P*2~1~2~1~2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 846 reflections *a* = 14.616 (3) Å θ = 2.4--24.2° *b* = 15.213 (3) Å µ = 23.27 mm^−1^ *c* = 26.735 (6) Å *T* = 100 K *V* = 5944 (2) Å^3^ Plate, colourless *Z* = 4 0.12 × 0.11 × 0.06 mm ------------------------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e613 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD area-detector diffractometer 12321 independent reflections Radiation source: fine-focus sealed tube 9617 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.159 ω scans θ~max~ = 26.5°, θ~min~ = 1.5° Absorption correction: multi-scan (*SADABS*; Bruker, 2005) *h* = −18→18 *T*~min~ = 0.078, *T*~max~ = 0.246 *k* = −19→19 59635 measured reflections *l* = −33→33 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e727 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------ Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.052 H-atom parameters constrained *wR*(*F*^2^) = 0.104 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.015*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.00 (Δ/σ)~max~ = 0.001 12321 reflections Δρ~max~ = 2.80 e Å^−3^ 446 parameters Δρ~min~ = −2.72 e Å^−3^ 6 restraints Absolute structure: Flack (1983), 5544 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.041 (19) ---------------------------------------------------------------- ------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e889 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e988 .table-wrap} ------ -------------- -------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ W1 0.13685 (6) 0.08083 (6) 0.78414 (3) 0.0071 (2) W2 0.12581 (6) −0.11475 (6) 0.84527 (3) 0.00680 (19) W3 −0.01178 (6) 0.05564 (6) 0.88273 (3) 0.00663 (19) W4 0.23993 (6) 0.27465 (6) 0.84686 (3) 0.0063 (2) W5 0.32328 (6) 0.25584 (6) 0.96592 (3) 0.00742 (19) W6 0.09215 (6) 0.24836 (6) 0.94429 (3) 0.00671 (19) W7 0.38668 (6) 0.08881 (6) 0.80600 (3) 0.0069 (2) W8 0.46950 (6) 0.07104 (6) 0.92481 (3) 0.0077 (2) W9 0.37534 (7) −0.10728 (6) 0.86647 (3) 0.0078 (2) W10 0.21725 (7) −0.13462 (6) 0.97307 (3) 0.0076 (2) W11 0.08109 (6) 0.03551 (6) 1.01029 (3) 0.0071 (2) W12 0.31213 (6) 0.04266 (6) 1.03168 (3) 0.0075 (2) P1 0.2295 (4) 0.0669 (4) 0.9062 (2) 0.0048 (11) O1B 0.1641 (10) 0.1949 (9) 0.8099 (5) 0.004 (3)\* O2B 0.2655 (11) 0.0633 (9) 0.7824 (5) 0.010 (3)\* O3B 0.2554 (11) −0.1191 (10) 0.8382 (6) 0.015 (4)\* O4B 0.1447 (10) −0.1393 (10) 0.9133 (5) 0.009 (3)\* O5B 0.0152 (10) 0.0215 (9) 0.9489 (5) 0.006 (3)\* O6B 0.0257 (11) 0.1702 (9) 0.9025 (5) 0.009 (3)\* O7B 0.3371 (11) 0.1990 (10) 0.8259 (6) 0.011 (4)\* O8B 0.4150 (11) 0.1809 (9) 0.9367 (5) 0.009 (3)\* O9B 0.3045 (11) 0.1634 (9) 1.0121 (5) 0.007 (3)\* O10B 0.0901 (11) 0.1564 (10) 0.9929 (6) 0.013 (4)\* O11B 0.4062 (11) 0.0320 (10) 0.9827 (5) 0.012 (3)\* O12B 0.3195 (10) −0.1331 (9) 0.9280 (5) 0.008 (3)\* O1C 0.1542 (10) 0.0355 (9) 0.8695 (5) 0.006 (3)\* O2C 0.1237 (10) −0.0454 (9) 0.7853 (5) 0.009 (3)\* O3C 0.0181 (10) 0.0886 (9) 0.8151 (5) 0.006 (3)\* O4C 0.0105 (10) −0.0617 (9) 0.8616 (5) 0.009 (3)\* O5C 0.2234 (11) 0.1677 (9) 0.9125 (5) 0.010 (4)\* O6C 0.1364 (11) 0.3072 (9) 0.8851 (5) 0.008 (3)\* O7C 0.3141 (10) 0.3122 (9) 0.9011 (5) 0.002 (3)\* O8C 0.1998 (10) 0.2924 (9) 0.9769 (5) 0.004 (3)\* O9C 0.3222 (11) 0.0400 (10) 0.8850 (5) 0.009 (3)\* O10C 0.4081 (11) −0.0347 (10) 0.8101 (5) 0.012 (3)\* O11C 0.4790 (11) 0.1034 (10) 0.8545 (5) 0.012 (3)\* O12C 0.4726 (12) −0.0506 (11) 0.9018 (6) 0.017 (4)\* O13C 0.2162 (10) 0.0225 (9) 0.9574 (5) 0.004 (3)\* O14C 0.2926 (10) −0.0796 (9) 1.0242 (5) 0.005 (3)\* O15C 0.1137 (11) −0.0849 (10) 1.0077 (5) 0.012 (3)\* O16C 0.1849 (11) 0.0503 (10) 1.0520 (6) 0.014 (4)\* O1T 0.1113 (11) 0.1009 (9) 0.7229 (5) 0.008 (3)\* O2T 0.0886 (12) −0.2120 (11) 0.8230 (6) 0.021 (4)\* O3T −0.1262 (11) 0.0627 (10) 0.8820 (5) 0.009 (3)\* O4T 0.2503 (11) 0.3612 (9) 0.8069 (6) 0.011 (3)\* O5T 0.3826 (11) 0.3329 (10) 0.9988 (6) 0.013 (4)\* O6T 0.0161 (12) 0.3183 (10) 0.9630 (6) 0.015 (4)\* O7T 0.4435 (10) 0.1134 (10) 0.7519 (5) 0.008 (3)\* O8T 0.5799 (10) 0.0855 (10) 0.9435 (5) 0.009 (3)\* O9T 0.4278 (10) −0.2028 (9) 0.8515 (5) 0.008 (3)\* O10T 0.2142 (10) −0.2426 (9) 0.9929 (5) 0.007 (3)\* O11T −0.0015 (10) 0.0336 (9) 1.0544 (5) 0.007 (3)\* O12T 0.3661 (11) 0.0419 (10) 1.0867 (5) 0.010 (3)\* O1 −0.0329 (11) 0.6253 (10) 0.9033 (6) 0.014 (4)\* O2 0.3910 (12) 0.1840 (10) 0.6455 (6) 0.014 (4)\* O3 0.7992 (11) 0.3157 (10) 0.8498 (6) 0.013 (4)\* N1A 0.2428 (14) 0.5669 (13) 1.0482 (7) 0.016 (5)\* N2A 0.3121 (13) 0.6174 (12) 1.0671 (6) 0.010 (4)\* N3A 0.3715 (13) 0.6348 (12) 1.0333 (7) 0.012 (4)\* N4A 0.3446 (13) 0.5980 (12) 0.9905 (7) 0.014 (4)\* H4A 0.3725 0.6005 0.9614 0.017\* N5A 0.1426 (13) 0.5627 (13) 0.9376 (7) 0.014 (4)\* H5A 0.1673 0.5989 0.9147 0.017\* N1B 0.1622 (12) 0.4400 (11) 0.7087 (6) 0.006 (4)\* N2B 0.1362 (15) 0.4894 (13) 0.7487 (7) 0.019 (5)\* N3B 0.0718 (14) 0.4460 (13) 0.7736 (7) 0.017 (5)\* N4B 0.0632 (13) 0.3681 (12) 0.7506 (6) 0.009 (4)\* H4B 0.0263 0.3256 0.7601 0.010\* N5B 0.2227 (13) 0.2763 (12) 0.6584 (7) 0.010 (4)\* H5B 0.2237 0.3313 0.6460 0.012\* N1C 0.4485 (14) 0.3858 (13) 0.7645 (7) 0.015 (5)\* N2C 0.4037 (14) 0.4569 (13) 0.7477 (7) 0.015 (4)\* N3C 0.3909 (14) 0.5159 (13) 0.7846 (7) 0.017 (5)\* N4C 0.4281 (14) 0.4820 (13) 0.8246 (7) 0.017 (5)\* H4C 0.4293 0.5058 0.8546 0.020\* N5C 0.6017 (12) 0.3217 (11) 0.8337 (6) 0.005 (4)\* H5C 0.6146 0.3135 0.8023 0.006\* C1A 0.2647 (16) 0.5557 (14) 1.0014 (8) 0.013 (5)\* C2A 0.2074 (16) 0.5054 (14) 0.9619 (8) 0.012 (5)\* H2A 0.2489 0.4797 0.9365 0.014\* H2B 0.1742 0.4566 0.9784 0.014\* C3A 0.0767 (16) 0.6076 (15) 0.9709 (9) 0.014 (5)\* H3A 0.1105 0.6373 0.9981 0.017\* H3B 0.0358 0.5633 0.9863 0.017\* C4A 0.0184 (18) 0.6757 (15) 0.9428 (8) 0.016 (5)\* H4D −0.0247 0.7050 0.9660 0.019\* H4E 0.0579 0.7210 0.9273 0.019\* C5A 0.0289 (14) 0.5823 (13) 0.8701 (7) 0.004 (4)\* H5D 0.0670 0.6270 0.8531 0.005\* H5E −0.0066 0.5507 0.8442 0.005\* C6A 0.0924 (15) 0.5159 (13) 0.8974 (7) 0.004 (4)\* H6A 0.0556 0.4676 0.9119 0.004\* H6B 0.1364 0.4901 0.8733 0.004\* C1B 0.1192 (16) 0.3644 (14) 0.7108 (8) 0.011 (5)\* C2B 0.1251 (15) 0.2898 (13) 0.6748 (7) 0.006 (4)\* H2C 0.0864 0.3024 0.6452 0.007\* H2D 0.1020 0.2355 0.6908 0.007\* C3B 0.2338 (17) 0.2013 (14) 0.6242 (9) 0.013 (5)\* H3C 0.2175 0.1464 0.6420 0.016\* H3D 0.1910 0.2080 0.5957 0.016\* C4B 0.3270 (17) 0.1938 (16) 0.6050 (9) 0.017 (6)\* H4F 0.3313 0.1422 0.5825 0.021\* H4G 0.3424 0.2469 0.5853 0.021\* C5B 0.3838 (16) 0.2549 (14) 0.6768 (8) 0.011 (5)\* H5F 0.3981 0.3090 0.6578 0.013\* H5G 0.4299 0.2491 0.7038 0.013\* C6B 0.2899 (14) 0.2648 (13) 0.7004 (7) 0.006 (5)\* H6C 0.2746 0.2118 0.7202 0.007\* H6D 0.2886 0.3165 0.7228 0.007\* C1C 0.4646 (16) 0.4033 (15) 0.8114 (8) 0.013 (5)\* C2C 0.5061 (16) 0.3423 (15) 0.8466 (8) 0.013 (5)\* H2E 0.4701 0.2872 0.8472 0.016\* H2F 0.5040 0.3682 0.8806 0.016\* C3C 0.6655 (15) 0.3995 (14) 0.8253 (8) 0.007 (5)\* H3E 0.6405 0.4372 0.7983 0.008\* H3F 0.6691 0.4351 0.8562 0.008\* C4C 0.7572 (18) 0.3700 (16) 0.8114 (9) 0.019 (6)\* H4H 0.7536 0.3361 0.7799 0.022\* H4I 0.7964 0.4220 0.8052 0.022\* C5C 0.7445 (17) 0.2421 (15) 0.8584 (9) 0.015 (5)\* H5H 0.7725 0.2068 0.8855 0.018\* H5I 0.7439 0.2054 0.8278 0.018\* C6C 0.6498 (17) 0.2625 (16) 0.8723 (8) 0.015 (5)\* H6E 0.6495 0.2922 0.9053 0.019\* H6F 0.6150 0.2069 0.8757 0.019\* O1W 0.9409 (11) 0.2541 (10) 0.7904 (5) 0.013 (4)\* H1W 0.9675 0.2096 0.8030 0.016\* H2W 0.8972 0.2730 0.8085 0.016\* O2W 0.4266 (11) 0.6202 (10) 0.8979 (5) 0.014 (4)\* H35 0.4805 0.6109 0.9087 0.017\* H36 0.4465 0.6690 0.8867 0.017\* O3W 0.3234 (12) 0.4705 (11) 0.6534 (7) 0.027 (4)\* H5W 0.3264 0.4896 0.6236 0.033\* H6W 0.3570 0.4951 0.6752 0.033\* O4W 0.6176 (14) 0.2121 (12) 0.7543 (6) 0.029 (5)\* H7W 0.5676 0.1836 0.7536 0.035\* H8W 0.6645 0.1847 0.7436 0.035\* O5W 0.2453 (12) 0.6697 (10) 0.8761 (6) 0.018 (4)\* H9W 0.2960 0.6448 0.8824 0.022\* H10W 0.2317 0.6666 0.8452 0.022\* O6W 0.2054 (12) 0.6585 (11) 0.7745 (6) 0.020 (4)\* H71 0.1806 0.6207 0.7554 0.024\* H72 0.1714 0.7033 0.7707 0.024\* ------ -------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2795 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ W1 0.0073 (5) 0.0071 (4) 0.0068 (4) −0.0005 (4) −0.0002 (4) −0.0001 (4) W2 0.0071 (5) 0.0054 (4) 0.0079 (4) 0.0006 (4) −0.0003 (4) −0.0009 (4) W3 0.0049 (5) 0.0065 (4) 0.0085 (4) 0.0006 (4) 0.0000 (4) −0.0006 (4) W4 0.0061 (5) 0.0051 (4) 0.0077 (5) −0.0002 (4) 0.0001 (4) 0.0006 (4) W5 0.0080 (5) 0.0055 (4) 0.0088 (5) −0.0005 (4) −0.0015 (4) 0.0001 (4) W6 0.0060 (5) 0.0051 (4) 0.0091 (4) 0.0001 (4) 0.0014 (4) −0.0003 (4) W7 0.0050 (5) 0.0068 (4) 0.0090 (4) 0.0005 (4) 0.0007 (4) 0.0007 (4) W8 0.0061 (5) 0.0076 (4) 0.0094 (4) −0.0004 (4) −0.0014 (4) 0.0007 (4) W9 0.0058 (5) 0.0061 (4) 0.0114 (5) 0.0012 (4) 0.0015 (4) −0.0002 (4) W10 0.0088 (5) 0.0052 (4) 0.0088 (5) −0.0003 (4) −0.0004 (4) 0.0008 (4) W11 0.0070 (5) 0.0068 (4) 0.0076 (5) 0.0000 (4) 0.0010 (4) 0.0009 (4) W12 0.0089 (5) 0.0073 (4) 0.0064 (5) 0.0002 (4) −0.0008 (4) 0.0008 (4) P1 0.0043 (18) 0.0060 (17) 0.0042 (17) −0.0007 (15) −0.0014 (15) 0.0003 (15) ----- ------------- ------------- ------------- -------------- -------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3072 .table-wrap} ----------------------- ------------- ----------------------- ------------- W1---O1T 1.706 (14) N1A---C1A 1.30 (3) W1---O2B 1.900 (16) N1A---N2A 1.37 (3) W1---O1B 1.909 (14) N2A---N3A 1.28 (2) W1---O3C 1.926 (15) N3A---N4A 1.33 (2) W1---O2C 1.930 (14) N4A---C1A 1.37 (3) W1---O1C 2.396 (14) N4A---H4A 0.8800 W2---O2T 1.685 (17) N5A---C2A 1.44 (3) W2---O4B 1.878 (14) N5A---C6A 1.48 (3) W2---O3B 1.905 (17) N5A---C3A 1.48 (3) W2---O2C 1.920 (14) N5A---H5A 0.8997 W2---O4C 1.919 (15) N1B---C1B 1.31 (3) W2---O1C 2.412 (14) N1B---N2B 1.36 (3) W3---O3T 1.676 (15) N2B---N3B 1.33 (3) W3---O5B 1.886 (14) N3B---N4B 1.34 (3) W3---O4C 1.900 (14) N4B---C1B 1.34 (3) W3---O6B 1.902 (15) N4B---H4B 0.8800 W3---O3C 1.925 (13) N5B---C3B 1.47 (3) W3---O1C 2.471 (15) N5B---C6B 1.50 (3) W4---O4T 1.703 (15) N5B---C2B 1.51 (3) W4---O6C 1.893 (15) N5B---H5B 0.9000 W4---O7C 1.899 (14) N1C---C1C 1.30 (3) W4---O7B 1.912 (16) N1C---N2C 1.34 (3) W4---O1B 1.917 (14) N2C---N3C 1.35 (3) W4---O5C 2.405 (14) N3C---N4C 1.31 (3) W5---O5T 1.702 (16) N4C---C1C 1.36 (3) W5---O9B 1.892 (14) N4C---H4C 0.8800 W5---O8C 1.911 (15) N5C---C2C 1.47 (3) W5---O8B 1.925 (15) N5C---C3C 1.52 (3) W5---O7C 1.938 (13) N5C---C6C 1.54 (3) W5---O5C 2.444 (15) N5C---H5C 0.8698 W6---O6T 1.619 (16) C1A---C2A 1.55 (3) W6---O6B 1.898 (15) C2A---H2A 0.9900 W6---O10B 1.910 (15) C2A---H2B 0.9900 W6---O8C 1.919 (14) C3A---C4A 1.54 (3) W6---O6C 1.928 (14) C3A---H3A 0.9900 W6---O5C 2.430 (15) C3A---H3B 0.9900 W7---O7T 1.710 (14) C4A---H4D 0.9900 W7---O11C 1.884 (15) C4A---H4E 0.9900 W7---O7B 1.902 (15) C5A---C6A 1.55 (3) W7---O10C 1.908 (15) C5A---H5D 0.9900 W7---O2B 1.920 (15) C5A---H5E 0.9900 W7---O9C 2.428 (14) C6A---H6A 0.9900 W8---O8T 1.704 (15) C6A---H6B 0.9900 W8---O8B 1.879 (15) C1B---C2B 1.49 (3) W8---O11B 1.900 (15) C2B---H2C 0.9900 W8---O12C 1.950 (16) C2B---H2D 0.9900 W8---O11C 1.949 (14) C3B---C4B 1.46 (3) W8---O9C 2.448 (15) C3B---H3C 0.9900 W9---O9T 1.691 (14) C3B---H3D 0.9900 W9---O12B 1.878 (15) C4B---H4F 0.9900 W9---O12C 1.913 (17) C4B---H4G 0.9900 W9---O3B 1.918 (17) C5B---C6B 1.52 (3) W9---O10C 1.928 (15) C5B---H5F 0.9900 W9---O9C 2.423 (15) C5B---H5G 0.9900 W10---O10T 1.727 (14) C6B---H6C 0.9900 W10---O12B 1.920 (15) C6B---H6D 0.9900 W10---O4B 1.918 (14) C1C---C2C 1.46 (3) W10---O15C 1.929 (15) C2C---H2E 0.9900 W10---O14C 1.944 (14) C2C---H2F 0.9900 W10---O13C 2.427 (13) C3C---C4C 1.46 (3) W11---O11T 1.687 (14) C3C---H3E 0.9900 W11---O15C 1.895 (15) C3C---H3F 0.9900 W11---O16C 1.897 (16) C4C---H4H 0.9900 W11---O10B 1.901 (15) C4C---H4I 0.9900 W11---O5B 1.914 (14) C5C---C6C 1.47 (3) W11---O13C 2.437 (14) C5C---H5H 0.9900 W12---O12T 1.668 (14) C5C---H5I 0.9900 W12---O14C 1.892 (13) C6C---H6E 0.9900 W12---O11B 1.904 (15) C6C---H6F 0.9900 W12---O9B 1.913 (14) O1W---H1W 0.8498 W12---O16C 1.941 (16) O1W---H2W 0.8501 W12---O13C 2.451 (14) O2W---H35 0.8500 P1---O9C 1.525 (16) O2W---H36 0.8500 P1---O13C 1.538 (14) O3W---H5W 0.8498 P1---O5C 1.545 (15) O3W---H6W 0.8501 P1---O1C 1.550 (15) O4W---H7W 0.8500 O1---C5A 1.43 (2) O4W---H8W 0.8500 O1---C4A 1.51 (3) O5W---H9W 0.8499 O2---C5B 1.37 (2) O5W---H10W 0.8500 O2---C4B 1.44 (3) O6W---H71 0.8500 O3---C5C 1.40 (3) O6W---H72 0.8499 O3---C4C 1.45 (3) O1T---W1---O2B 102.6 (7) W2---O4B---W10 151.7 (9) O1T---W1---O1B 103.2 (6) W3---O5B---W11 151.5 (8) O2B---W1---O1B 86.0 (6) W6---O6B---W3 152.2 (9) O1T---W1---O3C 101.8 (7) W7---O7B---W4 153.5 (9) O2B---W1---O3C 155.6 (6) W8---O8B---W5 153.0 (9) O1B---W1---O3C 88.7 (6) W5---O9B---W12 152.2 (8) O1T---W1---O2C 99.9 (6) W11---O10B---W6 151.1 (9) O2B---W1---O2C 87.7 (6) W8---O11B---W12 152.3 (9) O1B---W1---O2C 156.8 (6) W9---O12B---W10 152.9 (9) O3C---W1---O2C 87.9 (6) P1---O1C---W1 126.1 (8) O1T---W1---O1C 171.0 (6) P1---O1C---W2 125.7 (8) O2B---W1---O1C 83.0 (6) W1---O1C---W2 90.0 (5) O1B---W1---O1C 84.0 (5) P1---O1C---W3 124.6 (8) O3C---W1---O1C 72.7 (5) W1---O1C---W3 89.8 (5) O2C---W1---O1C 73.1 (5) W2---O1C---W3 89.3 (5) O2T---W2---O4B 102.4 (7) W2---O2C---W1 124.0 (7) O2T---W2---O3B 104.8 (8) W1---O3C---W3 126.3 (7) O4B---W2---O3B 86.7 (7) W3---O4C---W2 127.8 (8) O2T---W2---O2C 100.5 (7) P1---O5C---W4 125.9 (8) O4B---W2---O2C 157.1 (6) P1---O5C---W6 125.8 (9) O3B---W2---O2C 87.3 (7) W4---O5C---W6 89.6 (5) O2T---W2---O4C 99.5 (8) P1---O5C---W5 125.0 (9) O4B---W2---O4C 89.6 (6) W4---O5C---W5 89.7 (5) O3B---W2---O4C 155.6 (6) W6---O5C---W5 89.4 (5) O2C---W2---O4C 86.8 (6) W4---O6C---W6 126.2 (8) O2T---W2---O1C 169.3 (7) W4---O7C---W5 126.1 (7) O4B---W2---O1C 84.5 (6) W5---O8C---W6 127.1 (7) O3B---W2---O1C 83.6 (6) P1---O9C---W9 127.5 (9) O2C---W2---O1C 72.9 (5) P1---O9C---W7 125.9 (8) O4C---W2---O1C 72.0 (6) W9---O9C---W7 88.9 (5) O3T---W3---O5B 103.7 (7) P1---O9C---W8 124.6 (8) O3T---W3---O4C 103.1 (7) W9---O9C---W8 89.1 (5) O5B---W3---O4C 89.1 (6) W7---O9C---W8 88.7 (5) O3T---W3---O6B 103.4 (7) W7---O10C---W9 124.6 (8) O5B---W3---O6B 86.1 (6) W7---O11C---W8 125.6 (8) O4C---W3---O6B 153.4 (7) W9---O12C---W8 124.5 (9) O3T---W3---O3C 101.5 (7) P1---O13C---W10 125.8 (8) O5B---W3---O3C 154.8 (6) P1---O13C---W11 125.7 (8) O4C---W3---O3C 85.8 (6) W10---O13C---W11 89.1 (5) O6B---W3---O3C 87.5 (6) P1---O13C---W12 126.4 (8) O3T---W3---O1C 170.4 (6) W10---O13C---W12 88.8 (4) O5B---W3---O1C 84.0 (6) W11---O13C---W12 89.0 (4) O4C---W3---O1C 70.9 (6) W12---O14C---W10 125.7 (7) O6B---W3---O1C 82.6 (6) W11---O15C---W10 126.4 (8) O3C---W3---O1C 71.0 (5) W11---O16C---W12 126.5 (8) O4T---W4---O6C 102.0 (7) C5A---O1---C4A 110.7 (17) O4T---W4---O7C 101.3 (7) C5B---O2---C4B 109.3 (17) O6C---W4---O7C 88.0 (6) C5C---O3---C4C 109.4 (18) O4T---W4---O7B 102.4 (7) C1A---N1A---N2A 104.3 (19) O6C---W4---O7B 155.5 (6) N3A---N2A---N1A 110.9 (17) O7C---W4---O7B 88.9 (6) N2A---N3A---N4A 108.6 (18) O4T---W4---O1B 102.5 (7) N3A---N4A---C1A 105.5 (18) O6C---W4---O1B 89.0 (6) N3A---N4A---H4A 127.3 O7C---W4---O1B 156.1 (6) C1A---N4A---H4A 127.3 O7B---W4---O1B 84.1 (6) C2A---N5A---C6A 111.2 (17) O4T---W4---O5C 171.9 (6) C2A---N5A---C3A 115.9 (18) O6C---W4---O5C 72.7 (6) C6A---N5A---C3A 109.6 (18) O7C---W4---O5C 72.8 (5) C2A---N5A---H5A 114.4 O7B---W4---O5C 83.2 (6) C6A---N5A---H5A 89.9 O1B---W4---O5C 83.7 (5) C3A---N5A---H5A 112.8 O5T---W5---O9B 104.5 (7) C1B---N1B---N2B 108.5 (18) O5T---W5---O8C 101.7 (7) N3B---N2B---N1B 108.5 (18) O9B---W5---O8C 88.8 (6) N2B---N3B---N4B 106.0 (18) O5T---W5---O8B 105.2 (7) N3B---N4B---C1B 110.1 (19) O9B---W5---O8B 85.7 (6) N3B---N4B---H4B 124.9 O8C---W5---O8B 153.1 (6) C1B---N4B---H4B 124.9 O5T---W5---O7C 101.1 (6) C3B---N5B---C6B 107.6 (17) O9B---W5---O7C 154.5 (6) C3B---N5B---C2B 113.0 (17) O8C---W5---O7C 86.7 (6) C6B---N5B---C2B 114.7 (16) O8B---W5---O7C 87.0 (6) C3B---N5B---H5B 119.4 O5T---W5---O5C 169.7 (6) C6B---N5B---H5B 111.8 O9B---W5---O5C 83.5 (6) C2B---N5B---H5B 89.8 O8C---W5---O5C 71.6 (6) C1C---N1C---N2C 104.1 (19) O8B---W5---O5C 81.6 (6) N1C---N2C---N3C 111.2 (18) O7C---W5---O5C 71.3 (5) N4C---N3C---N2C 106.2 (19) O6T---W6---O6B 104.1 (8) N3C---N4C---C1C 107.4 (19) O6T---W6---O10B 105.1 (7) N3C---N4C---H4C 126.3 O6B---W6---O10B 86.2 (6) C1C---N4C---H4C 126.3 O6T---W6---O8C 101.1 (7) C2C---N5C---C3C 116.8 (16) O6B---W6---O8C 154.8 (6) C2C---N5C---C6C 113.6 (17) O10B---W6---O8C 87.7 (6) C3C---N5C---C6C 105.9 (16) O6T---W6---O6C 100.3 (7) C2C---N5C---H5C 117.6 O6B---W6---O6C 88.8 (6) C3C---N5C---H5C 80.4 O10B---W6---O6C 154.6 (7) C6C---N5C---H5C 117.6 O8C---W6---O6C 86.3 (6) N1A---C1A---N4A 111 (2) O6T---W6---O5C 169.2 (7) N1A---C1A---C2A 126 (2) O6B---W6---O5C 83.2 (6) N4A---C1A---C2A 123 (2) O10B---W6---O5C 83.1 (6) N5A---C2A---C1A 111.3 (18) O8C---W6---O5C 71.8 (5) N5A---C2A---H2A 109.4 O6C---W6---O5C 71.5 (6) C1A---C2A---H2A 109.4 O7T---W7---O11C 102.0 (7) N5A---C2A---H2B 109.4 O7T---W7---O7B 103.2 (7) C1A---C2A---H2B 109.4 O11C---W7---O7B 88.6 (7) H2A---C2A---H2B 108.0 O7T---W7---O10C 100.6 (7) N5A---C3A---C4A 112.2 (18) O11C---W7---O10C 87.6 (6) N5A---C3A---H3A 109.2 O7B---W7---O10C 156.1 (7) C4A---C3A---H3A 109.2 O7T---W7---O2B 102.4 (7) N5A---C3A---H3B 109.2 O11C---W7---O2B 155.6 (6) C4A---C3A---H3B 109.2 O7B---W7---O2B 85.4 (6) H3A---C3A---H3B 107.9 O10C---W7---O2B 88.4 (6) O1---C4A---C3A 106.0 (18) O7T---W7---O9C 172.4 (6) O1---C4A---H4D 110.5 O11C---W7---O9C 73.5 (6) C3A---C4A---H4D 110.5 O7B---W7---O9C 83.0 (6) O1---C4A---H4E 110.5 O10C---W7---O9C 73.3 (6) C3A---C4A---H4E 110.5 O2B---W7---O9C 82.3 (6) H4D---C4A---H4E 108.7 O8T---W8---O8B 103.7 (7) O1---C5A---C6A 112.7 (16) O8T---W8---O11B 105.2 (7) O1---C5A---H5D 109.1 O8B---W8---O11B 86.2 (6) C6A---C5A---H5D 109.1 O8T---W8---O12C 101.1 (7) O1---C5A---H5E 109.1 O8B---W8---O12C 155.2 (7) C6A---C5A---H5E 109.1 O11B---W8---O12C 88.4 (6) H5D---C5A---H5E 107.8 O8T---W8---O11C 100.6 (7) N5A---C6A---C5A 108.9 (16) O8B---W8---O11C 88.2 (6) N5A---C6A---H6A 109.9 O11B---W8---O11C 154.2 (7) C5A---C6A---H6A 109.9 O12C---W8---O11C 86.2 (6) N5A---C6A---H6B 109.9 O8T---W8---O9C 170.3 (6) C5A---C6A---H6B 109.9 O8B---W8---O9C 82.7 (6) H6A---C6A---H6B 108.3 O11B---W8---O9C 82.3 (6) N1B---C1B---N4B 106.8 (19) O12C---W8---O9C 72.6 (6) N1B---C1B---C2B 128 (2) O11C---W8---O9C 72.0 (6) N4B---C1B---C2B 125 (2) O9T---W9---O12B 102.9 (7) C1B---C2B---N5B 110.3 (18) O9T---W9---O12C 99.6 (7) C1B---C2B---H2C 109.6 O12B---W9---O12C 89.1 (6) N5B---C2B---H2C 109.6 O9T---W9---O3B 103.9 (7) C1B---C2B---H2D 109.6 O12B---W9---O3B 85.9 (7) N5B---C2B---H2D 109.6 O12C---W9---O3B 156.4 (7) H2C---C2B---H2D 108.1 O9T---W9---O10C 101.2 (7) C4B---C3B---N5B 112 (2) O12B---W9---O10C 155.8 (6) C4B---C3B---H3C 109.1 O12C---W9---O10C 86.7 (7) N5B---C3B---H3C 109.1 O3B---W9---O10C 88.5 (7) C4B---C3B---H3D 109.1 O9T---W9---O9C 171.3 (6) N5B---C3B---H3D 109.1 O12B---W9---O9C 82.9 (6) H3C---C3B---H3D 107.8 O12C---W9---O9C 73.8 (6) O2---C4B---C3B 110.5 (19) O3B---W9---O9C 82.8 (6) O2---C4B---H4F 109.5 O10C---W9---O9C 73.1 (6) C3B---C4B---H4F 109.5 O10T---W10---O12B 102.9 (6) O2---C4B---H4G 109.5 O10T---W10---O4B 101.9 (6) C3B---C4B---H4G 109.5 O12B---W10---O4B 84.7 (6) H4F---C4B---H4G 108.1 O10T---W10---O15C 101.9 (7) O2---C5B---C6B 113.7 (19) O12B---W10---O15C 155.2 (6) O2---C5B---H5F 108.8 O4B---W10---O15C 88.9 (6) C6B---C5B---H5F 108.8 O10T---W10---O14C 102.1 (6) O2---C5B---H5G 108.8 O12B---W10---O14C 89.7 (6) C6B---C5B---H5G 108.8 O4B---W10---O14C 156.1 (6) H5F---C5B---H5G 107.7 O15C---W10---O14C 86.5 (6) N5B---C6B---C5B 107.0 (16) O10T---W10---O13C 171.9 (6) N5B---C6B---H6C 110.3 O12B---W10---O13C 83.4 (6) C5B---C6B---H6C 110.3 O4B---W10---O13C 83.6 (6) N5B---C6B---H6D 110.3 O15C---W10---O13C 72.1 (6) C5B---C6B---H6D 110.3 O14C---W10---O13C 72.6 (5) H6C---C6B---H6D 108.6 O11T---W11---O15C 100.9 (7) N1C---C1C---N4C 111 (2) O11T---W11---O16C 99.4 (7) N1C---C1C---C2C 125 (2) O15C---W11---O16C 86.3 (7) N4C---C1C---C2C 124 (2) O11T---W11---O10B 103.7 (7) C1C---C2C---N5C 112.3 (19) O15C---W11---O10B 155.4 (7) C1C---C2C---H2E 109.1 O16C---W11---O10B 88.5 (7) N5C---C2C---H2E 109.1 O11T---W11---O5B 103.7 (7) C1C---C2C---H2F 109.1 O15C---W11---O5B 89.3 (6) N5C---C2C---H2F 109.1 O16C---W11---O5B 156.9 (6) H2E---C2C---H2F 107.9 O10B---W11---O5B 86.2 (6) C4C---C3C---N5C 111.2 (18) O11T---W11---O13C 169.7 (6) C4C---C3C---H3E 109.4 O15C---W11---O13C 72.4 (6) N5C---C3C---H3E 109.4 O16C---W11---O13C 72.7 (6) C4C---C3C---H3F 109.4 O10B---W11---O13C 83.1 (6) N5C---C3C---H3F 109.4 O5B---W11---O13C 84.3 (5) H3E---C3C---H3F 108.0 O12T---W12---O14C 99.1 (7) O3---C4C---C3C 112.5 (19) O12T---W12---O11B 105.3 (7) O3---C4C---H4H 109.1 O14C---W12---O11B 87.2 (6) C3C---C4C---H4H 109.1 O12T---W12---O9B 106.0 (7) O3---C4C---H4I 109.1 O14C---W12---O9B 154.9 (6) C3C---C4C---H4I 109.1 O11B---W12---O9B 86.3 (6) H4H---C4C---H4I 107.8 O12T---W12---O16C 101.9 (7) O3---C5C---C6C 114 (2) O14C---W12---O16C 86.8 (6) O3---C5C---H5H 108.7 O11B---W12---O16C 152.8 (6) C6C---C5C---H5H 108.7 O9B---W12---O16C 87.9 (7) O3---C5C---H5I 108.7 O12T---W12---O13C 169.7 (6) C6C---C5C---H5I 108.7 O14C---W12---O13C 72.8 (5) H5H---C5C---H5I 107.6 O11B---W12---O13C 81.1 (6) C5C---C6C---N5C 112.7 (19) O9B---W12---O13C 82.2 (5) C5C---C6C---H6E 109.1 O16C---W12---O13C 71.7 (6) N5C---C6C---H6E 109.1 O9C---P1---O13C 109.0 (9) C5C---C6C---H6F 109.1 O9C---P1---O5C 111.0 (9) N5C---C6C---H6F 109.1 O13C---P1---O5C 109.3 (8) H6E---C6C---H6F 107.8 O9C---P1---O1C 108.2 (8) H1W---O1W---H2W 112.9 O13C---P1---O1C 109.8 (8) H35---O2W---H36 87.1 O5C---P1---O1C 109.5 (9) H5W---O3W---H6W 117.6 W1---O1B---W4 151.8 (8) H7W---O4W---H8W 115.8 W1---O2B---W7 151.2 (8) H9W---O5W---H10W 111.9 W2---O3B---W9 150.1 (9) H71---O6W---H72 102.9 C1A---N1A---N2A---N3A 0(2) N1B---C1B---C2B---N5B 41 (3) N1A---N2A---N3A---N4A 1(2) N4B---C1B---C2B---N5B −143 (2) N2A---N3A---N4A---C1A −1(2) C3B---N5B---C2B---C1B 177.8 (18) C1B---N1B---N2B---N3B −4(3) C6B---N5B---C2B---C1B 54 (2) N1B---N2B---N3B---N4B 4(2) C6B---N5B---C3B---C4B −58 (2) N2B---N3B---N4B---C1B −2(2) C2B---N5B---C3B---C4B 174.7 (18) C1C---N1C---N2C---N3C −2(3) C5B---O2---C4B---C3B −58 (2) N1C---N2C---N3C---N4C 0(3) N5B---C3B---C4B---O2 59 (3) N2C---N3C---N4C---C1C 1(3) C4B---O2---C5B---C6B 61 (2) N2A---N1A---C1A---N4A −1(2) C3B---N5B---C6B---C5B 55 (2) N2A---N1A---C1A---C2A −178 (2) C2B---N5B---C6B---C5B −178.3 (17) N3A---N4A---C1A---N1A 1(3) O2---C5B---C6B---N5B −60 (2) N3A---N4A---C1A---C2A 178.3 (19) N2C---N1C---C1C---N4C 2(3) C6A---N5A---C2A---C1A 176.0 (18) N2C---N1C---C1C---C2C 175 (2) C3A---N5A---C2A---C1A −58 (3) N3C---N4C---C1C---N1C −2(3) N1A---C1A---C2A---N5A 88 (3) N3C---N4C---C1C---C2C −175 (2) N4A---C1A---C2A---N5A −89 (3) N1C---C1C---C2C---N5C 66 (3) C2A---N5A---C3A---C4A 172.9 (19) N4C---C1C---C2C---N5C −122 (2) C6A---N5A---C3A---C4A −60 (2) C3C---N5C---C2C---C1C 52 (2) C5A---O1---C4A---C3A −60 (2) C6C---N5C---C2C---C1C 176.0 (18) N5A---C3A---C4A---O1 61 (2) C2C---N5C---C3C---C4C −178.4 (19) C4A---O1---C5A---C6A 60 (2) C6C---N5C---C3C---C4C 54 (2) C2A---N5A---C6A---C5A −176.0 (17) C5C---O3---C4C---C3C 59 (2) C3A---N5A---C6A---C5A 55 (2) N5C---C3C---C4C---O3 −60 (2) O1---C5A---C6A---N5A −56 (2) C4C---O3---C5C---C6C −56 (3) N2B---N1B---C1B---N4B 3(2) O3---C5C---C6C---N5C 55 (3) N2B---N1B---C1B---C2B 179 (2) C2C---N5C---C6C---C5C 179.4 (19) N3B---N4B---C1B---N1B 0(3) C3C---N5C---C6C---C5C −51 (2) N3B---N4B---C1B---C2B −177 (2) ----------------------- ------------- ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5871 .table-wrap} ---------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N4A---H4A···O2W 0.88 1.90 2.77 (2) 173 N5A---H5A···O5W 0.90 1.88 2.76 (3) 166 N4B---H4B···O1W^i^ 0.88 1.84 2.71 (2) 168 N5B---H5B···N2A^ii^ 0.90 2.31 2.97 (2) 130 N4C---H4C···O2W 0.88 2.09 2.87 (3) 149 N5C---H5C···O4W 0.87 2.01 2.71 (2) 137 O1W---H1W···O3C^iii^ 0.85 2.01 2.84 (2) 164 O1W---H2W···O3 0.85 1.92 2.77 (2) 180 O2W---H3W···O11T^iv^ 0.85 2.43 2.87 (2) 113 O2W---H4W···O9T^v^ 0.85 2.18 2.96 (2) 153 O2W---H4W···O2^vi^ 0.85 2.54 3.06 (2) 121 O3W---H5W···N1A^ii^ 0.85 2.41 3.03 (3) 130 O3W---H6W···N2C 0.85 2.14 2.79 (3) 134 O4W---H7W···O7T 0.85 2.11 2.96 (2) 180 O4W---H8W···O6W^vii^ 0.85 2.00 2.82 (2) 161 O5W---H9W···O2W 0.85 1.99 2.82 (2) 164 O5W---H10W···O6W 0.85 1.93 2.78 (2) 178 O6W---H11W···N2B 0.85 2.11 2.85 (2) 146 O6W---H12W···O2T^v^ 0.85 2.25 2.91 (2) 134 O6W---H12W···O1W^vi^ 0.85 2.44 3.11 (2) 137 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*−1, *y*, *z*; (ii) −*x*+1/2, −*y*+1, *z*−1/2; (iii) *x*+1, *y*, *z*; (iv) *x*+1/2, −*y*+1/2, −*z*+2; (v) *x*, *y*+1, *z*; (vi) −*x*+1, *y*+1/2, −*z*+3/2; (vii) −*x*+1, *y*−1/2, −*z*+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------------- --------- ------- ---------- ------------- N4*A*---H4*A*⋯O2*W* 0.88 1.90 2.77 (2) 173 N5*A*---H5*A*⋯O5*W* 0.90 1.88 2.76 (3) 166 N4*B*---H4*B*⋯O1*W*^i^ 0.88 1.84 2.71 (2) 168 N5*B*---H5*B*⋯N2*A*^ii^ 0.90 2.31 2.97 (2) 130 N4*C*---H4*C*⋯O2*W* 0.88 2.09 2.87 (3) 149 N5*C*---H5*C*⋯O4*W* 0.87 2.01 2.71 (2) 137 O1*W*---H1*W*⋯O3*C*^iii^ 0.85 2.01 2.84 (2) 164 O1*W*---H2*W*⋯O3 0.85 1.92 2.77 (2) 180 O2*W*---H3W⋯O11*T*^iv^ 0.85 2.43 2.87 (2) 113 O2*W*---H4W⋯O9*T*^v^ 0.85 2.18 2.96 (2) 153 O2*W*---H4W⋯O2^vi^ 0.85 2.54 3.06 (2) 121 O3*W*---H5*W*⋯N1*A*^ii^ 0.85 2.41 3.03 (3) 130 O3*W*---H6*W*⋯N2*C* 0.85 2.14 2.79 (3) 134 O4*W*---H7*W*⋯O7*T* 0.85 2.11 2.96 (2) 180 O4*W*---H8*W*⋯O6*W*^vii^ 0.85 2.00 2.82 (2) 161 O5*W*---H9*W*⋯O2*W* 0.85 1.99 2.82 (2) 164 O5*W*---H10*W*⋯O6*W* 0.85 1.93 2.78 (2) 178 O6*W*---H11W⋯N2*B* 0.85 2.11 2.85 (2) 146 O6*W*---H12W⋯O2*T*^v^ 0.85 2.25 2.91 (2) 134 O6*W*---H12W⋯O1*W*^vi^ 0.85 2.44 3.11 (2) 137 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) . :::

PubMed Central

2024-06-05T04:04:18.406162

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052096/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):m301-m302", "authors": [ { "first": "Babak", "last": "Feizyzadeh" }, { "first": "Masoud", "last": "Mirzaei" }, { "first": "Hossein", "last": "Eshtiagh-Hosseini" }, { "first": "Ahmad", "last": "Gholizadeh" } ] }

PMC3052097

Related literature {#sec1} ================== For related compounds, see: Berrah *et al.* (2005*a* [@bb3],*b* [@bb2], 2011[@bb4]); Bouacida *et al.* (2005[@bb6], 2009[@bb5]); Dobson & Gerkin (1996[@bb11]). For hydrogen-bond motifs, see: Bernstein *et al.* (1995[@bb1]); Etter *et al.* (1990[@bb13]). For similar intermolecular interactions, see: Dorn *et al.* (2005[@bb12]), Janiak (2000[@bb16]); Desiraju (2003[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} 2C~5~H~6~N~3~O~2~ ^+^·SO~4~ ^2−^·2H~2~O*M* *~r~* = 412.36Monoclinic,*a* = 7.7214 (4) Å*b* = 20.7043 (14) Å*c* = 10.6398 (7) Åβ = 109.299 (2)°*V* = 1605.36 (17) Å^3^*Z* = 4Mo *K*α radiationμ = 0.27 mm^−1^*T* = 150 K0.55 × 0.36 × 0.15 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 2002[@bb17]) *T* ~min~ = 0.708, *T* ~max~ = 0.96013466 measured reflections3675 independent reflections3146 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.039 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.035*wR*(*F* ^2^) = 0.096*S* = 1.033675 reflections246 parametersH-atom parameters constrainedΔρ~max~ = 0.47 e Å^−3^Δρ~min~ = −0.48 e Å^−3^ {#d5e799} Data collection: *APEX2* (Bruker, 2001[@bb8]); cell refinement: *SAINT* (Bruker, 2001[@bb8]); data reduction: *SAINT*; program(s) used to solve structure: *SIR2002* (Burla *et al.*, 2003[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb18]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb14]) and *DIAMOND* (Brandenburg & Berndt, 2001[@bb7]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb15]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005824/dn2656sup1.cif](http://dx.doi.org/10.1107/S1600536811005824/dn2656sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005824/dn2656Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005824/dn2656Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?dn2656&file=dn2656sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?dn2656sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?dn2656&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DN2656](http://scripts.iucr.org/cgi-bin/sendsup?dn2656)). We are grateful to the LCATM laboratory, Université Larbi Ben M'Hidi, Oum El Bouaghi, Algeria, for financial support. Comment ======= Hydrogen bonds are object of several studies, that aim at elucidate their influence on crystal construction and compounds properties (Desiraju, 2003). N-heterocyclic compounds such as pyrazine and its derivatives may be interesting units to built new edifices involving original hydrogen-bonding scheme since they include a variety of potential hydrogen donors and acceptors. In this perspective and as a part of our search for new hybrid compounds based on protonated amines and imines (Berrah *et al.* 2011, 2005*a*,*b*; Bouacida *et al.* 2005,2009), we present here the structure of Bis (2-Amino-3-carboxypyrazin-1-ium) sulfate dihydrate. The asymmetric units of (I) includes two symmetry- independent cations and water molecules, and one sulfate anion. Cations and anions are interconnected to form *R*~3~^3^(10) and *R*~2~^2^(8) ring motifs (Etter *et al.*, 1990; Bernstein *et al.*, 1995) (Fig 1). Bond lengths and angles are as expected (Berrah *et al.* 2011; Dobson & Gerkin, 1996). The three-dimensional structure of (I), results from undulating sheets of cations dimmers parallel to (011) plane(Fig.2 and Fig.3 )and sulfate-water chains extending along \[100\](Fig.3). An interesting hydrogen bonds network, in which all potential donors and acceptors are involved, and especially marked by the presence of *R*~6~^6^(26)and *R*~2~^3^(10) set-graph motifs (Etter *et al.*, 1990; Bernstein *et al.*, 1995), ensures the coherence of the structure(Fig.2 and Fig.3, table 1). This later is reinforced by the contribution of π-π, S---O··· π and C---O··· π interactions (Dorn *et al.* 2005; Janiak, 2000) (table 2,3). Experimental {#experimental} ============ The title compound was synthesized by reacting 3-amino-pyrazine 2- carboxylic acid with some excess of sulphiric acid in aqueous solution. Slow evaporation leads to well crystallized yellow needles. Refinement {#refinement} ========== All non-H atoms were refined with anisotropic atomic displacement parameters. H atoms of water molecule were located in difference Fourier maps and treated as riding on their parent oxygen atoms with O---H = 0.85, H···H = 1.40 and *U*~iso~(H) = 1.5*U*~eq~(O). The remaining H atoms were localized on Fourier maps but introduced in calculated positions and treated as riding on their parent atoms (C, N or O) with C---H = 0.95 Å, O---H = 0.84 Å and N---H = 0.88 Å with *U*~iso~(H) = 1.2*U*~eq~(C or N) and *U*~iso~(H = 1.5 *U*~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound with the atomic labelling scheme.Displacement are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o677-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing view showing undulating sheets parallel to (011) plane and R66(26) rings set motif. Hydrogen bonds are shown as dashed lines. Hydrogen atoms not involved in H-bonds have been omitted for clarity ::: ![](e-67-0o677-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Partial packing view showing sulfate-water chains extending along \[100\] direction and undulating sheets. Hydrogen bonds are shown as dashed lines.Hydrogen atoms not involved in H-bonds have been omitted for clarity. ::: ![](e-67-0o677-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e216 .table-wrap} --------------------------------------- --------------------------------------- 2C~5~H~6~N~3~O~2~^+^·SO~4~^2−^·2H~2~O *F*(000) = 856 *M~r~* = 412.36 *D*~x~ = 1.706 Mg m^−3^ Monoclinic, *P*2~1~/*a* Mo *K*α radiation, λ = 0.71073 Å *a* = 7.7214 (4) Å Cell parameters from 5179 reflections *b* = 20.7043 (14) Å θ = 2.8--27.5° *c* = 10.6398 (7) Å µ = 0.27 mm^−1^ β = 109.299 (2)° *T* = 150 K *V* = 1605.36 (17) Å^3^ Prism, yellow *Z* = 4 0.55 × 0.36 × 0.15 mm --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e357 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII diffractometer 3146 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.039 CCD rotation images, thin slices scans θ~max~ = 27.6°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Sheldrick, 2002) *h* = −8→9 *T*~min~ = 0.708, *T*~max~ = 0.960 *k* = −26→26 13466 measured reflections *l* = −13→13 3675 independent reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e468 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.035 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.096 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0491*P*)^2^ + 0.7394*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3675 reflections (Δ/σ)~max~ = 0.001 246 parameters Δρ~max~ = 0.47 e Å^−3^ 0 restraints Δρ~min~ = −0.48 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e625 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e724 .table-wrap} ------ --------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O5A 0.17659 (16) 0.04617 (6) 0.03501 (11) 0.0221 (3) H5A 0.1515 0.0732 −0.0273 0.033\* O6A 0.03846 (18) 0.11842 (6) 0.12557 (11) 0.0258 (3) N1A 0.0567 (2) 0.10587 (7) 0.37979 (13) 0.0231 (3) H1A1 0.0399 0.1167 0.4549 0.028\* H1A2 0.0122 0.1303 0.3087 0.028\* N2A 0.21592 (19) 0.01604 (6) 0.48490 (13) 0.0195 (3) H2A 0.1989 0.0288 0.5588 0.023\* N3A 0.27826 (19) −0.02410 (6) 0.25952 (13) 0.0194 (3) C1A 0.1266 (2) 0.06905 (7) 0.13275 (15) 0.0185 (3) C2A 0.1875 (2) 0.02980 (7) 0.25829 (15) 0.0177 (3) C3A 0.1485 (2) 0.05305 (7) 0.37379 (15) 0.0183 (3) C4A 0.3079 (2) −0.03946 (8) 0.48622 (16) 0.0207 (3) H4A 0.3518 −0.0644 0.5654 0.025\* C5A 0.3374 (2) −0.05941 (8) 0.37264 (16) 0.0214 (3) H5C 0.4006 −0.0988 0.3731 0.026\* O5B −0.03794 (19) 0.32977 (6) 1.37046 (12) 0.0273 (3) H5B −0.0768 0.3055 1.4185 0.041\* O6B −0.03786 (17) 0.23824 (5) 1.25812 (11) 0.0241 (3) N1B 0.0619 (2) 0.24559 (7) 1.03668 (14) 0.0238 (3) H1B1 0.0821 0.2313 0.9649 0.029\* H1B2 0.0315 0.2184 1.0895 0.029\* N2B 0.12393 (19) 0.34886 (7) 0.98346 (13) 0.0205 (3) H2B 0.1422 0.3332 0.912 0.025\* N3B 0.07073 (19) 0.39911 (6) 1.20349 (13) 0.0206 (3) C1B −0.0126 (2) 0.29617 (8) 1.27448 (15) 0.0196 (3) C2B 0.0482 (2) 0.33663 (7) 1.17934 (14) 0.0178 (3) C3B 0.0773 (2) 0.30786 (8) 1.06522 (15) 0.0187 (3) C4B 0.1438 (2) 0.41269 (8) 1.00633 (16) 0.0227 (3) H4B 0.1752 0.4403 0.9458 0.027\* C5B 0.1180 (2) 0.43737 (8) 1.11810 (16) 0.0233 (3) H5D 0.1338 0.4824 1.1357 0.028\* S1 0.15317 (5) 0.131125 (18) 0.73117 (4) 0.01813 (11) O1 0.2146 (2) 0.06509 (6) 0.71883 (12) 0.0337 (3) O2 0.09536 (18) 0.13565 (6) 0.85065 (12) 0.0262 (3) O3 0.30149 (17) 0.17773 (7) 0.74478 (12) 0.0306 (3) O4 −0.00482 (16) 0.14708 (6) 0.61180 (11) 0.0236 (3) O1W 0.23309 (17) 0.30737 (6) 0.78406 (12) 0.0262 (3) H1W 0.2465 0.2676 0.7697 0.039\* H2W 0.3352 0.3253 0.7903 0.039\* O2W −0.15818 (19) 0.26453 (6) 1.52193 (12) 0.0296 (3) H3W −0.1068 0.2285 1.5511 0.044\* H4W −0.1653 0.2863 1.5886 0.044\* ------ --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1307 .table-wrap} ----- ------------ -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O5A 0.0332 (7) 0.0213 (6) 0.0140 (5) 0.0044 (5) 0.0109 (5) 0.0030 (4) O6A 0.0400 (7) 0.0206 (6) 0.0184 (6) 0.0076 (5) 0.0115 (5) 0.0036 (4) N1A 0.0340 (8) 0.0227 (7) 0.0140 (6) 0.0063 (6) 0.0100 (6) 0.0012 (5) N2A 0.0269 (7) 0.0193 (6) 0.0128 (6) −0.0002 (5) 0.0072 (5) 0.0001 (5) N3A 0.0253 (7) 0.0168 (6) 0.0158 (6) −0.0013 (5) 0.0063 (5) −0.0003 (5) C1A 0.0232 (8) 0.0172 (7) 0.0153 (7) −0.0026 (6) 0.0065 (6) −0.0007 (6) C2A 0.0225 (8) 0.0159 (7) 0.0154 (7) −0.0020 (6) 0.0072 (6) −0.0008 (6) C3A 0.0229 (8) 0.0175 (7) 0.0144 (7) −0.0027 (6) 0.0062 (6) −0.0007 (6) C4A 0.0259 (8) 0.0177 (7) 0.0168 (7) −0.0016 (6) 0.0048 (6) 0.0035 (6) C5A 0.0279 (9) 0.0163 (7) 0.0186 (7) 0.0011 (6) 0.0056 (6) 0.0000 (6) O5B 0.0480 (8) 0.0198 (6) 0.0201 (6) −0.0009 (5) 0.0194 (5) −0.0004 (5) O6B 0.0355 (7) 0.0185 (6) 0.0193 (6) −0.0015 (5) 0.0104 (5) 0.0003 (4) N1B 0.0372 (8) 0.0188 (7) 0.0167 (6) −0.0035 (6) 0.0105 (6) −0.0037 (5) N2B 0.0267 (7) 0.0221 (7) 0.0128 (6) −0.0027 (5) 0.0069 (5) −0.0024 (5) N3B 0.0267 (7) 0.0172 (6) 0.0167 (6) 0.0005 (5) 0.0056 (5) −0.0008 (5) C1B 0.0231 (8) 0.0198 (8) 0.0141 (7) 0.0019 (6) 0.0039 (6) 0.0008 (6) C2B 0.0216 (8) 0.0173 (7) 0.0127 (7) 0.0005 (6) 0.0033 (6) 0.0001 (5) C3B 0.0203 (8) 0.0194 (7) 0.0142 (7) −0.0010 (6) 0.0029 (6) −0.0014 (6) C4B 0.0276 (9) 0.0201 (8) 0.0195 (7) −0.0035 (6) 0.0068 (6) 0.0020 (6) C5B 0.0324 (9) 0.0177 (7) 0.0193 (7) −0.0019 (6) 0.0077 (7) 0.0004 (6) S1 0.0259 (2) 0.01758 (19) 0.01276 (18) 0.00290 (14) 0.00883 (15) 0.00224 (13) O1 0.0605 (9) 0.0245 (6) 0.0186 (6) 0.0188 (6) 0.0163 (6) 0.0047 (5) O2 0.0429 (7) 0.0230 (6) 0.0193 (6) 0.0051 (5) 0.0192 (5) 0.0035 (5) O3 0.0291 (7) 0.0384 (7) 0.0238 (6) −0.0067 (5) 0.0080 (5) 0.0029 (5) O4 0.0266 (6) 0.0246 (6) 0.0179 (6) 0.0031 (5) 0.0049 (5) 0.0017 (4) O1W 0.0294 (6) 0.0273 (6) 0.0252 (6) −0.0009 (5) 0.0136 (5) −0.0005 (5) O2W 0.0460 (8) 0.0244 (6) 0.0229 (6) 0.0086 (5) 0.0174 (6) 0.0061 (5) ----- ------------ -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1809 .table-wrap} ----------------------- -------------- ----------------------- -------------- O5A---C1A 1.3116 (19) N1B---H1B1 0.88 O5A---H5A 0.84 N1B---H1B2 0.88 O6A---C1A 1.216 (2) N2B---C4B 1.343 (2) N1A---C3A 1.316 (2) N2B---C3B 1.347 (2) N1A---H1A1 0.88 N2B---H2B 0.88 N1A---H1A2 0.88 N3B---C2B 1.319 (2) N2A---C4A 1.349 (2) N3B---C5B 1.344 (2) N2A---C3A 1.360 (2) C1B---C2B 1.503 (2) N2A---H2A 0.88 C2B---C3B 1.435 (2) N3A---C2A 1.315 (2) C4B---C5B 1.368 (2) N3A---C5A 1.352 (2) C4B---H4B 0.95 C1A---C2A 1.500 (2) C5B---H5D 0.95 C2A---C3A 1.442 (2) S1---O1 1.4670 (12) C4A---C5A 1.365 (2) S1---O3 1.4677 (13) C4A---H4A 0.95 S1---O4 1.4786 (12) C5A---H5C 0.95 S1---O2 1.4831 (12) O5B---C1B 1.3028 (19) O1W---H1W 0.8491 O5B---H5B 0.84 O1W---H2W 0.8542 O6B---C1B 1.218 (2) O2W---H3W 0.8543 N1B---C3B 1.321 (2) O2W---H4W 0.8582 C1A---O5A---H5A 109.5 C4B---N2B---C3B 122.81 (14) C3A---N1A---H1A1 120 C4B---N2B---H2B 118.6 C3A---N1A---H1A2 120 C3B---N2B---H2B 118.6 H1A1---N1A---H1A2 120 C2B---N3B---C5B 119.63 (14) C4A---N2A---C3A 122.57 (14) O6B---C1B---O5B 125.38 (15) C4A---N2A---H2A 118.7 O6B---C1B---C2B 121.55 (14) C3A---N2A---H2A 118.7 O5B---C1B---C2B 113.05 (14) C2A---N3A---C5A 119.32 (14) N3B---C2B---C3B 121.62 (14) O6A---C1A---O5A 123.99 (14) N3B---C2B---C1B 117.76 (14) O6A---C1A---C2A 121.03 (14) C3B---C2B---C1B 120.62 (14) O5A---C1A---C2A 114.98 (13) N1B---C3B---N2B 119.31 (15) N3A---C2A---C3A 122.39 (14) N1B---C3B---C2B 124.91 (15) N3A---C2A---C1A 118.54 (14) N2B---C3B---C2B 115.78 (14) C3A---C2A---C1A 119.06 (14) N2B---C4B---C5B 118.98 (15) N1A---C3A---N2A 118.94 (14) N2B---C4B---H4B 120.5 N1A---C3A---C2A 125.91 (14) C5B---C4B---H4B 120.5 N2A---C3A---C2A 115.15 (14) N3B---C5B---C4B 121.17 (15) N2A---C4A---C5A 119.33 (14) N3B---C5B---H5D 119.4 N2A---C4A---H4A 120.3 C4B---C5B---H5D 119.4 C5A---C4A---H4A 120.3 O1---S1---O3 110.91 (9) N3A---C5A---C4A 121.21 (15) O1---S1---O4 109.31 (7) N3A---C5A---H5C 119.4 O3---S1---O4 109.46 (7) C4A---C5A---H5C 119.4 O1---S1---O2 109.47 (7) C1B---O5B---H5B 109.5 O3---S1---O2 108.66 (7) C3B---N1B---H1B1 120 O4---S1---O2 109.00 (7) C3B---N1B---H1B2 120 H1W---O1W---H2W 105.7 H1B1---N1B---H1B2 120 H3W---O2W---H4W 108 C5A---N3A---C2A---C3A 0.1 (2) C5B---N3B---C2B---C3B 1.6 (2) C5A---N3A---C2A---C1A 178.70 (14) C5B---N3B---C2B---C1B −177.43 (14) O6A---C1A---C2A---N3A 178.18 (15) O6B---C1B---C2B---N3B 179.35 (15) O5A---C1A---C2A---N3A −2.2 (2) O5B---C1B---C2B---N3B 0.9 (2) O6A---C1A---C2A---C3A −3.2 (2) O6B---C1B---C2B---C3B 0.3 (2) O5A---C1A---C2A---C3A 176.41 (14) O5B---C1B---C2B---C3B −178.12 (14) C4A---N2A---C3A---N1A 178.56 (15) C4B---N2B---C3B---N1B −179.42 (15) C4A---N2A---C3A---C2A −1.9 (2) C4B---N2B---C3B---C2B 0.5 (2) N3A---C2A---C3A---N1A −179.04 (16) N3B---C2B---C3B---N1B 178.17 (15) C1A---C2A---C3A---N1A 2.4 (2) C1B---C2B---C3B---N1B −2.9 (2) N3A---C2A---C3A---N2A 1.5 (2) N3B---C2B---C3B---N2B −1.7 (2) C1A---C2A---C3A---N2A −177.09 (13) C1B---C2B---C3B---N2B 177.27 (14) C3A---N2A---C4A---C5A 0.8 (2) C3B---N2B---C4B---C5B 0.8 (2) C2A---N3A---C5A---C4A −1.4 (2) C2B---N3B---C5B---C4B −0.2 (3) N2A---C4A---C5A---N3A 0.9 (2) N2B---C4B---C5B---N3B −1.0 (3) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2424 .table-wrap} ---------------------- --------- --------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1A---H1A1···O4 0.88 1.92 2.7970 (18) 175. N1A---H1A2···O6A 0.88 2.04 2.6741 (18) 128. N1A---H1A2···O6B^i^ 0.88 2.30 3.0158 (18) 138. N2A---H2A···O1 0.88 1.83 2.6915 (18) 167. N1B---H1B1···O2 0.88 2.34 3.0827 (18) 142. N1B---H1B2···O6B 0.88 2.08 2.7144 (19) 129. N1B---H1B2···O6A^ii^ 0.88 2.10 2.8237 (18) 139. N2B---H2B···O1W 0.88 1.81 2.6705 (18) 167. O5B---H5B···O2W 0.84 1.67 2.5046 (17) 174. O5A---H5A···O2^i^ 0.84 1.78 2.6192 (16) 175. O1W---H1W···O3 0.85 1.95 2.7934 (19) 175. O1W---H2W···O2^iii^ 0.85 2.06 2.8996 (18) 167 O1W---H2W···O4^iii^ 0.85 2.65 3.2856 (17) 133. O2W---H3W···O4^ii^ 0.85 1.88 2.7351 (17) 177. O2W---H4W···O3^iv^ 0.86 1.91 2.7633 (17) 171. C4A---H4A···O5B^v^ 0.95 2.58 3.320 (2) 134. C4A---H4A···N3B^v^ 0.95 2.45 3.369 (2) 163. C4B---H4B···O5A^vi^ 0.95 2.45 3.187 (2) 134. C4B---H4B···N3A^vi^ 0.95 2.44 3.347 (2) 159 C5A---H5C···O1W^vii^ 0.95 2.55 3.175 (2) 124. C5B---H5D···O1^viii^ 0.95 2.35 3.192 (2) 148. ---------------------- --------- --------- ------------- --------------- ::: Symmetry codes: (i) *x*, *y*, *z*−1; (ii) *x*, *y*, *z*+1; (iii) *x*+1/2, −*y*+1/2, *z*; (iv) *x*−1/2, −*y*+1/2, *z*+1; (v) −*x*+1/2, *y*−1/2, −*z*+2; (vi) −*x*+1/2, *y*+1/2, −*z*+1; (vii) −*x*+1/2, *y*−1/2, −*z*+1; (viii) −*x*+1/2, *y*+1/2, −*z*+2. Table 2 π--π stacking interactions (Å, °) {#d1e2805} ========================================= Cg1 is the centroid of the N2A--C4A ring. ::: {#d1e2827 .table-wrap} ----- -------- -------------- --- ------- ------- --------------- --------------- ---------- CgI CgJ CgI···CgJ^a^ α β γ CgI···P(J)^b^ CgJ···P(I)^c^ Slippage Cg1 Cg1^i^ 3.9678 (9) 0 34.94 34.94 3.2528 (6) 3.2527 (6) 2.272 ----- -------- -------------- --- ------- ------- --------------- --------------- ---------- ::: Symmetry codes: (i)1-x,-y,1-z Notes: a : Distance between centroids b : Perpendicular distance of CgI on ring plan J c : Perpendicular distance of CgJ on ring plan I α = Dihedral Angle between the ring planes β = Angle between the centroid vector CgI···CgJ and the normal to the plane I. γ = Angle between the centroid vector CgI···CgJ and the normal to the plane J. Slippage = vertical displacement between ring centroids. Table 3 S---O···π and C---O···π interactions (Å, °). {#d1e2891} ==================================================== Cg1 and Cg2 are the centroids of the N2A--C4A and N2B--C4B rings, respectively. ::: {#d1e2914 .table-wrap} ----- ----- ---------- ------------- ------------- ------------- X I J I···J X--I···J X···J S1 O1 Cg1^i^ 3.5922 (17) 91.83 (7) 3.9233 (8) S1 O2 Cg1^i^ 3.9845 (14) 76.88 (5) 3.9233 (8) S1 O2 Cg2^ii^ 3.8831 (15) 92.77 (6) 4.2231 (8) C1A O6A Cg2^iii^ 3.3136 (16) 125.62 (11) 4.1418 (18) ----- ----- ---------- ------------- ------------- ------------- ::: Symmetry codes: (i) -x, -y, 1-z; (ii) x, y, 1+z; (iii) x-1, y, z. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------------- --------- ------- ------------- ------------- N1*A*---H1*A*1⋯O4 0.88 1.92 2.7970 (18) 175 N1*A*---H1*A*2⋯O6*A* 0.88 2.04 2.6741 (18) 128 N1*A*---H1*A*2⋯O6*B*^i^ 0.88 2.30 3.0158 (18) 138 N2*A*---H2*A*⋯O1 0.88 1.83 2.6915 (18) 167 N1*B*---H1*B*1⋯O2 0.88 2.34 3.0827 (18) 142 N1*B*---H1*B*2⋯O6*B* 0.88 2.08 2.7144 (19) 129 N1*B*---H1*B*2⋯O6*A*^ii^ 0.88 2.10 2.8237 (18) 139 N2*B*---H2*B*⋯O1*W* 0.88 1.81 2.6705 (18) 167 O5*B*---H5*B*⋯O2*W* 0.84 1.67 2.5046 (17) 174 O5*A*---H5*A*⋯O2^i^ 0.84 1.78 2.6192 (16) 175 O1*W*---H1*W*⋯O3 0.85 1.95 2.7934 (19) 175 O1*W*---H2*W*⋯O2^iii^ 0.85 2.06 2.8996 (18) 167 O1*W*---H2*W*⋯O4^iii^ 0.85 2.65 3.2856 (17) 133 O2*W*---H3*W*⋯O4^ii^ 0.85 1.88 2.7351 (17) 177 O2*W*---H4*W*⋯O3^iv^ 0.86 1.91 2.7633 (17) 171 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::

PubMed Central

2024-06-05T04:04:18.420014

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052097/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o677-o678", "authors": [ { "first": "Fadila", "last": "Berrah" }, { "first": "Amira", "last": "Ouakkaf" }, { "first": "Sofiane", "last": "Bouacida" }, { "first": "Thierry", "last": "Roisnel" } ] }

PMC3052098

Related literature {#sec1} ================== For the synthesis, see: Couldwell & House (1972[@bb8]); House (1970[@bb9]). For related structures, see: Choi *et al.* (2002[@bb7], 2007[@bb5], 2008[@bb6], 2010[@bb4]); Vaughn & Rogers (1985[@bb14]); Kou *et al.* (2001[@bb10]). For tn ligand geometry, see: Vaughn (1981[@bb13]). For the standard Cambridge Structural Database description, see: Allen (2002[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[CrCl~2~(C~3~H~10~N~2~)~2~\]ClO~4~*M* *~r~* = 370.61Monoclinic,*a* = 6.4306 (5) Å*b* = 17.2588 (15) Å*c* = 13.0235 (11) Åβ = 92.840 (4)°*V* = 1443.6 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 1.36 mm^−1^*T* = 173 K0.16 × 0.08 × 0.05 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*TWINABS*; Sheldrick, 2008*a* [@bb11]) *T* ~min~ = 0.815, *T* ~max~ = 0.93028308 measured reflections6269 independent reflections5585 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.039 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.028*wR*(*F* ^2^) = 0.075*S* = 1.076269 reflections245 parametersAll H-atom parameters refinedΔρ~max~ = 0.36 e Å^−3^Δρ~min~ = −0.32 e Å^−3^ {#d5e576} Data collection: *APEX2* (Bruker, 2010[@bb3]); cell refinement: *SAINT* (Bruker, 2010[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008*b* [@bb12]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *DIAMOND* (Brandenburg, 2010[@bb2]); software used to prepare material for publication: *SHELXTL* and local programs. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006349/nk2086sup1.cif](http://dx.doi.org/10.1107/S1600536811006349/nk2086sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006349/nk2086Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006349/nk2086Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?nk2086&file=nk2086sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?nk2086sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?nk2086&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NK2086](http://scripts.iucr.org/cgi-bin/sendsup?nk2086)). This work was supported by a grant from the 2010 Research Fund of Andong National University. Comment ======= The \[Cr(tn)~2~*L*~2~\]^+^ cation (tn = propane-1,3-diamine, *L* = monodentate ligand) can exist as *trans* and *cis* geometric isomers. There are also two possible conformations with respect to the six-membered chelate rings (present as chairs) in the *trans* geometric isomer: the carbon atoms of these rings in the two tn ligands can be located on the same side (*syn* conformer) or on opposite side (*anti* conformer) of the equatorial plane. In the crystal structures of *trans*-\[Cr(Me~2~tn)~2~Cl~2~\]Cl and *trans*-\[Cr(Me~2~tn)~2~Br~2~\]~2~Br~2~.HClO~4~.6H~2~O (Me~2~tn = 2,2-dimethylpropane-1,3-diamine), both *syn* and *anti* conformational isomers are found together (Choi *et al.*, 2002; Choi *et al.*, 2007), while *trans*-\[Cr(Me~2~tn)~2~Cl~2~\]ClO~4~ (Choi *et al.*, 2008) has only the *anti* conformer, as do *trans*-\[Cr(tn)~2~F~2~\]ClO~4~ (Vaughn & Rogers, 1985) and *trans*-\[Cr(tn)~2~Cl~2~\]~3~\[Fe(CN)~6~.6H~2~O (Kou *et al.*, 2001). The preference for *syn* or *anti* conformation of chelate rings in *trans* complex cations with tn or Me~2~tn ligands is thus subtle and worthy of further study. Infrared and electronic absorption spectroscopic methods are not useful in distinguishing such *syn* and *anti* conformations in these metal complexes. Structural studies of bromido-containing chromium(III) complexes are relatively rare compared to those with chlorido ligands. Therefore we attempted to prepare *trans*-\[Cr(tn)~2~Br~2~\]ClO~4~ by a literature method (Couldwell & House, 1972); its UV-visible and IR spectra are nearly the same as those of *trans*-\[Cr(tn)~2~Cl~2~\]ClO~4~ (House, 1970), and it was only with a crystal structure analysis that we established that the product was actually the dichlorido rather than the dibromido complex. We report here the structure of *trans*-\[Cr(tn)~2~Cl~2~\]ClO~4~ (I) which provides further information on the conformation of the two six-membered chelate rings. In the title complex (I), the chromium(III) ion is coplanar with the four coordinating N atoms and adopts an octahedral geometry, in which the four nitrogen atoms of two tn ligands occupy the equatorial sites and the two chlorine atoms coordinate axially in a *trans* configuration. The two six-membered rings have their usual stable chair conformations, and they are exclusively in the *anti* conformation with respect to each other in the unique cation of the asymmetric unit (Fig. 1). The Cr---N distances (Table 1) are in the range 2.0831 (18)--2.0917 (19) Å, typical for Cr---N bonds involving primary amines (Choi *et al.*, 2002; Choi *et al.*, 2007). The Cr---Cl distances \[2.3135 (6) and 2.3148 (6) Å\] are very close to the values 2.3179 (9) and 2.3212 (4) Å found in *trans*-\[Cr(Me~2~tn)~2~Cl~2~\]ClO~4~ (Choi *et al.*, 2008), and typical generally of Cr---Cl bond lengths in the Cambridge Structural Database (Allen, 2002), but shorter than the 2.4743 (10) Å for Cr---Br bond lengths in *trans*-\[Cr(en)~2~Br~2~\]ClO~4~ (Choi *et al.*, 2010). The assignment of the axial ligands as Cl rather than the Br intended and expected from the synthesis is also clearly correct from the satisfactory refinement of anisotropic displacement parameters, demonstrating an appropriate electron density. The internal geometry of the tn ligands is typical for these in chair conformations (Vaughn, 1981). The uncoordinated ClO~4~^-^ anion shows an essentially tetrahedral arrangement with Cl---O distances in the range 1.4268 (19)--1.4380 (19) Å and the angles at Cl ranging from 108.32 (11) to 110.48 (13)°. There is an extensive weak hydrogen bonding network involving the oxygen atoms of the anions, chlorido ligands, and the N---H groups of the tn ligands (Table 2), which supports the main ionic interactions in this complex salt. Experimental {#experimental} ============ The ligand propane-1,3-diamine was obtained from Aldrich Chemical Co. and was used as supplied. All other chemicals were reagent grade materials and were used without further purification. We intended to prepare *trans*-\[Cr(tn)~2~Br~2~\]ClO~4~ as described in the literature (Couldwell & House, 1972) but obtained instead *trans*-\[Cr(tn)~2~Cl~2~\]ClO~4~, as demonstrated by this crystal structure analysis. CrCl~3~.6H~2~O (5.4 g) was dissolved in DMSO (25 ml) and the solution was boiled for 10 min. A mixture of 1,3-propanediamine (3 ml) and DMSO (15 ml) was added and boiling was continued for 2 min. After cooling to 60°C, the solution was poured into well stirred acetone (300 ml). The precipitate was filtered off and washed with acetone, then dissolved in aqueous HBr (20 ml, 48%) and the solution was heated on a steam bath for 15 min. and filtered. The filtrate was heated on a steam bath for a further 15 min. Aqueous HClO~4~ (5 ml, 60%) was added to the solution. The resulting green crystals were collected and washed with ethanol. The infrared spectrum (nujol) was consistent with the crystallographically determined structure. The chloro ligands in the title compound are clearly retained from the chromium(III) chloride starting material, and were not substituted as intended by Br in the reaction with HBr. Refinement {#refinement} ========== The crystal was a non-merohedral twin with a 23.45 (6)% contribution of the minor component according to the refinement; because of the twinning, merging of symmetry-equivalent data could not be performed prior to refinement. The twin law is 1 0 0 / 0 - 1 0 / -0.2 0 - 1, corresponding to a 180° rotation about the *a* axis. Hydrogen atoms were located in a difference map and refined freely with individual isotropic displacement parameters. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the complex cation and anion (displacement ellipsoids are drawn at the 50% probability level). ::: ![](e-67-0m381-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e380 .table-wrap} ------------------------------------- --------------------------------------- \[CrCl~2~(C~3~H~10~N~2~)~2~\]ClO~4~ *F*(000) = 764 *M~r~* = 370.61 *D*~x~ = 1.705 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 6530 reflections *a* = 6.4306 (5) Å θ = 2.8--28.3° *b* = 17.2588 (15) Å µ = 1.36 mm^−1^ *c* = 13.0235 (11) Å *T* = 173 K β = 92.840 (4)° Block, green *V* = 1443.6 (2) Å^3^ 0.16 × 0.08 × 0.05 mm *Z* = 4 ------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e517 .table-wrap} ----------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 6269 independent reflections Radiation source: sealed tube 5585 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.039 Thin--slice ω scans θ~max~ = 28.4°, θ~min~ = 2.0° Absorption correction: multi-scan (TWINABS; Sheldrick, 2008*a*) *h* = −8→8 *T*~min~ = 0.815, *T*~max~ = 0.930 *k* = 0→23 28308 measured reflections *l* = 0→17 ----------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e626 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.028 All H-atom parameters refined *wR*(*F*^2^) = 0.075 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0391*P*)^2^ + 1.9009*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.07 (Δ/σ)~max~ = 0.001 6269 reflections Δρ~max~ = 0.36 e Å^−3^ 245 parameters Δρ~min~ = −0.32 e Å^−3^ 0 restraints Extinction correction: *SHELXTL* (Sheldrick, 2008a), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0011 (6) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e807 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e906 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cr 0.49360 (5) 0.396455 (18) 0.29650 (2) 0.01236 (9) Cl1 0.24916 (7) 0.41493 (3) 0.41882 (4) 0.01906 (12) Cl2 0.74177 (7) 0.37755 (3) 0.17627 (4) 0.01921 (12) N1 0.7262 (3) 0.42985 (10) 0.40534 (14) 0.0149 (3) H1A 0.840 (4) 0.4296 (16) 0.375 (2) 0.026 (7)\* H1B 0.707 (4) 0.4791 (15) 0.4214 (19) 0.015 (6)\* N2 0.5301 (3) 0.28012 (11) 0.33866 (15) 0.0177 (4) H2A 0.619 (5) 0.2656 (17) 0.301 (2) 0.028 (8)\* H2B 0.417 (5) 0.2552 (18) 0.321 (2) 0.039 (8)\* N3 0.2572 (3) 0.36594 (12) 0.18892 (14) 0.0182 (4) H3A 0.258 (4) 0.3159 (17) 0.182 (2) 0.027 (7)\* H3B 0.138 (5) 0.3757 (16) 0.219 (2) 0.030 (8)\* N4 0.4523 (3) 0.51159 (11) 0.25055 (15) 0.0194 (4) H4A 0.556 (4) 0.5348 (16) 0.271 (2) 0.024 (7)\* H4B 0.356 (5) 0.5272 (16) 0.284 (2) 0.029 (8)\* C1 0.7561 (3) 0.38579 (13) 0.50303 (17) 0.0190 (4) H1C 0.872 (4) 0.4054 (15) 0.543 (2) 0.022 (7)\* H1D 0.634 (4) 0.3944 (13) 0.5441 (19) 0.011 (6)\* C2 0.7850 (4) 0.29977 (13) 0.48554 (19) 0.0236 (5) H2C 0.894 (4) 0.2925 (15) 0.439 (2) 0.022 (7)\* H2D 0.821 (4) 0.2755 (17) 0.550 (2) 0.034 (8)\* C3 0.5888 (4) 0.25891 (13) 0.44656 (18) 0.0222 (5) H3C 0.605 (4) 0.2040 (16) 0.450 (2) 0.024 (7)\* H3D 0.476 (4) 0.2728 (15) 0.490 (2) 0.023 (7)\* C4 0.2446 (4) 0.40246 (14) 0.08533 (18) 0.0232 (5) H4C 0.366 (4) 0.3889 (15) 0.051 (2) 0.022 (7)\* H4D 0.121 (4) 0.3793 (15) 0.045 (2) 0.021 (6)\* C5 0.2255 (4) 0.48944 (15) 0.09247 (19) 0.0244 (5) H5C 0.203 (4) 0.5077 (16) 0.021 (2) 0.032 (8)\* H5D 0.104 (4) 0.5017 (16) 0.129 (2) 0.029 (7)\* C6 0.4160 (4) 0.52997 (14) 0.13932 (19) 0.0242 (5) H6C 0.542 (4) 0.5136 (15) 0.106 (2) 0.021 (6)\* H6D 0.403 (4) 0.5848 (17) 0.135 (2) 0.029 (7)\* Cl3 0.07592 (8) 0.14746 (3) 0.25004 (4) 0.01984 (12) O1 0.1011 (3) 0.06757 (10) 0.22292 (16) 0.0363 (4) O2 0.1833 (3) 0.19442 (11) 0.17838 (16) 0.0384 (5) O3 −0.1425 (3) 0.16517 (11) 0.24445 (15) 0.0358 (4) O4 0.1632 (3) 0.16154 (14) 0.35117 (15) 0.0475 (5) ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1403 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cr 0.00998 (15) 0.01357 (16) 0.01352 (17) −0.00015 (11) 0.00047 (11) −0.00070 (12) Cl1 0.0142 (2) 0.0238 (3) 0.0196 (3) 0.00007 (18) 0.00468 (18) −0.00218 (19) Cl2 0.0131 (2) 0.0257 (3) 0.0190 (3) 0.00135 (18) 0.00347 (18) −0.00246 (19) N1 0.0135 (8) 0.0154 (9) 0.0160 (9) −0.0014 (6) 0.0014 (6) −0.0011 (7) N2 0.0171 (8) 0.0166 (9) 0.0192 (9) −0.0015 (7) −0.0009 (7) −0.0017 (7) N3 0.0133 (8) 0.0238 (10) 0.0175 (9) −0.0010 (7) −0.0003 (7) −0.0028 (7) N4 0.0197 (9) 0.0179 (9) 0.0206 (10) 0.0006 (7) 0.0006 (8) 0.0014 (7) C1 0.0222 (10) 0.0194 (10) 0.0150 (10) −0.0019 (8) −0.0024 (8) −0.0007 (8) C2 0.0281 (12) 0.0194 (11) 0.0226 (12) 0.0020 (9) −0.0065 (10) 0.0011 (9) C3 0.0310 (12) 0.0155 (10) 0.0201 (11) −0.0035 (9) −0.0004 (9) 0.0030 (8) C4 0.0191 (10) 0.0338 (13) 0.0164 (11) 0.0023 (9) −0.0017 (8) −0.0017 (9) C5 0.0210 (11) 0.0329 (13) 0.0193 (11) 0.0081 (9) 0.0005 (9) 0.0048 (9) C6 0.0269 (11) 0.0243 (12) 0.0216 (11) 0.0040 (9) 0.0031 (9) 0.0080 (9) Cl3 0.0206 (2) 0.0175 (2) 0.0210 (3) −0.00116 (19) −0.00290 (19) −0.00153 (19) O1 0.0380 (10) 0.0179 (8) 0.0530 (13) 0.0042 (7) 0.0012 (9) −0.0030 (8) O2 0.0452 (11) 0.0343 (10) 0.0364 (11) −0.0138 (9) 0.0092 (9) 0.0050 (8) O3 0.0246 (9) 0.0394 (10) 0.0434 (12) 0.0087 (8) 0.0019 (8) −0.0052 (9) O4 0.0523 (13) 0.0653 (15) 0.0235 (10) −0.0131 (11) −0.0121 (9) −0.0053 (10) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1777 .table-wrap} -------------------- -------------- -------------------- -------------- Cr---Cl1 2.3148 (6) C1---H1D 0.98 (2) Cr---Cl2 2.3135 (6) C1---C2 1.515 (3) Cr---N1 2.0903 (18) C2---H2C 0.95 (3) Cr---N2 2.0917 (19) C2---H2D 0.96 (3) Cr---N3 2.0831 (18) C2---C3 1.511 (3) Cr---N4 2.0884 (19) C3---H3C 0.95 (3) N1---H1A 0.85 (3) C3---H3D 0.97 (3) N1---H1B 0.89 (3) C4---H4C 0.95 (3) N1---C1 1.486 (3) C4---H4D 1.02 (3) N2---H2A 0.81 (3) C4---C5 1.510 (3) N2---H2B 0.86 (3) C5---H5C 0.99 (3) N2---C3 1.483 (3) C5---H5D 0.95 (3) N3---H3A 0.87 (3) C5---C6 1.513 (3) N3---H3B 0.89 (3) C6---H6C 0.98 (3) N3---C4 1.488 (3) C6---H6D 0.95 (3) N4---H4A 0.81 (3) Cl3---O1 1.4346 (18) N4---H4B 0.82 (3) Cl3---O2 1.4380 (19) N4---C6 1.490 (3) Cl3---O3 1.4360 (18) C1---H1C 0.95 (3) Cl3---O4 1.4268 (19) Cl1---Cr---Cl2 179.11 (2) N1---C1---C2 112.60 (19) Cl1---Cr---N1 89.02 (5) H1C---C1---H1D 106 (2) Cl1---Cr---N2 91.31 (6) H1C---C1---C2 109.5 (15) Cl1---Cr---N3 90.00 (6) H1D---C1---C2 109.7 (13) Cl1---Cr---N4 89.14 (6) C1---C2---H2C 108.8 (16) Cl2---Cr---N1 90.19 (5) C1---C2---H2D 108.8 (18) Cl2---Cr---N2 88.28 (6) C1---C2---C3 113.6 (2) Cl2---Cr---N3 90.80 (6) H2C---C2---H2D 110 (2) Cl2---Cr---N4 91.29 (6) H2C---C2---C3 110.8 (16) N1---Cr---N2 91.11 (7) H2D---C2---C3 104.7 (17) N1---Cr---N3 178.42 (8) N2---C3---C2 111.85 (19) N1---Cr---N4 90.49 (7) N2---C3---H3C 108.4 (16) N2---Cr---N3 90.15 (8) N2---C3---H3D 108.9 (16) N2---Cr---N4 178.34 (8) C2---C3---H3C 111.0 (16) N3---Cr---N4 88.26 (8) C2---C3---H3D 109.1 (16) Cr---N1---H1A 106.5 (19) H3C---C3---H3D 107 (2) Cr---N1---H1B 108.7 (16) N3---C4---H4C 108.4 (16) Cr---N1---C1 119.81 (13) N3---C4---H4D 108.1 (15) H1A---N1---H1B 104 (2) N3---C4---C5 111.49 (19) H1A---N1---C1 108.7 (19) H4C---C4---H4D 107 (2) H1B---N1---C1 107.6 (16) H4C---C4---C5 110.2 (16) Cr---N2---H2A 102 (2) H4D---C4---C5 111.1 (14) Cr---N2---H2B 109 (2) C4---C5---H5C 105.6 (16) Cr---N2---C3 120.38 (14) C4---C5---H5D 108.8 (17) H2A---N2---H2B 107 (3) C4---C5---C6 114.71 (19) H2A---N2---C3 110 (2) H5C---C5---H5D 108 (2) H2B---N2---C3 108 (2) H5C---C5---C6 108.0 (16) Cr---N3---H3A 108.3 (19) H5D---C5---C6 111.2 (17) Cr---N3---H3B 105.8 (19) N4---C6---C5 112.24 (19) Cr---N3---C4 120.53 (14) N4---C6---H6C 106.3 (15) H3A---N3---H3B 104 (3) N4---C6---H6D 106.0 (17) H3A---N3---C4 109.2 (19) C5---C6---H6C 110.9 (15) H3B---N3---C4 107.9 (19) C5---C6---H6D 111.8 (17) Cr---N4---H4A 107 (2) H6C---C6---H6D 109 (2) Cr---N4---H4B 104 (2) O1---Cl3---O2 108.55 (12) Cr---N4---C6 119.53 (15) O1---Cl3---O3 108.32 (11) H4A---N4---H4B 107 (3) O1---Cl3---O4 110.29 (13) H4A---N4---C6 108 (2) O2---Cl3---O3 110.30 (12) H4B---N4---C6 111 (2) O2---Cl3---O4 108.88 (13) N1---C1---H1C 110.3 (16) O3---Cl3---O4 110.48 (13) N1---C1---H1D 108.4 (14) Cl1---Cr---N1---C1 59.00 (15) Cl1---Cr---N4---C6 −130.76 (17) Cl2---Cr---N1---C1 −120.57 (15) Cl2---Cr---N4---C6 50.02 (17) N2---Cr---N1---C1 −32.28 (16) N1---Cr---N4---C6 140.22 (17) N4---Cr---N1---C1 148.14 (16) N3---Cr---N4---C6 −40.74 (17) Cl1---Cr---N2---C3 −56.16 (16) Cr---N1---C1---C2 53.7 (2) Cl2---Cr---N2---C3 123.04 (16) N1---C1---C2---C3 −71.2 (3) N1---Cr---N2---C3 32.88 (17) Cr---N2---C3---C2 −54.3 (2) N3---Cr---N2---C3 −146.17 (17) C1---C2---C3---N2 71.1 (3) Cl1---Cr---N3---C4 130.33 (16) Cr---N3---C4---C5 −58.4 (2) Cl2---Cr---N3---C4 −50.08 (16) N3---C4---C5---C6 67.0 (3) N2---Cr---N3---C4 −138.36 (17) Cr---N4---C6---C5 58.4 (2) N4---Cr---N3---C4 41.19 (17) C4---C5---C6---N4 −67.7 (3) -------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2479 .table-wrap} --------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···Cl1^i^ 0.85 (3) 2.68 (3) 3.3684 (19) 139 (2) N1---H1B···Cl1^ii^ 0.89 (3) 2.77 (3) 3.5229 (19) 143 (2) N2---H2A···O3^i^ 0.81 (3) 2.45 (3) 3.182 (3) 151 (3) N2---H2A···Cl2 0.81 (3) 2.67 (3) 3.072 (2) 112 (2) N2---H2B···O4 0.86 (3) 2.35 (3) 3.134 (3) 151 (3) N2---H2B···O2 0.86 (3) 2.56 (3) 3.326 (3) 149 (3) N3---H3A···O2 0.87 (3) 2.15 (3) 3.000 (3) 166 (3) N3---H3B···Cl2^iii^ 0.89 (3) 2.58 (3) 3.3168 (19) 140 (2) N4---H4A···O1^iv^ 0.81 (3) 2.28 (3) 3.033 (3) 156 (3) --------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) *x*+1, *y*, *z*; (ii) −*x*+1, −*y*+1, −*z*+1; (iii) *x*−1, *y*, *z*; (iv) −*x*+1, *y*+1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- ---------- ---------- ------------- ------------- N1---H1*A*⋯Cl1^i^ 0.85 (3) 2.68 (3) 3.3684 (19) 139 (2) N1---H1*B*⋯Cl1^ii^ 0.89 (3) 2.77 (3) 3.5229 (19) 143 (2) N2---H2*A*⋯O3^i^ 0.81 (3) 2.45 (3) 3.182 (3) 151 (3) N2---H2*A*⋯Cl2 0.81 (3) 2.67 (3) 3.072 (2) 112 (2) N2---H2*B*⋯O4 0.86 (3) 2.35 (3) 3.134 (3) 151 (3) N2---H2*B*⋯O2 0.86 (3) 2.56 (3) 3.326 (3) 149 (3) N3---H3*A*⋯O2 0.87 (3) 2.15 (3) 3.000 (3) 166 (3) N3---H3*B*⋯Cl2^iii^ 0.89 (3) 2.58 (3) 3.3168 (19) 140 (2) N4---H4*A*⋯O1^iv^ 0.81 (3) 2.28 (3) 3.033 (3) 156 (3) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::

PubMed Central

2024-06-05T04:04:18.426484

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052098/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m381", "authors": [ { "first": "Jong-Ha", "last": "Choi" }, { "first": "William", "last": "Clegg" } ] }

PMC3052099

Related literature {#sec1} ================== For background to the chemistry of α-tocopherol \[systematic name 2,7,8-trimethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-ol\] and its derivatives and their applications, see: Dubbs & Gupta (1998[@bb3]); Azzi & Stoker (2000[@bb1]); Traber & Atkinson (2007[@bb8]). For the preparation, see: Witkowski & Walejko (2002[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~28~H~38~O~11~*M* *~r~* = 550.58Triclinic,*a* = 8.66 (1) Å*b* = 11.30 (1) Å*c* = 14.55 (1) Åα = 85.74 (5)°β = 89.13 (5)°γ = 88.16 (5)°*V* = 1419 (2) Å^3^*Z* = 2Synchrotron radiationλ = 0.59040 Åμ = 0.06 mm^−1^*T* = 100 K0.25 × 0.15 × 0.09 mm ### Data collection {#sec2.1.2} Mar Research MAR315 CCD diffractometerAbsorption correction: multi-scan (*SCALEPACK*; Otwinowski & Minor, 2003[@bb5]) *T* ~min~ = 0.985, *T* ~max~ = 0.9958538 measured reflections5956 independent reflections5260 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.023 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.045*wR*(*F* ^2^) = 0.118*S* = 0.995956 reflections795 parameters752 restraintsH-atom parameters constrainedΔρ~max~ = 0.21 e Å^−3^Δρ~min~ = −0.23 e Å^−3^ {#d5e353} Data collection: NECAT APS beamline software (unpublished); cell refinement: *HKL-2000* (Otwinowski & Minor, 1997[@bb6]); data reduction: *HKL-2000*; program(s) used to solve structure: *SHELXD* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb4]) and *pyMOL* (DeLano, 2002[@bb2]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100626X/gk2341sup1.cif](http://dx.doi.org/10.1107/S160053681100626X/gk2341sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100626X/gk2341Isup2.hkl](http://dx.doi.org/10.1107/S160053681100626X/gk2341Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2341&file=gk2341sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2341sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2341&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2341](http://scripts.iucr.org/cgi-bin/sendsup?gk2341)). This work was in part supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. X-ray data were collected at the NECAT 24ID-C beamline of the Advanced Photon Source, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy under contract No. W-31--109-Eng-38. Comment ======= α-Tocopherol (vitamin E) is a lipophilic compound, poorly soluble in water (Dubbs & Gupta, 1998). It is also poorly absorbed after oral administration. 2,2,5,7,8-Pentamethyl-6-hydroxychroman in which the lipophylic phytyl chain was replaced with a methyl group is often used as a model compound for structural and biological investigations. Enhancing of aqueous solubility is of interest because of challenges in supplying the vitamin E preparations. In order to improve pharmacological properties, the model compound was converted into the water-soluble glucoside which is easy cleavable by the appropriate enzymes or acidic medium (Witkowski & Walejko, 2002). In both symmetrically independent molecules, the heterocyclic ring of chroman system exists in the approximate half-chair conformation with two possible alternative positions, *exo* or *endo*, of the out of plane atom C03 (C53), as illustrated in the packing diagram, Fig. 2. As a consequence, there are also two alternative positions of the methyl substituents at C02 (C52) atoms. The occupancy ratio is 0.858:0.142 (0.005) and 0.523:0.477 (0.005), in the first and the second molecule, respectively. Two independent molecules in the cell are in the relation resembling the 2~1~ axis parallel to *a* direction, Fig. 2. This effect is emphasized by the β and γ unit-cell angles being close to 90°. Experimental {#experimental} ============ The title glucoside was synthesized by a modified Helferich method according to the published procedure (Witkowski & Walejko, 2002). The crystallization was carried out at room temperature by slow evaporation of 2,2,5,7,8-pentamethyl-6-hydroxychromanyl 2,3,4,6-tetra-*O*-acetyl-α-*D*-glucopyranoside solution in ethanol. Refinement {#refinement} ========== Fridel related reflections were averaged. The D configuration and anomeric state of the sugar moiety has been attributed according to synthesis and NMR studies (Witkowski & Walejko, 2002). Distance and angle restraints were only applied to the disordered parts of chroman moieties. All hydrogen atoms were constrained to idealized positions with C---H distances fixed at 0.98--1.00 Å and *U*~iso~(H) = 1.5*U*~eq~(C) for methyl hydrogen atoms and 1.2*U*~eq~(C) for others. The sum of occupancies of alternative positions of disordered atoms of was constrained to unity. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. For clarity, two symmetrically independent molecules are shown separately (a and b) with hydrogen atoms omitted. Carbon atoms of the chroman systems which adopt two different conformations, are shown in green and blue, respectively. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o718-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram viewed along a axis. Only non-hydrogen atoms are shown. ::: ![](e-67-0o718-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e145 .table-wrap} --------------------- --------------------------------------- C~28~H~38~O~11~ *Z* = 2 *M~r~* = 550.58 *F*(000) = 588 Triclinic, *P*1 *D*~x~ = 1.289 Mg m^−3^ Hall symbol: P 1 Synchrotron radiation, λ = 0.59040 Å *a* = 8.66 (1) Å Cell parameters from 5956 reflections *b* = 11.30 (1) Å θ = 1.5--22.6° *c* = 14.55 (1) Å µ = 0.06 mm^−1^ α = 85.74 (5)° *T* = 100 K β = 89.13 (5)° Needle, colourless γ = 88.16 (5)° 0.25 × 0.15 × 0.09 mm *V* = 1419 (2) Å^3^ --------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e272 .table-wrap} ---------------------------------------------------------------------------- -------------------------------------- Mar Research MAR315 CCD diffractometer 5956 independent reflections Radiation source: NECAT 24ID-C synchrotron beamline APS, USA 5260 reflections with *I* \> 2σ(*I*) Si111 double crystal *R*~int~ = 0.023 ω scans θ~max~ = 22.6°, θ~min~ = 1.5° Absorption correction: multi-scan (*SCALEPACK*; Otwinowski *et al.*, 2003) *h* = 0→11 *T*~min~ = 0.985, *T*~max~ = 0.995 *k* = −14→14 8538 measured reflections *l* = −18→18 ---------------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e386 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.118 H-atom parameters constrained *S* = 0.99 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0671*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5956 reflections (Δ/σ)~max~ \< 0.001 795 parameters Δρ~max~ = 0.21 e Å^−3^ 752 restraints Δρ~min~ = −0.23 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e540 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The crystal was mounted with vaseline on a pin attached capillary. Upon mounting, the crystal was quenched to 100 K in a nitrogen-gas stream supplied by an Oxford Cryo-Jet. Diffraction data were measured at the station 24-ID---C of the APS synchrotron by rotation method. Geometry. All e.s.d.\'s are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. Refinement. Refinement of *F*^2^ against all reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e641 .table-wrap} ------- ------------- --------------- --------------- -------------------- ------------ *x* *y* *z* *U*~iso~\*/*U*~eq~ Occ. (\<1) O01 0.7561 (2) 0.6151 (2) 0.69759 (14) 0.0488 (5) C02A 0.9136 (8) 0.6057 (5) 0.7333 (3) 0.0389 (13) 0.858 (5) C03A 1.0148 (4) 0.5345 (3) 0.6699 (2) 0.0389 (8) 0.858 (5) HA03A 0.9747 0.4536 0.6689 0.047\* 0.858 (5) HA03B 1.1210 0.5272 0.6944 0.047\* 0.858 (5) C04A 1.0197 (5) 0.5922 (4) 0.5721 (4) 0.0409 (10) 0.858 (5) HA04A 1.0866 0.6618 0.5697 0.049\* 0.858 (5) HA04B 1.0647 0.5350 0.5301 0.049\* 0.858 (5) C02B 0.885 (5) 0.612 (2) 0.7368 (19) 0.051 (9) 0.142 (5) C03B 1.013 (3) 0.672 (2) 0.6797 (13) 0.064 (6) 0.142 (5) HB03A 1.1138 0.6506 0.7090 0.077\* 0.142 (5) HB03B 0.9975 0.7594 0.6803 0.077\* 0.142 (5) C04B 1.020 (2) 0.639 (3) 0.5796 (15) 0.048 (6) 0.142 (5) HB04A 1.0786 0.6992 0.5417 0.058\* 0.142 (5) HB04B 1.0758 0.5614 0.5765 0.058\* 0.142 (5) C05 0.8296 (3) 0.6572 (2) 0.4453 (2) 0.0394 (6) C06 0.6793 (3) 0.6888 (2) 0.41880 (19) 0.0353 (5) C07 0.5552 (3) 0.6891 (2) 0.48235 (19) 0.0366 (6) C08 0.5853 (3) 0.6646 (2) 0.5762 (2) 0.0392 (6) C09 0.7371 (3) 0.6387 (2) 0.6032 (2) 0.0400 (6) C10 0.8588 (3) 0.6314 (3) 0.5404 (2) 0.0415 (6) C11A 0.9684 (4) 0.7319 (3) 0.7378 (3) 0.0473 (9) 0.858 (5) HA11A 0.9710 0.7715 0.6756 0.071\* 0.858 (5) HA11B 1.0722 0.7295 0.7639 0.071\* 0.858 (5) HA11C 0.8972 0.7758 0.7768 0.071\* 0.858 (5) C12A 0.8999 (4) 0.5440 (4) 0.8282 (3) 0.0474 (9) 0.858 (5) HA12A 0.8627 0.4637 0.8235 0.071\* 0.858 (5) HA12B 0.8267 0.5888 0.8653 0.071\* 0.858 (5) HA12C 1.0013 0.5394 0.8574 0.071\* 0.858 (5) C11B 0.902 (3) 0.4772 (19) 0.7345 (14) 0.051 (6) 0.142 (5) HB11A 0.8710 0.4392 0.7943 0.077\* 0.142 (5) HB11B 1.0103 0.4552 0.7214 0.077\* 0.142 (5) HB11C 0.8365 0.4507 0.6862 0.077\* 0.142 (5) C12B 0.892 (3) 0.646 (3) 0.8367 (16) 0.061 (7) 0.142 (5) HB12A 0.9000 0.7324 0.8372 0.092\* 0.142 (5) HB12B 0.9819 0.6067 0.8669 0.092\* 0.142 (5) HB12C 0.7975 0.6213 0.8699 0.092\* 0.142 (5) C13 0.9577 (3) 0.6458 (3) 0.3752 (2) 0.0443 (7) H13A 0.9135 0.6440 0.3137 0.066\* H13B 1.0181 0.5722 0.3901 0.066\* H13C 1.0250 0.7138 0.3761 0.066\* O14 0.6441 (2) 0.71514 (15) 0.32506 (13) 0.0379 (4) C15 0.3903 (3) 0.7082 (2) 0.4519 (2) 0.0403 (6) H15A 0.3880 0.7258 0.3850 0.060\* H15B 0.3428 0.7750 0.4824 0.060\* H15C 0.3327 0.6364 0.4685 0.060\* C16 0.4554 (4) 0.6646 (3) 0.6465 (2) 0.0442 (6) H16A 0.4985 0.6602 0.7086 0.066\* H16B 0.3913 0.5958 0.6401 0.066\* H16C 0.3921 0.7377 0.6364 0.066\* C17 0.7064 (3) 0.8206 (2) 0.28211 (18) 0.0366 (6) H17A 0.7912 0.8480 0.3205 0.044\* C18 0.5803 (3) 0.9181 (2) 0.26962 (19) 0.0370 (6) H18A 0.6253 0.9914 0.2387 0.044\* C19 0.4521 (3) 0.8772 (2) 0.21147 (19) 0.0376 (6) H19A 0.4010 0.8078 0.2443 0.045\* C20 0.5187 (3) 0.8427 (2) 0.11993 (19) 0.0367 (6) H20A 0.5521 0.9145 0.0813 0.044\* C21 0.6533 (3) 0.7531 (2) 0.13481 (19) 0.0369 (6) H21A 0.6143 0.6762 0.1632 0.044\* C22 0.7377 (3) 0.7323 (2) 0.0457 (2) 0.0412 (6) H22A 0.6662 0.6991 0.0026 0.049\* H22B 0.7735 0.8089 0.0170 0.049\* O23 0.7644 (2) 0.79836 (16) 0.19401 (13) 0.0378 (4) O24 0.5137 (2) 0.94463 (16) 0.35732 (13) 0.0395 (4) C25 0.5971 (3) 1.0157 (2) 0.4072 (2) 0.0409 (6) O26 0.7141 (2) 1.05995 (18) 0.37950 (15) 0.0467 (5) C27 0.5227 (4) 1.0309 (3) 0.4989 (2) 0.0516 (8) H27A 0.4863 0.9542 0.5250 0.077\* H27B 0.4350 1.0876 0.4915 0.077\* H27C 0.5981 1.0609 0.5403 0.077\* O28 0.3402 (2) 0.97388 (16) 0.19391 (13) 0.0397 (4) C29 0.1984 (3) 0.9609 (2) 0.2340 (2) 0.0419 (6) O30 0.1621 (3) 0.8758 (2) 0.28195 (16) 0.0535 (5) C31 0.0959 (4) 1.0682 (3) 0.2114 (3) 0.0538 (8) H31A 0.1392 1.1373 0.2374 0.081\* H31B −0.0074 1.0546 0.2378 0.081\* H31C 0.0888 1.0828 0.1444 0.081\* O32 0.3995 (2) 0.78273 (16) 0.07392 (13) 0.0403 (4) C33 0.3230 (4) 0.8441 (3) 0.0039 (2) 0.0435 (6) C34 0.1947 (4) 0.7725 (3) −0.0281 (3) 0.0618 (9) H34A 0.1207 0.8249 −0.0630 0.093\* H34B 0.1423 0.7331 0.0254 0.093\* H34C 0.2371 0.7125 −0.0677 0.093\* O35 0.3556 (3) 0.94005 (19) −0.02650 (15) 0.0519 (5) O36 0.8680 (2) 0.65193 (17) 0.06139 (14) 0.0443 (5) C37 0.8400 (4) 0.5356 (3) 0.0729 (2) 0.0458 (7) C38 0.9850 (4) 0.4649 (3) 0.0940 (3) 0.0607 (9) H38A 1.0619 0.4824 0.0452 0.091\* H38B 0.9632 0.3801 0.0976 0.091\* H38C 1.0252 0.4856 0.1532 0.091\* O39 0.7119 (3) 0.49706 (19) 0.06786 (16) 0.0533 (5) O51 0.2336 (2) 0.3517 (3) 0.28927 (15) 0.0623 (7) C52A 0.371 (2) 0.3815 (16) 0.2494 (14) 0.037 (3) 0.523 (5) C53A 0.5086 (7) 0.3217 (6) 0.3023 (4) 0.0447 (14) 0.523 (5) HA53A 0.5085 0.2348 0.2971 0.054\* 0.523 (5) HA53B 0.6064 0.3518 0.2750 0.054\* 0.523 (5) C54A 0.4982 (11) 0.3477 (8) 0.4039 (6) 0.0405 (19) 0.523 (5) HA54A 0.5682 0.2912 0.4395 0.049\* 0.523 (5) HA54B 0.5352 0.4287 0.4102 0.049\* 0.523 (5) C52B 0.398 (2) 0.377 (2) 0.2549 (13) 0.038 (3) 0.477 (5) C53B 0.4895 (7) 0.4495 (5) 0.3180 (4) 0.0389 (14) 0.477 (5) HB53A 0.5959 0.4585 0.2932 0.047\* 0.477 (5) HB53B 0.4405 0.5297 0.3197 0.047\* 0.477 (5) C54B 0.4957 (11) 0.3904 (7) 0.4148 (7) 0.0355 (19) 0.477 (5) HB54A 0.5254 0.4491 0.4581 0.043\* 0.477 (5) HB54B 0.5755 0.3255 0.4173 0.043\* 0.477 (5) C55 0.3091 (3) 0.3160 (2) 0.53997 (19) 0.0365 (6) C56 0.1604 (3) 0.2858 (2) 0.56897 (18) 0.0345 (5) C57 0.0357 (3) 0.2893 (2) 0.50902 (19) 0.0342 (5) C58 0.0645 (3) 0.3129 (2) 0.41409 (19) 0.0366 (6) C59 0.2153 (3) 0.3346 (3) 0.3839 (2) 0.0437 (6) C60 0.3370 (3) 0.3390 (3) 0.4452 (2) 0.0441 (7) C61A 0.3660 (7) 0.5140 (5) 0.2516 (4) 0.0457 (14) 0.523 (5) HA61A 0.3073 0.5496 0.1990 0.069\* 0.523 (5) HA61B 0.4715 0.5429 0.2484 0.069\* 0.523 (5) HA61C 0.3159 0.5360 0.3091 0.069\* 0.523 (5) C62A 0.3814 (7) 0.3441 (6) 0.1501 (4) 0.0449 (14) 0.523 (5) HA62A 0.3859 0.2573 0.1510 0.067\* 0.523 (5) HA62B 0.4749 0.3759 0.1201 0.067\* 0.523 (5) HA62C 0.2904 0.3752 0.1160 0.067\* 0.523 (5) C61B 0.4591 (8) 0.2526 (6) 0.2504 (5) 0.0485 (16) 0.477 (5) HB61A 0.5649 0.2534 0.2256 0.073\* 0.477 (5) HB61B 0.3936 0.2104 0.2103 0.073\* 0.477 (5) HB61C 0.4589 0.2123 0.3124 0.073\* 0.477 (5) C62B 0.3773 (8) 0.4428 (7) 0.1606 (4) 0.0498 (17) 0.477 (5) HB62A 0.3323 0.5223 0.1681 0.075\* 0.477 (5) HB62B 0.3082 0.3989 0.1237 0.075\* 0.477 (5) HB62C 0.4779 0.4498 0.1292 0.075\* 0.477 (5) C63 0.4369 (3) 0.3278 (2) 0.60830 (19) 0.0404 (6) H63A 0.4980 0.3969 0.5887 0.061\* H63B 0.5037 0.2560 0.6109 0.061\* H63C 0.3916 0.3380 0.6694 0.061\* O64 0.1302 (2) 0.25883 (15) 0.66386 (12) 0.0352 (4) C65 −0.1279 (3) 0.2750 (2) 0.5431 (2) 0.0383 (6) H65A −0.1896 0.3467 0.5242 0.058\* H65B −0.1291 0.2627 0.6104 0.058\* H65C −0.1717 0.2063 0.5167 0.058\* C66 −0.0684 (3) 0.3201 (3) 0.3479 (2) 0.0418 (6) H66A −0.1293 0.2486 0.3580 0.063\* H66B −0.0282 0.3261 0.2845 0.063\* H66C −0.1340 0.3902 0.3583 0.063\* C67 0.1988 (3) 0.1507 (2) 0.70335 (19) 0.0370 (6) H67A 0.2818 0.1218 0.6613 0.044\* C68 0.0754 (3) 0.0573 (2) 0.71880 (18) 0.0358 (5) H68A 0.1241 −0.0177 0.7474 0.043\* C69 −0.0498 (3) 0.1007 (2) 0.78254 (19) 0.0368 (6) H69A −0.1018 0.1741 0.7533 0.044\* C70 0.0221 (3) 0.1284 (2) 0.87262 (19) 0.0360 (6) H70A 0.0622 0.0535 0.9061 0.043\* C71 0.1532 (3) 0.2149 (2) 0.85451 (18) 0.0359 (6) H71A 0.1100 0.2939 0.8300 0.043\* C72 0.2424 (3) 0.2292 (2) 0.9411 (2) 0.0404 (6) H72A 0.1761 0.2712 0.9851 0.049\* H72B 0.2713 0.1499 0.9705 0.049\* O73 0.2619 (2) 0.16994 (16) 0.78913 (12) 0.0373 (4) O74 0.0062 (2) 0.03338 (16) 0.63368 (13) 0.0390 (4) C75 0.0909 (3) −0.0373 (2) 0.5785 (2) 0.0402 (6) O76 0.2155 (2) −0.07916 (18) 0.60091 (15) 0.0470 (5) C77 0.0086 (4) −0.0553 (3) 0.4925 (2) 0.0510 (7) H77A 0.0792 −0.0936 0.4497 0.077\* H77B −0.0280 0.0217 0.4642 0.077\* H77C −0.0797 −0.1058 0.5066 0.077\* O78 −0.1617 (2) 0.01101 (16) 0.80209 (13) 0.0386 (4) C79 −0.3014 (3) 0.0277 (3) 0.7598 (2) 0.0439 (6) O80 −0.3347 (2) 0.1129 (2) 0.71021 (16) 0.0539 (6) C81 −0.4040 (4) −0.0740 (3) 0.7847 (3) 0.0565 (8) H81A −0.5076 −0.0436 0.8001 0.085\* H81B −0.3616 −0.1218 0.8380 0.085\* H81C −0.4098 −0.1234 0.7323 0.085\* O82 −0.0937 (2) 0.18503 (15) 0.92817 (13) 0.0384 (4) C83 −0.1639 (3) 0.1161 (2) 0.9962 (2) 0.0396 (6) C84 −0.2941 (4) 0.1831 (3) 1.0383 (2) 0.0542 (8) H84A −0.2727 0.2679 1.0334 0.081\* H84B −0.3057 0.1552 1.1034 0.081\* H84C −0.3898 0.1701 1.0058 0.081\* O85 −0.1246 (3) 0.01617 (18) 1.01807 (15) 0.0516 (5) O86 0.3803 (2) 0.2954 (2) 0.92082 (15) 0.0484 (5) C87 0.3644 (4) 0.4134 (3) 0.9065 (2) 0.0524 (8) C88 0.5135 (5) 0.4673 (5) 0.8774 (3) 0.0841 (14) H88A 0.4979 0.5534 0.8660 0.126\* H88B 0.5514 0.4336 0.8209 0.126\* H88C 0.5895 0.4504 0.9263 0.126\* O89 0.2423 (3) 0.4656 (2) 0.91500 (18) 0.0616 (6) ------- ------------- --------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e3044 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O01 0.0416 (11) 0.0643 (14) 0.0400 (12) −0.0051 (10) −0.0039 (9) 0.0009 (10) C02A 0.038 (2) 0.040 (3) 0.039 (2) 0.0009 (18) −0.0043 (16) −0.0008 (19) C03A 0.0435 (17) 0.0315 (15) 0.0412 (18) 0.0003 (13) −0.0014 (13) −0.0001 (13) C04A 0.042 (2) 0.033 (2) 0.047 (2) −0.0019 (15) 0.0032 (15) −0.0004 (17) C02B 0.057 (17) 0.030 (13) 0.066 (16) 0.002 (12) −0.010 (13) −0.005 (12) C03B 0.085 (13) 0.051 (11) 0.053 (12) 0.023 (11) 0.001 (11) 0.009 (10) C04B 0.041 (11) 0.077 (16) 0.024 (10) 0.000 (12) −0.009 (8) 0.011 (11) C05 0.0466 (15) 0.0285 (12) 0.0431 (16) −0.0058 (11) 0.0021 (12) −0.0003 (11) C06 0.0421 (14) 0.0265 (12) 0.0371 (14) −0.0025 (10) −0.0029 (11) −0.0007 (10) C07 0.0447 (14) 0.0275 (12) 0.0380 (14) −0.0052 (10) −0.0005 (11) −0.0021 (10) C08 0.0497 (16) 0.0302 (13) 0.0375 (15) −0.0053 (11) −0.0005 (12) −0.0001 (11) C09 0.0454 (15) 0.0340 (13) 0.0403 (16) −0.0042 (11) 0.0002 (12) 0.0005 (11) C10 0.0426 (14) 0.0377 (14) 0.0440 (16) −0.0010 (11) −0.0049 (12) −0.0010 (12) C11A 0.055 (2) 0.0369 (17) 0.052 (2) −0.0079 (15) −0.0018 (16) −0.0083 (15) C12A 0.0456 (19) 0.051 (2) 0.045 (2) 0.0000 (16) −0.0002 (15) 0.0025 (16) C11B 0.065 (14) 0.054 (13) 0.031 (10) 0.025 (10) 0.007 (9) 0.006 (9) C12B 0.042 (11) 0.086 (18) 0.056 (14) 0.011 (12) 0.005 (10) −0.015 (13) C13 0.0491 (16) 0.0374 (15) 0.0459 (17) −0.0032 (12) 0.0016 (13) −0.0006 (12) O14 0.0472 (10) 0.0316 (9) 0.0348 (10) −0.0071 (8) −0.0001 (8) 0.0004 (8) C15 0.0444 (15) 0.0362 (14) 0.0404 (15) −0.0043 (11) 0.0011 (11) −0.0023 (11) C16 0.0495 (16) 0.0403 (15) 0.0428 (16) −0.0012 (12) 0.0008 (12) −0.0034 (12) C17 0.0456 (15) 0.0307 (13) 0.0330 (14) −0.0055 (11) 0.0003 (11) 0.0019 (10) C18 0.0435 (14) 0.0319 (13) 0.0359 (14) −0.0055 (11) 0.0020 (11) −0.0025 (11) C19 0.0430 (14) 0.0287 (12) 0.0410 (15) −0.0021 (11) −0.0035 (11) −0.0008 (11) C20 0.0449 (15) 0.0286 (13) 0.0371 (14) −0.0070 (11) −0.0059 (11) −0.0019 (10) C21 0.0412 (14) 0.0336 (13) 0.0360 (14) −0.0042 (11) −0.0011 (11) −0.0009 (11) C22 0.0487 (16) 0.0344 (14) 0.0402 (15) −0.0017 (12) 0.0022 (12) −0.0022 (11) O23 0.0419 (10) 0.0358 (10) 0.0361 (10) −0.0060 (8) 0.0008 (8) −0.0039 (8) O24 0.0487 (11) 0.0308 (9) 0.0398 (11) −0.0077 (8) 0.0009 (8) −0.0065 (8) C25 0.0525 (16) 0.0282 (13) 0.0427 (16) −0.0037 (12) −0.0019 (12) −0.0056 (11) O26 0.0496 (12) 0.0398 (11) 0.0516 (13) −0.0096 (9) −0.0027 (9) −0.0066 (9) C27 0.068 (2) 0.0439 (17) 0.0453 (17) −0.0103 (15) 0.0048 (15) −0.0139 (13) O28 0.0440 (10) 0.0308 (9) 0.0439 (11) −0.0009 (8) −0.0013 (8) 0.0001 (8) C29 0.0472 (15) 0.0375 (15) 0.0421 (16) −0.0078 (12) −0.0043 (12) −0.0062 (12) O30 0.0516 (12) 0.0491 (12) 0.0587 (14) −0.0070 (10) 0.0070 (10) 0.0045 (10) C31 0.0489 (17) 0.0507 (18) 0.062 (2) 0.0046 (14) −0.0029 (14) −0.0087 (15) O32 0.0483 (11) 0.0307 (9) 0.0423 (11) −0.0031 (8) −0.0080 (8) −0.0026 (8) C33 0.0524 (16) 0.0374 (15) 0.0408 (15) 0.0018 (12) −0.0064 (12) −0.0027 (12) C34 0.060 (2) 0.0548 (19) 0.071 (2) −0.0059 (16) −0.0217 (17) −0.0072 (17) O35 0.0635 (14) 0.0443 (12) 0.0470 (13) −0.0027 (10) −0.0102 (10) 0.0049 (10) O36 0.0431 (10) 0.0422 (11) 0.0478 (12) −0.0019 (9) 0.0010 (8) −0.0047 (9) C37 0.0570 (18) 0.0419 (16) 0.0381 (16) −0.0010 (14) 0.0017 (13) −0.0007 (12) C38 0.065 (2) 0.060 (2) 0.055 (2) 0.0152 (17) 0.0055 (16) 0.0012 (16) O39 0.0559 (13) 0.0428 (12) 0.0616 (15) −0.0070 (10) 0.0014 (10) −0.0045 (10) O51 0.0351 (11) 0.112 (2) 0.0362 (12) −0.0017 (12) 0.0016 (9) 0.0153 (12) C52A 0.031 (7) 0.029 (4) 0.051 (5) 0.000 (4) −0.005 (4) −0.003 (3) C53A 0.041 (3) 0.057 (4) 0.036 (3) −0.005 (3) −0.003 (2) 0.000 (3) C54A 0.040 (4) 0.042 (5) 0.039 (4) −0.007 (4) 0.002 (3) −0.002 (3) C52B 0.027 (6) 0.050 (6) 0.037 (6) −0.009 (4) 0.010 (4) 0.001 (4) C53B 0.038 (3) 0.034 (3) 0.044 (3) −0.010 (2) 0.000 (2) 0.000 (2) C54B 0.032 (3) 0.032 (4) 0.042 (4) −0.004 (3) −0.001 (3) −0.003 (3) C55 0.0381 (13) 0.0325 (13) 0.0382 (15) −0.0011 (10) −0.0034 (11) 0.0033 (11) C56 0.0429 (14) 0.0275 (12) 0.0325 (14) −0.0001 (10) 0.0016 (11) 0.0018 (10) C57 0.0375 (13) 0.0279 (12) 0.0366 (14) −0.0020 (10) 0.0017 (10) 0.0023 (10) C58 0.0370 (14) 0.0347 (13) 0.0376 (15) −0.0029 (11) 0.0001 (10) 0.0020 (11) C59 0.0416 (14) 0.0523 (17) 0.0353 (15) 0.0005 (13) −0.0034 (11) 0.0088 (12) C60 0.0378 (14) 0.0516 (17) 0.0410 (16) −0.0032 (12) 0.0001 (11) 0.0100 (13) C61A 0.053 (3) 0.039 (3) 0.046 (3) −0.017 (2) −0.003 (3) −0.003 (2) C62A 0.041 (3) 0.061 (4) 0.033 (3) −0.009 (3) 0.001 (2) −0.004 (3) C61B 0.053 (4) 0.044 (3) 0.050 (4) −0.003 (3) 0.003 (3) −0.012 (3) C62B 0.055 (4) 0.057 (4) 0.038 (3) −0.018 (3) 0.001 (3) −0.001 (3) C63 0.0436 (15) 0.0379 (14) 0.0394 (15) −0.0039 (12) −0.0051 (11) 0.0004 (11) O64 0.0412 (10) 0.0301 (9) 0.0337 (10) 0.0015 (7) 0.0003 (7) 0.0004 (7) C65 0.0382 (13) 0.0368 (14) 0.0396 (15) −0.0026 (11) 0.0019 (11) 0.0002 (11) C66 0.0377 (14) 0.0443 (15) 0.0429 (16) −0.0021 (12) −0.0041 (11) 0.0015 (12) C67 0.0443 (15) 0.0299 (13) 0.0362 (14) 0.0023 (11) 0.0001 (11) −0.0001 (11) C68 0.0440 (14) 0.0302 (12) 0.0328 (14) −0.0004 (10) 0.0004 (11) −0.0005 (10) C69 0.0436 (14) 0.0277 (12) 0.0386 (15) −0.0018 (10) 0.0046 (11) −0.0009 (10) C70 0.0408 (14) 0.0288 (12) 0.0378 (14) 0.0025 (10) 0.0061 (11) −0.0025 (10) C71 0.0400 (14) 0.0298 (13) 0.0377 (15) 0.0006 (11) 0.0028 (11) −0.0030 (10) C72 0.0474 (15) 0.0350 (14) 0.0386 (15) −0.0035 (12) −0.0005 (12) 0.0001 (11) O73 0.0394 (10) 0.0377 (10) 0.0345 (10) 0.0022 (8) 0.0005 (8) −0.0023 (8) O74 0.0472 (10) 0.0335 (9) 0.0364 (10) 0.0013 (8) 0.0014 (8) −0.0056 (8) C75 0.0511 (17) 0.0276 (13) 0.0419 (16) −0.0015 (12) 0.0079 (12) −0.0037 (11) O76 0.0495 (12) 0.0390 (11) 0.0528 (13) 0.0044 (9) 0.0010 (9) −0.0087 (9) C77 0.064 (2) 0.0446 (16) 0.0454 (18) 0.0022 (14) −0.0022 (14) −0.0091 (14) O78 0.0425 (10) 0.0315 (9) 0.0415 (11) −0.0038 (8) −0.0005 (8) 0.0009 (8) C79 0.0415 (15) 0.0460 (16) 0.0438 (16) −0.0025 (12) −0.0012 (12) 0.0000 (13) O80 0.0455 (12) 0.0523 (13) 0.0617 (14) 0.0003 (10) −0.0047 (10) 0.0104 (11) C81 0.0499 (17) 0.0492 (18) 0.070 (2) −0.0116 (15) −0.0026 (15) 0.0007 (16) O82 0.0431 (10) 0.0305 (9) 0.0413 (11) 0.0005 (8) 0.0068 (8) −0.0023 (8) C83 0.0434 (14) 0.0361 (14) 0.0395 (15) −0.0072 (12) 0.0023 (11) −0.0032 (11) C84 0.0579 (19) 0.0458 (17) 0.058 (2) −0.0022 (14) 0.0196 (15) −0.0041 (14) O85 0.0649 (14) 0.0396 (11) 0.0483 (13) 0.0003 (10) 0.0079 (10) 0.0064 (9) O86 0.0447 (11) 0.0559 (13) 0.0455 (12) −0.0094 (10) −0.0035 (9) −0.0048 (10) C87 0.058 (2) 0.057 (2) 0.0420 (17) −0.0141 (16) −0.0108 (14) 0.0056 (14) C88 0.075 (3) 0.113 (4) 0.063 (3) −0.049 (3) −0.016 (2) 0.019 (2) O89 0.0707 (17) 0.0452 (13) 0.0693 (17) −0.0071 (12) −0.0181 (12) −0.0014 (11) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e4737 .table-wrap} --------------------------- ------------- --------------------------- -------------- O01---C02B 1.26 (4) O51---C52A 1.36 (2) O01---C09 1.390 (4) O51---C59 1.383 (4) O01---C02A 1.465 (7) O51---C52B 1.53 (2) C02A---C12A 1.504 (6) C52A---C61A 1.499 (19) C02A---C03A 1.518 (6) C52A---C62A 1.53 (2) C02A---C11A 1.524 (7) C52A---C53A 1.541 (15) C03A---C04A 1.521 (6) C53A---C54A 1.529 (9) C03A---HA03A 0.9900 C53A---HA53A 0.9900 C03A---HA03B 0.9900 C53A---HA53B 0.9900 C04A---C10 1.517 (5) C54A---C60 1.515 (9) C04A---HA04A 0.9900 C54A---HA54A 0.9900 C04A---HA04B 0.9900 C54A---HA54B 0.9900 C02B---C11B 1.526 (19) C52B---C61B 1.49 (2) C02B---C03B 1.526 (19) C52B---C53B 1.521 (16) C02B---C12B 1.535 (19) C52B---C62B 1.52 (2) C03B---C04B 1.532 (17) C53B---C54B 1.514 (11) C03B---HB03A 0.9900 C53B---HB53A 0.9900 C03B---HB03B 0.9900 C53B---HB53B 0.9900 C04B---C10 1.525 (17) C54B---C60 1.554 (10) C04B---HB04A 0.9900 C54B---HB54A 0.9900 C04B---HB04B 0.9900 C54B---HB54B 0.9900 C05---C06 1.391 (4) C55---C56 1.394 (4) C05---C10 1.417 (4) C55---C60 1.403 (4) C05---C13 1.504 (4) C55---C63 1.514 (4) C06---O14 1.410 (3) C56---C57 1.396 (4) C06---C07 1.407 (4) C56---O64 1.414 (3) C07---C08 1.400 (4) C57---C58 1.407 (4) C07---C15 1.506 (4) C57---C65 1.504 (4) C08---C09 1.394 (4) C58---C59 1.395 (4) C08---C16 1.508 (4) C58---C66 1.508 (4) C09---C10 1.389 (4) C59---C60 1.396 (4) C11A---HA11A 0.9800 C61A---HA61A 0.9800 C11A---HA11B 0.9800 C61A---HA61B 0.9800 C11A---HA11C 0.9800 C61A---HA61C 0.9800 C12A---HA12A 0.9800 C62A---HA62A 0.9800 C12A---HA12B 0.9800 C62A---HA62B 0.9800 C12A---HA12C 0.9800 C62A---HA62C 0.9800 C11B---HB11A 0.9800 C61B---HB61A 0.9800 C11B---HB11B 0.9800 C61B---HB61B 0.9800 C11B---HB11C 0.9800 C61B---HB61C 0.9800 C12B---HB12A 0.9800 C62B---HB62A 0.9800 C12B---HB12B 0.9800 C62B---HB62B 0.9800 C12B---HB12C 0.9800 C62B---HB62C 0.9800 C13---H13A 0.9800 C63---H63A 0.9800 C13---H13B 0.9800 C63---H63B 0.9800 C13---H13C 0.9800 C63---H63C 0.9800 O14---C17 1.422 (3) O64---C67 1.426 (3) C15---H15A 0.9800 C65---H65A 0.9800 C15---H15B 0.9800 C65---H65B 0.9800 C15---H15C 0.9800 C65---H65C 0.9800 C16---H16A 0.9800 C66---H66A 0.9800 C16---H16B 0.9800 C66---H66B 0.9800 C16---H16C 0.9800 C66---H66C 0.9800 C17---O23 1.407 (3) C67---O73 1.404 (3) C17---C18 1.530 (4) C67---C68 1.529 (4) C17---H17A 1.0000 C67---H67A 1.0000 C18---O24 1.440 (3) C68---O74 1.432 (3) C18---C19 1.510 (4) C68---C69 1.510 (3) C18---H18A 1.0000 C68---H68A 1.0000 C19---O28 1.447 (3) C69---O78 1.435 (3) C19---C20 1.516 (4) C69---C70 1.517 (4) C19---H19A 1.0000 C69---H69A 1.0000 C20---O32 1.451 (3) C70---O82 1.442 (3) C20---C21 1.526 (4) C70---C71 1.530 (4) C20---H20A 1.0000 C70---H70A 1.0000 C21---O23 1.433 (3) C71---O73 1.436 (3) C21---C22 1.508 (4) C71---C72 1.509 (4) C21---H21A 1.0000 C71---H71A 1.0000 C22---O36 1.435 (4) C72---O86 1.445 (4) C22---H22A 0.9900 C72---H72A 0.9900 C22---H22B 0.9900 C72---H72B 0.9900 O24---C25 1.354 (3) O74---C75 1.364 (3) C25---O26 1.196 (3) C75---O76 1.204 (4) C25---C27 1.491 (4) C75---C77 1.480 (4) C27---H27A 0.9800 C77---H77A 0.9800 C27---H27B 0.9800 C77---H77B 0.9800 C27---H27C 0.9800 C77---H77C 0.9800 O28---C29 1.359 (4) O78---C79 1.367 (3) C29---O30 1.193 (3) C79---O80 1.190 (4) C29---C31 1.499 (4) C79---C81 1.495 (4) C31---H31A 0.9800 C81---H81A 0.9800 C31---H31B 0.9800 C81---H81B 0.9800 C31---H31C 0.9800 C81---H81C 0.9800 O32---C33 1.358 (4) O82---C83 1.361 (3) C33---O35 1.181 (4) C83---O85 1.190 (4) C33---C34 1.496 (5) C83---C84 1.488 (4) C34---H34A 0.9800 C84---H84A 0.9800 C34---H34B 0.9800 C84---H84B 0.9800 C34---H34C 0.9800 C84---H84C 0.9800 O36---C37 1.342 (4) O86---C87 1.337 (4) C37---O39 1.211 (4) C87---O89 1.204 (4) C37---C38 1.490 (5) C87---C88 1.488 (5) C38---H38A 0.9800 C88---H88A 0.9800 C38---H38B 0.9800 C88---H88B 0.9800 C38---H38C 0.9800 C88---H88C 0.9800 C02B---O01---C09 123.9 (11) C52A---O51---C59 122.0 (7) C02B---O01---C02A 6.8 (12) C52A---O51---C52B 7.3 (13) C09---O01---C02A 118.2 (3) C59---O51---C52B 115.5 (6) O01---C02A---C12A 105.5 (4) O51---C52A---C61A 102.3 (13) O01---C02A---C03A 109.1 (4) O51---C52A---C62A 111.0 (10) C12A---C02A---C03A 111.8 (4) C61A---C52A---C62A 111.4 (14) O01---C02A---C11A 106.9 (4) O51---C52A---C53A 112.0 (14) C12A---C02A---C11A 111.0 (4) C61A---C52A---C53A 112.7 (10) C03A---C02A---C11A 112.1 (4) C62A---C52A---C53A 107.5 (13) C02A---C03A---C04A 112.0 (3) C54A---C53A---C52A 110.2 (9) C02A---C03A---HA03A 109.2 C54A---C53A---HA53A 109.6 C04A---C03A---HA03A 109.2 C52A---C53A---HA53A 109.6 C02A---C03A---HA03B 109.2 C54A---C53A---HA53B 109.6 C04A---C03A---HA03B 109.2 C52A---C53A---HA53B 109.6 HA03A---C03A---HA03B 107.9 HA53A---C53A---HA53B 108.1 C10---C04A---C03A 110.8 (3) C60---C54A---C53A 114.0 (6) C10---C04A---HA04A 109.5 C60---C54A---HA54A 108.8 C03A---C04A---HA04A 109.5 C53A---C54A---HA54A 108.8 C10---C04A---HA04B 109.5 C60---C54A---HA54B 108.8 C03A---C04A---HA04B 109.5 C53A---C54A---HA54B 108.8 HA04A---C04A---HA04B 108.1 HA54A---C54A---HA54B 107.6 O01---C02B---C11B 92.6 (19) C61B---C52B---O51 99.3 (13) O01---C02B---C03B 114 (2) C61B---C52B---C53B 113.7 (12) C11B---C02B---C03B 110 (2) O51---C52B---C53B 114.0 (14) O01---C02B---C12B 119 (2) C61B---C52B---C62B 113.4 (13) C11B---C02B---C12B 110 (2) O51---C52B---C62B 104.6 (11) C03B---C02B---C12B 110 (2) C53B---C52B---C62B 111.0 (14) C02B---C03B---C04B 113.4 (18) C54B---C53B---C52B 111.1 (9) C02B---C03B---HB03A 108.9 C54B---C53B---HB53A 109.4 C04B---C03B---HB03A 108.9 C52B---C53B---HB53A 109.4 C02B---C03B---HB03B 108.9 C54B---C53B---HB53B 109.4 C04B---C03B---HB03B 108.9 C52B---C53B---HB53B 109.4 HB03A---C03B---HB03B 107.7 HB53A---C53B---HB53B 108.0 C10---C04B---C03B 111.4 (16) C53B---C54B---C60 111.2 (7) C10---C04B---HB04A 109.3 C53B---C54B---HB54A 109.4 C03B---C04B---HB04A 109.3 C60---C54B---HB54A 109.4 C10---C04B---HB04B 109.3 C53B---C54B---HB54B 109.4 C03B---C04B---HB04B 109.3 C60---C54B---HB54B 109.4 HB04A---C04B---HB04B 108.0 HB54A---C54B---HB54B 108.0 C06---C05---C10 118.3 (3) C56---C55---C60 118.2 (2) C06---C05---C13 121.3 (3) C56---C55---C63 121.5 (2) C10---C05---C13 120.3 (3) C60---C55---C63 120.3 (2) C05---C06---O14 120.6 (2) C55---C56---C57 122.8 (2) C05---C06---C07 122.2 (3) C55---C56---O64 119.3 (2) O14---C06---C07 117.1 (2) C57---C56---O64 117.7 (2) C08---C07---C06 119.0 (3) C56---C57---C58 118.4 (2) C08---C07---C15 119.0 (2) C56---C57---C65 122.2 (2) C06---C07---C15 121.9 (2) C58---C57---C65 119.3 (2) C09---C08---C07 118.7 (3) C59---C58---C57 118.9 (2) C09---C08---C16 120.8 (3) C59---C58---C66 121.4 (3) C07---C08---C16 120.5 (3) C57---C58---C66 119.6 (2) O01---C09---C10 122.6 (3) O51---C59---C58 114.8 (2) O01---C09---C08 114.7 (2) O51---C59---C60 123.2 (3) C10---C09---C08 122.6 (3) C58---C59---C60 122.0 (3) C09---C10---C05 119.0 (3) C59---C60---C55 119.3 (3) C09---C10---C04A 120.8 (3) C59---C60---C54A 117.0 (4) C05---C10---C04A 120.1 (3) C55---C60---C54A 122.8 (4) C09---C10---C04B 115.9 (9) C59---C60---C54B 122.1 (4) C05---C10---C04B 121.7 (10) C55---C60---C54B 117.6 (4) C04A---C10---C04B 20.7 (12) C54A---C60---C54B 19.4 (3) C02A---C11A---HA11A 109.5 C52A---C61A---HA61A 109.5 C02A---C11A---HA11B 109.5 C52A---C61A---HA61B 109.5 HA11A---C11A---HA11B 109.5 HA61A---C61A---HA61B 109.5 C02A---C11A---HA11C 109.5 C52A---C61A---HA61C 109.5 HA11A---C11A---HA11C 109.5 HA61A---C61A---HA61C 109.5 HA11B---C11A---HA11C 109.5 HA61B---C61A---HA61C 109.5 C02A---C12A---HA12A 109.5 C52A---C62A---HA62A 109.5 C02A---C12A---HA12B 109.5 C52A---C62A---HA62B 109.5 HA12A---C12A---HA12B 109.5 HA62A---C62A---HA62B 109.5 C02A---C12A---HA12C 109.5 C52A---C62A---HA62C 109.5 HA12A---C12A---HA12C 109.5 HA62A---C62A---HA62C 109.5 HA12B---C12A---HA12C 109.5 HA62B---C62A---HA62C 109.5 C02B---C11B---HB11A 109.5 C52B---C61B---HB61A 109.5 C02B---C11B---HB11B 109.5 C52B---C61B---HB61B 109.5 HB11A---C11B---HB11B 109.5 HB61A---C61B---HB61B 109.5 C02B---C11B---HB11C 109.5 C52B---C61B---HB61C 109.5 HB11A---C11B---HB11C 109.5 HB61A---C61B---HB61C 109.5 HB11B---C11B---HB11C 109.5 HB61B---C61B---HB61C 109.5 C02B---C12B---HB12A 109.5 C52B---C62B---HB62A 109.5 C02B---C12B---HB12B 109.5 C52B---C62B---HB62B 109.5 HB12A---C12B---HB12B 109.5 HB62A---C62B---HB62B 109.5 C02B---C12B---HB12C 109.5 C52B---C62B---HB62C 109.5 HB12A---C12B---HB12C 109.5 HB62A---C62B---HB62C 109.5 HB12B---C12B---HB12C 109.5 HB62B---C62B---HB62C 109.5 C05---C13---H13A 109.5 C55---C63---H63A 109.5 C05---C13---H13B 109.5 C55---C63---H63B 109.5 H13A---C13---H13B 109.5 H63A---C63---H63B 109.5 C05---C13---H13C 109.5 C55---C63---H63C 109.5 H13A---C13---H13C 109.5 H63A---C63---H63C 109.5 H13B---C13---H13C 109.5 H63B---C63---H63C 109.5 C06---O14---C17 116.4 (2) C56---O64---C67 116.09 (18) C07---C15---H15A 109.5 C57---C65---H65A 109.5 C07---C15---H15B 109.5 C57---C65---H65B 109.5 H15A---C15---H15B 109.5 H65A---C65---H65B 109.5 C07---C15---H15C 109.5 C57---C65---H65C 109.5 H15A---C15---H15C 109.5 H65A---C65---H65C 109.5 H15B---C15---H15C 109.5 H65B---C65---H65C 109.5 C08---C16---H16A 109.5 C58---C66---H66A 109.5 C08---C16---H16B 109.5 C58---C66---H66B 109.5 H16A---C16---H16B 109.5 H66A---C66---H66B 109.5 C08---C16---H16C 109.5 C58---C66---H66C 109.5 H16A---C16---H16C 109.5 H66A---C66---H66C 109.5 H16B---C16---H16C 109.5 H66B---C66---H66C 109.5 O23---C17---O14 109.6 (2) O73---C67---O64 109.6 (2) O23---C17---C18 107.5 (2) O73---C67---C68 108.2 (2) O14---C17---C18 110.4 (2) O64---C67---C68 109.7 (2) O23---C17---H17A 109.8 O73---C67---H67A 109.8 O14---C17---H17A 109.8 O64---C67---H67A 109.8 C18---C17---H17A 109.8 C68---C67---H67A 109.8 O24---C18---C19 107.6 (2) O74---C68---C69 108.4 (2) O24---C18---C17 110.7 (2) O74---C68---C67 111.1 (2) C19---C18---C17 109.9 (2) C69---C68---C67 109.9 (2) O24---C18---H18A 109.5 O74---C68---H68A 109.1 C19---C18---H18A 109.5 C69---C68---H68A 109.1 C17---C18---H18A 109.5 C67---C68---H68A 109.1 O28---C19---C18 109.2 (2) O78---C69---C68 110.5 (2) O28---C19---C20 108.5 (2) O78---C69---C70 108.4 (2) C18---C19---C20 109.3 (2) C68---C69---C70 109.1 (2) O28---C19---H19A 109.9 O78---C69---H69A 109.6 C18---C19---H19A 109.9 C68---C69---H69A 109.6 C20---C19---H19A 109.9 C70---C69---H69A 109.6 O32---C20---C19 107.5 (2) O82---C70---C69 108.8 (2) O32---C20---C21 106.5 (2) O82---C70---C71 107.7 (2) C19---C20---C21 110.7 (2) C69---C70---C71 110.4 (2) O32---C20---H20A 110.7 O82---C70---H70A 110.0 C19---C20---H20A 110.7 C69---C70---H70A 110.0 C21---C20---H20A 110.7 C71---C70---H70A 110.0 O23---C21---C22 106.2 (2) O73---C71---C72 106.5 (2) O23---C21---C20 109.8 (2) O73---C71---C70 110.1 (2) C22---C21---C20 111.7 (2) C72---C71---C70 111.3 (2) O23---C21---H21A 109.7 O73---C71---H71A 109.6 C22---C21---H21A 109.7 C72---C71---H71A 109.6 C20---C21---H21A 109.7 C70---C71---H71A 109.6 O36---C22---C21 111.0 (2) O86---C72---C71 111.0 (2) O36---C22---H22A 109.4 O86---C72---H72A 109.4 C21---C22---H22A 109.4 C71---C72---H72A 109.4 O36---C22---H22B 109.4 O86---C72---H72B 109.4 C21---C22---H22B 109.4 C71---C72---H72B 109.4 H22A---C22---H22B 108.0 H72A---C72---H72B 108.0 C17---O23---C21 114.2 (2) C67---O73---C71 114.6 (2) C25---O24---C18 115.6 (2) C75---O74---C68 116.2 (2) O26---C25---O24 123.3 (3) O76---C75---O74 121.9 (3) O26---C25---C27 125.7 (3) O76---C75---C77 126.6 (3) O24---C25---C27 111.1 (3) O74---C75---C77 111.5 (3) C25---C27---H27A 109.5 C75---C77---H77A 109.5 C25---C27---H27B 109.5 C75---C77---H77B 109.5 H27A---C27---H27B 109.5 H77A---C77---H77B 109.5 C25---C27---H27C 109.5 C75---C77---H77C 109.5 H27A---C27---H27C 109.5 H77A---C77---H77C 109.5 H27B---C27---H27C 109.5 H77B---C77---H77C 109.5 C29---O28---C19 116.9 (2) C79---O78---C69 117.1 (2) O30---C29---O28 124.1 (3) O80---C79---O78 123.5 (3) O30---C29---C31 124.9 (3) O80---C79---C81 125.5 (3) O28---C29---C31 111.1 (2) O78---C79---C81 111.0 (2) C29---C31---H31A 109.5 C79---C81---H81A 109.5 C29---C31---H31B 109.5 C79---C81---H81B 109.5 H31A---C31---H31B 109.5 H81A---C81---H81B 109.5 C29---C31---H31C 109.5 C79---C81---H81C 109.5 H31A---C31---H31C 109.5 H81A---C81---H81C 109.5 H31B---C31---H31C 109.5 H81B---C81---H81C 109.5 C33---O32---C20 118.1 (2) C83---O82---C70 117.3 (2) O35---C33---O32 123.9 (3) O85---C83---O82 123.9 (3) O35---C33---C34 125.9 (3) O85---C83---C84 125.5 (3) O32---C33---C34 110.2 (3) O82---C83---C84 110.6 (2) C33---C34---H34A 109.5 C83---C84---H84A 109.5 C33---C34---H34B 109.5 C83---C84---H84B 109.5 H34A---C34---H34B 109.5 H84A---C84---H84B 109.5 C33---C34---H34C 109.5 C83---C84---H84C 109.5 H34A---C34---H34C 109.5 H84A---C84---H84C 109.5 H34B---C34---H34C 109.5 H84B---C84---H84C 109.5 C37---O36---C22 117.4 (2) C87---O86---C72 117.7 (3) O39---C37---O36 122.8 (3) O89---C87---O86 122.5 (3) O39---C37---C38 126.3 (3) O89---C87---C88 126.2 (4) O36---C37---C38 110.9 (3) O86---C87---C88 111.2 (4) C37---C38---H38A 109.5 C87---C88---H88A 109.5 C37---C38---H38B 109.5 C87---C88---H88B 109.5 H38A---C38---H38B 109.5 H88A---C88---H88B 109.5 C37---C38---H38C 109.5 C87---C88---H88C 109.5 H38A---C38---H38C 109.5 H88A---C88---H88C 109.5 H38B---C38---H38C 109.5 H88B---C88---H88C 109.5 C02B---O01---C02A---C12A 48 (11) C59---O51---C52A---C61A −85.3 (10) C09---O01---C02A---C12A −162.9 (3) C52B---O51---C52A---C61A −114 (12) C02B---O01---C02A---C03A 169 (12) C59---O51---C52A---C62A 155.7 (7) C09---O01---C02A---C03A −42.6 (5) C52B---O51---C52A---C62A 127 (12) C02B---O01---C02A---C11A −70 (11) C59---O51---C52A---C53A 35.6 (15) C09---O01---C02A---C11A 78.9 (4) C52B---O51---C52A---C53A 7(11) O01---C02A---C03A---C04A 59.6 (5) O51---C52A---C53A---C54A −53.6 (13) C12A---C02A---C03A---C04A 175.9 (4) C61A---C52A---C53A---C54A 61.1 (17) C11A---C02A---C03A---C04A −58.6 (5) C62A---C52A---C53A---C54A −175.7 (9) C02A---C03A---C04A---C10 −45.5 (5) C52A---C53A---C54A---C60 42.3 (12) C09---O01---C02B---C11B −95.5 (14) C52A---O51---C52B---C61B −120 (12) C02A---O01---C02B---C11B −62 (11) C59---O51---C52B---C61B 86.5 (9) C09---O01---C02B---C03B 18 (3) C52A---O51---C52B---C53B 118 (12) C02A---O01---C02B---C03B 52 (10) C59---O51---C52B---C53B −34.8 (16) C09---O01---C02B---C12B 150.1 (16) C52A---O51---C52B---C62B −3(11) C02A---O01---C02B---C12B −176 (13) C59---O51---C52B---C62B −156.2 (7) O01---C02B---C03B---C04B −46 (3) C61B---C52B---C53B---C54B −56.8 (17) C11B---C02B---C03B---C04B 56 (3) O51---C52B---C53B---C54B 56.1 (16) C12B---C02B---C03B---C04B 178 (2) C62B---C52B---C53B---C54B 173.9 (11) C02B---C03B---C04B---C10 40 (3) C52B---C53B---C54B---C60 −41.4 (12) C10---C05---C06---O14 −179.9 (2) C60---C55---C56---C57 −6.7 (4) C13---C05---C06---O14 −2.2 (4) C63---C55---C56---C57 171.5 (2) C10---C05---C06---C07 −3.9 (4) C60---C55---C56---O64 178.2 (2) C13---C05---C06---C07 173.9 (2) C63---C55---C56---O64 −3.7 (4) C05---C06---C07---C08 4.5 (4) C55---C56---C57---C58 6.4 (4) O14---C06---C07---C08 −179.3 (2) O64---C56---C57---C58 −178.4 (2) C05---C06---C07---C15 −172.1 (2) C55---C56---C57---C65 −170.3 (2) O14---C06---C07---C15 4.1 (3) O64---C56---C57---C65 4.9 (4) C06---C07---C08---C09 −1.2 (4) C56---C57---C58---C59 −1.4 (4) C15---C07---C08---C09 175.5 (2) C65---C57---C58---C59 175.4 (3) C06---C07---C08---C16 179.7 (2) C56---C57---C58---C66 −178.5 (2) C15---C07---C08---C16 −3.5 (4) C65---C57---C58---C66 −1.7 (4) C02B---O01---C09---C10 16.6 (15) C52A---O51---C59---C58 175.5 (9) C02A---O01---C09---C10 12.4 (4) C52B---O51---C59---C58 179.4 (9) C02B---O01---C09---C08 −166.3 (15) C52A---O51---C59---C60 −4.2 (10) C02A---O01---C09---C08 −170.5 (3) C52B---O51---C59---C60 −0.3 (10) C07---C08---C09---O01 −179.7 (2) C57---C58---C59---O51 177.2 (3) C16---C08---C09---O01 −0.7 (4) C66---C58---C59---O51 −5.7 (4) C07---C08---C09---C10 −2.7 (4) C57---C58---C59---C60 −3.1 (4) C16---C08---C09---C10 176.4 (3) C66---C58---C59---C60 174.0 (3) O01---C09---C10---C05 −179.9 (2) O51---C59---C60---C55 −177.5 (3) C08---C09---C10---C05 3.3 (4) C58---C59---C60---C55 2.8 (5) O01---C09---C10---C04A 2.4 (4) O51---C59---C60---C54A −7.9 (6) C08---C09---C10---C04A −174.5 (3) C58---C59---C60---C54A 172.5 (5) O01---C09---C10---C04B −20.6 (15) O51---C59---C60---C54B 13.7 (6) C08---C09---C10---C04B 162.6 (15) C58---C59---C60---C54B −165.9 (4) C06---C05---C10---C09 0.0 (4) C56---C55---C60---C59 1.9 (4) C13---C05---C10---C09 −177.8 (3) C63---C55---C60---C59 −176.2 (3) C06---C05---C10---C04A 177.8 (3) C56---C55---C60---C54A −167.1 (4) C13---C05---C10---C04A 0.0 (4) C63---C55---C60---C54A 14.7 (6) C06---C05---C10---C04B −158.1 (15) C56---C55---C60---C54B 171.2 (4) C13---C05---C10---C04B 24.2 (15) C63---C55---C60---C54B −6.9 (5) C03A---C04A---C10---C09 14.9 (5) C53A---C54A---C60---C59 −13.4 (8) C03A---C04A---C10---C05 −162.8 (3) C53A---C54A---C60---C55 155.9 (5) C03A---C04A---C10---C04B 97 (3) C53A---C54A---C60---C54B −124 (2) C03B---C04B---C10---C09 −9(3) C53B---C54B---C60---C59 8.7 (8) C03B---C04B---C10---C05 150.0 (15) C53B---C54B---C60---C55 −160.2 (4) C03B---C04B---C10---C04A −118 (4) C53B---C54B---C60---C54A 89 (2) C05---C06---O14---C17 −68.2 (3) C55---C56---O64---C67 −69.3 (3) C07---C06---O14---C17 115.6 (3) C57---C56---O64---C67 115.3 (3) C06---O14---C17---O23 137.0 (2) C56---O64---C67---O73 136.3 (2) C06---O14---C17---C18 −104.8 (3) C56---O64---C67---C68 −105.0 (2) O23---C17---C18---O24 179.22 (19) O73---C67---C68---O74 −179.99 (19) O14---C17---C18---O24 59.8 (3) O64---C67---C68---O74 60.5 (3) O23---C17---C18---C19 60.5 (3) O73---C67---C68---C69 60.0 (3) O14---C17---C18---C19 −59.0 (3) O64---C67---C68---C69 −59.4 (3) O24---C18---C19---O28 64.1 (3) O74---C68---C69---O78 61.9 (3) C17---C18---C19---O28 −175.3 (2) C67---C68---C69---O78 −176.5 (2) O24---C18---C19---C20 −177.3 (2) O74---C68---C69---C70 −179.1 (2) C17---C18---C19---C20 −56.7 (3) C67---C68---C69---C70 −57.5 (3) O28---C19---C20---O32 −71.9 (2) O78---C69---C70---O82 −67.5 (3) C18---C19---C20---O32 169.06 (19) C68---C69---C70---O82 172.2 (2) O28---C19---C20---C21 172.1 (2) O78---C69---C70---C71 174.6 (2) C18---C19---C20---C21 53.1 (3) C68---C69---C70---C71 54.2 (3) O32---C20---C21---O23 −169.9 (2) O82---C70---C71---O73 −172.12 (19) C19---C20---C21---O23 −53.3 (3) C69---C70---C71---O73 −53.4 (3) O32---C20---C21---C22 72.6 (3) O82---C70---C71---C72 70.1 (3) C19---C20---C21---C22 −170.8 (2) C69---C70---C71---C72 −171.3 (2) O23---C21---C22---O36 57.8 (3) O73---C71---C72---O86 50.8 (3) C20---C21---C22---O36 177.5 (2) C70---C71---C72---O86 170.7 (2) O14---C17---O23---C21 56.5 (3) O64---C67---O73---C71 57.8 (3) C18---C17---O23---C21 −63.5 (3) C68---C67---O73---C71 −61.8 (3) C22---C21---O23---C17 −178.6 (2) C72---C71---O73---C67 180.0 (2) C20---C21---O23---C17 60.5 (3) C70---C71---O73---C67 59.1 (3) C19---C18---O24---C25 −160.4 (2) C69---C68---O74---C75 −161.9 (2) C17---C18---O24---C25 79.4 (3) C67---C68---O74---C75 77.3 (3) C18---O24---C25---O26 4.1 (4) C68---O74---C75---O76 1.4 (4) C18---O24---C25---C27 −176.4 (2) C68---O74---C75---C77 −179.6 (2) C18---C19---O28---C29 −112.1 (3) C68---C69---O78---C79 −105.6 (3) C20---C19---O28---C29 128.8 (2) C70---C69---O78---C79 134.9 (2) C19---O28---C29---O30 0.0 (4) C69---O78---C79---O80 −1.7 (4) C19---O28---C29---C31 178.9 (2) C69---O78---C79---C81 178.5 (2) C19---C20---O32---C33 103.3 (3) C69---C70---O82---C83 99.7 (3) C21---C20---O32---C33 −138.0 (2) C71---C70---O82---C83 −140.7 (2) C20---O32---C33---O35 6.1 (4) C70---O82---C83---O85 7.9 (4) C20---O32---C33---C34 −174.2 (3) C70---O82---C83---C84 −172.3 (2) C21---C22---O36---C37 79.0 (3) C71---C72---O86---C87 78.2 (3) C22---O36---C37---O39 2.3 (4) C72---O86---C87---O89 4.3 (4) C22---O36---C37---C38 −176.6 (2) C72---O86---C87---C88 −174.4 (3) --------------------------- ------------- --------------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.431553

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052099/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o718", "authors": [ { "first": "Krzysztof", "last": "Brzezinski" }, { "first": "Piotr", "last": "Wałejko" }, { "first": "Aneta", "last": "Baj" }, { "first": "Stanisław", "last": "Witkowski" }, { "first": "Zbigniew", "last": "Dauter" } ] }

PMC3052100

Related literature {#sec1} ================== For the isolation of β-himachalene, see: Joseph & Dev (1968[@bb10]); Plattier & Teisseire (1974[@bb12]). For the reactivity of this sesquiterpene, see: Lassaba *et al.* (1998[@bb11]); Chekroun *et al.* (2000[@bb2]); El Jamili *et al.* (2002[@bb6]); Sbai *et al.* (2002[@bb13]); Dakir *et al.* (2004[@bb4]). For its biological activity, see: Daoubi *et al.* (2004[@bb5]). For conformational analysis, see: Cremer & Pople (1975[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~24~Cl~2~O*M* *~r~* = 303.25Trigonal,*a* = 13.2323 (13) Å*c* = 7.9807 (8) Å*V* = 1210.2 (2) Å^3^*Z* = 3Mo *K*α radiationμ = 0.39 mm^−1^*T* = 298 K0.41 × 0.33 × 0.26 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometer8123 measured reflections3135 independent reflections2995 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.019 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.045*wR*(*F* ^2^) = 0.126*S* = 1.093135 reflections180 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.52 e Å^−3^Δρ~min~ = −0.33 e Å^−3^Absolute structure: Flack (1983[@bb9]), 1940 Friedel pairsFlack parameter: −0.11 (7) {#d5e437} Data collection: *APEX2* (Bruker, 2009[@bb1]); cell refinement: *SAINT* (Bruker, 2009[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb14]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb14]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb7]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004788/tk2714sup1.cif](http://dx.doi.org/10.1107/S1600536811004788/tk2714sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004788/tk2714Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004788/tk2714Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?tk2714&file=tk2714sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?tk2714sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?tk2714&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [TK2714](http://scripts.iucr.org/cgi-bin/sendsup?tk2714)). We thank the National Center of Scientific and Technological Research (CNRST) which supports our scientific research. Comment ======= The bicyclic sesquiterpene β-himachalene is the main constituent of the essential oil of the Atlas cedar (*Cedrus atlantica*) (Joseph & Dev, 1968; Plattier & Teisseire, 1974). The reactivity of this sesquiterpene and its derivatives has been studied extensively by our team in order to prepare new products having biological proprieties (Lassaba *et al.*, 1998; Chekroun *et al.*, 2000; El Jamili *et al.*, 2002; Sbai *et al.*, 2002; Dakir *et al.*, 2004). Indeed, these compounds were tested, using the food poisoning technique, for their potential antifungal activity against the phytopathogen *Botrytis cinerea* (Daoubi *et al.*, 2004). The action of one equivalent of dichlorocarbene, generated *in situ* from chloroform in the presence of sodium hydroxide as base and n-benzyltriethylammonium chloride as catalyst, on β-himachalene produces only (1*S*,3*R*,8*R*)-2,2-dichloro-3,7,7,10- tetramethyltricyclo\[6.4.0.0^1,3^\]dodec-9-ene (El Jamili *et al.*, 2002). Treatment of the latter compound with two equivalents of *N*-bromosuccinimide gives (1*S*, 3*R*, 8*R*, 11S)-2,2-dichloro -3,7,7,10-tetralethyltricyclo\[6.4.0.0^1,3^\]dodec-9-en-11-ol in a very low yield (5%), along with other products. The structure of this new product was determined by NMR (^1^H & ^13^C) spectral analysis and mass spectroscopy, and confirmed by a crystallographic study, reported herein. The molecule is built up from two fused six-membered and seven-membered rings (Fig. 1). The six-membered ring has a screw boat conformation, as indicated by the total puckering amplitude QT = 0.480 (3) Å and spherical polar angle θ = 130.6 (4) ° with φ = 151.5 (5) °, whereas the seven-membered ring displays a boat conformation with QT = 1.1449 (30) Å, θ~2~ = 88.29 (15) °, φ~2~ = -47.13 (14) ° and φ~3~ =-144.24 (5) ° (Cremer & Pople, 1975). In the crystal structure, molecules are linked into supramolecular chains (Fig. 2) running along the *c* axis by O---H···O hydrogen bonds (Table 1). Owing to the presence of Cl atoms, the absolute configuration could be fully confirmed, as C1(*S*), C3(*R*), C8(*R*) and C11(*S*). Experimental {#experimental} ============ In a reactor containing a solution of (1*S*, 3*R*, 8*R*)-2,2-dichloro-3,7,7,10 tetramethyltricyclo \[6.4.0.0^1,3^\] dodec-9-ene (1 g, 3.48 mmol) in 50 ml of tetrahydrofuran and water (THF/H~2~O) (4:1) cooled to 273 K and kept in the dark, was added in small portions 1.23 g (6.96 mmol) of *N*-bromosccinimide. The reaction mixture was left stirring for 1 h, after which 20 ml of a saturated solution of NaHCO~3~ was added. Subsequently, the extraction was performed three times with diethyl ether (3 x 20 ml). The organic extracts were dried over Na~2~SO~4~, filtered, concentrated, and chromatographed. The title compound, (1*S*, 3*R*, 8*R*, 11*S*,)-2,2-dichloro-3,7,7,10-tetralethyltricyclo \[6.4.0.0^1,3^\] dodec-9-by-11-ol was obtained with in a yield of 5% and was recrystallized its pentane solution. Refinement {#refinement} ========== All H atoms were fixed geometrically and treated as riding with O---H = 0.82 Å and C---H = 0.93 (ethylene), 0.96 Å (methyl), 0.97 Å (methylene) and 0.98Å (methine), and with *U*~iso~(H) = 1.2U~eq~ (ethylene, methylene, methine) or *U*~iso~(H) = 1.5*U*~eq~ (O, methyl). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o615-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing diagram showing the O---H···O interactions (dashed lines) and the formation of supramolecular chains parallel to the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o615-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e274 .table-wrap} ----------------------- --------------------------------------- C~16~H~24~Cl~2~O *D*~x~ = 1.244 Mg m^−3^ *M~r~* = 303.25 Mo *K*α radiation, λ = 0.71073 Å Trigonal, *P*3~2~ Cell parameters from 8123 reflections Hall symbol: P 32 θ = 4--26.4° *a* = 13.2323 (13) Å µ = 0.39 mm^−1^ *c* = 7.9807 (8) Å *T* = 298 K *V* = 1210.2 (2) Å^3^ Prism, colourless *Z* = 3 0.41 × 0.33 × 0.26 mm *F*(000) = 486 ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e390 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2995 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.019 graphite θ~max~ = 26.4°, θ~min~ = 4.0° ω and φ scans *h* = −15→16 8123 measured reflections *k* = −14→16 3135 independent reflections *l* = −9→9 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e488 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.045 H-atom parameters constrained *wR*(*F*^2^) = 0.126 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0761*P*)^2^ + 0.4405*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.09 (Δ/σ)~max~ \< 0.001 3135 reflections Δρ~max~ = 0.52 e Å^−3^ 180 parameters Δρ~min~ = −0.33 e Å^−3^ 1 restraint Absolute structure: Flack & Bernardinelli (2000), 1940 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.11 (7) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e653 .table-wrap} -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e673 .table-wrap} ------ -------------- ------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 1.0043 (2) 0.6432 (2) 0.5388 (3) 0.0304 (5) C2 0.9057 (2) 0.5880 (2) 0.4113 (4) 0.0370 (5) C3 0.8790 (2) 0.5564 (2) 0.5938 (4) 0.0392 (6) C4 0.8143 (3) 0.6069 (3) 0.6915 (4) 0.0464 (7) H4A 0.8228 0.6749 0.6329 0.056\* H4B 0.7319 0.5493 0.6955 0.056\* C5 0.8600 (3) 0.6411 (3) 0.8682 (5) 0.0541 (8) H5A 0.8234 0.5720 0.9384 0.065\* H5B 0.8370 0.6953 0.9106 0.065\* C6 0.9973 (3) 0.6991 (4) 0.8854 (5) 0.0591 (9) H6A 1.0178 0.7232 1.0010 0.071\* H6B 1.0175 0.6394 0.8633 0.071\* C7 1.0733 (2) 0.8032 (3) 0.7746 (4) 0.0426 (6) C8 1.0545 (2) 0.7728 (2) 0.5810 (3) 0.0308 (5) H8 0.9966 0.7933 0.5426 0.041 (8)\* C9 1.1625 (2) 0.8449 (2) 0.4781 (4) 0.0394 (6) H9 1.1895 0.9246 0.4721 0.039 (8)\* C10 1.2228 (2) 0.8058 (2) 0.3951 (4) 0.0367 (5) C11 1.1869 (2) 0.6778 (2) 0.3958 (3) 0.0333 (5) H11 1.1523 0.6443 0.2867 0.029 (7)\* C12 1.0980 (2) 0.6089 (2) 0.5320 (4) 0.0364 (5) H12A 1.0624 0.5260 0.5090 0.044\* H12B 1.1371 0.6242 0.6396 0.044\* C13 1.3285 (3) 0.8828 (3) 0.2905 (5) 0.0549 (8) H13A 1.3407 0.9607 0.2893 0.082\* H13B 1.3164 0.8532 0.1780 0.082\* H13C 1.3957 0.8837 0.3373 0.082\* C14 0.8465 (3) 0.4338 (3) 0.6503 (6) 0.0633 (10) H14A 0.7653 0.3913 0.6796 0.095\* H14B 0.8927 0.4386 0.7459 0.095\* H14C 0.8611 0.3943 0.5608 0.095\* C15 1.0481 (4) 0.9031 (4) 0.8042 (6) 0.0718 (11) H15A 0.9719 0.8811 0.7621 0.108\* H15B 1.1055 0.9718 0.7469 0.108\* H15C 1.0512 0.9188 0.9221 0.108\* C16 1.2019 (4) 0.8507 (4) 0.8255 (6) 0.0730 (11) H16A 1.2122 0.8740 0.9410 0.109\* H16B 1.2515 0.9168 0.7568 0.109\* H16C 1.2219 0.7909 0.8102 0.109\* O1 1.28683 (18) 0.6633 (2) 0.4212 (3) 0.0453 (5) H1 1.3211 0.6727 0.3319 0.068\* Cl1 0.85533 (6) 0.67322 (7) 0.30875 (9) 0.0497 (2) Cl2 0.90015 (7) 0.48357 (7) 0.26866 (11) 0.0605 (2) ------ -------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1228 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0314 (11) 0.0304 (11) 0.0315 (12) 0.0170 (10) 0.0015 (9) 0.0018 (9) C2 0.0353 (12) 0.0343 (12) 0.0391 (14) 0.0157 (10) −0.0032 (10) −0.0049 (10) C3 0.0350 (13) 0.0374 (13) 0.0431 (15) 0.0164 (11) 0.0042 (11) 0.0079 (11) C4 0.0365 (14) 0.0604 (18) 0.0436 (16) 0.0253 (13) 0.0107 (11) 0.0114 (13) C5 0.0556 (19) 0.069 (2) 0.0418 (16) 0.0344 (17) 0.0144 (14) 0.0117 (15) C6 0.065 (2) 0.079 (2) 0.0401 (17) 0.0407 (19) −0.0012 (14) 0.0047 (16) C7 0.0435 (14) 0.0539 (16) 0.0364 (14) 0.0289 (13) −0.0053 (11) −0.0123 (12) C8 0.0306 (11) 0.0319 (12) 0.0351 (12) 0.0197 (10) 0.0012 (9) −0.0015 (9) C9 0.0409 (14) 0.0287 (12) 0.0461 (16) 0.0155 (10) 0.0048 (11) 0.0006 (10) C10 0.0320 (12) 0.0339 (13) 0.0409 (14) 0.0141 (10) 0.0025 (10) −0.0003 (10) C11 0.0327 (12) 0.0367 (12) 0.0365 (14) 0.0218 (10) −0.0017 (9) −0.0045 (10) C12 0.0369 (12) 0.0343 (12) 0.0451 (14) 0.0230 (11) 0.0031 (10) 0.0023 (10) C13 0.0452 (16) 0.0493 (17) 0.064 (2) 0.0190 (14) 0.0200 (15) 0.0072 (14) C14 0.0562 (19) 0.0404 (16) 0.082 (3) 0.0158 (15) 0.0123 (17) 0.0191 (16) C15 0.078 (3) 0.071 (2) 0.078 (3) 0.046 (2) 0.002 (2) −0.023 (2) C16 0.058 (2) 0.087 (3) 0.069 (3) 0.033 (2) −0.0150 (19) −0.023 (2) O1 0.0410 (10) 0.0614 (13) 0.0479 (12) 0.0365 (10) 0.0009 (8) −0.0025 (9) Cl1 0.0471 (4) 0.0680 (5) 0.0384 (3) 0.0321 (4) −0.0065 (3) 0.0047 (3) Cl2 0.0541 (4) 0.0536 (4) 0.0643 (5) 0.0199 (4) −0.0071 (4) −0.0266 (4) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1591 .table-wrap} ---------------- ------------- ------------------- ----------- C1---C12 1.521 (3) C9---C10 1.326 (4) C1---C2 1.522 (3) C9---H9 0.9300 C1---C3 1.534 (3) C10---C13 1.506 (4) C1---C8 1.535 (3) C10---C11 1.513 (4) C2---C3 1.507 (4) C11---O1 1.442 (3) C2---Cl2 1.764 (3) C11---C12 1.524 (4) C2---Cl1 1.771 (3) C11---H11 0.9800 C3---C14 1.524 (4) C12---H12A 0.9700 C3---C4 1.535 (4) C12---H12B 0.9700 C4---C5 1.512 (5) C13---H13A 0.9600 C4---H4A 0.9700 C13---H13B 0.9600 C4---H4B 0.9700 C13---H13C 0.9600 C5---C6 1.584 (5) C14---H14A 0.9600 C5---H5A 0.9700 C14---H14B 0.9600 C5---H5B 0.9700 C14---H14C 0.9600 C6---C7 1.518 (5) C15---H15A 0.9600 C6---H6A 0.9700 C15---H15B 0.9600 C6---H6B 0.9700 C15---H15C 0.9600 C7---C15 1.534 (5) C16---H16A 0.9600 C7---C16 1.545 (5) C16---H16B 0.9600 C7---C8 1.585 (4) C16---H16C 0.9600 C8---C9 1.505 (3) O1---H1 0.8200 C8---H8 0.9800 C12---C1---C2 117.7 (2) C1---C8---H8 106.2 C12---C1---C3 121.6 (2) C7---C8---H8 106.2 C2---C1---C3 59.08 (17) C10---C9---C8 126.2 (2) C12---C1---C8 112.3 (2) C10---C9---H9 116.9 C2---C1---C8 118.1 (2) C8---C9---H9 116.9 C3---C1---C8 118.4 (2) C9---C10---C13 123.3 (3) C3---C2---C1 60.86 (17) C9---C10---C11 121.5 (2) C3---C2---Cl2 119.6 (2) C13---C10---C11 115.2 (2) C1---C2---Cl2 119.77 (19) O1---C11---C10 110.7 (2) C3---C2---Cl1 120.9 (2) O1---C11---C12 107.7 (2) C1---C2---Cl1 120.59 (18) C10---C11---C12 112.9 (2) Cl2---C2---Cl1 108.61 (15) O1---C11---H11 108.5 C2---C3---C14 118.9 (3) C10---C11---H11 108.5 C2---C3---C1 60.06 (16) C12---C11---H11 108.5 C14---C3---C1 120.3 (3) C1---C12---C11 110.3 (2) C2---C3---C4 118.3 (2) C1---C12---H12A 109.6 C14---C3---C4 113.0 (3) C11---C12---H12A 109.6 C1---C3---C4 116.7 (2) C1---C12---H12B 109.6 C5---C4---C3 112.2 (3) C11---C12---H12B 109.6 C5---C4---H4A 109.2 H12A---C12---H12B 108.1 C3---C4---H4A 109.2 C10---C13---H13A 109.5 C5---C4---H4B 109.2 C10---C13---H13B 109.5 C3---C4---H4B 109.2 H13A---C13---H13B 109.5 H4A---C4---H4B 107.9 C10---C13---H13C 109.5 C4---C5---C6 114.6 (3) H13A---C13---H13C 109.5 C4---C5---H5A 108.6 H13B---C13---H13C 109.5 C6---C5---H5A 108.6 C3---C14---H14A 109.5 C4---C5---H5B 108.6 C3---C14---H14B 109.5 C6---C5---H5B 108.6 H14A---C14---H14B 109.5 H5A---C5---H5B 107.6 C3---C14---H14C 109.5 C7---C6---C5 118.0 (3) H14A---C14---H14C 109.5 C7---C6---H6A 107.8 H14B---C14---H14C 109.5 C5---C6---H6A 107.8 C7---C15---H15A 109.5 C7---C6---H6B 107.8 C7---C15---H15B 109.5 C5---C6---H6B 107.8 H15A---C15---H15B 109.5 H6A---C6---H6B 107.2 C7---C15---H15C 109.5 C6---C7---C15 111.2 (3) H15A---C15---H15C 109.5 C6---C7---C16 108.2 (3) H15B---C15---H15C 109.5 C15---C7---C16 106.2 (3) C7---C16---H16A 109.5 C6---C7---C8 112.8 (2) C7---C16---H16B 109.5 C15---C7---C8 107.1 (3) H16A---C16---H16B 109.5 C16---C7---C8 111.1 (3) C7---C16---H16C 109.5 C9---C8---C1 109.4 (2) H16A---C16---H16C 109.5 C9---C8---C7 113.1 (2) H16B---C16---H16C 109.5 C1---C8---C7 115.0 (2) C11---O1---H1 109.5 C9---C8---H8 106.2 ---------------- ------------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2235 .table-wrap} ----------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1···O1^i^ 0.82 2.10 2.853 (4) 153 ----------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*y*+2, *x*−*y*, *z*−1/3. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- --------- ------- ----------- ------------- O1---H1⋯O1^i^ 0.82 2.10 2.853 (4) 153 Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.449460

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052100/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o615", "authors": [ { "first": "Ahmed", "last": "Benharref" }, { "first": "Essêdiya", "last": "Lassaba" }, { "first": "Daniel", "last": "Avignant" }, { "first": "Abdelghani", "last": "Oudahmane" }, { "first": "Moha", "last": "Berraho" } ] }

PMC3052101

Related literature {#sec1} ================== For background to to the use of transition metal complexes with Schiff bases as potential enzyme inhibitors, see: You *et al.* (2008[@bb10]); Shi *et al.* (2007[@bb9]). For the use of transition metal complexes for the development of catalysis, magnetism and molecular architectures, see: Yu *et al.* (2007[@bb14]); You & Zhu (2004[@bb12]); You & Zhou (2007[@bb11]). For the use of transition metal complexes for optoelectronic and also for photo- and electroluminescence applications, see: Yu *et al.* (2008[@bb15]). For the potential use of transition metal complexes in the modeling of multisite metalloproteins and in nano-science, see: Chattopadhyay *et al.* (2006[@bb2]). For the importance of tri-nuclear cobalt Schiff base complexes as catalysts for organic molecules and as antiviral agents due to their ability to interact with proteins and nucleic acids, see: Chattopadhyay *et al.* (2006[@bb2], 2008[@bb3]); Babushkin & Talsi (1998)[@bb1]. For background to metallosalen complexes, see: Dong *et al.* (2008[@bb4]). For the magnetic properties of quadridentate metal complexes of Schiff bases, see: He *et al.* (2006[@bb6]); Gerli *et al.* (1991[@bb5]). For the antimicrobial activity of Schiff base ligands and their complexes, see: You *et al.* (2004[@bb13]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co~3~(C~2~H~3~O~2~)~4~(C~20~H~22~N~2~O~6~)~2~\]·2CH~2~Cl~2~*M* *~r~* = 1355.61Monoclinic,*a* = 13.9235 (9) Å*b* = 13.4407 (8) Å*c* = 16.0019 (11) Åβ = 112.724 (8)°*V* = 2762.2 (3) Å^3^*Z* = 2Cu *K*α radiationμ = 9.45 mm^−1^*T* = 110 K0.42 × 0.25 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcalibur diffractometer with a Ruby detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2009[@bb7]) *T* ~min~ = 0.320, *T* ~max~ = 1.00010708 measured reflections5306 independent reflections3777 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.043 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.083*wR*(*F* ^2^) = 0.251*S* = 1.035306 reflections373 parametersH-atom parameters constrainedΔρ~max~ = 1.11 e Å^−3^Δρ~min~ = −1.66 e Å^−3^ {#d5e710} Data collection: *CrysAlis PRO* (Oxford Diffraction, 2009[@bb7]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb8]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003783/jj2072sup1.cif](http://dx.doi.org/10.1107/S1600536811003783/jj2072sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003783/jj2072Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003783/jj2072Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jj2072&file=jj2072sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jj2072sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jj2072&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JJ2072](http://scripts.iucr.org/cgi-bin/sendsup?jj2072)). RJB wishes to acknowledge the NSF-MRI program (grant CHE-0619278) for funds to purchase the diffractometer. Comment ======= A number of transition metal complexes with Schiff base ligands have been studied as potential inhibitors for the xanthine oxidase (XO) enzyme (You *et al.*, 2008) and also for the jack bean urease enzyme (jbU) (Shi *et al.*, 2007). The enzyme XO catalyzes the hydroxylation of hypoxanthine and xanthine to yield uric acid and superoxide anions. Other areas where complexes of transition metals have played roles are in the development of catalysis, magnetism and molecular architecture (Yu *et al.*, 2007, You & Zhu, 2004, You & Zhou, 2007). Complexes of transition metals with Schiff base ligands have also been shown to be useful materials for optoelectronics and also for photo and electro-luminance applications (Yu *et al.*, 2008). Studies for antimicrobial activities of Schiff base ligands as well as those of their corresponding complexes have been investigated (You *et al.*, 2004) where it was shown that Schiff base ligands as well as their complexes exhibited good antibacterial properties. Metallosalen complexes are of great importance due to their use in various catalytic chemical transformations that includes, epoxidation of olefins, symmetric ring opening, azirdination of olefins, olefine cyclopropanation and formation of linear and cyclic hydrocarbonation (Dong *et al.*, 2008). The importance of tri-nuclear cobalt Schiff base complexes ranges from, catalysts for oxidation of organic molecules, antiviral agents due to their ability to interact with proteins and nucleic acids and they have also used to mimic the biological co-factor such as cobalamin (Chattopadhyay *et al.*, 2008, Babushkin & Talsi, 1998). The quadridentate metal complexes of Schiff bases have been studied extensively as B12 models, their magnetic interaction between bridged paramagnetic metal ions and their applications (Gerli *et al.*, 1991). Magnetic susceptibilities data for the trinuclear mixed valence compound \[Co^II^(OAc)~2~(hapt)~2~Co~2~(III)(py)~2~\](ClO~4~)~2~ \[where (hapt) is bis-(2-hydroxyacetophenone) trimethylenediimine\] were measured in the temperature range of 300--2 K and it was found that µ~eff~ values are almost constant ranging from 4.37 to 5.00 BM (He *et al.*, 2006). The values obtained suggested that the oxidation states are Co^III^(S = 0)-Co^II^(S = 3/2)-Co^III^(S = 0). Cyclic tri-nuclear cobalt complexes have also shown some catalytic activities in epoxidation of olefins, autoxidation of hydrocarbons, utility in modeling multinuclear active sites of metalloproteins and their potential use in nanoscience (Chattopadhyay *et al.*, 2006). The title compound C~50~H~60~Cl~4~Co~3~N~4~O~20~ is a trinuclear cobalt Schiff base complex containing a central high spin Co^II^ and two terminal low spin Co^III^ centers. The environment around Co(1) is hexacoordinated with two imine nitrogen atoms, N(1) and N(2), two phenolate oxygen atoms, O(1) and O(2), and two oxygen atoms, O(11 A) and O(21 A), from two acetate groups. The central Co(2) ion is coordinated by four phenolate oxygen atoms and two acetate oxygen atoms O(12 A), O(2)\#2, O(2), O(1), O(1), O(1)\#1 and O(12)\#1. The bond distances of the coordination atoms around Co(1) are Co(1)---N(2) = 1.861 (5) Å, Co(1)---N(1) = 1.871 (5) Å, Co(1)---O(2) = 1.887 (4) Å, Co(1)---O(1) = 1.89 (4) Å, Co(1)---O(21 A) = 1.891 (4) Å, Co(1)---O(11 A) = 1.929 (4) Å and the bond lengths between Co(2) and its coordinating atoms are Co(2)---O(12 A)\#1 = 2.043 (4) Å, Co(2)---O(12 A) = 2.043 (4) Å, Co(2)---O(2)\#1 = 2.117 (4) Å, Co(A)---O(2) = 2.117 (4) Å, Co(2)---O(1) = 2.160 (4) Å, Co(2)---O(1)\#1 = 2.160 (4) Å. The coordination around the central metal ion displays a slight distortion from octahedral geometry as shown by the *cis* angles are mostly close to 90°. The main deviations are caused by the small bite of the salen O donors \[72.15 (15)°\]. The basal planes of the complex are formed by the two bridging O atoms and two N atoms of the Schiff base ligand. The O atoms of the acetate group occupy apical positions. There are weak intermolecular C---H···O interactions involving the methoxy groups and acetate anions. In addition the dichoromethane solvate molecules are held in place by weak C---H···Cl interactions. Experimental {#experimental} ============ The synthesis of the ligand ethylene-bis(2,4-dimethoxy-salicylaldimine) was achieved by adding a solution of (2 g, 33.3 mmol) ethylenediamine in 25 ml s of methanol to the solution of (12.13 g, 66.6 mmol) 2,4-dimethoxysalicylaldehyde in 40 ml s of methanol. The mixture was refluxed overnight while stirring. The reaction mixture was then evaporated under reduced pressure to afford yellow solids. The synthesis of the complex C~50~H~60~Cl~4~Co~3~N~4~O~20~ was accomplished by adding a solution of (0.38 g, 1 mmol) of ethylene-bis(2,4-dimethoxy-salicylaldimine) in 20 ml dichloromethane to a solution of Co(CH~3~COO)~2~.H~2~O in 5 ml me thanol. The mixture was stirred for 3 h, filtered and layered with di-ethyl ether for crystallization. Crystals suitable for X-ray diffraction were obtained. Refinement {#refinement} ========== H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with a C---H distances of 0.95 and 0.99 Å *U*~iso~(H) = 1.2*U*~eq~(C) and 0.98 Å for CH~3~ \[*U*~iso~(H) = 1.5*U*~eq~(C)\]. In the final difference Fourier the maximum and minimum electron density of 1.11 and -1.66 e^-^/Å^3^ were located 0.93 Å and 0.44 Å from H0A and Cl1 respectively Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Diagram of trinuclear C48H56Co3N4O20 unit showing atom labeling. Thermal ellipsoids are at the 30% probability level. ::: ![](e-67-0m303-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular packing for C48H56Co3N4O20.2(CH2Cl2) viewed down the b axis. C---H···Cl and C---H···O interactions bonds are shown by dashed lines. ::: ![](e-67-0m303-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e297 .table-wrap} --------------------------------------------------------------- --------------------------------------- \[Co~3~(C~2~H~3~O~2~)~4~(C~20~H~22~N~2~O~6~)~2~\]·2CH~2~Cl~2~ *F*(000) = 1394 *M~r~* = 1355.61 *D*~x~ = 1.630 Mg m^−3^ Monoclinic, *P*2~1~/*n* Cu *K*α radiation, λ = 1.54178 Å Hall symbol: -P 2yn Cell parameters from 4463 reflections *a* = 13.9235 (9) Å θ = 4.4--73.9° *b* = 13.4407 (8) Å µ = 9.45 mm^−1^ *c* = 16.0019 (11) Å *T* = 110 K β = 112.724 (8)° Thick needle, red-brown *V* = 2762.2 (3) Å^3^ 0.42 × 0.25 × 0.18 mm *Z* = 2 --------------------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e453 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcalibur diffractometer with a Ruby (Gemini Cu) detector 5306 independent reflections Radiation source: Enhance (Cu) X-ray Source 3777 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.043 Detector resolution: 10.5081 pixels mm^-1^ θ~max~ = 74.2°, θ~min~ = 4.5° ω scans *h* = −17→13 Absorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2009) *k* = −16→13 *T*~min~ = 0.320, *T*~max~ = 1.000 *l* = −19→18 10708 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e573 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.083 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.251 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.1718*P*)^2^ + 2.5393*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5306 reflections (Δ/σ)~max~ \< 0.001 373 parameters Δρ~max~ = 1.11 e Å^−3^ 0 restraints Δρ~min~ = −1.66 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e730 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e829 .table-wrap} ------ -------------- ------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Co1 0.31088 (7) 0.37441 (7) 0.38337 (6) 0.0133 (3) Co2 0.5000 0.5000 0.5000 0.0138 (3) Cl1 −0.1730 (2) 0.4911 (2) 0.0248 (2) 0.0736 (8) Cl2 −0.2861 (3) 0.3805 (3) 0.1142 (2) 0.0826 (10) O1 0.4170 (3) 0.4463 (3) 0.3637 (3) 0.0142 (8) O2 0.3510 (3) 0.4519 (3) 0.4897 (3) 0.0176 (9) O3 0.5670 (4) 0.6103 (3) 0.1809 (3) 0.0229 (10) O4 0.3576 (4) 0.3258 (4) 0.0695 (3) 0.0239 (10) O5 0.0593 (4) 0.3797 (4) 0.5633 (3) 0.0276 (11) O6 0.2587 (4) 0.6707 (4) 0.6799 (3) 0.0279 (11) O11A 0.4076 (3) 0.2697 (3) 0.4437 (3) 0.0178 (9) O12A 0.5482 (3) 0.3568 (3) 0.5344 (3) 0.0182 (9) O21A 0.2186 (3) 0.4771 (3) 0.3178 (3) 0.0213 (10) O22A 0.0637 (4) 0.3991 (4) 0.2533 (3) 0.0296 (11) N1 0.2737 (4) 0.2957 (4) 0.2792 (3) 0.0154 (10) N2 0.2130 (4) 0.3016 (4) 0.4107 (3) 0.0179 (11) C −0.1698 (10) 0.3882 (8) 0.0942 (7) 0.062 (3) H0A −0.1096 0.3946 0.1527 0.075\* H0B −0.1608 0.3263 0.0644 0.075\* C1 0.4274 (4) 0.4539 (5) 0.2860 (4) 0.0146 (12) C2 0.4903 (4) 0.5312 (5) 0.2754 (4) 0.0129 (11) H2A 0.5195 0.5790 0.3222 0.015\* C3 0.5093 (5) 0.5373 (5) 0.1979 (4) 0.0190 (13) C4 0.6125 (5) 0.6836 (5) 0.2508 (4) 0.0265 (15) H4A 0.6550 0.7298 0.2323 0.040\* H4B 0.6563 0.6503 0.3072 0.040\* H4C 0.5570 0.7205 0.2607 0.040\* C5 0.4666 (5) 0.4690 (5) 0.1259 (4) 0.0188 (13) H5A 0.4817 0.4740 0.0731 0.023\* C6 0.4019 (5) 0.3940 (5) 0.1342 (4) 0.0170 (12) C7 0.3851 (7) 0.3271 (6) −0.0085 (5) 0.0353 (18) H7A 0.3580 0.2671 −0.0448 0.053\* H7B 0.4611 0.3288 0.0114 0.053\* H7C 0.3550 0.3861 −0.0452 0.053\* C8 0.3786 (5) 0.3854 (5) 0.2132 (4) 0.0179 (12) C9 0.3083 (4) 0.3071 (5) 0.2162 (4) 0.0150 (12) H9A 0.2861 0.2607 0.1678 0.018\* C10 0.1969 (5) 0.2181 (5) 0.2716 (4) 0.0210 (13) H10A 0.2179 0.1549 0.2518 0.025\* H10B 0.1280 0.2376 0.2261 0.025\* C11 0.1902 (6) 0.2044 (5) 0.3629 (5) 0.0267 (15) H11A 0.1197 0.1814 0.3551 0.032\* H11B 0.2413 0.1538 0.3987 0.032\* C12 0.1734 (4) 0.3272 (5) 0.4676 (4) 0.0176 (12) H12A 0.1235 0.2839 0.4752 0.021\* C13 0.1990 (5) 0.4164 (5) 0.5206 (4) 0.0181 (13) C14 0.1394 (5) 0.4440 (5) 0.5709 (4) 0.0238 (14) C15 −0.0028 (6) 0.4037 (6) 0.6139 (5) 0.0316 (17) H15A −0.0562 0.3525 0.6038 0.047\* H15B −0.0363 0.4684 0.5941 0.047\* H15C 0.0417 0.4067 0.6786 0.047\* C16 0.1603 (5) 0.5288 (5) 0.6242 (5) 0.0231 (14) H16A 0.1192 0.5456 0.6577 0.028\* C17 0.2433 (5) 0.5885 (5) 0.6274 (4) 0.0223 (14) C18 0.3486 (6) 0.7310 (6) 0.6947 (6) 0.041 (2) H18A 0.3498 0.7866 0.7347 0.061\* H18B 0.3458 0.7570 0.6366 0.061\* H18C 0.4116 0.6907 0.7229 0.061\* C19 0.3059 (5) 0.5648 (5) 0.5799 (4) 0.0185 (13) H19A 0.3616 0.6072 0.5825 0.022\* C20 0.2851 (4) 0.4775 (5) 0.5283 (4) 0.0178 (13) C11A 0.5005 (5) 0.2775 (5) 0.5022 (4) 0.0175 (12) C12A 0.5555 (5) 0.1810 (5) 0.5336 (5) 0.0272 (15) H12B 0.5189 0.1282 0.4910 0.041\* H12C 0.5569 0.1651 0.5938 0.041\* H12D 0.6270 0.1863 0.5367 0.041\* C21A 0.1218 (5) 0.4706 (5) 0.2639 (4) 0.0210 (13) C22A 0.0821 (6) 0.5634 (6) 0.2093 (5) 0.0308 (16) H22A 0.0067 0.5580 0.1758 0.046\* H22B 0.1163 0.5717 0.1665 0.046\* H22C 0.0974 0.6210 0.2500 0.046\* ------ -------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1745 .table-wrap} ------ ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Co1 0.0088 (5) 0.0168 (5) 0.0142 (5) −0.0035 (4) 0.0043 (3) −0.0026 (4) Co2 0.0088 (6) 0.0186 (7) 0.0142 (6) −0.0039 (5) 0.0046 (5) −0.0031 (5) Cl1 0.0671 (18) 0.0709 (19) 0.0748 (18) −0.0053 (15) 0.0184 (15) 0.0120 (15) Cl2 0.087 (2) 0.093 (2) 0.075 (2) −0.0023 (19) 0.0400 (18) 0.0040 (18) O1 0.0090 (19) 0.020 (2) 0.0145 (19) −0.0039 (17) 0.0058 (15) −0.0011 (17) O2 0.0118 (19) 0.024 (2) 0.019 (2) −0.0044 (18) 0.0085 (16) −0.0089 (18) O3 0.023 (2) 0.022 (2) 0.027 (2) −0.0050 (19) 0.0145 (19) 0.001 (2) O4 0.025 (2) 0.033 (3) 0.014 (2) −0.005 (2) 0.0088 (18) −0.004 (2) O5 0.017 (2) 0.035 (3) 0.037 (3) −0.004 (2) 0.017 (2) −0.005 (2) O6 0.023 (2) 0.031 (3) 0.034 (3) 0.004 (2) 0.016 (2) −0.010 (2) O11A 0.013 (2) 0.019 (2) 0.018 (2) −0.0029 (17) 0.0019 (16) −0.0023 (17) O12A 0.010 (2) 0.022 (2) 0.019 (2) −0.0030 (17) 0.0019 (16) −0.0040 (18) O21A 0.014 (2) 0.023 (2) 0.024 (2) 0.0015 (18) 0.0034 (17) −0.0020 (19) O22A 0.023 (2) 0.024 (3) 0.034 (3) −0.006 (2) 0.002 (2) 0.001 (2) N1 0.011 (2) 0.017 (2) 0.016 (2) −0.001 (2) 0.0028 (18) −0.004 (2) N2 0.012 (2) 0.020 (3) 0.021 (2) −0.007 (2) 0.005 (2) −0.001 (2) C 0.084 (8) 0.044 (5) 0.052 (6) −0.003 (6) 0.019 (6) 0.009 (5) C1 0.007 (2) 0.017 (3) 0.016 (3) 0.003 (2) 0.001 (2) 0.000 (2) C2 0.006 (2) 0.018 (3) 0.014 (3) 0.002 (2) 0.003 (2) 0.001 (2) C3 0.011 (3) 0.019 (3) 0.024 (3) 0.007 (2) 0.003 (2) 0.005 (3) C4 0.025 (3) 0.033 (4) 0.023 (3) −0.015 (3) 0.012 (3) −0.002 (3) C5 0.024 (3) 0.024 (3) 0.014 (3) 0.005 (3) 0.013 (2) 0.002 (3) C6 0.015 (3) 0.022 (3) 0.011 (3) 0.005 (2) 0.002 (2) 0.001 (2) C7 0.046 (5) 0.042 (5) 0.024 (3) −0.009 (4) 0.020 (3) −0.012 (3) C8 0.012 (3) 0.017 (3) 0.025 (3) 0.003 (2) 0.008 (2) 0.001 (3) C9 0.013 (3) 0.016 (3) 0.011 (2) 0.006 (2) 0.000 (2) −0.001 (2) C10 0.019 (3) 0.020 (3) 0.027 (3) −0.008 (3) 0.011 (3) −0.008 (3) C11 0.027 (4) 0.025 (4) 0.026 (3) −0.016 (3) 0.007 (3) −0.011 (3) C12 0.011 (3) 0.023 (3) 0.019 (3) −0.007 (2) 0.006 (2) −0.001 (3) C13 0.011 (3) 0.027 (3) 0.015 (3) 0.003 (2) 0.004 (2) 0.004 (3) C14 0.015 (3) 0.033 (4) 0.022 (3) 0.006 (3) 0.006 (3) 0.004 (3) C15 0.027 (4) 0.043 (4) 0.038 (4) 0.003 (3) 0.027 (3) 0.007 (3) C16 0.014 (3) 0.029 (4) 0.031 (3) 0.008 (3) 0.014 (3) 0.000 (3) C17 0.019 (3) 0.027 (3) 0.020 (3) 0.004 (3) 0.006 (2) 0.001 (3) C18 0.029 (4) 0.038 (4) 0.052 (5) 0.000 (4) 0.011 (4) −0.030 (4) C19 0.012 (3) 0.019 (3) 0.024 (3) 0.005 (2) 0.006 (2) −0.001 (3) C20 0.009 (3) 0.026 (3) 0.015 (3) 0.002 (2) 0.001 (2) 0.001 (3) C11A 0.012 (3) 0.026 (3) 0.017 (3) −0.001 (2) 0.008 (2) 0.004 (3) C12A 0.022 (3) 0.027 (4) 0.024 (3) −0.002 (3) −0.001 (3) −0.004 (3) C21A 0.017 (3) 0.028 (3) 0.019 (3) 0.006 (3) 0.008 (2) −0.003 (3) C22A 0.024 (3) 0.035 (4) 0.034 (4) −0.004 (3) 0.011 (3) 0.007 (3) ------ ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2500 .table-wrap} --------------------------- -------------- -------------------------- ------------ Co1---N2 1.861 (5) C4---H4B 0.9800 Co1---N1 1.871 (5) C4---H4C 0.9800 Co1---O2 1.887 (4) C5---C6 1.391 (9) Co1---O1 1.891 (4) C5---H5A 0.9500 Co1---O21A 1.902 (5) C6---C8 1.425 (9) Co1---O11A 1.929 (4) C7---H7A 0.9800 Co2---O12A^i^ 2.043 (4) C7---H7B 0.9800 Co2---O12A 2.043 (4) C7---H7C 0.9800 Co2---O2^i^ 2.117 (4) C8---C9 1.451 (8) Co2---O2 2.117 (4) C9---H9A 0.9500 Co2---O1 2.160 (4) C10---C11 1.511 (9) Co2---O1^i^ 2.160 (4) C10---H10A 0.9900 Cl1---C 1.763 (10) C10---H10B 0.9900 Cl2---C 1.771 (13) C11---H11A 0.9900 O1---C1 1.310 (7) C11---H11B 0.9900 O2---C20 1.334 (7) C12---C13 1.432 (9) O3---C3 1.361 (8) C12---H12A 0.9500 O3---C4 1.441 (8) C13---C14 1.411 (9) O4---C6 1.342 (7) C13---C20 1.418 (9) O4---C7 1.440 (8) C14---C16 1.385 (10) O5---C14 1.380 (8) C15---H15A 0.9800 O5---C15 1.431 (8) C15---H15B 0.9800 O6---C17 1.353 (8) C15---H15C 0.9800 O6---C18 1.432 (9) C16---C17 1.393 (9) O11A---C11A 1.275 (7) C16---H16A 0.9500 O12A---C11A 1.256 (8) C17---C19 1.397 (9) O21A---C21A 1.293 (8) C18---H18A 0.9800 O22A---C21A 1.226 (8) C18---H18B 0.9800 N1---C9 1.282 (8) C18---H18C 0.9800 N1---C10 1.465 (8) C19---C20 1.400 (9) N2---C12 1.281 (8) C19---H19A 0.9500 N2---C11 1.485 (8) C11A---C12A 1.491 (9) C---H0A 0.9900 C12A---H12B 0.9800 C---H0B 0.9900 C12A---H12C 0.9800 C1---C2 1.411 (8) C12A---H12D 0.9800 C1---C8 1.433 (8) C21A---C22A 1.500 (10) C2---C3 1.366 (9) C22A---H22A 0.9800 C2---H2A 0.9500 C22A---H22B 0.9800 C3---C5 1.412 (9) C22A---H22C 0.9800 C4---H4A 0.9800 N2---Co1---N1 86.4 (2) O4---C7---H7A 109.5 N2---Co1---O2 93.9 (2) O4---C7---H7B 109.5 N1---Co1---O2 178.7 (2) H7A---C7---H7B 109.5 N2---Co1---O1 176.1 (2) O4---C7---H7C 109.5 N1---Co1---O1 96.1 (2) H7A---C7---H7C 109.5 O2---Co1---O1 83.65 (18) H7B---C7---H7C 109.5 N2---Co1---O21A 96.4 (2) C6---C8---C1 118.0 (6) N1---Co1---O21A 91.4 (2) C6---C8---C9 118.4 (6) O2---Co1---O21A 89.90 (19) C1---C8---C9 123.5 (6) O1---Co1---O21A 86.66 (19) N1---C9---C8 125.2 (6) N2---Co1---O11A 86.1 (2) N1---C9---H9A 117.4 N1---Co1---O11A 86.2 (2) C8---C9---H9A 117.4 O2---Co1---O11A 92.57 (18) N1---C10---C11 108.8 (5) O1---Co1---O11A 90.98 (18) N1---C10---H10A 109.9 O21A---Co1---O11A 176.38 (19) C11---C10---H10A 109.9 O12A^i^---Co2---O12A 180.000 (1) N1---C10---H10B 109.9 O12A^i^---Co2---O2^i^ 86.78 (17) C11---C10---H10B 109.9 O12A---Co2---O2^i^ 93.22 (17) H10A---C10---H10B 108.3 O12A^i^---Co2---O2 93.22 (17) N2---C11---C10 108.0 (5) O12A---Co2---O2 86.78 (17) N2---C11---H11A 110.1 O2^i^---Co2---O2 180.0 C10---C11---H11A 110.1 O12A^i^---Co2---O1 92.92 (16) N2---C11---H11B 110.1 O12A---Co2---O1 87.08 (16) C10---C11---H11B 110.1 O2^i^---Co2---O1 107.85 (15) H11A---C11---H11B 108.4 O2---Co2---O1 72.15 (15) N2---C12---C13 124.7 (6) O12A^i^---Co2---O1^i^ 87.08 (16) N2---C12---H12A 117.7 O12A---Co2---O1^i^ 92.92 (16) C13---C12---H12A 117.7 O2^i^---Co2---O1^i^ 72.15 (15) C14---C13---C20 117.5 (6) O2---Co2---O1^i^ 107.85 (15) C14---C13---C12 119.5 (6) O1---Co2---O1^i^ 180.000 (1) C20---C13---C12 123.0 (5) C1---O1---Co1 125.3 (4) O5---C14---C16 122.7 (6) C1---O1---Co2 136.1 (4) O5---C14---C13 114.7 (6) Co1---O1---Co2 98.66 (17) C16---C14---C13 122.6 (6) C20---O2---Co1 122.9 (4) O5---C15---H15A 109.5 C20---O2---Co2 135.6 (4) O5---C15---H15B 109.5 Co1---O2---Co2 100.29 (18) H15A---C15---H15B 109.5 C3---O3---C4 117.0 (5) O5---C15---H15C 109.5 C6---O4---C7 117.7 (5) H15A---C15---H15C 109.5 C14---O5---C15 116.9 (6) H15B---C15---H15C 109.5 C17---O6---C18 118.9 (5) C14---C16---C17 118.1 (6) C11A---O11A---Co1 128.5 (4) C14---C16---H16A 121.0 C11A---O12A---Co2 128.5 (4) C17---C16---H16A 121.0 C21A---O21A---Co1 128.8 (4) O6---C17---C16 115.1 (6) C9---N1---C10 120.3 (5) O6---C17---C19 122.8 (6) C9---N1---Co1 125.0 (4) C16---C17---C19 122.2 (6) C10---N1---Co1 114.7 (4) O6---C18---H18A 109.5 C12---N2---C11 122.4 (5) O6---C18---H18B 109.5 C12---N2---Co1 125.5 (4) H18A---C18---H18B 109.5 C11---N2---Co1 111.9 (4) O6---C18---H18C 109.5 Cl1---C---Cl2 110.9 (7) H18A---C18---H18C 109.5 Cl1---C---H0A 109.5 H18B---C18---H18C 109.5 Cl2---C---H0A 109.5 C17---C19---C20 118.8 (6) Cl1---C---H0B 109.5 C17---C19---H19A 120.6 Cl2---C---H0B 109.5 C20---C19---H19A 120.6 H0A---C---H0B 108.0 O2---C20---C19 117.8 (5) O1---C1---C2 118.2 (5) O2---C20---C13 121.3 (6) O1---C1---C8 122.0 (5) C19---C20---C13 120.9 (6) C2---C1---C8 119.8 (5) O12A---C11A---O11A 126.6 (6) C3---C2---C1 119.9 (6) O12A---C11A---C12A 118.5 (5) C3---C2---H2A 120.0 O11A---C11A---C12A 114.9 (6) C1---C2---H2A 120.0 C11A---C12A---H12B 109.5 O3---C3---C2 124.1 (6) C11A---C12A---H12C 109.5 O3---C3---C5 113.6 (6) H12B---C12A---H12C 109.5 C2---C3---C5 122.3 (6) C11A---C12A---H12D 109.5 O3---C4---H4A 109.5 H12B---C12A---H12D 109.5 O3---C4---H4B 109.5 H12C---C12A---H12D 109.5 H4A---C4---H4B 109.5 O22A---C21A---O21A 127.5 (6) O3---C4---H4C 109.5 O22A---C21A---C22A 119.8 (6) H4A---C4---H4C 109.5 O21A---C21A---C22A 112.8 (6) H4B---C4---H4C 109.5 C21A---C22A---H22A 109.5 C6---C5---C3 118.5 (5) C21A---C22A---H22B 109.5 C6---C5---H5A 120.8 H22A---C22A---H22B 109.5 C3---C5---H5A 120.8 C21A---C22A---H22C 109.5 O4---C6---C5 122.9 (5) H22A---C22A---H22C 109.5 O4---C6---C8 115.8 (5) H22B---C22A---H22C 109.5 C5---C6---C8 121.4 (6) N1---Co1---O1---C1 18.7 (5) Co2---O1---C1---C8 160.4 (4) O2---Co1---O1---C1 −162.6 (5) O1---C1---C2---C3 175.2 (5) O21A---Co1---O1---C1 −72.3 (5) C8---C1---C2---C3 −3.6 (8) O11A---Co1---O1---C1 104.9 (5) C4---O3---C3---C2 1.8 (9) N1---Co1---O1---Co2 −160.9 (2) C4---O3---C3---C5 179.5 (5) O2---Co1---O1---Co2 17.86 (18) C1---C2---C3---O3 178.4 (5) O21A---Co1---O1---Co2 108.13 (19) C1---C2---C3---C5 0.9 (9) O11A---Co1---O1---Co2 −74.62 (18) O3---C3---C5---C6 −176.8 (5) O12A^i^---Co2---O1---C1 71.5 (5) C2---C3---C5---C6 1.0 (9) O12A---Co2---O1---C1 −108.5 (5) C7---O4---C6---C5 4.5 (9) O2^i^---Co2---O1---C1 −16.1 (6) C7---O4---C6---C8 −175.5 (6) O2---Co2---O1---C1 163.9 (6) C3---C5---C6---O4 180.0 (5) O12A^i^---Co2---O1---Co1 −109.03 (19) C3---C5---C6---C8 −0.1 (9) O12A---Co2---O1---Co1 70.97 (19) O4---C6---C8---C1 177.4 (5) O2^i^---Co2---O1---Co1 163.42 (17) C5---C6---C8---C1 −2.5 (9) O2---Co2---O1---Co1 −16.58 (17) O4---C6---C8---C9 −1.7 (8) N2---Co1---O2---C20 −32.5 (5) C5---C6---C8---C9 178.4 (6) O1---Co1---O2---C20 150.6 (5) O1---C1---C8---C6 −174.4 (5) O21A---Co1---O2---C20 63.9 (5) C2---C1---C8---C6 4.4 (8) O11A---Co1---O2---C20 −118.7 (5) O1---C1---C8---C9 4.6 (9) N2---Co1---O2---Co2 158.6 (2) C2---C1---C8---C9 −176.6 (5) O1---Co1---O2---Co2 −18.32 (19) C10---N1---C9---C8 175.5 (6) O21A---Co1---O2---Co2 −105.0 (2) Co1---N1---C9---C8 −2.7 (8) O11A---Co1---O2---Co2 72.4 (2) C6---C8---C9---N1 −173.9 (6) O12A^i^---Co2---O2---C20 −57.9 (6) C1---C8---C9---N1 7.1 (9) O12A---Co2---O2---C20 122.1 (6) C9---N1---C10---C11 166.1 (6) O1---Co2---O2---C20 −149.9 (6) Co1---N1---C10---C11 −15.5 (7) O1^i^---Co2---O2---C20 30.1 (6) C12---N2---C11---C10 149.8 (6) O12A^i^---Co2---O2---Co1 108.7 (2) Co1---N2---C11---C10 −34.2 (6) O12A---Co2---O2---Co1 −71.3 (2) N1---C10---C11---N2 30.8 (7) O1---Co2---O2---Co1 16.70 (17) C11---N2---C12---C13 174.9 (6) O1^i^---Co2---O2---Co1 −163.30 (17) Co1---N2---C12---C13 −0.6 (9) N2---Co1---O11A---C11A −133.8 (5) N2---C12---C13---C14 170.6 (6) N1---Co1---O11A---C11A 139.6 (5) N2---C12---C13---C20 −12.1 (10) O2---Co1---O11A---C11A −40.1 (5) C15---O5---C14---C16 −0.3 (9) O1---Co1---O11A---C11A 43.6 (5) C15---O5---C14---C13 179.3 (6) O2^i^---Co2---O12A---C11A −140.5 (5) C20---C13---C14---O5 −177.6 (5) O2---Co2---O12A---C11A 39.5 (5) C12---C13---C14---O5 −0.2 (9) O1---Co2---O12A---C11A −32.8 (5) C20---C13---C14---C16 2.0 (10) O1^i^---Co2---O12A---C11A 147.2 (5) C12---C13---C14---C16 179.4 (6) N2---Co1---O21A---C21A −37.0 (6) O5---C14---C16---C17 179.8 (6) N1---Co1---O21A---C21A 49.5 (5) C13---C14---C16---C17 0.2 (10) O2---Co1---O21A---C21A −130.8 (5) C18---O6---C17---C16 173.6 (6) O1---Co1---O21A---C21A 145.5 (5) C18---O6---C17---C19 −6.2 (10) N2---Co1---N1---C9 175.4 (5) C14---C16---C17---O6 179.2 (6) O1---Co1---N1---C9 −7.7 (5) C14---C16---C17---C19 −0.9 (10) O21A---Co1---N1---C9 79.1 (5) O6---C17---C19---C20 179.1 (6) O11A---Co1---N1---C9 −98.3 (5) C16---C17---C19---C20 −0.8 (10) N2---Co1---N1---C10 −2.9 (4) Co1---O2---C20---C19 −153.3 (4) O1---Co1---N1---C10 174.0 (4) Co2---O2---C20---C19 11.0 (9) O21A---Co1---N1---C10 −99.2 (4) Co1---O2---C20---C13 29.1 (8) O11A---Co1---N1---C10 83.4 (4) Co2---O2---C20---C13 −166.6 (4) N1---Co1---N2---C12 −162.8 (6) C17---C19---C20---O2 −174.5 (6) O2---Co1---N2---C12 18.5 (5) C17---C19---C20---C13 3.1 (9) O1---Co1---N2---C12 69 (3) C14---C13---C20---O2 173.8 (6) O21A---Co1---N2---C12 −71.9 (5) C12---C13---C20---O2 −3.5 (9) O11A---Co1---N2---C12 110.8 (5) C14---C13---C20---C19 −3.6 (9) N1---Co1---N2---C11 21.3 (4) C12---C13---C20---C19 179.0 (6) O2---Co1---N2---C11 −157.4 (4) Co2---O12A---C11A---O11A −4.4 (9) O21A---Co1---N2---C11 112.3 (4) Co2---O12A---C11A---C12A 175.4 (4) O11A---Co1---N2---C11 −65.1 (4) Co1---O11A---C11A---O12A 1.6 (9) Co1---O1---C1---C2 162.2 (4) Co1---O11A---C11A---C12A −178.2 (4) Co2---O1---C1---C2 −18.5 (8) Co1---O21A---C21A---O22A 11.6 (10) Co1---O1---C1---C8 −19.0 (8) Co1---O21A---C21A---C22A −167.3 (4) --------------------------- -------------- -------------------------- ------------ ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4365 .table-wrap} ------------------------ --------- --------- ------------ --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C---H0A···O22A 0.99 2.33 3.269 (13) 158 C4---H4A···O6^ii^ 0.98 2.35 3.326 (8) 175 C7---H7A···O6^iii^ 0.98 2.51 3.421 (9) 156 C11---H11A···O3^iii^ 0.99 2.62 3.602 (8) 174 C11---H11B···Cl1^iv^ 0.99 2.73 3.664 (8) 158 C15---H15A···O4^v^ 0.98 2.64 3.568 (10) 158 C12A---H12B···Cl1^iii^ 0.98 2.91 3.354 (8) 108 ------------------------ --------- --------- ------------ --------------- ::: Symmetry codes: (ii) *x*+1/2, −*y*+3/2, *z*−1/2; (iii) −*x*+1/2, *y*−1/2, −*z*+1/2; (iv) *x*+1/2, −*y*+1/2, *z*+1/2; (v) *x*−1/2, −*y*+1/2, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------------- --------- ------- ------------ ------------- C---H0*A*⋯O22*A* 0.99 2.33 3.269 (13) 158 C4---H4*A*⋯O6^i^ 0.98 2.35 3.326 (8) 175 C7---H7*A*⋯O6^ii^ 0.98 2.51 3.421 (9) 156 C11---H11*A*⋯O3^ii^ 0.99 2.62 3.602 (8) 174 C11---H11*B*⋯Cl1^iii^ 0.99 2.73 3.664 (8) 158 C15---H15*A*⋯O4^iv^ 0.98 2.64 3.568 (10) 158 C12*A*---H12*B*⋯Cl1^ii^ 0.98 2.91 3.354 (8) 108 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::

PubMed Central

2024-06-05T04:04:18.455573

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052101/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):m303-m304", "authors": [ { "first": "Gervas E.", "last": "Assey" }, { "first": "Ray J.", "last": "Butcher" }, { "first": "Yilma", "last": "Gultneh" } ] }

PMC3052102

Related literature {#sec1} ================== For applications of long-chain *n*-alkylammonium halides, see: Aratono *et al.* (1998[@bb1]); Tornblom *et al.* (2000[@bb10]); Ringsdorf *et al.* (1988[@bb5]). For details of phase transitions in *n-*alkylammonium chlorides, see: Terreros *et al.* (2000[@bb9]). For related structures, see: Rademeyer *et al.* (2009[@bb4]); Lundén (1974[@bb3]); Clark & Hudgens (1950[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~30~N^+^·Cl^−^·H~2~O*M* *~r~* = 253.85Monoclinic,*a* = 4.7420 (5) Å*b* = 45.250 (3) Å*c* = 7.8191 (9) Åβ = 106.332 (2)°*V* = 1610.1 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 0.22 mm^−1^*T* = 298 K0.34 × 0.33 × 0.03 mm ### Data collection {#sec2.1.2} Siemens SMART CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb6]) *T* ~min~ = 0.928, *T* ~max~ = 0.9938230 measured reflections2845 independent reflections1379 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.077 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.067*wR*(*F* ^2^) = 0.124*S* = 1.032845 reflections147 parametersH-atom parameters constrainedΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e506} Data collection: *SMART* (Siemens, 1996[@bb8]); cell refinement: *SAINT* (Siemens, 1996[@bb8]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb7]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006246/lh5197sup1.cif](http://dx.doi.org/10.1107/S1600536811006246/lh5197sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006246/lh5197Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006246/lh5197Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5197&file=lh5197sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5197sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5197&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5197](http://scripts.iucr.org/cgi-bin/sendsup?lh5197)). We acknowledge the National Natural Science Foundation of China (20973089) for financial support. Comment ======= Long-chain *n*-alkylammonium halides are widely used as surfactants (Aratono *et al.*, 1998; Tornblom *et al.*, 2000) and as models for biological membranes (Ringsdorf *et al.*, 1988). It has been shown that phase transitions occur in *n*-alkylammonium chlorides (Terreros *et al.*, 2000). As a part of our studies on novel potential phase transition materials with thermochemical properties, we report herein the crystal structure of the title compound (Fig. 1). Atoms C2--C13 are essentially co-planar with a maximum deviation of 0.048 (3)Å for atom C2. The alkyl chain in related compounds is typically in the extended conformation e.g. in the isostructural *n*-tridecylamine bromide monohydrate compound (Rademeyer *et al.*, 2009), *n*--dodecylammonium bromide (Lundén, 1974) and *n*--tridecylamine chloride (Clark & Hudgens, 1950). Although the methylene chain has the extended all--*trans* conformation, it is slightly bent in the vicinity of the ammonium group possibly to accommodate the hydrogen--bonding interactions. Only the C1--C2--C3--C4 torsion angle deviates significantly from 180 °, with a value of 169.84 (3)°. The crystal packing (Fig. 2) is stabilized by intermolecular N---H···Cl, N---H···O and O---H···Cl hydrogen bonds (Table 1 and Fig.2). Experimental {#experimental} ============ *n*--Tridecylamine chloride monohydrate was prepared by the addition of hydrochloric acid to an ethanolic solution of *n*--tridecylamine. The mixture was heated and stirred under reflux for 6 h. Single crystals suitable for *X*--ray diffraction were prepared by evaporation of the resulting solution at room temperature. Analysis, calculated for C~13~H~32~ClNO (Mr =253.85): C 61.51, H 12.71, N 5.52, Cl 13.96%; found: C 61.50, H 12.72, N 5.51, Cl 13.95%. Refinement {#refinement} ========== All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with methylene C---H = 0.97 Å, methyl C---H = 0.96 Å, N---H = 0.89 Å, O-H = 0.85 Å and refined as riding on their parent atoms. The*U*~iso~(H) values were set at 1.2*U*~eq~(C~methylene~, O) at 1.5*U*~eq~(C~methyl~,N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o717-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds shown as dashed lines. ::: ![](e-67-0o717-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e167 .table-wrap} ---------------------------- -------------------------------------- C~13~H~30~N^+^·Cl^−^·H~2~O *F*(000) = 568 *M~r~* = 253.85 *D*~x~ = 1.047 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 817 reflections *a* = 4.7420 (5) Å θ = 2.7--20.8° *b* = 45.250 (3) Å µ = 0.22 mm^−1^ *c* = 7.8191 (9) Å *T* = 298 K β = 106.332 (2)° Acicular, colourless *V* = 1610.1 (3) Å^3^ 0.34 × 0.33 × 0.03 mm *Z* = 4 ---------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e302 .table-wrap} --------------------------------------------------------------- -------------------------------------- Siemens SMART CCD area-detector diffractometer 2845 independent reflections Radiation source: fine-focus sealed tube 1379 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.077 Detector resolution: 10 pixels mm^-1^ θ~max~ = 25.0°, θ~min~ = 2.7° φ and ω scans *h* = −5→5 Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *k* = −53→46 *T*~min~ = 0.928, *T*~max~ = 0.993 *l* = −7→9 8230 measured reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e425 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.067 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.124 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0256*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2845 reflections (Δ/σ)~max~ = 0.001 147 parameters Δρ~max~ = 0.25 e Å^−3^ 0 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e579 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cl1 0.77004 (19) 0.727389 (19) 0.54882 (12) 0.0578 (3) N1 0.2908 (5) 0.72396 (5) 0.1504 (4) 0.0486 (8) H1A 0.4378 0.7281 0.2466 0.073\* H1B 0.1648 0.7390 0.1270 0.073\* H1C 0.3618 0.7210 0.0578 0.073\* O1 0.3848 (5) 0.70538 (5) 0.8156 (3) 0.0690 (8) H1H 0.5034 0.7102 0.7566 0.083\* H1I 0.2125 0.7103 0.7554 0.083\* C1 0.1369 (7) 0.69683 (6) 0.1834 (4) 0.0462 (9) H1D −0.0396 0.6941 0.0856 0.055\* H1E 0.0779 0.6994 0.2915 0.055\* C2 0.3263 (7) 0.66944 (6) 0.2017 (4) 0.0445 (9) H2A 0.5028 0.6722 0.2995 0.053\* H2B 0.3852 0.6668 0.0935 0.053\* C3 0.1677 (7) 0.64186 (6) 0.2355 (4) 0.0467 (9) H3A −0.0251 0.6412 0.1498 0.056\* H3B 0.1397 0.6431 0.3534 0.056\* C4 0.3305 (7) 0.61334 (6) 0.2221 (4) 0.0444 (9) H4A 0.5222 0.6140 0.3090 0.053\* H4B 0.3616 0.6123 0.1049 0.053\* C5 0.1730 (7) 0.58533 (6) 0.2526 (4) 0.0471 (9) H5A 0.1495 0.5860 0.3718 0.056\* H5B −0.0219 0.5851 0.1691 0.056\* C6 0.3292 (7) 0.55675 (6) 0.2317 (4) 0.0440 (9) H6A 0.3543 0.5562 0.1128 0.053\* H6B 0.5234 0.5569 0.3159 0.053\* C7 0.1722 (7) 0.52882 (6) 0.2603 (4) 0.0450 (9) H7A −0.0231 0.5288 0.1773 0.054\* H7B 0.1496 0.5292 0.3798 0.054\* C8 0.3260 (6) 0.50019 (6) 0.2369 (4) 0.0440 (9) H8A 0.3473 0.4997 0.1171 0.053\* H8B 0.5218 0.5003 0.3193 0.053\* C9 0.1705 (7) 0.47222 (6) 0.2666 (4) 0.0448 (9) H9A −0.0251 0.4721 0.1839 0.054\* H9B 0.1485 0.4727 0.3862 0.054\* C10 0.3245 (7) 0.44364 (6) 0.2439 (4) 0.0438 (9) H10A 0.3458 0.4431 0.1242 0.053\* H10B 0.5204 0.4438 0.3263 0.053\* C11 0.1702 (7) 0.41561 (6) 0.2745 (4) 0.0448 (9) H11A 0.1479 0.4162 0.3940 0.054\* H11B −0.0253 0.4154 0.1917 0.054\* C12 0.3236 (7) 0.38729 (6) 0.2530 (5) 0.0522 (10) H12A 0.5194 0.3876 0.3355 0.063\* H12B 0.3452 0.3867 0.1333 0.063\* C13 0.1688 (8) 0.35920 (7) 0.2844 (5) 0.0703 (12) H13A 0.1532 0.3591 0.4042 0.105\* H13B 0.2798 0.3423 0.2668 0.105\* H13C −0.0242 0.3584 0.2021 0.105\* ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1308 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cl1 0.0520 (5) 0.0590 (6) 0.0612 (6) −0.0052 (5) 0.0137 (4) −0.0036 (5) N1 0.0485 (16) 0.0358 (17) 0.061 (2) 0.0041 (15) 0.0145 (14) 0.0002 (14) O1 0.0659 (17) 0.0752 (17) 0.0683 (19) 0.0036 (15) 0.0230 (13) 0.0100 (14) C1 0.044 (2) 0.034 (2) 0.062 (3) 0.0005 (18) 0.0178 (17) 0.0039 (16) C2 0.046 (2) 0.035 (2) 0.053 (2) −0.0022 (18) 0.0152 (17) −0.0021 (16) C3 0.052 (2) 0.039 (2) 0.053 (2) −0.0043 (19) 0.0209 (18) 0.0011 (17) C4 0.050 (2) 0.036 (2) 0.050 (2) −0.0033 (18) 0.0191 (18) 0.0020 (16) C5 0.053 (2) 0.041 (2) 0.049 (2) −0.005 (2) 0.0189 (18) 0.0004 (17) C6 0.048 (2) 0.039 (2) 0.048 (2) −0.0014 (19) 0.0177 (17) 0.0012 (16) C7 0.048 (2) 0.039 (2) 0.050 (2) −0.0024 (19) 0.0178 (17) 0.0029 (17) C8 0.047 (2) 0.040 (2) 0.047 (2) −0.003 (2) 0.0170 (17) 0.0042 (16) C9 0.051 (2) 0.037 (2) 0.049 (2) −0.0035 (19) 0.0190 (18) −0.0009 (16) C10 0.048 (2) 0.040 (2) 0.047 (2) −0.0014 (19) 0.0194 (17) −0.0011 (16) C11 0.050 (2) 0.039 (2) 0.048 (2) −0.0033 (19) 0.0167 (17) 0.0026 (16) C12 0.062 (2) 0.041 (2) 0.054 (3) 0.004 (2) 0.0163 (19) 0.0000 (17) C13 0.094 (3) 0.043 (2) 0.076 (3) −0.005 (2) 0.026 (2) 0.001 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1626 .table-wrap} ------------------- ------------ ----------------------- ------------ N1---C1 1.487 (3) C6---H6B 0.9700 N1---H1A 0.8900 C7---C8 1.523 (4) N1---H1B 0.8900 C7---H7A 0.9700 N1---H1C 0.8900 C7---H7B 0.9700 O1---H1H 0.8499 C8---C9 1.515 (4) O1---H1I 0.8499 C8---H8A 0.9700 C1---C2 1.513 (4) C8---H8B 0.9700 C1---H1D 0.9700 C9---C10 1.520 (4) C1---H1E 0.9700 C9---H9A 0.9700 C2---C3 1.518 (4) C9---H9B 0.9700 C2---H2A 0.9700 C10---C11 1.517 (4) C2---H2B 0.9700 C10---H10A 0.9700 C3---C4 1.523 (4) C10---H10B 0.9700 C3---H3A 0.9700 C11---C12 1.506 (4) C3---H3B 0.9700 C11---H11A 0.9700 C4---C5 1.524 (4) C11---H11B 0.9700 C4---H4A 0.9700 C12---C13 1.522 (4) C4---H4B 0.9700 C12---H12A 0.9700 C5---C6 1.522 (4) C12---H12B 0.9700 C5---H5A 0.9700 C13---H13A 0.9600 C5---H5B 0.9700 C13---H13B 0.9600 C6---C7 1.515 (4) C13---H13C 0.9600 C6---H6A 0.9700 C1---N1---H1A 109.5 C6---C7---C8 114.8 (3) C1---N1---H1B 109.5 C6---C7---H7A 108.6 H1A---N1---H1B 109.5 C8---C7---H7A 108.6 C1---N1---H1C 109.5 C6---C7---H7B 108.6 H1A---N1---H1C 109.5 C8---C7---H7B 108.6 H1B---N1---H1C 109.5 H7A---C7---H7B 107.5 H1H---O1---H1I 108.1 C9---C8---C7 114.9 (2) N1---C1---C2 112.7 (3) C9---C8---H8A 108.5 N1---C1---H1D 109.1 C7---C8---H8A 108.5 C2---C1---H1D 109.1 C9---C8---H8B 108.5 N1---C1---H1E 109.1 C7---C8---H8B 108.5 C2---C1---H1E 109.1 H8A---C8---H8B 107.5 H1D---C1---H1E 107.8 C8---C9---C10 115.0 (3) C1---C2---C3 112.3 (3) C8---C9---H9A 108.5 C1---C2---H2A 109.1 C10---C9---H9A 108.5 C3---C2---H2A 109.1 C8---C9---H9B 108.5 C1---C2---H2B 109.1 C10---C9---H9B 108.5 C3---C2---H2B 109.1 H9A---C9---H9B 107.5 H2A---C2---H2B 107.9 C11---C10---C9 115.1 (3) C2---C3---C4 113.5 (3) C11---C10---H10A 108.5 C2---C3---H3A 108.9 C9---C10---H10A 108.5 C4---C3---H3A 108.9 C11---C10---H10B 108.5 C2---C3---H3B 108.9 C9---C10---H10B 108.5 C4---C3---H3B 108.9 H10A---C10---H10B 107.5 H3A---C3---H3B 107.7 C12---C11---C10 115.1 (3) C3---C4---C5 114.5 (3) C12---C11---H11A 108.5 C3---C4---H4A 108.6 C10---C11---H11A 108.5 C5---C4---H4A 108.6 C12---C11---H11B 108.5 C3---C4---H4B 108.6 C10---C11---H11B 108.5 C5---C4---H4B 108.6 H11A---C11---H11B 107.5 H4A---C4---H4B 107.6 C11---C12---C13 115.0 (3) C6---C5---C4 114.5 (3) C11---C12---H12A 108.5 C6---C5---H5A 108.6 C13---C12---H12A 108.5 C4---C5---H5A 108.6 C11---C12---H12B 108.5 C6---C5---H5B 108.6 C13---C12---H12B 108.5 C4---C5---H5B 108.6 H12A---C12---H12B 107.5 H5A---C5---H5B 107.6 C12---C13---H13A 109.5 C7---C6---C5 114.8 (3) C12---C13---H13B 109.5 C7---C6---H6A 108.6 H13A---C13---H13B 109.5 C5---C6---H6A 108.6 C12---C13---H13C 109.5 C7---C6---H6B 108.6 H13A---C13---H13C 109.5 C5---C6---H6B 108.6 H13B---C13---H13C 109.5 H6A---C6---H6B 107.6 N1---C1---C2---C3 180.0 (3) C6---C7---C8---C9 179.6 (3) C1---C2---C3---C4 169.9 (3) C7---C8---C9---C10 −179.8 (3) C2---C3---C4---C5 −179.1 (3) C8---C9---C10---C11 179.7 (3) C3---C4---C5---C6 177.6 (3) C9---C10---C11---C12 −179.7 (3) C4---C5---C6---C7 −179.5 (3) C10---C11---C12---C13 179.8 (3) C5---C6---C7---C8 179.2 (3) ------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2308 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···Cl1 0.89 2.44 3.303 (3) 162 N1---H1B···Cl1^i^ 0.89 2.36 3.236 (2) 170 N1---H1C···O1^ii^ 0.89 2.05 2.901 (4) 159 O1---H1H···Cl1 0.85 2.45 3.290 (3) 170 O1---H1I···Cl1^iii^ 0.85 2.39 3.228 (2) 170 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*−1, −*y*+3/2, *z*−1/2; (ii) *x*, *y*, *z*−1; (iii) *x*−1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- N1---H1*A*⋯Cl1 0.89 2.44 3.303 (3) 162 N1---H1*B*⋯Cl1^i^ 0.89 2.36 3.236 (2) 170 N1---H1*C*⋯O1^ii^ 0.89 2.05 2.901 (4) 159 O1---H1*H*⋯Cl1 0.85 2.45 3.290 (3) 170 O1---H1*I*⋯Cl1^iii^ 0.85 2.39 3.228 (2) 170 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.465859

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052102/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o717", "authors": [ { "first": "Lijun", "last": "Zhang" }, { "first": "Youying", "last": "Di" }, { "first": "Wenyan", "last": "Dan" } ] }

PMC3052103

Related literature {#sec1} ================== For pyrazole derivatives and their microbial activity, see: Ragavan *et al.* (2009[@bb4], 2010[@bb5]). For related structures, see: Shahani *et al.* (2009[@bb6], 2010*a* [@bb7],*b* [@bb8],*c* [@bb9]). For bond-length data, see: Allen *et al.* (1987[@bb1]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~11~H~12~N~2~OS*M* *~r~* = 220.30Orthorhombic,*a* = 10.9479 (2) Å*b* = 11.3470 (3) Å*c* = 17.7392 (4) Å*V* = 2203.67 (9) Å^3^*Z* = 8Mo *K*α radiationμ = 0.27 mm^−1^*T* = 100 K0.33 × 0.13 × 0.11 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2009[@bb2]) *T* ~min~ = 0.917, *T* ~max~ = 0.97112209 measured reflections3027 independent reflections2406 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.041 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.039*wR*(*F* ^2^) = 0.104*S* = 1.043027 reflections142 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.31 e Å^−3^ {#d5e452} Data collection: *APEX2* (Bruker, 2009[@bb2]); cell refinement: *SAINT* (Bruker, 2009[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb10]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL* and *PLATON* (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004922/is2676sup1.cif](http://dx.doi.org/10.1107/S1600536811004922/is2676sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004922/is2676Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004922/is2676Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2676&file=is2676sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2676sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2676&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2676](http://scripts.iucr.org/cgi-bin/sendsup?is2676)). HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSH also thanks USM for the award of a research fellowship. Comment ======= Antibacterial and antifungal activities of the azoles are most widely studied and some of them are in clinical practice as anti-microbial agents. However, the azole-resistant strain had led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have the broad spectrum of biological properties, such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling, and antiviral activities. Pyrazole derivatives also act as antiangiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity, and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan *et al.*, 2009, 2010). The structure of the title compound is presented here. In the title compound, (Fig. 1), the 1*H*-pyrazol ring (C7--C9/N1/N2) \[maximum deviation of 0.00117 (14) Å\] makes a dihedral angle of 85.40 (8)° with the phenyl ring (C1--C6). The bond lengths (Allen *et al.*, 1987) and angles are within normal ranges and comparable to those closely related structures (Shahani *et al.*, 2009, 2010*a*,*b*,*c*). In the crystal packing (Fig. 2), pairs of intermolecular N1---H1N1···O1 and C3---H3A···O1 hydrogen bonds (Table 1) link the molecules into two-dimensional networks parallel to the *bc* plane. Experimental {#experimental} ============ The compound has been synthesized using the method available in the literature (Ragavan *et al.*, 2009) and recrystallized using the ethanol-chloroform 1:1 mixture (yield 60%, *m.p.* 444 K). Refinement {#refinement} ========== The H atoms bound to C atoms were positioned geometrically (C---H = 0.93--0.96 Å) with *U*~iso~(H) =1.2 or 1.5*U*~eq~(C). The H atoms attached to the N atom was located from the difference map and refined freely, \[N---H = 0.94 (2) Å\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom numbering scheme. ::: ![](e-67-0o633-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal structure of the title compound viewed approximately along the b axis. Intermolecular interactions are shown in dashed lines. Hydrogen bond not involved in intermolecular interactions are omitted for clarity. ::: ![](e-67-0o633-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------- --------------------------------------- C~11~H~12~N~2~OS *F*(000) = 928 *M~r~* = 220.30 *D*~x~ = 1.328 Mg m^−3^ Orthorhombic, *Pbca* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ac 2ab Cell parameters from 2873 reflections *a* = 10.9479 (2) Å θ = 2.8--29.1° *b* = 11.3470 (3) Å µ = 0.27 mm^−1^ *c* = 17.7392 (4) Å *T* = 100 K *V* = 2203.67 (9) Å^3^ Block, colourless *Z* = 8 0.33 × 0.13 × 0.11 mm ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e265 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 3027 independent reflections Radiation source: fine-focus sealed tube 2406 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.041 φ and ω scans θ~max~ = 29.4°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Bruker, 2009) *h* = −11→15 *T*~min~ = 0.917, *T*~max~ = 0.971 *k* = −15→15 12209 measured reflections *l* = −16→24 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e382 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.039 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.104 H atoms treated by a mixture of independent and constrained refinement *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0481*P*)^2^ + 0.8061*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3027 reflections (Δ/σ)~max~ \< 0.001 142 parameters Δρ~max~ = 0.33 e Å^−3^ 0 restraints Δρ~min~ = −0.31 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e539 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e644 .table-wrap} ------ -------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ S1 0.09449 (3) 0.31932 (3) 0.09298 (2) 0.01802 (11) O1 0.32686 (10) 0.34450 (8) −0.02532 (6) 0.0207 (2) N1 0.20240 (12) 0.61926 (10) 0.00845 (8) 0.0202 (3) N2 0.28173 (12) 0.54374 (10) −0.02791 (7) 0.0192 (3) C1 0.28747 (15) 0.36136 (13) 0.19278 (9) 0.0225 (3) H1A 0.3057 0.4285 0.1649 0.027\* C2 0.35663 (15) 0.33304 (13) 0.25590 (9) 0.0254 (3) H2A 0.4211 0.3816 0.2700 0.031\* C3 0.33066 (15) 0.23327 (14) 0.29808 (9) 0.0236 (3) H3A 0.3766 0.2154 0.3407 0.028\* C4 0.23531 (15) 0.16043 (13) 0.27606 (9) 0.0243 (3) H4A 0.2180 0.0929 0.3037 0.029\* C5 0.16551 (14) 0.18758 (13) 0.21304 (9) 0.0212 (3) H5A 0.1019 0.1382 0.1986 0.025\* C6 0.19092 (13) 0.28904 (12) 0.17148 (8) 0.0173 (3) C7 0.16428 (13) 0.43840 (11) 0.04922 (8) 0.0166 (3) C8 0.26321 (13) 0.43076 (11) −0.00304 (8) 0.0164 (3) C9 0.13144 (14) 0.55679 (12) 0.05474 (8) 0.0178 (3) C10 0.38173 (15) 0.58669 (13) −0.07387 (10) 0.0239 (3) H10A 0.4171 0.5222 −0.1013 0.036\* H10B 0.4427 0.6217 −0.0420 0.036\* H10C 0.3517 0.6446 −0.1087 0.036\* C11 0.03683 (15) 0.61354 (14) 0.10271 (9) 0.0248 (3) H11A 0.0198 0.6912 0.0839 0.037\* H11B 0.0661 0.6189 0.1536 0.037\* H11C −0.0365 0.5672 0.1016 0.037\* H1N1 0.1983 (19) 0.700 (2) −0.0036 (13) 0.047 (6)\* ------ -------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1024 .table-wrap} ----- -------------- -------------- ------------ --------------- --------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ S1 0.01876 (19) 0.01847 (18) 0.0168 (2) −0.00372 (13) −0.00109 (13) 0.00267 (13) O1 0.0267 (6) 0.0139 (4) 0.0215 (6) 0.0008 (4) 0.0046 (4) 0.0000 (4) N1 0.0264 (7) 0.0129 (5) 0.0212 (7) 0.0017 (5) −0.0005 (5) −0.0006 (5) N2 0.0240 (6) 0.0131 (5) 0.0206 (7) −0.0002 (5) 0.0034 (5) 0.0007 (5) C1 0.0273 (8) 0.0198 (7) 0.0204 (8) −0.0046 (6) −0.0027 (6) 0.0034 (6) C2 0.0285 (8) 0.0257 (7) 0.0221 (9) −0.0037 (6) −0.0065 (7) −0.0002 (6) C3 0.0255 (8) 0.0298 (8) 0.0155 (8) 0.0053 (6) −0.0012 (6) 0.0006 (6) C4 0.0247 (8) 0.0260 (7) 0.0222 (8) 0.0015 (6) 0.0032 (6) 0.0082 (6) C5 0.0197 (7) 0.0213 (7) 0.0225 (8) −0.0015 (6) 0.0013 (6) 0.0043 (6) C6 0.0196 (7) 0.0188 (6) 0.0134 (7) 0.0007 (5) 0.0019 (5) 0.0003 (5) C7 0.0193 (7) 0.0148 (6) 0.0156 (7) −0.0014 (5) −0.0003 (5) 0.0005 (5) C8 0.0224 (7) 0.0127 (6) 0.0141 (7) −0.0017 (5) −0.0018 (6) 0.0001 (5) C9 0.0207 (7) 0.0179 (6) 0.0149 (7) 0.0009 (5) −0.0035 (6) −0.0002 (5) C10 0.0283 (8) 0.0184 (7) 0.0250 (8) −0.0043 (6) 0.0050 (7) 0.0032 (6) C11 0.0248 (8) 0.0250 (7) 0.0245 (9) 0.0071 (6) −0.0008 (6) −0.0021 (6) ----- -------------- -------------- ------------ --------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1337 .table-wrap} -------------------- -------------- -------------------- -------------- S1---C7 1.7356 (14) C3---H3A 0.9300 S1---C6 1.7809 (15) C4---C5 1.389 (2) O1---C8 1.2648 (17) C4---H4A 0.9300 N1---C9 1.3343 (19) C5---C6 1.395 (2) N1---N2 1.3801 (17) C5---H5A 0.9300 N1---H1N1 0.94 (2) C7---C9 1.3942 (19) N2---C8 1.3708 (17) C7---C8 1.428 (2) N2---C10 1.4494 (19) C9---C11 1.487 (2) C1---C2 1.389 (2) C10---H10A 0.9600 C1---C6 1.391 (2) C10---H10B 0.9600 C1---H1A 0.9300 C10---H10C 0.9600 C2---C3 1.387 (2) C11---H11A 0.9600 C2---H2A 0.9300 C11---H11B 0.9600 C3---C4 1.388 (2) C11---H11C 0.9600 C7---S1---C6 103.83 (7) C1---C6---S1 123.32 (11) C9---N1---N2 108.92 (11) C5---C6---S1 117.02 (11) C9---N1---H1N1 129.0 (13) C9---C7---C8 107.44 (12) N2---N1---H1N1 121.9 (13) C9---C7---S1 127.24 (12) C8---N2---N1 109.70 (12) C8---C7---S1 125.24 (10) C8---N2---C10 127.39 (13) O1---C8---N2 122.79 (13) N1---N2---C10 121.97 (11) O1---C8---C7 131.88 (13) C2---C1---C6 119.79 (14) N2---C8---C7 105.33 (12) C2---C1---H1A 120.1 N1---C9---C7 108.57 (13) C6---C1---H1A 120.1 N1---C9---C11 121.85 (13) C3---C2---C1 120.80 (15) C7---C9---C11 129.57 (14) C3---C2---H2A 119.6 N2---C10---H10A 109.5 C1---C2---H2A 119.6 N2---C10---H10B 109.5 C2---C3---C4 119.26 (15) H10A---C10---H10B 109.5 C2---C3---H3A 120.4 N2---C10---H10C 109.5 C4---C3---H3A 120.4 H10A---C10---H10C 109.5 C3---C4---C5 120.56 (14) H10B---C10---H10C 109.5 C3---C4---H4A 119.7 C9---C11---H11A 109.5 C5---C4---H4A 119.7 C9---C11---H11B 109.5 C4---C5---C6 119.92 (14) H11A---C11---H11B 109.5 C4---C5---H5A 120.0 C9---C11---H11C 109.5 C6---C5---H5A 120.0 H11A---C11---H11C 109.5 C1---C6---C5 119.66 (14) H11B---C11---H11C 109.5 C9---N1---N2---C8 −1.48 (17) N1---N2---C8---O1 −177.46 (13) C9---N1---N2---C10 −171.15 (14) C10---N2---C8---O1 −8.5 (2) C6---C1---C2---C3 0.0 (2) N1---N2---C8---C7 2.10 (16) C1---C2---C3---C4 0.9 (2) C10---N2---C8---C7 171.06 (14) C2---C3---C4---C5 −0.8 (2) C9---C7---C8---O1 177.55 (16) C3---C4---C5---C6 −0.2 (2) S1---C7---C8---O1 −5.6 (2) C2---C1---C6---C5 −1.0 (2) C9---C7---C8---N2 −1.96 (16) C2---C1---C6---S1 178.43 (12) S1---C7---C8---N2 174.91 (11) C4---C5---C6---C1 1.1 (2) N2---N1---C9---C7 0.18 (17) C4---C5---C6---S1 −178.38 (12) N2---N1---C9---C11 179.36 (13) C7---S1---C6---C1 7.87 (15) C8---C7---C9---N1 1.12 (17) C7---S1---C6---C5 −172.70 (12) S1---C7---C9---N1 −175.67 (11) C6---S1---C7---C9 −100.38 (14) C8---C7---C9---C11 −177.97 (15) C6---S1---C7---C8 83.36 (14) S1---C7---C9---C11 5.2 (2) -------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1854 .table-wrap} ------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1N1···O1^i^ 0.94 (2) 1.71 (2) 2.6446 (16) 173 (2) C3---H3A···O1^ii^ 0.93 2.53 3.2549 (19) 135 ------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −*x*+1/2, *y*+1/2, *z*; (ii) *x*, −*y*+1/2, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- ---------- ---------- ------------- ------------- N1---H1*N*1⋯O1^i^ 0.94 (2) 1.71 (2) 2.6446 (16) 173 (2) C3---H3*A*⋯O1^ii^ 0.93 2.53 3.2549 (19) 135 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.

PubMed Central

2024-06-05T04:04:18.473048

2011-2-16

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052103/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o633", "authors": [ { "first": "Tara", "last": "Shahani" }, { "first": "Hoong-Kun", "last": "Fun" }, { "first": "R. Venkat", "last": "Ragavan" }, { "first": "V.", "last": "Vijayakumar" }, { "first": "S.", "last": "Sarveswari" } ] }

PMC3052104

Related literature {#sec1} ================== Kumagai *et al.* (2002[@bb7]) describe different coordinations for carboxylate groups. For background information about the title compound and its metal complexes, see: Viola-Villegas & Doyle (2009[@bb11]). For macrocycle configurations, see: Bosnich *et al.* (1965[@bb1]); Dale (1973[@bb4], 1976[@bb5], 1980[@bb6]); Meyer *et al.* (1998[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~28~N~4~O~8~·2H~2~O*M* *~r~* = 440.46Orthorhombic,*a* = 17.183 (2) Å*b* = 6.5826 (9) Å*c* = 17.983 (2) Å*V* = 2034.0 (5) Å^3^*Z* = 4Mo *K*α radiationμ = 0.12 mm^−1^*T* = 100 K0.43 × 0.27 × 0.27 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker 2003[@bb3]) *T* ~min~ = 0.810, *T* ~max~ = 1.00019408 measured reflections2520 independent reflections2236 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.037 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.042*wR*(*F* ^2^) = 0.112*S* = 1.082520 reflections144 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.70 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e478} Data collection: *SMART* (Bruker, 2001[@bb2]); cell refinement: *SAINT-Plus* (Bruker, 2001[@bb2]); data reduction: *SAINT-Plus*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb9]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb9]); software used to prepare material for publication: *SHELXL97* and *PLATON* Spek (2009)[@bb10]. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004843/kp2290sup1.cif](http://dx.doi.org/10.1107/S1600536811004843/kp2290sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004843/kp2290Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004843/kp2290Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?kp2290&file=kp2290sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?kp2290sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?kp2290&checkcif=yes) Enhanced figure: [interactive version of Fig. 3](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=fignum&cnor=kp2290&fignum=3) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [KP2290](http://scripts.iucr.org/cgi-bin/sendsup?kp2290)). MZ was supported by NSF grant 0111511. The diffractometer was funded by NSF grant 0087210, by the Ohio Board of Regents grant CAP-491 and by Youngstown State University. Comment ======= In the course of our studies to prepare coordination polymer and metal-organic framework type compounds we investigated the title compound as a potentional building block. The molecule 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid DOTAH~4~ and its deprotonated analogs, \[DOTAH~2~\]^2-^ and \[DOTA\]^4-^ have several features desirable in coordination chemistry. The ligand offers a macrocycle with four neutral nitrogen donor sites as well as four dangling carboxylic acid groups. Carboxylate groups when deprotonated have been shown to exhibit nine different coordination modes with metal ions, seven of which coordinate two or more metal ions (Kumagai *et al.*, 2002). Therefore, the potential for forming molecular species as well as coordination polymers or metal-organic framework type compounds exists for this organic building block. For numerous examples of metal containing DOTAH~4~ compounds and its charged analogues see Viola-Villegas & Doyle (2009). Only half of DOTAH~4~ molecule (Fig. 1) in the structure is an asymmetric unit. The other half of the macrocycle is generated by a twofold rotation axis parallel to the *b* axis. There is no significant ring strain based on an analysis of the bond angles withing the ring. The ring is composed of eight methylene carbons (C1---C4, C1^i^---C4^i^), two ammonium N atoms (N1, N1^i^) and two tertiary N atoms (N2, N2^i^) (symmetry operator (i): -*x* + 1, *y*, -*z* + 3/2). The bond angles between them range from 110--112°. The configuration has all four N atoms located above the eight methylene carbons along the direction of the twofold axis in the centre of the ring producing a basket-like shape that would be able to coordinate a metal without large changes of the overall structure of the molecule. According to the system outlined by Dale this arrangement would be described as (3,3,3,3)-B (Dale, 1973, 1976, 1980, Meyer *et al.*, 1998). This system uses numbers to indicate the number of chemical bonds between the genuinie corners in the macrocycle. Genuine corners are the central atoms in an anti-*gauche*-*gauche*-anti bond sequence. In the title compound the atoms C1, C3, C1A, and C3A constitute genuine corners which are separated from each other along the macrocycle by three bonds. The \"B\" designation indicates that the four heteroatoms in this 12-membered macrocylce reside in a square planar arrangement above the methylene carbons (as described above). Using the terminology of Bosnich *et al.* (1965) the configuration of the macrocycle would be *cis*-I since all of the carboxylate containing groups project in the same direction. The weighted average ring bond distance is 1.503 Å (*PLATON*, Spek (2009)). The weighted average absolute torsion angle is 100.45°. The total puckering amplitude of the ring is 1.526 Å. The four carboxylic acid and carboxylate groups are bound to the N atoms and also all reside above the macrocycle. This arrangement leads to well separated hydrophobic and hydrophilic parts within the molecule. The H atoms bound to the N atoms within the macrocyle are engaged in two equivalent hydrogen bonds with the adjacent nitrogen atoms (N1---H1···N2, N1^i^---H1^i^···N2^i^, Table 1). The N1---H1 and H1···N2 distances are 0.93 Å and 2.44 Å respectively. The angle between the donor and acceptor is 110.1° in accord with the donor and acceptor both residing within the ring and being separated by two atoms. The crystal packing (Figs. 2 and 3) is dominated by hydrogen bonding between the crystal water molecules and the carboxylic acid and carboxylate groups. Each water molecule forms three hydrogen bonding interactions with the two hydrogen atoms oriented towards carboxylate groups (O5---H5D···O1^ii^, O5---H5C···O1^iii^, Table 1) and the oxygen directed towards a carboxylic acid group (O3---H3···O5, Table 1). Experimental {#experimental} ============ The title compound 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid was purchased from Strem Chemicals and used without further purification. The compound was crystallized from a saturated DMSO solution. A DMSO solution (2 mL) was saturated with DOTAH~4~ at 323 K. Upon cooling to room temperature and sitting for four days colourless block shaped crystals were formed. Refinement {#refinement} ========== The oxygen to hydrogen bond distances in the solvent water molecule were restrained to be 0.84 Å with a standard deviation of 0.02 Å. They were set to have an isotropic displacement parameter of 1.5 times that of the adjacent oxygen atom. The same displacement parameter was used for the hydrogen bound to the carboxylic acid, which were placed in calculated positions at a distance of 0.84 Å from the O atom but that were allowed to freely rotate at a fixed angle around the C---O bond to best fit the experimental electron density. All other hydrogen atoms in the structure were placed in calculated positions with *X*---H distances of 0.99 (methylene) or 0.93 Å (amine) with *U*~iso~(H) = 1.2 *U*~eq~(*X*). The highest residual electron density peak in the final Fourier map, with a heigth of 0.70 e^-^×Å^-3^, is located at the center of the macrocylce. An electron density difference Fourier map cutting through the protonated amine N atoms and the center of the residual electron density in the middle of the ring (with the protic amine H atoms removed prior to generation of the map) shows electron densities in the positions of the amine H atoms that are substantially larger than that of the residual electron density in the center of the ring, thus indicating that the amine H atoms are indeed fully protonated (which is supported by a refinement of the amine H atom occupancy, which yielded full occupancy). The residual density in the center of the ring refines to about 60% of one electron and it is located on a special position (site symmetry of 4c). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the title compound \[DOTAH4\] and water molecule (hydrogen atoms bound to carbon atoms are omitted for clarity). Dispalacement ellipsoids are shown at the 50% probability level. The two fold rotation axis that generates the symmetry related half of the molecule has a site symmetry of 4c. ::: ![](e-67-0o644-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A packing diagram of \[DOTAH4\] as viewed along the c axis. ::: ![](e-67-0o644-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Enhanced figure view of the packing of the title compound along the b axis. ::: ![](e-67-0o644-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e230 .table-wrap} --------------------------- ---------------------------------------- C~16~H~28~N~4~O~8~·2H~2~O *D*~x~ = 1.438 Mg m^−3^ *M~r~* = 440.46 Mo *K*α radiation, λ = 0.71073 Å Orthorhombic, *Pbcn* Cell parameters from 13988 reflections *a* = 17.183 (2) Å θ = 1.0--28.3° *b* = 6.5826 (9) Å µ = 0.12 mm^−1^ *c* = 17.983 (2) Å *T* = 100 K *V* = 2034.0 (5) Å^3^ Block, colourless *Z* = 4 0.43 × 0.27 × 0.27 mm *F*(000) = 944 --------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e357 .table-wrap} ----------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD diffractometer 2520 independent reflections Radiation source: fine-focus sealed tube 2236 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.037 ω scans θ~max~ = 28.3°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Bruker 2003) *h* = −22→22 *T*~min~ = 0.810, *T*~max~ = 1.000 *k* = −8→8 19408 measured reflections *l* = −23→23 ----------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e471 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.042 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.112 H atoms treated by a mixture of independent and constrained refinement *S* = 1.08 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0616*P*)^2^ + 0.8651*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2520 reflections (Δ/σ)~max~ = 0.003 144 parameters Δρ~max~ = 0.70 e Å^−3^ 2 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e628 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e727 .table-wrap} ----- ------------- -------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.52319 (7) 0.29809 (18) 0.59684 (7) 0.0172 (2) H1A 0.5484 0.1817 0.5716 0.021\* H1B 0.5118 0.4028 0.5588 0.021\* C2 0.44727 (7) 0.22770 (18) 0.63205 (7) 0.0169 (2) H2A 0.4101 0.1899 0.5923 0.020\* H2B 0.4573 0.1052 0.6625 0.020\* C3 0.35164 (7) 0.29561 (18) 0.72810 (7) 0.0161 (2) H3A 0.3257 0.1827 0.7015 0.019\* H3B 0.3118 0.3994 0.7398 0.019\* C4 0.61331 (7) 0.21651 (18) 0.70032 (7) 0.0165 (2) H4A 0.6542 0.1467 0.6711 0.020\* H4B 0.5724 0.1157 0.7123 0.020\* C5 0.64046 (7) 0.50850 (18) 0.61660 (7) 0.0175 (2) H5A 0.6619 0.4297 0.5744 0.021\* H5B 0.6833 0.5319 0.6524 0.021\* C6 0.61183 (7) 0.71385 (19) 0.58773 (7) 0.0190 (3) C7 0.37872 (7) 0.54695 (18) 0.63298 (7) 0.0167 (2) H7A 0.3332 0.4922 0.6058 0.020\* H7B 0.4178 0.5900 0.5957 0.020\* C8 0.35349 (7) 0.73022 (18) 0.67787 (7) 0.0187 (3) N1 0.57832 (6) 0.38475 (15) 0.65388 (5) 0.0147 (2) H1 0.5502 0.4699 0.6852 0.018\* N2 0.41201 (5) 0.38638 (15) 0.67930 (6) 0.0156 (2) O1 0.66535 (6) 0.81050 (15) 0.55408 (6) 0.0293 (2) O2 0.54404 (5) 0.76758 (14) 0.59796 (6) 0.0248 (2) O3 0.31304 (5) 0.86834 (13) 0.64068 (5) 0.0201 (2) H3 0.3110 0.8356 0.5956 0.030\* O4 0.36798 (7) 0.75428 (15) 0.74325 (5) 0.0286 (2) O5 0.29964 (6) 0.82984 (15) 0.50131 (5) 0.0218 (2) H5C 0.2571 (9) 0.800 (3) 0.4810 (9) 0.033\* H5D 0.3139 (11) 0.942 (2) 0.4806 (10) 0.033\* ----- ------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1137 .table-wrap} ---- ------------ ------------ ------------ ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0153 (5) 0.0185 (5) 0.0176 (5) −0.0004 (4) −0.0003 (4) −0.0007 (4) C2 0.0144 (5) 0.0160 (5) 0.0204 (6) −0.0006 (4) −0.0001 (4) −0.0015 (4) C3 0.0124 (5) 0.0153 (5) 0.0205 (6) −0.0014 (4) −0.0004 (4) −0.0014 (4) C4 0.0159 (5) 0.0127 (5) 0.0209 (6) 0.0024 (4) −0.0001 (4) 0.0018 (4) C5 0.0141 (5) 0.0164 (5) 0.0219 (6) −0.0006 (4) 0.0033 (4) 0.0026 (4) C6 0.0210 (6) 0.0160 (5) 0.0201 (6) −0.0001 (4) −0.0001 (4) 0.0014 (4) C7 0.0148 (5) 0.0157 (5) 0.0195 (5) 0.0005 (4) −0.0017 (4) 0.0005 (4) C8 0.0183 (6) 0.0143 (5) 0.0236 (6) −0.0037 (4) 0.0004 (4) 0.0004 (4) N1 0.0132 (4) 0.0137 (5) 0.0173 (5) 0.0007 (3) 0.0010 (3) 0.0008 (4) N2 0.0127 (4) 0.0142 (5) 0.0198 (5) 0.0004 (3) 0.0003 (4) 0.0010 (4) O1 0.0287 (5) 0.0212 (5) 0.0381 (6) 0.0002 (4) 0.0111 (4) 0.0102 (4) O2 0.0187 (5) 0.0196 (4) 0.0361 (5) 0.0025 (4) −0.0007 (4) 0.0035 (4) O3 0.0218 (4) 0.0158 (4) 0.0227 (4) 0.0021 (3) 0.0013 (3) −0.0007 (3) O4 0.0445 (6) 0.0186 (5) 0.0227 (5) −0.0021 (4) −0.0053 (4) −0.0026 (4) O5 0.0234 (5) 0.0173 (4) 0.0246 (5) 0.0009 (4) −0.0023 (4) 0.0023 (3) ---- ------------ ------------ ------------ ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1450 .table-wrap} ------------------- -------------- ---------------------- -------------- C1---N1 1.5082 (15) C5---C6 1.5294 (17) C1---C2 1.5223 (16) C5---H5A 0.9900 C1---H1A 0.9900 C5---H5B 0.9900 C1---H1B 0.9900 C6---O2 1.2312 (16) C2---N2 1.4765 (15) C6---O1 1.2715 (16) C2---H2A 0.9900 C7---N2 1.4622 (15) C2---H2B 0.9900 C7---C8 1.5149 (17) C3---N2 1.4844 (15) C7---H7A 0.9900 C3---C4^i^ 1.5136 (16) C7---H7B 0.9900 C3---H3A 0.9900 C8---O4 1.2122 (16) C3---H3B 0.9900 C8---O3 1.3255 (15) C4---N1 1.5117 (15) N1---H1 0.9300 C4---C3^i^ 1.5136 (17) O3---H3 0.8400 C4---H4A 0.9900 O5---H5C 0.840 (15) C4---H4B 0.9900 O5---H5D 0.865 (15) C5---N1 1.5011 (15) N1---C1---C2 111.75 (10) N1---C5---H5B 108.8 N1---C1---H1A 109.3 C6---C5---H5B 108.8 C2---C1---H1A 109.3 H5A---C5---H5B 107.7 N1---C1---H1B 109.3 O2---C6---O1 127.71 (12) C2---C1---H1B 109.3 O2---C6---C5 120.50 (11) H1A---C1---H1B 107.9 O1---C6---C5 111.78 (11) N2---C2---C1 112.06 (10) N2---C7---C8 112.59 (10) N2---C2---H2A 109.2 N2---C7---H7A 109.1 C1---C2---H2A 109.2 C8---C7---H7A 109.1 N2---C2---H2B 109.2 N2---C7---H7B 109.1 C1---C2---H2B 109.2 C8---C7---H7B 109.1 H2A---C2---H2B 107.9 H7A---C7---H7B 107.8 N2---C3---C4^i^ 111.30 (9) O4---C8---O3 120.49 (12) N2---C3---H3A 109.4 O4---C8---C7 124.21 (12) C4^i^---C3---H3A 109.4 O3---C8---C7 115.30 (11) N2---C3---H3B 109.4 C5---N1---C1 110.39 (9) C4^i^---C3---H3B 109.4 C5---N1---C4 111.18 (9) H3A---C3---H3B 108.0 C1---N1---C4 110.39 (9) N1---C4---C3^i^ 112.09 (9) C5---N1---H1 108.3 N1---C4---H4A 109.2 C1---N1---H1 108.3 C3^i^---C4---H4A 109.2 C4---N1---H1 108.3 N1---C4---H4B 109.2 C7---N2---C2 110.13 (9) C3^i^---C4---H4B 109.2 C7---N2---C3 110.75 (9) H4A---C4---H4B 107.9 C2---N2---C3 110.02 (9) N1---C5---C6 113.73 (10) C8---O3---H3 109.5 N1---C5---H5A 108.8 H5C---O5---H5D 105.1 (18) C6---C5---H5A 108.8 N1---C1---C2---N2 51.11 (13) C3^i^---C4---N1---C5 74.84 (12) N1---C5---C6---O2 2.30 (17) C3^i^---C4---N1---C1 −162.30 (9) N1---C5---C6---O1 −177.48 (11) C8---C7---N2---C2 −170.60 (9) N2---C7---C8---O4 8.99 (17) C8---C7---N2---C3 67.48 (12) N2---C7---C8---O3 −170.88 (10) C1---C2---N2---C7 73.24 (12) C6---C5---N1---C1 73.84 (12) C1---C2---N2---C3 −164.40 (10) C6---C5---N1---C4 −163.30 (10) C4^i^---C3---N2---C7 −150.74 (10) C2---C1---N1---C5 −162.75 (9) C4^i^---C3---N2---C2 87.27 (11) C2---C1---N1---C4 73.93 (12) ------------------- -------------- ---------------------- -------------- ::: Symmetry codes: (i) −*x*+1, *y*, −*z*+3/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2003 .table-wrap} -------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O3---H3···O5 0.84 1.71 2.5295 (14) 166 N1---H1···N2 0.93 2.44 2.8940 (14) 110 O5---H5D···O1^ii^ 0.86 (1) 1.78 (2) 2.6380 (14) 173.(2) O5---H5C···O1^iii^ 0.84 (1) 1.85 (2) 2.6776 (14) 170.(2) -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (ii) −*x*+1, −*y*+2, −*z*+1; (iii) *x*−1/2, −*y*+3/2, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- ---------- ---------- ------------- ------------- O3---H3⋯O5 0.84 1.71 2.5295 (14) 166 N1---H1⋯N2 0.93 2.44 2.8940 (14) 110 O5---H5*D*⋯O1^i^ 0.86 (1) 1.78 (2) 2.6380 (14) 173 (2) O5---H5*C*⋯O1^ii^ 0.84 (1) 1.85 (2) 2.6776 (14) 170 (2) Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.476815

2011-2-16

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052104/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o644", "authors": [ { "first": "Paul S.", "last": "Szalay" }, { "first": "Matthias", "last": "Zeller" }, { "first": "Allen D.", "last": "Hunter" } ] }

PMC3052105

Related literature {#sec1} ================== For the preparation of 1,2-dihydroquinoline, see: Dauphinee & Forrest (1978[@bb3]); Katritzky *et al.* (1996[@bb8]); Elmore *et al.* (2001[@bb4]); Lu & Malinakova (2004[@bb10]); Wang *et al.* (2009[@bb16]); Rezgui *et al.* (1999[@bb11]). For related structures, see: Yadav *et al.* (2007[@bb17]); Kamakshi & Reddy (2007[@bb7]); Kim *et al.* (2001[@bb9]); Sundèn *et al.* (2007[@bb14]); Waldmann *et al.* (2008[@bb15]). For ring puckering analysis, see: Cremer & Pople (1975[@bb2]). For graph-set theory, see: Bernstein *et al.* (1995[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~17~NO~5~*M* *~r~* = 303.31Monoclinic,*a* = 8.0222 (3) Å*b* = 18.2466 (9) Å*c* = 10.3478 (4) Åβ = 101.042 (3)°*V* = 1486.65 (11) Å^3^*Z* = 4Mo *K*α radiationμ = 0.10 mm^−1^*T* = 296 K0.74 × 0.43 × 0.23 mm ### Data collection {#sec2.1.2} Stoe IPDS 2 diffractometerAbsorption correction: integration (*X-RED32*; Stoe & Cie, 2002[@bb13]) *T* ~min~ = 0.823, *T* ~max~ = 0.96814613 measured reflections3068 independent reflections2221 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.055 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.059*wR*(*F* ^2^) = 0.169*S* = 1.0714613 reflections205 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.43 e Å^−3^Δρ~min~ = −0.36 e Å^−3^ {#d5e528} Data collection: *X-AREA* (Stoe & Cie, 2002[@bb13]); cell refinement: *X-AREA*; data reduction: *X-RED32* (Stoe & Cie, 2002[@bb13]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb12]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb12]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb5]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003564/si2329sup1.cif](http://dx.doi.org/10.1107/S1600536811003564/si2329sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003564/si2329Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003564/si2329Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2329&file=si2329sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2329sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2329&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2329](http://scripts.iucr.org/cgi-bin/sendsup?si2329)). The title product was synthesized at RWTH Aachen University. The authors thank Professor Magnus Rueping of RWTH Aachen University, Germany, for helpful discussions and acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund). Comment ======= Dihydroquinoline moiety is found in a wide variety of natural products and they have attracted a lot of attention from synthetic organic chemists (Kamakshi & Reddy, 2007). 1,2-Dihydroquinolines have received substantial attention due to their potential biological activities arising from their antioxidative properties as well as their usefulness as precursors of some other biologically active compounds (Kim *et al.*, 2001). 1,2-Dihydroquinoline derivatives are known to exhibit a wide spectrum of biological activities such as antimalarial, antibacterial and anti-inflammatory behavior (Yadav *et al.*, 2007). Asymmetric synthesis of 1,2-dihydroquinolin have been attracted in recent years (Wang *et al.*, 2009; Rezgui *et al.*, 1999). Sundèn and co-worker has reported asymmetric synthesis of 1,2-dihydroquinolines using Domino reactions between 2-aminobenzaldehyde and α,β-unsaturated aldehydes to give pharmaceutically valuable 1,2-dihydroquinolines in high enantioselectivity (Sundèn *et al.*, 2007). 1,2-dihydroquinolines was used for several applications, such as synthesis of quinolines: (Dauphinee & Forrest, 1978; Lu & Malinakova, 2004), 1,2,3,4- tetrahydroquinolines: (Katritzky *et al.*, 1996) and natural products: (Elmore *et al.*, 2001). The molecule of the title compound contains dihydroquinoline, two methoxycarbonyl (O=C---O---CH~3~) and acetyl group (O=C---CH~3~). The two --CO~2~Me groups are antisymmetric with respect to atom C10 (Fig. 1). The six-membered N containing ring of the quinoline system displays a half-boat conformation with the puckering parameters of Q~T~=0.261 (2) Å, Φ=146.7 (6)° and Θ=112.7 (4) ° (Cremer & Pople, 1975) and the spiro carbon atom deviates 0.34 (2) Å from the plane (r.m.s. deviation 0.051 Å) defined by the N1 and C1, C6, C9, C10 atoms. The intramolecular N---H..O hydrogen bond generate S(6) ring motif (Bernstein *et al.*, 1995) (Fig. 1, Table 1). The dihedral angle between the S(6) ring mean plane and the half-boat plane of five atoms is 3.39 (2)°. The crystal packing is stabilized by C10---H10···O3^i^ intermolecular hydrogen bonds linking the molecules into chains in a zigzag mode along \[0 0 1\] due to *c*-glide symmetry, and there are also two C---H···π interactions C14---H14*c*···*Cg*1^i^ and C8---H8b···*Cg*1^ii^ \[(i): *x*,1/2 - *y*,-1/2 + *z*; (ii):1 - *x*,1 - *y*,1 - *z*\] extending along the *b* axis (Fig. 2., Table 1.). Experimental {#experimental} ============ The title compound was synthesized after a method described by Waldmann *et al.*, (2008). 2\'-aminoacetophenone (100 mg, 1 eq) was dissolved in acetonitrile (1.5 ml) in a screw-capped test tube and Bi(OTf)~3~ (5 mol %, 0.05 eq) was added to the mixture. This mixture were stirred at room temperature for 4 days until the starting material was completely consumed as monitored by TLC. The resultant residue was directly purified by flash chromatography on silica (EtOAc: Cyclohexane 2:98) gave 27% yield as a yellow solid. Recrystallized over pentan and ethyl acetate gave yellow crystalline solid. *R*~f~ 0.5 (2:1 Cyclohexane/EtOAc); m.p: (374--375 K). Refinement {#refinement} ========== The H atom of the NH group was located in a difference Fourier map and refined with the constraint N---H = 0.86 (2) Å. All other H atoms were positioned with idealized geometry using a riding model, \[C---H = 0.93--0.96Å and *U*~iso~ = 1.2*U*~eq~(C)\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### An ORTEP view of (I), with the atom-numbering scheme and 30% probability displacement ellipsoids. Dashed lines indicate H-bonds. ::: ![](e-67-0o544-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A packing diagram for (I), showing the C---H···O hydrogen bonds and C---H···π interactions. H atoms not involved in hydrogen bonding (dashed lines) have been omitted for clarity. \[Symmetry code; (i): x,1/2 - y,-1/2 + z; (ii): 1 - x,1 - y,1 - z\]. (Cg1 is the centroid of the C1---C6 ring). ::: ![](e-67-0o544-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e248 .table-wrap} ------------------------- ---------------------------------------- C~16~H~17~NO~5~ *F*(000) = 640 *M~r~* = 303.31 *D*~x~ = 1.355 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 14613 reflections *a* = 8.0222 (3) Å θ = 2.0--28.0° *b* = 18.2466 (9) Å µ = 0.10 mm^−1^ *c* = 10.3478 (4) Å *T* = 296 K β = 101.042 (3)° Prism, brown *V* = 1486.65 (11) Å^3^ 0.74 × 0.43 × 0.23 mm *Z* = 4 ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e375 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Stoe IPDS 2 diffractometer 3068 independent reflections Radiation source: fine-focus sealed tube 2221 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.055 rotation method scans θ~max~ = 26.5°, θ~min~ = 2.2° Absorption correction: integration (*X-RED32*; Stoe & Cie, 2002) *h* = −10→10 *T*~min~ = 0.823, *T*~max~ = 0.968 *k* = −22→22 14613 measured reflections *l* = −12→12 ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.059 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.169 H atoms treated by a mixture of independent and constrained refinement *S* = 1.07 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0846*P*)^2^ + 0.2827*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 14613 reflections (Δ/σ)~max~ \< 0.001 205 parameters Δρ~max~ = 0.43 e Å^−3^ 1 restraint Δρ~min~ = −0.36 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ------ ------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.4104 (2) 0.37012 (12) 0.3615 (2) 0.0427 (5) C2 0.5203 (3) 0.39441 (12) 0.4782 (2) 0.0458 (5) C3 0.4559 (3) 0.39964 (14) 0.5939 (2) 0.0537 (6) H3 0.5267 0.4161 0.6702 0.064\* C4 0.2911 (3) 0.38117 (16) 0.5987 (2) 0.0582 (6) H4 0.2512 0.3853 0.6771 0.070\* C5 0.1846 (3) 0.35628 (15) 0.4853 (2) 0.0529 (6) H5 0.0732 0.3436 0.4887 0.064\* C6 0.2403 (2) 0.34998 (13) 0.3675 (2) 0.0436 (5) C7 0.6980 (3) 0.41517 (14) 0.4779 (2) 0.0507 (6) C8 0.8065 (3) 0.44802 (16) 0.5984 (3) 0.0618 (7) H8A 0.8402 0.4104 0.6630 0.074\* H8B 0.7431 0.4850 0.6341 0.074\* H8C 0.9058 0.4697 0.5751 0.074\* C9 0.1341 (2) 0.32351 (13) 0.2442 (2) 0.0454 (5) C10 0.1863 (3) 0.32944 (14) 0.1302 (2) 0.0491 (5) H10 0.1169 0.3113 0.0547 0.059\* C11 0.3514 (3) 0.36395 (13) 0.1178 (2) 0.0462 (5) C12 −0.0356 (3) 0.28883 (15) 0.2385 (2) 0.0521 (6) C13 −0.2120 (3) 0.21400 (18) 0.3394 (3) 0.0732 (8) H13A −0.2844 0.2489 0.3708 0.088\* H13B −0.1979 0.1719 0.3960 0.088\* H13C −0.2625 0.1993 0.2515 0.088\* C14 0.4362 (3) 0.32316 (16) 0.0183 (2) 0.0572 (6) H14A 0.5410 0.3470 0.0119 0.069\* H14B 0.3620 0.3234 −0.0663 0.069\* H14C 0.4588 0.2735 0.0469 0.069\* C15 0.3165 (3) 0.44329 (14) 0.0688 (2) 0.0496 (6) C16 0.1661 (4) 0.51590 (18) −0.1039 (3) 0.0788 (9) H16A 0.1176 0.5463 −0.0450 0.095\* H16B 0.0861 0.5102 −0.1851 0.095\* H16C 0.2678 0.5384 −0.1211 0.095\* N1 0.4639 (2) 0.36371 (12) 0.24524 (18) 0.0508 (5) O1 0.7624 (2) 0.40668 (13) 0.38037 (19) 0.0708 (6) O2 −0.1528 (2) 0.29932 (15) 0.1485 (2) 0.0906 (8) O3 −0.0469 (2) 0.24724 (11) 0.33918 (18) 0.0657 (5) O4 0.3796 (3) 0.49676 (12) 0.1243 (2) 0.0794 (6) O5 0.2062 (2) 0.44499 (10) −0.04465 (18) 0.0641 (5) H1 0.566 (2) 0.3785 (15) 0.248 (3) 0.065 (8)\* ------ ------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1276 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0390 (10) 0.0448 (12) 0.0419 (11) 0.0046 (9) 0.0017 (8) 0.0007 (9) C2 0.0438 (11) 0.0449 (12) 0.0450 (12) 0.0039 (9) −0.0014 (9) 0.0003 (10) C3 0.0524 (12) 0.0619 (16) 0.0425 (12) −0.0001 (11) −0.0015 (10) −0.0073 (11) C4 0.0540 (13) 0.0755 (18) 0.0454 (13) 0.0000 (12) 0.0099 (10) −0.0068 (12) C5 0.0463 (11) 0.0635 (15) 0.0486 (13) 0.0016 (10) 0.0081 (10) −0.0037 (11) C6 0.0397 (10) 0.0455 (12) 0.0431 (12) 0.0025 (8) 0.0018 (8) −0.0009 (9) C7 0.0441 (11) 0.0536 (14) 0.0507 (14) 0.0021 (10) −0.0005 (10) −0.0018 (11) C8 0.0503 (12) 0.0684 (17) 0.0611 (16) −0.0086 (11) −0.0031 (11) −0.0069 (13) C9 0.0392 (10) 0.0497 (13) 0.0446 (12) 0.0008 (9) 0.0013 (9) 0.0021 (10) C10 0.0422 (10) 0.0575 (14) 0.0440 (12) −0.0040 (10) −0.0007 (9) −0.0034 (10) C11 0.0407 (10) 0.0574 (14) 0.0391 (11) −0.0018 (9) 0.0041 (8) −0.0030 (10) C12 0.0461 (12) 0.0657 (16) 0.0424 (12) −0.0063 (10) 0.0027 (10) −0.0011 (11) C13 0.0639 (15) 0.086 (2) 0.0689 (18) −0.0292 (15) 0.0113 (13) 0.0083 (16) C14 0.0509 (12) 0.0676 (17) 0.0534 (15) 0.0019 (11) 0.0108 (10) −0.0106 (12) C15 0.0463 (11) 0.0599 (15) 0.0428 (12) −0.0056 (10) 0.0095 (9) −0.0046 (11) C16 0.0801 (19) 0.077 (2) 0.074 (2) 0.0029 (16) 0.0012 (15) 0.0221 (17) N1 0.0375 (9) 0.0726 (14) 0.0405 (10) −0.0042 (9) 0.0032 (8) −0.0029 (9) O1 0.0446 (9) 0.1052 (16) 0.0605 (11) −0.0100 (9) 0.0051 (8) −0.0129 (11) O2 0.0528 (10) 0.149 (2) 0.0624 (12) −0.0263 (11) −0.0078 (9) 0.0270 (13) O3 0.0573 (9) 0.0731 (13) 0.0615 (11) −0.0174 (8) −0.0020 (8) 0.0178 (10) O4 0.1003 (15) 0.0624 (12) 0.0673 (13) −0.0137 (11) −0.0043 (11) −0.0087 (10) O5 0.0648 (10) 0.0631 (12) 0.0566 (11) −0.0039 (8) −0.0079 (8) 0.0080 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1725 .table-wrap} --------------------- ------------- ---------------------- -------------- C1---N1 1.358 (3) C10---H10 0.9300 C1---C2 1.423 (3) C11---N1 1.448 (3) C1---C6 1.426 (3) C11---C14 1.531 (3) C2---C3 1.395 (3) C11---C15 1.542 (3) C2---C7 1.475 (3) C12---O2 1.205 (3) C3---C4 1.374 (3) C12---O3 1.306 (3) C3---H3 0.9300 C13---O3 1.457 (3) C4---C5 1.389 (3) C13---H13A 0.9600 C4---H4 0.9300 C13---H13B 0.9600 C5---C6 1.381 (3) C13---H13C 0.9600 C5---H5 0.9300 C14---H14A 0.9600 C6---C9 1.474 (3) C14---H14B 0.9600 C7---O1 1.229 (3) C14---H14C 0.9600 C7---C8 1.502 (3) C15---O4 1.195 (3) C8---H8A 0.9600 C15---O5 1.328 (3) C8---H8B 0.9600 C16---O5 1.442 (3) C8---H8C 0.9600 C16---H16A 0.9600 C9---C10 1.330 (3) C16---H16B 0.9600 C9---C12 1.492 (3) C16---H16C 0.9600 C10---C11 1.494 (3) N1---H1 0.858 (17) N1---C1---C2 121.97 (18) N1---C11---C14 109.33 (18) N1---C1---C6 118.91 (19) C10---C11---C14 111.6 (2) C2---C1---C6 119.11 (19) N1---C11---C15 110.15 (19) C3---C2---C1 118.56 (19) C10---C11---C15 108.43 (18) C3---C2---C7 120.1 (2) C14---C11---C15 108.15 (19) C1---C2---C7 121.3 (2) O2---C12---O3 123.1 (2) C4---C3---C2 122.1 (2) O2---C12---C9 122.3 (2) C4---C3---H3 118.9 O3---C12---C9 114.68 (19) C2---C3---H3 118.9 O3---C13---H13A 109.5 C3---C4---C5 119.3 (2) O3---C13---H13B 109.5 C3---C4---H4 120.3 H13A---C13---H13B 109.5 C5---C4---H4 120.3 O3---C13---H13C 109.5 C6---C5---C4 121.5 (2) H13A---C13---H13C 109.5 C6---C5---H5 119.3 H13B---C13---H13C 109.5 C4---C5---H5 119.3 C11---C14---H14A 109.5 C5---C6---C1 119.4 (2) C11---C14---H14B 109.5 C5---C6---C9 124.05 (19) H14A---C14---H14B 109.5 C1---C6---C9 116.55 (19) C11---C14---H14C 109.5 O1---C7---C2 121.9 (2) H14A---C14---H14C 109.5 O1---C7---C8 117.6 (2) H14B---C14---H14C 109.5 C2---C7---C8 120.5 (2) O4---C15---O5 123.7 (2) C7---C8---H8A 109.5 O4---C15---C11 125.1 (2) C7---C8---H8B 109.5 O5---C15---C11 111.1 (2) H8A---C8---H8B 109.5 O5---C16---H16A 109.5 C7---C8---H8C 109.5 O5---C16---H16B 109.5 H8A---C8---H8C 109.5 H16A---C16---H16B 109.5 H8B---C8---H8C 109.5 O5---C16---H16C 109.5 C10---C9---C6 120.85 (19) H16A---C16---H16C 109.5 C10---C9---C12 116.1 (2) H16B---C16---H16C 109.5 C6---C9---C12 123.04 (19) C1---N1---C11 124.00 (17) C9---C10---C11 123.1 (2) C1---N1---H1 114.2 (19) C9---C10---H10 118.5 C11---N1---H1 116.7 (19) C11---C10---H10 118.5 C12---O3---C13 116.44 (19) N1---C11---C10 109.17 (18) C15---O5---C16 117.0 (2) N1---C1---C2---C3 179.9 (2) C12---C9---C10---C11 178.9 (2) C6---C1---C2---C3 −1.8 (3) C9---C10---C11---N1 20.8 (3) N1---C1---C2---C7 1.1 (3) C9---C10---C11---C14 141.8 (2) C6---C1---C2---C7 179.3 (2) C9---C10---C11---C15 −99.2 (3) C1---C2---C3---C4 0.9 (4) C10---C9---C12---O2 −37.6 (4) C7---C2---C3---C4 179.8 (2) C6---C9---C12---O2 142.5 (3) C2---C3---C4---C5 0.2 (4) C10---C9---C12---O3 143.2 (2) C3---C4---C5---C6 −0.3 (4) C6---C9---C12---O3 −36.7 (3) C4---C5---C6---C1 −0.6 (4) N1---C11---C15---O4 3.5 (3) C4---C5---C6---C9 179.6 (2) C10---C11---C15---O4 122.9 (3) N1---C1---C6---C5 180.0 (2) C14---C11---C15---O4 −115.9 (3) C2---C1---C6---C5 1.7 (3) N1---C11---C15---O5 −176.59 (17) N1---C1---C6---C9 −0.2 (3) C10---C11---C15---O5 −57.2 (2) C2---C1---C6---C9 −178.5 (2) C14---C11---C15---O5 64.0 (2) C3---C2---C7---O1 175.0 (3) C2---C1---N1---C11 −158.1 (2) C1---C2---C7---O1 −6.1 (4) C6---C1---N1---C11 23.6 (3) C3---C2---C7---C8 −5.2 (4) C10---C11---N1---C1 −32.7 (3) C1---C2---C7---C8 173.6 (2) C14---C11---N1---C1 −155.0 (2) C5---C6---C9---C10 169.4 (2) C15---C11---N1---C1 86.3 (3) C1---C6---C9---C10 −10.4 (3) O2---C12---O3---C13 −0.9 (4) C5---C6---C9---C12 −10.7 (4) C9---C12---O3---C13 178.3 (2) C1---C6---C9---C12 169.5 (2) O4---C15---O5---C16 1.8 (4) C6---C9---C10---C11 −1.3 (4) C11---C15---O5---C16 −178.1 (2) --------------------- ------------- ---------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2493 .table-wrap} ----------------------------------------- Cg1 is the centroid of the C1--C6 ring. ----------------------------------------- ::: ::: {#d1e2497 .table-wrap} --------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1···O1 0.86 (2) 1.95 (2) 2.650 (2) 138 (2) C10---H10···O3^i^ 0.93 2.59 3.517 (3) 174 C14---H14C···Cg1^i^ 0.96 2.89 3.692 (3) 142 C8---H8B···Cg1^ii^ 0.96 2.85 3.501 (3) 126 --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) *x*, −*y*+1/2, *z*−1/2; (ii) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 is the centroid of the C1--C6 ring. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ----------------------- ---------- ---------- ----------- ------------- N1---H1⋯O1 0.86 (2) 1.95 (2) 2.650 (2) 138 (2) C10---H10⋯O3^i^ 0.93 2.59 3.517 (3) 174 C14---H14*C*⋯*Cg*1^i^ 0.96 2.89 3.692 (3) 142 C8---H8*B*⋯*Cg*1^ii^ 0.96 2.85 3.501 (3) 126 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.480567

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052105/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o544-o545", "authors": [ { "first": "Zeynep", "last": "Keleşoğlu" }, { "first": "Zeynep", "last": "Gültekin" }, { "first": "Orhan", "last": "Büyükgüngör" } ] }

PMC3052106

Related literature {#sec1} ================== For related structures, see: Mikuriya *et al.* (1992[@bb4]); Li *et al.* (1997[@bb1]); Lu *et al.* (2006[@bb2]); Wang *et al.* (2008[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Mn(C~16~H~12~Br~2~N~2~O~2~)(N~3~)\]*M* *~r~* = 1042.13Monoclinic,*a* = 8.7068 (17) Å*b* = 15.269 (3) Å*c* = 13.684 (3) Åβ = 107.47 (3)°*V* = 1735.4 (6) Å^3^*Z* = 2Mo *K*α radiationμ = 5.39 mm^−1^*T* = 153 K0.20 × 0.17 × 0.10 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (*SORTAV*; Blessing, 1995[@bb7]) *T* ~min~ = 0.352, *T* ~max~ = 0.5837747 measured reflections3961 independent reflections3093 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.015 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.030*wR*(*F* ^2^) = 0.074*S* = 1.043961 reflections235 parametersH-atom parameters constrainedΔρ~max~ = 0.82 e Å^−3^Δρ~min~ = −0.90 e Å^−3^ {#d5e370} Data collection: *COLLECT* (Nonius, 1998[@bb5]); cell refinement: *SCALEPACK* (Otwinowski & Minor, 1997[@bb6]); data reduction: *DENZO* (Otwinowski & Minor, 1997[@bb6]) and *maXus* (Mackay *et al.*, 1998[@bb3]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb8]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004594/pk2299sup1.cif](http://dx.doi.org/10.1107/S1600536811004594/pk2299sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004594/pk2299Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004594/pk2299Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?pk2299&file=pk2299sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?pk2299sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?pk2299&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [PK2299](http://scripts.iucr.org/cgi-bin/sendsup?pk2299)). Comment ======= In the past decade there has been much interest in the magneto-chemistry of manganese because of its special magnetic properties. As is well known, manganese (III) Schiff base complexes display interesting structural, magnetic properties and electronic effects which rank it among the most appealing candidates as a building paramagnetic motif for multidimensional expanded structures. The variation of in-plane chelating and axial sites often leads to a change in the spin state of the metal ions: high-spin, low-spin or spin-crossover state. The nature and the tuning of magnetic interactions between metal centers are crucial points in the conception of molecular-based magnetic materials. The molecular structure of the title compound is shown in Figure 1. The Mn^III^ ion is involved in a distorted square-pyramidal arrangement by a N3O2 unit, in which the four basal sites are occupied by two N atoms and two O atoms from the Schiff base ligand, and the apical position is occupied by the N atom of an azido ligand. The bond distances are comparable to those found in related structures (Lu, *et al.*, 2006; Mikuriya, *et al.*, 1992; Li, *et al.*, 1997; Wang, *et al.*, 2008). The Mn^III^ ion lies above the basal plane formed by N2O2 unit by 0.228 (1) Å. The short intermolecular distance of Mn···O~phenolate~ 2.667 (2) Å indicates that there exists weak interaction between the two complexes related by inversion centers in the crystal (Figure 2). The phenyl groups of the Schiff base are involved in an offset face-to-face π-π inter-complexes stacking interaction (ring centroid separation *C*g···*C*g^i^, 3.598 (2) Å) \[symmetry code: 2 - *x*,1 - *y*,1 - *z*\]. Experimental {#experimental} ============ This compound was synthesized by mixing a solution of Schiff base (2,2\'-((1*E*,1\'*E*)-(ethane-1,2-diylbis(azanylylidene)) bis(methanylylidene))bis(4-bromophenol)) (0.5 mmol) in methanol (5 ml) with a solution of MnCl~2~.4H~2~O (0.5 mmol) in methanol (5 ml), followed by the dropwise addition of an aqueous solution NaN~3~(0.6 mmol, 2 mL) without stirring. The black mixture was allowed to stand for several days until good quality black block crystals of the compound were obtained in a yield of 68.3%. Refinement {#refinement} ========== All the H atoms bonded to the C atoms were placed using the HFIX commands in *SHELXL97* (Sheldrick, 2008) with C---H distances of 0.93 and 0.97 Å, respectively, and were allowed for as riding atoms with *U*~iso~(H) = 1.2Ueq(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure (30% thermal probability ellipsoids) of the compound showing the atom numbering. ::: ![](e-67-0m322-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A pair of inversion-related molecules, showing the intermolecular weak interactions between Mn and Ophenolate atoms. The \'A\' molecule is related to the \'B\' molecule by \[A: (x, y, z) ---\> B: (2-x, 1-y, -z)\]. ::: ![](e-67-0m322-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e170 .table-wrap} --------------------------------------- ---------------------------------------- \[Mn(C~16~H~12~Br~2~N~2~O~2~)(N~3~)\] *F*(000) = 1016 *M~r~* = 1042.13 *D*~x~ = 1.994 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 19417 reflections *a* = 8.7068 (17) Å θ = 3.4--27.5° *b* = 15.269 (3) Å µ = 5.39 mm^−1^ *c* = 13.684 (3) Å *T* = 153 K β = 107.47 (3)° Block, black *V* = 1735.4 (6) Å^3^ 0.20 × 0.17 × 0.10 mm *Z* = 2 --------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e308 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 3961 independent reflections Radiation source: fine-focus sealed tube 3093 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.015 ω scans θ~max~ = 27.5°, θ~min~ = 3.5° Absorption correction: multi-scan (*SORTAV*; Blessing, 1995) *h* = −11→11 *T*~min~ = 0.352, *T*~max~ = 0.583 *k* = −19→19 7747 measured reflections *l* = −17→17 -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e422 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.074 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0376*P*)^2^ + 0.8161*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3961 reflections (Δ/σ)~max~ = 0.001 235 parameters Δρ~max~ = 0.82 e Å^−3^ 0 restraints Δρ~min~ = −0.90 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e579 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Mn1 0.85052 (5) 0.50918 (2) 0.38001 (3) 0.02912 (10) Br1 1.11255 (4) 0.95137 (2) 0.37896 (3) 0.05433 (11) Br2 0.43251 (4) 0.106181 (19) 0.44904 (2) 0.04785 (10) C1 0.9787 (3) 0.67065 (17) 0.46365 (19) 0.0282 (5) C2 0.9438 (3) 0.74469 (17) 0.5129 (2) 0.0323 (6) H2 0.8919 0.7381 0.5627 0.039\* C3 0.9851 (3) 0.82750 (18) 0.4890 (2) 0.0358 (6) H3 0.9580 0.8764 0.5208 0.043\* C4 1.0675 (3) 0.83713 (17) 0.4168 (2) 0.0336 (6) C5 1.1113 (3) 0.76578 (18) 0.3710 (2) 0.0321 (6) H5 1.1715 0.7732 0.3258 0.039\* C6 1.0655 (3) 0.68135 (17) 0.39187 (19) 0.0279 (5) C7 1.1100 (3) 0.60754 (17) 0.33963 (19) 0.0307 (5) H7 1.1928 0.6147 0.3104 0.037\* C8 1.0902 (4) 0.45714 (18) 0.2823 (2) 0.0403 (7) H8A 1.1603 0.4191 0.3333 0.048\* H8B 1.1476 0.4763 0.2354 0.048\* C9 0.9380 (4) 0.4093 (2) 0.2250 (2) 0.0446 (7) H9A 0.8813 0.4411 0.1634 0.054\* H9B 0.9636 0.3512 0.2056 0.054\* C10 0.7619 (3) 0.33187 (17) 0.30160 (19) 0.0314 (5) H10 0.7730 0.2845 0.2615 0.038\* C11 0.6617 (3) 0.32053 (16) 0.36746 (19) 0.0274 (5) C12 0.6028 (3) 0.23581 (17) 0.37468 (19) 0.0309 (5) H12 0.6289 0.1898 0.3380 0.037\* C13 0.5066 (3) 0.22139 (16) 0.4361 (2) 0.0316 (6) C14 0.4649 (3) 0.28895 (18) 0.4908 (2) 0.0348 (6) H14 0.3986 0.2780 0.5315 0.042\* C15 0.5215 (3) 0.37191 (18) 0.4848 (2) 0.0344 (6) H15 0.4912 0.4173 0.5204 0.041\* C16 0.6248 (3) 0.38931 (16) 0.4256 (2) 0.0285 (5) N1 1.0407 (3) 0.53307 (14) 0.33190 (16) 0.0304 (5) N2 0.8372 (3) 0.40293 (14) 0.29446 (16) 0.0314 (5) N3 0.7109 (3) 0.60055 (17) 0.2717 (2) 0.0449 (6) N4 0.5810 (3) 0.62722 (17) 0.26329 (18) 0.0412 (6) N5 0.4533 (4) 0.6552 (3) 0.2518 (3) 0.0747 (10) O1 0.9342 (2) 0.59151 (11) 0.48779 (14) 0.0333 (4) O2 0.6852 (2) 0.46910 (12) 0.42930 (15) 0.0362 (4) ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1173 .table-wrap} ----- ------------- -------------- -------------- --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Mn1 0.0366 (2) 0.02311 (19) 0.0337 (2) −0.00517 (16) 0.01976 (18) −0.00327 (16) Br1 0.0655 (2) 0.02778 (16) 0.0791 (3) −0.00838 (14) 0.03595 (19) 0.00547 (15) Br2 0.0672 (2) 0.02952 (16) 0.05173 (19) −0.01626 (14) 0.02536 (16) −0.00135 (13) C1 0.0296 (12) 0.0273 (13) 0.0273 (12) −0.0038 (10) 0.0079 (11) 0.0013 (10) C2 0.0329 (13) 0.0305 (13) 0.0362 (14) −0.0032 (11) 0.0147 (12) −0.0028 (11) C3 0.0336 (14) 0.0287 (14) 0.0472 (16) −0.0010 (11) 0.0154 (13) −0.0036 (12) C4 0.0332 (14) 0.0243 (12) 0.0417 (15) −0.0062 (11) 0.0090 (12) 0.0028 (11) C5 0.0304 (13) 0.0330 (14) 0.0331 (14) −0.0066 (11) 0.0096 (11) 0.0033 (11) C6 0.0284 (12) 0.0273 (13) 0.0285 (13) −0.0026 (10) 0.0092 (11) 0.0025 (10) C7 0.0322 (13) 0.0331 (14) 0.0293 (13) −0.0012 (11) 0.0129 (11) 0.0040 (11) C8 0.0549 (18) 0.0305 (14) 0.0490 (17) 0.0016 (13) 0.0359 (15) −0.0012 (12) C9 0.070 (2) 0.0367 (16) 0.0416 (16) −0.0095 (14) 0.0383 (16) −0.0092 (13) C10 0.0389 (14) 0.0269 (13) 0.0282 (13) 0.0003 (11) 0.0101 (11) −0.0034 (10) C11 0.0288 (12) 0.0250 (13) 0.0282 (13) −0.0032 (10) 0.0080 (11) −0.0008 (10) C12 0.0363 (14) 0.0244 (13) 0.0305 (13) −0.0038 (11) 0.0076 (11) −0.0027 (10) C13 0.0355 (14) 0.0239 (13) 0.0327 (13) −0.0065 (10) 0.0061 (12) 0.0009 (10) C14 0.0326 (14) 0.0335 (14) 0.0417 (15) −0.0060 (11) 0.0162 (13) −0.0004 (12) C15 0.0349 (14) 0.0295 (14) 0.0438 (16) −0.0020 (11) 0.0194 (13) −0.0047 (12) C16 0.0290 (12) 0.0219 (12) 0.0357 (14) −0.0037 (10) 0.0112 (11) −0.0011 (10) N1 0.0386 (12) 0.0272 (11) 0.0309 (11) −0.0008 (9) 0.0189 (10) 0.0017 (9) N2 0.0432 (12) 0.0282 (11) 0.0283 (11) −0.0045 (10) 0.0190 (10) −0.0033 (9) N3 0.0442 (15) 0.0419 (15) 0.0490 (15) −0.0026 (12) 0.0146 (12) 0.0109 (12) N4 0.0473 (15) 0.0413 (14) 0.0349 (13) −0.0036 (12) 0.0121 (12) 0.0038 (11) N5 0.061 (2) 0.105 (3) 0.060 (2) 0.028 (2) 0.0223 (17) 0.0147 (19) O1 0.0480 (11) 0.0255 (9) 0.0327 (9) −0.0090 (8) 0.0215 (9) −0.0016 (7) O2 0.0427 (11) 0.0239 (9) 0.0514 (12) −0.0061 (8) 0.0283 (10) −0.0083 (8) ----- ------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1686 .table-wrap} ----------------------- ------------- ---------------------- -------------- Mn1---O2 1.8669 (18) C8---C9 1.511 (4) Mn1---O1 1.9083 (19) C8---H8A 0.9700 Mn1---N2 1.984 (2) C8---H8B 0.9700 Mn1---N1 1.991 (2) C9---N2 1.478 (3) Mn1---N3 2.130 (3) C9---H9A 0.9700 Br1---C4 1.894 (3) C9---H9B 0.9700 Br2---C13 1.900 (2) C10---N2 1.286 (3) C1---O1 1.340 (3) C10---C11 1.441 (3) C1---C2 1.396 (4) C10---H10 0.9300 C1---C6 1.418 (3) C11---C12 1.406 (3) C2---C3 1.381 (4) C11---C16 1.411 (3) C2---H2 0.9300 C12---C13 1.371 (4) C3---C4 1.392 (4) C12---H12 0.9300 C3---H3 0.9300 C13---C14 1.385 (4) C4---C5 1.367 (4) C14---C15 1.371 (4) C5---C6 1.404 (4) C14---H14 0.9300 C5---H5 0.9300 C15---C16 1.405 (4) C6---C7 1.448 (4) C15---H15 0.9300 C7---N1 1.277 (3) C16---O2 1.322 (3) C7---H7 0.9300 N3---N4 1.175 (3) C8---N1 1.472 (3) N4---N5 1.157 (4) O2---Mn1---O1 95.38 (8) N2---C9---C8 107.2 (2) O2---Mn1---N2 91.73 (8) N2---C9---H9A 110.3 O1---Mn1---N2 159.40 (9) C8---C9---H9A 110.3 O2---Mn1---N1 171.04 (9) N2---C9---H9B 110.3 O1---Mn1---N1 88.41 (9) C8---C9---H9B 110.3 N2---Mn1---N1 82.06 (9) H9A---C9---H9B 108.5 O2---Mn1---N3 97.19 (10) N2---C10---C11 124.5 (2) O1---Mn1---N3 96.43 (10) N2---C10---H10 117.7 N2---Mn1---N3 101.83 (10) C11---C10---H10 117.7 N1---Mn1---N3 90.43 (9) C12---C11---C16 119.7 (2) O1---C1---C2 119.4 (2) C12---C11---C10 117.2 (2) O1---C1---C6 121.9 (2) C16---C11---C10 123.1 (2) C2---C1---C6 118.7 (2) C13---C12---C11 119.6 (2) C3---C2---C1 121.2 (2) C13---C12---H12 120.2 C3---C2---H2 119.4 C11---C12---H12 120.2 C1---C2---H2 119.4 C12---C13---C14 121.3 (2) C2---C3---C4 119.4 (3) C12---C13---Br2 119.5 (2) C2---C3---H3 120.3 C14---C13---Br2 119.22 (19) C4---C3---H3 120.3 C15---C14---C13 119.9 (2) C5---C4---C3 121.0 (2) C15---C14---H14 120.0 C5---C4---Br1 119.94 (19) C13---C14---H14 120.0 C3---C4---Br1 119.0 (2) C14---C15---C16 120.9 (2) C4---C5---C6 120.2 (2) C14---C15---H15 119.6 C4---C5---H5 119.9 C16---C15---H15 119.6 C6---C5---H5 119.9 O2---C16---C15 117.9 (2) C5---C6---C1 119.3 (2) O2---C16---C11 123.6 (2) C5---C6---C7 118.7 (2) C15---C16---C11 118.5 (2) C1---C6---C7 122.0 (2) C7---N1---C8 122.9 (2) N1---C7---C6 123.0 (2) C7---N1---Mn1 123.72 (18) N1---C7---H7 118.5 C8---N1---Mn1 113.33 (16) C6---C7---H7 118.5 C10---N2---C9 121.2 (2) N1---C8---C9 106.7 (2) C10---N2---Mn1 125.88 (17) N1---C8---H8A 110.4 C9---N2---Mn1 112.66 (17) C9---C8---H8A 110.4 N4---N3---Mn1 128.8 (2) N1---C8---H8B 110.4 N5---N4---N3 177.5 (3) C9---C8---H8B 110.4 C1---O1---Mn1 118.36 (16) H8A---C8---H8B 108.6 C16---O2---Mn1 128.97 (16) O1---C1---C2---C3 −178.9 (3) O1---Mn1---N1---C7 −33.1 (2) C6---C1---C2---C3 3.3 (4) N2---Mn1---N1---C7 165.2 (2) C1---C2---C3---C4 −2.1 (4) N3---Mn1---N1---C7 63.3 (2) C2---C3---C4---C5 −1.4 (4) O2---Mn1---N1---C8 34.1 (7) C2---C3---C4---Br1 176.4 (2) O1---Mn1---N1---C8 149.32 (19) C3---C4---C5---C6 3.6 (4) N2---Mn1---N1---C8 −12.37 (19) Br1---C4---C5---C6 −174.3 (2) N3---Mn1---N1---C8 −114.3 (2) C4---C5---C6---C1 −2.3 (4) C11---C10---N2---C9 179.9 (3) C4---C5---C6---C7 178.2 (2) C11---C10---N2---Mn1 6.0 (4) O1---C1---C6---C5 −178.9 (2) C8---C9---N2---C10 −137.6 (3) C2---C1---C6---C5 −1.2 (4) C8---C9---N2---Mn1 37.1 (3) O1---C1---C6---C7 0.6 (4) O2---Mn1---N2---C10 −13.6 (2) C2---C1---C6---C7 178.3 (2) O1---Mn1---N2---C10 96.7 (3) C5---C6---C7---N1 −161.0 (3) N1---Mn1---N2---C10 159.9 (2) C1---C6---C7---N1 19.5 (4) N3---Mn1---N2---C10 −111.3 (2) N1---C8---C9---N2 −45.4 (3) O2---Mn1---N2---C9 172.0 (2) N2---C10---C11---C12 −173.0 (3) O1---Mn1---N2---C9 −77.7 (3) N2---C10---C11---C16 5.3 (4) N1---Mn1---N2---C9 −14.4 (2) C16---C11---C12---C13 1.7 (4) N3---Mn1---N2---C9 74.3 (2) C10---C11---C12---C13 −179.9 (2) O2---Mn1---N3---N4 12.9 (3) C11---C12---C13---C14 0.5 (4) O1---Mn1---N3---N4 −83.4 (3) C11---C12---C13---Br2 −178.1 (2) N2---Mn1---N3---N4 106.2 (3) C12---C13---C14---C15 −0.7 (4) N1---Mn1---N3---N4 −171.8 (3) Br2---C13---C14---C15 178.0 (2) Mn1---N3---N4---N5 −177 (100) C13---C14---C15---C16 −1.5 (4) C2---C1---O1---Mn1 139.8 (2) C14---C15---C16---O2 −174.8 (3) C6---C1---O1---Mn1 −42.5 (3) C14---C15---C16---C11 3.7 (4) O2---Mn1---O1---C1 −138.02 (18) C12---C11---C16---O2 174.7 (2) N2---Mn1---O1---C1 112.3 (3) C10---C11---C16---O2 −3.6 (4) N1---Mn1---O1---C1 50.12 (18) C12---C11---C16---C15 −3.8 (4) N3---Mn1---O1---C1 −40.14 (19) C10---C11---C16---C15 177.9 (2) C15---C16---O2---Mn1 168.3 (2) C6---C7---N1---C8 −177.5 (2) C11---C16---O2---Mn1 −10.2 (4) C6---C7---N1---Mn1 5.1 (4) O1---Mn1---O2---C16 −144.9 (2) C9---C8---N1---C7 −142.4 (3) N2---Mn1---O2---C16 15.7 (2) C9---C8---N1---Mn1 35.2 (3) N1---Mn1---O2---C16 −30.2 (7) O2---Mn1---N1---C7 −148.3 (5) N3---Mn1---O2---C16 117.9 (2) ----------------------- ------------- ---------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.486759

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052106/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m322", "authors": [ { "first": "Yingxia", "last": "Liu" } ] }

PMC3052107

Related literature {#sec1} ================== For general background to the biological activity of salicylaldehydes and their derivatives, see: Jahnke *et al.* (1993[@bb4]); Pelttari *et al.* (2007[@bb6]); Fillebeen & Pantopoulos (2010[@bb3]); Fan *et al.* (2010[@bb2]). For related structures, see: Mori *et al.* (2010[@bb5]); Potapov *et al.* (2009[@bb7]); Purushothaman & Raghunathan (2009[@bb8]). For the preparation of the title compound, see: Purushothaman & Raghunathan (2009[@bb8]); Zhang *et al.* (2010[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~23~H~20~Br~2~O~4~*M* *~r~* = 520.19Monoclinic,*a* = 12.867 (7) Å*b* = 18.07 (1) Å*c* = 9.649 (5) Åβ = 108.955 (6)°*V* = 2122 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 3.85 mm^−1^*T* = 296 K0.34 × 0.32 × 0.28 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb9]) *T* ~min~ = 0.281, *T* ~max~ = 0.34115392 measured reflections3944 independent reflections1905 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.063 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.062*wR*(*F* ^2^) = 0.207*S* = 1.023944 reflections263 parametersH-atom parameters constrainedΔρ~max~ = 0.79 e Å^−3^Δρ~min~ = −0.75 e Å^−3^ {#d5e452} Data collection: *APEX2* (Bruker, 2007[@bb1]); cell refinement: *SAINT* (Bruker, 2007[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb10]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb10]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb10]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100643X/rk2257sup1.cif](http://dx.doi.org/10.1107/S160053681100643X/rk2257sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100643X/rk2257Isup2.hkl](http://dx.doi.org/10.1107/S160053681100643X/rk2257Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rk2257&file=rk2257sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rk2257sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rk2257&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RK2257](http://scripts.iucr.org/cgi-bin/sendsup?rk2257)). The authors acknowledge the Fundamental Research Funds for the Central Universities (lzujbky-2010-43) and the Research Foundation for Young Teachers Possessing a Doctoral Degree of Lanzhou University for financial support. Comment ======= It is reported that salicylaldehydes and their derivatives have showed a wide variety of biological activities, such as antiseptic, labelling cell, antiproliferative and pesticidal (Jahnke *et al.*, 1993; Pelttari *et al.*, 2007; Fillebeen & Pantopoulos, 2010; Fan *et al.*, 2010). As an important class of aldehydes, substituted aldehydes also exhibit potential biological activities. The related structures also have been reported (Mori *et al.*, 2010; Potapov *et al.*, 2009; Purushothaman & Raghunathan, 2009). On this base, the title compound was synthesized. In the title compound (Fig. 1), a dihedral angle 63.0 (2)° is observed between benzene rings on the both ends of molecule. The crystal structure is stabilized by weak intramolecular C---H···O bonds. The molecule of the title compound is linked by the C---H···Br bonding (Fig. 2) in to the *Z* formation. Furthermore, the weak intermolecular π--π stacking interactions - *Cg*1···*Cg*2^ii^= 3.698 (4)Å, *Cg*3···*Cg*3^iii^ = 4.193 (5)Å, where *Cg*1 is centroid of the ring C2--C7, *Cg*2 is centroid of the ring C9--C14 and *Cg*3 is centroid of the ring C17--C22. Symmetry codes: (ii) -*x*, 1-*y*, -*z*; (iii) 1-*x*, 1-*y*, 1-*z*. Experimental {#experimental} ============ All reagents and solvents were obtained from commercial sources and needed to be further purified. The title compound was synthesized according to the related literature (Purushothaman & Raghunathan, 2009). A solution of salicylaldehyde (2 mmol in 10 ml acetone) was slowly added dropwise to a suspension of 1,2-bis(2-(bromomethyl)phenoxy) ethane (1 mmol in 20 ml acetone) prepared according to the reported method (Zhang *et al.*, 2010) and anhydrous potassium carbonate (2 mmol). The mixture was refluxed for 8 h. The reaction mixture was then cooled to room temperature and filtered. After this period, the residue was dissolved and extracted by ethyl acetate. The combined organical layer was washed with water and then dried with anhydrous sodium sulfate. After that the solvent was evaporated under vacuum to give the product. The obtained residue was purified by flash column chromatography on silica gel using petroleum ether/ethylacetate (5:2) mixtures as eluent. Refinement {#refinement} ========== All H atoms were found from difference Fourier maps and were subsequently refined in a riding-model approximation with C---H distances ranging from 0.93Å to 0.98Å and with *U*~iso~(H) = 1.2 *U*~eq~(C) of the carrier atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o714-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the C---H···Bri interactions in the crystal structure of the title compound. Symmetry code: (i) -x+1, y+1/2, -z+1/2). ::: ![](e-67-0o714-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e197 .table-wrap} ------------------------- --------------------------------------- C~23~H~20~Br~2~O~4~ *F*(000) = 1040 *M~r~* = 520.19 *D*~x~ = 1.628 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 1808 reflections *a* = 12.867 (7) Å θ = 2.3--17.5° *b* = 18.07 (1) Å µ = 3.85 mm^−1^ *c* = 9.649 (5) Å *T* = 296 K β = 108.955 (6)° Block, colourless *V* = 2122 (2) Å^3^ 0.34 × 0.32 × 0.28 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e327 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 3944 independent reflections Radiation source: fine-focus sealed tube 1905 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.063 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −15→15 *T*~min~ = 0.281, *T*~max~ = 0.341 *k* = −21→21 15392 measured reflections *l* = −11→11 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e444 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.062 H-atom parameters constrained *wR*(*F*^2^) = 0.207 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.1049*P*)^2^ + 0.4797*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.02 (Δ/σ)~max~ \< 0.001 3944 reflections Δρ~max~ = 0.79 e Å^−3^ 263 parameters Δρ~min~ = −0.75 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0020 (3) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e625 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*-factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e724 .table-wrap} ------ ------------- ------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.56817 (7) 0.30130 (6) 0.29797 (13) 0.1092 (5) Br2 0.37069 (9) 0.31794 (5) −0.00106 (10) 0.0986 (5) C1 −0.1269 (7) 0.7137 (4) −0.1294 (8) 0.069 (2) H1 −0.1621 0.6777 −0.0919 0.083\* C2 −0.0059 (6) 0.7075 (3) −0.0932 (6) 0.0509 (16) C3 0.0495 (7) 0.7556 (4) −0.1572 (7) 0.0658 (19) H3 0.0096 0.7922 −0.2199 0.079\* C4 0.1583 (7) 0.7514 (4) −0.1323 (8) 0.073 (2) H4 0.1932 0.7846 −0.1761 0.088\* C5 0.2176 (6) 0.6962 (4) −0.0397 (8) 0.070 (2) H5 0.2930 0.6929 −0.0213 0.084\* C6 0.1660 (6) 0.6458 (4) 0.0260 (7) 0.0551 (16) H6 0.2062 0.6085 0.0865 0.066\* C7 0.0548 (6) 0.6522 (3) −0.0001 (6) 0.0511 (16) C8 0.0522 (5) 0.5531 (3) 0.1655 (7) 0.0487 (15) H8A 0.1057 0.5775 0.2474 0.058\* H8B 0.0905 0.5182 0.1229 0.058\* C9 −0.0317 (5) 0.5130 (3) 0.2169 (6) 0.0470 (15) C10 −0.1419 (6) 0.5287 (4) 0.1643 (7) 0.0617 (18) H10 −0.1676 0.5664 0.0961 0.074\* C11 −0.2162 (6) 0.4878 (5) 0.2135 (8) 0.070 (2) H11 −0.2910 0.4979 0.1766 0.084\* C12 −0.1791 (7) 0.4340 (4) 0.3138 (8) 0.071 (2) H12 −0.2284 0.4073 0.3465 0.085\* C13 −0.0685 (6) 0.4184 (4) 0.3684 (7) 0.0602 (17) H13 −0.0436 0.3811 0.4378 0.072\* C14 0.0057 (5) 0.4576 (3) 0.3211 (7) 0.0487 (16) C15 0.1611 (5) 0.3890 (3) 0.4722 (6) 0.0536 (16) H15A 0.1381 0.3412 0.4268 0.064\* H15B 0.1347 0.3939 0.5552 0.064\* C16 0.2849 (6) 0.3950 (4) 0.5223 (7) 0.0670 (19) H16A 0.3066 0.4437 0.5639 0.080\* H16B 0.3163 0.3586 0.5984 0.080\* C17 0.3652 (5) 0.4407 (4) 0.3435 (7) 0.0556 (17) C18 0.3584 (6) 0.5154 (4) 0.3772 (8) 0.0675 (19) H18 0.3226 0.5295 0.4426 0.081\* C19 0.4055 (6) 0.5681 (4) 0.3121 (9) 0.077 (2) H19 0.4046 0.6176 0.3381 0.092\* C20 0.4531 (6) 0.5485 (5) 0.2106 (9) 0.076 (2) H20 0.4825 0.5846 0.1656 0.091\* C21 0.4579 (6) 0.4750 (5) 0.1743 (8) 0.071 (2) H21 0.4906 0.4622 0.1047 0.086\* C22 0.4145 (5) 0.4197 (4) 0.2401 (7) 0.0536 (16) C23 0.4210 (6) 0.3400 (4) 0.2060 (8) 0.0657 (19) H23 0.3725 0.3135 0.2490 0.079\* O1 −0.1819 (4) 0.7608 (3) −0.2023 (5) 0.0824 (16) O2 −0.0053 (3) 0.6067 (2) 0.0578 (4) 0.0549 (11) O3 0.1171 (4) 0.4474 (2) 0.3681 (4) 0.0560 (11) O4 0.3266 (4) 0.3834 (2) 0.4054 (5) 0.0737 (14) ------ ------------- ------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1404 .table-wrap} ----- ------------ ------------ ------------- ------------ ------------ ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0693 (7) 0.0994 (8) 0.1485 (10) 0.0213 (5) 0.0212 (6) 0.0112 (6) Br2 0.1243 (9) 0.0954 (7) 0.0791 (7) 0.0014 (5) 0.0372 (6) −0.0179 (5) C1 0.084 (6) 0.059 (4) 0.059 (5) 0.000 (4) 0.015 (4) 0.000 (4) C2 0.070 (5) 0.037 (3) 0.042 (4) −0.006 (3) 0.013 (3) −0.004 (3) C3 0.087 (6) 0.052 (4) 0.054 (4) −0.005 (4) 0.017 (4) −0.002 (3) C4 0.096 (6) 0.059 (5) 0.065 (5) −0.022 (4) 0.027 (5) 0.010 (4) C5 0.063 (5) 0.082 (5) 0.064 (5) −0.015 (4) 0.019 (4) −0.008 (4) C6 0.058 (5) 0.051 (4) 0.049 (4) −0.005 (3) 0.008 (3) −0.001 (3) C7 0.062 (5) 0.046 (4) 0.041 (4) −0.004 (3) 0.011 (3) −0.007 (3) C8 0.056 (4) 0.040 (3) 0.051 (4) 0.001 (3) 0.019 (3) 0.004 (3) C9 0.056 (4) 0.044 (4) 0.042 (4) 0.000 (3) 0.016 (3) −0.010 (3) C10 0.073 (5) 0.055 (4) 0.060 (4) 0.005 (4) 0.026 (4) −0.005 (3) C11 0.051 (4) 0.087 (5) 0.077 (5) −0.013 (4) 0.030 (4) −0.016 (5) C12 0.083 (6) 0.078 (5) 0.071 (5) −0.028 (4) 0.049 (5) −0.019 (4) C13 0.069 (5) 0.062 (4) 0.051 (4) −0.008 (4) 0.021 (4) 0.002 (3) C14 0.058 (5) 0.045 (4) 0.049 (4) −0.005 (3) 0.025 (3) −0.001 (3) C15 0.071 (5) 0.056 (4) 0.034 (3) 0.001 (3) 0.017 (3) 0.006 (3) C16 0.082 (5) 0.069 (5) 0.053 (4) 0.004 (4) 0.025 (4) 0.006 (4) C17 0.047 (4) 0.060 (4) 0.056 (4) 0.000 (3) 0.012 (3) 0.003 (3) C18 0.064 (5) 0.065 (5) 0.075 (5) 0.008 (4) 0.024 (4) 0.011 (4) C19 0.064 (5) 0.057 (4) 0.086 (6) 0.004 (4) −0.006 (5) 0.003 (4) C20 0.063 (5) 0.082 (6) 0.079 (6) −0.023 (4) 0.020 (4) 0.013 (4) C21 0.061 (5) 0.088 (6) 0.064 (5) −0.019 (4) 0.018 (4) −0.002 (4) C22 0.038 (4) 0.069 (4) 0.052 (4) −0.005 (3) 0.011 (3) −0.003 (3) C23 0.061 (5) 0.064 (4) 0.081 (5) 0.007 (3) 0.035 (4) 0.001 (4) O1 0.089 (4) 0.072 (3) 0.068 (3) 0.029 (3) 0.000 (3) 0.008 (3) O2 0.058 (3) 0.050 (3) 0.057 (3) 0.002 (2) 0.019 (2) 0.014 (2) O3 0.061 (3) 0.058 (3) 0.051 (3) −0.002 (2) 0.021 (2) 0.011 (2) O4 0.097 (4) 0.059 (3) 0.084 (3) 0.006 (3) 0.056 (3) 0.007 (3) ----- ------------ ------------ ------------- ------------ ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1942 .table-wrap} ----------------------- ------------ ----------------------- ------------ Br1---C23 1.941 (7) C12---C13 1.377 (10) Br2---C23 1.931 (7) C12---H12 0.9300 C1---O1 1.182 (8) C13---C14 1.380 (8) C1---C2 1.485 (10) C13---H13 0.9300 C1---H1 0.9300 C14---O3 1.368 (7) C2---C3 1.389 (9) C15---O3 1.441 (7) C2---C7 1.400 (8) C15---C16 1.510 (9) C3---C4 1.344 (10) C15---H15A 0.9700 C3---H3 0.9300 C15---H15B 0.9700 C4---C5 1.389 (10) C16---O4 1.414 (7) C4---H4 0.9300 C16---H16A 0.9700 C5---C6 1.395 (9) C16---H16B 0.9700 C5---H5 0.9300 C17---O4 1.367 (7) C6---C7 1.376 (9) C17---C18 1.397 (9) C6---H6 0.9300 C17---C22 1.397 (9) C7---O2 1.366 (7) C18---C19 1.385 (10) C8---O2 1.437 (7) C18---H18 0.9300 C8---C9 1.510 (8) C19---C20 1.361 (11) C8---H8A 0.9700 C19---H19 0.9300 C8---H8B 0.9700 C20---C21 1.379 (11) C9---C10 1.372 (9) C20---H20 0.9300 C9---C14 1.390 (8) C21---C22 1.394 (9) C10---C11 1.408 (9) C21---H21 0.9300 C10---H10 0.9300 C22---C23 1.486 (9) C11---C12 1.344 (10) C23---H23 0.9800 C11---H11 0.9300 O1---C1---C2 124.9 (7) O3---C14---C13 125.8 (6) O1---C1---H1 117.5 O3---C14---C9 114.6 (5) C2---C1---H1 117.5 C13---C14---C9 119.7 (6) C3---C2---C7 118.2 (7) O3---C15---C16 107.8 (5) C3---C2---C1 119.9 (6) O3---C15---H15A 110.1 C7---C2---C1 121.9 (6) C16---C15---H15A 110.1 C4---C3---C2 122.7 (7) O3---C15---H15B 110.1 C4---C3---H3 118.7 C16---C15---H15B 110.1 C2---C3---H3 118.7 H15A---C15---H15B 108.5 C3---C4---C5 118.6 (7) O4---C16---C15 111.6 (5) C3---C4---H4 120.7 O4---C16---H16A 109.3 C5---C4---H4 120.7 C15---C16---H16A 109.3 C4---C5---C6 121.2 (7) O4---C16---H16B 109.3 C4---C5---H5 119.4 C15---C16---H16B 109.3 C6---C5---H5 119.4 H16A---C16---H16B 108.0 C7---C6---C5 118.8 (6) O4---C17---C18 124.7 (6) C7---C6---H6 120.6 O4---C17---C22 114.9 (6) C5---C6---H6 120.6 C18---C17---C22 120.4 (6) O2---C7---C6 124.6 (6) C19---C18---C17 119.3 (7) O2---C7---C2 114.9 (6) C19---C18---H18 120.4 C6---C7---C2 120.5 (6) C17---C18---H18 120.4 O2---C8---C9 107.8 (5) C20---C19---C18 120.8 (7) O2---C8---H8A 110.1 C20---C19---H19 119.6 C9---C8---H8A 110.1 C18---C19---H19 119.6 O2---C8---H8B 110.1 C19---C20---C21 120.1 (7) C9---C8---H8B 110.1 C19---C20---H20 119.9 H8A---C8---H8B 108.5 C21---C20---H20 119.9 C10---C9---C14 119.3 (6) C20---C21---C22 121.1 (7) C10---C9---C8 122.8 (6) C20---C21---H21 119.5 C14---C9---C8 117.8 (5) C22---C21---H21 119.5 C9---C10---C11 120.0 (7) C17---C22---C21 118.2 (7) C9---C10---H10 120.0 C17---C22---C23 119.5 (6) C11---C10---H10 120.0 C21---C22---C23 122.3 (6) C12---C11---C10 120.1 (7) C22---C23---Br2 113.9 (5) C12---C11---H11 120.0 C22---C23---Br1 111.4 (5) C10---C11---H11 120.0 Br2---C23---Br1 110.4 (3) C11---C12---C13 120.3 (6) C22---C23---H23 106.9 C11---C12---H12 119.8 Br2---C23---H23 106.9 C13---C12---H12 119.8 Br1---C23---H23 106.9 C14---C13---C12 120.6 (7) C7---O2---C8 118.4 (5) C14---C13---H13 119.7 C14---O3---C15 117.5 (5) C12---C13---H13 119.7 C17---O4---C16 121.6 (5) O1---C1---C2---C3 −6.0 (10) O3---C15---C16---O4 −63.5 (7) O1---C1---C2---C7 176.8 (6) O4---C17---C18---C19 176.8 (6) C7---C2---C3---C4 −0.6 (10) C22---C17---C18---C19 −3.0 (10) C1---C2---C3---C4 −178.0 (6) C17---C18---C19---C20 3.4 (11) C2---C3---C4---C5 0.6 (10) C18---C19---C20---C21 −1.9 (11) C3---C4---C5---C6 0.3 (10) C19---C20---C21---C22 0.0 (11) C4---C5---C6---C7 −1.1 (10) O4---C17---C22---C21 −178.7 (6) C5---C6---C7---O2 −179.8 (5) C18---C17---C22---C21 1.1 (9) C5---C6---C7---C2 1.1 (9) O4---C17---C22---C23 0.1 (9) C3---C2---C7---O2 −179.5 (5) C18---C17---C22---C23 179.9 (6) C1---C2---C7---O2 −2.2 (8) C20---C21---C22---C17 0.4 (10) C3---C2---C7---C6 −0.3 (9) C20---C21---C22---C23 −178.3 (7) C1---C2---C7---C6 177.0 (6) C17---C22---C23---Br2 130.6 (5) O2---C8---C9---C10 0.0 (8) C21---C22---C23---Br2 −50.7 (8) O2---C8---C9---C14 179.3 (5) C17---C22---C23---Br1 −103.8 (6) C14---C9---C10---C11 −1.3 (9) C21---C22---C23---Br1 75.0 (7) C8---C9---C10---C11 178.0 (5) C6---C7---O2---C8 6.8 (8) C9---C10---C11---C12 1.0 (10) C2---C7---O2---C8 −174.1 (5) C10---C11---C12---C13 −0.4 (10) C9---C8---O2---C7 177.1 (4) C11---C12---C13---C14 0.0 (10) C13---C14---O3---C15 2.5 (8) C12---C13---C14---O3 179.5 (6) C9---C14---O3---C15 −177.8 (5) C12---C13---C14---C9 −0.3 (9) C16---C15---O3---C14 −172.6 (5) C10---C9---C14---O3 −178.8 (5) C18---C17---O4---C16 −6.4 (10) C8---C9---C14---O3 1.8 (7) C22---C17---O4---C16 173.5 (5) C10---C9---C14---C13 1.0 (9) C15---C16---O4---C17 105.9 (7) C8---C9---C14---C13 −178.4 (5) ----------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2866 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C1---H1···O2 0.93 2.42 2.753 (9) 101 C10---H10···O2 0.93 2.35 2.710 (8) 102 C23---H23···O4 0.98 2.19 2.700 (8) 111 C5---H5···Br1^i^ 0.93 3.03 3.529 (7) 116 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, *y*+1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- C5---H5⋯Br1^i^ 0.93 3.03 3.529 (7) 116 Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.493152

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052107/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o714", "authors": [ { "first": "Juan", "last": "Xia" }, { "first": "Xiang", "last": "Liu" }, { "first": "An-Qi", "last": "Wang" }, { "first": "Zhong-Xing", "last": "Su" } ] }

PMC3052108

Related literature {#sec1} ================== For the pharmacological activity of benzofuran compounds, see: Aslam *et al.* (2006[@bb2]); Galal *et al.* (2009[@bb8]); Khan *et al.* (2005[@bb9]). For natural products with benzofuran rings, see: Akgul & Anil (2003[@bb1]); Soekamto *et al.* (2003[@bb12]). For structural studies of related 3-arylsulfonyl-5-bromo-2-methyl-1-benzofuran derivatives, see: Choi *et al.* (2008[@bb5], 2010[@bb6]). For a review of halogen bonding, see: Politzer *et al.* (2007[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~15~H~17~BrO~3~S*M* *~r~* = 357.26Triclinic,*a* = 6.3452 (1) Å*b* = 8.2065 (1) Å*c* = 14.4866 (2) Åα = 98.842 (1)°β = 97.693 (1)°γ = 96.385 (1)°*V* = 731.95 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 2.95 mm^−1^*T* = 173 K0.33 × 0.26 × 0.23 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2009[@bb4]) *T* ~min~ = 0.585, *T* ~max~ = 0.74613107 measured reflections3377 independent reflections3109 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.034 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.028*wR*(*F* ^2^) = 0.073*S* = 1.073377 reflections182 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.70 e Å^−3^ {#d5e476} Data collection: *APEX2* (Bruker, 2009[@bb4]); cell refinement: *SAINT* (Bruker, 2009[@bb4]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb11]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb11]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb7]) and *DIAMOND* (Brandenburg, 1998[@bb3]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003515/ld2001sup1.cif](http://dx.doi.org/10.1107/S1600536811003515/ld2001sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003515/ld2001Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003515/ld2001Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ld2001&file=ld2001sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ld2001sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ld2001&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LD2001](http://scripts.iucr.org/cgi-bin/sendsup?ld2001)). Comment ======= Many compounds containing a benzofuran ring show diverse pharmacological properties such as antifungal, antitumor and antiviral, and antimicrobial activities (Aslam *et al.*, 2006, Galal *et al.*, 2009, Khan *et al.*, 2005). These compounds occur in a wide range of natural products (Akgul & Anil, 2003; Soekamto *et al.*, 2003). As a part of our ongoing study of the substituent effect on the solid state structures of 3-arylsulfonyl-5-bromo-2-methyl-1-benzofuran analogues (Choi *et al.*, 2008, 2010), we report herein the crystal structure of the title compound. In the title molecule (Fig. 1), the benzofuran unit is essentially planar, with a mean deviation of 0.006 (2) Å from the least-squares plane defined by the nine constituent atoms. The cyclohexyl ring is in the chair form and arylsulfonyl moiety is positioned equatorial relative to the cyclohexyl group. The molecular packing (Fig. 2) is stabilized by intermolecular C---H···O hydrogen bonds - between an arene H atom and the furan O atom (Table 1; C6---H6···O1^i^), and between a methyl H atom and a sulfonyl oxygen (Table 1; C9---H9B···O3^ii^). The crystal structure is further stabilized by Br···O halogen bonding between the bromine and an oxygen of the sulfonyl group \[Br1···O3^iii^ = 3.250 (2) Å, C4---Br1···O3^iii^ = 165.29 (6)°\] (Politzer *et al.*, 2007). The crystal packing (Fig. 2) also exhibits π--π overlap between the benzene and furan rings of neighbouring molecules, with a Cg1···Cg2^iv^ distance of 3.633 (2) Å (Cg1 and Cg2 are the centroids of the C2-C7 benzene ring and the C1/C2/C7/O1/C8 furan ring, respectively), wherein the inter-planar distance between the benzene and furan rings is 3.391 (2) Å. Experimental {#experimental} ============ 77% 3-chloroperoxybenzoic acid (381 mg, 1.7 mmol) was added in small portions to a stirred solution of 5-bromo-3-cyclohexylsulfanyl-2-methyl-1-benzofuran (260 mg, 0.8 mmol) in dichloromethane (40 mL) at 273 K. After being stirred at room temperature for 5h, the mixture was washed with saturated sodium bicarbonate solution and the organic layer was separated, dried over magnesium sulfate, filtered and concentrated at reduced pressure. The residue was purified by column chromatography (hexane--ethyl acetate, 4:1 v/v) to afford the title compound as a colorless solid \[yield 76%, m.p. 446--447 K; *R*~f~ = 0.58 (hexane--ethyl acetate, 4:1 v/v)\]. Single crystals suitable for X-ray diffraction were prepared by slow evaporation of acetone solution of the title compound at room temperature. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding and rotating model, with C---H = 0.95 Å for aryl, 1.00 Å for methine, 0.99 Å for methylene and 0.98 Å for methyl H atoms, respectively. *U*~iso~(H) = 1.2*U*~eq~(C) for aryl, methine, methylene and 1.5*U*~eq~(C) for methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radius. ::: ![](e-67-0o542-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the C---H···O, Br···O and π--π interactions (dotted lines) in the crystal structure of the title compound. \[Symmetry codes: (i) - x + 2, - y + 2, - z + 1; (ii) x + 1, y, z; (iii) - x, - y + 1, - z + 1 ; (iv) - x + 1, - y + 2, - z + 1; (v) x - 1, y, z .\] ::: ![](e-67-0o542-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e198 .table-wrap} ----------------------- --------------------------------------- C~15~H~17~BrO~3~S *Z* = 2 *M~r~* = 357.26 *F*(000) = 364 Triclinic, *P*1 *D*~x~ = 1.621 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 6.3452 (1) Å Cell parameters from 8112 reflections *b* = 8.2065 (1) Å θ = 2.7--27.5° *c* = 14.4866 (2) Å µ = 2.95 mm^−1^ α = 98.842 (1)° *T* = 173 K β = 97.693 (1)° Block, colourless γ = 96.385 (1)° 0.33 × 0.26 × 0.23 mm *V* = 731.95 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e332 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD diffractometer 3377 independent reflections Radiation source: rotating anode 3109 reflections with *I* \> 2σ(*I*) graphite multilayer *R*~int~ = 0.034 Detector resolution: 10.0 pixels mm^-1^ θ~max~ = 27.6°, θ~min~ = 1.4° φ and ω scans *h* = −8→8 Absorption correction: multi-scan (*SADABS*; Bruker, 2009) *k* = −10→10 *T*~min~ = 0.585, *T*~max~ = 0.746 *l* = −18→18 13107 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e455 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.028 Hydrogen site location: difference Fourier map *wR*(*F*^2^) = 0.073 H-atom parameters constrained *S* = 1.07 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0389*P*)^2^ + 0.2624*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3377 reflections (Δ/σ)~max~ = 0.001 182 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.70 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e612 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e657 .table-wrap} ------ ------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.24178 (3) 0.58796 (3) 0.634104 (12) 0.03547 (8) S1 0.21139 (7) 0.69361 (6) 0.22168 (3) 0.02801 (11) O1 0.7467 (2) 0.92120 (16) 0.38017 (9) 0.0310 (3) O2 0.2068 (3) 0.78049 (19) 0.14233 (10) 0.0400 (3) O3 0.0254 (2) 0.6830 (2) 0.26875 (10) 0.0396 (3) C1 0.4294 (3) 0.7824 (2) 0.30762 (12) 0.0267 (4) C2 0.4500 (3) 0.7619 (2) 0.40566 (12) 0.0261 (3) C3 0.3234 (3) 0.6829 (2) 0.46111 (12) 0.0284 (4) H3 0.1862 0.6225 0.4355 0.034\* C4 0.4078 (3) 0.6967 (2) 0.55581 (13) 0.0286 (4) C5 0.6076 (3) 0.7838 (3) 0.59542 (13) 0.0324 (4) H5 0.6582 0.7887 0.6607 0.039\* C6 0.7337 (3) 0.8635 (3) 0.54056 (14) 0.0330 (4) H6 0.8706 0.9243 0.5663 0.040\* C7 0.6495 (3) 0.8496 (2) 0.44644 (13) 0.0284 (4) C8 0.6100 (3) 0.8776 (2) 0.29616 (13) 0.0290 (4) C9 0.6862 (4) 0.9444 (3) 0.21558 (15) 0.0365 (4) H9A 0.5693 0.9244 0.1619 0.055\* H9B 0.8070 0.8887 0.1974 0.055\* H9C 0.7330 1.0643 0.2340 0.055\* C10 0.2636 (3) 0.4859 (2) 0.18543 (12) 0.0244 (3) H10 0.3071 0.4386 0.2436 0.029\* C11 0.4467 (3) 0.4811 (2) 0.12705 (13) 0.0288 (4) H11A 0.5802 0.5433 0.1657 0.035\* H11B 0.4124 0.5353 0.0714 0.035\* C12 0.4807 (3) 0.3011 (3) 0.09420 (14) 0.0328 (4) H12A 0.5919 0.2997 0.0523 0.039\* H12B 0.5334 0.2522 0.1498 0.039\* C13 0.2750 (3) 0.1955 (3) 0.04136 (16) 0.0419 (5) H13A 0.2310 0.2363 −0.0182 0.050\* H13B 0.3015 0.0787 0.0249 0.050\* C14 0.0960 (4) 0.2023 (3) 0.10074 (18) 0.0474 (6) H14A 0.1341 0.1512 0.1573 0.057\* H14B −0.0373 0.1371 0.0636 0.057\* C15 0.0563 (3) 0.3812 (3) 0.13187 (14) 0.0358 (4) H15A −0.0560 0.3825 0.1732 0.043\* H15B 0.0050 0.4294 0.0757 0.043\* ------ ------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1146 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.03585 (12) 0.04254 (13) 0.02647 (11) 0.00000 (9) 0.00393 (8) 0.00562 (8) S1 0.0262 (2) 0.0334 (2) 0.0240 (2) 0.00874 (18) 0.00065 (16) 0.00314 (18) O1 0.0298 (7) 0.0289 (7) 0.0321 (7) 0.0000 (6) 0.0053 (5) 0.0004 (5) O2 0.0471 (8) 0.0414 (8) 0.0332 (7) 0.0134 (7) −0.0016 (6) 0.0129 (6) O3 0.0277 (7) 0.0553 (10) 0.0352 (7) 0.0134 (7) 0.0045 (6) 0.0009 (7) C1 0.0294 (9) 0.0247 (9) 0.0243 (8) 0.0049 (7) 0.0024 (7) −0.0003 (7) C2 0.0272 (8) 0.0236 (8) 0.0248 (8) 0.0043 (7) 0.0017 (6) −0.0026 (7) C3 0.0280 (9) 0.0290 (9) 0.0251 (8) 0.0023 (7) 0.0012 (7) −0.0013 (7) C4 0.0308 (9) 0.0270 (9) 0.0266 (8) 0.0035 (7) 0.0038 (7) 0.0007 (7) C5 0.0348 (10) 0.0330 (10) 0.0255 (8) 0.0026 (8) −0.0020 (7) −0.0002 (7) C6 0.0278 (9) 0.0323 (10) 0.0327 (10) −0.0025 (8) −0.0031 (7) −0.0025 (8) C7 0.0282 (9) 0.0256 (9) 0.0296 (9) 0.0029 (7) 0.0045 (7) −0.0009 (7) C8 0.0337 (9) 0.0242 (9) 0.0287 (9) 0.0076 (7) 0.0051 (7) 0.0000 (7) C9 0.0413 (11) 0.0336 (10) 0.0379 (10) 0.0078 (9) 0.0114 (9) 0.0098 (8) C10 0.0228 (8) 0.0285 (9) 0.0197 (7) 0.0003 (7) 0.0004 (6) 0.0023 (6) C11 0.0243 (8) 0.0303 (9) 0.0312 (9) 0.0018 (7) 0.0057 (7) 0.0032 (7) C12 0.0284 (9) 0.0316 (10) 0.0353 (10) 0.0052 (8) 0.0019 (7) −0.0018 (8) C13 0.0363 (11) 0.0423 (12) 0.0377 (11) 0.0002 (9) −0.0012 (9) −0.0124 (9) C14 0.0374 (11) 0.0441 (13) 0.0496 (13) −0.0147 (10) 0.0052 (10) −0.0107 (10) C15 0.0213 (8) 0.0485 (12) 0.0313 (9) −0.0042 (8) 0.0018 (7) −0.0047 (9) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1526 .table-wrap} -------------------- -------------- ----------------------- -------------- Br1---O3^i^ 3.250 (2) C9---H9A 0.9800 Br1---C4 1.901 (2) C9---H9B 0.9800 S1---O3 1.4409 (15) C9---H9C 0.9800 S1---O2 1.4416 (15) C10---C11 1.526 (2) S1---C1 1.7408 (18) C10---C15 1.530 (2) S1---C10 1.7852 (18) C10---H10 1.0000 O1---C8 1.370 (2) C11---C12 1.529 (3) O1---C7 1.378 (2) C11---H11A 0.9900 C1---C8 1.357 (3) C11---H11B 0.9900 C1---C2 1.446 (2) C12---C13 1.523 (3) C2---C3 1.388 (3) C12---H12A 0.9900 C2---C7 1.392 (3) C12---H12B 0.9900 C3---C4 1.387 (2) C13---C14 1.515 (3) C3---H3 0.9500 C13---H13A 0.9900 C4---C5 1.387 (3) C13---H13B 0.9900 C5---C6 1.383 (3) C14---C15 1.527 (3) C5---H5 0.9500 C14---H14A 0.9900 C6---C7 1.379 (3) C14---H14B 0.9900 C6---H6 0.9500 C15---H15A 0.9900 C8---C9 1.479 (3) C15---H15B 0.9900 C4---Br1---O3^i^ 165.29 (6) H9B---C9---H9C 109.5 O3---S1---O2 118.38 (9) C11---C10---C15 112.06 (14) O3---S1---C1 106.84 (9) C11---C10---S1 111.82 (13) O2---S1---C1 109.77 (9) C15---C10---S1 108.98 (13) O3---S1---C10 107.26 (9) C11---C10---H10 107.9 O2---S1---C10 109.22 (9) C15---C10---H10 107.9 C1---S1---C10 104.45 (8) S1---C10---H10 107.9 C8---O1---C7 106.96 (14) C10---C11---C12 110.24 (15) C8---C1---C2 107.72 (16) C10---C11---H11A 109.6 C8---C1---S1 127.65 (14) C12---C11---H11A 109.6 C2---C1---S1 124.60 (14) C10---C11---H11B 109.6 C3---C2---C7 119.65 (16) C12---C11---H11B 109.6 C3---C2---C1 135.86 (17) H11A---C11---H11B 108.1 C7---C2---C1 104.48 (16) C13---C12---C11 111.97 (16) C4---C3---C2 116.54 (17) C13---C12---H12A 109.2 C4---C3---H3 121.7 C11---C12---H12A 109.2 C2---C3---H3 121.7 C13---C12---H12B 109.2 C3---C4---C5 123.20 (18) C11---C12---H12B 109.2 C3---C4---Br1 118.01 (14) H12A---C12---H12B 107.9 C5---C4---Br1 118.78 (14) C14---C13---C12 111.09 (17) C6---C5---C4 120.46 (17) C14---C13---H13A 109.4 C6---C5---H5 119.8 C12---C13---H13A 109.4 C4---C5---H5 119.8 C14---C13---H13B 109.4 C7---C6---C5 116.23 (17) C12---C13---H13B 109.4 C7---C6---H6 121.9 H13A---C13---H13B 108.0 C5---C6---H6 121.9 C13---C14---C15 111.34 (19) O1---C7---C6 125.59 (17) C13---C14---H14A 109.4 O1---C7---C2 110.49 (16) C15---C14---H14A 109.4 C6---C7---C2 123.91 (18) C13---C14---H14B 109.4 C1---C8---O1 110.33 (16) C15---C14---H14B 109.4 C1---C8---C9 134.57 (18) H14A---C14---H14B 108.0 O1---C8---C9 115.09 (17) C14---C15---C10 110.09 (16) C8---C9---H9A 109.5 C14---C15---H15A 109.6 C8---C9---H9B 109.5 C10---C15---H15A 109.6 H9A---C9---H9B 109.5 C14---C15---H15B 109.6 C8---C9---H9C 109.5 C10---C15---H15B 109.6 H9A---C9---H9C 109.5 H15A---C15---H15B 108.2 O3---S1---C1---C8 −150.39 (17) C3---C2---C7---C6 0.4 (3) O2---S1---C1---C8 −20.86 (19) C1---C2---C7---C6 179.62 (18) C10---S1---C1---C8 96.14 (18) C2---C1---C8---O1 −0.3 (2) O3---S1---C1---C2 31.47 (18) S1---C1---C8---O1 −178.67 (13) O2---S1---C1---C2 161.01 (15) C2---C1---C8---C9 −179.0 (2) C10---S1---C1---C2 −81.99 (16) S1---C1---C8---C9 2.6 (3) C8---C1---C2---C3 178.9 (2) C7---O1---C8---C1 0.59 (19) S1---C1---C2---C3 −2.7 (3) C7---O1---C8---C9 179.58 (15) C8---C1---C2---C7 −0.1 (2) O3---S1---C10---C11 175.09 (12) S1---C1---C2---C7 178.32 (13) O2---S1---C10---C11 45.64 (14) C7---C2---C3---C4 −0.3 (3) C1---S1---C10---C11 −71.74 (14) C1---C2---C3---C4 −179.25 (19) O3---S1---C10---C15 50.66 (14) C2---C3---C4---C5 −0.1 (3) O2---S1---C10---C15 −78.79 (14) C2---C3---C4---Br1 −179.16 (13) C1---S1---C10---C15 163.83 (13) C3---C4---C5---C6 0.4 (3) C15---C10---C11---C12 −55.1 (2) Br1---C4---C5---C6 179.53 (15) S1---C10---C11---C12 −177.82 (12) C4---C5---C6---C7 −0.4 (3) C10---C11---C12---C13 54.5 (2) C8---O1---C7---C6 −179.79 (18) C11---C12---C13---C14 −55.5 (3) C8---O1---C7---C2 −0.68 (19) C12---C13---C14---C15 56.4 (3) C5---C6---C7---O1 178.95 (17) C13---C14---C15---C10 −56.4 (2) C5---C6---C7---C2 0.0 (3) C11---C10---C15---C14 56.2 (2) C3---C2---C7---O1 −178.72 (15) S1---C10---C15---C14 −179.50 (15) C1---C2---C7---O1 0.5 (2) -------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) −*x*, −*y*+1, −*z*+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2340 .table-wrap} -------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C6---H6···O1^ii^ 0.95 2.57 3.518 (2) 174 C9---H9B···O3^iii^ 0.98 2.55 3.303 (2) 134 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −*x*+2, −*y*+2, −*z*+1; (iii) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- --------- ------- ----------- ------------- C6---H6⋯O1^i^ 0.95 2.57 3.518 (2) 174 C9---H9*B*⋯O3^ii^ 0.98 2.55 3.303 (2) 134 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.499799

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052108/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o542", "authors": [ { "first": "Hong Dae", "last": "Choi" }, { "first": "Pil Ja", "last": "Seo" }, { "first": "Byeng Wha", "last": "Son" }, { "first": "Uk", "last": "Lee" } ] }

PMC3052109

Related literature {#sec1} ================== For the isolation of β-himachalene, see: Joseph & Dev (1968[@bb10]); Plattier & Teisseire (1974[@bb12]). For the reactivity of β-himachalene, see: Lassaba *et al.* (1998[@bb11]); Chekroun *et al.* (2000[@bb2]); El Jamili *et al.* (2002[@bb6]); Dakir *et al.* (2004[@bb4]). For the biological activity of β-himachalene, see: Daoubi *et al.* (2004[@bb5]). For conformational analysis, see: Cremer & Pople (1975[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~23~Cl~2~NO*M* *~r~* = 316.25Monoclinic,*a* = 7.7570 (7) Å*b* = 9.7041 (9) Å*c* = 10.6901 (10) Åβ = 93.432 (3)°*V* = 803.25 (13) Å^3^*Z* = 2Mo *K*α radiationμ = 0.40 mm^−1^*T* = 298 K0.41 × 0.33 × 0.26 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometer4954 measured reflections2355 independent reflections2297 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.015 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.028*wR*(*F* ^2^) = 0.080*S* = 1.082355 reflections193 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.22 e Å^−3^Absolute structure: Flack & Bernardinelli (2000[@bb9]), 614 Friedel pairsFlack parameter: −0.02 (5) {#d5e465} Data collection: *APEX2* (Bruker, 2009[@bb1]); cell refinement: *SAINT-Plus* (Bruker, 2009[@bb1]); data reduction: *SAINT-Plus*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb13]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb13]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb7]) and *PLATON* (Spek, 2009[@bb14]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005307/fj2396sup1.cif](http://dx.doi.org/10.1107/S1600536811005307/fj2396sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005307/fj2396Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005307/fj2396Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?fj2396&file=fj2396sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?fj2396sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?fj2396&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [FJ2396](http://scripts.iucr.org/cgi-bin/sendsup?fj2396)). We thank the National Center of Scientific and Technological Research (CNRST) which supports our scientific research. Comment ======= The essential oil of the Alas cedar (Cedrus atlantica) consist mainly (50%) of a bicyclic hydrocarbon called β-himachalene (Joseph & Dev (1968); Plattier & Teisseire(1974)). The reactivity of this sesquiterpene and its derivatives has been studied extensively by our team in order to prepare new products having biological proprieties (Lassaba *et al.*, 1998; Chekroun *et al.*, 2000; El Jamili *et al.*, 2002; Dakir *et al.*, 2004). Indeed, these compounds were tested, using the food poisoning technique, for their potential antifungal activity against phytopathogen Botrytis cinerea (Daoubi *et al.*, 2004). Thus the action of one equivalent of dichlorocarbene, generated *in situ* from chloroform in the presence of sodium hydroxide as base and n-benzyltriethylammonium chloride as catalyst, on β-himachalene produces only (1*S*,3*R*,8*R*)-2,2-dichloro-3,7,7,10- tetramethyltricyclo\[6.4.0.0^1,3^\] dodec-9-ene (El Jamili *et al.*, 2002). Treatment of the latter by two equivalents of *N*-bromosccinimide (NBS) give (1*S*, 3*R*, 8*R*, 11*R*)-2,2-dichloro-3,7,7,10-tetralethyltricyclo\[6.4.0.0^1,3^\] dodec-9-en-11-one(Dakir *et al.*, 2004). This enone was treated with the sodium azide in trifluoroacetic acide medium, give with a yield (60%) (1*S*, 3*R*, 8*R*) -9-(1-aminoethylidene)-2,2-dichloro-3,7,7- trimethyltricyclo\[6.3.0.0^1,3^\]undecan -10-one. The structure of this new product was determined by NMR spectral analysis of 1H, 13 C and mass spectroscopy and confirmed by its single-crystal X-ray structure. The molecule is built up from two fused five-membered and seven-membered rings (Fig. 1). The five-membered ring adopts a twisted conformation,as indicated by Cremer & Pople (1975) puckering parameters Q = 0.2822 (2) Å and φ = 199.2 (4)°. The seven-membered ring displays a chair conformation with QT = 0.7470 (2) Å, θ2 = 27.72 (2)°, φ2 = -51.85 (14)° and φ3 =-78.15 (2)°. In the crystal structure, molecules are linked into chains (Fig. 2) running along the *b* axis by intermolecular N---H···O hydrogen bonds (Table 1) involving the O1 and N atoms. Owing to the presence of Cl atoms, the absolute configuration could be fully confirmed, by refining the Flack parameter (Flack & Bernardinelli (2000)) as C1(S), C3(*R*)and C8(*R*). Experimental {#experimental} ============ To a solution of enone 1 g (3.32 mmol) in 20 ml of trifluoroacetic acid at 10 °C was added with stirring 1 g (15.38 mmol) of NaN3. After being stirred at room temperature for 24 h, the reaction mixture was neutralized with a solution of Na2CO3 (10%) and extracted three time with diethylether (3x20ml). The combined organic phases were dried on Na2SO4, filtred and concentrated at reduced pressure to give the crude product which was chromatographed on a silica gel column with hexane- ether as eluent (20/80) to give 630 mg(1.99 mmol) of (1*S*, 3*R*, 8*R*)-9-(1-aminoethylidene)-2,2-dichloro-3,7,7-trimethyltricyclo \[6.3.0.0^1,3^\]undecan -10-one.The title compound was recrystallized in diethylether. Refinement {#refinement} ========== except H1 and H2,all H atoms were fixed geometrically and treated as riding with C---H = 0.96 Å (methyl), 0.97 Å (methylene), 0.98Å (methine) with *U*~iso~(H) = 1.2U~eq~ (methylene, methine) or *U*~iso~(H) = 1.5*U*~eq~ (methyl). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### : Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability. level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o645-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### : Partial packing view showing the C---H···O interactions (dashed lines) and the formation of a chain parallel to the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity. \[Symmetry code:(i) 2 - y, x-y, z - 1/3\] ::: ![](e-67-0o645-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e238 .table-wrap} ------------------------ --------------------------------------- C~16~H~23~Cl~2~NO *F*(000) = 336 *M~r~* = 316.25 *D*~x~ = 1.308 Mg m^−3^ Monoclinic, *P*2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2yb Cell parameters from 4954 reflections *a* = 7.7570 (7) Å θ = 3.4--26.4° *b* = 9.7041 (9) Å µ = 0.40 mm^−1^ *c* = 10.6901 (10) Å *T* = 298 K β = 93.432 (3)° Prism, colourless *V* = 803.25 (13) Å^3^ 0.41 × 0.33 × 0.26 mm *Z* = 2 ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e363 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2297 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.015 graphite θ~max~ = 26.4°, θ~min~ = 3.4° ω and φ scans *h* = −9→9 4954 measured reflections *k* = −12→6 2355 independent reflections *l* = −12→13 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e461 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.028 H atoms treated by a mixture of independent and constrained refinement *wR*(*F*^2^) = 0.080 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0528*P*)^2^ + 0.0821*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.08 (Δ/σ)~max~ = 0.001 2355 reflections Δρ~max~ = 0.24 e Å^−3^ 193 parameters Δρ~min~ = −0.22 e Å^−3^ 1 restraint Absolute structure: Flack & Bernardinelli (2000), 614 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: −0.02 (5) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e629 .table-wrap} -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e649 .table-wrap} ------ ------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ H2 1.000 (3) −0.257 (3) 0.553 (2) 0.042 (6)\* H1 0.933 (3) −0.125 (4) 0.502 (3) 0.050 (7)\* Cl1 0.88492 (8) 0.36063 (7) 0.85606 (7) 0.06081 (18) Cl2 0.79425 (7) 0.12962 (6) 1.00496 (4) 0.05055 (16) C9 0.7491 (2) −0.0408 (2) 0.66044 (16) 0.0293 (4) O1 0.8629 (2) 0.07077 (17) 0.48287 (13) 0.0448 (4) C8 0.6205 (2) 0.0004 (2) 0.75543 (15) 0.0274 (4) H8 0.6565 −0.0383 0.8375 0.033\* C1 0.6443 (2) 0.15793 (19) 0.75843 (15) 0.0297 (4) C12 0.8402 (2) −0.16350 (19) 0.65295 (17) 0.0321 (4) C10 0.7797 (2) 0.0713 (2) 0.57971 (17) 0.0333 (4) N1 0.9341 (3) −0.1878 (2) 0.5548 (2) 0.0444 (4) C7 0.4310 (2) −0.0475 (2) 0.71640 (17) 0.0357 (4) C3 0.5434 (3) 0.2575 (2) 0.83808 (17) 0.0362 (4) C2 0.7312 (2) 0.2285 (2) 0.87178 (18) 0.0363 (4) C4 0.4090 (3) 0.2029 (3) 0.9238 (2) 0.0462 (5) H4A 0.4656 0.1417 0.9852 0.055\* H4B 0.3620 0.2797 0.9688 0.055\* C16 0.4318 (3) −0.2036 (3) 0.6976 (2) 0.0451 (5) H16A 0.5082 −0.2267 0.6333 0.068\* H16B 0.3171 −0.2344 0.6731 0.068\* H16C 0.4707 −0.2478 0.7745 0.068\* C11 0.7012 (3) 0.2010 (2) 0.62976 (17) 0.0386 (5) H11A 0.6033 0.2311 0.5759 0.046\* H11B 0.7855 0.2747 0.6371 0.046\* C14 0.4943 (4) 0.3966 (3) 0.7812 (2) 0.0543 (6) H14A 0.5823 0.4261 0.7276 0.082\* H14B 0.4834 0.4629 0.8469 0.082\* H14C 0.3863 0.3887 0.7330 0.082\* C5 0.2612 (3) 0.1259 (3) 0.8557 (2) 0.0551 (6) H5A 0.2260 0.1757 0.7798 0.066\* H5B 0.1637 0.1242 0.9084 0.066\* C6 0.3060 (3) −0.0212 (3) 0.8212 (2) 0.0491 (5) H6A 0.1986 −0.0681 0.7975 0.059\* H6B 0.3545 −0.0657 0.8966 0.059\* C15 0.3604 (3) 0.0199 (3) 0.5944 (2) 0.0512 (6) H15A 0.3540 0.1178 0.6058 0.077\* H15B 0.2472 −0.0157 0.5721 0.077\* H15C 0.4358 −0.0003 0.5287 0.077\* C13 0.8492 (3) −0.2716 (3) 0.7522 (2) 0.0488 (5) H13A 0.9673 −0.2981 0.7700 0.073\* H13B 0.7832 −0.3504 0.7236 0.073\* H13C 0.8028 −0.2358 0.8268 0.073\* ------ ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1244 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cl1 0.0562 (3) 0.0361 (3) 0.0907 (4) −0.0136 (3) 0.0093 (3) −0.0118 (3) Cl2 0.0568 (3) 0.0510 (3) 0.0424 (2) 0.0037 (3) −0.0094 (2) −0.0038 (2) C9 0.0310 (8) 0.0247 (9) 0.0331 (8) −0.0017 (7) 0.0087 (6) −0.0004 (7) O1 0.0579 (9) 0.0357 (8) 0.0439 (7) −0.0015 (7) 0.0276 (6) 0.0035 (6) C8 0.0315 (8) 0.0246 (9) 0.0266 (7) −0.0005 (7) 0.0060 (6) 0.0011 (6) C1 0.0335 (8) 0.0239 (10) 0.0326 (8) 0.0028 (7) 0.0085 (6) 0.0003 (7) C12 0.0317 (8) 0.0242 (11) 0.0406 (9) −0.0021 (7) 0.0043 (7) −0.0033 (7) C10 0.0380 (9) 0.0274 (10) 0.0354 (8) −0.0023 (8) 0.0103 (7) 0.0017 (7) N1 0.0467 (10) 0.0312 (10) 0.0571 (11) 0.0074 (9) 0.0187 (8) −0.0038 (10) C7 0.0328 (9) 0.0380 (11) 0.0365 (9) −0.0049 (8) 0.0048 (7) −0.0009 (8) C3 0.0429 (10) 0.0292 (10) 0.0372 (9) 0.0069 (8) 0.0097 (7) −0.0042 (8) C2 0.0410 (10) 0.0262 (10) 0.0419 (9) −0.0012 (8) 0.0055 (8) −0.0051 (8) C4 0.0469 (11) 0.0492 (14) 0.0444 (10) 0.0094 (10) 0.0175 (8) −0.0066 (10) C16 0.0449 (11) 0.0412 (13) 0.0493 (11) −0.0131 (10) 0.0039 (9) −0.0024 (10) C11 0.0546 (12) 0.0245 (10) 0.0382 (9) 0.0020 (8) 0.0159 (8) 0.0049 (8) C14 0.0698 (15) 0.0353 (13) 0.0589 (13) 0.0194 (11) 0.0119 (11) −0.0001 (11) C5 0.0365 (10) 0.0652 (17) 0.0656 (12) 0.0064 (12) 0.0196 (9) −0.0057 (14) C6 0.0361 (10) 0.0549 (15) 0.0579 (12) −0.0084 (10) 0.0156 (9) −0.0035 (11) C15 0.0459 (12) 0.0577 (16) 0.0484 (11) 0.0006 (11) −0.0093 (9) 0.0019 (11) C13 0.0531 (12) 0.0324 (12) 0.0613 (12) 0.0075 (10) 0.0052 (10) 0.0115 (10) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1640 .table-wrap} ---------------- ------------- ------------------- ------------- Cl1---C2 1.766 (2) C4---C5 1.517 (4) Cl2---C2 1.762 (2) C4---H4A 0.9700 C9---C12 1.389 (3) C4---H4B 0.9700 C9---C10 1.418 (3) C16---H16A 0.9600 C9---C8 1.519 (2) C16---H16B 0.9600 O1---C10 1.253 (2) C16---H16C 0.9600 C8---C1 1.539 (3) C11---H11A 0.9700 C8---C7 1.574 (2) C11---H11B 0.9700 C8---H8 0.9800 C14---H14A 0.9600 C1---C2 1.515 (3) C14---H14B 0.9600 C1---C11 1.528 (2) C14---H14C 0.9600 C1---C3 1.533 (2) C5---C6 1.519 (4) C12---N1 1.334 (3) C5---H5A 0.9700 C12---C13 1.490 (3) C5---H5B 0.9700 C10---C11 1.509 (3) C6---H6A 0.9700 N1---H2 0.84 (3) C6---H6B 0.9700 N1---H1 0.83 (3) C15---H15A 0.9600 C7---C16 1.528 (3) C15---H15B 0.9600 C7---C15 1.531 (3) C15---H15C 0.9600 C7---C6 1.546 (3) C13---H13A 0.9600 C3---C2 1.506 (3) C13---H13B 0.9600 C3---C14 1.520 (3) C13---H13C 0.9600 C3---C4 1.524 (3) C12---C9---C10 121.23 (16) C5---C4---H4B 108.7 C12---C9---C8 128.39 (17) C3---C4---H4B 108.7 C10---C9---C8 110.19 (16) H4A---C4---H4B 107.6 C9---C8---C1 101.12 (14) C7---C16---H16A 109.5 C9---C8---C7 112.64 (14) C7---C16---H16B 109.5 C1---C8---C7 114.08 (16) H16A---C16---H16B 109.5 C9---C8---H8 109.6 C7---C16---H16C 109.5 C1---C8---H8 109.6 H16A---C16---H16C 109.5 C7---C8---H8 109.6 H16B---C16---H16C 109.5 C2---C1---C11 117.28 (17) C10---C11---C1 103.64 (15) C2---C1---C3 59.21 (12) C10---C11---H11A 111.0 C11---C1---C3 120.82 (16) C1---C11---H11A 111.0 C2---C1---C8 120.85 (16) C10---C11---H11B 111.0 C11---C1---C8 107.05 (14) C1---C11---H11B 111.0 C3---C1---C8 124.93 (16) H11A---C11---H11B 109.0 N1---C12---C9 120.03 (19) C3---C14---H14A 109.5 N1---C12---C13 115.56 (19) C3---C14---H14B 109.5 C9---C12---C13 124.34 (17) H14A---C14---H14B 109.5 O1---C10---C9 127.82 (19) C3---C14---H14C 109.5 O1---C10---C11 122.38 (17) H14A---C14---H14C 109.5 C9---C10---C11 109.76 (15) H14B---C14---H14C 109.5 C12---N1---H2 120.9 (16) C4---C5---C6 113.71 (19) C12---N1---H1 115.2 (19) C4---C5---H5A 108.8 H2---N1---H1 123 (2) C6---C5---H5A 108.8 C16---C7---C15 108.37 (18) C4---C5---H5B 108.8 C16---C7---C6 105.49 (18) C6---C5---H5B 108.8 C15---C7---C6 109.80 (18) H5A---C5---H5B 107.7 C16---C7---C8 108.48 (17) C5---C6---C7 119.6 (2) C15---C7---C8 112.35 (17) C5---C6---H6A 107.4 C6---C7---C8 112.04 (16) C7---C6---H6A 107.4 C2---C3---C14 118.5 (2) C5---C6---H6B 107.4 C2---C3---C4 118.56 (17) C7---C6---H6B 107.4 C14---C3---C4 112.69 (18) H6A---C6---H6B 107.0 C2---C3---C1 59.77 (12) C7---C15---H15A 109.5 C14---C3---C1 117.47 (17) C7---C15---H15B 109.5 C4---C3---C1 120.35 (18) H15A---C15---H15B 109.5 C3---C2---C1 61.01 (12) C7---C15---H15C 109.5 C3---C2---Cl2 120.86 (14) H15A---C15---H15C 109.5 C1---C2---Cl2 119.26 (15) H15B---C15---H15C 109.5 C3---C2---Cl1 119.40 (16) C12---C13---H13A 109.5 C1---C2---Cl1 121.53 (14) C12---C13---H13B 109.5 Cl2---C2---Cl1 108.41 (11) H13A---C13---H13B 109.5 C5---C4---C3 114.04 (18) C12---C13---H13C 109.5 C5---C4---H4A 108.7 H13A---C13---H13C 109.5 C3---C4---H4A 108.7 H13B---C13---H13C 109.5 ---------------- ------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2277 .table-wrap} ----------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H2···O1^i^ 0.85 (3) 2.03 (3) 2.865 (3) 170 (2) N1---H1···O1 0.83 (4) 1.98 (4) 2.672 (3) 140 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+2, *y*−1/2, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- ---------- ---------- ----------- ------------- N1---H2⋯O1^i^ 0.85 (3) 2.03 (3) 2.865 (3) 170 (2) N1---H1⋯O1 0.83 (4) 1.98 (4) 2.672 (3) 140 (3) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.505082

2011-2-16

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052109/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o645-o646", "authors": [ { "first": "Ahmed", "last": "Benharref" }, { "first": "Essêdiya", "last": "Lassaba" }, { "first": "Daniel", "last": "Avignant" }, { "first": "Abdelghani", "last": "Oudahmane" }, { "first": "Moha", "last": "Berraho" } ] }

PMC3052110

Related literature {#sec1} ================== For related structures, see: Keypour *et al.* (2009[@bb3]). For background information on diimine complexes, see: Mahmoudi *et al.* (2009[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~29~H~25~N~3~O~3~*M* *~r~* = 463.52Monoclinic,*a* = 9.1097 (6) Å*b* = 18.1946 (11) Å*c* = 13.7769 (5) Åβ = 93.405 (4)°*V* = 2279.5 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 0.09 mm^−1^*T* = 150 K0.25 × 0.12 × 0.10 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (*SORTAV*; Blessing, 1995[@bb2]) *T* ~min~ = 0.866, *T* ~max~ = 0.99316359 measured reflections5135 independent reflections3083 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.054 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.055*wR*(*F* ^2^) = 0.137*S* = 1.065135 reflections318 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e439} Data collection: *COLLECT* (Nonius, 2002[@bb5]); cell refinement: *DENZO-SMN* (Otwinowski & Minor, 1997[@bb6]); data reduction: *DENZO-SMN*; program(s) used to solve structure: *SIR92* (Altomare *et al.*, 1994[@bb1]); program(s) used to refine structure: *SHELXTL* (Sheldrick, 2008[@bb7]); molecular graphics: *PLATON* (Spek, 2009[@bb8]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005319/bh2338sup1.cif](http://dx.doi.org/10.1107/S1600536811005319/bh2338sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005319/bh2338Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005319/bh2338Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bh2338&file=bh2338sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bh2338sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bh2338&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BH2338](http://scripts.iucr.org/cgi-bin/sendsup?bh2338)). We are grateful to Bu-Ali Sina and Alzahra Universities for financial support. Comment ======= In our ongoing studies on the synthesis, structural and spectroscopic characterization of the products derived from *N*^1^-(3-(2-aminophenoxy)propyl)-benzene-1,2-diamine with aldehydes (Keypour *et al.*, 2009; Mahmoudi *et al.*, 2009) we report herein the crystal structure of the title compound, prepared by the reaction of *N*^1^-(3-(2-aminophenoxy)propyl)-benzene-1,2-diamine with salicyl aldehyde. The molecular structure of the title compound is shown in Fig. 1. The molecule adopts the *E* configuration with respect to the imine C═N bond. Two hydroxyl groups are located close to N atoms, and form strong intramolecular hydrogen bonds (Table 1). Experimental {#experimental} ============ *N*^1^-(3-(2-aminophenoxy)propyl)benzene-1,2-diamine (0.064 g, 0.25 mmol) in methanol (20 ml) was added dropwise with stirring to a solution of salicylaldehyde (0.061 g, 0.5 mmol) in methanol (30 ml). The mixture was refluxed for 12 h. Then, the solution volume was reduced to 10 ml by evaporation, and a precipitate was formed. This was filtered off, washed with ether, and dried *in vacuo*. Vapour diffusion of diethyl ether into a methanolic solution of the product afforded yellow crystals in 60% yield. Refinement {#refinement} ========== All C-bonded H atoms positions were calculated and refined with a riding model and *U*~iso~(H) parameters set to 1.2 times *U*~eq~(carrier C atom). Hydroxyl H atoms also ride on their O atoms, with O---H bond lengths fixed to 0.84 Å and *U*~iso~(H) = 1.5 *U*~eq~(carrier O atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the structure of the title complex, with displacement ellipsoids drawn at the 50% probability level. ::: ![](e-67-0o657-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e140 .table-wrap} ------------------------- ---------------------------------------- C~29~H~25~N~3~O~3~ *F*(000) = 976 *M~r~* = 463.52 *D*~x~ = 1.351 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 16359 reflections *a* = 9.1097 (6) Å θ = 2.7--27.5° *b* = 18.1946 (11) Å µ = 0.09 mm^−1^ *c* = 13.7769 (5) Å *T* = 150 K β = 93.405 (4)° Needle, yellow *V* = 2279.5 (2) Å^3^ 0.25 × 0.12 × 0.10 mm *Z* = 4 ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 5135 independent reflections Radiation source: fine-focus sealed tube 3083 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.054 Detector resolution: 9 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.7° φ scans and ω scans with κ offsets *h* = −11→11 Absorption correction: multi-scan (*SORTAV*; Blessing, 1995) *k* = −22→23 *T*~min~ = 0.866, *T*~max~ = 0.993 *l* = −17→17 16359 measured reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e396 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.137 H-atom parameters constrained *S* = 1.06 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0536*P*)^2^ + 0.4485*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5135 reflections (Δ/σ)~max~ = 0.001 318 parameters Δρ~max~ = 0.23 e Å^−3^ 1 restraint Δρ~min~ = −0.20 e Å^−3^ 0 constraints ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e559 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.98262 (18) 0.22668 (8) 0.88875 (9) 0.0465 (4) H1O 0.9212 0.1922 0.8864 0.070\* O2 0.80830 (16) 0.02045 (7) 0.35975 (9) 0.0369 (4) O3 0.69646 (17) −0.13681 (8) 0.49252 (9) 0.0418 (4) H2O 0.7212 −0.1156 0.4418 0.063\* N1 0.82575 (18) 0.08636 (9) 0.66217 (11) 0.0352 (4) N2 0.80517 (19) 0.13040 (9) 0.81279 (11) 0.0378 (4) N3 0.70199 (18) −0.10938 (9) 0.31140 (11) 0.0323 (4) C1 0.8674 (2) 0.13987 (11) 0.72906 (13) 0.0348 (5) C2 0.7258 (2) 0.04118 (11) 0.70695 (14) 0.0355 (5) C3 0.6454 (2) −0.01894 (12) 0.67220 (16) 0.0424 (5) H3A 0.6527 −0.0369 0.6079 0.051\* C4 0.5538 (2) −0.05139 (12) 0.73642 (17) 0.0461 (6) H4A 0.4961 −0.0926 0.7155 0.055\* C5 0.5439 (2) −0.02520 (12) 0.83139 (17) 0.0462 (6) H5A 0.4805 −0.0492 0.8736 0.055\* C6 0.6241 (2) 0.03446 (12) 0.86451 (16) 0.0428 (5) H6A 0.6173 0.0520 0.9290 0.051\* C7 0.7156 (2) 0.06849 (11) 0.80071 (14) 0.0371 (5) C8 0.9683 (2) 0.20146 (11) 0.71522 (14) 0.0342 (5) C9 1.0249 (2) 0.24102 (12) 0.79778 (14) 0.0358 (5) C10 1.1272 (2) 0.29677 (12) 0.78825 (15) 0.0406 (5) H10A 1.1682 0.3211 0.8445 0.049\* C11 1.1694 (2) 0.31703 (12) 0.69784 (16) 0.0433 (5) H11A 1.2402 0.3549 0.6920 0.052\* C12 1.1092 (2) 0.28247 (12) 0.61553 (15) 0.0411 (5) H12A 1.1353 0.2979 0.5530 0.049\* C13 1.0116 (2) 0.22574 (11) 0.62434 (14) 0.0375 (5) H13A 0.9720 0.2021 0.5671 0.045\* C14 0.8752 (2) 0.07122 (11) 0.56509 (13) 0.0354 (5) H14A 0.8771 0.0174 0.5545 0.042\* H14B 0.9765 0.0900 0.5607 0.042\* C15 0.7747 (2) 0.10687 (12) 0.48571 (13) 0.0372 (5) H15A 0.6749 0.0856 0.4877 0.045\* H15B 0.7675 0.1602 0.4991 0.045\* C16 0.8287 (2) 0.09626 (11) 0.38527 (14) 0.0375 (5) H16A 0.7725 0.1280 0.3380 0.045\* H16B 0.9341 0.1095 0.3847 0.045\* C17 0.8190 (2) 0.00152 (11) 0.26392 (13) 0.0319 (5) C18 0.8766 (2) 0.04669 (12) 0.19473 (14) 0.0382 (5) H18A 0.9154 0.0936 0.2127 0.046\* C19 0.8774 (2) 0.02298 (12) 0.09868 (15) 0.0420 (5) H19A 0.9156 0.0542 0.0510 0.050\* C20 0.8233 (2) −0.04524 (12) 0.07220 (14) 0.0408 (5) H20A 0.8249 −0.0611 0.0066 0.049\* C21 0.7667 (2) −0.09051 (12) 0.14125 (14) 0.0367 (5) H21A 0.7311 −0.1379 0.1230 0.044\* C22 0.7614 (2) −0.06751 (11) 0.23715 (13) 0.0320 (5) C23 0.5987 (2) −0.15625 (11) 0.29380 (14) 0.0344 (5) H23A 0.5604 −0.1634 0.2288 0.041\* C24 0.5396 (2) −0.19841 (11) 0.37172 (14) 0.0339 (5) C25 0.4292 (2) −0.25061 (12) 0.35230 (16) 0.0403 (5) H25A 0.3930 −0.2584 0.2870 0.048\* C26 0.3717 (2) −0.29106 (12) 0.42569 (17) 0.0458 (6) H26A 0.2965 −0.3263 0.4114 0.055\* C27 0.4258 (2) −0.27940 (12) 0.52143 (16) 0.0444 (6) H27A 0.3875 −0.3073 0.5725 0.053\* C28 0.5338 (2) −0.22813 (12) 0.54275 (15) 0.0407 (5) H28A 0.5687 −0.2206 0.6083 0.049\* C29 0.5923 (2) −0.18717 (11) 0.46906 (14) 0.0340 (5) ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1372 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0556 (11) 0.0529 (11) 0.0310 (8) −0.0016 (8) 0.0015 (7) −0.0072 (7) O2 0.0491 (9) 0.0346 (8) 0.0271 (7) −0.0053 (7) 0.0029 (6) −0.0018 (6) O3 0.0502 (10) 0.0431 (9) 0.0320 (8) −0.0091 (7) 0.0014 (6) 0.0014 (6) N1 0.0373 (10) 0.0394 (10) 0.0289 (9) 0.0047 (8) 0.0017 (7) −0.0045 (7) N2 0.0435 (11) 0.0402 (11) 0.0298 (9) 0.0039 (9) 0.0032 (7) −0.0015 (7) N3 0.0351 (10) 0.0305 (10) 0.0314 (9) 0.0023 (8) 0.0033 (7) 0.0000 (7) C1 0.0339 (12) 0.0397 (13) 0.0307 (11) 0.0079 (9) −0.0001 (8) −0.0026 (9) C2 0.0312 (12) 0.0353 (12) 0.0401 (12) 0.0057 (9) 0.0023 (9) 0.0017 (9) C3 0.0427 (13) 0.0416 (14) 0.0423 (13) 0.0072 (11) −0.0021 (10) −0.0059 (10) C4 0.0393 (14) 0.0382 (13) 0.0604 (15) 0.0013 (11) −0.0010 (11) −0.0007 (11) C5 0.0420 (14) 0.0399 (14) 0.0577 (15) 0.0057 (11) 0.0120 (11) 0.0111 (11) C6 0.0461 (14) 0.0430 (14) 0.0398 (12) 0.0082 (11) 0.0076 (10) 0.0045 (10) C7 0.0366 (12) 0.0392 (13) 0.0354 (12) 0.0060 (10) 0.0017 (9) −0.0001 (9) C8 0.0298 (11) 0.0366 (12) 0.0358 (11) 0.0035 (9) −0.0005 (8) −0.0022 (9) C9 0.0358 (12) 0.0432 (13) 0.0283 (11) 0.0114 (10) 0.0000 (8) −0.0022 (9) C10 0.0368 (13) 0.0430 (13) 0.0410 (13) 0.0051 (11) −0.0046 (9) −0.0104 (10) C11 0.0356 (13) 0.0408 (13) 0.0533 (14) 0.0008 (10) 0.0021 (10) −0.0037 (10) C12 0.0413 (13) 0.0444 (14) 0.0380 (12) 0.0029 (11) 0.0062 (9) −0.0009 (10) C13 0.0387 (13) 0.0415 (13) 0.0321 (11) 0.0024 (10) 0.0001 (9) −0.0048 (9) C14 0.0390 (12) 0.0399 (12) 0.0275 (11) 0.0067 (10) 0.0041 (8) −0.0067 (9) C15 0.0392 (12) 0.0392 (13) 0.0327 (11) 0.0039 (10) −0.0007 (9) −0.0045 (9) C16 0.0437 (13) 0.0349 (12) 0.0335 (11) −0.0050 (10) −0.0003 (9) −0.0007 (9) C17 0.0323 (11) 0.0390 (12) 0.0244 (10) 0.0016 (9) 0.0011 (8) −0.0013 (8) C18 0.0417 (13) 0.0408 (13) 0.0325 (12) −0.0043 (10) 0.0051 (9) 0.0012 (9) C19 0.0448 (14) 0.0487 (14) 0.0334 (12) −0.0011 (11) 0.0102 (9) 0.0040 (10) C20 0.0458 (14) 0.0488 (14) 0.0286 (11) 0.0046 (11) 0.0080 (9) −0.0028 (9) C21 0.0398 (13) 0.0366 (13) 0.0336 (11) 0.0047 (10) 0.0024 (9) −0.0041 (9) C22 0.0308 (11) 0.0342 (12) 0.0310 (11) 0.0050 (9) 0.0027 (8) 0.0025 (8) C23 0.0376 (12) 0.0333 (12) 0.0322 (11) 0.0058 (10) 0.0019 (9) −0.0013 (9) C24 0.0346 (12) 0.0297 (11) 0.0377 (12) 0.0050 (9) 0.0040 (9) −0.0009 (9) C25 0.0384 (13) 0.0353 (12) 0.0471 (13) 0.0004 (10) 0.0025 (10) −0.0056 (10) C26 0.0382 (14) 0.0345 (13) 0.0649 (16) −0.0034 (10) 0.0058 (11) 0.0011 (11) C27 0.0413 (14) 0.0381 (13) 0.0549 (14) 0.0044 (11) 0.0116 (10) 0.0133 (10) C28 0.0406 (13) 0.0407 (13) 0.0414 (12) 0.0051 (11) 0.0061 (9) 0.0085 (10) C29 0.0330 (12) 0.0295 (12) 0.0397 (12) 0.0026 (9) 0.0043 (9) 0.0005 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2018 .table-wrap} ------------------ ------------- ------------------- ------------- O1---C9 1.358 (2) C12---H12A 0.9500 O1---H1O 0.8400 C13---H13A 0.9500 O2---C17 1.373 (2) C14---C15 1.528 (3) O2---C16 1.433 (2) C14---H14A 0.9900 O3---C29 1.344 (2) C14---H14B 0.9900 O3---H2O 0.8400 C15---C16 1.508 (3) N1---C1 1.378 (2) C15---H15A 0.9900 N1---C2 1.397 (3) C15---H15B 0.9900 N1---C14 1.462 (2) C16---H16A 0.9900 N2---C1 1.326 (2) C16---H16B 0.9900 N2---C7 1.395 (3) C17---C18 1.385 (3) N3---C23 1.282 (2) C17---C22 1.402 (3) N3---C22 1.409 (2) C18---C19 1.392 (3) C1---C8 1.469 (3) C18---H18A 0.9500 C2---C3 1.386 (3) C19---C20 1.377 (3) C2---C7 1.392 (3) C19---H19A 0.9500 C3---C4 1.384 (3) C20---C21 1.381 (3) C3---H3A 0.9500 C20---H20A 0.9500 C4---C5 1.400 (3) C21---C22 1.390 (3) C4---H4A 0.9500 C21---H21A 0.9500 C5---C6 1.371 (3) C23---C24 1.449 (3) C5---H5A 0.9500 C23---H23A 0.9500 C6---C7 1.392 (3) C24---C25 1.397 (3) C6---H6A 0.9500 C24---C29 1.412 (3) C8---C13 1.406 (3) C25---C26 1.379 (3) C8---C9 1.417 (3) C25---H25A 0.9500 C9---C10 1.388 (3) C26---C27 1.397 (3) C10---C11 1.376 (3) C26---H26A 0.9500 C10---H10A 0.9500 C27---C28 1.374 (3) C11---C12 1.381 (3) C27---H27A 0.9500 C11---H11A 0.9500 C28---C29 1.391 (3) C12---C13 1.372 (3) C28---H28A 0.9500 C9---O1---H1O 109.5 H14A---C14---H14B 107.9 C17---O2---C16 117.50 (14) C16---C15---C14 112.85 (17) C29---O3---H2O 109.5 C16---C15---H15A 109.0 C1---N1---C2 106.32 (16) C14---C15---H15A 109.0 C1---N1---C14 131.09 (17) C16---C15---H15B 109.0 C2---N1---C14 122.48 (16) C14---C15---H15B 109.0 C1---N2---C7 106.17 (16) H15A---C15---H15B 107.8 C23---N3---C22 122.11 (16) O2---C16---C15 107.68 (16) N2---C1---N1 112.02 (18) O2---C16---H16A 110.2 N2---C1---C8 121.00 (17) C15---C16---H16A 110.2 N1---C1---C8 126.98 (18) O2---C16---H16B 110.2 C3---C2---C7 122.6 (2) C15---C16---H16B 110.2 C3---C2---N1 131.05 (19) H16A---C16---H16B 108.5 C7---C2---N1 106.32 (18) O2---C17---C18 124.33 (18) C4---C3---C2 116.2 (2) O2---C17---C22 115.51 (17) C4---C3---H3A 121.9 C18---C17---C22 120.12 (17) C2---C3---H3A 121.9 C17---C18---C19 119.6 (2) C3---C4---C5 121.8 (2) C17---C18---H18A 120.2 C3---C4---H4A 119.1 C19---C18---H18A 120.2 C5---C4---H4A 119.1 C20---C19---C18 120.6 (2) C6---C5---C4 121.2 (2) C20---C19---H19A 119.7 C6---C5---H5A 119.4 C18---C19---H19A 119.7 C4---C5---H5A 119.4 C19---C20---C21 119.83 (19) C5---C6---C7 118.0 (2) C19---C20---H20A 120.1 C5---C6---H6A 121.0 C21---C20---H20A 120.1 C7---C6---H6A 121.0 C20---C21---C22 120.7 (2) C6---C7---C2 120.2 (2) C20---C21---H21A 119.6 C6---C7---N2 130.68 (19) C22---C21---H21A 119.6 C2---C7---N2 109.13 (17) C21---C22---C17 119.08 (18) C13---C8---C9 116.56 (19) C21---C22---N3 124.35 (18) C13---C8---C1 124.48 (18) C17---C22---N3 116.57 (16) C9---C8---C1 118.95 (18) N3---C23---C24 120.85 (18) O1---C9---C10 117.15 (18) N3---C23---H23A 119.6 O1---C9---C8 122.22 (19) C24---C23---H23A 119.6 C10---C9---C8 120.63 (18) C25---C24---C29 118.71 (18) C11---C10---C9 120.45 (19) C25---C24---C23 120.85 (18) C11---C10---H10A 119.8 C29---C24---C23 120.43 (18) C9---C10---H10A 119.8 C26---C25---C24 121.5 (2) C10---C11---C12 120.2 (2) C26---C25---H25A 119.2 C10---C11---H11A 119.9 C24---C25---H25A 119.2 C12---C11---H11A 119.9 C25---C26---C27 118.9 (2) C13---C12---C11 119.8 (2) C25---C26---H26A 120.6 C13---C12---H12A 120.1 C27---C26---H26A 120.6 C11---C12---H12A 120.1 C28---C27---C26 120.9 (2) C12---C13---C8 122.18 (18) C28---C27---H27A 119.6 C12---C13---H13A 118.9 C26---C27---H27A 119.6 C8---C13---H13A 118.9 C27---C28---C29 120.5 (2) N1---C14---C15 111.78 (16) C27---C28---H28A 119.7 N1---C14---H14A 109.3 C29---C28---H28A 119.7 C15---C14---H14A 109.3 O3---C29---C28 119.03 (18) N1---C14---H14B 109.3 O3---C29---C24 121.48 (18) C15---C14---H14B 109.3 C28---C29---C24 119.48 (19) ------------------ ------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2803 .table-wrap} --------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1O···N2 0.84 1.81 2.564 (2) 148 O3---H2O···N3 0.84 1.80 2.548 (2) 148 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- --------- ------- ----------- ------------- O1---H1*O*⋯N2 0.84 1.81 2.564 (2) 148 O3---H2*O*⋯N3 0.84 1.80 2.548 (2) 148 :::

PubMed Central

2024-06-05T04:04:18.510005

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052110/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o657-o658", "authors": [ { "first": "Hassan", "last": "Keypour" }, { "first": "Sareh", "last": "Tamizi" }, { "first": "Saeed", "last": "Dehghanpour" }, { "first": "Reza", "last": "Azadbakht" }, { "first": "Mehdi", "last": "Khalaj" } ] }

PMC3052111

Related literature {#sec1} ================== For other metal complexes based on the *N*,*N*-dimethylaminomethane-1,1- diphosphonate ligand, see: Du *et al.* (2009[@bb4], 2010*a* [@bb5],*b* [@bb6]). For bond-length data, see: Lutz & Muller (1995[@bb7]); Distler *et al.* (1999[@bb3]); Stock & Bein (2004[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Mg(C~3~H~10~NO~6~P~2~)~2~\]*M* *~r~* = 460.43Monoclinic,*a* = 5.4507 (3) Å*b* = 11.2166 (6) Å*c* = 12.5770 (7) Åβ = 94.984 (1)°*V* = 766.03 (7) Å^3^*Z* = 2Mo *K*α radiationμ = 0.61 mm^−1^*T* = 296 K0.40 × 0.30 × 0.24 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2008[@bb2]) *T* ~min~ = 0.675, *T* ~max~ = 0.7464801 measured reflections1492 independent reflections1447 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.014 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.024*wR*(*F* ^2^) = 0.066*S* = 1.091492 reflections115 parametersH-atom parameters constrainedΔρ~max~ = 0.38 e Å^−3^Δρ~min~ = −0.33 e Å^−3^ {#d5e617} Data collection: *SMART* (Bruker, 2008[@bb2]); cell refinement: *SAINT* (Bruker, 2008[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb8]) and *DIAMOND* (Brandenburg, 1999[@bb1]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005976/sj5102sup1.cif](http://dx.doi.org/10.1107/S1600536811005976/sj5102sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005976/sj5102Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005976/sj5102Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5102&file=sj5102sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5102sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5102&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5102](http://scripts.iucr.org/cgi-bin/sendsup?sj5102)). This work was supported by the Natural Science Foundation of Jiangxi Province (grant 2008GQH0013) and the Natural Science Foundation of Jiangxi Provincial Education Department (grant GJJ09317). Comment ======= Among many of the phosphonate ligands studied so far, methylenediphosphonic acid and its derivatives are quite unique because they feature a close connection of two phosphonate moieties *via* one carbon atom, which facilitate their combined coordination ability to act as a \[CP~2~O~6~\] unit rather than two \[CPO~3~\] units. As a result, they show diversified coordination capabilities with metal ions and thus lead to the formation of new structural types. Recently, by using such ligand types, *i.e. N*,*N*-dimethylaminomethane-1,1-diphosphonate, we have isolated a series of diphosphonate complexes of metals such as Al^III^, Fe^III^, Cd^II^, Pb^II^ and Ba^II^, which exhibit variable structures such as zero-dimensional, one-dimensional, double-1-dimensional, double-2-dimensional, and three-dimensional structures (Du *et al.*, 2009, 2010*a*,*b*). As an expansion of our previous work, we have also obtained a one-dimensional magnesium(II) diphosphonate, namely \[Mg(C~6~H~20~N~2~O~12~P~4~)\]~n~, which is isostructural with the previously reported cadmium(II) complex based on the same ligand and shows a one-dimensional chain structure. The asymmetric unit contains a half Mg^2+^ cation and one H~3~*L*^-^ anion. The unique Mg^2+^ cation lies on an inversion center and is octahedrally coordinated by the O atoms of six phosphonate groups from four H~3~*L*^-^ anions. The Mg---O \[2.0448 (11) -- 2.1879 (11) Å\] bond lengths are comparable to those reported for other Mg^II^ phosphonate complexes (Lutz & Muller, 1995; Distler *et al.*, 1999; Stock & Bein, 2004). The unique H~3~*L*^-^ anion, with one protonated N atom and two phosphonate OH groups, serves as a tridentate ligand. By using three of its six phosphonate O atoms, it chelates in a bidentate fashion with one Mg^2+^ cation and also bridges to a second Mg^2+^ ion. The interconnection of Mg^2+^ cations by the H~3~*L*^-^ anions leads to the formation of a one-dimensional chain along the *a*-axis, in which the adjacent Mg^2+^ ions are doubly bridged by two equivalent H~3~*L*^-^ anions. These discrete one-dimensional chains are further assembled into a three-dimensional supramolecular network *via* O---H···O and N---H···O hydrogen bonds involving the non-coordinated phosphonate O atoms and the protonated N atoms. Experimental {#experimental} ============ For the preparation of (I), a mixture of Mg(NO~3~)~2~ (0.20 mmol) and H~4~L (0.50 mmol) and ethanol (3 ml) in 10 ml distilled water, was sealed into a Parr Teflon-lined autoclave (23 ml) and heated at 393 K for 3 d. Colorless block-shaped crystals were collected in *ca* 55% yield based on Mg. Analysis calculated for C~6~H~20~N~2~O~12~Mg~1~P~4~: C 15.65, H 4.38, N 6.08%; found: C 15.59, H 4.48, N 6.03%. Refinement {#refinement} ========== The N-bound and the tertiary C-bound H atoms were positioned geometrically and refined using a riding model: N---H = 0.91 and C---H = 0.98 Å, with *U*iso(H) = 1.2*U*~eq~(N, C); while the O-bound and the primary C-bound H atoms were placed in idealized positions and constrained to ride on their parent atoms: O---H = 0.82 and C---H = 0.96 Å, with *U*~iso~(H) = 1.5 times *U*~eq~(O, C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the selected unit of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms have been omitted for clarity. \[Symmetry codes: (i) x - 1, y, z; (ii) -x + 1, -y + 1, -z + 1; (iii) -x, -y + 1, -z + 1; (iv) x + 1, y, z.\] ::: ![](e-67-0m362-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the chain structure of (I) along the a-axis. The CPO3 tetrahedra are shaded in purple. Mg, N and C atoms are drawn as cyan, blue and grey circles, respectively. Hydrogen atoms have been omitted for clarity. ::: ![](e-67-0m362-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view of the three-dimensional supramolecular structure of (I) down the a-axis. The MgO6 octahedra and CPO3 tetrahedra are shaded in cyan and purple, respectively. N, C and H atoms are drawn as blue, grey and green circles, respectively. Hydrogen bonds are represented by dashed lines. ::: ![](e-67-0m362-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e335 .table-wrap} ------------------------------- --------------------------------------- \[Mg(C~3~H~10~NO~6~P~2~)~2~\] *F*(000) = 476 *M~r~* = 460.43 *D*~x~ = 1.996 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 4647 reflections *a* = 5.4507 (3) Å θ = 2.4--29.4° *b* = 11.2166 (6) Å µ = 0.61 mm^−1^ *c* = 12.5770 (7) Å *T* = 296 K β = 94.984 (1)° Block, colourless *V* = 766.03 (7) Å^3^ 0.40 × 0.30 × 0.24 mm *Z* = 2 ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e469 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEX CCD area-detector diffractometer 1492 independent reflections Radiation source: fine-focus sealed tube 1447 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.014 φ and ω scans θ~max~ = 26.0°, θ~min~ = 2.4° Absorption correction: multi-scan (*SADABS*; Bruker, 2008) *h* = −6→6 *T*~min~ = 0.675, *T*~max~ = 0.746 *k* = −13→13 4801 measured reflections *l* = −15→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e586 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.024 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.066 H-atom parameters constrained *S* = 1.09 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0347*P*)^2^ + 0.6187*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 1492 reflections (Δ/σ)~max~ = 0.001 115 parameters Δρ~max~ = 0.38 e Å^−3^ 0 restraints Δρ~min~ = −0.33 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e743 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. IR data (KBr, ν, cm^-1^): 3437 (*m*), 3137 (*s*), 3071 (*m*), 2986 (*m*), 2826 (*m*), 2280 (*m*), 1815 (*m*), 1473 (*m*), 1457 (*m*), 1421 (*m*), 1388 (*m*), 1256 (*s*), 1225 (*s*), 1200 (*versus*), 1155 (*s*), 1128 (*s*), 1088 (*s*), 1036 (*s*), 995 (*s*), 950 (*s*), 928 (*s*), 854 (*m*), 827 (*m*), 725 (*m*), 615 (*m*), 573 (*s*), 517 (*m*), 476 (*m*). Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e943 .table-wrap} ----- ------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Mg1 0.0000 0.5000 0.5000 0.01237 (17) P1 0.52519 (7) 0.34374 (3) 0.59421 (3) 0.01109 (12) P2 0.34788 (7) 0.55738 (3) 0.72234 (3) 0.01225 (13) N1 0.5807 (3) 0.35032 (12) 0.81729 (11) 0.0161 (3) H1B 0.6307 0.2757 0.8007 0.019\* C1 0.4187 (3) 0.39596 (14) 0.72149 (12) 0.0126 (3) H1A 0.2596 0.3565 0.7262 0.015\* C2 0.4447 (4) 0.33952 (16) 0.91574 (13) 0.0217 (4) H2A 0.5545 0.3102 0.9737 0.032\* H2B 0.3096 0.2851 0.9024 0.032\* H2C 0.3831 0.4163 0.9341 0.032\* C3 0.8076 (3) 0.42374 (19) 0.84083 (15) 0.0264 (4) H3A 0.9027 0.3918 0.9021 0.040\* H3B 0.7620 0.5045 0.8550 0.040\* H3C 0.9041 0.4221 0.7805 0.040\* O1 0.7774 (2) 0.38860 (10) 0.57970 (9) 0.0168 (3) O2 0.3180 (2) 0.38023 (10) 0.51279 (9) 0.0160 (2) O3 0.5417 (2) 0.20563 (10) 0.60652 (10) 0.0182 (3) H3D 0.4114 0.1800 0.6253 0.027\* O4 0.5780 (2) 0.62560 (11) 0.68532 (9) 0.0177 (3) H4A 0.5846 0.6161 0.6210 0.027\* O5 0.1277 (2) 0.57125 (10) 0.64393 (9) 0.0167 (3) O6 0.3209 (2) 0.59441 (11) 0.83501 (9) 0.0187 (3) ----- ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1257 .table-wrap} ----- ------------- ------------- ------------ --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Mg1 0.0099 (4) 0.0144 (4) 0.0127 (4) −0.0013 (3) 0.0006 (3) 0.0007 (3) P1 0.0111 (2) 0.0108 (2) 0.0117 (2) −0.00042 (14) 0.00234 (15) 0.00033 (14) P2 0.0116 (2) 0.0127 (2) 0.0124 (2) 0.00185 (14) 0.00060 (15) −0.00118 (14) N1 0.0179 (7) 0.0157 (7) 0.0144 (6) 0.0044 (5) −0.0008 (5) 0.0006 (5) C1 0.0116 (7) 0.0146 (7) 0.0114 (7) 0.0011 (6) 0.0004 (6) 0.0000 (6) C2 0.0286 (10) 0.0216 (9) 0.0150 (8) 0.0014 (7) 0.0029 (7) 0.0032 (6) C3 0.0153 (9) 0.0371 (10) 0.0257 (9) −0.0014 (8) −0.0047 (7) 0.0022 (8) O1 0.0137 (6) 0.0172 (6) 0.0200 (6) −0.0027 (4) 0.0041 (4) 0.0022 (5) O2 0.0142 (6) 0.0197 (6) 0.0141 (5) 0.0016 (4) 0.0008 (4) 0.0009 (4) O3 0.0178 (6) 0.0122 (6) 0.0253 (6) −0.0009 (4) 0.0067 (5) 0.0010 (5) O4 0.0171 (6) 0.0191 (6) 0.0171 (5) −0.0036 (5) 0.0022 (5) −0.0025 (5) O5 0.0147 (6) 0.0173 (6) 0.0174 (6) 0.0022 (4) −0.0018 (5) −0.0004 (4) O6 0.0196 (6) 0.0217 (6) 0.0148 (6) 0.0060 (5) 0.0015 (5) −0.0033 (5) ----- ------------- ------------- ------------ --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1524 .table-wrap} ------------------------ ------------- ------------------- ------------- Mg1---O5^i^ 2.0448 (11) N1---C3 1.494 (2) Mg1---O5 2.0448 (11) N1---C2 1.502 (2) Mg1---O1^ii^ 2.0615 (11) N1---C1 1.5196 (19) Mg1---O1^iii^ 2.0616 (11) N1---H1B 0.9100 Mg1---O2 2.1879 (11) C1---H1A 0.9800 Mg1---O2^i^ 2.1879 (11) C2---H2A 0.9600 P1---O1 1.4898 (12) C2---H2B 0.9600 P1---O2 1.5134 (12) C2---H2C 0.9600 P1---O3 1.5587 (12) C3---H3A 0.9600 P1---C1 1.8451 (15) C3---H3B 0.9600 P2---O5 1.4938 (12) C3---H3C 0.9600 P2---O6 1.4961 (12) O1---Mg1^iv^ 2.0615 (11) P2---O4 1.5737 (12) O3---H3D 0.8200 P2---C1 1.8515 (16) O4---H4A 0.8200 O5^i^---Mg1---O5 179.999 (1) C3---N1---C1 112.68 (13) O5^i^---Mg1---O1^ii^ 88.62 (5) C2---N1---C1 112.71 (13) O5---Mg1---O1^ii^ 91.38 (5) C3---N1---H1B 107.1 O5^i^---Mg1---O1^iii^ 91.38 (5) C2---N1---H1B 107.1 O5---Mg1---O1^iii^ 88.62 (5) C1---N1---H1B 107.1 O1^ii^---Mg1---O1^iii^ 180.0 N1---C1---P1 112.08 (10) O5^i^---Mg1---O2 91.82 (4) N1---C1---P2 115.59 (10) O5---Mg1---O2 88.18 (4) P1---C1---P2 113.39 (8) O1^ii^---Mg1---O2 84.94 (4) N1---C1---H1A 104.8 O1^iii^---Mg1---O2 95.06 (4) P1---C1---H1A 104.8 O5^i^---Mg1---O2^i^ 88.19 (4) P2---C1---H1A 104.8 O5---Mg1---O2^i^ 91.82 (4) N1---C2---H2A 109.5 O1^ii^---Mg1---O2^i^ 95.06 (4) N1---C2---H2B 109.5 O1^iii^---Mg1---O2^i^ 84.94 (4) H2A---C2---H2B 109.5 O2---Mg1---O2^i^ 180.00 (6) N1---C2---H2C 109.5 O1---P1---O2 117.90 (7) H2A---C2---H2C 109.5 O1---P1---O3 107.58 (7) H2B---C2---H2C 109.5 O2---P1---O3 111.67 (7) N1---C3---H3A 109.5 O1---P1---C1 111.24 (7) N1---C3---H3B 109.5 O2---P1---C1 103.22 (7) H3A---C3---H3B 109.5 O3---P1---C1 104.42 (7) N1---C3---H3C 109.5 O5---P2---O6 117.19 (7) H3A---C3---H3C 109.5 O5---P2---O4 111.67 (7) H3B---C3---H3C 109.5 O6---P2---O4 106.96 (7) P1---O1---Mg1^iv^ 148.50 (8) O5---P2---C1 104.71 (7) P1---O2---Mg1 139.08 (7) O6---P2---C1 108.34 (7) P1---O3---H3D 109.5 O4---P2---C1 107.57 (7) P2---O4---H4A 109.5 C3---N1---C2 109.91 (14) P2---O5---Mg1 137.38 (7) ------------------------ ------------- ------------------- ------------- ::: Symmetry codes: (i) −*x*, −*y*+1, −*z*+1; (ii) −*x*+1, −*y*+1, −*z*+1; (iii) *x*−1, *y*, *z*; (iv) *x*+1, *y*, *z*. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2030 .table-wrap} ------------------- --------- --------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1B···O3 0.91 2.57 3.0997 (18) 118 N1---H1B···O4^v^ 0.91 2.31 3.1346 (18) 151 O3---H3D···O6^vi^ 0.82 1.70 2.5011 (16) 166 O4---H4A···O2^ii^ 0.82 1.81 2.6037 (16) 163 ------------------- --------- --------- ------------- --------------- ::: Symmetry codes: (v) −*x*+3/2, *y*−1/2, −*z*+3/2; (vi) −*x*+1/2, *y*−1/2, −*z*+3/2; (ii) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- --------- ------- ------------- ------------- N1---H1*B*⋯O3 0.91 2.57 3.0997 (18) 118 N1---H1*B*⋯O4^i^ 0.91 2.31 3.1346 (18) 151 O3---H3*D*⋯O6^ii^ 0.82 1.70 2.5011 (16) 166 O4---H4*A*⋯O2^iii^ 0.82 1.81 2.6037 (16) 163 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.515437

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052111/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m362-m363", "authors": [ { "first": "Qiao-Sheng", "last": "Hu" }, { "first": "Xiao-Yu", "last": "Deng" }, { "first": "Yu-Hui", "last": "Sun" }, { "first": "Zi-Yi", "last": "Du" } ] }

PMC3052112

Related literature {#sec1} ================== For tetrahydrocarbazole systems present in the framework of a number of indole-type alkaloids of biological interest, see: Saxton (1983[@bb10]). For related structures and background references, see: Patır *et al.* (1997[@bb7]); Hökelek & Patır (1999[@bb6]). For applications of carbazole derivatives, see: Cloutet *et al.* (1999[@bb3]); Wei *et al.* (2006[@bb15]); Tirapattur *et al.* (2003[@bb14]); Taoudi *et al.* (2001[@bb13]); Saraswathi *et al.* (1999[@bb9]); Sarac *et al.* (2000[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~17~H~14~Br~2~N~2~*M* *~r~* = 406.10Monoclinic,*a* = 10.5654 (2) Å*b* = 13.1471 (3) Å*c* = 11.6260 (2) Åβ = 105.257 (2)°*V* = 1557.99 (6) Å^3^*Z* = 4Mo *K*α radiationμ = 5.20 mm^−1^*T* = 100 K0.34 × 0.27 × 0.24 mm ### Data collection {#sec2.1.2} Bruker Kappa APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2005[@bb1]) *T* ~min~ = 0.201, *T* ~max~ = 0.28615409 measured reflections3906 independent reflections3344 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.022 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.023*wR*(*F* ^2^) = 0.054*S* = 1.043906 reflections190 parametersH-atom parameters constrainedΔρ~max~ = 0.52 e Å^−3^Δρ~min~ = −0.36 e Å^−3^ {#d5e381} Data collection: *APEX2* (Bruker, 2007[@bb2]); cell refinement: *SAINT* (Bruker, 2007[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb11]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb11]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb4]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb5]) and *PLATON* (Spek, 2009[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005162/xu5160sup1.cif](http://dx.doi.org/10.1107/S1600536811005162/xu5160sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005162/xu5160Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005162/xu5160Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5160&file=xu5160sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5160sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5160&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5160](http://scripts.iucr.org/cgi-bin/sendsup?xu5160)). The authors are indebted to Anadolu University and the Medicinal Plants and Medicine Research Centre of Anadolu University, Eskişehir, Turkey, for the use of X-ray diffractometer. This work was supported financially by the Turkish Scientific Research Council (grant No. TUBITAK-105 T516). Comment ======= Tetrahydrocarbazole systems are present in the framework of a number of indole-type alkaloids of biological interest (Saxton, 1983). The structures of tricyclic, tetracyclic and pentacyclic ring systems with dithiolane and other substituents of the tetrahydrocarbazole core, have been reported previously (Patır *et al.*, 1997; Hökelek & Patır, 1999). Substituted carbazole based monomers exhibit good electroactive and photoactive properties which make them the most promising candidates for hole transporting mobility of charge carriers (Cloutet *et al.*, 1999) and photoluminescence efficiencies (Wei *et al.*, 2006). Carbazole based heterocyclic polymer systems can be chemically or electrochemically polymerized to yield materials with interesting properties with a number of applications, such as electroluminescent (Tirapattur *et al.*, 2003), photoactive devices (Taoudi *et al.*, 2001), sensors and rechargable batteries (Saraswathi *et al.*, 1999) and electrochromic displays (Sarac *et al.*, 2000). The title compound, (I), may be considered as a synthetic precursor of tetracyclic indole alkaloids of biological interests. The present study was undertaken to ascertain its crystal structure. The title compound consists of a carbazole skeleton with a pentanenitrile group (Fig. 1), where the bond lengths and angles are within normal ranges, and generally agree with those in the previously reported compounds. In all structures atom N9 is substituted. An examination of the deviations from the least-squares planes through individual rings shows that rings A (C1---C4/C4a/C9a), B (C4a/C5a/C8a/N9/C9a) and C (C5a/C5---C8/C8a) are planar. The carbazole skeleton, containing the rings A, B and C is also nearly coplanar \[with a maximum deviation of 0.055 (2) Å for atom C2\] with dihedral angles of A/B = 2.10 (6), A/C = 2.79 (5) and B/C = 0.69 (5) °. Atoms Br1, C10 and Br2 displaced by 0.0476 (2), 0.062 (2) and 0.0052 (2) Å from the corresponding planes of the carbazole skeleton. In the crystal structure, molecules are alongated along the *b* axis and stacked nearly parallel to (101) (Fig. 2). The π···π contacts between the pyrrole and benzene rings and the benzene rings, *Cg*2---*Cg*3^i^ and *Cg*3···*Cg*3^i^ \[symmetry code: (i) -*x*, 1 - *y*, -*z*, where *Cg*1, *Cg*2 and *Cg*3 are centroids of the rings A (C1---C4/C4a/C9a), B (C4a/C5a/C8a/N9/C9a) and C (C5a/C5---C8/C8a), respectively\] may stabilize the structure, with centroid-centroid distances of 3.548 (1) and 3.4769 (11) Å, respectively. Experimental {#experimental} ============ For the preparation of the title compound, (I), sodium hydride (1.16 g, 30.76 mmol) was added to a solution of 3,6-dibromocarbazole (5.00 g, 15.38 mmol) in dry tetrahydrofuran (200 ml) in several portions, and stirred at 353 K for 2 h under argon atmosphere. Then, chlorovaleronitrile (3.46 ml, 30.76 mmol) was added and stirred at 373 K for 6 d. The reaction mixture was cooled in an ice bath, and hydrochloric acid (10%, 200 ml) was added. After the extraction with chloroform (300 ml), the organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography using silica gel and chloroform, and the product was recrystallized from diethyl ether (yield 4.50 g, 80.12%; m.p. 327 K). Refinement {#refinement} ========== H atoms were positioned geometrically with C---H = 0.95 and 0.99 Å for aromatic and methylene H atoms, respectively, and constrained to ride on their parent atoms, with *U*~iso~(H) = *1.2U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title molecule with the atom-numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o642-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A partial packing diagram. Hydrogen atoms have been omitted for clarity. ::: ![](e-67-0o642-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e180 .table-wrap} ------------------------- --------------------------------------- C~17~H~14~Br~2~N~2~ *F*(000) = 800 *M~r~* = 406.10 *D*~x~ = 1.731 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 6957 reflections *a* = 10.5654 (2) Å θ = 2.3--28.3° *b* = 13.1471 (3) Å µ = 5.20 mm^−1^ *c* = 11.6260 (2) Å *T* = 100 K β = 105.257 (2)° Block, colorless *V* = 1557.99 (6) Å^3^ 0.34 × 0.27 × 0.24 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e310 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker Kappa APEXII CCD area-detector diffractometer 3906 independent reflections Radiation source: fine-focus sealed tube 3344 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.022 φ and ω scans θ~max~ = 28.4°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Bruker, 2005) *h* = −14→12 *T*~min~ = 0.201, *T*~max~ = 0.286 *k* = −17→16 15409 measured reflections *l* = −15→15 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e427 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.023 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.054 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0246*P*)^2^ + 0.8394*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3906 reflections (Δ/σ)~max~ = 0.001 190 parameters Δρ~max~ = 0.52 e Å^−3^ 0 restraints Δρ~min~ = −0.36 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e584 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e683 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 1.00971 (2) 0.746932 (15) 0.392293 (17) 0.02544 (6) Br2 0.636774 (19) 1.287581 (14) 0.589087 (17) 0.02193 (6) C1 0.6131 (2) 0.78706 (15) 0.22924 (16) 0.0211 (4) H1 0.5468 0.7526 0.1712 0.025\* C2 0.7401 (2) 0.75033 (15) 0.26348 (16) 0.0210 (4) H2 0.7622 0.6904 0.2274 0.025\* C3 0.83635 (18) 0.80073 (14) 0.35103 (16) 0.0190 (4) C4 0.81077 (18) 0.88872 (14) 0.40557 (15) 0.0172 (4) H4 0.8771 0.9213 0.4655 0.021\* C4A 0.68395 (18) 0.92805 (13) 0.36933 (15) 0.0157 (3) C5 0.66897 (18) 1.09921 (13) 0.47909 (15) 0.0160 (3) H5 0.7573 1.1017 0.5261 0.019\* C5A 0.62282 (17) 1.01868 (14) 0.40085 (14) 0.0152 (3) C6 0.58032 (18) 1.17500 (14) 0.48494 (15) 0.0177 (4) C7 0.44886 (19) 1.17234 (15) 0.41908 (16) 0.0196 (4) H7 0.3913 1.2259 0.4268 0.024\* C8 0.40232 (18) 1.09231 (15) 0.34294 (16) 0.0193 (4) H8 0.3130 1.0893 0.2984 0.023\* C8A 0.49060 (18) 1.01611 (14) 0.33353 (15) 0.0168 (4) C9A 0.58570 (18) 0.87634 (14) 0.28268 (15) 0.0175 (4) N9 0.46917 (15) 0.92922 (12) 0.26366 (13) 0.0185 (3) N10 −0.06092 (19) 0.97527 (16) −0.28226 (17) 0.0359 (4) C10 0.34532 (18) 0.90394 (15) 0.17760 (16) 0.0208 (4) H10A 0.2718 0.9203 0.2125 0.025\* H10B 0.3428 0.8299 0.1615 0.025\* C11 0.32683 (18) 0.96151 (14) 0.06050 (16) 0.0189 (4) H11A 0.3385 1.0353 0.0771 0.023\* H11B 0.3944 0.9395 0.0208 0.023\* C12 0.19112 (18) 0.94248 (15) −0.02221 (15) 0.0193 (4) H12A 0.1235 0.9614 0.0189 0.023\* H12B 0.1810 0.8692 −0.0421 0.023\* C13 0.17058 (19) 1.00466 (16) −0.13739 (16) 0.0234 (4) H13A 0.1815 1.0778 −0.1169 0.028\* H13B 0.2388 0.9857 −0.1778 0.028\* C14 0.0405 (2) 0.98855 (16) −0.21986 (17) 0.0247 (4) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1158 .table-wrap} ----- -------------- -------------- -------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.02541 (11) 0.02488 (11) 0.02659 (10) 0.00894 (8) 0.00780 (8) −0.00022 (8) Br2 0.02582 (11) 0.01562 (10) 0.02420 (10) −0.00012 (7) 0.00630 (8) −0.00316 (7) C1 0.0282 (10) 0.0212 (10) 0.0139 (8) −0.0040 (8) 0.0054 (7) −0.0019 (7) C2 0.0304 (11) 0.0171 (9) 0.0174 (9) 0.0008 (8) 0.0096 (8) −0.0014 (7) C3 0.0194 (9) 0.0205 (10) 0.0184 (9) 0.0034 (7) 0.0072 (7) 0.0033 (7) C4 0.0198 (9) 0.0190 (9) 0.0131 (8) −0.0001 (7) 0.0050 (7) 0.0014 (6) C4A 0.0202 (9) 0.0164 (9) 0.0111 (8) −0.0023 (7) 0.0051 (7) 0.0003 (6) C5 0.0169 (9) 0.0167 (9) 0.0145 (8) −0.0004 (7) 0.0046 (7) 0.0019 (6) C5A 0.0165 (9) 0.0177 (9) 0.0123 (8) −0.0001 (7) 0.0052 (7) 0.0034 (6) C6 0.0241 (10) 0.0140 (9) 0.0155 (8) −0.0021 (7) 0.0059 (7) −0.0002 (6) C7 0.0205 (9) 0.0193 (9) 0.0204 (9) 0.0054 (7) 0.0077 (7) 0.0052 (7) C8 0.0167 (9) 0.0233 (10) 0.0173 (9) 0.0010 (7) 0.0033 (7) 0.0037 (7) C8A 0.0195 (9) 0.0182 (9) 0.0124 (8) −0.0013 (7) 0.0036 (7) 0.0030 (6) C9A 0.0208 (9) 0.0195 (9) 0.0129 (8) −0.0009 (7) 0.0054 (7) 0.0019 (6) N9 0.0186 (8) 0.0212 (8) 0.0138 (7) −0.0016 (6) 0.0010 (6) −0.0002 (6) N10 0.0297 (11) 0.0438 (12) 0.0288 (10) −0.0051 (9) −0.0018 (8) 0.0102 (8) C10 0.0199 (10) 0.0229 (10) 0.0177 (9) −0.0049 (7) 0.0015 (7) 0.0004 (7) C11 0.0192 (9) 0.0196 (10) 0.0169 (8) −0.0014 (7) 0.0030 (7) 0.0022 (7) C12 0.0186 (9) 0.0216 (10) 0.0166 (8) −0.0030 (7) 0.0029 (7) 0.0005 (7) C13 0.0240 (10) 0.0257 (11) 0.0184 (9) −0.0050 (8) 0.0017 (7) 0.0035 (7) C14 0.0279 (11) 0.0258 (11) 0.0197 (9) −0.0012 (8) 0.0048 (8) 0.0053 (8) ----- -------------- -------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1565 .table-wrap} ----------------------- -------------- ----------------------- -------------- Br1---C3 1.9033 (19) C9A---C1 1.394 (3) Br2---C6 1.9059 (18) C9A---C4A 1.416 (2) C1---H1 0.9500 N9---C8A 1.385 (2) C2---C1 1.382 (3) N9---C9A 1.380 (2) C2---H2 0.9500 N9---C10 1.461 (2) C3---C2 1.402 (3) N10---C14 1.138 (3) C4---C3 1.380 (3) C10---H10A 0.9900 C4---H4 0.9500 C10---H10B 0.9900 C4A---C4 1.394 (3) C11---C10 1.525 (2) C4A---C5A 1.448 (2) C11---H11A 0.9900 C5---C5A 1.397 (2) C11---H11B 0.9900 C5---H5 0.9500 C12---C11 1.522 (3) C5A---C8A 1.411 (3) C12---H12A 0.9900 C6---C5 1.381 (3) C12---H12B 0.9900 C6---C7 1.399 (3) C13---C12 1.535 (2) C7---H7 0.9500 C13---H13A 0.9900 C8---C7 1.380 (3) C13---H13B 0.9900 C8---H8 0.9500 C14---C13 1.470 (3) C8A---C8 1.393 (3) C2---C1---C9A 117.75 (18) N9---C8A---C8 129.03 (17) C2---C1---H1 121.1 C1---C9A---C4A 121.49 (17) C9A---C1---H1 121.1 N9---C9A---C1 129.35 (18) C1---C2---C3 120.53 (17) N9---C9A---C4A 109.16 (16) C1---C2---H2 119.7 C8A---N9---C10 124.59 (16) C3---C2---H2 119.7 C9A---N9---C8A 108.68 (15) C2---C3---Br1 118.28 (14) C9A---N9---C10 126.55 (16) C4---C3---Br1 119.19 (15) N9---C10---C11 112.32 (15) C4---C3---C2 122.51 (18) N9---C10---H10A 109.1 C3---C4---C4A 117.46 (17) N9---C10---H10B 109.1 C3---C4---H4 121.3 C11---C10---H10A 109.1 C4A---C4---H4 121.3 C11---C10---H10B 109.1 C4---C4A---C5A 133.33 (17) H10A---C10---H10B 107.9 C4---C4A---C9A 120.22 (16) C10---C11---H11A 109.4 C9A---C4A---C5A 106.44 (16) C10---C11---H11B 109.4 C5A---C5---H5 121.5 C12---C11---C10 111.13 (15) C6---C5---C5A 116.97 (17) C12---C11---H11A 109.4 C6---C5---H5 121.5 C12---C11---H11B 109.4 C5---C5A---C4A 133.30 (17) H11A---C11---H11B 108.0 C5---C5A---C8A 120.28 (16) C11---C12---C13 110.92 (15) C8A---C5A---C4A 106.41 (16) C11---C12---H12A 109.5 C5---C6---Br2 119.25 (14) C11---C12---H12B 109.5 C5---C6---C7 122.91 (17) C13---C12---H12A 109.5 C7---C6---Br2 117.83 (14) C13---C12---H12B 109.5 C6---C7---H7 119.8 H12A---C12---H12B 108.0 C8---C7---C6 120.35 (17) C12---C13---H13A 109.1 C8---C7---H7 119.8 C12---C13---H13B 109.1 C7---C8---C8A 117.78 (17) C14---C13---C12 112.69 (16) C7---C8---H8 121.1 C14---C13---H13A 109.1 C8A---C8---H8 121.1 C14---C13---H13B 109.1 C8---C8A---C5A 121.68 (17) H13A---C13---H13B 107.8 C1---C9A---C4A 121.49 (17) N10---C14---C13 178.9 (2) N9---C8A---C5A 109.28 (16) C3---C2---C1---C9A 1.4 (3) N9---C8A---C8---C7 −179.45 (16) Br1---C3---C2---C1 −179.17 (14) C5A---C8A---C8---C7 1.3 (2) C4---C3---C2---C1 −0.9 (3) N9---C9A---C1---C2 179.02 (17) C4A---C4---C3---Br1 177.36 (12) C4A---C9A---C1---C2 −0.1 (3) C4A---C4---C3---C2 −0.9 (3) N9---C9A---C4A---C4 179.02 (15) C5A---C4A---C4---C3 −176.78 (17) N9---C9A---C4A---C5A −1.80 (18) C9A---C4A---C4---C3 2.1 (2) C1---C9A---C4A---C4 −1.7 (3) C4---C4A---C5A---C5 −0.1 (3) C1---C9A---C4A---C5A 177.48 (15) C4---C4A---C5A---C8A −179.90 (18) C9A---N9---C8A---C5A −1.15 (19) C9A---C4A---C5A---C5 −179.15 (17) C9A---N9---C8A---C8 179.49 (17) C9A---C4A---C5A---C8A 1.08 (18) C10---N9---C8A---C5A −176.60 (15) C6---C5---C5A---C4A 179.22 (17) C10---N9---C8A---C8 4.0 (3) C6---C5---C5A---C8A −1.0 (2) C8A---N9---C9A---C1 −177.36 (17) C4A---C5A---C8A---N9 0.02 (18) C8A---N9---C9A---C4A 1.85 (19) C4A---C5A---C8A---C8 179.44 (15) C10---N9---C9A---C1 −2.0 (3) C5---C5A---C8A---N9 −179.80 (14) C10---N9---C9A---C4A 177.18 (15) C5---C5A---C8A---C8 −0.4 (2) C8A---N9---C10---C11 79.5 (2) Br2---C6---C5---C5A −179.64 (12) C9A---N9---C10---C11 −95.1 (2) C7---C6---C5---C5A 1.6 (2) C12---C11---C10---N9 −173.89 (15) Br2---C6---C7---C8 −179.52 (13) C13---C12---C11---C10 177.23 (16) C5---C6---C7---C8 −0.7 (3) C14---C13---C12---C11 −179.95 (17) C8A---C8---C7---C6 −0.7 (3) ----------------------- -------------- ----------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.519020

2011-2-16

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052112/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o642", "authors": [ { "first": "Nesimi", "last": "Uludağ" }, { "first": "Murat", "last": "Ateş" }, { "first": "Barış", "last": "Tercan" }, { "first": "Tuncer", "last": "Hökelek" } ] }

PMC3052113

Related literature {#sec1} ================== For the sulfanilamide moiety in sulfonamide drugs, see; Maren (1976[@bb5]). For its ability to form hydrogen bonds in the solid state, see; Yang & Guillory (1972[@bb9]). For the hydrogen-bonding characteristics of sulfonamides, see; Adsmond & Grant (2001[@bb1]). For the effect of substituents on the crystal structures of sulfonoamides, see: Gowda *et al.* (2008[@bb4], 2009[@bb2], 2010[@bb3]) Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~12~ClNO~3~S*M* *~r~* = 261.72Triclinic,*a* = 8.365 (1) Å*b* = 8.719 (1) Å*c* = 9.143 (1) Åα = 92.74 (1)°β = 104.22 (1)°γ = 108.75 (1)°*V* = 606.24 (12) Å^3^*Z* = 2Mo *K*α radiationμ = 0.48 mm^−1^*T* = 293 K0.45 × 0.35 × 0.35 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorAbsorption correction: multi-scan (*CrysAlis RED*; Oxford Diffraction, 2009[@bb6]) *T* ~min~ = 0.814, *T* ~max~ = 0.8514031 measured reflections2481 independent reflections2200 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.011 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.036*wR*(*F* ^2^) = 0.102*S* = 1.042481 reflections149 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.39 e Å^−3^Δρ~min~ = −0.27 e Å^−3^ {#d5e418} Data collection: *CrysAlis CCD* (Oxford Diffraction, 2009[@bb6]); cell refinement: *CrysAlis RED* (Oxford Diffraction, 2009[@bb6]); data reduction: *CrysAlis RED*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *PLATON* (Spek, 2009[@bb8]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004284/ds2091sup1.cif](http://dx.doi.org/10.1107/S1600536811004284/ds2091sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004284/ds2091Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004284/ds2091Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ds2091&file=ds2091sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ds2091sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ds2091&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DS2091](http://scripts.iucr.org/cgi-bin/sendsup?ds2091)). KS thanks the University Grants Commission, Government of India, New Delhi, for the award of a research fellowship under its faculty improvement program. Comment ======= The molecular structures of sulfonamide drugs contain the sulfanilamide moiety (Maren, 1976). The affinity for hydrogen bonding in the solid state due to the presence of various hydrogen bond donors and acceptors can give rise to polymorphism (Yang & Guillory, 1972). The hydrogen bonding preferences of sulfonamides has also been investigated (Adsmond & Grant, 2001). The nature and position of substituents play a significant role on the crystal structures of *N*-(aryl)sulfonoamides (Gowda *et al.*, 2008, 2009, 2010). As a part of studying the substituent effects on the structures of this class of compounds, the structure of *N*-(2-chlorophenylsulfonyl)-2,2-dimethylacetamide (I) has been determined. The conformations of the N---H and C=O bonds of the SO~2~---NH---CO---C segment in the structure are anti to each other (Fig. 1), similar to that observed in *N*-(phenylsulfonyl)-acetamide (II) (Gowda *et al.*, 2010), 2,2-dimethyl-*N*-(phenylsulfonyl)- acetamide (III)(Gowda *et al.*, 2009) and 2,2-dichloro-*N*- (phenylsulfonyl)-acetamide (IV) (Gowda *et al.*, 2008). The molecule in (I) is bent at the *S*-atom with a C1---S1---N1---C7 torsion angle of 64.4 (2)°, compared to the values of -58.8 (4)° in (II), 67.1 (3)° in (III) and -66.3 (3)° in (IV). Further, the dihedral angle between the benzene ring and the SO2---NH---CO---C group in (I) is 87.4 (1)°, compared to the values of 89.0 (2)° in (II), 87.4 (1)° in (III) and 79.8 (1)° in (IV), In the crystal structure, the intermolecular N--H···O hydrogen bonds (Table 1) link the molecules through inversion-related dimers into zigzag chains in the *bc*-plane. Part of the crystal structure is shown in Fig. 2. Experimental {#experimental} ============ The title compound was prepared by refluxing 2-chlorobenzenesulfonamide (0.10 mole) with an excess of 2,2-dimethylacetyl chloride (0.20 mole) for one hour on a water bath. The reaction mixture was cooled and poured into ice cold water. The resulting solid was separated, washed thoroughly with water and dissolved in warm dilute sodium hydrogen carbonate solution. The title compound was reprecipitated by acidifying the filtered solution with glacial acetic acid. It was filtered, dried and recrystallized from ethanol. The purity of the compound was checked by determining its melting point. It was further characterized by recording its infrared spectra. Prism like colorless single crystals of the title compound used in X-ray diffraction studies were obtained from a slow evaporation of an ethanolic solution of the compound. Refinement {#refinement} ========== The H atom of the NH group was located in a difference map and later restrained to the distance N---H = 0.86 (2) Å. The other H atoms were positioned with idealized geometry using a riding model with C---H = 0.93--0.98 Å. All H atoms were refined with isotropic displacement parameters (set to 1.2 times of the *U*~eq~ of the parent atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound, showing the atom- labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o595-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Molecular packing in the title compound. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o595-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------ --------------------------------------- C~10~H~12~ClNO~3~S *Z* = 2 *M~r~* = 261.72 *F*(000) = 272 Triclinic, *P*1 *D*~x~ = 1.434 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.365 (1) Å Cell parameters from 2678 reflections *b* = 8.719 (1) Å θ = 3.0--27.7° *c* = 9.143 (1) Å µ = 0.48 mm^−1^ α = 92.74 (1)° *T* = 293 K β = 104.22 (1)° Prism, colourless γ = 108.75 (1)° 0.45 × 0.35 × 0.35 mm *V* = 606.24 (12) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e277 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector 2481 independent reflections Radiation source: fine-focus sealed tube 2200 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.011 Rotation method data acquisition using ω scans θ~max~ = 26.4°, θ~min~ = 3.0° Absorption correction: multi-scan (*CrysAlis RED*; Oxford Diffraction, 2009) *h* = −10→10 *T*~min~ = 0.814, *T*~max~ = 0.851 *k* = −10→9 4031 measured reflections *l* = −11→11 ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e392 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.036 H atoms treated by a mixture of independent and constrained refinement *wR*(*F*^2^) = 0.102 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0589*P*)^2^ + 0.1796*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.04 (Δ/σ)~max~ \< 0.001 2481 reflections Δρ~max~ = 0.39 e Å^−3^ 149 parameters Δρ~min~ = −0.27 e Å^−3^ 1 restraint Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.074 (7) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e573 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. CrysAlis RED (Oxford Diffraction, 2009) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e678 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.8887 (2) 0.33504 (18) 0.17180 (18) 0.0374 (3) C2 0.9618 (2) 0.2693 (2) 0.07502 (19) 0.0455 (4) C3 1.1391 (3) 0.3366 (3) 0.0881 (2) 0.0571 (5) H3 1.1882 0.2924 0.0234 0.069\* C4 1.2436 (3) 0.4688 (3) 0.1967 (3) 0.0581 (5) H4 1.3630 0.5137 0.2051 0.070\* C5 1.1725 (3) 0.5347 (2) 0.2926 (2) 0.0546 (5) H5 1.2436 0.6243 0.3656 0.065\* C6 0.9956 (2) 0.4682 (2) 0.2808 (2) 0.0441 (4) H6 0.9477 0.5128 0.3462 0.053\* C7 0.7107 (2) 0.0482 (2) 0.36475 (18) 0.0397 (4) C8 0.6623 (2) −0.1303 (2) 0.3835 (2) 0.0481 (4) H8 0.5375 −0.1848 0.3306 0.058\* C9 0.6889 (5) −0.1514 (4) 0.5501 (3) 0.0922 (9) H9A 0.6168 −0.1053 0.5915 0.111\* H9B 0.8101 −0.0965 0.6046 0.111\* H9C 0.6566 −0.2657 0.5599 0.111\* C10 0.7668 (3) −0.2058 (3) 0.3089 (3) 0.0720 (6) H10A 0.8900 −0.1503 0.3556 0.086\* H10B 0.7401 −0.1958 0.2023 0.086\* H10C 0.7368 −0.3194 0.3215 0.086\* Cl1 0.83725 (8) 0.10188 (7) −0.06290 (7) 0.0749 (2) N1 0.63339 (19) 0.07529 (16) 0.22009 (16) 0.0418 (3) H1N 0.578 (3) −0.005 (2) 0.150 (2) 0.050\* O1 0.55713 (17) 0.22202 (16) 0.00990 (15) 0.0571 (4) O2 0.63345 (17) 0.36011 (15) 0.27093 (17) 0.0567 (4) O3 0.8089 (2) 0.16099 (17) 0.46098 (15) 0.0609 (4) S1 0.66390 (5) 0.25610 (5) 0.16468 (5) 0.04147 (16) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1076 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0413 (8) 0.0280 (7) 0.0386 (8) 0.0104 (6) 0.0055 (6) 0.0046 (6) C2 0.0544 (10) 0.0359 (8) 0.0409 (8) 0.0119 (7) 0.0098 (7) −0.0009 (7) C3 0.0622 (12) 0.0528 (11) 0.0604 (11) 0.0176 (9) 0.0277 (10) 0.0037 (9) C4 0.0452 (10) 0.0501 (11) 0.0717 (13) 0.0050 (8) 0.0189 (9) 0.0054 (9) C5 0.0481 (10) 0.0384 (9) 0.0610 (11) 0.0013 (8) 0.0072 (8) −0.0068 (8) C6 0.0469 (9) 0.0341 (8) 0.0452 (9) 0.0108 (7) 0.0077 (7) −0.0024 (7) C7 0.0393 (8) 0.0378 (8) 0.0400 (8) 0.0126 (7) 0.0090 (7) 0.0020 (6) C8 0.0424 (9) 0.0400 (9) 0.0549 (10) 0.0088 (7) 0.0070 (8) 0.0130 (8) C9 0.118 (2) 0.0910 (19) 0.0757 (17) 0.0331 (18) 0.0383 (16) 0.0458 (15) C10 0.0806 (16) 0.0527 (12) 0.0824 (16) 0.0358 (12) 0.0069 (12) −0.0016 (11) Cl1 0.0767 (4) 0.0630 (4) 0.0670 (4) 0.0134 (3) 0.0098 (3) −0.0306 (3) N1 0.0444 (8) 0.0286 (7) 0.0412 (7) 0.0055 (6) 0.0017 (6) 0.0008 (5) O1 0.0500 (7) 0.0446 (7) 0.0586 (8) 0.0094 (6) −0.0090 (6) 0.0123 (6) O2 0.0506 (7) 0.0399 (7) 0.0824 (10) 0.0184 (6) 0.0210 (7) 0.0004 (6) O3 0.0738 (9) 0.0465 (7) 0.0459 (7) 0.0160 (7) −0.0040 (6) −0.0078 (6) S1 0.0381 (2) 0.0302 (2) 0.0493 (3) 0.01005 (16) 0.00256 (17) 0.00424 (17) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1378 .table-wrap} -------------------- -------------- ------------------- -------------- C1---C6 1.387 (2) C7---C8 1.507 (2) C1---C2 1.389 (2) C8---C10 1.511 (3) C1---S1 1.7659 (17) C8---C9 1.514 (3) C2---C3 1.380 (3) C8---H8 0.9800 C2---Cl1 1.7344 (18) C9---H9A 0.9600 C3---C4 1.377 (3) C9---H9B 0.9600 C3---H3 0.9300 C9---H9C 0.9600 C4---C5 1.371 (3) C10---H10A 0.9600 C4---H4 0.9300 C10---H10B 0.9600 C5---C6 1.379 (3) C10---H10C 0.9600 C5---H5 0.9300 N1---S1 1.6396 (14) C6---H6 0.9300 N1---H1N 0.843 (15) C7---O3 1.208 (2) O1---S1 1.4341 (13) C7---N1 1.390 (2) O2---S1 1.4202 (14) C6---C1---C2 119.32 (16) C7---C8---H8 108.1 C6---C1---S1 117.57 (13) C10---C8---H8 108.1 C2---C1---S1 123.11 (13) C9---C8---H8 108.1 C3---C2---C1 119.91 (16) C8---C9---H9A 109.5 C3---C2---Cl1 118.08 (14) C8---C9---H9B 109.5 C1---C2---Cl1 122.01 (14) H9A---C9---H9B 109.5 C4---C3---C2 120.17 (18) C8---C9---H9C 109.5 C4---C3---H3 119.9 H9A---C9---H9C 109.5 C2---C3---H3 119.9 H9B---C9---H9C 109.5 C5---C4---C3 120.34 (18) C8---C10---H10A 109.5 C5---C4---H4 119.8 C8---C10---H10B 109.5 C3---C4---H4 119.8 H10A---C10---H10B 109.5 C4---C5---C6 119.98 (17) C8---C10---H10C 109.5 C4---C5---H5 120.0 H10A---C10---H10C 109.5 C6---C5---H5 120.0 H10B---C10---H10C 109.5 C5---C6---C1 120.28 (17) C7---N1---S1 124.59 (11) C5---C6---H6 119.9 C7---N1---H1N 119.7 (15) C1---C6---H6 119.9 S1---N1---H1N 115.1 (14) O3---C7---N1 120.87 (16) O2---S1---O1 118.79 (9) O3---C7---C8 125.77 (16) O2---S1---N1 109.66 (8) N1---C7---C8 113.34 (14) O1---S1---N1 104.14 (8) C7---C8---C10 109.40 (16) O2---S1---C1 107.71 (8) C7---C8---C9 110.55 (18) O1---S1---C1 110.42 (8) C10---C8---C9 112.5 (2) N1---S1---C1 105.30 (8) C6---C1---C2---C3 0.1 (3) O3---C7---C8---C9 23.2 (3) S1---C1---C2---C3 −179.39 (15) N1---C7---C8---C9 −158.19 (19) C6---C1---C2---Cl1 179.41 (13) O3---C7---N1---S1 −0.2 (2) S1---C1---C2---Cl1 0.0 (2) C8---C7---N1---S1 −178.89 (12) C1---C2---C3---C4 −0.1 (3) C7---N1---S1---O2 −51.29 (16) Cl1---C2---C3---C4 −179.50 (16) C7---N1---S1---O1 −179.42 (14) C2---C3---C4---C5 0.0 (3) C7---N1---S1---C1 64.35 (16) C3---C4---C5---C6 0.2 (3) C6---C1---S1---O2 4.95 (16) C4---C5---C6---C1 −0.3 (3) C2---C1---S1---O2 −175.59 (14) C2---C1---C6---C5 0.1 (3) C6---C1---S1---O1 136.13 (13) S1---C1---C6---C5 179.61 (14) C2---C1---S1---O1 −44.41 (16) O3---C7---C8---C10 −101.1 (2) C6---C1---S1---N1 −112.02 (14) N1---C7---C8---C10 77.45 (19) C2---C1---S1---N1 67.44 (15) -------------------- -------------- ------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1893 .table-wrap} ------------------ ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1N···O1^i^ 0.84 (2) 2.14 (2) 2.976 (2) 174 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*, −*z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ ---------- ---------- ----------- ------------- N1---H1*N*⋯O1^i^ 0.84 (2) 2.14 (2) 2.976 (2) 174 (2) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.524143

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052113/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o595", "authors": [ { "first": "K.", "last": "Shakuntala" }, { "first": "Sabine", "last": "Foro" }, { "first": "B. Thimme", "last": "Gowda" } ] }

PMC3052114

Related literature {#sec1} ================== For applications of *N*-heterocyclic carbenes, see: Tryg *et al.* (2005[@bb12]); Herrmann (2002[@bb4]); Tominaga *et al.* (2004[@bb11]); Magill *et al.* (2001[@bb7]); Arduengo *et al.* (1991[@bb1]); Herrmann & Kocher (1997[@bb6]); Herrmann *et al.* (1998[@bb5]); McGuinness *et al.* (1999[@bb8]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~38~N~4~ ^2+^·2PF~6~ ^−^*M* *~r~* = 684.53Monoclinic,*a* = 12.3851 (2) Å*b* = 19.6516 (3) Å*c* = 12.7586 (2) Åβ = 104.698 (1)°*V* = 3003.66 (8) Å^3^*Z* = 4Mo *K*α radiationμ = 0.24 mm^−1^*T* = 100 K0.39 × 0.17 × 0.12 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2009[@bb2]) *T* ~min~ = 0.911, *T* ~max~ = 0.97134854 measured reflections8766 independent reflections5113 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.064 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.055*wR*(*F* ^2^) = 0.135*S* = 1.038766 reflections453 parameters177 restraintsH-atom parameters constrainedΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e591} Data collection: *APEX2* (Bruker, 2009[@bb2]); cell refinement: *SAINT* (Bruker, 2009[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL* and *PLATON* (Spek, 2009[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003916/sj5098sup1.cif](http://dx.doi.org/10.1107/S1600536811003916/sj5098sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003916/sj5098Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003916/sj5098Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5098&file=sj5098sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5098sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5098&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5098](http://scripts.iucr.org/cgi-bin/sendsup?sj5098)). RAH thanks Universiti Sains Malaysia for the FRGS fund (203/PKIMIA/671115), short-term grant (304/PKIMIA/639001) and RU grants (1001/PKIMIA/813023 and 1001/PKIMIA/811157). AWS thanks Universiti Sains Malaysia for the RU grant (1001/PKIMIA/843090). HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for the Research University grant No. 1001/PFIZIK/811160. MH also thanks Universiti Sains Malaysia for a post-doctoral research fellowship. Comment ======= *N*-heterocyclic carbenes (NHCs) are now ubiquitous in their usage as ligands for transition metals (Tryg *et al.*, 2005; Herrmann, 2002). These complexes with different metals such as Pd and Ru have been used as catalysts for many reactions; for example C-C coupling reactions and reactions involving olefin metathesis (Tominaga *et al.*, 2004; Magill *et al.*, 2001). This has become an important area of research after the isolation of the first stable crystalline carbene (Arduengo *et al.*, 1991). NHCs are neutral 2-electron donors, with an ability to bond to both hard and soft metals making them more versatile ligands than phosphines (Herrmann & Kocher, 1997). They are easier to synthesise and functionalise and form stronger bonds to metals leading to more stable metal complexes than metal phosphine complexes (Herrmann *et al.*, 1998). The coordination chemistry of NHCs and their metal complexes continues to be actively studied, particularly for catalytic applications (McGuinness *et al.*, 1999). The asymmetric unit of the title compound, (Fig. 1), consists of a 1,3-bis(3-butylimidazolium-1-ylmethyl)mesitylene cation and two hexafluorophosphate anions. One of the butyl groups and four F atoms in the basal plane of one of the PF~6~^-^ octahedra are disordered over two sets of sites, with occupancy ratios of 0.704 (5):0.296 (5) and 0.71 (3):0.29 (3) respectively. The central benzene (C9--C14) ring makes dihedral angles of 85.17 (12)° and 81.97 (12)° with the terminal imidazole (N1/N2/C5--C7)/(N3/N4/C16--C18) rings. In the crystal structure (Fig. 2), the cations and anions are linked together *via* intermolecular C2---H2A···F5, C5---H5A···F9A, C6---H6A···F6, C6---H6A···F12, C7---H7A···F4, C15---H15A···F10A, C15---H15A···F11 and C19---H19B···F6 (Table 1) hydrogen bonds forming a three-dimensional network. Experimental {#experimental} ============ A mixture of 1,3-bis(bromomethyl)mesitylene (0.9 g, 3.0 mmol) and 1-butylimidazole (0.75 g, 6.0 mmol) in 25 ml of 1,4-dioxane was refluxed at 373 K for 24 h. The resulting slurry was isolated by decantation and washed with fresh 1,4-dioxane (2 x 5 ml) and diethyl ether (2 x 3 ml). The bromide salt was converted directly to its corresponding hexafluorophosphate by a metathesis reaction with methanolic KPF~6~ (1.2 g, 6.5 mmol). The resulting yellowish solid was washed with distilled water and recrystallised from acetonitrile to give pale-yellow crystals. (yield 1.4 g, 88.26 %). Crystals suitable for X-ray diffraction studies were obtained by slow evaporation of the salt solution in acetonitrile at ambient temperature. Refinement {#refinement} ========== All the H atoms were positioned geometrically \[ C--H = 0.93--0.97 Å \] and were refined using a riding model, with *U*~iso~(H) = 1.2 or 1.5 *U*~eq~(C). One of the butyl groups and the F7, F8, F9 and F10 fluorine atoms in the one of the phosphate anions are disordered over two sets of sites, with occupancy ratios of 0.704 (5):0.296 (5) and 0.71 (3):0.29 (3) respectively. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. Open bonds represents the minor disorder components \[H atoms are omitted for clarity\]. ::: ![](e-67-0o562-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound, showing a hydrogen-bonded (dashed lines) network. Only atoms of the major disorder components are shown for clarity. ::: ![](e-67-0o562-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e141 .table-wrap} ------------------------------ --------------------------------------- C~25~H~38~N~4~^2+^·2PF~6~^−^ *F*(000) = 1416 *M~r~* = 684.53 *D*~x~ = 1.514 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 5155 reflections *a* = 12.3851 (2) Å θ = 2.9--27.3° *b* = 19.6516 (3) Å µ = 0.24 mm^−1^ *c* = 12.7586 (2) Å *T* = 100 K β = 104.698 (1)° Block, pale yellow *V* = 3003.66 (8) Å^3^ 0.39 × 0.17 × 0.12 mm *Z* = 4 ------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e276 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 8766 independent reflections Radiation source: fine-focus sealed tube 5113 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.064 φ and ω scans θ~max~ = 30.1°, θ~min~ = 2.0° Absorption correction: multi-scan (*SADABS*; Bruker, 2009) *h* = −17→16 *T*~min~ = 0.911, *T*~max~ = 0.971 *k* = −25→27 34854 measured reflections *l* = −17→17 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e393 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.135 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.051*P*)^2^ + 0.7397*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 8766 reflections (Δ/σ)~max~ = 0.001 453 parameters Δρ~max~ = 0.33 e Å^−3^ 177 restraints Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e550 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e604 .table-wrap} ------ -------------- --------------- --------------- -------------------- ------------ *x* *y* *z* *U*~iso~\*/*U*~eq~ Occ. (\<1) P1 0.20895 (5) 0.21416 (3) 0.70794 (5) 0.02528 (14) F1 0.27007 (13) 0.19236 (8) 0.82874 (11) 0.0516 (4) F2 0.15016 (13) 0.23475 (8) 0.58707 (12) 0.0539 (4) F3 0.12414 (12) 0.25961 (7) 0.75254 (13) 0.0506 (4) F4 0.29111 (12) 0.27811 (7) 0.71659 (12) 0.0457 (4) F5 0.12931 (11) 0.14951 (7) 0.69934 (12) 0.0440 (4) F6 0.29625 (11) 0.16855 (7) 0.66468 (12) 0.0411 (4) P2 0.10834 (6) 0.08585 (3) 0.25608 (5) 0.03360 (16) F7A 0.1954 (7) 0.1328 (5) 0.2220 (9) 0.086 (2) 0.71 (3) F8A 0.0192 (10) 0.1437 (7) 0.2271 (10) 0.095 (3) 0.71 (3) F9A 0.0210 (6) 0.0378 (6) 0.2895 (7) 0.067 (2) 0.71 (3) F10A 0.1988 (7) 0.0260 (4) 0.2873 (7) 0.0559 (15) 0.71 (3) F7B 0.172 (3) 0.1469 (16) 0.231 (3) 0.137 (11) 0.29 (3) F8B −0.0055 (14) 0.1272 (12) 0.227 (2) 0.063 (4) 0.29 (3) F9B 0.0389 (18) 0.0197 (8) 0.2790 (14) 0.060 (4) 0.29 (3) F10B 0.2128 (15) 0.0415 (15) 0.279 (2) 0.088 (7) 0.29 (3) F11 0.07227 (13) 0.05889 (8) 0.13307 (11) 0.0469 (4) F12 0.14197 (13) 0.11048 (8) 0.37886 (11) 0.0539 (4) N1 0.85438 (15) 0.08695 (9) 0.41927 (14) 0.0265 (4) N2 0.73557 (15) 0.01726 (9) 0.32089 (14) 0.0269 (4) N3 0.84666 (14) 0.11056 (9) −0.07330 (14) 0.0259 (4) N4 0.94852 (15) 0.19703 (9) −0.00729 (15) 0.0288 (4) C1 0.8135 (2) 0.22441 (12) 0.6905 (2) 0.0394 (6) H1A 0.7985 0.2044 0.7539 0.059\* H1B 0.7463 0.2443 0.6467 0.059\* H1C 0.8695 0.2590 0.7117 0.059\* C2 0.85494 (19) 0.16985 (12) 0.62574 (19) 0.0333 (5) H2A 0.9262 0.1527 0.6679 0.040\* H2B 0.8025 0.1323 0.6124 0.040\* C3 0.8684 (2) 0.19657 (12) 0.51876 (18) 0.0344 (6) H3A 0.7952 0.2088 0.4743 0.041\* H3B 0.9126 0.2379 0.5325 0.041\* C4 0.92215 (19) 0.14853 (12) 0.45473 (18) 0.0322 (5) H4A 0.9334 0.1721 0.3915 0.039\* H4B 0.9948 0.1351 0.4990 0.039\* C5 0.85966 (19) 0.02770 (11) 0.47726 (18) 0.0306 (5) H5A 0.9056 0.0193 0.5459 0.037\* C6 0.78581 (19) −0.01605 (11) 0.41627 (18) 0.0301 (5) H6A 0.7714 −0.0603 0.4349 0.036\* C7 0.77865 (18) 0.07964 (11) 0.32502 (17) 0.0272 (5) H7A 0.7591 0.1125 0.2711 0.033\* C8 0.64688 (19) −0.01183 (11) 0.23136 (18) 0.0307 (5) H8A 0.5788 −0.0166 0.2551 0.037\* H8B 0.6694 −0.0568 0.2139 0.037\* C9 0.62393 (17) 0.03175 (10) 0.13126 (17) 0.0253 (5) C10 0.69484 (17) 0.02784 (10) 0.06159 (17) 0.0247 (5) C11 0.67302 (17) 0.06873 (11) −0.03184 (17) 0.0255 (5) C12 0.58185 (18) 0.11365 (11) −0.05516 (18) 0.0293 (5) C13 0.51248 (18) 0.11498 (11) 0.0150 (2) 0.0320 (5) H13A 0.4505 0.1435 −0.0012 0.038\* C14 0.53172 (18) 0.07571 (11) 0.10792 (19) 0.0295 (5) C15 0.74935 (18) 0.06444 (12) −0.10679 (18) 0.0311 (5) H15A 0.7756 0.0180 −0.1079 0.037\* H15B 0.7077 0.0761 −0.1797 0.037\* C16 0.94168 (18) 0.10753 (12) −0.11101 (18) 0.0304 (5) H16A 0.9588 0.0743 −0.1562 0.036\* C17 1.0046 (2) 0.16150 (12) −0.07013 (19) 0.0328 (5) H17A 1.0735 0.1728 −0.0820 0.039\* C18 0.85343 (18) 0.16506 (11) −0.01042 (17) 0.0266 (5) H18A 0.8003 0.1786 0.0254 0.032\* C19 0.9808 (2) 0.26251 (12) 0.0467 (2) 0.0404 (6) H19A 1.0614 0.2662 0.0701 0.048\* 0.704 (5) H19B 0.9509 0.2666 0.1097 0.048\* 0.704 (5) H19C 1.0461 0.2548 0.1047 0.048\* 0.296 (5) H19D 0.9222 0.2762 0.0790 0.048\* 0.296 (5) C20A 0.9304 (4) 0.32135 (17) −0.0399 (3) 0.0387 (9) 0.704 (5) H20A 0.9613 0.3165 −0.1022 0.046\* 0.704 (5) H20B 0.8502 0.3157 −0.0646 0.046\* 0.704 (5) C21A 0.9560 (3) 0.39198 (18) 0.0069 (3) 0.0426 (10) 0.704 (5) H21A 0.9283 0.3962 0.0712 0.051\* 0.704 (5) H21B 0.9173 0.4252 −0.0455 0.051\* 0.704 (5) C22A 1.0797 (4) 0.4072 (3) 0.0360 (5) 0.0587 (13) 0.704 (5) H22A 1.0920 0.4533 0.0609 0.088\* 0.704 (5) H22B 1.1081 0.4010 −0.0267 0.088\* 0.704 (5) H22C 1.1176 0.3768 0.0924 0.088\* 0.704 (5) C20B 1.0049 (9) 0.3150 (4) −0.0097 (8) 0.040 (2) 0.296 (5) H20C 0.9405 0.3245 −0.0693 0.048\* 0.296 (5) H20D 1.0657 0.3019 −0.0407 0.048\* 0.296 (5) C21B 1.0374 (10) 0.3794 (5) 0.0545 (8) 0.047 (3) 0.296 (5) H21C 1.0987 0.3702 0.1171 0.057\* 0.296 (5) H21D 0.9747 0.3957 0.0801 0.057\* 0.296 (5) C22B 1.0725 (10) 0.4342 (6) −0.0164 (11) 0.0587 (13) 0.296 (5) H22D 1.1108 0.4703 0.0289 0.088\* 0.296 (5) H22E 1.0074 0.4522 −0.0665 0.088\* 0.296 (5) H22F 1.1212 0.4144 −0.0558 0.088\* 0.296 (5) C23 0.79482 (18) −0.01942 (11) 0.08577 (19) 0.0327 (5) H23A 0.8134 −0.0317 0.1611 0.049\* H23B 0.8572 0.0032 0.0693 0.049\* H23C 0.7772 −0.0597 0.0423 0.049\* C24 0.4549 (2) 0.08292 (13) 0.1822 (2) 0.0422 (6) H24A 0.3953 0.1137 0.1504 0.063\* H24B 0.4961 0.1004 0.2510 0.063\* H24C 0.4243 0.0392 0.1923 0.063\* C25 0.5587 (2) 0.16090 (13) −0.1517 (2) 0.0424 (6) H25A 0.4941 0.1881 −0.1522 0.064\* H25B 0.5451 0.1346 −0.2172 0.064\* H25C 0.6219 0.1900 −0.1471 0.064\* ------ -------------- --------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1919 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ P1 0.0270 (3) 0.0194 (3) 0.0286 (3) −0.0011 (2) 0.0055 (2) −0.0012 (2) F1 0.0674 (10) 0.0463 (9) 0.0311 (8) 0.0023 (8) −0.0061 (7) −0.0005 (7) F2 0.0686 (10) 0.0479 (9) 0.0357 (8) 0.0083 (8) −0.0042 (7) 0.0101 (7) F3 0.0523 (9) 0.0371 (8) 0.0731 (11) 0.0098 (7) 0.0355 (8) −0.0018 (8) F4 0.0525 (9) 0.0246 (7) 0.0672 (11) −0.0149 (6) 0.0281 (8) −0.0157 (7) F5 0.0394 (8) 0.0342 (8) 0.0592 (10) −0.0139 (6) 0.0142 (7) −0.0038 (7) F6 0.0426 (8) 0.0257 (7) 0.0603 (10) −0.0008 (6) 0.0226 (7) −0.0104 (7) P2 0.0460 (4) 0.0291 (3) 0.0283 (3) 0.0019 (3) 0.0144 (3) 0.0021 (3) F7A 0.105 (4) 0.094 (5) 0.069 (3) −0.063 (3) 0.041 (3) −0.002 (3) F8A 0.166 (8) 0.081 (4) 0.038 (3) 0.087 (5) 0.023 (6) 0.014 (3) F9A 0.047 (2) 0.114 (6) 0.041 (2) −0.032 (3) 0.0124 (16) 0.014 (3) F10A 0.081 (4) 0.054 (3) 0.031 (2) 0.0346 (19) 0.009 (2) −0.0015 (14) F7B 0.26 (3) 0.079 (10) 0.073 (9) −0.093 (14) 0.052 (14) 0.008 (8) F8B 0.047 (6) 0.107 (13) 0.033 (5) 0.040 (6) 0.010 (3) 0.001 (8) F9B 0.103 (10) 0.036 (6) 0.025 (5) −0.021 (5) −0.014 (6) 0.015 (3) F10B 0.030 (5) 0.171 (18) 0.057 (9) 0.036 (8) 0.004 (5) −0.022 (10) F11 0.0660 (10) 0.0470 (9) 0.0271 (8) 0.0099 (8) 0.0105 (7) 0.0005 (6) F12 0.0779 (11) 0.0462 (9) 0.0348 (8) 0.0090 (8) 0.0092 (8) −0.0085 (7) N1 0.0313 (10) 0.0241 (10) 0.0227 (9) −0.0024 (7) 0.0045 (7) 0.0013 (7) N2 0.0347 (10) 0.0199 (9) 0.0258 (9) −0.0025 (8) 0.0074 (8) 0.0018 (7) N3 0.0299 (10) 0.0260 (10) 0.0221 (9) 0.0002 (8) 0.0069 (7) 0.0023 (8) N4 0.0306 (10) 0.0254 (10) 0.0315 (10) −0.0016 (8) 0.0094 (8) 0.0000 (8) C1 0.0413 (14) 0.0328 (14) 0.0431 (15) 0.0032 (11) 0.0090 (11) −0.0040 (11) C2 0.0339 (13) 0.0310 (13) 0.0361 (13) 0.0022 (10) 0.0110 (10) 0.0014 (10) C3 0.0428 (14) 0.0264 (12) 0.0294 (12) −0.0080 (10) 0.0009 (10) 0.0010 (10) C4 0.0363 (13) 0.0351 (13) 0.0236 (11) −0.0125 (10) 0.0045 (9) −0.0017 (10) C5 0.0367 (12) 0.0273 (12) 0.0269 (12) 0.0054 (10) 0.0065 (9) 0.0063 (9) C6 0.0430 (13) 0.0198 (11) 0.0293 (12) 0.0030 (9) 0.0125 (10) 0.0061 (9) C7 0.0339 (12) 0.0236 (11) 0.0231 (11) −0.0044 (9) 0.0053 (9) 0.0034 (9) C8 0.0378 (13) 0.0233 (11) 0.0305 (12) −0.0077 (9) 0.0079 (10) −0.0031 (9) C9 0.0294 (11) 0.0184 (10) 0.0267 (11) −0.0054 (8) 0.0045 (9) −0.0040 (9) C10 0.0257 (11) 0.0172 (10) 0.0275 (11) −0.0017 (8) −0.0001 (8) −0.0030 (8) C11 0.0264 (11) 0.0230 (11) 0.0239 (11) −0.0038 (8) 0.0006 (8) −0.0026 (9) C12 0.0285 (11) 0.0214 (11) 0.0324 (12) −0.0038 (9) −0.0026 (9) −0.0017 (9) C13 0.0246 (11) 0.0203 (11) 0.0459 (14) 0.0006 (9) −0.0008 (10) −0.0069 (10) C14 0.0269 (11) 0.0219 (11) 0.0390 (13) −0.0053 (9) 0.0072 (10) −0.0117 (10) C15 0.0355 (12) 0.0308 (12) 0.0252 (12) −0.0059 (10) 0.0044 (9) −0.0045 (9) C16 0.0361 (13) 0.0296 (12) 0.0296 (12) 0.0058 (10) 0.0157 (10) 0.0035 (10) C17 0.0358 (13) 0.0295 (13) 0.0367 (13) 0.0026 (10) 0.0158 (10) 0.0038 (10) C18 0.0285 (11) 0.0268 (11) 0.0256 (11) −0.0010 (9) 0.0089 (9) 0.0026 (9) C19 0.0357 (13) 0.0321 (13) 0.0552 (17) −0.0076 (11) 0.0152 (12) −0.0116 (12) C20A 0.048 (2) 0.033 (2) 0.034 (2) 0.0015 (17) 0.0102 (18) 0.0030 (16) C21A 0.044 (2) 0.036 (2) 0.049 (2) 0.0031 (17) 0.0127 (19) 0.0075 (17) C22A 0.059 (3) 0.040 (3) 0.078 (4) −0.010 (2) 0.020 (3) 0.008 (2) C20B 0.045 (6) 0.029 (4) 0.045 (5) −0.009 (4) 0.010 (4) −0.006 (4) C21B 0.046 (6) 0.043 (6) 0.053 (6) −0.015 (5) 0.011 (5) −0.005 (4) C22B 0.059 (3) 0.040 (3) 0.078 (4) −0.010 (2) 0.020 (3) 0.008 (2) C23 0.0332 (12) 0.0266 (12) 0.0359 (13) 0.0053 (9) 0.0042 (10) 0.0014 (10) C24 0.0405 (14) 0.0383 (15) 0.0515 (16) −0.0043 (11) 0.0184 (12) −0.0166 (12) C25 0.0394 (14) 0.0377 (14) 0.0423 (15) −0.0002 (11) −0.0042 (11) 0.0103 (12) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2838 .table-wrap} ----------------------- -------------- -------------------------- -------------- P1---F2 1.5819 (15) C10---C11 1.406 (3) P1---F3 1.5901 (14) C10---C23 1.516 (3) P1---F1 1.5937 (14) C11---C12 1.404 (3) P1---F5 1.5950 (14) C11---C15 1.508 (3) P1---F4 1.6032 (13) C12---C13 1.389 (3) P1---F6 1.6063 (14) C12---C25 1.511 (3) P2---F7B 1.515 (18) C13---C14 1.384 (3) P2---F10B 1.525 (16) C13---H13A 0.9300 P2---F8A 1.562 (7) C14---C24 1.510 (3) P2---F7A 1.562 (6) C15---H15A 0.9700 P2---F9A 1.575 (6) C15---H15B 0.9700 P2---F8B 1.587 (15) C16---C17 1.341 (3) P2---F12 1.5907 (15) C16---H16A 0.9300 P2---F10A 1.604 (6) C17---H17A 0.9300 P2---F11 1.6087 (15) C18---H18A 0.9300 P2---F9B 1.626 (14) C19---C20B 1.335 (9) N1---C7 1.332 (3) C19---C20A 1.611 (4) N1---C5 1.372 (3) C19---H19A 0.9700 N1---C4 1.477 (3) C19---H19B 0.9700 N2---C7 1.333 (3) C19---H19C 0.9600 N2---C6 1.383 (3) C19---H19D 0.9601 N2---C8 1.484 (3) C20A---C21A 1.512 (5) N3---C18 1.328 (3) C20A---H20A 0.9700 N3---C16 1.381 (3) C20A---H20B 0.9700 N3---C15 1.482 (3) C21A---C22A 1.512 (5) N4---C18 1.326 (3) C21A---H21A 0.9700 N4---C17 1.377 (3) C21A---H21B 0.9700 N4---C19 1.466 (3) C22A---H22A 0.9600 C1---C2 1.520 (3) C22A---H22B 0.9600 C1---H1A 0.9600 C22A---H22C 0.9600 C1---H1B 0.9600 C20B---C21B 1.505 (11) C1---H1C 0.9600 C20B---H20C 0.9700 C2---C3 1.511 (3) C20B---H20D 0.9700 C2---H2A 0.9700 C21B---C22B 1.538 (12) C2---H2B 0.9700 C21B---H21C 0.9700 C3---C4 1.510 (3) C21B---H21D 0.9700 C3---H3A 0.9700 C22B---H22D 0.9600 C3---H3B 0.9700 C22B---H22E 0.9600 C4---H4A 0.9700 C22B---H22F 0.9600 C4---H4B 0.9700 C23---H23A 0.9600 C5---C6 1.349 (3) C23---H23B 0.9600 C5---H5A 0.9300 C23---H23C 0.9600 C6---H6A 0.9300 C24---H24A 0.9600 C7---H7A 0.9300 C24---H24B 0.9600 C8---C9 1.504 (3) C24---H24C 0.9600 C8---H8A 0.9700 C25---H25A 0.9600 C8---H8B 0.9700 C25---H25B 0.9600 C9---C10 1.401 (3) C25---H25C 0.9600 C9---C14 1.402 (3) F2---P1---F3 91.31 (9) C9---C8---H8A 109.2 F2---P1---F1 178.71 (9) N2---C8---H8B 109.2 F3---P1---F1 89.98 (9) C9---C8---H8B 109.2 F2---P1---F5 90.75 (8) H8A---C8---H8B 107.9 F3---P1---F5 91.09 (8) C10---C9---C14 120.5 (2) F1---P1---F5 89.20 (8) C10---C9---C8 119.58 (19) F2---P1---F4 89.64 (8) C14---C9---C8 120.0 (2) F3---P1---F4 90.02 (8) C9---C10---C11 119.33 (19) F1---P1---F4 90.38 (8) C9---C10---C23 121.0 (2) F5---P1---F4 178.81 (8) C11---C10---C23 119.6 (2) F2---P1---F6 89.49 (8) C12---C11---C10 120.7 (2) F3---P1---F6 179.03 (9) C12---C11---C15 120.0 (2) F1---P1---F6 89.22 (8) C10---C11---C15 119.28 (19) F5---P1---F6 89.44 (7) C13---C12---C11 118.1 (2) F4---P1---F6 89.44 (7) C13---C12---C25 119.5 (2) F7B---P2---F10B 91.8 (11) C11---C12---C25 122.4 (2) F7B---P2---F8A 75.5 (12) C14---C13---C12 122.8 (2) F10B---P2---F8A 167.3 (10) C14---C13---H13A 118.6 F10B---P2---F7A 77.3 (12) C12---C13---H13A 118.6 F8A---P2---F7A 90.0 (5) C13---C14---C9 118.6 (2) F7B---P2---F9A 164.5 (13) C13---C14---C24 119.1 (2) F10B---P2---F9A 102.2 (10) C9---C14---C24 122.2 (2) F8A---P2---F9A 90.5 (4) N3---C15---C11 112.20 (17) F7A---P2---F9A 179.3 (6) N3---C15---H15A 109.2 F7B---P2---F8B 91.5 (12) C11---C15---H15A 109.2 F10B---P2---F8B 175.6 (12) N3---C15---H15B 109.2 F7A---P2---F8B 105.5 (9) C11---C15---H15B 109.2 F9A---P2---F8B 74.9 (9) H15A---C15---H15B 107.9 F7B---P2---F12 86.9 (13) C17---C16---N3 107.0 (2) F10B---P2---F12 89.2 (9) C17---C16---H16A 126.5 F8A---P2---F12 90.2 (5) N3---C16---H16A 126.5 F7A---P2---F12 93.9 (4) C16---C17---N4 107.3 (2) F9A---P2---F12 86.7 (4) C16---C17---H17A 126.3 F8B---P2---F12 94.0 (10) N4---C17---H17A 126.3 F7B---P2---F10A 105.3 (14) N4---C18---N3 108.6 (2) F8A---P2---F10A 179.0 (5) N4---C18---H18A 125.7 F7A---P2---F10A 90.9 (4) N3---C18---H18A 125.7 F9A---P2---F10A 88.7 (4) C20B---C19---N4 119.8 (4) F8B---P2---F10A 163.1 (9) N4---C19---C20A 107.2 (2) F12---P2---F10A 89.2 (3) C20B---C19---H19A 75.8 F7B---P2---F11 95.0 (13) N4---C19---H19A 110.3 F10B---P2---F11 90.8 (9) C20A---C19---H19A 110.3 F8A---P2---F11 90.2 (5) C20B---C19---H19B 124.6 F7A---P2---F11 87.9 (4) N4---C19---H19B 110.3 F9A---P2---F11 91.5 (4) C20A---C19---H19B 110.3 F8B---P2---F11 86.0 (10) H19A---C19---H19B 108.5 F12---P2---F11 178.15 (9) C20B---C19---H19C 106.1 F10A---P2---F11 90.3 (3) N4---C19---H19C 107.4 F7B---P2---F9B 178.3 (14) C20A---C19---H19C 138.2 F10B---P2---F9B 88.2 (10) H19B---C19---H19C 78.4 F8A---P2---F9B 104.5 (7) C20B---C19---H19D 108.2 F7A---P2---F9B 163.0 (9) N4---C19---H19D 107.7 F8B---P2---F9B 88.4 (9) C20A---C19---H19D 83.7 F12---P2---F9B 94.9 (7) H19A---C19---H19D 132.7 F10A---P2---F9B 74.7 (8) H19C---C19---H19D 107.1 F11---P2---F9B 83.3 (7) C21A---C20A---C19 112.5 (3) C7---N1---C5 108.76 (18) C21A---C20A---H20A 109.1 C7---N1---C4 125.47 (18) C19---C20A---H20A 109.1 C5---N1---C4 125.77 (18) C21A---C20A---H20B 109.1 C7---N2---C6 108.33 (18) C19---C20A---H20B 109.1 C7---N2---C8 126.56 (18) H20A---C20A---H20B 107.8 C6---N2---C8 125.10 (17) C20A---C21A---C22A 112.1 (4) C18---N3---C16 108.45 (19) C20A---C21A---H21A 109.2 C18---N3---C15 126.12 (19) C22A---C21A---H21A 109.2 C16---N3---C15 125.17 (19) C20A---C21A---H21B 109.2 C18---N4---C17 108.53 (19) C22A---C21A---H21B 109.2 C18---N4---C19 124.3 (2) H21A---C21A---H21B 107.9 C17---N4---C19 126.94 (19) C19---C20B---C21B 114.9 (8) C2---C1---H1A 109.5 C19---C20B---H20C 108.5 C2---C1---H1B 109.5 C21B---C20B---H20C 108.5 H1A---C1---H1B 109.5 C19---C20B---H20D 108.5 C2---C1---H1C 109.5 C21B---C20B---H20D 108.5 H1A---C1---H1C 109.5 H20C---C20B---H20D 107.5 H1B---C1---H1C 109.5 C20B---C21B---C22B 110.2 (9) C3---C2---C1 112.05 (19) C20B---C21B---H21C 109.6 C3---C2---H2A 109.2 C22B---C21B---H21C 109.6 C1---C2---H2A 109.2 C20B---C21B---H21D 109.6 C3---C2---H2B 109.2 C22B---C21B---H21D 109.6 C1---C2---H2B 109.2 H21C---C21B---H21D 108.1 H2A---C2---H2B 107.9 C21B---C22B---H22D 109.5 C4---C3---C2 115.88 (19) C21B---C22B---H22E 109.5 C4---C3---H3A 108.3 H22D---C22B---H22E 109.5 C2---C3---H3A 108.3 C21B---C22B---H22F 109.5 C4---C3---H3B 108.3 H22D---C22B---H22F 109.5 C2---C3---H3B 108.3 H22E---C22B---H22F 109.5 H3A---C3---H3B 107.4 C10---C23---H23A 109.5 N1---C4---C3 112.56 (18) C10---C23---H23B 109.5 N1---C4---H4A 109.1 H23A---C23---H23B 109.5 C3---C4---H4A 109.1 C10---C23---H23C 109.5 N1---C4---H4B 109.1 H23A---C23---H23C 109.5 C3---C4---H4B 109.1 H23B---C23---H23C 109.5 H4A---C4---H4B 107.8 C14---C24---H24A 109.5 C6---C5---N1 107.29 (19) C14---C24---H24B 109.5 C6---C5---H5A 126.4 H24A---C24---H24B 109.5 N1---C5---H5A 126.4 C14---C24---H24C 109.5 C5---C6---N2 107.08 (19) H24A---C24---H24C 109.5 C5---C6---H6A 126.5 H24B---C24---H24C 109.5 N2---C6---H6A 126.5 C12---C25---H25A 109.5 N1---C7---N2 108.55 (19) C12---C25---H25B 109.5 N1---C7---H7A 125.7 H25A---C25---H25B 109.5 N2---C7---H7A 125.7 C12---C25---H25C 109.5 N2---C8---C9 112.20 (17) H25A---C25---H25C 109.5 N2---C8---H8A 109.2 H25B---C25---H25C 109.5 C1---C2---C3---C4 172.95 (19) C25---C12---C13---C14 −176.7 (2) C7---N1---C4---C3 92.1 (3) C12---C13---C14---C9 −1.3 (3) C5---N1---C4---C3 −88.6 (3) C12---C13---C14---C24 177.1 (2) C2---C3---C4---N1 64.3 (3) C10---C9---C14---C13 0.0 (3) C7---N1---C5---C6 0.2 (3) C8---C9---C14---C13 −179.73 (18) C4---N1---C5---C6 −179.2 (2) C10---C9---C14---C24 −178.4 (2) N1---C5---C6---N2 −0.1 (3) C8---C9---C14---C24 1.9 (3) C7---N2---C6---C5 0.0 (2) C18---N3---C15---C11 −21.2 (3) C8---N2---C6---C5 −178.6 (2) C16---N3---C15---C11 165.40 (19) C5---N1---C7---N2 −0.2 (3) C12---C11---C15---N3 92.8 (2) C4---N1---C7---N2 179.2 (2) C10---C11---C15---N3 −86.7 (2) C6---N2---C7---N1 0.1 (2) C18---N3---C16---C17 −0.5 (2) C8---N2---C7---N1 178.71 (19) C15---N3---C16---C17 173.93 (19) C7---N2---C8---C9 11.8 (3) N3---C16---C17---N4 0.3 (2) C6---N2---C8---C9 −169.8 (2) C18---N4---C17---C16 −0.1 (2) N2---C8---C9---C10 80.2 (2) C19---N4---C17---C16 −174.8 (2) N2---C8---C9---C14 −100.1 (2) C17---N4---C18---N3 −0.2 (2) C14---C9---C10---C11 0.3 (3) C19---N4---C18---N3 174.7 (2) C8---C9---C10---C11 −179.96 (18) C16---N3---C18---N4 0.4 (2) C14---C9---C10---C23 179.98 (18) C15---N3---C18---N4 −173.91 (18) C8---C9---C10---C23 −0.3 (3) C18---N4---C19---C20B −122.8 (6) C9---C10---C11---C12 0.6 (3) C17---N4---C19---C20B 51.1 (7) C23---C10---C11---C12 −179.06 (19) C18---N4---C19---C20A −87.6 (3) C9---C10---C11---C15 −179.96 (18) C17---N4---C19---C20A 86.3 (3) C23---C10---C11---C15 0.4 (3) C20B---C19---C20A---C21A −63.4 (7) C10---C11---C12---C13 −1.8 (3) N4---C19---C20A---C21A 178.8 (3) C15---C11---C12---C13 178.77 (19) C19---C20A---C21A---C22A 65.0 (5) C10---C11---C12---C25 177.0 (2) N4---C19---C20B---C21B −179.7 (7) C15---C11---C12---C25 −2.4 (3) C20A---C19---C20B---C21B 103.6 (12) C11---C12---C13---C14 2.2 (3) C19---C20B---C21B---C22B 175.3 (9) ----------------------- -------------- -------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4572 .table-wrap} ----------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C2---H2A···F5^i^ 0.97 2.45 3.312 (3) 149 C5---H5A···F9A^ii^ 0.93 2.35 3.235 (9) 159 C6---H6A···F6^ii^ 0.93 2.51 3.248 (3) 136 C6---H6A···F12^ii^ 0.93 2.54 3.145 (3) 123 C7---H7A···F4^iii^ 0.93 2.32 3.140 (3) 146. C15---H15A···F10A^iv^ 0.97 2.54 3.103 (9) 117 C15---H15A···F11^iv^ 0.97 2.50 3.353 (3) 147 C19---H19B···F6^iii^ 0.97 2.54 3.327 (3) 138 ----------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*+1, *y*, *z*; (ii) −*x*+1, −*y*, −*z*+1; (iii) *x*+1/2, −*y*+1/2, *z*−1/2; (iv) −*x*+1, −*y*, −*z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------------- --------- ------- ----------- ------------- C2---H2*A*⋯F5^i^ 0.97 2.45 3.312 (3) 149 C5---H5*A*⋯F9*A*^ii^ 0.93 2.35 3.235 (9) 159 C6---H6*A*⋯F6^ii^ 0.93 2.51 3.248 (3) 136 C6---H6*A*⋯F12^ii^ 0.93 2.54 3.145 (3) 123 C7---H7*A*⋯F4^iii^ 0.93 2.32 3.140 (3) 146 C15---H15*A*⋯F10*A*^iv^ 0.97 2.54 3.103 (9) 117 C15---H15*A*⋯F11^iv^ 0.97 2.50 3.353 (3) 147 C19---H19*B*⋯F6^iii^ 0.97 2.54 3.327 (3) 138 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.

PubMed Central

2024-06-05T04:04:18.528372

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052114/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o562-o563", "authors": [ { "first": "Rosenani A.", "last": "Haque" }, { "first": "Abbas Washeel", "last": "Salman" }, { "first": "Madhukar", "last": "Hemamalini" }, { "first": "Hoong-Kun", "last": "Fun" } ] }

PMC3052115

Related literature {#sec1} ================== For the structures of similar crown ether clathrates, see: Akutagawa *et al.* (2002[@bb1]); Ge & Zhao (2010*a* [@bb3],*b* [@bb4];); Guo & Zhao (2010[@bb5]); Zhao (2010[@bb10]); Zhao & Qu (2010*a* [@bb11],*b* [@bb12]). The title compound was prepared as part of a study of ferroelectric materials. For their properties, see: Fu *et al.* (2007[@bb2]); Zhang *et al.* (2009[@bb9]); Ye *et al.* (2009[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~7~H~9~BrN^+^·ClO~4~ ^−^·C~12~H~24~O~6~*M* *~r~* = 550.81Monoclinic,*a* = 11.967 (2) Å*b* = 13.446 (3) Å*c* = 15.677 (3) Åβ = 94.05 (3)°*V* = 2516.3 (9) Å^3^*Z* = 4Mo *K*α radiationμ = 1.79 mm^−1^*T* = 296 K0.40 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Rigaku SCXmini diffractometerAbsorption correction: multi-scan (*CrystalClear*; Rigaku, 2005[@bb6]) *T* ~min~ = 0.530, *T* ~max~ = 0.69925007 measured reflections5665 independent reflections4005 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.066 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.060*wR*(*F* ^2^) = 0.157*S* = 1.095665 reflections289 parametersH-atom parameters constrainedΔρ~max~ = 0.41 e Å^−3^Δρ~min~ = −0.98 e Å^−3^ {#d5e529} Data collection: *CrystalClear* (Rigaku, 2005[@bb6]); cell refinement: *CrystalClear*; data reduction: *CrystalClear*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb7]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003540/jh2260sup1.cif](http://dx.doi.org/10.1107/S1600536811003540/jh2260sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003540/jh2260Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003540/jh2260Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2260&file=jh2260sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2260sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2260&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2260](http://scripts.iucr.org/cgi-bin/sendsup?jh2260)). The authors are grateful to the starter fund of Southeast University for financial support to purchase the X-ray diffractometer. Comment ======= There is currently a great deal of interest in crown ethers because of their ability to form non-covalent, H-bonding complexes with ammonium cations both in solid and in solution (Akutagawa *et al.*, 2002; Ge *et al.*, 2010*a*,*b*; Guo *et al.*, 2010; Zhao *et al.*, 2010*a*,*b*). Not only the size of the crown ether, but also the nature of the ammonium cation (--NH~4~^+^, RNH~3~^+^, *R*~2~NH~2~^+^, *etc*) can influence on the stoichiometry and stability of these host--guest complexes. The host molecules combine with the guest species by intermolecular interaction, and if the host molecule possess some specific sites, it is easy to realise high selectivity in ion or molecular recognitions. 18-Crown-6 have the highest affinity for ammonium cation RNH~3~^+^, while most studies of 18-crown-6 and its derivatives invariably showed a 1:1 stoichiometry with RNH~3~^+^ cations. Dielectric permittivity of the title compound is tested to systematically investigate the ferroelectric phase transitions materials (Ye *et al.*, 2009; Zhang *et al.*, 2009). The title compound has no dielectric anomaly with the value of 5 and 8 under 1*M* Hz in the temperature from 80 to 433 K (the compound m.p.\> 453 K), suggesting that the compound should be no distinct phase transition occurred within the measured temperature range. The title compound is composed of cationic \[C~7~H~9~NBr(18-Crown-6)\]^+^ and one single anionic \[ClO~4~\]^-^ anions (Fig. 1). Supramolecular rotators was assembled between protonated 4-bromo-3-methylanilinium \[C~7~H~6~Br---NH~3~\]^+^ and 18-crown-6 by hydrogen-bonding. The ammonium moieties of (--NH~3~^+^) cations were interacted with the oxygen atom of crown ethers through six simple N---H···O hydrogen bonding, forming 1:1 supramolecular rotator-stator structures. The macrocycle adopts a conformation with approximate D~3\ d~ symmetry, with all O---C---C---O torsion angles being *gauche* and alternating in sign, and all C---O---C---C torsion angles being *trans*. The C---N bonds of \[C~7~H~6~Br---NH~3~\]^+^ were almost perpendicular to the mean oxygen planes of crown ethers. Supramolecular cation structure, \[C~7~H~9~NBr(18-Crown-6)\]^+^, were introduced as counter cations to \[ClO~4~\]^-^ anions. Cl has a flattened tetrahedral coordination by four O^2-^ ions \[range of *cis*-bond angles = 108.4 (2)--110.3 (2) °; dav(Cl---O) = 1.426 (3)--1.457 (3) Å\]. The title compound was stabilized by intramolecular N---H···O hydrogen bonds, but no intermolecular hydrogen bond was observed. The intramolecular N---H···O hydrogen bonding length are within the usual range: 2.893 (4) and 2.970 (4) Å. Experimental {#experimental} ============ C~7~H~8~NBr. HClO~4~ (2 mmol, 0.57 g) and 18-crown-6 (2 mmol, 0.528 g) were dissolved in 40 ml me thanol solution. The precipitate was filtered out. Two days later, single crystals suitable for X-ray diffraction analysis were obtained from slow evaporation of methanol solution at 0°C. Refinement {#refinement} ========== All the C---H hydrogen atoms were calculated geometrically, with C---H = 0.93, 0.97 and 0.96 Å for aromatic, methylene and methyl H respectively, and constrained to ride on their parent atoms with *U*~iso~(H) = *xU*~eq~(C), where *x* = 1.5 for methyl H and *x* = 1.2 for all other H atoms. All the N---H hydrogen atoms were calculated geometrically. The positions of the H atoms of the nitrogen atoms were refined using a riding model with N---H = 0.89 Å and *U*~iso~(H) = 1.5*U*~eq~(N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The title molecules with the atomic numbering scheme. The displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0o579-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e281 .table-wrap} ----------------------------------------- ---------------------------------------- C~7~H~9~BrN^+^·ClO~4~^−^·C~12~H~24~O~6~ *F*(000) = 1144 *M~r~* = 550.81 *D*~x~ = 1.454 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 20001 reflections *a* = 11.967 (2) Å θ = 3.0--27.3° *b* = 13.446 (3) Å µ = 1.79 mm^−1^ *c* = 15.677 (3) Å *T* = 296 K β = 94.05 (3)° Prism, colorless *V* = 2516.3 (9) Å^3^ 0.40 × 0.30 × 0.20 mm *Z* = 4 ----------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e424 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Rigaku SCXmini diffractometer 5665 independent reflections Radiation source: fine-focus sealed tube 4005 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.066 Detector resolution: 28.5714 pixels mm^-1^ θ~max~ = 27.3°, θ~min~ = 3.0° CCD\_Profile\_fitting scans *h* = −15→15 Absorption correction: multi-scan (*CrystalClear*; Rigaku, 2005) *k* = −17→17 *T*~min~ = 0.530, *T*~max~ = 0.699 *l* = −20→20 25007 measured reflections ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e542 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.060 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.157 H-atom parameters constrained *S* = 1.09 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0769*P*)^2^ + 0.8528*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5665 reflections (Δ/σ)~max~ = 0.001 289 parameters Δρ~max~ = 0.41 e Å^−3^ 0 restraints Δρ~min~ = −0.98 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e699 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e798 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.19928 (4) 1.01458 (3) −0.00712 (3) 0.06334 (18) O8 0.0452 (2) 0.60635 (19) 0.30049 (15) 0.0495 (6) N1 0.2459 (2) 0.72782 (19) 0.29922 (16) 0.0367 (6) H1A 0.1796 0.7195 0.3206 0.055\* H1B 0.2937 0.7545 0.3389 0.055\* H1E 0.2719 0.6692 0.2833 0.055\* O9 0.0542 (2) 0.78578 (18) 0.39854 (15) 0.0499 (6) C15 0.3203 (3) 0.8828 (2) 0.1107 (2) 0.0370 (7) C16 0.2147 (3) 0.9217 (2) 0.08602 (19) 0.0398 (7) O6 0.4462 (2) 0.59829 (19) 0.29366 (17) 0.0551 (7) O5 0.4715 (2) 0.78411 (19) 0.37212 (16) 0.0518 (6) O7 0.2319 (2) 0.53548 (19) 0.21645 (17) 0.0554 (7) O10 0.2751 (2) 0.84908 (18) 0.45312 (16) 0.0506 (6) C13 0.2336 (3) 0.7946 (2) 0.22444 (19) 0.0332 (7) C17 0.1196 (3) 0.8976 (3) 0.1282 (2) 0.0453 (8) H17A 0.0503 0.9242 0.1098 0.054\* C18 0.1292 (3) 0.8336 (2) 0.1982 (2) 0.0415 (8) H18A 0.0664 0.8171 0.2270 0.050\* C14 0.3275 (3) 0.8187 (2) 0.1809 (2) 0.0398 (7) H14A 0.3966 0.7914 0.1990 0.048\* C11 0.5624 (3) 0.7135 (3) 0.3751 (3) 0.0545 (10) H11A 0.5601 0.6721 0.4256 0.065\* H11B 0.6335 0.7484 0.3781 0.065\* C6 −0.0296 (3) 0.7105 (3) 0.4065 (2) 0.0537 (9) H6A −0.0976 0.7405 0.4250 0.064\* H6B −0.0033 0.6619 0.4490 0.064\* C10 0.4740 (3) 0.8459 (3) 0.4471 (3) 0.0600 (10) H10A 0.5406 0.8872 0.4499 0.072\* H10B 0.4766 0.8045 0.4979 0.072\* C7 0.0804 (3) 0.8360 (3) 0.4778 (2) 0.0562 (10) H7A 0.1013 0.7881 0.5224 0.067\* H7B 0.0155 0.8726 0.4944 0.067\* C19 0.4241 (3) 0.9087 (3) 0.0644 (3) 0.0580 (10) H19A 0.4878 0.8747 0.0911 0.087\* H19B 0.4366 0.9792 0.0673 0.087\* H19C 0.4132 0.8887 0.0056 0.087\* C8 0.1762 (3) 0.9065 (3) 0.4666 (3) 0.0579 (10) H8A 0.1585 0.9496 0.4180 0.070\* H8B 0.1891 0.9476 0.5172 0.070\* C3 0.1271 (4) 0.4814 (3) 0.2176 (3) 0.0600 (10) H3A 0.1286 0.4386 0.2675 0.072\* H3B 0.1164 0.4401 0.1670 0.072\* C5 −0.0538 (3) 0.6604 (3) 0.3215 (2) 0.0517 (9) H5A −0.1164 0.6149 0.3244 0.062\* H5B −0.0733 0.7096 0.2778 0.062\* C4 0.0330 (3) 0.5545 (3) 0.2200 (2) 0.0539 (9) H4A 0.0356 0.6014 0.1731 0.065\* H4B −0.0383 0.5201 0.2144 0.065\* C9 0.3713 (3) 0.9105 (3) 0.4438 (3) 0.0583 (10) H9A 0.3780 0.9592 0.4895 0.070\* H9B 0.3633 0.9457 0.3897 0.070\* C12 0.5517 (3) 0.6502 (3) 0.2967 (3) 0.0573 (10) H12A 0.5554 0.6914 0.2462 0.069\* H12B 0.6128 0.6027 0.2978 0.069\* C1 0.4329 (4) 0.5300 (4) 0.2234 (4) 0.0794 (15) H1C 0.4969 0.4856 0.2243 0.095\* H1D 0.4290 0.5664 0.1698 0.095\* C2 0.3278 (4) 0.4705 (3) 0.2295 (4) 0.0794 (15) H2A 0.3239 0.4185 0.1866 0.095\* H2B 0.3280 0.4395 0.2854 0.095\* Cl2 0.75937 (7) 0.70425 (7) 0.09959 (6) 0.0485 (2) O2 0.7570 (3) 0.6235 (2) 0.15986 (19) 0.0709 (8) O1 0.6613 (3) 0.7637 (3) 0.1044 (3) 0.0979 (12) O4 0.7607 (3) 0.6624 (3) 0.01394 (19) 0.0784 (9) O3 0.8582 (3) 0.7636 (3) 0.1177 (2) 0.0849 (10) ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1635 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0687 (3) 0.0700 (3) 0.0526 (3) 0.0157 (2) 0.0132 (2) 0.02676 (19) O8 0.0416 (13) 0.0607 (16) 0.0458 (13) −0.0055 (11) −0.0003 (11) −0.0053 (11) N1 0.0388 (14) 0.0358 (14) 0.0359 (14) −0.0015 (11) 0.0058 (11) 0.0020 (11) O9 0.0502 (14) 0.0543 (15) 0.0469 (14) −0.0092 (11) 0.0152 (11) −0.0020 (11) C15 0.0384 (17) 0.0343 (16) 0.0393 (17) 0.0015 (13) 0.0110 (14) −0.0005 (13) C16 0.052 (2) 0.0352 (17) 0.0332 (16) 0.0051 (14) 0.0053 (14) 0.0025 (13) O6 0.0451 (14) 0.0589 (16) 0.0627 (16) 0.0068 (12) 0.0125 (12) −0.0091 (13) O5 0.0417 (14) 0.0535 (15) 0.0588 (16) 0.0012 (11) −0.0066 (12) 0.0054 (12) O7 0.0568 (16) 0.0443 (14) 0.0657 (17) 0.0002 (12) 0.0081 (13) −0.0090 (12) O10 0.0548 (15) 0.0390 (13) 0.0585 (16) −0.0048 (11) 0.0074 (12) −0.0054 (11) C13 0.0372 (16) 0.0302 (15) 0.0326 (15) −0.0003 (12) 0.0049 (13) 0.0004 (12) C17 0.0337 (17) 0.053 (2) 0.050 (2) 0.0103 (15) 0.0032 (15) 0.0062 (16) C18 0.0326 (17) 0.0468 (19) 0.0459 (18) 0.0020 (14) 0.0089 (14) 0.0067 (15) C14 0.0338 (17) 0.0399 (18) 0.0461 (18) 0.0050 (14) 0.0054 (14) 0.0034 (14) C11 0.0356 (19) 0.056 (2) 0.072 (3) −0.0006 (16) 0.0029 (18) 0.019 (2) C6 0.044 (2) 0.064 (2) 0.056 (2) −0.0041 (17) 0.0191 (17) 0.0041 (18) C10 0.053 (2) 0.050 (2) 0.073 (3) −0.0102 (18) −0.016 (2) −0.007 (2) C7 0.065 (3) 0.059 (2) 0.047 (2) −0.0005 (19) 0.0175 (18) −0.0075 (17) C19 0.047 (2) 0.061 (2) 0.068 (3) 0.0070 (18) 0.0247 (19) 0.015 (2) C8 0.066 (3) 0.051 (2) 0.058 (2) 0.0028 (19) 0.0092 (19) −0.0115 (18) C3 0.072 (3) 0.046 (2) 0.062 (3) −0.0129 (19) 0.003 (2) −0.0103 (18) C5 0.0389 (19) 0.057 (2) 0.059 (2) −0.0073 (17) 0.0030 (17) 0.0075 (18) C4 0.059 (2) 0.058 (2) 0.045 (2) −0.0166 (19) −0.0031 (17) −0.0041 (17) C9 0.056 (2) 0.045 (2) 0.073 (3) −0.0110 (18) −0.004 (2) −0.0066 (18) C12 0.0360 (19) 0.073 (3) 0.064 (2) 0.0088 (18) 0.0142 (17) 0.013 (2) C1 0.065 (3) 0.084 (3) 0.091 (4) 0.021 (2) 0.015 (3) −0.035 (3) C2 0.080 (3) 0.051 (3) 0.107 (4) 0.008 (2) 0.003 (3) −0.032 (3) Cl2 0.0381 (4) 0.0543 (5) 0.0526 (5) 0.0011 (4) −0.0005 (4) 0.0077 (4) O2 0.075 (2) 0.0661 (19) 0.0713 (19) −0.0057 (15) 0.0047 (15) 0.0206 (15) O1 0.074 (2) 0.105 (3) 0.114 (3) 0.043 (2) 0.002 (2) −0.002 (2) O4 0.080 (2) 0.101 (3) 0.0551 (18) −0.0078 (19) 0.0068 (15) −0.0074 (16) O3 0.074 (2) 0.097 (2) 0.081 (2) −0.0366 (19) −0.0162 (17) 0.0177 (18) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2240 .table-wrap} ----------------------- ------------ --------------------- ------------- Br1---C16 1.921 (3) C6---H6B 0.9700 O8---C4 1.440 (4) C10---C9 1.503 (5) O8---C5 1.448 (4) C10---H10A 0.9700 N1---C13 1.476 (4) C10---H10B 0.9700 N1---H1A 0.8900 C7---C8 1.507 (5) N1---H1B 0.8900 C7---H7A 0.9700 N1---H1E 0.8900 C7---H7B 0.9700 O9---C7 1.430 (4) C19---H19A 0.9600 O9---C6 1.437 (4) C19---H19B 0.9600 C15---C14 1.396 (4) C19---H19C 0.9600 C15---C16 1.397 (4) C8---H8A 0.9700 C15---C19 1.523 (4) C8---H8B 0.9700 C16---C17 1.393 (5) C3---C4 1.497 (6) O6---C1 1.435 (5) C3---H3A 0.9700 O6---C12 1.440 (4) C3---H3B 0.9700 O5---C10 1.437 (5) C5---H5A 0.9700 O5---C11 1.442 (4) C5---H5B 0.9700 O7---C2 1.445 (5) C4---H4A 0.9700 O7---C3 1.451 (5) C4---H4B 0.9700 O10---C9 1.432 (4) C9---H9A 0.9700 O10---C8 1.440 (4) C9---H9B 0.9700 C13---C18 1.390 (4) C12---H12A 0.9700 C13---C14 1.394 (4) C12---H12B 0.9700 C17---C18 1.393 (4) C1---C2 1.498 (7) C17---H17A 0.9300 C1---H1C 0.9700 C18---H18A 0.9300 C1---H1D 0.9700 C14---H14A 0.9300 C2---H2A 0.9700 C11---C12 1.493 (6) C2---H2B 0.9700 C11---H11A 0.9700 Cl2---O1 1.426 (3) C11---H11B 0.9700 Cl2---O3 1.439 (3) C6---C5 1.503 (5) Cl2---O2 1.441 (3) C6---H6A 0.9700 Cl2---O4 1.457 (3) C4---O8---C5 114.1 (3) C15---C19---H19C 109.5 C13---N1---H1A 109.5 H19A---C19---H19C 109.5 C13---N1---H1B 109.5 H19B---C19---H19C 109.5 H1A---N1---H1B 109.5 O10---C8---C7 108.7 (3) C13---N1---H1E 109.5 O10---C8---H8A 110.0 H1A---N1---H1E 109.5 C7---C8---H8A 110.0 H1B---N1---H1E 109.5 O10---C8---H8B 110.0 C7---O9---C6 111.6 (3) C7---C8---H8B 110.0 C14---C15---C16 117.0 (3) H8A---C8---H8B 108.3 C14---C15---C19 120.6 (3) O7---C3---C4 108.9 (3) C16---C15---C19 122.3 (3) O7---C3---H3A 109.9 C17---C16---C15 122.3 (3) C4---C3---H3A 109.9 C17---C16---Br1 118.3 (2) O7---C3---H3B 109.9 C15---C16---Br1 119.4 (2) C4---C3---H3B 109.9 C1---O6---C12 112.7 (3) H3A---C3---H3B 108.3 C10---O5---C11 112.5 (3) O8---C5---C6 108.5 (3) C2---O7---C3 112.0 (3) O8---C5---H5A 110.0 C9---O10---C8 112.4 (3) C6---C5---H5A 110.0 C18---C13---C14 120.5 (3) O8---C5---H5B 110.0 C18---C13---N1 120.1 (3) C6---C5---H5B 110.0 C14---C13---N1 119.4 (3) H5A---C5---H5B 108.4 C18---C17---C16 119.5 (3) O8---C4---C3 108.0 (3) C18---C17---H17A 120.2 O8---C4---H4A 110.1 C16---C17---H17A 120.2 C3---C4---H4A 110.1 C13---C18---C17 119.2 (3) O8---C4---H4B 110.1 C13---C18---H18A 120.4 C3---C4---H4B 110.1 C17---C18---H18A 120.4 H4A---C4---H4B 108.4 C13---C14---C15 121.4 (3) O10---C9---C10 108.9 (3) C13---C14---H14A 119.3 O10---C9---H9A 109.9 C15---C14---H14A 119.3 C10---C9---H9A 109.9 O5---C11---C12 109.2 (3) O10---C9---H9B 109.9 O5---C11---H11A 109.8 C10---C9---H9B 109.9 C12---C11---H11A 109.8 H9A---C9---H9B 108.3 O5---C11---H11B 109.8 O6---C12---C11 109.1 (3) C12---C11---H11B 109.8 O6---C12---H12A 109.9 H11A---C11---H11B 108.3 C11---C12---H12A 109.9 O9---C6---C5 109.3 (3) O6---C12---H12B 109.9 O9---C6---H6A 109.8 C11---C12---H12B 109.9 C5---C6---H6A 109.8 H12A---C12---H12B 108.3 O9---C6---H6B 109.8 O6---C1---C2 109.9 (4) C5---C6---H6B 109.8 O6---C1---H1C 109.7 H6A---C6---H6B 108.3 C2---C1---H1C 109.7 O5---C10---C9 109.7 (3) O6---C1---H1D 109.7 O5---C10---H10A 109.7 C2---C1---H1D 109.7 C9---C10---H10A 109.7 H1C---C1---H1D 108.2 O5---C10---H10B 109.7 O7---C2---C1 109.3 (4) C9---C10---H10B 109.7 O7---C2---H2A 109.8 H10A---C10---H10B 108.2 C1---C2---H2A 109.8 O9---C7---C8 108.5 (3) O7---C2---H2B 109.8 O9---C7---H7A 110.0 C1---C2---H2B 109.8 C8---C7---H7A 110.0 H2A---C2---H2B 108.3 O9---C7---H7B 110.0 O1---Cl2---O3 110.3 (2) C8---C7---H7B 110.0 O1---Cl2---O2 109.5 (2) H7A---C7---H7B 108.4 O3---Cl2---O2 110.04 (19) C15---C19---H19A 109.5 O1---Cl2---O4 109.1 (2) C15---C19---H19B 109.5 O3---Cl2---O4 109.5 (2) H19A---C19---H19B 109.5 O2---Cl2---O4 108.4 (2) C14---C15---C16---C17 −0.6 (5) C6---O9---C7---C8 174.6 (3) C19---C15---C16---C17 179.8 (3) C9---O10---C8---C7 −178.6 (3) C14---C15---C16---Br1 177.5 (2) O9---C7---C8---O10 −67.0 (4) C19---C15---C16---Br1 −2.1 (4) C2---O7---C3---C4 169.7 (4) C15---C16---C17---C18 0.7 (5) C4---O8---C5---C6 180.0 (3) Br1---C16---C17---C18 −177.4 (3) O9---C6---C5---O8 66.3 (4) C14---C13---C18---C17 −0.5 (5) C5---O8---C4---C3 −164.9 (3) N1---C13---C18---C17 179.1 (3) O7---C3---C4---O8 −66.0 (4) C16---C17---C18---C13 −0.2 (5) C8---O10---C9---C10 169.2 (3) C18---C13---C14---C15 0.6 (5) O5---C10---C9---O10 68.3 (4) N1---C13---C14---C15 −178.9 (3) C1---O6---C12---C11 −175.7 (4) C16---C15---C14---C13 −0.1 (5) O5---C11---C12---O6 −60.0 (4) C19---C15---C14---C13 179.6 (3) C12---O6---C1---C2 173.7 (4) C10---O5---C11---C12 178.1 (3) C3---O7---C2---C1 177.2 (4) C7---O9---C6---C5 180.0 (3) O6---C1---C2---O7 67.1 (5) C11---O5---C10---C9 −174.4 (3) ----------------------- ------------ --------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3246 .table-wrap} ---------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1B···O5 0.89 2.19 2.955 (4) 144 N1---H1E···O6 0.89 2.29 2.970 (4) 133 N1---H1E···O7 0.89 2.12 2.893 (4) 145 N1---H1A···O8 0.89 2.22 2.905 (4) 134 N1---H1A···O9 0.89 2.19 2.966 (4) 145 N1---H1B···O10 0.89 2.22 2.912 (4) 134 ---------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- N1---H1*A*⋯O8 0.89 2.22 2.905 (4) 134 N1---H1*A*⋯O9 0.89 2.19 2.966 (4) 145 N1---H1*B*⋯O5 0.89 2.19 2.955 (4) 144 N1---H1*B*⋯O10 0.89 2.22 2.912 (4) 134 N1---H1*E*⋯O6 0.89 2.29 2.970 (4) 133 N1---H1*E*⋯O7 0.89 2.12 2.893 (4) 145 :::

PubMed Central

2024-06-05T04:04:18.539368

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052115/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o579", "authors": [ { "first": "Qian", "last": "Xu" }, { "first": "Min Min", "last": "Zhao" } ] }

PMC3052116

Related literature {#sec1} ================== For the coordinating ability of *N*,*N*-dialkyl-*N*′-benzoylthioureas; see: Binzet *et al.* (2009[@bb3]); Gunasekaran *et al.* (2010[@bb7]); Sacht *et al.* (2000[@bb10]). For the utility of Cd derivatives to serve as synthetic precursors for CdS nanoparticles, see: Bruce *et al.* (2007[@bb5]). For their biological activity, see: Arslan *et al.* (2006[@bb2]). For related structures, see: Gunasekaran *et al.* (2010*a* [@bb8],*b* [@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~24~N~2~OS*M* *~r~* = 292.43Triclinic,*a* = 8.9331 (10) Å*b* = 10.1023 (9) Å*c* = 11.0725 (12) Åα = 105.776 (9)°β = 112.734 (10)°γ = 100.782 (9)°*V* = 837.47 (19) Å^3^*Z* = 2Mo *K*α radiationμ = 0.19 mm^−1^*T* = 295 K0.35 × 0.30 × 0.25 mm ### Data collection {#sec2.1.2} Agilent Supernova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb1]) *T* ~min~ = 0.936, *T* ~max~ = 0.9546265 measured reflections3693 independent reflections2232 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.025 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.074*wR*(*F* ^2^) = 0.219*S* = 1.043693 reflections181 parameters12 restraintsH-atom parameters constrainedΔρ~max~ = 0.86 e Å^−3^Δρ~min~ = −0.58 e Å^−3^ {#d5e466} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb1]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb11]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb11]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb6]) and *DIAMOND* (Brandenburg, 2006[@bb4]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004557/ez2230sup1.cif](http://dx.doi.org/10.1107/S1600536811004557/ez2230sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004557/ez2230Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004557/ez2230Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2230&file=ez2230sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2230sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2230&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2230](http://scripts.iucr.org/cgi-bin/sendsup?ez2230)). NS thanks the NITT for a Fellowship. The authors thank the University of Malaya for supporting this study. Comment ======= *N*,*N*-Dialkyl-*N*\'-benzoylthioureas are versatile ligands which can coordinate to transition metal centres either as neutral species or in an anionic form. The complexation capacity of thiourea derivatives has been reported in several studies (Binzet *et al.*, 2009; Gunasekaran *et al.*, 2010). Chiral and achiral platinum(II) complexes of these ligands have been used as chemotherapeutic agents (Sacht *et al.*, 2000) while cadmium(II) complexes of *N*,*N*-diethyl-*N*\'-benzoylthiourea have been used as single-source precursors for the preparation of CdS nanoparticles (Bruce *et al.*, 2007). In addition, thioureas have been shown to possess anti-tubercular, anti-helmintic, anti-bacterial, insecticidal and rodenticidal properties (Arslan *et al.*, 2006). In continuation of structural studies of these derivatives (Gunasekaran *et al.*, 2010*a*; Gunasekaran *et al.*, 2010*b*), the title compound, (I), was investigated. In (I), Fig. 1, the molecule exhibits a significant twist about the central N(H)--C bond as seen in the value of the C7--N1--C8--S1 torsion angle of 119.6 (3) °. This arrangement causes the carbonyl-O and thione-S atoms to lie on opposite sides of the molecule. Similarly, the carbonyl and N--H groups are directed away from each other. This conformation allows for the formation of N--H···S hydrogen bonds, Table 1, *via* an eight-membered {···HNCS}~2~ ring which has the shape of an elongated chair. These are connected into supramolecular chains along \[1 1 1\] *via* C--H···O contacts that close 14-membered {···HCNCNCO}~2~ synthons, also adopting the shape of an elongated chair, Table 1 and Fig. 2. Chains are arranged into layers *via* weak π···π interactions \[*Cg*(C1--C6)···*Cg*(C1--C6)^i^ = 3.806 (3) Å for *i*: 2 - *x*, 1 - *y*, 2 - *z*\] and these stack as shown in Fig. 3. Experimental {#experimental} ============ A solution of benzoyl chloride (0.7029 g, 5 mmol) in acetone (50 ml) was added drop wise to a suspension of potassium thiocyanate (0.4859 g, 5 mmol) in anhydrous acetone (50 ml). The reaction mixture was heated under reflux for 45 min. and then cooled to room temperature. A solution of diisobutyl amine (0.6462 g, 5 mmol) in acetone (30 ml) was added and the resulting mixture was stirred for 2 h. Hydrochloric acid (0.1 N, 300 ml) was added and the resulting white solid was filtered, washed with water and dried *in vacuo*. Single crystals for X-ray diffraction were grown at room temperature from an acetonitrile solution of the compound. Yield 72%; *M*.Pt. 415 K. FT---IR (KBr) ν(N---H) 3268, ν(C═O) 1688, ν(C=S) 1264 cm^-1^. Refinement {#refinement} ========== The H-atoms were placed in calculated positions (N---H = 0.88; C---H 0.93 to 0.98 Å) and were included in the refinement in the riding model approximation, with *U*~iso~(H) set to 1.2 to 1.5*U*~equiv~(N, C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o602-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Supramolecular chain in (I) mediated by N--H···S hydrogen bonds and C--H···O contacts, shown as orange and blue dashed lines, respectively. ::: ![](e-67-0o602-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### View in projection down the b axis of the unit cell contents of (I). The N--H···S hydrogen bonds and C--H···O contacts are shown as orange and blue dashed lines, respectively. ::: ![](e-67-0o602-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e226 .table-wrap} ------------------------ --------------------------------------- C~16~H~24~N~2~OS *Z* = 2 *M~r~* = 292.43 *F*(000) = 316 Triclinic, *P*1 *D*~x~ = 1.160 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.9331 (10) Å Cell parameters from 1845 reflections *b* = 10.1023 (9) Å θ = 2.2--29.2° *c* = 11.0725 (12) Å µ = 0.19 mm^−1^ α = 105.776 (9)° *T* = 295 K β = 112.734 (10)° Block, colourless γ = 100.782 (9)° 0.35 × 0.30 × 0.25 mm *V* = 837.47 (19) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e360 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent Supernova Dual diffractometer with an Atlas detector 3693 independent reflections Radiation source: SuperNova (Mo) X-ray Source 2232 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.025 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.2° ω scans *h* = −10→11 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −13→12 *T*~min~ = 0.936, *T*~max~ = 0.954 *l* = −14→12 6265 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e480 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.074 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.219 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.078*P*)^2^ + 0.7593*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3693 reflections (Δ/σ)~max~ = 0.001 181 parameters Δρ~max~ = 0.86 e Å^−3^ 12 restraints Δρ~min~ = −0.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e637 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e736 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ S1 0.74828 (14) 0.92803 (11) 0.99096 (12) 0.0711 (4) O1 0.6998 (3) 0.5295 (2) 0.7153 (3) 0.0585 (7) N1 0.8690 (3) 0.7638 (3) 0.8494 (3) 0.0512 (7) H1 0.9753 0.8236 0.8909 0.061\* N2 0.6172 (3) 0.7981 (3) 0.7098 (3) 0.0515 (7) C1 0.9961 (4) 0.5699 (3) 0.8524 (3) 0.0431 (7) C2 0.9697 (5) 0.4222 (4) 0.8112 (4) 0.0535 (9) H2 0.8597 0.3566 0.7487 0.064\* C3 1.1045 (5) 0.3706 (4) 0.8615 (5) 0.0653 (11) H3 1.0847 0.2708 0.8335 0.078\* C4 1.2664 (5) 0.4656 (5) 0.9522 (5) 0.0669 (11) H4 1.3568 0.4306 0.9866 0.080\* C5 1.2961 (5) 0.6133 (5) 0.9929 (5) 0.0661 (11) H5 1.4069 0.6780 1.0542 0.079\* C6 1.1618 (4) 0.6657 (4) 0.9431 (4) 0.0538 (9) H6 1.1826 0.7656 0.9705 0.065\* C7 0.8421 (4) 0.6165 (3) 0.7986 (3) 0.0426 (7) C8 0.7372 (4) 0.8250 (3) 0.8392 (4) 0.0513 (9) C9 0.6351 (4) 0.7432 (3) 0.5811 (4) 0.0526 (9) H9A 0.5352 0.6588 0.5122 0.063\* H9B 0.7353 0.7118 0.6035 0.063\* C10 0.6535 (5) 0.8564 (4) 0.5150 (4) 0.0654 (11) H10 0.5463 0.8792 0.4831 0.079\* C11 0.6790 (7) 0.7906 (5) 0.3856 (4) 0.0892 (15) H11A 0.5849 0.7025 0.3204 0.134\* H11B 0.7847 0.7691 0.4149 0.134\* H11C 0.6835 0.8587 0.3403 0.134\* C12 0.7998 (6) 0.9970 (4) 0.6237 (5) 0.0877 (15) H12A 0.8091 1.0661 0.5801 0.132\* H12B 0.9057 0.9765 0.6583 0.132\* H12C 0.7765 1.0367 0.7012 0.132\* C13 0.4659 (4) 0.8426 (4) 0.6909 (5) 0.0662 (11) H13A 0.4206 0.8536 0.6005 0.079\* H13B 0.5025 0.9377 0.7640 0.079\* C14 0.3240 (5) 0.7441 (4) 0.6949 (7) 0.106 (2) H14 0.3640 0.7625 0.7957 0.127\* C15 0.1645 (5) 0.7914 (5) 0.6518 (6) 0.0888 (15) H15A 0.1979 0.8950 0.6987 0.133\* H15B 0.0863 0.7435 0.6785 0.133\* H15C 0.1094 0.7655 0.5512 0.133\* C16 0.2816 (6) 0.5830 (4) 0.6261 (6) 0.0816 (13) H16A 0.3853 0.5586 0.6554 0.122\* H16B 0.2264 0.5542 0.5251 0.122\* H16C 0.2058 0.5330 0.6536 0.122\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1304 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ S1 0.0676 (7) 0.0507 (6) 0.0765 (7) 0.0191 (5) 0.0294 (6) 0.0036 (5) O1 0.0434 (13) 0.0383 (13) 0.0653 (16) 0.0071 (11) 0.0031 (12) 0.0157 (12) N1 0.0344 (14) 0.0355 (15) 0.0622 (18) 0.0091 (12) 0.0100 (13) 0.0078 (13) N2 0.0364 (14) 0.0400 (15) 0.0659 (19) 0.0137 (12) 0.0144 (14) 0.0156 (14) C1 0.0428 (17) 0.0444 (18) 0.0423 (17) 0.0167 (15) 0.0181 (14) 0.0176 (14) C2 0.054 (2) 0.0427 (19) 0.059 (2) 0.0190 (16) 0.0215 (17) 0.0169 (17) C3 0.069 (3) 0.054 (2) 0.088 (3) 0.034 (2) 0.040 (2) 0.034 (2) C4 0.055 (2) 0.077 (3) 0.089 (3) 0.039 (2) 0.035 (2) 0.046 (3) C5 0.0419 (19) 0.071 (3) 0.077 (3) 0.0192 (19) 0.0186 (18) 0.029 (2) C6 0.0451 (19) 0.050 (2) 0.060 (2) 0.0171 (16) 0.0180 (16) 0.0193 (17) C7 0.0417 (17) 0.0384 (17) 0.0383 (16) 0.0125 (14) 0.0111 (14) 0.0128 (14) C8 0.0403 (17) 0.0325 (17) 0.067 (2) 0.0098 (14) 0.0173 (16) 0.0118 (16) C9 0.0438 (18) 0.0412 (19) 0.060 (2) 0.0136 (15) 0.0125 (16) 0.0183 (17) C10 0.055 (2) 0.052 (2) 0.075 (3) 0.0160 (18) 0.0104 (19) 0.032 (2) C11 0.113 (4) 0.077 (3) 0.071 (3) 0.025 (3) 0.033 (3) 0.038 (3) C12 0.092 (3) 0.052 (3) 0.089 (3) 0.000 (2) 0.021 (3) 0.030 (2) C13 0.046 (2) 0.057 (2) 0.089 (3) 0.0247 (18) 0.022 (2) 0.027 (2) C14 0.065 (3) 0.072 (3) 0.203 (7) 0.033 (3) 0.070 (4) 0.065 (4) C15 0.060 (3) 0.097 (4) 0.139 (5) 0.039 (3) 0.057 (3) 0.060 (4) C16 0.071 (3) 0.057 (3) 0.113 (4) 0.012 (2) 0.047 (3) 0.027 (3) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1650 .table-wrap} ------------------- ------------ ---------------------- ------------ S1---C8 1.673 (4) C9---H9B 0.9700 O1---C7 1.214 (4) C10---C12 1.528 (4) N1---C7 1.377 (4) C10---C11 1.529 (4) N1---C8 1.410 (4) C10---H10 0.9800 N1---H1 0.8800 C11---H11A 0.9600 N2---C8 1.330 (4) C11---H11B 0.9600 N2---C13 1.461 (4) C11---H11C 0.9600 N2---C9 1.464 (5) C12---H12A 0.9600 C1---C2 1.380 (5) C12---H12B 0.9600 C1---C6 1.386 (5) C12---H12C 0.9600 C1---C7 1.493 (4) C13---C14 1.482 (4) C2---C3 1.381 (5) C13---H13A 0.9700 C2---H2 0.9300 C13---H13B 0.9700 C3---C4 1.362 (6) C14---C16 1.498 (4) C3---H3 0.9300 C14---C15 1.530 (4) C4---C5 1.376 (6) C14---H14 0.9800 C4---H4 0.9300 C15---H15A 0.9600 C5---C6 1.382 (5) C15---H15B 0.9600 C5---H5 0.9300 C15---H15C 0.9600 C6---H6 0.9300 C16---H16A 0.9600 C9---C10 1.533 (4) C16---H16B 0.9600 C9---H9A 0.9700 C16---H16C 0.9600 C7---N1---C8 124.2 (3) C12---C10---H10 108.2 C7---N1---H1 117.9 C11---C10---H10 108.2 C8---N1---H1 117.9 C9---C10---H10 108.2 C8---N2---C13 120.0 (3) C10---C11---H11A 109.5 C8---N2---C9 124.2 (3) C10---C11---H11B 109.5 C13---N2---C9 115.2 (3) H11A---C11---H11B 109.5 C2---C1---C6 118.6 (3) C10---C11---H11C 109.5 C2---C1---C7 117.4 (3) H11A---C11---H11C 109.5 C6---C1---C7 124.0 (3) H11B---C11---H11C 109.5 C1---C2---C3 120.9 (4) C10---C12---H12A 109.5 C1---C2---H2 119.6 C10---C12---H12B 109.5 C3---C2---H2 119.6 H12A---C12---H12B 109.5 C4---C3---C2 120.1 (4) C10---C12---H12C 109.5 C4---C3---H3 119.9 H12A---C12---H12C 109.5 C2---C3---H3 119.9 H12B---C12---H12C 109.5 C3---C4---C5 120.0 (3) N2---C13---C14 116.6 (3) C3---C4---H4 120.0 N2---C13---H13A 108.1 C5---C4---H4 120.0 C14---C13---H13A 108.1 C4---C5---C6 120.2 (4) N2---C13---H13B 108.1 C4---C5---H5 119.9 C14---C13---H13B 108.1 C6---C5---H5 119.9 H13A---C13---H13B 107.3 C5---C6---C1 120.2 (3) C13---C14---C16 118.4 (4) C5---C6---H6 119.9 C13---C14---C15 111.0 (3) C1---C6---H6 119.9 C16---C14---C15 112.5 (4) O1---C7---N1 121.4 (3) C13---C14---H14 104.5 O1---C7---C1 122.1 (3) C16---C14---H14 104.5 N1---C7---C1 116.6 (3) C15---C14---H14 104.5 N2---C8---N1 117.1 (3) C14---C15---H15A 109.5 N2---C8---S1 125.9 (3) C14---C15---H15B 109.5 N1---C8---S1 117.1 (3) H15A---C15---H15B 109.5 N2---C9---C10 113.3 (3) C14---C15---H15C 109.5 N2---C9---H9A 108.9 H15A---C15---H15C 109.5 C10---C9---H9A 108.9 H15B---C15---H15C 109.5 N2---C9---H9B 108.9 C14---C16---H16A 109.5 C10---C9---H9B 108.9 C14---C16---H16B 109.5 H9A---C9---H9B 107.7 H16A---C16---H16B 109.5 C12---C10---C11 112.2 (3) C14---C16---H16C 109.5 C12---C10---C9 110.9 (3) H16A---C16---H16C 109.5 C11---C10---C9 109.1 (3) H16B---C16---H16C 109.5 C6---C1---C2---C3 1.4 (5) C13---N2---C8---N1 172.5 (3) C7---C1---C2---C3 −177.1 (3) C9---N2---C8---N1 −16.3 (5) C1---C2---C3---C4 −0.5 (6) C13---N2---C8---S1 −9.0 (5) C2---C3---C4---C5 −0.5 (6) C9---N2---C8---S1 162.2 (3) C3---C4---C5---C6 0.6 (7) C7---N1---C8---N2 −61.8 (5) C4---C5---C6---C1 0.4 (6) C7---N1---C8---S1 119.6 (3) C2---C1---C6---C5 −1.4 (5) C8---N2---C9---C10 −109.9 (4) C7---C1---C6---C5 177.1 (3) C13---N2---C9---C10 61.7 (4) C8---N1---C7---O1 15.7 (5) N2---C9---C10---C12 53.6 (4) C8---N1---C7---C1 −163.6 (3) N2---C9---C10---C11 177.6 (3) C2---C1---C7---O1 −4.2 (5) C8---N2---C13---C14 −82.1 (5) C6---C1---C7---O1 177.4 (3) C9---N2---C13---C14 105.9 (4) C2---C1---C7---N1 175.2 (3) N2---C13---C14---C16 −39.2 (7) C6---C1---C7---N1 −3.3 (5) N2---C13---C14---C15 −171.4 (4) ------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2386 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1···S1^i^ 0.88 2.74 3.586 (3) 162 C9---H9a···O1^ii^ 0.97 2.49 3.424 (5) 162 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+2, −*y*+2, −*z*+2; (ii) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ----------------- --------- ------- ----------- ------------- N1---H1⋯S1^i^ 0.88 2.74 3.586 (3) 162 C9---H9a⋯O1^ii^ 0.97 2.49 3.424 (5) 162 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Additional correspondence author, e-mail: kar@nitt.edu.

PubMed Central

2024-06-05T04:04:18.547641

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052116/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o602", "authors": [ { "first": "N.", "last": "Selvakumaran" }, { "first": "R.", "last": "Karvembu" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }

PMC3052117

Related literature {#sec1} ================== For background to chalcone chemistry, see: Roman (2004[@bb6]). For related structures, see: Prasath *et al.* (2010[@bb4]); Reddy *et al.* (2010[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~17~Cl~2~NO*M* *~r~* = 418.30Triclinic,*a* = 11.1704 (3) Å*b* = 12.8497 (5) Å*c* = 16.0591 (6) Åα = 74.914 (3)°β = 80.603 (3)°γ = 70.789 (3)°*V* = 2094.05 (13) Å^3^*Z* = 4Cu *K*α radiationμ = 2.91 mm^−1^*T* = 295 K0.30 × 0.30 × 0.10 mm ### Data collection {#sec2.1.2} Agilent Supernova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb1]) *T* ~min~ = 0.574, *T* ~max~ = 1.00014958 measured reflections8252 independent reflections7088 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.026 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.052*wR*(*F* ^2^) = 0.158*S* = 1.038252 reflections525 parametersH-atom parameters constrainedΔρ~max~ = 0.43 e Å^−3^Δρ~min~ = −0.41 e Å^−3^ {#d5e448} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb1]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb3]) and *DIAMOND* (Brandenburg, 2006[@bb2]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004740/hg2798sup1.cif](http://dx.doi.org/10.1107/S1600536811004740/hg2798sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004740/hg2798Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004740/hg2798Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg2798&file=hg2798sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg2798sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg2798&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG2798](http://scripts.iucr.org/cgi-bin/sendsup?hg2798)). VV is grateful to the DST, India, for funding through the Young Scientist Scheme (Fast Track Proposal). The authors are also grateful to the University of Malaya for support of the crystallographic facility. Comment ======= Chalcones and its analogs are valuable intermediates in organic synthesis and exhibit a multitude of biological activities. From a chemical point of view, an important feature of chalcones and their heteroanalogs is the ability to act as activated unsaturated systems in conjugated addition reactions of carbanions in the presence of basic catalysts (Roman, 2004). The title compound, (I), was examined in continuation of our interest in the structural chemistry of chalcones (Prasath *et al.*, 2010; Reddy *et al.*, 2010). Two independent molecules comprise the asymmetric unit of (I), one with an *anti* relationship between the carbonyl and ethylene double bonds, Fig. 1, and one with a *syn* relationship, Fig. 2. In each, the conformation about the ethylene bond \[C18═C19 = 1.319 (3) Å and C43═C44 = 1.328 (3) Å\] is *E*. For both molecules, the benzene ring is twisted out of the plane of the quinoline residue to which it is connected; the C6---C7---C11---C12 and C31---C32---C36---C37 torsion angles are -69.0 (2) and -107.1 (2) °, respectively. The prop-2-en-1-one substituents are also twisted out of the plane of the respective quinoline residues as seen in the values of the C7---C8---C17---O1 and C32---C33---C42---O2 torsion angles of 91.2 (2) and -119.1 (3) °, respectively. Within the prop-2-en-1-one substituents themselves, the terminal benzene rings are not co-planar with the C18---C19---C20---C21 and C43---C44---C45---C46 torsion angles being -159.6 (2) and -170.8 (2) °, respectively. The molecules are stabilized in the crystal packing by a combination of C---H···π, π--π, and C---Cl···π interactions. The C---H···π contacts, Table 1, occur between the two molecules comprising the asymmetric unit. The π--π interactions occur between centrosymmetrically related quinoline rings belonging to like molecules \[*Cg*(N1,C1,C6---C9)···*Cg*(C1---C6)^ii^ = 3.8446 (11) ° for *ii*: 1 - *x*, 1 - *y*, -*z*; and *Cg*(N2,C26,C31---C34)···*Cg*(C26---C31)^iii^ = 3.7809 (12) ° for *iii*: 1 - *x*, 1 - *y*, 1 - *z*\]. The C---H···Cl contacts \[C4---Cl1···*Cg*(C20---C25)^iv^ = 3.6082 (13) Å and angle at Cl1 = 116.34 (7) ° for *iv*: -1 + *x*, *y*, *z*\] also occur between like molecules. A view of the crystal packing is shown in Fig. 3. Experimental {#experimental} ============ A mixture of 3-acetyl-6-chloro-2-methyl-4-phenylquinoline (3.1 g, 0.01 *M*) and 4-chlorobenzaldehyde (1.4 g, 0.01 *M*) and a catalytic amount of KOH in distilled ethanol (40 ml) was stirred for about 12 h. The resulting mixture was concentrated to remove ethanol, poured onto ice and neutralized with dilute acetic acid. The resultant solid was filtered, dried and purified by column chromatography using a 1:1 mixture of ethyl acetate and petroleum ether. Recrystallization was from acetone; Yield: 64% and m.pt: 397--399 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.93 to 0.96 Å) and were included in the refinement in the riding model approximation, with *U*~iso~(H) set to 1.2 to 1.5*U*~equiv~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the first independent molecule of (I), i.e. the anti form, showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o624-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular structure of the second independent molecule of (I), i.e. the syn form, showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. ::: ![](e-67-0o624-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view in projection down the c axis of the unit-cell contents of (I). The C---H···π, π--π, and C---Cl···π interactions are shown as purple, orange and green dashed lines, respectively. ::: ![](e-67-0o624-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e255 .table-wrap} ------------------------- --------------------------------------- C~25~H~17~Cl~2~NO *Z* = 4 *M~r~* = 418.30 *F*(000) = 864 Triclinic, *P*1 *D*~x~ = 1.327 Mg m^−3^ Hall symbol: -P 1 Cu *K*α radiation, λ = 1.54184 Å *a* = 11.1704 (3) Å Cell parameters from 8901 reflections *b* = 12.8497 (5) Å θ = 2.9--74.1° *c* = 16.0591 (6) Å µ = 2.91 mm^−1^ α = 74.914 (3)° *T* = 295 K β = 80.603 (3)° Prism, colourless γ = 70.789 (3)° 0.30 × 0.30 × 0.10 mm *V* = 2094.05 (13) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e389 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent Supernova Dual diffractometer with an Atlas detector 8252 independent reflections Radiation source: SuperNova (Cu) X-ray Source 7088 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.026 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 74.3°, θ~min~ = 2.9° ω scans *h* = −11→13 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −16→15 *T*~min~ = 0.574, *T*~max~ = 1.000 *l* = −20→19 14958 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e509 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.052 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.158 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0899*P*)^2^ + 0.4585*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 8252 reflections (Δ/σ)~max~ = 0.001 525 parameters Δρ~max~ = 0.43 e Å^−3^ 0 restraints Δρ~min~ = −0.41 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e666 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e765 .table-wrap} ------ -------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cl1 0.16358 (5) 0.49560 (5) 0.26030 (4) 0.06920 (17) Cl2 1.33991 (8) 0.11218 (7) 0.45986 (5) 0.0924 (2) O1 0.86575 (14) 0.22234 (15) 0.02125 (11) 0.0691 (4) N1 0.61911 (15) 0.56418 (13) 0.04091 (10) 0.0501 (4) C1 0.51604 (16) 0.54394 (15) 0.09308 (11) 0.0443 (4) C2 0.40157 (18) 0.63350 (16) 0.09149 (13) 0.0512 (4) H2 0.3986 0.7037 0.0554 0.061\* C3 0.29485 (18) 0.61886 (17) 0.14218 (14) 0.0541 (4) H3 0.2196 0.6783 0.1404 0.065\* C4 0.30038 (17) 0.51310 (16) 0.19691 (13) 0.0501 (4) C5 0.40840 (17) 0.42366 (16) 0.20038 (12) 0.0486 (4) H5 0.4092 0.3542 0.2370 0.058\* C6 0.51918 (16) 0.43729 (14) 0.14790 (11) 0.0433 (4) C7 0.63491 (17) 0.34658 (15) 0.14543 (12) 0.0463 (4) C8 0.73523 (17) 0.36816 (16) 0.08963 (12) 0.0486 (4) C9 0.72457 (17) 0.47965 (17) 0.03906 (13) 0.0503 (4) C10 0.8367 (2) 0.5062 (2) −0.01747 (17) 0.0686 (6) H10A 0.8075 0.5746 −0.0603 0.103\* H10B 0.8815 0.4452 −0.0456 0.103\* H10C 0.8926 0.5159 0.0174 0.103\* C11 0.64371 (16) 0.23274 (15) 0.20244 (13) 0.0485 (4) C12 0.6432 (2) 0.21729 (18) 0.29087 (14) 0.0595 (5) H12 0.6381 0.2775 0.3146 0.071\* C13 0.6502 (2) 0.11177 (19) 0.34435 (16) 0.0692 (6) H13 0.6508 0.1012 0.4038 0.083\* C14 0.6564 (2) 0.02285 (19) 0.30963 (16) 0.0675 (6) H14 0.6597 −0.0474 0.3458 0.081\* C15 0.6575 (2) 0.03717 (19) 0.22225 (17) 0.0665 (6) H15 0.6624 −0.0234 0.1990 0.080\* C16 0.6514 (2) 0.14203 (18) 0.16806 (15) 0.0584 (5) H16 0.6524 0.1515 0.1086 0.070\* C17 0.85560 (18) 0.27261 (18) 0.07789 (13) 0.0542 (4) C18 0.95710 (19) 0.2412 (2) 0.13521 (15) 0.0622 (5) H18 1.0323 0.1867 0.1230 0.075\* C19 0.95068 (19) 0.28387 (19) 0.20273 (14) 0.0601 (5) H19 0.8771 0.3412 0.2127 0.072\* C20 1.0485 (2) 0.24950 (19) 0.26344 (14) 0.0597 (5) C21 1.0179 (2) 0.2730 (2) 0.34513 (15) 0.0667 (6) H21 0.9357 0.3158 0.3598 0.080\* C22 1.1072 (3) 0.2339 (2) 0.40532 (16) 0.0718 (6) H22 1.0853 0.2496 0.4601 0.086\* C23 1.2288 (2) 0.1717 (2) 0.38295 (15) 0.0657 (5) C24 1.2642 (2) 0.1516 (3) 0.30134 (17) 0.0769 (7) H24 1.3477 0.1123 0.2862 0.092\* C25 1.1743 (2) 0.1906 (2) 0.24211 (16) 0.0747 (7) H25 1.1981 0.1772 0.1867 0.090\* Cl3 0.90535 (6) 0.58126 (7) 0.40484 (4) 0.0849 (2) Cl4 0.90415 (7) −0.25246 (7) 1.15298 (5) 0.0979 (3) O2 0.4659 (2) 0.17598 (16) 0.71587 (14) 0.0901 (6) N2 0.45355 (15) 0.52142 (13) 0.63374 (11) 0.0513 (4) C26 0.56090 (18) 0.53029 (15) 0.58190 (12) 0.0473 (4) C27 0.5587 (2) 0.63632 (17) 0.52686 (14) 0.0595 (5) H27 0.4852 0.6972 0.5274 0.071\* C28 0.6626 (2) 0.65091 (18) 0.47297 (14) 0.0641 (5) H28 0.6597 0.7208 0.4365 0.077\* C29 0.7733 (2) 0.55961 (19) 0.47328 (13) 0.0578 (5) C30 0.78037 (19) 0.45574 (18) 0.52438 (13) 0.0530 (4) H30 0.8551 0.3963 0.5228 0.064\* C31 0.67341 (17) 0.43863 (15) 0.57993 (11) 0.0452 (4) C32 0.67093 (17) 0.33154 (15) 0.63337 (12) 0.0474 (4) C33 0.55979 (18) 0.32275 (16) 0.68166 (12) 0.0488 (4) C34 0.45213 (18) 0.42134 (17) 0.68166 (12) 0.0500 (4) C35 0.3321 (2) 0.4172 (2) 0.73827 (16) 0.0666 (6) H35A 0.2747 0.4924 0.7340 0.100\* H35B 0.3519 0.3848 0.7972 0.100\* H35C 0.2929 0.3717 0.7198 0.100\* C36 0.78570 (19) 0.23100 (16) 0.63245 (14) 0.0545 (4) C37 0.7881 (2) 0.1469 (2) 0.5930 (2) 0.0778 (7) H37 0.7175 0.1524 0.5665 0.093\* C38 0.8959 (3) 0.0539 (2) 0.5930 (3) 0.1036 (11) H38 0.8976 −0.0022 0.5657 0.124\* C39 0.9992 (3) 0.0443 (2) 0.6328 (3) 0.1048 (11) H39 1.0704 −0.0188 0.6334 0.126\* C40 0.9983 (3) 0.1272 (3) 0.6717 (2) 0.0936 (9) H40 1.0689 0.1204 0.6987 0.112\* C41 0.8928 (2) 0.2212 (2) 0.67094 (18) 0.0717 (6) H41 0.8934 0.2783 0.6964 0.086\* C42 0.5465 (2) 0.21028 (17) 0.73280 (14) 0.0578 (5) C43 0.6285 (2) 0.14702 (17) 0.80398 (13) 0.0555 (4) H43 0.6941 0.1725 0.8115 0.067\* C44 0.6106 (2) 0.05441 (17) 0.85759 (14) 0.0565 (5) H44 0.5444 0.0319 0.8470 0.068\* C45 0.68219 (19) −0.01640 (16) 0.93118 (13) 0.0534 (4) C46 0.6598 (2) −0.11931 (18) 0.97154 (15) 0.0632 (5) H46 0.5982 −0.1395 0.9523 0.076\* C47 0.7274 (2) −0.19163 (19) 1.03947 (15) 0.0676 (6) H47 0.7122 −0.2603 1.0655 0.081\* C48 0.8172 (2) −0.1612 (2) 1.06821 (14) 0.0655 (6) C49 0.8405 (2) −0.0588 (2) 1.03070 (16) 0.0661 (5) H49 0.9008 −0.0384 1.0513 0.079\* C50 0.7730 (2) 0.01233 (17) 0.96251 (14) 0.0599 (5) H50 0.7886 0.0809 0.9370 0.072\* ------ -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1945 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cl1 0.0485 (3) 0.0690 (3) 0.0810 (4) −0.0169 (2) 0.0158 (2) −0.0153 (3) Cl2 0.1064 (5) 0.0972 (5) 0.0794 (4) −0.0360 (4) −0.0375 (4) −0.0041 (4) O1 0.0567 (8) 0.0792 (10) 0.0693 (9) −0.0061 (7) −0.0043 (7) −0.0323 (8) N1 0.0507 (8) 0.0490 (8) 0.0522 (8) −0.0209 (7) −0.0003 (7) −0.0091 (7) C1 0.0447 (9) 0.0438 (9) 0.0456 (9) −0.0159 (7) −0.0037 (7) −0.0088 (7) C2 0.0532 (10) 0.0413 (9) 0.0542 (10) −0.0113 (8) −0.0039 (8) −0.0065 (8) C3 0.0474 (10) 0.0469 (10) 0.0610 (11) −0.0053 (8) −0.0037 (8) −0.0122 (8) C4 0.0434 (9) 0.0515 (10) 0.0537 (10) −0.0143 (8) 0.0019 (7) −0.0124 (8) C5 0.0472 (9) 0.0439 (9) 0.0513 (10) −0.0137 (7) 0.0007 (7) −0.0075 (7) C6 0.0413 (8) 0.0424 (9) 0.0455 (9) −0.0121 (7) −0.0030 (7) −0.0097 (7) C7 0.0437 (9) 0.0446 (9) 0.0475 (9) −0.0103 (7) −0.0028 (7) −0.0094 (7) C8 0.0404 (9) 0.0526 (10) 0.0519 (10) −0.0116 (7) −0.0016 (7) −0.0144 (8) C9 0.0452 (9) 0.0573 (11) 0.0525 (10) −0.0219 (8) 0.0014 (7) −0.0142 (8) C10 0.0540 (12) 0.0765 (14) 0.0781 (15) −0.0321 (11) 0.0114 (10) −0.0162 (12) C11 0.0383 (8) 0.0429 (9) 0.0567 (10) −0.0065 (7) −0.0001 (7) −0.0078 (8) C12 0.0637 (12) 0.0496 (10) 0.0579 (11) −0.0110 (9) 0.0003 (9) −0.0107 (9) C13 0.0793 (15) 0.0576 (12) 0.0578 (12) −0.0157 (11) −0.0012 (10) 0.0000 (10) C14 0.0659 (13) 0.0482 (11) 0.0749 (14) −0.0127 (9) 0.0006 (11) −0.0002 (10) C15 0.0656 (13) 0.0491 (11) 0.0833 (16) −0.0167 (9) 0.0014 (11) −0.0177 (10) C16 0.0586 (11) 0.0534 (11) 0.0616 (12) −0.0156 (9) −0.0024 (9) −0.0131 (9) C17 0.0436 (9) 0.0602 (11) 0.0550 (11) −0.0124 (8) 0.0025 (8) −0.0146 (9) C18 0.0435 (10) 0.0694 (13) 0.0672 (13) −0.0024 (9) −0.0036 (9) −0.0237 (10) C19 0.0473 (10) 0.0616 (12) 0.0645 (12) −0.0061 (9) −0.0003 (9) −0.0182 (10) C20 0.0565 (11) 0.0612 (12) 0.0596 (12) −0.0132 (9) −0.0025 (9) −0.0176 (10) C21 0.0698 (13) 0.0630 (13) 0.0652 (13) −0.0134 (10) 0.0016 (10) −0.0238 (11) C22 0.0950 (17) 0.0696 (14) 0.0553 (12) −0.0279 (13) −0.0025 (11) −0.0198 (11) C23 0.0756 (14) 0.0624 (13) 0.0633 (13) −0.0268 (11) −0.0144 (11) −0.0079 (10) C24 0.0577 (13) 0.0975 (19) 0.0731 (15) −0.0140 (12) −0.0089 (11) −0.0251 (14) C25 0.0580 (12) 0.1000 (19) 0.0616 (13) −0.0094 (12) −0.0046 (10) −0.0290 (13) Cl3 0.0766 (4) 0.1135 (5) 0.0664 (3) −0.0543 (4) 0.0053 (3) 0.0031 (3) Cl4 0.0807 (4) 0.1019 (5) 0.0778 (4) −0.0143 (4) −0.0140 (3) 0.0241 (4) O2 0.1015 (13) 0.0784 (11) 0.1015 (14) −0.0568 (11) −0.0422 (11) 0.0203 (10) N2 0.0514 (8) 0.0475 (8) 0.0523 (8) −0.0102 (7) −0.0031 (7) −0.0133 (7) C26 0.0530 (10) 0.0436 (9) 0.0450 (9) −0.0144 (7) −0.0042 (7) −0.0094 (7) C27 0.0722 (13) 0.0430 (10) 0.0570 (11) −0.0127 (9) −0.0058 (9) −0.0063 (8) C28 0.0881 (15) 0.0506 (11) 0.0527 (11) −0.0293 (11) −0.0055 (10) 0.0007 (9) C29 0.0638 (12) 0.0673 (12) 0.0469 (10) −0.0331 (10) −0.0024 (8) −0.0049 (9) C30 0.0489 (10) 0.0575 (11) 0.0525 (10) −0.0187 (8) −0.0034 (8) −0.0090 (8) C31 0.0475 (9) 0.0437 (9) 0.0455 (9) −0.0164 (7) −0.0043 (7) −0.0080 (7) C32 0.0471 (9) 0.0430 (9) 0.0516 (9) −0.0144 (7) −0.0070 (7) −0.0068 (7) C33 0.0512 (10) 0.0461 (9) 0.0491 (9) −0.0185 (8) −0.0069 (7) −0.0039 (7) C34 0.0487 (9) 0.0544 (10) 0.0476 (9) −0.0170 (8) −0.0034 (7) −0.0110 (8) C35 0.0556 (12) 0.0802 (15) 0.0641 (13) −0.0249 (11) 0.0053 (10) −0.0167 (11) C36 0.0510 (10) 0.0442 (9) 0.0626 (11) −0.0136 (8) −0.0022 (8) −0.0049 (8) C37 0.0637 (13) 0.0593 (13) 0.114 (2) −0.0181 (11) −0.0014 (13) −0.0297 (14) C38 0.0825 (19) 0.0600 (15) 0.170 (3) −0.0183 (14) 0.015 (2) −0.0479 (19) C39 0.0656 (17) 0.0584 (15) 0.164 (3) 0.0017 (12) 0.0044 (18) −0.0139 (18) C40 0.0580 (14) 0.0813 (18) 0.121 (3) 0.0008 (12) −0.0186 (15) −0.0100 (17) C41 0.0559 (12) 0.0682 (14) 0.0839 (16) −0.0075 (10) −0.0137 (11) −0.0146 (12) C42 0.0596 (11) 0.0514 (10) 0.0620 (12) −0.0247 (9) −0.0069 (9) −0.0008 (9) C43 0.0590 (11) 0.0495 (10) 0.0567 (11) −0.0203 (9) −0.0040 (9) −0.0048 (8) C44 0.0571 (11) 0.0497 (10) 0.0600 (11) −0.0191 (8) −0.0023 (9) −0.0055 (9) C45 0.0554 (10) 0.0450 (9) 0.0525 (10) −0.0126 (8) 0.0050 (8) −0.0074 (8) C46 0.0676 (13) 0.0562 (11) 0.0635 (12) −0.0262 (10) 0.0025 (10) −0.0044 (10) C47 0.0739 (14) 0.0528 (11) 0.0627 (13) −0.0189 (10) 0.0073 (10) 0.0020 (10) C48 0.0588 (12) 0.0623 (12) 0.0542 (11) −0.0054 (10) 0.0054 (9) 0.0002 (9) C49 0.0602 (12) 0.0679 (13) 0.0653 (13) −0.0170 (10) −0.0036 (10) −0.0104 (11) C50 0.0640 (12) 0.0478 (10) 0.0628 (12) −0.0167 (9) −0.0024 (9) −0.0055 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3159 .table-wrap} ----------------------- -------------- ----------------------- -------------- Cl1---C4 1.7382 (19) Cl3---C29 1.744 (2) Cl2---C23 1.742 (2) Cl4---C48 1.739 (2) O1---C17 1.217 (2) O2---C42 1.218 (3) N1---C9 1.316 (3) N2---C34 1.319 (3) N1---C1 1.365 (2) N2---C26 1.363 (3) C1---C2 1.410 (3) C26---C27 1.413 (3) C1---C6 1.416 (2) C26---C31 1.414 (3) C2---C3 1.368 (3) C27---C28 1.364 (3) C2---H2 0.9300 C27---H27 0.9300 C3---C4 1.401 (3) C28---C29 1.397 (3) C3---H3 0.9300 C28---H28 0.9300 C4---C5 1.362 (3) C29---C30 1.358 (3) C5---C6 1.413 (2) C30---C31 1.412 (3) C5---H5 0.9300 C30---H30 0.9300 C6---C7 1.431 (2) C31---C32 1.426 (2) C7---C8 1.372 (3) C32---C33 1.374 (3) C7---C11 1.492 (3) C32---C36 1.492 (3) C8---C9 1.428 (3) C33---C34 1.431 (3) C8---C17 1.517 (3) C33---C42 1.506 (3) C9---C10 1.503 (3) C34---C35 1.501 (3) C10---H10A 0.9600 C35---H35A 0.9600 C10---H10B 0.9600 C35---H35B 0.9600 C10---H10C 0.9600 C35---H35C 0.9600 C11---C12 1.381 (3) C36---C37 1.379 (3) C11---C16 1.387 (3) C36---C41 1.390 (3) C12---C13 1.388 (3) C37---C38 1.390 (4) C12---H12 0.9300 C37---H37 0.9300 C13---C14 1.374 (3) C38---C39 1.364 (5) C13---H13 0.9300 C38---H38 0.9300 C14---C15 1.365 (4) C39---C40 1.364 (5) C14---H14 0.9300 C39---H39 0.9300 C15---C16 1.388 (3) C40---C41 1.382 (3) C15---H15 0.9300 C40---H40 0.9300 C16---H16 0.9300 C41---H41 0.9300 C17---C18 1.464 (3) C42---C43 1.474 (3) C18---C19 1.319 (3) C43---C44 1.328 (3) C18---H18 0.9300 C43---H43 0.9300 C19---C20 1.465 (3) C44---C45 1.461 (3) C19---H19 0.9300 C44---H44 0.9300 C20---C21 1.386 (3) C45---C50 1.389 (3) C20---C25 1.394 (3) C45---C46 1.396 (3) C21---C22 1.384 (4) C46---C47 1.380 (3) C21---H21 0.9300 C46---H46 0.9300 C22---C23 1.375 (4) C47---C48 1.369 (4) C22---H22 0.9300 C47---H47 0.9300 C23---C24 1.371 (4) C48---C49 1.387 (3) C24---C25 1.377 (3) C49---C50 1.378 (3) C24---H24 0.9300 C49---H49 0.9300 C25---H25 0.9300 C50---H50 0.9300 C9---N1---C1 118.46 (16) C34---N2---C26 118.56 (16) N1---C1---C2 118.14 (16) N2---C26---C27 118.09 (17) N1---C1---C6 122.92 (16) N2---C26---C31 123.31 (17) C2---C1---C6 118.93 (16) C27---C26---C31 118.60 (18) C3---C2---C1 121.07 (17) C28---C27---C26 121.1 (2) C3---C2---H2 119.5 C28---C27---H27 119.4 C1---C2---H2 119.5 C26---C27---H27 119.4 C2---C3---C4 119.13 (17) C27---C28---C29 119.23 (19) C2---C3---H3 120.4 C27---C28---H28 120.4 C4---C3---H3 120.4 C29---C28---H28 120.4 C5---C4---C3 122.07 (17) C30---C29---C28 122.08 (19) C5---C4---Cl1 119.37 (15) C30---C29---Cl3 119.69 (17) C3---C4---Cl1 118.55 (14) C28---C29---Cl3 118.22 (16) C4---C5---C6 119.44 (17) C29---C30---C31 119.53 (19) C4---C5---H5 120.3 C29---C30---H30 120.2 C6---C5---H5 120.3 C31---C30---H30 120.2 C5---C6---C1 119.35 (16) C30---C31---C26 119.43 (17) C5---C6---C7 122.85 (16) C30---C31---C32 123.25 (17) C1---C6---C7 117.78 (15) C26---C31---C32 117.30 (16) C8---C7---C6 118.00 (16) C33---C32---C31 118.61 (16) C8---C7---C11 122.04 (16) C33---C32---C36 121.53 (16) C6---C7---C11 119.96 (15) C31---C32---C36 119.79 (16) C7---C8---C9 120.17 (16) C32---C33---C34 119.91 (17) C7---C8---C17 120.18 (17) C32---C33---C42 121.42 (17) C9---C8---C17 119.57 (16) C34---C33---C42 118.64 (17) N1---C9---C8 122.56 (16) N2---C34---C33 122.17 (17) N1---C9---C10 116.73 (18) N2---C34---C35 116.12 (18) C8---C9---C10 120.69 (18) C33---C34---C35 121.69 (18) C9---C10---H10A 109.5 C34---C35---H35A 109.5 C9---C10---H10B 109.5 C34---C35---H35B 109.5 H10A---C10---H10B 109.5 H35A---C35---H35B 109.5 C9---C10---H10C 109.5 C34---C35---H35C 109.5 H10A---C10---H10C 109.5 H35A---C35---H35C 109.5 H10B---C10---H10C 109.5 H35B---C35---H35C 109.5 C12---C11---C16 119.32 (19) C37---C36---C41 118.8 (2) C12---C11---C7 119.69 (17) C37---C36---C32 120.9 (2) C16---C11---C7 120.99 (18) C41---C36---C32 120.26 (19) C11---C12---C13 120.0 (2) C36---C37---C38 120.0 (3) C11---C12---H12 120.0 C36---C37---H37 120.0 C13---C12---H12 120.0 C38---C37---H37 120.0 C14---C13---C12 120.2 (2) C39---C38---C37 120.4 (3) C14---C13---H13 119.9 C39---C38---H38 119.8 C12---C13---H13 119.9 C37---C38---H38 119.8 C15---C14---C13 120.3 (2) C40---C39---C38 120.2 (3) C15---C14---H14 119.9 C40---C39---H39 119.9 C13---C14---H14 119.9 C38---C39---H39 119.9 C14---C15---C16 120.1 (2) C39---C40---C41 120.1 (3) C14---C15---H15 120.0 C39---C40---H40 119.9 C16---C15---H15 120.0 C41---C40---H40 119.9 C11---C16---C15 120.2 (2) C40---C41---C36 120.4 (3) C11---C16---H16 119.9 C40---C41---H41 119.8 C15---C16---H16 119.9 C36---C41---H41 119.8 O1---C17---C18 120.89 (18) O2---C42---C43 122.00 (19) O1---C17---C8 119.33 (18) O2---C42---C33 119.04 (19) C18---C17---C8 119.78 (17) C43---C42---C33 118.92 (17) C19---C18---C17 125.35 (19) C44---C43---C42 121.33 (19) C19---C18---H18 117.3 C44---C43---H43 119.3 C17---C18---H18 117.3 C42---C43---H43 119.3 C18---C19---C20 126.18 (19) C43---C44---C45 127.8 (2) C18---C19---H19 116.9 C43---C44---H44 116.1 C20---C19---H19 116.9 C45---C44---H44 116.1 C21---C20---C25 117.8 (2) C50---C45---C46 118.0 (2) C21---C20---C19 120.6 (2) C50---C45---C44 123.49 (18) C25---C20---C19 121.6 (2) C46---C45---C44 118.5 (2) C22---C21---C20 121.2 (2) C47---C46---C45 121.2 (2) C22---C21---H21 119.4 C47---C46---H46 119.4 C20---C21---H21 119.4 C45---C46---H46 119.4 C23---C22---C21 119.1 (2) C48---C47---C46 119.3 (2) C23---C22---H22 120.5 C48---C47---H47 120.4 C21---C22---H22 120.5 C46---C47---H47 120.4 C24---C23---C22 121.2 (2) C47---C48---C49 121.2 (2) C24---C23---Cl2 118.6 (2) C47---C48---Cl4 119.60 (18) C22---C23---Cl2 120.08 (19) C49---C48---Cl4 119.2 (2) C23---C24---C25 119.1 (2) C50---C49---C48 119.0 (2) C23---C24---H24 120.4 C50---C49---H49 120.5 C25---C24---H24 120.4 C48---C49---H49 120.5 C24---C25---C20 121.4 (2) C49---C50---C45 121.3 (2) C24---C25---H25 119.3 C49---C50---H50 119.4 C20---C25---H25 119.3 C45---C50---H50 119.4 C9---N1---C1---C2 −176.90 (17) C34---N2---C26---C27 176.12 (18) C9---N1---C1---C6 2.7 (3) C34---N2---C26---C31 −3.2 (3) N1---C1---C2---C3 −179.97 (18) N2---C26---C27---C28 −179.62 (19) C6---C1---C2---C3 0.4 (3) C31---C26---C27---C28 −0.2 (3) C1---C2---C3---C4 0.5 (3) C26---C27---C28---C29 −0.9 (3) C2---C3---C4---C5 −1.0 (3) C27---C28---C29---C30 1.3 (3) C2---C3---C4---Cl1 −179.51 (16) C27---C28---C29---Cl3 −179.09 (17) C3---C4---C5---C6 0.5 (3) C28---C29---C30---C31 −0.7 (3) Cl1---C4---C5---C6 179.04 (14) Cl3---C29---C30---C31 179.77 (15) C4---C5---C6---C1 0.4 (3) C29---C30---C31---C26 −0.5 (3) C4---C5---C6---C7 −177.66 (17) C29---C30---C31---C32 177.63 (18) N1---C1---C6---C5 179.54 (17) N2---C26---C31---C30 −179.74 (17) C2---C1---C6---C5 −0.9 (3) C27---C26---C31---C30 0.9 (3) N1---C1---C6---C7 −2.3 (3) N2---C26---C31---C32 2.0 (3) C2---C1---C6---C7 177.31 (16) C27---C26---C31---C32 −177.30 (17) C5---C6---C7---C8 177.51 (17) C30---C31---C32---C33 −176.60 (17) C1---C6---C7---C8 −0.6 (3) C26---C31---C32---C33 1.5 (3) C5---C6---C7---C11 −2.4 (3) C30---C31---C32---C36 0.4 (3) C1---C6---C7---C11 179.46 (16) C26---C31---C32---C36 178.50 (17) C6---C7---C8---C9 2.9 (3) C31---C32---C33---C34 −3.8 (3) C11---C7---C8---C9 −177.17 (17) C36---C32---C33---C34 179.30 (17) C6---C7---C8---C17 −173.98 (16) C31---C32---C33---C42 174.06 (17) C11---C7---C8---C17 6.0 (3) C36---C32---C33---C42 −2.8 (3) C1---N1---C9---C8 −0.2 (3) C26---N2---C34---C33 0.8 (3) C1---N1---C9---C10 −178.50 (17) C26---N2---C34---C35 179.19 (17) C7---C8---C9---N1 −2.6 (3) C32---C33---C34---N2 2.7 (3) C17---C8---C9---N1 174.28 (18) C42---C33---C34---N2 −175.19 (18) C7---C8---C9---C10 175.59 (19) C32---C33---C34---C35 −175.55 (18) C17---C8---C9---C10 −7.5 (3) C42---C33---C34---C35 6.5 (3) C8---C7---C11---C12 111.0 (2) C33---C32---C36---C37 69.7 (3) C6---C7---C11---C12 −69.0 (2) C31---C32---C36---C37 −107.1 (2) C8---C7---C11---C16 −69.5 (3) C33---C32---C36---C41 −110.8 (2) C6---C7---C11---C16 110.4 (2) C31---C32---C36---C41 72.3 (3) C16---C11---C12---C13 0.0 (3) C41---C36---C37---C38 0.6 (4) C7---C11---C12---C13 179.45 (19) C32---C36---C37---C38 −179.9 (3) C11---C12---C13---C14 −0.7 (4) C36---C37---C38---C39 0.9 (5) C12---C13---C14---C15 1.0 (4) C37---C38---C39---C40 −1.2 (6) C13---C14---C15---C16 −0.5 (4) C38---C39---C40---C41 0.0 (6) C12---C11---C16---C15 0.5 (3) C39---C40---C41---C36 1.5 (5) C7---C11---C16---C15 −178.98 (18) C37---C36---C41---C40 −1.8 (4) C14---C15---C16---C11 −0.2 (3) C32---C36---C41---C40 178.7 (2) C7---C8---C17---O1 91.2 (2) C32---C33---C42---O2 −119.1 (3) C9---C8---C17---O1 −85.7 (2) C34---C33---C42---O2 58.8 (3) C7---C8---C17---C18 −88.1 (2) C32---C33---C42---C43 63.1 (3) C9---C8---C17---C18 95.0 (2) C34---C33---C42---C43 −119.0 (2) O1---C17---C18---C19 −174.0 (2) O2---C42---C43---C44 −5.8 (4) C8---C17---C18---C19 5.3 (4) C33---C42---C43---C44 171.9 (2) C17---C18---C19---C20 176.6 (2) C42---C43---C44---C45 −179.3 (2) C18---C19---C20---C21 −159.6 (2) C43---C44---C45---C50 8.2 (3) C18---C19---C20---C25 19.1 (4) C43---C44---C45---C46 −170.8 (2) C25---C20---C21---C22 −3.5 (4) C50---C45---C46---C47 −1.2 (3) C19---C20---C21---C22 175.3 (2) C44---C45---C46---C47 177.8 (2) C20---C21---C22---C23 0.6 (4) C45---C46---C47---C48 0.6 (3) C21---C22---C23---C24 2.7 (4) C46---C47---C48---C49 0.5 (3) C21---C22---C23---Cl2 −175.03 (19) C46---C47---C48---Cl4 −179.29 (17) C22---C23---C24---C25 −2.9 (4) C47---C48---C49---C50 −1.0 (3) Cl2---C23---C24---C25 174.8 (2) Cl4---C48---C49---C50 178.82 (17) C23---C24---C25---C20 −0.2 (5) C48---C49---C50---C45 0.3 (3) C21---C20---C25---C24 3.3 (4) C46---C45---C50---C49 0.8 (3) C19---C20---C25---C24 −175.5 (3) C44---C45---C50---C49 −178.2 (2) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5010 .table-wrap} ------------------------------------------- Cg1 is the centroid of the C20--C25 ring. ------------------------------------------- ::: ::: {#d1e5014 .table-wrap} -------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C38---H38···Cg1^i^ 0.93 2.93 3.458 (3) 117 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+2, −*y*, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 is the centroid of the C20--C25 ring. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- --------- ------- ----------- ------------- C38---H38⋯*Cg*1^i^ 0.93 2.93 3.458 (3) 117 Symmetry code: (i) . ::: [^1]: ‡ Additional correspondence author, e-mail: kvpsvijayakumar@gmail.com.

PubMed Central

2024-06-05T04:04:18.553560

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052117/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o624", "authors": [ { "first": "S.", "last": "Sarveswari" }, { "first": "V.", "last": "Vijayakumar" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }

PMC3052118

Related literature {#sec1} ================== For background to metal salicylaldiminato complexes as optoelectronic materials, see: Liuzzo *et al.* (2010[@bb6]); Shirai *et al.*, (2000[@bb10]). For background to zinc complexes as organic light-emitting diodes, see: Chen *et al.* (2009[@bb4]). For related structures, see: MacLachlan *et al.* (1996[@bb7]). For geometrical analysis, see: Addison *et al.* (1984[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(C~34~H~42~N~4~O~2~)(C~2~H~6~OS)\]·C~2~H~3~N*M* *~r~* = 723.27Monoclinic,*a* = 12.3288 (7) Å*b* = 17.7043 (9) Å*c* = 17.3932 (9) Åβ = 92.4391 (8)°*V* = 3793.0 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 0.74 mm^−1^*T* = 100 K0.45 × 0.30 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb8]) *T* ~min~ = 0.603, *T* ~max~ = 0.74635700 measured reflections8699 independent reflections7157 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.041 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.032*wR*(*F* ^2^) = 0.080*S* = 1.028699 reflections448 parametersH-atom parameters constrainedΔρ~max~ = 0.56 e Å^−3^Δρ~min~ = −0.29 e Å^−3^ {#d5e465} Data collection: *APEX2* (Bruker, 2008[@bb3]); cell refinement: *SAINT* (Bruker, 2008[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb9]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb5]), *DIAMOND* (Brandenburg, 2006[@bb2]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb12]) and *PLATON* (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100359X/hb5794sup1.cif](http://dx.doi.org/10.1107/S160053681100359X/hb5794sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100359X/hb5794Isup2.hkl](http://dx.doi.org/10.1107/S160053681100359X/hb5794Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5794&file=hb5794sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5794sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5794&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5794](http://scripts.iucr.org/cgi-bin/sendsup?hb5794)). The authors acknowledge King Abdulaziz University for financial support (grant No. 17--013/430). The authors also thank the University of Malaya for support of the crystallographic facility. Comment ======= Metal complexes with salicylaldiminato ligands are promising materials for optoelectronic applications due to their outstanding photo- and electro-luminescent properties (Liuzzo *et al.*, 2010; Shirai *et al.*, 2000). One of the main appeals of this class of coordination complexes is that molecular engineering permits systematically the optimizing of spectroscopic and chemical properties. This chemical flexibility allows for the design of systems that respond to specific environmental variables. Recently, zinc complexes have been introduced to OLED\'s (organic light-emitting diodes) and recognized as useful electron transport materials (Chen *et al.*, 2009). The above motivated the synthesis and structural characterization of the title complex, (I). The Zn atom in (I), Fig. 1, is tetracoordinated by the N~2~O~2~ donor atoms of the tetradentate Schiff-base ligand and the O atom derived from the dimethyl sulfoxide ligand, Table 1; the asymmetric unit is completed by a non-coordinating acetonitrile molecule. The resulting N~2~O~3~ donor set is based on a square pyramidal arrangement with the dimethyl sulfoxide-O3 atom occupying an axial site. The value of τ = 0.16 compares with τ = 0 and 1.0 for ideal square pyramidal and trigonal bipyramidal geometries, respectively (Addison *et al.*, 1984). The r.m.s. deviation of the O1, O2, N1 and N2 atoms from their least-squares plane is 0.0836 Å and the Zn atom lies 0.3976 (7) Å out of the plane towards the O3 atom. The tetradentate mode of coordination of the Schiff-base leads to the formation of a five- and two six-membered rings. The former has a conformation based on an envelope on Zn (Spek, 2009). While the chelate ring involving the O1 atom is approximately planar (r.m.s. = 0.054 Å), there is significantly more distortion in the O2-containing chelate ring (r.m.s. = 0.203 Å). Schiff-base ligands derived from diaminomaleonitrile have been documented and shown to adopt comparable coordination modes towards transition metals (MacLachlan *et al.*, 1996). Experimental {#experimental} ============ A mixture of diaminemaleonitrile (0.1 g, 0.93 mmol), 3,5-di-*tert*-butyl-2-hydroxybenzaldehyde (0.1 g, 1.86 mmol), zinc(II) acetate dihydrate (0.2 g, 0.93 mmol) and ethanol (5 ml) were placed in a glass Petri dish and capped with a glass cover. The dish was placed in a microwave oven (700 W) and irradiated for 1 min. The reaction mixture was cooled and washed with 15 ml of ethanol. The purple solid was filtered off and washed with ethanol. Re-crystallization was by slow evaporation of an acetonitrile/dimethyl sulfoxide (90/10 *v*/*v*) solution which yielded purple blocks of (I). Yield: 70%. *M*.pt. \> 623 K (dec.). ^1^H NMR (DMSO-d6, 500 MHz): δ = 1.25 (s, 18H, C(CH~3~)~3~), 1.47 (s, 18H, C(CH~3~)~3~), 2.06 (MeCN), 2.50 (DMSO), 7.24 (s, 2H, Ar---H), 7.43 (s, 2H, Ar---H), 8.58 (s, 2H, N═CH) p.p.m.. ^13^C NMR (DMSO-d6, 500 MHz): δ = 28.19, 29.80 (C(CH~3~)~3~), 32.61, 34.13 (C(CH~3~)~3~), 110.48, 116.85, 120.31, 128.10, 130.17, 134.20, 141.11, 161.68 and 172.33 p.p.m. IR: 2952, 2212 (C≡N), 1616 (C═N), 1569, 1519, 1433, 1372, 1170, 1154, 1119, 1032, 795, 656 cm^-1^. λ~max~ (DMSO, 10 ^-5^ mol *L*^-1^): 574, 501, 380, 375, 318, 245 nm. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C--H = 0.95 to 0.98 Å) and were included in the refinement in the riding model approximation, with *U*~iso~(H) set to 1.2--1.5*U*~equiv~(C). In the final refinement three low angle reflections evidently effected by the beam stop were omitted, *i.e*. (011), (101) and (110). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing displacement ellipsoids at the 50% probability level. ::: ![](e-67-0m314-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e217 .table-wrap} -------------------------------------------------- --------------------------------------- \[Zn(C~34~H~42~N~4~O~2~)(C~2~H~6~OS)\]·C~2~H~3~N *F*(000) = 1536 *M~r~* = 723.27 *D*~x~ = 1.267 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 9906 reflections *a* = 12.3288 (7) Å θ = 2.3--28.3° *b* = 17.7043 (9) Å µ = 0.74 mm^−1^ *c* = 17.3932 (9) Å *T* = 100 K β = 92.4391 (8)° Block, purple *V* = 3793.0 (3) Å^3^ 0.45 × 0.30 × 0.10 mm *Z* = 4 -------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e361 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD diffractometer 8699 independent reflections Radiation source: fine-focus sealed tube 7157 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.041 ω scans θ~max~ = 27.5°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −16→16 *T*~min~ = 0.603, *T*~max~ = 0.746 *k* = −23→23 35700 measured reflections *l* = −22→22 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e475 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.032 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.080 H-atom parameters constrained *S* = 1.02 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.036*P*)^2^ + 1.6768*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 8699 reflections (Δ/σ)~max~ = 0.002 448 parameters Δρ~max~ = 0.56 e Å^−3^ 0 restraints Δρ~min~ = −0.29 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e632 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e731 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Zn 0.516854 (14) 0.654898 (11) 0.558637 (10) 0.01242 (6) S1 0.41362 (3) 0.82176 (2) 0.50384 (2) 0.01635 (9) O1 0.63893 (9) 0.70123 (7) 0.61554 (7) 0.0184 (3) O2 0.44436 (9) 0.61428 (7) 0.64636 (6) 0.0167 (2) O3 0.41323 (9) 0.73722 (7) 0.51757 (7) 0.0198 (3) N1 0.61797 (11) 0.64054 (7) 0.46602 (8) 0.0129 (3) N2 0.42744 (10) 0.57668 (7) 0.49091 (7) 0.0121 (3) N3 0.64563 (12) 0.60956 (9) 0.27021 (9) 0.0224 (3) N4 0.34261 (12) 0.51244 (9) 0.30973 (9) 0.0221 (3) N5 0.63439 (16) 1.00678 (11) 0.54854 (14) 0.0500 (6) C1 0.73798 (13) 0.71491 (9) 0.59846 (9) 0.0133 (3) C2 0.81352 (12) 0.74304 (9) 0.65753 (9) 0.0127 (3) C3 0.91590 (13) 0.76392 (9) 0.63645 (9) 0.0136 (3) H3 0.9635 0.7851 0.6751 0.016\* C4 0.95562 (12) 0.75609 (9) 0.56135 (9) 0.0128 (3) C5 0.88612 (12) 0.72505 (9) 0.50676 (9) 0.0129 (3) H5 0.9107 0.7177 0.4563 0.015\* C6 0.77787 (12) 0.70320 (9) 0.52280 (9) 0.0130 (3) C7 0.78027 (12) 0.74618 (9) 0.74153 (9) 0.0138 (3) C8 0.87537 (14) 0.77112 (11) 0.79528 (10) 0.0212 (4) H8A 0.9355 0.7353 0.7914 0.032\* H8B 0.8520 0.7724 0.8484 0.032\* H8C 0.8994 0.8216 0.7804 0.032\* C9 0.68745 (14) 0.80283 (10) 0.75108 (10) 0.0206 (4) H9A 0.6683 0.8044 0.8052 0.031\* H9B 0.6240 0.7871 0.7191 0.031\* H9C 0.7108 0.8531 0.7350 0.031\* C10 0.74430 (15) 0.66745 (10) 0.76792 (10) 0.0211 (4) H10A 0.8033 0.6312 0.7613 0.032\* H10B 0.6801 0.6515 0.7370 0.032\* H10C 0.7266 0.6695 0.8223 0.032\* C11 1.07286 (13) 0.77942 (9) 0.54726 (9) 0.0148 (3) C12 1.08302 (14) 0.86593 (10) 0.55278 (11) 0.0221 (4) H12A 1.0340 0.8894 0.5140 0.033\* H12B 1.1580 0.8809 0.5437 0.033\* H12C 1.0636 0.8826 0.6042 0.033\* C13 1.10819 (14) 0.75406 (11) 0.46817 (10) 0.0226 (4) H13A 1.0609 0.7773 0.4281 0.034\* H13B 1.1029 0.6989 0.4643 0.034\* H13C 1.1834 0.7697 0.4614 0.034\* C14 1.15020 (13) 0.74290 (10) 0.60857 (10) 0.0186 (4) H14A 1.1375 0.6883 0.6098 0.028\* H14B 1.1367 0.7645 0.6591 0.028\* H14C 1.2256 0.7527 0.5958 0.028\* C15 0.71711 (12) 0.66741 (9) 0.46187 (9) 0.0131 (3) H15 0.7509 0.6624 0.4141 0.016\* C16 0.56431 (13) 0.60475 (9) 0.40459 (9) 0.0122 (3) C17 0.60834 (13) 0.60514 (9) 0.32927 (9) 0.0140 (3) C18 0.46527 (12) 0.57224 (9) 0.41737 (9) 0.0119 (3) C19 0.40078 (13) 0.53784 (9) 0.35600 (9) 0.0141 (3) C20 0.33269 (12) 0.55019 (9) 0.50908 (9) 0.0130 (3) H20 0.2899 0.5258 0.4697 0.016\* C21 0.28904 (12) 0.55523 (9) 0.58319 (9) 0.0122 (3) C22 0.18261 (13) 0.52592 (9) 0.59065 (9) 0.0144 (3) H22 0.1463 0.5038 0.5469 0.017\* C23 0.13077 (13) 0.52844 (9) 0.65864 (9) 0.0139 (3) C24 0.18870 (13) 0.56085 (9) 0.72222 (10) 0.0153 (3) H24 0.1538 0.5625 0.7699 0.018\* C25 0.29211 (13) 0.59022 (9) 0.72021 (9) 0.0143 (3) C26 0.34663 (13) 0.58787 (9) 0.64890 (9) 0.0137 (3) C27 0.01364 (13) 0.50025 (10) 0.66406 (10) 0.0170 (3) C28 0.00085 (18) 0.42155 (12) 0.63012 (14) 0.0377 (5) H28A 0.0470 0.3861 0.6599 0.056\* H28B 0.0225 0.4220 0.5766 0.056\* H28C −0.0752 0.4057 0.6320 0.056\* C29 −0.02449 (15) 0.49953 (13) 0.74654 (11) 0.0312 (5) H29A 0.0230 0.4666 0.7783 0.047\* H29B −0.0992 0.4806 0.7468 0.047\* H29C −0.0217 0.5509 0.7675 0.047\* C30 −0.06285 (15) 0.55409 (12) 0.61742 (12) 0.0287 (4) H30A −0.1381 0.5372 0.6214 0.043\* H30B −0.0437 0.5538 0.5633 0.043\* H30C −0.0552 0.6054 0.6380 0.043\* C31 0.34962 (14) 0.62514 (10) 0.79195 (10) 0.0175 (3) C32 0.27723 (16) 0.62444 (13) 0.86125 (11) 0.0293 (4) H32A 0.2104 0.6527 0.8487 0.044\* H32B 0.3159 0.6480 0.9054 0.044\* H32C 0.2590 0.5722 0.8740 0.044\* C33 0.45222 (14) 0.57956 (10) 0.81404 (10) 0.0213 (4) H33A 0.4881 0.6017 0.8601 0.032\* H33B 0.5018 0.5808 0.7715 0.032\* H33C 0.4322 0.5271 0.8246 0.032\* C34 0.37892 (15) 0.70810 (10) 0.77625 (11) 0.0227 (4) H34A 0.3126 0.7366 0.7629 0.034\* H34B 0.4280 0.7105 0.7335 0.034\* H34C 0.4147 0.7300 0.8224 0.034\* C35 0.44163 (17) 0.86449 (11) 0.59519 (11) 0.0272 (4) H35A 0.3795 0.8573 0.6277 0.041\* H35B 0.4546 0.9186 0.5883 0.041\* H35C 0.5062 0.8411 0.6198 0.041\* C36 0.53942 (15) 0.84257 (11) 0.46161 (12) 0.0260 (4) H36A 0.5411 0.8186 0.4109 0.039\* H36B 0.5994 0.8232 0.4947 0.039\* H36C 0.5469 0.8974 0.4560 0.039\* C37 0.71611 (16) 0.99001 (11) 0.57521 (12) 0.0284 (4) C38 0.82087 (17) 0.96856 (14) 0.60957 (14) 0.0398 (5) H38A 0.8254 0.9844 0.6636 0.060\* H38B 0.8786 0.9932 0.5818 0.060\* H38C 0.8294 0.9136 0.6066 0.060\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1980 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Zn 0.01068 (9) 0.01551 (10) 0.01115 (10) −0.00142 (7) 0.00141 (7) −0.00244 (7) S1 0.01486 (19) 0.0156 (2) 0.0185 (2) −0.00009 (15) −0.00009 (15) −0.00080 (16) O1 0.0123 (6) 0.0290 (7) 0.0141 (6) −0.0051 (5) 0.0029 (4) −0.0070 (5) O2 0.0122 (5) 0.0260 (7) 0.0120 (6) −0.0043 (5) 0.0008 (4) 0.0004 (5) O3 0.0160 (6) 0.0143 (6) 0.0291 (7) 0.0003 (5) −0.0007 (5) −0.0002 (5) N1 0.0125 (6) 0.0148 (7) 0.0112 (7) 0.0002 (5) −0.0010 (5) −0.0006 (5) N2 0.0133 (6) 0.0126 (7) 0.0105 (7) 0.0012 (5) 0.0014 (5) 0.0003 (5) N3 0.0248 (8) 0.0260 (8) 0.0167 (8) −0.0025 (6) 0.0036 (6) −0.0005 (6) N4 0.0203 (8) 0.0251 (8) 0.0207 (8) −0.0033 (6) −0.0005 (6) −0.0046 (6) N5 0.0405 (11) 0.0296 (11) 0.0778 (16) −0.0031 (9) −0.0226 (11) 0.0054 (10) C1 0.0124 (7) 0.0145 (8) 0.0130 (8) 0.0003 (6) 0.0007 (6) −0.0011 (6) C2 0.0135 (7) 0.0121 (8) 0.0125 (8) 0.0012 (6) 0.0002 (6) −0.0018 (6) C3 0.0139 (7) 0.0134 (8) 0.0132 (8) −0.0004 (6) −0.0015 (6) −0.0020 (6) C4 0.0120 (7) 0.0132 (8) 0.0131 (8) 0.0007 (6) 0.0014 (6) 0.0019 (6) C5 0.0129 (7) 0.0150 (8) 0.0109 (8) 0.0023 (6) 0.0018 (6) 0.0013 (6) C6 0.0126 (7) 0.0141 (8) 0.0122 (8) 0.0004 (6) 0.0002 (6) 0.0006 (6) C7 0.0135 (8) 0.0169 (8) 0.0113 (8) 0.0004 (6) 0.0013 (6) −0.0024 (6) C8 0.0187 (9) 0.0323 (10) 0.0125 (8) −0.0032 (7) −0.0005 (7) −0.0052 (7) C9 0.0215 (9) 0.0236 (10) 0.0169 (9) 0.0038 (7) 0.0037 (7) −0.0046 (7) C10 0.0271 (9) 0.0213 (9) 0.0154 (9) −0.0026 (7) 0.0060 (7) 0.0006 (7) C11 0.0118 (7) 0.0191 (8) 0.0135 (8) −0.0022 (6) 0.0020 (6) 0.0004 (7) C12 0.0181 (8) 0.0208 (9) 0.0274 (10) −0.0044 (7) 0.0011 (7) 0.0040 (8) C13 0.0136 (8) 0.0375 (11) 0.0171 (9) −0.0064 (7) 0.0040 (7) −0.0040 (8) C14 0.0124 (8) 0.0231 (9) 0.0203 (9) 0.0004 (7) 0.0017 (7) 0.0024 (7) C15 0.0135 (7) 0.0147 (8) 0.0112 (8) 0.0020 (6) 0.0017 (6) 0.0010 (6) C16 0.0144 (7) 0.0121 (8) 0.0100 (8) 0.0020 (6) 0.0001 (6) −0.0003 (6) C17 0.0127 (7) 0.0145 (8) 0.0146 (8) −0.0008 (6) −0.0014 (6) −0.0007 (6) C18 0.0138 (7) 0.0110 (8) 0.0108 (7) 0.0013 (6) 0.0000 (6) 0.0005 (6) C19 0.0139 (7) 0.0149 (8) 0.0138 (8) 0.0007 (6) 0.0033 (6) 0.0002 (6) C20 0.0144 (7) 0.0108 (8) 0.0138 (8) 0.0004 (6) −0.0010 (6) −0.0010 (6) C21 0.0125 (7) 0.0118 (8) 0.0125 (8) 0.0010 (6) 0.0009 (6) 0.0011 (6) C22 0.0150 (8) 0.0135 (8) 0.0145 (8) −0.0008 (6) −0.0003 (6) 0.0001 (6) C23 0.0131 (7) 0.0126 (8) 0.0162 (8) 0.0002 (6) 0.0018 (6) 0.0029 (6) C24 0.0167 (8) 0.0166 (8) 0.0129 (8) 0.0007 (6) 0.0038 (6) −0.0003 (6) C25 0.0160 (8) 0.0149 (8) 0.0118 (8) 0.0017 (6) 0.0005 (6) 0.0001 (6) C26 0.0136 (7) 0.0134 (8) 0.0140 (8) 0.0013 (6) −0.0006 (6) 0.0022 (6) C27 0.0166 (8) 0.0175 (9) 0.0172 (8) −0.0054 (6) 0.0055 (6) −0.0020 (7) C28 0.0358 (12) 0.0261 (11) 0.0527 (14) −0.0109 (9) 0.0218 (10) −0.0110 (10) C29 0.0212 (9) 0.0500 (13) 0.0228 (10) −0.0085 (9) 0.0055 (8) 0.0026 (9) C30 0.0181 (9) 0.0363 (12) 0.0316 (11) −0.0033 (8) −0.0012 (8) 0.0057 (9) C31 0.0181 (8) 0.0221 (9) 0.0125 (8) −0.0027 (7) 0.0018 (6) −0.0027 (7) C32 0.0260 (10) 0.0454 (12) 0.0168 (9) −0.0096 (9) 0.0045 (8) −0.0105 (9) C33 0.0236 (9) 0.0263 (10) 0.0136 (8) −0.0007 (7) −0.0037 (7) 0.0002 (7) C34 0.0257 (9) 0.0225 (9) 0.0196 (9) −0.0002 (7) −0.0022 (7) −0.0049 (7) C35 0.0344 (11) 0.0256 (10) 0.0215 (10) −0.0044 (8) 0.0019 (8) −0.0061 (8) C36 0.0213 (9) 0.0274 (10) 0.0300 (10) −0.0052 (8) 0.0092 (8) −0.0012 (8) C37 0.0312 (11) 0.0192 (10) 0.0345 (11) −0.0027 (8) −0.0034 (9) 0.0023 (8) C38 0.0298 (11) 0.0479 (14) 0.0412 (13) 0.0011 (10) −0.0056 (10) 0.0119 (11) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2883 .table-wrap} --------------------- -------------- ----------------------- -------------- Zn---O1 1.9470 (11) C14---H14C 0.9800 Zn---O2 1.9390 (11) C15---H15 0.9500 Zn---O3 2.0467 (12) C16---C18 1.377 (2) Zn---N1 2.0939 (14) C16---C17 1.439 (2) Zn---N2 2.1001 (13) C18---C19 1.439 (2) S1---O3 1.5155 (12) C20---C21 1.421 (2) S1---C35 1.7803 (19) C20---H20 0.9500 S1---C36 1.7826 (18) C21---C22 1.422 (2) O1---C1 1.2919 (19) C21---C26 1.440 (2) O2---C26 1.2950 (19) C22---C23 1.369 (2) N1---C15 1.317 (2) C22---H22 0.9500 N1---C16 1.386 (2) C23---C24 1.412 (2) N2---C20 1.310 (2) C23---C27 1.535 (2) N2---C18 1.382 (2) C24---C25 1.379 (2) N3---C17 1.146 (2) C24---H24 0.9500 N4---C19 1.147 (2) C25---C26 1.436 (2) N5---C37 1.131 (3) C25---C31 1.538 (2) C1---C6 1.439 (2) C27---C28 1.519 (3) C1---C2 1.446 (2) C27---C29 1.529 (2) C2---C3 1.380 (2) C27---C30 1.546 (3) C2---C7 1.535 (2) C28---H28A 0.9800 C3---C4 1.421 (2) C28---H28B 0.9800 C3---H3 0.9500 C28---H28C 0.9800 C4---C5 1.367 (2) C29---H29A 0.9800 C4---C11 1.533 (2) C29---H29B 0.9800 C5---C6 1.428 (2) C29---H29C 0.9800 C5---H5 0.9500 C30---H30A 0.9800 C6---C15 1.421 (2) C30---H30B 0.9800 C7---C8 1.533 (2) C30---H30C 0.9800 C7---C9 1.536 (2) C31---C32 1.530 (2) C7---C10 1.539 (2) C31---C33 1.535 (2) C8---H8A 0.9800 C31---C34 1.540 (3) C8---H8B 0.9800 C32---H32A 0.9800 C8---H8C 0.9800 C32---H32B 0.9800 C9---H9A 0.9800 C32---H32C 0.9800 C9---H9B 0.9800 C33---H33A 0.9800 C9---H9C 0.9800 C33---H33B 0.9800 C10---H10A 0.9800 C33---H33C 0.9800 C10---H10B 0.9800 C34---H34A 0.9800 C10---H10C 0.9800 C34---H34B 0.9800 C11---C13 1.528 (2) C34---H34C 0.9800 C11---C12 1.540 (2) C35---H35A 0.9800 C11---C14 1.542 (2) C35---H35B 0.9800 C12---H12A 0.9800 C35---H35C 0.9800 C12---H12B 0.9800 C36---H36A 0.9800 C12---H12C 0.9800 C36---H36B 0.9800 C13---H13A 0.9800 C36---H36C 0.9800 C13---H13B 0.9800 C37---C38 1.450 (3) C13---H13C 0.9800 C38---H38A 0.9800 C14---H14A 0.9800 C38---H38B 0.9800 C14---H14B 0.9800 C38---H38C 0.9800 O2---Zn---O1 97.38 (5) N3---C17---C16 176.04 (18) O2---Zn---O3 103.71 (5) C16---C18---N2 117.53 (14) O1---Zn---O3 109.57 (5) C16---C18---C19 121.55 (14) O2---Zn---N1 150.43 (5) N2---C18---C19 120.86 (14) O1---Zn---N1 88.26 (5) N4---C19---C18 174.84 (17) O3---Zn---N1 101.60 (5) N2---C20---C21 124.94 (14) O2---Zn---N2 87.04 (5) N2---C20---H20 117.5 O1---Zn---N2 159.88 (5) C21---C20---H20 117.5 O3---Zn---N2 88.21 (5) C20---C21---C22 116.52 (14) N1---Zn---N2 78.69 (5) C20---C21---C26 123.51 (14) O3---S1---C35 106.31 (8) C22---C21---C26 119.97 (14) O3---S1---C36 106.12 (8) C23---C22---C21 122.24 (15) C35---S1---C36 98.09 (9) C23---C22---H22 118.9 C1---O1---Zn 132.84 (10) C21---C22---H22 118.9 C26---O2---Zn 128.42 (10) C22---C23---C24 116.77 (15) S1---O3---Zn 138.77 (7) C22---C23---C27 121.18 (15) C15---N1---C16 122.47 (14) C24---C23---C27 122.00 (14) C15---N1---Zn 125.65 (11) C25---C24---C23 124.81 (15) C16---N1---Zn 111.62 (10) C25---C24---H24 117.6 C20---N2---C18 122.86 (14) C23---C24---H24 117.6 C20---N2---Zn 123.57 (11) C24---C25---C26 118.56 (15) C18---N2---Zn 111.52 (10) C24---C25---C31 121.73 (14) O1---C1---C6 123.11 (14) C26---C25---C31 119.71 (14) O1---C1---C2 119.20 (14) O2---C26---C25 119.29 (14) C6---C1---C2 117.68 (14) O2---C26---C21 123.08 (14) C3---C2---C1 118.19 (14) C25---C26---C21 117.63 (14) C3---C2---C7 121.84 (14) C28---C27---C29 109.03 (16) C1---C2---C7 119.93 (14) C28---C27---C23 110.91 (15) C2---C3---C4 124.96 (15) C29---C27---C23 112.83 (14) C2---C3---H3 117.5 C28---C27---C30 108.11 (16) C4---C3---H3 117.5 C29---C27---C30 107.01 (15) C5---C4---C3 116.58 (14) C23---C27---C30 108.77 (14) C5---C4---C11 124.38 (14) C27---C28---H28A 109.5 C3---C4---C11 119.00 (14) C27---C28---H28B 109.5 C4---C5---C6 122.44 (15) H28A---C28---H28B 109.5 C4---C5---H5 118.8 C27---C28---H28C 109.5 C6---C5---H5 118.8 H28A---C28---H28C 109.5 C15---C6---C5 116.26 (14) H28B---C28---H28C 109.5 C15---C6---C1 123.81 (14) C27---C29---H29A 109.5 C5---C6---C1 119.87 (14) C27---C29---H29B 109.5 C8---C7---C2 111.26 (13) H29A---C29---H29B 109.5 C8---C7---C9 107.46 (14) C27---C29---H29C 109.5 C2---C7---C9 110.91 (13) H29A---C29---H29C 109.5 C8---C7---C10 107.55 (14) H29B---C29---H29C 109.5 C2---C7---C10 110.07 (13) C27---C30---H30A 109.5 C9---C7---C10 109.50 (14) C27---C30---H30B 109.5 C7---C8---H8A 109.5 H30A---C30---H30B 109.5 C7---C8---H8B 109.5 C27---C30---H30C 109.5 H8A---C8---H8B 109.5 H30A---C30---H30C 109.5 C7---C8---H8C 109.5 H30B---C30---H30C 109.5 H8A---C8---H8C 109.5 C32---C31---C33 107.50 (15) H8B---C8---H8C 109.5 C32---C31---C25 111.81 (14) C7---C9---H9A 109.5 C33---C31---C25 109.75 (14) C7---C9---H9B 109.5 C32---C31---C34 107.25 (15) H9A---C9---H9B 109.5 C33---C31---C34 110.41 (14) C7---C9---H9C 109.5 C25---C31---C34 110.06 (14) H9A---C9---H9C 109.5 C31---C32---H32A 109.5 H9B---C9---H9C 109.5 C31---C32---H32B 109.5 C7---C10---H10A 109.5 H32A---C32---H32B 109.5 C7---C10---H10B 109.5 C31---C32---H32C 109.5 H10A---C10---H10B 109.5 H32A---C32---H32C 109.5 C7---C10---H10C 109.5 H32B---C32---H32C 109.5 H10A---C10---H10C 109.5 C31---C33---H33A 109.5 H10B---C10---H10C 109.5 C31---C33---H33B 109.5 C13---C11---C4 111.82 (13) H33A---C33---H33B 109.5 C13---C11---C12 108.83 (14) C31---C33---H33C 109.5 C4---C11---C12 109.44 (13) H33A---C33---H33C 109.5 C13---C11---C14 107.92 (14) H33B---C33---H33C 109.5 C4---C11---C14 109.64 (13) C31---C34---H34A 109.5 C12---C11---C14 109.13 (14) C31---C34---H34B 109.5 C11---C12---H12A 109.5 H34A---C34---H34B 109.5 C11---C12---H12B 109.5 C31---C34---H34C 109.5 H12A---C12---H12B 109.5 H34A---C34---H34C 109.5 C11---C12---H12C 109.5 H34B---C34---H34C 109.5 H12A---C12---H12C 109.5 S1---C35---H35A 109.5 H12B---C12---H12C 109.5 S1---C35---H35B 109.5 C11---C13---H13A 109.5 H35A---C35---H35B 109.5 C11---C13---H13B 109.5 S1---C35---H35C 109.5 H13A---C13---H13B 109.5 H35A---C35---H35C 109.5 C11---C13---H13C 109.5 H35B---C35---H35C 109.5 H13A---C13---H13C 109.5 S1---C36---H36A 109.5 H13B---C13---H13C 109.5 S1---C36---H36B 109.5 C11---C14---H14A 109.5 H36A---C36---H36B 109.5 C11---C14---H14B 109.5 S1---C36---H36C 109.5 H14A---C14---H14B 109.5 H36A---C36---H36C 109.5 C11---C14---H14C 109.5 H36B---C36---H36C 109.5 H14A---C14---H14C 109.5 N5---C37---C38 179.9 (3) H14B---C14---H14C 109.5 C37---C38---H38A 109.5 N1---C15---C6 125.57 (15) C37---C38---H38B 109.5 N1---C15---H15 117.2 H38A---C38---H38B 109.5 C6---C15---H15 117.2 C37---C38---H38C 109.5 C18---C16---N1 117.67 (14) H38A---C38---H38C 109.5 C18---C16---C17 121.36 (14) H38B---C38---H38C 109.5 N1---C16---C17 120.90 (14) O2---Zn---O1---C1 150.82 (15) C3---C4---C11---C12 −69.76 (19) O3---Zn---O1---C1 −101.74 (15) C5---C4---C11---C14 −127.48 (17) N1---Zn---O1---C1 −0.04 (15) C3---C4---C11---C14 49.91 (19) N2---Zn---O1---C1 49.2 (2) C16---N1---C15---C6 −178.57 (15) O1---Zn---O2---C26 166.41 (14) Zn---N1---C15---C6 7.9 (2) O3---Zn---O2---C26 54.13 (14) C5---C6---C15---N1 177.20 (15) N1---Zn---O2---C26 −94.02 (16) C1---C6---C15---N1 0.0 (3) N2---Zn---O2---C26 −33.31 (14) C15---N1---C16---C18 173.74 (15) C35---S1---O3---Zn −60.18 (14) Zn---N1---C16---C18 −11.89 (17) C36---S1---O3---Zn 43.54 (14) C15---N1---C16---C17 −9.4 (2) O2---Zn---O3---S1 119.64 (12) Zn---N1---C16---C17 164.96 (12) O1---Zn---O3---S1 16.51 (13) C18---C16---C17---N3 142 (2) N1---Zn---O3---S1 −75.78 (12) N1---C16---C17---N3 −34 (3) N2---Zn---O3---S1 −153.85 (12) N1---C16---C18---N2 −1.0 (2) O2---Zn---N1---C15 −108.97 (15) C17---C16---C18---N2 −177.83 (14) O1---Zn---N1---C15 −7.03 (13) N1---C16---C18---C19 176.23 (14) O3---Zn---N1---C15 102.59 (13) C17---C16---C18---C19 −0.6 (2) N2---Zn---N1---C15 −171.63 (14) C20---N2---C18---C16 177.49 (14) O2---Zn---N1---C16 76.88 (14) Zn---N2---C18---C16 13.30 (17) O1---Zn---N1---C16 178.82 (11) C20---N2---C18---C19 0.2 (2) O3---Zn---N1---C16 −71.56 (11) Zn---N2---C18---C19 −163.95 (12) N2---Zn---N1---C16 14.22 (10) C16---C18---C19---N4 −144 (2) O2---Zn---N2---C20 27.25 (13) N2---C18---C19---N4 33 (2) O1---Zn---N2---C20 130.72 (15) C18---N2---C20---C21 −178.19 (15) O3---Zn---N2---C20 −76.57 (13) Zn---N2---C20---C21 −15.9 (2) N1---Zn---N2---C20 −178.78 (13) N2---C20---C21---C22 177.32 (15) O2---Zn---N2---C18 −168.69 (11) N2---C20---C21---C26 −2.7 (3) O1---Zn---N2---C18 −65.23 (19) C20---C21---C22---C23 −178.94 (15) O3---Zn---N2---C18 87.48 (11) C26---C21---C22---C23 1.0 (2) N1---Zn---N2---C18 −14.73 (10) C21---C22---C23---C24 −0.9 (2) Zn---O1---C1---C6 6.6 (2) C21---C22---C23---C27 176.69 (15) Zn---O1---C1---C2 −173.09 (11) C22---C23---C24---C25 0.5 (2) O1---C1---C2---C3 −174.06 (15) C27---C23---C24---C25 −176.99 (16) C6---C1---C2---C3 6.2 (2) C23---C24---C25---C26 −0.4 (3) O1---C1---C2---C7 8.2 (2) C23---C24---C25---C31 179.57 (15) C6---C1---C2---C7 −171.50 (14) Zn---O2---C26---C25 −153.79 (12) C1---C2---C3---C4 −3.7 (2) Zn---O2---C26---C21 26.7 (2) C7---C2---C3---C4 173.99 (15) C24---C25---C26---O2 −179.06 (15) C2---C3---C4---C5 −0.4 (2) C31---C25---C26---O2 1.0 (2) C2---C3---C4---C11 −177.95 (15) C24---C25---C26---C21 0.5 (2) C3---C4---C5---C6 1.7 (2) C31---C25---C26---C21 −179.45 (14) C11---C4---C5---C6 179.12 (15) C20---C21---C26---O2 −1.3 (2) C4---C5---C6---C15 −176.22 (15) C22---C21---C26---O2 178.71 (15) C4---C5---C6---C1 1.1 (2) C20---C21---C26---C25 179.17 (15) O1---C1---C6---C15 −7.7 (3) C22---C21---C26---C25 −0.8 (2) C2---C1---C6---C15 172.05 (15) C22---C23---C27---C28 50.7 (2) O1---C1---C6---C5 175.20 (15) C24---C23---C27---C28 −131.85 (18) C2---C1---C6---C5 −5.1 (2) C22---C23---C27---C29 173.39 (16) C3---C2---C7---C8 −2.6 (2) C24---C23---C27---C29 −9.2 (2) C1---C2---C7---C8 175.02 (15) C22---C23---C27---C30 −68.0 (2) C3---C2---C7---C9 116.96 (17) C24---C23---C27---C30 109.38 (18) C1---C2---C7---C9 −65.43 (19) C24---C25---C31---C32 −1.6 (2) C3---C2---C7---C10 −121.71 (17) C26---C25---C31---C32 178.31 (16) C1---C2---C7---C10 55.90 (19) C24---C25---C31---C33 117.58 (17) C5---C4---C11---C13 −7.8 (2) C26---C25---C31---C33 −62.5 (2) C3---C4---C11---C13 169.57 (15) C24---C25---C31---C34 −120.71 (17) C5---C4---C11---C12 112.85 (18) C26---C25---C31---C34 59.2 (2) --------------------- -------------- ----------------------- -------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: --------- ------------- Zn---O1 1.9470 (11) Zn---O2 1.9390 (11) Zn---O3 2.0467 (12) Zn---N1 2.0939 (14) Zn---N2 2.1001 (13) --------- ------------- ::: [^1]: ‡ Additional correspondence author, e-mail: wayfield8@yahoo.com.

PubMed Central

2024-06-05T04:04:18.565285

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052118/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m314-m315", "authors": [ { "first": "E. S.", "last": "Aazam" }, { "first": "Seik Weng", "last": "Ng" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }

PMC3052119

In the paper by Castillo, Luque, De la Pinta & Román (2001[@bb1]), the ligand reported as nitrate should be carbonate and the oxidation state of the cobalt metal atom should be Co^III^ rather than Co^II^, thus making the correct chemical composition \[Co(CO~3~)(C~10~H~9~N~3~)~2~\]NO~3~ and the correct chemical name '\[Bis(2-pyridyl)amine-κ^2^ *N*,*N*′\](carbonato-κ^2^ *O*,*O*′)cobalt(III) nitrate'. Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co(CO~3~)(C~10~H~9~N~3~)~2~\]NO~3~*M* *~r~* = 523.35Monoclinic,*a* = 17.191 (3) Å*b* = 7.3080 (10) Å*c* = 17.843 (5) Åβ = 104.94 (3)°*V* = 2165.9 (8) Å^3^*Z* = 4Mo *K*α radiationμ = 0.85 mm^−1^*T* = 293 K0.42 × 0.20 × 0.08 mm ### Data collection {#sec2.1.2} Stoe IPDS diffractometerAbsorption correction: numerical (Stoe & Cie, 1998[@bb4]) *T* ~min~ = 0.815, *T* ~max~ = 0.93414084 measured reflections4037 independent reflections2598 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.048 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.031*wR*(*F* ^2^) = 0.076*S* = 0.824037 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.31 e Å^−3^ {#d5e405} Data collection, cell refinement and data reduction: *IPDS Software* (Stoe & Cie, 1998[@bb4]); program(s) used to solve structure: *SIR92* (Altomare *et al.*, 1993[@bb2]); program(s) used to refine structure: *SHELXL93* (Sheldrick, 1993[@bb3]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536810050798/bt9068sup1.cif](http://dx.doi.org/10.1107/S1600536810050798/bt9068sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536810050798/bt9068Isup2.hkl](http://dx.doi.org/10.1107/S1600536810050798/bt9068Isup2.hkl) . DOI: [10.1107/S1600536810050798/bt9068fig1.tif](http://dx.doi.org/10.1107/S1600536810050798/bt9068fig1.tif) ? Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt9068&file=bt9068sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt9068sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt9068&checkcif=yes)

PubMed Central

2024-06-05T04:04:18.577654

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052119/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):e15", "authors": [ { "first": "Oscar", "last": "Castillo" }, { "first": "Antonio", "last": "Luque" }, { "first": "Noelia", "last": "De la Pinta" }, { "first": "Pascual", "last": "Román" } ] }

PMC3052120

Related literature {#sec1} ================== For our previous reports of the pharmacological properties of benzofurans, see: Abdel-Aziz & Mekawey (2009[@bb1]); Abdel-Aziz *et al.* (2009[@bb2]). For a related structure, see: Kossakowski *et al.* (2005[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~11~H~9~BrO~3~*M* *~r~* = 269.09Monoclinic,*a* = 3.8869 (3) Å*b* = 23.780 (2) Å*c* = 11.0820 (7) Åβ = 96.905 (8)°*V* = 1016.89 (13) Å^3^*Z* = 4Mo *K*α radiationμ = 4.02 mm^−1^*T* = 100 K0.30 × 0.20 × 0.10 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb3]) *T* ~min~ = 0.378, *T* ~max~ = 0.6896060 measured reflections2250 independent reflections1843 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.045 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.055*wR*(*F* ^2^) = 0.109*S* = 1.182250 reflections136 parametersH-atom parameters constrainedΔρ~max~ = 0.97 e Å^−3^Δρ~min~ = −0.71 e Å^−3^ {#d5e418} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb3]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *X-SEED* (Barbour, 2001[@bb4]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb7]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005897/xu5164sup1.cif](http://dx.doi.org/10.1107/S1600536811005897/xu5164sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005897/xu5164Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005897/xu5164Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5164&file=xu5164sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5164sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5164&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5164](http://scripts.iucr.org/cgi-bin/sendsup?xu5164)). We thank King Saud University and the University of Malaya for supporting this study. Comment ======= Ethyl 5-bromobenzofuran-2-carboxylate (Scheme I) is a commercially available chemical that has been evaluated for its pharmacological properties. We have reported the pharmacological properties of related compounds (Abdel-Aziz & Mekawey, 2009; Abdel-Aziz *et al.*, 2009). The title compound is an approximately planar molecule; the carboxyl --CO~2~ fragment is aligned at 4.8 (7)° with respect to the benzofuran fused-ring (Fig. 1). Bond dimensions are similar to those found in methyl 7-methoxybenzofuran-2-carboxylate (Kossakowski *et al.*, 2005). Experimental {#experimental} ============ 5-Bromosalicyladehyde (2.01 g, 10 mm l), diethyl bromomalonate (2.63 g 11 mmol) and potassium carbonate (2.28 g, 20 mmol) were heated in 2-butanone (20 ml) for 14 h. The solvent was evaporated and water was added to the residue. The organic compound was extracted by ether. The ether phase was washed with 5% sodium hydroxide. The ether was then evaporated and the product recrystallized from ethanol to give the title ester, m.p. 333--335 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.98 Å, *U*~iso~(H) 1.2 to 1.5*U*~eq~(C)\] and were included in the refinement in the riding model approximation. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C11H9BrO3 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o696-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e116 .table-wrap} ------------------------- --------------------------------------- C~11~H~9~BrO~3~ *F*(000) = 536 *M~r~* = 269.09 *D*~x~ = 1.758 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2599 reflections *a* = 3.8869 (3) Å θ = 2.5--29.3° *b* = 23.780 (2) Å µ = 4.02 mm^−1^ *c* = 11.0820 (7) Å *T* = 100 K β = 96.905 (8)° Prism, colorless *V* = 1016.89 (13) Å^3^ 0.30 × 0.20 × 0.10 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e243 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 2250 independent reflections Radiation source: SuperNova (Mo) X-ray Source 1843 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.045 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.5° ω scans *h* = −3→5 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −30→30 *T*~min~ = 0.378, *T*~max~ = 0.689 *l* = −13→14 6060 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e363 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.055 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.109 H-atom parameters constrained *S* = 1.18 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0086*P*)^2^ + 5.1797*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2250 reflections (Δ/σ)~max~ = 0.001 136 parameters Δρ~max~ = 0.97 e Å^−3^ 0 restraints Δρ~min~ = −0.71 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e522 .table-wrap} ------ -------------- -------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.84947 (14) 0.52531 (2) 0.18162 (5) 0.02119 (16) O1 0.2581 (9) 0.32380 (14) 0.4040 (3) 0.0157 (7) O2 0.0007 (10) 0.25870 (14) 0.5783 (3) 0.0228 (9) O3 0.1752 (9) 0.32488 (14) 0.7194 (3) 0.0165 (8) C1 0.3994 (13) 0.3662 (2) 0.3427 (4) 0.0146 (10) C2 0.4194 (14) 0.3670 (2) 0.2183 (4) 0.0189 (11) H2 0.3416 0.3363 0.1672 0.023\* C3 0.5588 (15) 0.4150 (2) 0.1733 (4) 0.0216 (12) H3 0.5746 0.4181 0.0886 0.026\* C4 0.6767 (13) 0.4590 (2) 0.2510 (4) 0.0163 (11) C5 0.6666 (13) 0.4576 (2) 0.3740 (4) 0.0151 (10) H5 0.7541 0.4878 0.4248 0.018\* C6 0.5205 (12) 0.4095 (2) 0.4220 (4) 0.0135 (10) C7 0.4517 (13) 0.3916 (2) 0.5397 (4) 0.0153 (10) H7 0.5060 0.4113 0.6141 0.018\* C8 0.2932 (14) 0.3408 (2) 0.5243 (4) 0.0161 (11) C9 0.1403 (13) 0.3029 (2) 0.6073 (4) 0.0157 (10) C10 0.0273 (14) 0.2924 (2) 0.8131 (4) 0.0202 (11) H10A 0.1957 0.2639 0.8488 0.024\* H10B −0.1857 0.2728 0.7775 0.024\* C11 −0.0555 (14) 0.3333 (2) 0.9091 (4) 0.0202 (11) H11A −0.1540 0.3130 0.9738 0.030\* H11B −0.2234 0.3611 0.8728 0.030\* H11C 0.1571 0.3526 0.9433 0.030\* ------ -------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e856 .table-wrap} ----- ------------ ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0225 (3) 0.0210 (3) 0.0205 (3) −0.0006 (2) 0.0046 (2) 0.0051 (2) O1 0.020 (2) 0.0151 (17) 0.0107 (15) −0.0015 (15) −0.0019 (14) −0.0010 (14) O2 0.032 (2) 0.0169 (19) 0.0191 (18) −0.0038 (17) 0.0022 (17) −0.0014 (15) O3 0.019 (2) 0.0196 (18) 0.0108 (15) −0.0032 (15) 0.0007 (14) 0.0015 (14) C1 0.015 (3) 0.016 (2) 0.013 (2) 0.003 (2) −0.0009 (19) 0.0018 (19) C2 0.021 (3) 0.022 (3) 0.013 (2) 0.002 (2) −0.001 (2) −0.002 (2) C3 0.032 (3) 0.021 (3) 0.013 (2) 0.004 (2) 0.006 (2) 0.002 (2) C4 0.013 (3) 0.018 (2) 0.019 (2) 0.002 (2) 0.005 (2) 0.007 (2) C5 0.013 (3) 0.014 (2) 0.018 (2) 0.000 (2) 0.001 (2) −0.003 (2) C6 0.008 (2) 0.018 (2) 0.012 (2) 0.001 (2) −0.0063 (19) −0.0007 (19) C7 0.016 (3) 0.016 (2) 0.013 (2) 0.004 (2) −0.001 (2) −0.0006 (19) C8 0.021 (3) 0.016 (2) 0.010 (2) 0.007 (2) 0.000 (2) 0.0000 (19) C9 0.014 (3) 0.019 (3) 0.013 (2) 0.005 (2) −0.003 (2) 0.001 (2) C10 0.023 (3) 0.022 (3) 0.016 (2) −0.003 (2) 0.004 (2) 0.006 (2) C11 0.020 (3) 0.027 (3) 0.014 (2) −0.007 (2) 0.001 (2) 0.003 (2) ----- ------------ ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1162 .table-wrap} -------------------- ------------ --------------------- ------------ Br1---C4 1.912 (5) C5---C6 1.410 (7) O1---C1 1.367 (6) C5---H5 0.9500 O1---C8 1.384 (5) C6---C7 1.428 (6) O2---C9 1.208 (6) C7---C8 1.357 (7) O3---C9 1.340 (5) C7---H7 0.9500 O3---C10 1.465 (6) C8---C9 1.464 (7) C1---C2 1.390 (6) C10---C11 1.505 (7) C1---C6 1.398 (7) C10---H10A 0.9900 C2---C3 1.382 (7) C10---H10B 0.9900 C2---H2 0.9500 C11---H11A 0.9800 C3---C4 1.397 (7) C11---H11B 0.9800 C3---H3 0.9500 C11---H11C 0.9800 C4---C5 1.369 (6) C1---O1---C8 105.3 (4) C8---C7---H7 126.8 C9---O3---C10 116.5 (4) C6---C7---H7 126.8 O1---C1---C2 125.2 (4) C7---C8---O1 111.9 (4) O1---C1---C6 110.8 (4) C7---C8---C9 133.0 (4) C2---C1---C6 124.0 (5) O1---C8---C9 115.1 (4) C3---C2---C1 116.1 (5) O2---C9---O3 125.3 (5) C3---C2---H2 121.9 O2---C9---C8 124.9 (4) C1---C2---H2 121.9 O3---C9---C8 109.8 (4) C2---C3---C4 120.6 (4) O3---C10---C11 107.2 (4) C2---C3---H3 119.7 O3---C10---H10A 110.3 C4---C3---H3 119.7 C11---C10---H10A 110.3 C5---C4---C3 123.4 (5) O3---C10---H10B 110.3 C5---C4---Br1 118.2 (4) C11---C10---H10B 110.3 C3---C4---Br1 118.4 (4) H10A---C10---H10B 108.5 C4---C5---C6 117.1 (4) C10---C11---H11A 109.5 C4---C5---H5 121.5 C10---C11---H11B 109.5 C6---C5---H5 121.5 H11A---C11---H11B 109.5 C1---C6---C5 118.8 (4) C10---C11---H11C 109.5 C1---C6---C7 105.6 (4) H11A---C11---H11C 109.5 C5---C6---C7 135.6 (5) H11B---C11---H11C 109.5 C8---C7---C6 106.4 (4) C8---O1---C1---C2 −179.8 (5) C4---C5---C6---C7 −178.1 (5) C8---O1---C1---C6 −0.3 (5) C1---C6---C7---C8 −1.0 (6) O1---C1---C2---C3 177.3 (5) C5---C6---C7---C8 177.8 (6) C6---C1---C2---C3 −2.1 (8) C6---C7---C8---O1 0.9 (6) C1---C2---C3---C4 1.2 (8) C6---C7---C8---C9 −175.5 (5) C2---C3---C4---C5 0.7 (8) C1---O1---C8---C7 −0.4 (6) C2---C3---C4---Br1 −177.6 (4) C1---O1---C8---C9 176.7 (4) C3---C4---C5---C6 −1.6 (7) C10---O3---C9---O2 −0.7 (7) Br1---C4---C5---C6 176.6 (4) C10---O3---C9---C8 178.6 (4) O1---C1---C6---C5 −178.3 (4) C7---C8---C9---O2 178.6 (6) C2---C1---C6---C5 1.2 (8) O1---C8---C9---O2 2.3 (7) O1---C1---C6---C7 0.8 (5) C7---C8---C9---O3 −0.7 (8) C2---C1---C6---C7 −179.7 (5) O1---C8---C9---O3 −177.1 (4) C4---C5---C6---C1 0.7 (7) C9---O3---C10---C11 −154.2 (4) -------------------- ------------ --------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1651 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C2---H2···O2^i^ 0.95 2.57 3.400 (6) 146 C11---H11A···O2^ii^ 0.98 2.53 3.472 (6) 160 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*+1/2, −*y*+1/2, *z*−1/2; (ii) *x*−1/2, −*y*+1/2, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- C2---H2⋯O2^i^ 0.95 2.57 3.400 (6) 146 C11---H11*A*⋯O2^ii^ 0.98 2.53 3.472 (6) 160 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.578028

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052120/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o696", "authors": [ { "first": "Hatem A.", "last": "Abdel-Aziz" }, { "first": "Ahmed", "last": "Bari" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052121

Related literature {#sec1} ================== For the structure of 9-aminoacridine hydrochloride monohydrate, see: Talacki *et al.* (1974[@bb8]). For positive-charge-assisted hydrogen bonds, see: Gilli *et al.* (1994[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~11~N~2~ ^+^·NO~3~ ^−^·H~2~O*M* *~r~* = 275.26Triclinic,*a* = 6.8556 (2) Å*b* = 10.0532 (2) Å*c* = 10.5912 (3) Åα = 117.016 (1)°β = 94.138 (1)°γ = 97.995 (1)°*V* = 636.36 (3) Å^3^*Z* = 2Mo *K*α radiationμ = 0.11 mm^−1^*T* = 293 K0.75 × 0.75 × 0.45 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (Blessing, 1995[@bb9]) *T* ~min~ = 0.923, *T* ~max~ = 0.9538945 measured reflections2822 independent reflections2054 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.028 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.045*wR*(*F* ^2^) = 0.132*S* = 1.042822 reflections201 parameters5 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.26 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e541} Data collection: *COLLECT* (Nonius, 2001[@bb5]); cell refinement: *SCALEPACK* (Otwinowski & Minor, 1997[@bb6]); data reduction: *DENZO* (Otwinowski & Minor, 1997[@bb6]) and *SCALEPACK*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *Mercury* (Macrae *et al.*, 2006[@bb4]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb2]) and *enCIFer* (Allen *et al.*, 2004[@bb1]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003953/ng5102sup1.cif](http://dx.doi.org/10.1107/S1600536811003953/ng5102sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003953/ng5102Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003953/ng5102Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5102&file=ng5102sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5102sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5102&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5102](http://scripts.iucr.org/cgi-bin/sendsup?ng5102)). Support of this investigation by Ferdowsi University of Mashhad and the Islamic Azad University Shahr-e-Rey Branch is gratefully acknowledged. Comment ======= In a previous work, the crystal structure of 9-aminoacridine hydrochloride monohydrate (Talacki *et al.*, 1974) has been investigated. Here, we report on the crystal structure of title hydrated salt, C~13~H~11~N~2~^+^.NO~3~^-^.H~2~O (Fig. 1). In 9-amino-acridinium cation, the heteroatom N1 and the nitrogen atom of NH~2~ unit (N2) have a *sp*^2^ character. The C1---N1---C13 angle is 122.68 (11)°; the fused tricyclic system is essentially planar. The protonated pyridine nitrogen atom is involving in a positive charge assisted (Gilli *et al.*, 1994) N---H···O hydrogen bond with a neighboring H~2~O molecule (N1···O4 = 2.7867 (15) Å). Moreover, the water molecule forms two O---H···O hydrogen bonds (O···O = 2.9058 (18) & 2.9147 (18) Å) with two adjacent NO~3~^-^ anions; also, the weak hydrogen bond O4---H4B···O2 (O4···O2 = 3.2039 (19) Å) may be considered which has not influence on the pattern of crystal packing. The NH~2~ unit of cation cooperates in three N---H···O hydrogen bonds (N···O = 2.9123 (15), 3.0619 (17) and 3.0662 (16) Å), with two neighboring nitrate anions. Cations, anions and water molecules are hydrogen bonded in a 2-D arrangement (Fig. 2). Experimental {#experimental} ============ The title hydrated salt was obtained fortuitously from the reaction between 9-aminoacridine and Fe(NO~3~)~3~.9H~2~O in CH~3~OH as follows: To a solution of 9-aminoacridine (0.194 g, 1 mmol) in CH~3~OH (5 ml), a solution of Fe(NO~3~)~3~.9H~2~O (0.202 g, 0.5 mmol) in CH~3~OH (5 ml) was added at 343 K. After 1 h stirring, the solid was filtered; the crystals were obtained from methanolic solution after a slow evaporation at room temperature. Refinement {#refinement} ========== The hydrogen atom of NH group and those of water molecule were found in difference Fourier synthesis.The NH H atoms were restrained to 0.90 A and the refinement give good values. The H atoms in the water molecule were refined with a restraint of 1.00 A for a ideal distance OH and obtained acceptable values. The H(C) atom positions were calculated. All hydrogen atoms were refined in isotropic approximation in riding model with the *U*~iso~(H) parameters equal to 1.2 *U*~eq~(Ci), for methyl groups equal to 1.5 *U*~eq~(Cii), where U(Ci) and U(Cii) are respectively the equivalent thermal parameters of the carbon atoms to which corresponding H atoms are bonded. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular view with the atom labeling scheme, displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. ::: ![](e-67-0o565-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Partial packing of cations, anions and water molecules in the title hydrated salt. H bonds are shown as dashed lines. ::: ![](e-67-0o565-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e187 .table-wrap} ---------------------------------- -------------------------------------- C~13~H~11~N~2~^+^·NO~3~^−^·H~2~O *Z* = 2 *M~r~* = 275.26 *F*(000) = 288 Triclinic, *P*1 *D*~x~ = 1.437 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 6.8556 (2) Å Cell parameters from 600 reflections *b* = 10.0532 (2) Å θ = 1--14° *c* = 10.5912 (3) Å µ = 0.11 mm^−1^ α = 117.016 (1)° *T* = 293 K β = 94.138 (1)° Block, colourless γ = 97.995 (1)° 0.75 × 0.75 × 0.45 mm *V* = 636.36 (3) Å^3^ ---------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e333 .table-wrap} ---------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 2822 independent reflections Radiation source: fine-focus sealed tube 2054 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.028 CCD rotation images, thick slices scans θ~max~ = 27.6°, θ~min~ = 3.0° Absorption correction: multi-scan (Blessing, 1995) *h* = −8→8 *T*~min~ = 0.923, *T*~max~ = 0.953 *k* = −12→13 8945 measured reflections *l* = −13→13 ---------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e442 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.132 H atoms treated by a mixture of independent and constrained refinement *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0799*P*)^2^ + 0.0299*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2822 reflections (Δ/σ)~max~ \< 0.001 201 parameters Δρ~max~ = 0.26 e Å^−3^ 5 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e599 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e698 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.28645 (17) 0.69390 (14) 0.48088 (14) 0.0392 (3) C2 0.3072 (2) 0.82982 (15) 0.46976 (16) 0.0491 (3) H2 0.3418 0.9237 0.5518 0.059\* C3 0.2764 (2) 0.82263 (16) 0.33871 (17) 0.0548 (4) H3 0.2900 0.9123 0.3317 0.066\* C4 0.2245 (2) 0.68227 (17) 0.21357 (17) 0.0545 (4) H4 0.2054 0.6794 0.1245 0.065\* C5 0.20191 (19) 0.54989 (15) 0.22257 (14) 0.0456 (3) H5 0.1663 0.4572 0.1393 0.055\* C6 0.23215 (17) 0.55232 (13) 0.35736 (13) 0.0377 (3) C7 0.20689 (17) 0.41608 (13) 0.37264 (13) 0.0368 (3) C8 0.23830 (16) 0.43023 (13) 0.51410 (13) 0.0369 (3) C9 0.21635 (19) 0.30332 (15) 0.54077 (15) 0.0438 (3) H9 0.1779 0.2057 0.4642 0.053\* C10 0.2506 (2) 0.32195 (17) 0.67683 (16) 0.0513 (4) H10 0.2353 0.2375 0.6924 0.062\* C11 0.3088 (2) 0.46790 (18) 0.79260 (16) 0.0554 (4) H11 0.3326 0.4797 0.8850 0.066\* C12 0.3312 (2) 0.59339 (17) 0.77252 (14) 0.0512 (4) H12 0.3695 0.6900 0.8507 0.061\* C13 0.29601 (17) 0.57631 (14) 0.63302 (13) 0.0393 (3) N1 0.31813 (16) 0.70224 (12) 0.61313 (12) 0.0437 (3) N2 0.15562 (19) 0.28113 (13) 0.25875 (12) 0.0507 (3) N3 0.0612 (2) 1.10579 (12) 0.88933 (12) 0.0521 (3) O1 0.22383 (17) 1.19337 (12) 0.95048 (12) 0.0721 (4) O2 0.04483 (18) 1.00530 (11) 0.76309 (11) 0.0674 (3) O3 −0.08334 (18) 1.12104 (15) 0.95548 (12) 0.0739 (4) O4 0.4979 (2) 0.98619 (13) 0.83821 (14) 0.0775 (4) H1 0.361 (2) 0.7928 (17) 0.6889 (16) 0.062 (5)\* H2A 0.133 (2) 0.2695 (19) 0.1668 (16) 0.061 (4)\* H2B 0.126 (2) 0.1971 (17) 0.2686 (18) 0.067 (5)\* H4A 0.626 (2) 1.017 (2) 0.883 (2) 0.094 (7)\* H4B 0.422 (3) 1.057 (2) 0.875 (2) 0.098 (7)\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1135 .table-wrap} ----- ------------ ------------- ------------- ------------- ------------- ------------ *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0320 (6) 0.0385 (6) 0.0459 (7) 0.0080 (5) 0.0077 (5) 0.0183 (6) C2 0.0462 (7) 0.0360 (6) 0.0613 (9) 0.0068 (5) 0.0078 (6) 0.0200 (6) C3 0.0529 (8) 0.0489 (8) 0.0750 (10) 0.0128 (6) 0.0108 (7) 0.0386 (8) C4 0.0580 (8) 0.0612 (9) 0.0577 (9) 0.0190 (7) 0.0121 (6) 0.0369 (8) C5 0.0480 (7) 0.0453 (7) 0.0441 (7) 0.0138 (6) 0.0073 (5) 0.0202 (6) C6 0.0321 (6) 0.0383 (6) 0.0432 (7) 0.0097 (5) 0.0083 (5) 0.0183 (6) C7 0.0315 (6) 0.0356 (6) 0.0398 (7) 0.0079 (5) 0.0061 (5) 0.0142 (5) C8 0.0288 (6) 0.0407 (7) 0.0418 (7) 0.0092 (5) 0.0076 (5) 0.0189 (6) C9 0.0407 (7) 0.0435 (7) 0.0495 (7) 0.0097 (5) 0.0093 (5) 0.0229 (6) C10 0.0475 (7) 0.0610 (9) 0.0605 (9) 0.0167 (6) 0.0154 (6) 0.0387 (8) C11 0.0543 (8) 0.0750 (10) 0.0448 (8) 0.0185 (7) 0.0128 (6) 0.0325 (8) C12 0.0494 (8) 0.0565 (8) 0.0390 (7) 0.0103 (6) 0.0078 (6) 0.0148 (6) C13 0.0326 (6) 0.0428 (7) 0.0399 (7) 0.0084 (5) 0.0077 (5) 0.0166 (6) N1 0.0450 (6) 0.0353 (6) 0.0412 (6) 0.0056 (5) 0.0052 (5) 0.0107 (5) N2 0.0694 (8) 0.0356 (6) 0.0397 (6) 0.0073 (5) 0.0013 (5) 0.0133 (5) N3 0.0707 (8) 0.0388 (6) 0.0428 (6) 0.0083 (6) −0.0041 (6) 0.0182 (5) O1 0.0757 (8) 0.0523 (6) 0.0587 (7) −0.0043 (6) −0.0034 (6) 0.0076 (5) O2 0.0965 (8) 0.0445 (6) 0.0431 (6) 0.0017 (5) −0.0006 (5) 0.0100 (5) O3 0.0681 (7) 0.0950 (9) 0.0604 (7) 0.0244 (6) 0.0096 (6) 0.0358 (7) O4 0.0701 (8) 0.0541 (7) 0.0758 (8) 0.0067 (6) −0.0002 (6) 0.0060 (6) ----- ------------ ------------- ------------- ------------- ------------- ------------ ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1491 .table-wrap} -------------------- -------------- ----------------------- -------------- C1---N1 1.3641 (18) C9---H9 0.9300 C1---C6 1.4024 (18) C10---C11 1.396 (2) C1---C2 1.4127 (18) C10---H10 0.9300 C2---C3 1.356 (2) C11---C12 1.362 (2) C2---H2 0.9300 C11---H11 0.9300 C3---C4 1.403 (2) C12---C13 1.4061 (19) C3---H3 0.9300 C12---H12 0.9300 C4---C5 1.3654 (19) C13---N1 1.3650 (17) C4---H4 0.9300 N1---H1 0.887 (14) C5---C6 1.4163 (18) N2---H2A 0.925 (14) C5---H5 0.9300 N2---H2B 0.895 (14) C6---C7 1.4393 (17) N3---O2 1.2411 (15) C7---N2 1.3186 (16) N3---O1 1.2417 (16) C7---C8 1.4361 (17) N3---O3 1.2417 (17) C8---C13 1.4091 (18) O4---H4A 0.909 (16) C8---C9 1.4178 (17) O4---H4B 0.901 (16) C9---C10 1.364 (2) N1---C1---C6 120.53 (11) C10---C9---H9 119.4 N1---C1---C2 119.19 (12) C8---C9---H9 119.4 C6---C1---C2 120.28 (12) C9---C10---C11 119.94 (13) C3---C2---C1 119.60 (13) C9---C10---H10 120.0 C3---C2---H2 120.2 C11---C10---H10 120.0 C1---C2---H2 120.2 C12---C11---C10 121.11 (13) C2---C3---C4 121.12 (13) C12---C11---H11 119.4 C2---C3---H3 119.4 C10---C11---H11 119.4 C4---C3---H3 119.4 C11---C12---C13 119.71 (13) C5---C4---C3 120.01 (13) C11---C12---H12 120.1 C5---C4---H4 120.0 C13---C12---H12 120.1 C3---C4---H4 120.0 N1---C13---C12 119.63 (12) C4---C5---C6 120.69 (13) N1---C13---C8 120.00 (11) C4---C5---H5 119.7 C12---C13---C8 120.37 (12) C6---C5---H5 119.7 C1---N1---C13 122.68 (11) C1---C6---C5 118.30 (11) C1---N1---H1 118.7 (11) C1---C6---C7 118.91 (11) C13---N1---H1 118.6 (11) C5---C6---C7 122.78 (11) C7---N2---H2A 122.2 (10) N2---C7---C8 120.83 (11) C7---N2---H2B 120.4 (11) N2---C7---C6 120.48 (11) H2A---N2---H2B 116.9 (16) C8---C7---C6 118.70 (11) O2---N3---O1 119.79 (14) C13---C8---C9 117.72 (11) O2---N3---O3 120.94 (13) C13---C8---C7 119.16 (11) O1---N3---O3 119.27 (12) C9---C8---C7 123.11 (11) H4A---O4---H4B 114 (2) C10---C9---C8 121.15 (13) N1---C1---C2---C3 179.86 (12) N2---C7---C8---C9 −0.21 (19) C6---C1---C2---C3 −0.71 (19) C6---C7---C8---C9 179.70 (10) C1---C2---C3---C4 −0.1 (2) C13---C8---C9---C10 −0.24 (18) C2---C3---C4---C5 0.7 (2) C7---C8---C9---C10 179.00 (11) C3---C4---C5---C6 −0.6 (2) C8---C9---C10---C11 −0.1 (2) N1---C1---C6---C5 −179.71 (11) C9---C10---C11---C12 0.4 (2) C2---C1---C6---C5 0.87 (17) C10---C11---C12---C13 −0.2 (2) N1---C1---C6---C7 1.12 (17) C11---C12---C13---N1 179.87 (12) C2---C1---C6---C7 −178.31 (10) C11---C12---C13---C8 −0.1 (2) C4---C5---C6---C1 −0.23 (19) C9---C8---C13---N1 −179.64 (10) C4---C5---C6---C7 178.91 (11) C7---C8---C13---N1 1.09 (17) C1---C6---C7---N2 179.90 (11) C9---C8---C13---C12 0.38 (17) C5---C6---C7---N2 0.77 (19) C7---C8---C13---C12 −178.89 (11) C1---C6---C7---C8 −0.01 (16) C6---C1---N1---C13 −1.16 (18) C5---C6---C7---C8 −179.14 (11) C2---C1---N1---C13 178.27 (10) N2---C7---C8---C13 179.02 (11) C12---C13---N1---C1 −179.99 (11) C6---C7---C8---C13 −1.08 (16) C8---C13---N1---C1 0.03 (18) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2085 .table-wrap} -------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N2---H2A···O1^i^ 0.93 (1) 2.23 (2) 3.0619 (17) 149.(1) N2---H2A···O3^i^ 0.93 (1) 2.30 (2) 3.0662 (16) 140.(1) N2---H2B···O2^ii^ 0.90 (1) 2.07 (1) 2.9123 (15) 157.(2) O4---H4A···O3^iii^ 0.91 (2) 2.03 (2) 2.9147 (18) 164.(2) N1---H1···O4 0.89 (1) 1.91 (1) 2.7867 (15) 170.(2) O4---H4B···O1 0.90 (2) 2.01 (2) 2.9058 (18) 173 (2) O4---H4B···O2 0.90 (2) 2.64 (2) 3.2039 (19) 122.(2) -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) *x*, *y*−1, *z*−1; (ii) −*x*, −*y*+1, −*z*+1; (iii) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- ---------- ---------- ------------- ------------- N2---H2*A*⋯O1^i^ 0.93 (1) 2.23 (2) 3.0619 (17) 149 (1) N2---H2*A*⋯O3^i^ 0.93 (1) 2.30 (2) 3.0662 (16) 140 (1) N2---H2*B*⋯O2^ii^ 0.90 (1) 2.07 (1) 2.9123 (15) 157 (2) O4---H4*A*⋯O3^iii^ 0.91 (2) 2.03 (2) 2.9147 (18) 164 (2) N1---H1⋯O4 0.89 (1) 1.91 (1) 2.7867 (15) 170 (2) O4---H4*B*⋯O1 0.90 (2) 2.01 (2) 2.9058 (18) 173 (2) O4---H4*B*⋯O2 0.90 (2) 2.64 (2) 3.2039 (19) 122 (2) Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.582755

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052121/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o565", "authors": [ { "first": "Mehrdad", "last": "Pourayoubi" }, { "first": "Hossein", "last": "Eshtiagh-Hosseini" }, { "first": "Somayyeh", "last": "Sanaei Ataabadi" }, { "first": "Teresa", "last": "Mancilla Percino" }, { "first": "Marco", "last": "A. Leyva Ramírez" } ] }

PMC3052122

Related literature {#sec1} ================== For the biological activity of pyrazole oxime ether derivatives, see: Drabek (1992[@bb3]); Motoba *et al.* (2000[@bb6]); Park *et al.* (2005[@bb7]); Watanabe *et al.* (2001[@bb10]). For the bioactivity of compounds containing a thiazole ring, see: Araki (2004[@bb1]); Fahmy & Bekhit (2002[@bb4]); Manabe *et al.* (2003[@bb5]); Zhang *et al.* (2000[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~22~H~19~ClN~4~O~2~S*M* *~r~* = 438.92Triclinic,*a* = 8.114 (3) Å*b* = 11.452 (4) Å*c* = 12.494 (4) Åα = 102.700 (6)°β = 107.885 (6)°γ = 93.634 (7)°*V* = 1067.1 (6) Å^3^*Z* = 2Mo *K*α radiationμ = 0.30 mm^−1^*T* = 294 K0.20 × 0.18 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb8]) *T* ~min~ = 0.938, *T* ~max~ = 0.9685562 measured reflections3755 independent reflections2030 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.029 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.049*wR*(*F* ^2^) = 0.124*S* = 1.003755 reflections273 parametersH-atom parameters constrainedΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e381} Data collection: *SMART* (Bruker, 2000[@bb2]); cell refinement: *SAINT* (Bruker, 2000[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb9]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb9]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006702/ds2094sup1.cif](http://dx.doi.org/10.1107/S1600536811006702/ds2094sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006702/ds2094Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006702/ds2094Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ds2094&file=ds2094sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ds2094sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ds2094&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [DS2094](http://scripts.iucr.org/cgi-bin/sendsup?ds2094)). This work was supported by the Science and Technology Projects Fund of Nantong City (grant Nos. K2010016, AS2010005), the Science Foundation of Nantong University (grant Nos. 09Z010, 09 C001) and the Scientific Research Foundation for Talent Introduction of Nantong University. Comment ======= In the past few years, pyrazole oxime ethers have been found to exhibit a wide range of bioactivities, such as fungicidal, insecticidal, acaricidal and anticancer activities (Drabek, 1992; Motoba *et al.*, 2000; Watanabe *et al.*, 2001;Park *et al.*, 2005). In addition, the biological activity of thiazole derivatives has been the subject of intense interest for past decades. They are widely used as fungicide, insecticide, herbicide and antitumor agents (Zhang *et al.*, 2000; Fahmy & Bekhit, 2002; Manabe *et al.*, 2003; Araki,2004). Having the above facts in mind and in continuation of our efforts to explore more biologically active moleculars, we synthesized a series of pyrazole oxime ether compounds containing a thiazole moiety. Herein we report the crystal structure of the title compound. The molecule of the title compound (Fig.1)contains four planar rings, the benzene ring (p1: C1/C2/C3/C4/C5/C6), the substituted phenyl ring (p2: C11/C12/C13/C14/C15/C16),the thiazole ring(p3: C20/C21/N4/C22/S1) and the pyrazole ring(p4: N1/N2/C8/C9/C10).The planes of p1, p2 and p3 make dihedral angles of 18.4 (3)°, 88.9 (2) ° and 63.0 (3) °,respectively, with p4. Experimental {#experimental} ============ To a well stirred solution of 1-phenyl-3-methyl-5-(4-methylphenoxy)-1*H*- pyrazole-4-carbaldehyde oxime (3 mmol),and powdered potassium carbonate (6 mmol) in 20 ml of anhydrous acetone, was added 2-chloro-5-chloromethyl thiazole (3.3 mmol) at room temperature. The mixture was heated to reflux for 10 h. The solvent was evaporated under reduced pressure, and then 80 ml of dichloromethane was added to the residue. The organic layer was washed with saturated brine(3 \* 20 ml),and dried over anhydrous magnesium sulfate. After removal of the solvent, the residue was separated by column chromatography on silica gel with petroleum ether/ethyl acetate(6:1 *v*/*v*) as eluent, and recrystallized from ethyl acetate to give a colourless crystal. Refinement {#refinement} ========== All H atoms were placed in calculated positions, with C--H = 0.93, 0.96 and 0.97 Å, and included in the final cycles of refinement using a riding model, with *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title compound, with displacement ellipsoids drawn at the 30% probability level. ::: ![](e-67-0o727-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e122 .table-wrap} ----------------------- --------------------------------------- C~22~H~19~ClN~4~O~2~S *Z* = 2 *M~r~* = 438.92 *F*(000) = 456 Triclinic, *P*1 *D*~x~ = 1.366 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.114 (3) Å Cell parameters from 1218 reflections *b* = 11.452 (4) Å θ = 2.7--22.3° *c* = 12.494 (4) Å µ = 0.30 mm^−1^ α = 102.700 (6)° *T* = 294 K β = 107.885 (6)° Triclinic, colourless γ = 93.634 (7)° 0.20 × 0.18 × 0.10 mm *V* = 1067.1 (6) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e259 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3755 independent reflections Radiation source: fine-focus sealed tube 2030 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.029 φ and ω scans θ~max~ = 25.0°, θ~min~ = 1.8° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −9→9 *T*~min~ = 0.938, *T*~max~ = 0.968 *k* = −10→13 5562 measured reflections *l* = −14→14 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.049 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.124 H-atom parameters constrained *S* = 1.00 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.049*P*)^2^ + 0.1132*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3755 reflections (Δ/σ)~max~ = 0.001 273 parameters Δρ~max~ = 0.17 e Å^−3^ 0 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e533 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e632 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ S1 0.45270 (11) 0.85178 (9) 0.33662 (8) 0.0647 (3) Cl1 0.61728 (16) 0.68418 (11) 0.47383 (9) 0.0975 (4) O1 −0.0621 (2) 0.84964 (18) 0.10876 (17) 0.0450 (5) O2 0.4577 (3) 1.0355 (2) 0.16837 (17) 0.0530 (6) N1 −0.2014 (3) 0.7626 (2) −0.0923 (2) 0.0434 (7) N2 −0.1696 (3) 0.7554 (2) −0.1953 (2) 0.0510 (7) N3 0.2917 (3) 0.9627 (2) 0.1279 (2) 0.0479 (7) N4 0.7640 (4) 0.8986 (3) 0.4813 (2) 0.0660 (9) C1 −0.3633 (4) 0.7038 (3) −0.0939 (3) 0.0471 (8) C2 −0.4206 (4) 0.7326 (3) 0.0001 (3) 0.0636 (10) H2 −0.3572 0.7937 0.0653 0.076\* C3 −0.5742 (5) 0.6692 (4) −0.0040 (4) 0.0768 (12) H3 −0.6126 0.6870 0.0599 0.092\* C4 −0.6702 (5) 0.5811 (4) −0.0999 (5) 0.0914 (14) H4 −0.7723 0.5384 −0.1009 0.110\* C5 −0.6157 (5) 0.5561 (4) −0.1939 (4) 0.0941 (14) H5 −0.6828 0.4975 −0.2602 0.113\* C6 −0.4610 (5) 0.6171 (4) −0.1921 (3) 0.0719 (11) H6 −0.4240 0.5994 −0.2566 0.086\* C7 0.0690 (4) 0.8267 (4) −0.2568 (3) 0.0676 (11) H7A 0.1699 0.7855 −0.2474 0.101\* H7B 0.1031 0.9108 −0.2490 0.101\* H7C −0.0152 0.7919 −0.3324 0.101\* C8 −0.0104 (4) 0.8142 (3) −0.1657 (3) 0.0465 (8) C9 0.0656 (4) 0.8599 (3) −0.0440 (2) 0.0400 (8) C10 −0.0610 (4) 0.8238 (3) −0.0019 (3) 0.0395 (8) C11 −0.0066 (4) 0.7658 (3) 0.1735 (2) 0.0408 (8) C12 −0.0280 (4) 0.7901 (3) 0.2804 (3) 0.0541 (9) H12 −0.0762 0.8582 0.3055 0.065\* C13 0.0232 (4) 0.7116 (3) 0.3504 (3) 0.0591 (10) H13 0.0085 0.7278 0.4230 0.071\* C14 0.0945 (4) 0.6111 (3) 0.3161 (3) 0.0531 (9) C15 0.1125 (4) 0.5889 (3) 0.2072 (3) 0.0550 (9) H15 0.1606 0.5209 0.1819 0.066\* C16 0.0612 (4) 0.6647 (3) 0.1352 (3) 0.0449 (8) H16 0.0725 0.6474 0.0617 0.054\* C17 0.1474 (5) 0.5256 (4) 0.3933 (3) 0.0871 (13) H17A 0.2202 0.5707 0.4695 0.131\* H17B 0.2110 0.4678 0.3609 0.131\* H17C 0.0447 0.4841 0.3984 0.131\* C18 0.2345 (4) 0.9303 (3) 0.0182 (3) 0.0437 (8) H18 0.3035 0.9525 −0.0233 0.052\* C19 0.5031 (4) 1.0792 (3) 0.2911 (3) 0.0565 (9) H19A 0.4004 1.1029 0.3096 0.068\* H19B 0.5904 1.1505 0.3175 0.068\* C20 0.5727 (4) 0.9879 (3) 0.3541 (3) 0.0468 (8) C21 0.7309 (4) 0.9944 (4) 0.4334 (3) 0.0606 (10) H21 0.8149 1.0620 0.4548 0.073\* C22 0.6282 (5) 0.8196 (4) 0.4373 (3) 0.0581 (10) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1336 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ S1 0.0518 (6) 0.0703 (7) 0.0665 (6) −0.0003 (5) 0.0059 (5) 0.0280 (5) Cl1 0.1287 (10) 0.0848 (9) 0.0856 (8) 0.0232 (7) 0.0255 (7) 0.0467 (7) O1 0.0519 (13) 0.0432 (14) 0.0441 (13) 0.0105 (11) 0.0182 (11) 0.0148 (11) O2 0.0445 (13) 0.0612 (16) 0.0491 (14) −0.0041 (11) 0.0079 (11) 0.0191 (12) N1 0.0359 (15) 0.0482 (18) 0.0457 (16) 0.0056 (13) 0.0095 (13) 0.0168 (14) N2 0.0474 (17) 0.062 (2) 0.0428 (16) 0.0036 (15) 0.0121 (14) 0.0170 (14) N3 0.0375 (15) 0.0513 (18) 0.0510 (18) −0.0010 (13) 0.0074 (13) 0.0170 (14) N4 0.062 (2) 0.077 (2) 0.0519 (19) 0.0171 (19) 0.0049 (16) 0.0184 (18) C1 0.0368 (18) 0.041 (2) 0.065 (2) 0.0078 (16) 0.0136 (18) 0.0205 (18) C2 0.049 (2) 0.073 (3) 0.073 (3) 0.005 (2) 0.026 (2) 0.019 (2) C3 0.059 (3) 0.084 (3) 0.099 (3) 0.009 (2) 0.042 (2) 0.025 (3) C4 0.058 (3) 0.072 (3) 0.150 (5) −0.003 (2) 0.051 (3) 0.020 (3) C5 0.057 (3) 0.080 (3) 0.118 (4) −0.016 (2) 0.025 (3) −0.017 (3) C6 0.049 (2) 0.070 (3) 0.084 (3) −0.002 (2) 0.022 (2) −0.002 (2) C7 0.069 (2) 0.089 (3) 0.050 (2) −0.001 (2) 0.0227 (19) 0.027 (2) C8 0.0408 (19) 0.053 (2) 0.048 (2) 0.0056 (17) 0.0118 (16) 0.0210 (17) C9 0.0383 (18) 0.043 (2) 0.0402 (19) 0.0085 (15) 0.0097 (15) 0.0171 (16) C10 0.0390 (18) 0.039 (2) 0.0418 (19) 0.0092 (15) 0.0118 (16) 0.0146 (16) C11 0.0399 (17) 0.045 (2) 0.0403 (19) 0.0021 (16) 0.0149 (15) 0.0149 (16) C12 0.067 (2) 0.053 (2) 0.050 (2) 0.0139 (19) 0.0300 (18) 0.0120 (18) C13 0.072 (2) 0.064 (3) 0.047 (2) 0.004 (2) 0.0266 (19) 0.016 (2) C14 0.060 (2) 0.049 (2) 0.058 (2) 0.0042 (19) 0.0227 (19) 0.0241 (19) C15 0.059 (2) 0.049 (2) 0.064 (2) 0.0136 (18) 0.0257 (18) 0.0194 (19) C16 0.0498 (19) 0.044 (2) 0.0461 (19) 0.0081 (17) 0.0217 (16) 0.0128 (17) C17 0.116 (3) 0.080 (3) 0.084 (3) 0.021 (3) 0.038 (3) 0.050 (3) C18 0.0398 (18) 0.050 (2) 0.049 (2) 0.0083 (16) 0.0161 (17) 0.0251 (17) C19 0.053 (2) 0.057 (2) 0.050 (2) 0.0042 (18) 0.0068 (17) 0.0090 (19) C20 0.0438 (19) 0.054 (2) 0.0397 (18) 0.0060 (17) 0.0121 (16) 0.0077 (17) C21 0.054 (2) 0.065 (3) 0.051 (2) 0.0035 (19) 0.0053 (18) 0.011 (2) C22 0.069 (2) 0.064 (3) 0.047 (2) 0.018 (2) 0.0207 (19) 0.020 (2) ----- ------------- ------------- ------------- -------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1851 .table-wrap} --------------------- ------------ ----------------------- ------------ S1---C22 1.708 (4) C7---H7A 0.9600 S1---C20 1.718 (3) C7---H7B 0.9600 Cl1---C22 1.714 (4) C7---H7C 0.9600 O1---C10 1.352 (3) C8---C9 1.414 (4) O1---C11 1.397 (3) C9---C10 1.370 (4) O2---N3 1.421 (3) C9---C18 1.436 (4) O2---C19 1.424 (3) C11---C16 1.368 (4) N1---C10 1.351 (3) C11---C12 1.370 (4) N1---N2 1.375 (3) C12---C13 1.384 (4) N1---C1 1.430 (4) C12---H12 0.9300 N2---C8 1.321 (4) C13---C14 1.365 (5) N3---C18 1.264 (4) C13---H13 0.9300 N4---C22 1.272 (4) C14---C15 1.383 (4) N4---C21 1.365 (4) C14---C17 1.512 (4) C1---C2 1.374 (4) C15---C16 1.377 (4) C1---C6 1.374 (5) C15---H15 0.9300 C2---C3 1.383 (5) C16---H16 0.9300 C2---H2 0.9300 C17---H17A 0.9600 C3---C4 1.362 (6) C17---H17B 0.9600 C3---H3 0.9300 C17---H17C 0.9600 C4---C5 1.358 (6) C18---H18 0.9300 C4---H4 0.9300 C19---C20 1.482 (4) C5---C6 1.388 (5) C19---H19A 0.9700 C5---H5 0.9300 C19---H19B 0.9700 C6---H6 0.9300 C20---C21 1.345 (4) C7---C8 1.497 (4) C21---H21 0.9300 C22---S1---C20 88.36 (18) C16---C11---C12 120.9 (3) C10---O1---C11 117.5 (2) C16---C11---O1 124.2 (3) N3---O2---C19 107.2 (2) C12---C11---O1 114.9 (3) C10---N1---N2 110.3 (2) C11---C12---C13 118.9 (3) C10---N1---C1 130.4 (3) C11---C12---H12 120.6 N2---N1---C1 119.3 (3) C13---C12---H12 120.6 C8---N2---N1 105.2 (2) C14---C13---C12 121.9 (3) C18---N3---O2 110.9 (2) C14---C13---H13 119.0 C22---N4---C21 108.2 (3) C12---C13---H13 119.0 C2---C1---C6 120.4 (3) C13---C14---C15 117.6 (3) C2---C1---N1 121.3 (3) C13---C14---C17 121.1 (3) C6---C1---N1 118.3 (3) C15---C14---C17 121.3 (3) C1---C2---C3 118.9 (4) C16---C15---C14 121.8 (3) C1---C2---H2 120.6 C16---C15---H15 119.1 C3---C2---H2 120.6 C14---C15---H15 119.1 C4---C3---C2 121.2 (4) C11---C16---C15 118.9 (3) C4---C3---H3 119.4 C11---C16---H16 120.5 C2---C3---H3 119.4 C15---C16---H16 120.5 C5---C4---C3 119.5 (4) C14---C17---H17A 109.5 C5---C4---H4 120.3 C14---C17---H17B 109.5 C3---C4---H4 120.3 H17A---C17---H17B 109.5 C4---C5---C6 120.7 (4) C14---C17---H17C 109.5 C4---C5---H5 119.6 H17A---C17---H17C 109.5 C6---C5---H5 119.6 H17B---C17---H17C 109.5 C1---C6---C5 119.2 (4) N3---C18---C9 121.6 (3) C1---C6---H6 120.4 N3---C18---H18 119.2 C5---C6---H6 120.4 C9---C18---H18 119.2 C8---C7---H7A 109.5 O2---C19---C20 112.5 (3) C8---C7---H7B 109.5 O2---C19---H19A 109.1 H7A---C7---H7B 109.5 C20---C19---H19A 109.1 C8---C7---H7C 109.5 O2---C19---H19B 109.1 H7A---C7---H7C 109.5 C20---C19---H19B 109.1 H7B---C7---H7C 109.5 H19A---C19---H19B 107.8 N2---C8---C9 112.1 (3) C21---C20---C19 128.5 (3) N2---C8---C7 120.5 (3) C21---C20---S1 108.3 (3) C9---C8---C7 127.4 (3) C19---C20---S1 123.1 (2) C10---C9---C8 103.7 (3) C20---C21---N4 117.8 (3) C10---C9---C18 129.1 (3) C20---C21---H21 121.1 C8---C9---C18 127.2 (3) N4---C21---H21 121.1 N1---C10---O1 122.1 (3) N4---C22---S1 117.4 (3) N1---C10---C9 108.8 (3) N4---C22---Cl1 122.8 (3) O1---C10---C9 128.9 (3) S1---C22---Cl1 119.9 (2) C10---N1---N2---C8 −0.8 (3) C8---C9---C10---O1 −175.4 (3) C1---N1---N2---C8 −178.1 (2) C18---C9---C10---O1 3.0 (5) C19---O2---N3---C18 173.5 (3) C10---O1---C11---C16 5.4 (4) C10---N1---C1---C2 20.1 (5) C10---O1---C11---C12 −173.3 (3) N2---N1---C1---C2 −163.2 (3) C16---C11---C12---C13 1.2 (5) C10---N1---C1---C6 −159.8 (3) O1---C11---C12---C13 179.9 (3) N2---N1---C1---C6 16.9 (4) C11---C12---C13---C14 0.1 (5) C6---C1---C2---C3 2.8 (5) C12---C13---C14---C15 −0.8 (5) N1---C1---C2---C3 −177.1 (3) C12---C13---C14---C17 −179.2 (3) C1---C2---C3---C4 −1.3 (6) C13---C14---C15---C16 0.1 (5) C2---C3---C4---C5 −1.0 (7) C17---C14---C15---C16 178.6 (3) C3---C4---C5---C6 1.8 (7) C12---C11---C16---C15 −1.8 (4) C2---C1---C6---C5 −2.0 (5) O1---C11---C16---C15 179.6 (3) N1---C1---C6---C5 177.9 (3) C14---C15---C16---C11 1.1 (5) C4---C5---C6---C1 −0.3 (6) O2---N3---C18---C9 −177.5 (2) N1---N2---C8---C9 0.4 (3) C10---C9---C18---N3 4.6 (5) N1---N2---C8---C7 −179.3 (3) C8---C9---C18---N3 −177.4 (3) N2---C8---C9---C10 0.0 (3) N3---O2---C19---C20 79.6 (3) C7---C8---C9---C10 179.7 (3) O2---C19---C20---C21 119.4 (3) N2---C8---C9---C18 −178.4 (3) O2---C19---C20---S1 −62.1 (3) C7---C8---C9---C18 1.3 (5) C22---S1---C20---C21 0.0 (2) N2---N1---C10---O1 176.1 (3) C22---S1---C20---C19 −178.9 (3) C1---N1---C10---O1 −7.0 (5) C19---C20---C21---N4 178.9 (3) N2---N1---C10---C9 0.8 (3) S1---C20---C21---N4 0.1 (4) C1---N1---C10---C9 177.8 (3) C22---N4---C21---C20 −0.2 (4) C11---O1---C10---N1 90.5 (3) C21---N4---C22---S1 0.1 (4) C11---O1---C10---C9 −95.2 (4) C21---N4---C22---Cl1 179.3 (2) C8---C9---C10---N1 −0.5 (3) C20---S1---C22---N4 −0.1 (3) C18---C9---C10---N1 177.9 (3) C20---S1---C22---Cl1 −179.3 (2) --------------------- ------------ ----------------------- ------------ :::

PubMed Central

2024-06-05T04:04:18.587187

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052122/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o727", "authors": [ { "first": "Hong", "last": "Dai" }, { "first": "Yu-Ting", "last": "Zhang" }, { "first": "Yu-Jun", "last": "Shi" }, { "first": "Wen-Wen", "last": "Zhang" }, { "first": "Yong-Jun", "last": "Shen" } ] }

PMC3052123

Related literature {#sec1} ================== For related structures of β-amino alcohols, see: Lohray *et al.* (2002[@bb11]); Bodkin *et al.* (2008[@bb2]). For the structures of tosylamino compounds, see: Coote *et al.* (2008[@bb5]); Liu *et al.* (2005[@bb10]); Fadlalla *et al.* (2010[@bb6]). For the synthesis of the title compound, see: Naicker *et al.* (2008[@bb12]); Govender *et al.* (2003[@bb9]). For hydrogen-bond motifs, see: Bernstein *et al.* (1995[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~15~H~23~NO~5~S*M* *~r~* = 329.4Triclinic,*a* = 9.6038 (8) Å*b* = 9.9059 (8) Å*c* = 10.1064 (11) Åα = 119.342 (2)°β = 92.307 (2)°γ = 93.422 (2)°*V* = 833.95 (13) Å^3^*Z* = 2Mo *K*α radiationμ = 0.22 mm^−1^*T* = 100 K0.22 × 0.18 × 0.14 mm ### Data collection {#sec2.1.2} Bruker X8 APEXII 4K Kappa CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2007[@bb4]) *T* ~min~ = 0.954, *T* ~max~ = 0.97024635 measured reflections4192 independent reflections3712 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.031 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.030*wR*(*F* ^2^) = 0.083*S* = 1.054192 reflections209 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.45 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e503} Data collection: *APEX2* (Bruker, 2007[@bb4]); cell refinement: *SAINT-Plus* (Bruker, 2007[@bb4]); data reduction: *SAINT-Plus* and *XPREP* (Bruker, 2007[@bb4]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb13]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb13]); molecular graphics: *DIAMOND* (Brandenburg & Putz, 2005[@bb3]) and *ORTEP-3* (Farrugia, 1997[@bb7]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004934/hg2795sup1.cif](http://dx.doi.org/10.1107/S1600536811004934/hg2795sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004934/hg2795Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004934/hg2795Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg2795&file=hg2795sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg2795sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg2795&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG2795](http://scripts.iucr.org/cgi-bin/sendsup?hg2795)). Financial assistance from Mintek and THRIP is gratefully acknowledged. Comment ======= The aminohydroxylation reaction of alkenes is the most simple, single step reaction in the production of β-amino alcohols. The product (β-amino alcohol) is present in many natural products and biologically active compounds (such as Acranil which is an antiprotozoal drug) (Bodkin *et al.*, 2008, Lohray *et al.*, 2002). Furthermore, β-amino alcohols are utilized in asymmetric catalysis in the synthesis of chiral ligands. As part of investigating new heterogeneous route to the aminohydroxylation reaction to produce β-amino alcohols, we report the crystal structure of the title compound (I). The molecular structure of (I) is related to that of (2,3)-Methyl 2-hydroxy-3-(4-methylbenzenesulfonamido)-3-phenylpropanoate (Fadlalla *et al.*, (2010). Other related structures have been reported by Coote *et al.* (2008) and Liu *et al.*, (2005). Fig. I shows the asymetric unit of (I). The compound is chiral and has an S chirality at C6 and an *R* chirality at C7. In the crystal, adjacent molecules are connected by a pair of N---H···O and O---H···O hydrogen bonds (Fig. 2) that result in centrosymmetric dimers that can be described by *R*~2~^2^(12) and *R*~2~^2^(14) graph set notations (Bernstein *et al.* 1995) respectively. In addition, weak C---H···O intermolecular interactions (Table 1) contribute to the stability of the crystal lattice. Experimental {#experimental} ============ The title compound (I) was obtained through a modified literature method (Naicker *et al.*, 2008, Govender *et al.*, 2003).To a nitrogen saturated Schlenk tube 6 ml of a mixture of acetonitrile and water (1:1 *v*/*v*), *tert*-butylcrotonate (76 µ*L*, 0.478 mmol), chloramine-T (0.956 g, 0.956 mmol), hydrotalcite-like catalyst (0.03 g) were added in that order. The catalyst was gravity filtered off after 15 h. The reaction mixture was then washed with sodium sulfite (1 g in 20 ml of de-ionized water) followed by 15 ml of ethyl acetate. The aqueous layer was separated from the organic layer and further washed by 3x 15 ml of ethyl acetate. The solvent of the combined organic mixture was removed *in vacuo*. The resulting crude product was purified by preparative high preasure liquid chromatography to yield the title compound as a white solid. Crystals of I were obtained by slow evaporation of a hexane layered solution of the compound in dichloro methane at room temperature (m.p. 142--145 K). Spectroscopic data: ^1^H NMR (400 MHz, CDCl~3~, δ. p.p.m.): = 0.9 (d, 3H), 1.5 (s, 9H), 2.4 (s, 3H), 3.2 (d, 1H), 3.8 (m, 2H), 4.7 (d, 1H), 7.3 (d, 2H), 7.7 (d, 2H). ^13^C NMR (100 MHz, CDCl~3~, δ. p.p.m.): = 17.9 (s,1 C), 21.5 (s, 1 C), 27.9 (s, 3 C), 51.5 (s, 1 C), 73.6 (s, 1 C), 84.1 (s, 1 C), 126.9 (s, 2 C), 138.6 (s, 1 C), 143.3 (s, 1 C), 171.6 (s, 1 C). IR (cm^-1^): = 3446 (*m*), (OH), 3260 (*m*), (NH), 2985 (w), 2919 (w), 1598 (w), (ar), 1716 (*m*), (C=O), 1048 (*m*), (S=O). Mass calculated = 329, MS = 351 m/*z* (*M* + Na). Refinement {#refinement} ========== The methyl, methine and aromatic H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C---H = 0.95 Å and *U*~iso~(H) = 1.2*U*~eq~(C) for aromatic, C---H = 0.98 Å and *U*~iso~(H) = 1.2*U*~eq~(C) for CH~3~, C---H = 1.00 Å and *U*~iso~(H) = 1.2*U*~eq~(C) for CH. N---H = 0.84 Å and *U*~iso~(H) = 1.2*U*~eq~(N) for N---H and O---H = 0.84 Å and *U*~iso~(H) = 1.5*U*~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of (I) (50% probability displacement ellipsoids). H atoms have been omited for clarity. ::: ![](e-67-0o648-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### N---H···O and O---H···O hydrogen bond interactions in the crystal structure of (I). \[Symmetry operators: (i) = 1 - x, 1 - y, 1 - z; (ii) = 1 - x, 2 - y, 2 - z\] ::: ![](e-67-0o648-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e285 .table-wrap} ------------------------ ---------------------------------------- C~15~H~23~NO~5~S *Z* = 2 *M~r~* = 329.4 *F*(000) = 352 Triclinic, *P*1 *D*~x~ = 1.312 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 9.6038 (8) Å Cell parameters from 24635 reflections *b* = 9.9059 (8) Å θ = 2.1--28.5° *c* = 10.1064 (11) Å µ = 0.22 mm^−1^ α = 119.342 (2)° *T* = 100 K β = 92.307 (2)° Block, colourless γ = 93.422 (2)° 0.22 × 0.18 × 0.14 mm *V* = 833.95 (13) Å^3^ ------------------------ ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e419 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker X8 APEXII 4K Kappa CCD diffractometer 3712 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.031 φ and ω scans θ~max~ = 28.5°, θ~min~ = 2.1° Absorption correction: multi-scan (*SADABS*; Bruker, 2007) *h* = −12→12 *T*~min~ = 0.954, *T*~max~ = 0.970 *k* = −13→13 24635 measured reflections *l* = −13→13 4192 independent reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e535 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.083 H atoms treated by a mixture of independent and constrained refinement *S* = 1.05 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0395*P*)^2^ + 0.3237*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4192 reflections (Δ/σ)~max~ = 0.005 209 parameters Δρ~max~ = 0.45 e Å^−3^ 0 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e692 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The intensity data was collected on a Bruker X8 Apex 4 K CCD diffractometer using an exposure time of 15 sec/per frame. A total of 3328 frames were collected with a frame width of 0.5° covering upto θ = 28.45° with 99.8% completeness accomplished. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e800 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.74584 (13) 1.08296 (13) 0.93414 (13) 0.0208 (2) H1A 0.6562 1.118 0.9193 0.031\* H1B 0.8195 1.1223 0.8942 0.031\* H1C 0.7685 1.1225 1.0431 0.031\* C2 0.87462 (12) 0.84588 (14) 0.86348 (14) 0.0241 (2) H2A 0.9444 0.8772 0.8132 0.036\* H2B 0.8629 0.7322 0.8145 0.036\* H2C 0.9061 0.8896 0.9712 0.036\* C3 0.61532 (13) 0.83957 (14) 0.90149 (13) 0.0222 (2) H3A 0.6156 0.7262 0.8517 0.033\* H3B 0.5263 0.8661 0.8736 0.033\* H3C 0.627 0.8836 1.0122 0.033\* C4 0.73538 (11) 0.90605 (13) 0.85019 (12) 0.0165 (2) C5 0.68030 (10) 0.71782 (12) 0.58068 (12) 0.0145 (2) C6 0.63194 (11) 0.69956 (12) 0.42678 (12) 0.0151 (2) H6 0.7064 0.7491 0.3939 0.018\* C7 0.49600 (11) 0.77696 (12) 0.43670 (12) 0.0152 (2) H7 0.5149 0.891 0.5094 0.018\* C8 0.44465 (12) 0.75423 (15) 0.28179 (13) 0.0223 (2) H8A 0.3603 0.8085 0.2919 0.033\* H8B 0.4228 0.643 0.2101 0.033\* H8C 0.5178 0.7965 0.2438 0.033\* C9 0.12195 (11) 0.73713 (13) 0.43575 (12) 0.0166 (2) C10 0.05152 (11) 0.58888 (13) 0.37062 (13) 0.0177 (2) H10 0.0739 0.5198 0.4067 0.021\* C11 −0.05154 (11) 0.54303 (14) 0.25272 (13) 0.0197 (2) H11 −0.0984 0.4414 0.2071 0.024\* C12 −0.08741 (11) 0.64442 (15) 0.19995 (13) 0.0209 (2) C13 −0.01768 (12) 0.79315 (15) 0.26927 (14) 0.0233 (2) H13 −0.0425 0.8639 0.2362 0.028\* C14 0.08753 (12) 0.84021 (14) 0.38584 (14) 0.0215 (2) H14 0.1352 0.9413 0.4308 0.026\* C15 −0.19933 (13) 0.59239 (18) 0.07100 (15) 0.0296 (3) H15A −0.1592 0.5302 −0.0263 0.044\* H15B −0.2358 0.6838 0.0733 0.044\* H15C −0.2756 0.5295 0.0824 0.044\* N1 0.39695 (9) 0.71013 (11) 0.50168 (10) 0.01484 (18) O1 0.70108 (8) 0.86607 (8) 0.68847 (8) 0.01528 (15) O2 0.69788 (8) 0.60683 (9) 0.59739 (9) 0.01913 (17) O3 0.60741 (8) 0.53975 (9) 0.31707 (9) 0.01922 (17) H3 0.6564 0.4879 0.3431 0.029\* O4 0.21687 (9) 0.71817 (10) 0.66814 (9) 0.02355 (18) O5 0.29082 (9) 0.95624 (10) 0.65376 (10) 0.02641 (19) S1 0.25877 (3) 0.79036 (3) 0.58022 (3) 0.01691 (8) H1D 0.3859 (16) 0.6124 (18) 0.4581 (17) 0.025 (4)\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1400 .table-wrap} ----- -------------- -------------- -------------- ------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0283 (6) 0.0164 (5) 0.0150 (5) −0.0004 (4) −0.0005 (4) 0.0059 (4) C2 0.0216 (5) 0.0238 (6) 0.0233 (6) 0.0015 (4) −0.0067 (4) 0.0095 (5) C3 0.0261 (6) 0.0222 (5) 0.0196 (5) 0.0003 (4) 0.0039 (4) 0.0114 (5) C4 0.0196 (5) 0.0169 (5) 0.0124 (5) 0.0001 (4) −0.0021 (4) 0.0072 (4) C5 0.0108 (4) 0.0148 (5) 0.0162 (5) 0.0007 (4) 0.0006 (4) 0.0065 (4) C6 0.0152 (5) 0.0141 (5) 0.0140 (5) 0.0003 (4) 0.0008 (4) 0.0055 (4) C7 0.0159 (5) 0.0144 (5) 0.0160 (5) 0.0000 (4) −0.0002 (4) 0.0083 (4) C8 0.0221 (5) 0.0290 (6) 0.0201 (5) 0.0010 (4) −0.0021 (4) 0.0159 (5) C9 0.0138 (5) 0.0186 (5) 0.0178 (5) 0.0042 (4) 0.0029 (4) 0.0088 (4) C10 0.0153 (5) 0.0201 (5) 0.0206 (5) 0.0044 (4) 0.0031 (4) 0.0119 (4) C11 0.0152 (5) 0.0230 (5) 0.0211 (5) 0.0016 (4) 0.0018 (4) 0.0112 (5) C12 0.0135 (5) 0.0337 (6) 0.0211 (5) 0.0060 (4) 0.0051 (4) 0.0171 (5) C13 0.0196 (5) 0.0310 (6) 0.0306 (6) 0.0089 (5) 0.0064 (5) 0.0229 (5) C14 0.0192 (5) 0.0197 (5) 0.0287 (6) 0.0046 (4) 0.0042 (4) 0.0140 (5) C15 0.0204 (6) 0.0507 (8) 0.0263 (6) 0.0044 (5) 0.0003 (5) 0.0256 (6) N1 0.0145 (4) 0.0121 (4) 0.0174 (4) 0.0014 (3) 0.0016 (3) 0.0068 (4) O1 0.0187 (4) 0.0130 (3) 0.0129 (3) 0.0001 (3) −0.0015 (3) 0.0058 (3) O2 0.0199 (4) 0.0148 (4) 0.0221 (4) 0.0016 (3) −0.0027 (3) 0.0090 (3) O3 0.0220 (4) 0.0143 (4) 0.0157 (4) 0.0026 (3) −0.0009 (3) 0.0031 (3) O4 0.0227 (4) 0.0316 (5) 0.0163 (4) 0.0011 (3) 0.0028 (3) 0.0118 (4) O5 0.0257 (4) 0.0159 (4) 0.0268 (4) 0.0034 (3) 0.0006 (3) 0.0022 (3) S1 0.01644 (13) 0.01627 (13) 0.01483 (13) 0.00257 (9) 0.00163 (9) 0.00506 (10) ----- -------------- -------------- -------------- ------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1795 .table-wrap} ----------------------- -------------- --------------------- -------------- C1---C4 1.5218 (15) C8---H8B 0.98 C1---H1A 0.98 C8---H8C 0.98 C1---H1B 0.98 C9---C14 1.3921 (15) C1---H1C 0.98 C9---C10 1.3949 (15) C2---C4 1.5235 (15) C9---S1 1.7733 (11) C2---H2A 0.98 C10---C11 1.3881 (15) C2---H2B 0.98 C10---H10 0.95 C2---H2C 0.98 C11---C12 1.4012 (16) C3---C4 1.5245 (16) C11---H11 0.95 C3---H3A 0.98 C12---C13 1.3938 (18) C3---H3B 0.98 C12---C15 1.5106 (16) C3---H3C 0.98 C13---C14 1.3914 (17) C4---O1 1.4978 (12) C13---H13 0.95 C5---O2 1.2115 (13) C14---H14 0.95 C5---O1 1.3277 (12) C15---H15A 0.98 C5---C6 1.5244 (14) C15---H15B 0.98 C6---O3 1.4161 (12) C15---H15C 0.98 C6---C7 1.5353 (14) N1---S1 1.6172 (9) C6---H6 1 N1---H1D 0.842 (16) C7---N1 1.4750 (13) O3---H3 0.84 C7---C8 1.5245 (15) O4---S1 1.4422 (9) C7---H7 1 O5---S1 1.4393 (9) C8---H8A 0.98 C4---C1---H1A 109.5 C7---C8---H8B 109.5 C4---C1---H1B 109.5 H8A---C8---H8B 109.5 H1A---C1---H1B 109.5 C7---C8---H8C 109.5 C4---C1---H1C 109.5 H8A---C8---H8C 109.5 H1A---C1---H1C 109.5 H8B---C8---H8C 109.5 H1B---C1---H1C 109.5 C14---C9---C10 120.57 (10) C4---C2---H2A 109.5 C14---C9---S1 120.59 (9) C4---C2---H2B 109.5 C10---C9---S1 118.82 (8) H2A---C2---H2B 109.5 C11---C10---C9 119.49 (10) C4---C2---H2C 109.5 C11---C10---H10 120.3 H2A---C2---H2C 109.5 C9---C10---H10 120.3 H2B---C2---H2C 109.5 C10---C11---C12 120.95 (11) C4---C3---H3A 109.5 C10---C11---H11 119.5 C4---C3---H3B 109.5 C12---C11---H11 119.5 H3A---C3---H3B 109.5 C13---C12---C11 118.43 (10) C4---C3---H3C 109.5 C13---C12---C15 121.30 (11) H3A---C3---H3C 109.5 C11---C12---C15 120.27 (11) H3B---C3---H3C 109.5 C14---C13---C12 121.41 (10) O1---C4---C1 102.44 (8) C14---C13---H13 119.3 O1---C4---C2 109.60 (9) C12---C13---H13 119.3 C1---C4---C2 111.41 (9) C13---C14---C9 119.13 (11) O1---C4---C3 108.99 (9) C13---C14---H14 120.4 C1---C4---C3 111.22 (9) C9---C14---H14 120.4 C2---C4---C3 112.66 (10) C12---C15---H15A 109.5 O2---C5---O1 125.85 (10) C12---C15---H15B 109.5 O2---C5---C6 122.05 (9) H15A---C15---H15B 109.5 O1---C5---C6 112.09 (9) C12---C15---H15C 109.5 O3---C6---C5 109.87 (8) H15A---C15---H15C 109.5 O3---C6---C7 108.58 (8) H15B---C15---H15C 109.5 C5---C6---C7 110.83 (8) C7---N1---S1 123.52 (7) O3---C6---H6 109.2 C7---N1---H1D 116.2 (10) C5---C6---H6 109.2 S1---N1---H1D 112.5 (10) C7---C6---H6 109.2 C5---O1---C4 119.50 (8) N1---C7---C8 114.28 (9) C6---O3---H3 109.5 N1---C7---C6 105.79 (8) O5---S1---O4 120.06 (5) C8---C7---C6 110.98 (9) O5---S1---N1 107.61 (5) N1---C7---H7 108.5 O4---S1---N1 105.57 (5) C8---C7---H7 108.5 O5---S1---C9 108.09 (5) C6---C7---H7 108.5 O4---S1---C9 106.33 (5) C7---C8---H8A 109.5 N1---S1---C9 108.80 (5) O2---C5---C6---O3 2.43 (14) S1---C9---C14---C13 178.17 (9) O1---C5---C6---O3 −178.31 (8) C8---C7---N1---S1 −76.81 (11) O2---C5---C6---C7 122.43 (11) C6---C7---N1---S1 160.79 (7) O1---C5---C6---C7 −58.31 (11) O2---C5---O1---C4 −6.69 (15) O3---C6---C7---N1 67.16 (10) C6---C5---O1---C4 174.08 (8) C5---C6---C7---N1 −53.61 (11) C1---C4---O1---C5 −178.29 (9) O3---C6---C7---C8 −57.32 (11) C2---C4---O1---C5 63.33 (12) C5---C6---C7---C8 −178.09 (9) C3---C4---O1---C5 −60.39 (12) C14---C9---C10---C11 1.46 (16) C7---N1---S1---O5 −33.34 (10) S1---C9---C10---C11 −177.12 (8) C7---N1---S1---O4 −162.69 (8) C9---C10---C11---C12 −1.07 (17) C7---N1---S1---C9 83.54 (9) C10---C11---C12---C13 −0.37 (17) C14---C9---S1---O5 15.26 (11) C10---C11---C12---C15 179.70 (10) C10---C9---S1---O5 −166.16 (9) C11---C12---C13---C14 1.47 (17) C14---C9---S1---O4 145.40 (9) C15---C12---C13---C14 −178.60 (11) C10---C9---S1---O4 −36.01 (10) C12---C13---C14---C9 −1.10 (18) C14---C9---S1---N1 −101.32 (10) C10---C9---C14---C13 −0.39 (17) C10---C9---S1---N1 77.26 (9) ----------------------- -------------- --------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2586 .table-wrap} ------------------- ------------ ------------ ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1D···O2^i^ 0.842 (16) 2.059 (16) 2.8625 (12) 159.5 (14) O3---H3···O4^i^ 0.84 2.40 3.2041 (12) 162 C1---H1C···O4^ii^ 0.98 2.54 3.4936 (14) 164 ------------------- ------------ ------------ ------------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*+1; (ii) −*x*+1, −*y*+2, −*z*+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- ------------ ------------ ------------- ------------- N1---H1*D*⋯O2^i^ 0.842 (16) 2.059 (16) 2.8625 (12) 159.5 (14) O3---H3⋯O4^i^ 0.84 2.40 3.2041 (12) 162 C1---H1*C*⋯O4^ii^ 0.98 2.54 3.4936 (14) 164 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.593258

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052123/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o648", "authors": [ { "first": "Mohamed I.", "last": "Fadlalla" }, { "first": "Holger B.", "last": "Friedrich" }, { "first": "Glenn E. M.", "last": "Maguire" }, { "first": "Bernard", "last": "Omondi" } ] }

PMC3052124

Related literature {#sec1} ================== For background to the coordination chemistry of 1,10-phenanthroline derivatives, see: Wang *et al.* (2010[@bb7]). For the synthetic procedure, see: Steck & Day (1943[@bb6]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~23~H~14~N~4~O*M* *~r~* = 362.38Tetragonal,*a* = 22.5800 (4) Å*c* = 13.7196 (5) Å*V* = 6995.0 (3) Å^3^*Z* = 16Mo *K*α radiationμ = 0.09 mm^−1^*T* = 293 K0.30 × 0.21 × 0.18 mm ### Data collection {#sec2.1.2} Bruker APEX diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb4]) *T* ~min~ = 0.41, *T* ~max~ = 0.7218374 measured reflections3433 independent reflections3153 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.022 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.031*wR*(*F* ^2^) = 0.081*S* = 1.063433 reflections253 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.14 e Å^−3^Absolute structure: Flack (1983[@bb3]), 1629 Friedel pairsFlack parameter: 0.0 (13) {#d5e416} Data collection: *SMART* (Bruker, 1997[@bb1]); cell refinement: *SAINT* (Bruker, 1999[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb5]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005861/lh5209sup1.cif](http://dx.doi.org/10.1107/S1600536811005861/lh5209sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005861/lh5209Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005861/lh5209Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5209&file=lh5209sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5209sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5209&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5209](http://scripts.iucr.org/cgi-bin/sendsup?lh5209)). The authors thank the Key Laboratory of Preparation and Applications of Environmentally Friendly Materials and the Institute Foundation of Siping City (No. 2009011) for supporting this work. Comment ======= 1,10-Phenanthroline and its derivatives, are potentially important chelating ligands with excellent coordinating abilities and have been extensively used to build supramolecular architectures (Wang *et al.*, 2010). We report herein the synthesis and crystal structure of the title compound The molecular structure of the title compound is shown in Fig. 1. The dihedral angle between the pyridine rings of the phenanthroline unit \[N2/C4-C8 and N1/C1/C2/C3/C11/C23\] is 4.43 (8)Å and the dihedral angle formed by the nine essentially planar non-hydrogen atoms of the benzimidazole unit \[C3/C4/C8-C12; maximum deviation 0.0389 (16)Å for C4\] and the naphthalene ring system is 74.22 (5)°. In the crystal, molecules are linked by intermolecular N---H···N and O---H···N hydrogen bonds to form a three-dimensional network. Experimental {#experimental} ============ The title compound was synthesized according to the literature method of Steck & Day (1943). We carried out the following reaction but the unreacted title compound was found in the reaction vessel. A mixture of Bi(NO~3~)~3~^.^5H~2~O (0.5 mmol) and L (0.5 mmol) in 10 mL distilled water was heated at 463 K in a Teflon-lined stainless steel autoclave for three days. The reaction system was then slowly cooled to room temperature. Pale yellow crystals suitable for single crystal X-ray diffraction analysis were collected from the final reaction system. Refinement {#refinement} ========== All H atoms were positioned geometrically (N---H = 0.86, C---H = 0.93 and O---H = 0.82 Å ) and refined as riding, with U~iso~(H) = 1.2U~eq~(C,N) or U~iso~(H) = 1.5U~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of of the title compound showing displacement ellipsoids drawn at the 30% probability. ::: ![](e-67-0o725-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e116 .table-wrap} ------------------------- --------------------------------------- C~23~H~14~N~4~O *D*~x~ = 1.376 Mg m^−3^ *M~r~* = 362.38 Mo *K*α radiation, λ = 0.71073 Å Tetragonal, *I*4~1~*cd* Cell parameters from 3433 reflections Hall symbol: I 4bw -2c θ = 1.8--26.0° *a* = 22.5800 (4) Å µ = 0.09 mm^−1^ *c* = 13.7196 (5) Å *T* = 293 K *V* = 6995.0 (3) Å^3^ Block, pale yellow *Z* = 16 0.30 × 0.21 × 0.18 mm *F*(000) = 3008 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e236 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEX diffractometer 3433 independent reflections Radiation source: fine-focus sealed tube 3153 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.022 φ and ω scans θ~max~ = 26.0°, θ~min~ = 1.8° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −27→27 *T*~min~ = 0.41, *T*~max~ = 0.72 *k* = −27→20 18374 measured reflections *l* = −16→16 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e353 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.031 H-atom parameters constrained *wR*(*F*^2^) = 0.081 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0457*P*)^2^ + 1.1603*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.06 (Δ/σ)~max~ = 0.001 3433 reflections Δρ~max~ = 0.12 e Å^−3^ 253 parameters Δρ~min~ = −0.14 e Å^−3^ 1 restraint Absolute structure: Flack (1983), 1629 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.0 (13) ---------------------------------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e515 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e560 .table-wrap} ----- -------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ N4 0.15231 (6) 0.04557 (6) 0.26423 (9) 0.0422 (3) H4 0.1345 0.0224 0.3045 0.051\* O1 0.15580 (7) 0.17926 (6) 0.40232 (9) 0.0690 (4) H1 0.1466 0.2049 0.4418 0.104\* N1 0.14620 (7) 0.08057 (7) −0.13144 (9) 0.0534 (4) C14 0.19348 (7) 0.14069 (7) 0.44439 (12) 0.0468 (4) N2 0.08332 (6) −0.01202 (7) −0.06297 (11) 0.0569 (4) C4 0.11269 (7) 0.02173 (7) 0.00293 (11) 0.0442 (4) C12 0.19309 (6) 0.08738 (6) 0.28685 (10) 0.0389 (3) N3 0.21230 (5) 0.11616 (5) 0.20892 (9) 0.0398 (3) C11 0.18392 (7) 0.10501 (6) 0.02914 (10) 0.0386 (3) C3 0.14849 (6) 0.07058 (7) −0.03403 (10) 0.0421 (3) C18 0.25212 (6) 0.05078 (7) 0.42951 (11) 0.0437 (3) C13 0.21381 (7) 0.09461 (7) 0.38867 (11) 0.0410 (3) C20 0.31013 (8) −0.03905 (8) 0.41619 (17) 0.0641 (5) H20 0.3238 −0.0707 0.3791 0.077\* C9 0.14476 (6) 0.04705 (6) 0.16521 (10) 0.0390 (3) C1 0.21610 (9) 0.15939 (8) −0.11023 (13) 0.0585 (5) H1A 0.2389 0.1889 −0.1391 0.070\* C19 0.27385 (7) 0.00224 (8) 0.37510 (13) 0.0516 (4) H19 0.2632 −0.0016 0.3099 0.062\* C21 0.30698 (8) 0.01212 (10) 0.56875 (15) 0.0677 (6) H21 0.3185 0.0151 0.6337 0.081\* C15 0.21017 (8) 0.14513 (9) 0.54344 (13) 0.0576 (4) H15 0.1961 0.1762 0.5815 0.069\* C8 0.10968 (7) 0.01000 (7) 0.10380 (11) 0.0422 (3) C10 0.18153 (6) 0.09101 (6) 0.13142 (10) 0.0373 (3) C7 0.07478 (8) −0.03699 (8) 0.13643 (14) 0.0582 (4) H7 0.0721 −0.0458 0.2025 0.070\* C17 0.26900 (7) 0.05588 (8) 0.52860 (13) 0.0516 (4) C2 0.17893 (9) 0.12442 (9) −0.16609 (13) 0.0613 (5) H2 0.1768 0.1323 −0.2325 0.074\* C16 0.24695 (8) 0.10373 (10) 0.58300 (13) 0.0601 (5) H16 0.2578 0.1073 0.6481 0.072\* C5 0.05054 (10) −0.05570 (10) −0.02947 (17) 0.0720 (6) H5 0.0300 −0.0787 −0.0744 0.086\* C6 0.04461 (9) −0.06976 (9) 0.06877 (17) 0.0729 (6) H6 0.0205 −0.1010 0.0882 0.087\* C23 0.21879 (8) 0.14991 (7) −0.01156 (12) 0.0473 (4) H23 0.2433 0.1729 0.0276 0.057\* C22 0.32682 (9) −0.03397 (10) 0.51413 (19) 0.0726 (6) H22 0.3516 −0.0623 0.5419 0.087\* ----- -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1147 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ N4 0.0482 (7) 0.0475 (7) 0.0308 (6) −0.0029 (6) 0.0025 (5) 0.0074 (5) O1 0.0956 (10) 0.0655 (8) 0.0461 (7) 0.0325 (7) −0.0183 (7) −0.0127 (6) N1 0.0634 (9) 0.0683 (9) 0.0286 (6) 0.0102 (7) 0.0019 (6) −0.0026 (6) C14 0.0506 (8) 0.0539 (9) 0.0358 (8) 0.0075 (7) −0.0057 (7) 0.0015 (7) N2 0.0590 (8) 0.0651 (9) 0.0467 (8) −0.0034 (7) 0.0024 (7) −0.0196 (7) C4 0.0427 (8) 0.0511 (9) 0.0387 (8) 0.0058 (7) 0.0031 (6) −0.0095 (7) C12 0.0418 (7) 0.0431 (7) 0.0318 (7) 0.0050 (6) −0.0003 (6) 0.0024 (6) N3 0.0430 (6) 0.0443 (6) 0.0321 (6) 0.0014 (5) 0.0008 (5) 0.0029 (5) C11 0.0424 (7) 0.0433 (8) 0.0303 (7) 0.0072 (6) 0.0043 (6) 0.0024 (6) C3 0.0438 (8) 0.0503 (8) 0.0321 (8) 0.0092 (6) 0.0043 (6) −0.0041 (6) C18 0.0381 (7) 0.0521 (8) 0.0409 (8) −0.0018 (6) −0.0005 (6) 0.0117 (7) C13 0.0442 (8) 0.0489 (8) 0.0299 (7) 0.0002 (6) −0.0014 (6) 0.0058 (6) C20 0.0497 (9) 0.0542 (10) 0.0883 (15) 0.0043 (7) 0.0029 (10) 0.0120 (10) C9 0.0421 (7) 0.0444 (8) 0.0304 (7) 0.0022 (6) 0.0033 (6) 0.0036 (6) C1 0.0691 (11) 0.0645 (11) 0.0417 (9) 0.0023 (8) 0.0123 (8) 0.0152 (8) C19 0.0458 (8) 0.0523 (9) 0.0566 (10) 0.0011 (7) 0.0016 (7) 0.0069 (8) C21 0.0561 (10) 0.0880 (15) 0.0590 (11) −0.0003 (10) −0.0157 (9) 0.0290 (10) C15 0.0649 (10) 0.0704 (11) 0.0375 (9) 0.0043 (8) −0.0026 (8) −0.0084 (8) C8 0.0417 (8) 0.0443 (8) 0.0405 (8) 0.0017 (6) 0.0039 (6) −0.0036 (6) C10 0.0398 (7) 0.0424 (8) 0.0297 (7) 0.0029 (6) 0.0016 (6) 0.0008 (6) C7 0.0633 (11) 0.0557 (10) 0.0557 (11) −0.0100 (8) 0.0084 (8) 0.0002 (8) C17 0.0441 (8) 0.0673 (10) 0.0433 (9) −0.0035 (7) −0.0061 (7) 0.0154 (8) C2 0.0767 (12) 0.0770 (12) 0.0302 (8) 0.0113 (10) 0.0063 (8) 0.0087 (8) C16 0.0627 (10) 0.0864 (13) 0.0314 (7) −0.0018 (10) −0.0115 (8) 0.0070 (8) C5 0.0764 (13) 0.0718 (12) 0.0679 (13) −0.0183 (10) 0.0033 (11) −0.0268 (11) C6 0.0809 (13) 0.0620 (12) 0.0756 (15) −0.0267 (10) 0.0108 (11) −0.0115 (10) C23 0.0529 (9) 0.0505 (9) 0.0387 (8) 0.0023 (7) 0.0061 (7) 0.0043 (7) C22 0.0569 (11) 0.0678 (13) 0.0932 (16) 0.0089 (9) −0.0099 (11) 0.0312 (12) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1670 .table-wrap} ----------------- ------------- ----------------- ------------- N4---C12 1.3548 (19) C20---H20 0.9300 N4---C9 1.3697 (19) C9---C10 1.375 (2) N4---H4 0.8600 C9---C8 1.427 (2) O1---C14 1.3476 (18) C1---C23 1.372 (2) O1---H1 0.8200 C1---C2 1.384 (3) N1---C2 1.324 (2) C1---H1A 0.9300 N1---C3 1.3563 (19) C19---H19 0.9300 C14---C13 1.370 (2) C21---C22 1.358 (3) C14---C15 1.414 (2) C21---C17 1.420 (2) N2---C5 1.316 (3) C21---H21 0.9300 N2---C4 1.356 (2) C15---C16 1.363 (3) C4---C8 1.411 (2) C15---H15 0.9300 C4---C3 1.459 (2) C8---C7 1.395 (2) C12---N3 1.3241 (18) C7---C6 1.369 (3) C12---C13 1.482 (2) C7---H7 0.9300 N3---C10 1.3912 (19) C17---C16 1.404 (3) C11---C23 1.400 (2) C2---H2 0.9300 C11---C3 1.413 (2) C16---H16 0.9300 C11---C10 1.4394 (19) C5---C6 1.391 (3) C18---C19 1.414 (2) C5---H5 0.9300 C18---C17 1.417 (2) C6---H6 0.9300 C18---C13 1.429 (2) C23---H23 0.9300 C20---C19 1.363 (3) C22---H22 0.9300 C20---C22 1.400 (3) C12---N4---C9 107.15 (12) C20---C19---H19 119.3 C12---N4---H4 126.4 C18---C19---H19 119.3 C9---N4---H4 126.4 C22---C21---C17 121.23 (19) C14---O1---H1 109.5 C22---C21---H21 119.4 C2---N1---C3 117.19 (16) C17---C21---H21 119.4 O1---C14---C13 117.60 (14) C16---C15---C14 119.76 (17) O1---C14---C15 122.28 (14) C16---C15---H15 120.1 C13---C14---C15 120.07 (14) C14---C15---H15 120.1 C5---N2---C4 117.62 (16) C7---C8---C4 118.98 (16) N2---C4---C8 121.68 (15) C7---C8---C9 124.73 (15) N2---C4---C3 117.67 (14) C4---C8---C9 116.26 (14) C8---C4---C3 120.64 (14) C9---C10---N3 109.79 (12) N3---C12---N4 112.31 (13) C9---C10---C11 120.66 (13) N3---C12---C13 127.13 (13) N3---C10---C11 129.55 (13) N4---C12---C13 120.47 (13) C6---C7---C8 118.34 (18) C12---N3---C10 104.67 (11) C6---C7---H7 120.8 C23---C11---C3 118.18 (14) C8---C7---H7 120.8 C23---C11---C10 124.68 (14) C16---C17---C18 118.50 (15) C3---C11---C10 117.14 (13) C16---C17---C21 122.93 (18) N1---C3---C11 122.32 (15) C18---C17---C21 118.57 (18) N1---C3---C4 116.56 (14) N1---C2---C1 124.50 (16) C11---C3---C4 121.11 (13) N1---C2---H2 117.8 C19---C18---C17 118.45 (15) C1---C2---H2 117.8 C19---C18---C13 122.67 (14) C15---C16---C17 122.14 (16) C17---C18---C13 118.88 (15) C15---C16---H16 118.9 C14---C13---C18 120.65 (14) C17---C16---H16 118.9 C14---C13---C12 120.25 (13) N2---C5---C6 124.30 (18) C18---C13---C12 118.97 (14) N2---C5---H5 117.9 C19---C20---C22 120.18 (19) C6---C5---H5 117.9 C19---C20---H20 119.9 C7---C6---C5 119.06 (18) C22---C20---H20 119.9 C7---C6---H6 120.5 N4---C9---C10 106.07 (13) C5---C6---H6 120.5 N4---C9---C8 129.82 (13) C1---C23---C11 118.80 (17) C10---C9---C8 124.02 (13) C1---C23---H23 120.6 C23---C1---C2 118.97 (17) C11---C23---H23 120.6 C23---C1---H1A 120.5 C21---C22---C20 120.22 (17) C2---C1---H1A 120.5 C21---C22---H22 119.9 C20---C19---C18 121.35 (17) C20---C22---H22 119.9 ----------------- ------------- ----------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2252 .table-wrap} ------------------ --------- --------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N4---H4···N2^i^ 0.86 2.17 2.9361 (19) 149 N4---H4···N1^i^ 0.86 2.50 3.191 (2) 138 O1---H1···N3^ii^ 0.82 2.01 2.7203 (17) 145 ------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (i) *x*, −*y*, *z*+1/2; (ii) *y*, −*x*+1/2, *z*+1/4. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ------------- ------------- N4---H4⋯N2^i^ 0.86 2.17 2.9361 (19) 149 N4---H4⋯N1^i^ 0.86 2.50 3.191 (2) 138 O1---H1⋯N3^ii^ 0.82 2.01 2.7203 (17) 145 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.598998

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052124/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o725", "authors": [ { "first": "Xiu-Yan", "last": "Wang" }, { "first": "Shuai", "last": "Ma" }, { "first": "Yu", "last": "He" } ] }

PMC3052125

Related literature {#sec1} ================== For the synthesis and pharmacological activity of compounds containing indole and tetrazole groups, see: Itoh *et al.* (1995[@bb3]); Semenov (2002[@bb5]). For the synthesis of 6-cyanoindole, a starting material for the title compound, see: Frederick (1949[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~9~H~7~N~5~·H~2~O*M* *~r~* = 203.21Monoclinic,*a* = 17.175 (3) Å*b* = 4.0653 (8) Å*c* = 14.421 (3) Åβ = 107.59 (3)°*V* = 959.8 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 0.10 mm^−1^*T* = 293 K0.20 × 0.05 × 0.05 mm ### Data collection {#sec2.1.2} Rigaku Mercury2 diffractometerAbsorption correction: multi-scan (*CrystalClear*; Rigaku, 2005[@bb4]) *T* ~min~ = 0.737, *T* ~max~ = 1.0007430 measured reflections1683 independent reflections945 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.120 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.066*wR*(*F* ^2^) = 0.131*S* = 1.011683 reflections144 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.15 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e466} Data collection: *CrystalClear* (Rigaku, 2005[@bb4]); cell refinement: *CrystalClear*; data reduction: *CrystalClear*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb6]) and *DIAMOND* (Brandenburg, 2006[@bb1]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003990/lh5195sup1.cif](http://dx.doi.org/10.1107/S1600536811003990/lh5195sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003990/lh5195Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003990/lh5195Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5195&file=lh5195sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5195sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5195&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5195](http://scripts.iucr.org/cgi-bin/sendsup?lh5195)). Comment ======= In recent decades, there have been some reports on the compounds which are synthesized by the combination of the tetrazole and indole rings (Itoh *et al.*,1995) and property studies reveals that these compounds always perform unique pharmacological activities (Semenov *et al.*, 2002). In order to obtain such compounds, we have attempted to synthesize the indole compounds with tetrazole as a substituent. Herein, we report the crystal structure of the title compound (I). The molecular structure of (1) is shown in Fig. 1. The indole unit is essentially planar, with a mean deviation of 0.007 (8)Å from the least-squares plane defined by the nine constituent atoms. The dihedral angle formed by the indole plane and the tetrazole ring is 1.82 (1)°. The crystal packing (Fig. 2) is stabilized by intermolecular O-H···N, N---H···O and N---H···N hydrogen bonds (Table 1). Further stabilization is provided by aromatic π--π interactions with a Cg1···Cg2(x, 1+y, z) distance of 3.698 (2) Å (Cg1 and Cg2 are the centroids of the N5/C4-C7 and C2-C4/C7-C9 rings, respectively). Experimental {#experimental} ============ All chemicals used (reagent grade) were commercially available. 6-Cyanoindole was synthesized following the methods described by Frederick (1949). To the stirring DMF solution of NaN~3~ and triethylamine, 6-cyanoindole was added. Then the mixture was heated to 120, about 1 h later, the solution was cooled to room temperature, and DMF was distilled in a vacuum. With some follow-up treatment, the crude product was recrystallized in methanol solution and seven days later, yellow prism crystal was obtained. Refinement {#refinement} ========== H atoms bound to C and N atoms were placed in calculated positions and refined using a riding model, with C---H = 0.94Å and *U*~iso~(H) =1.2*U*~eq~(C) or N---H = 0.86Å and *U*~iso~(H) =1.5*U*~eq~(N) . The H atoms of the water molecule were located in a difference map and refined freely. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. ::: ![](e-67-0o692-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds and π--π interactions shown as dashed lines. Only H atoms involed in hydrogen bonds are shown. CP denotes a ring centroid. \[Symmetry codes: (i) x, y-1,z; (ii) -x+1, y+1/2, -z+1/2; (iii)x, -y+1/2, z-1/2; (iv) x, -y+3/2, z-1/2\] ::: ![](e-67-0o692-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e139 .table-wrap} ------------------------- --------------------------------------- C~9~H~7~N~5~·H~2~O *F*(000) = 424 *M~r~* = 203.21 *D*~x~ = 1.406 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 2795 reflections *a* = 17.175 (3) Å θ = 3.1--27.5° *b* = 4.0653 (8) Å µ = 0.10 mm^−1^ *c* = 14.421 (3) Å *T* = 293 K β = 107.59 (3)° Needle, colorless *V* = 959.8 (3) Å^3^ 0.20 × 0.05 × 0.05 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} ------------------------------------------------------------------ ------------------------------------- Rigaku Mercury2 diffractometer 1683 independent reflections Radiation source: fine-focus sealed tube 945 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.120 Detector resolution: 13.6612 pixels mm^-1^ θ~max~ = 25.0°, θ~min~ = 3.2° CCD\_Profile\_fitting scans *h* = −20→20 Absorption correction: multi-scan (*CrystalClear*; Rigaku, 2005) *k* = −4→4 *T*~min~ = 0.737, *T*~max~ = 1.000 *l* = −17→17 7430 measured reflections ------------------------------------------------------------------ ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.066 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.131 H atoms treated by a mixture of independent and constrained refinement *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0398*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 1683 reflections (Δ/σ)~max~ \< 0.001 144 parameters Δρ~max~ = 0.15 e Å^−3^ 0 restraints Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e542 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e587 .table-wrap} ----- -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.0699 (2) −0.0517 (10) 0.1761 (2) 0.0720 (10) H1A 0.088 (2) −0.161 (10) 0.132 (3) 0.095 (17)\* H1B 0.033 (3) 0.048 (11) 0.147 (3) 0.10 (2)\* N1 0.19161 (16) −0.0016 (7) 0.5257 (2) 0.0453 (8) N2 0.12138 (17) −0.1708 (7) 0.5143 (2) 0.0518 (9) N3 0.08061 (16) −0.1971 (7) 0.4227 (2) 0.0509 (9) N4 0.12440 (15) −0.0389 (7) 0.37351 (19) 0.0415 (8) H4N 0.1108 −0.0189 0.3113 0.062\* N5 0.32387 (16) 0.6304 (7) 0.21458 (19) 0.0442 (8) H5N 0.2898 0.6026 0.1576 0.066\* C1 0.19266 (19) 0.0829 (8) 0.4367 (2) 0.0349 (8) C2 0.25600 (18) 0.2697 (8) 0.4122 (2) 0.0325 (8) C3 0.25007 (18) 0.3476 (8) 0.3176 (2) 0.0349 (8) H3 0.2048 0.2852 0.2666 0.042\* C4 0.31364 (19) 0.5219 (8) 0.3008 (2) 0.0346 (8) C5 0.3976 (2) 0.7902 (8) 0.2348 (2) 0.0436 (9) H5 0.4185 0.8834 0.1884 0.052\* C6 0.4357 (2) 0.7929 (8) 0.3320 (2) 0.0394 (9) H6 0.4862 0.8864 0.3636 0.047\* C7 0.38315 (18) 0.6239 (8) 0.3762 (2) 0.0339 (8) C8 0.38770 (19) 0.5422 (8) 0.4718 (2) 0.0403 (9) H8 0.4327 0.6052 0.5231 0.048\* C9 0.32503 (18) 0.3679 (8) 0.4894 (2) 0.0382 (9) H9 0.3280 0.3136 0.5530 0.046\* ----- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e927 .table-wrap} ---- ------------- ----------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.057 (2) 0.112 (3) 0.0391 (17) 0.0266 (19) 0.0019 (15) −0.0135 (18) N1 0.0348 (18) 0.058 (2) 0.0385 (18) −0.0073 (16) 0.0049 (14) 0.0043 (16) N2 0.0431 (19) 0.069 (2) 0.040 (2) −0.0068 (17) 0.0080 (16) 0.0037 (17) N3 0.0424 (19) 0.064 (2) 0.045 (2) −0.0102 (16) 0.0113 (16) 0.0047 (17) N4 0.0327 (16) 0.056 (2) 0.0329 (16) −0.0036 (15) 0.0047 (14) 0.0050 (15) N5 0.0454 (18) 0.057 (2) 0.0279 (16) 0.0038 (16) 0.0071 (13) 0.0024 (14) C1 0.032 (2) 0.037 (2) 0.032 (2) 0.0057 (16) 0.0037 (16) −0.0009 (16) C2 0.0322 (19) 0.034 (2) 0.0292 (19) 0.0031 (16) 0.0062 (15) −0.0008 (15) C3 0.0297 (18) 0.043 (2) 0.030 (2) 0.0060 (17) 0.0047 (15) −0.0045 (16) C4 0.038 (2) 0.040 (2) 0.0256 (19) 0.0101 (18) 0.0093 (16) 0.0014 (16) C5 0.038 (2) 0.046 (2) 0.048 (2) 0.0017 (19) 0.0154 (18) 0.0049 (19) C6 0.0371 (19) 0.045 (2) 0.034 (2) −0.0005 (18) 0.0075 (17) 0.0021 (17) C7 0.034 (2) 0.037 (2) 0.0288 (19) 0.0045 (16) 0.0072 (16) −0.0011 (16) C8 0.035 (2) 0.051 (2) 0.029 (2) −0.0065 (17) 0.0010 (16) −0.0045 (17) C9 0.041 (2) 0.047 (2) 0.0240 (19) −0.0011 (18) 0.0052 (16) −0.0010 (16) ---- ------------- ----------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1226 .table-wrap} ------------------- ------------ ------------------- ------------ O1---H1A 0.90 (4) C2---C9 1.417 (4) O1---H1B 0.77 (4) C3---C4 1.383 (4) N1---C1 1.333 (4) C3---H3 0.9300 N1---N2 1.355 (3) C4---C7 1.413 (4) N2---N3 1.298 (3) C5---C6 1.355 (4) N3---N4 1.344 (3) C5---H5 0.9300 N4---C1 1.344 (4) C6---C7 1.429 (4) N4---H4N 0.8600 C6---H6 0.9300 N5---C5 1.374 (4) C7---C8 1.397 (4) N5---C4 1.380 (4) C8---C9 1.375 (4) N5---H5N 0.8600 C8---H8 0.9300 C1---C2 1.456 (4) C9---H9 0.9300 C2---C3 1.373 (4) H1A---O1---H1B 106 (4) N5---C4---C3 130.1 (3) C1---N1---N2 106.5 (3) N5---C4---C7 107.0 (3) N3---N2---N1 110.6 (3) C3---C4---C7 122.9 (3) N2---N3---N4 106.4 (2) C6---C5---N5 110.5 (3) C1---N4---N3 109.3 (3) C6---C5---H5 124.8 C1---N4---H4N 125.3 N5---C5---H5 124.8 N3---N4---H4N 125.3 C5---C6---C7 106.6 (3) C5---N5---C4 108.7 (3) C5---C6---H6 126.7 C5---N5---H5N 125.7 C7---C6---H6 126.7 C4---N5---H5N 125.7 C8---C7---C4 118.2 (3) N1---C1---N4 107.2 (3) C8---C7---C6 134.5 (3) N1---C1---C2 126.7 (3) C4---C7---C6 107.3 (3) N4---C1---C2 126.2 (3) C9---C8---C7 119.4 (3) C3---C2---C9 120.6 (3) C9---C8---H8 120.3 C3---C2---C1 121.7 (3) C7---C8---H8 120.3 C9---C2---C1 117.7 (3) C8---C9---C2 121.0 (3) C2---C3---C4 117.8 (3) C8---C9---H9 119.5 C2---C3---H3 121.1 C2---C9---H9 119.5 C4---C3---H3 121.1 C1---N1---N2---N3 1.0 (4) C2---C3---C4---N5 179.7 (3) N1---N2---N3---N4 −0.8 (4) C2---C3---C4---C7 −0.6 (4) N2---N3---N4---C1 0.2 (4) C4---N5---C5---C6 −0.7 (4) N2---N1---C1---N4 −0.9 (4) N5---C5---C6---C7 0.1 (4) N2---N1---C1---C2 179.6 (3) N5---C4---C7---C8 −179.8 (3) N3---N4---C1---N1 0.4 (4) C3---C4---C7---C8 0.5 (5) N3---N4---C1---C2 179.9 (3) N5---C4---C7---C6 −0.8 (3) N1---C1---C2---C3 −178.9 (3) C3---C4---C7---C6 179.4 (3) N4---C1---C2---C3 1.6 (5) C5---C6---C7---C8 179.2 (3) N1---C1---C2---C9 1.5 (5) C5---C6---C7---C4 0.4 (3) N4---C1---C2---C9 −177.9 (3) C4---C7---C8---C9 −0.2 (5) C9---C2---C3---C4 0.4 (5) C6---C7---C8---C9 −178.8 (3) C1---C2---C3---C4 −179.1 (3) C7---C8---C9---C2 0.1 (5) C5---N5---C4---C3 −179.4 (3) C3---C2---C9---C8 −0.2 (5) C5---N5---C4---C7 0.9 (3) C1---C2---C9---C8 179.4 (3) ------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1701 .table-wrap} -------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1A···N2^i^ 0.90 (4) 2.07 (4) 2.957 (4) 169 (4) O1---H1B···N3^ii^ 0.76 (5) 2.17 (5) 2.927 (5) 172 (5) N4---H4N···O1 0.86 1.87 2.715 (4) 169 N5---H5N···N1^iii^ 0.86 2.17 3.019 (4) 171 -------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) *x*, −*y*−1/2, *z*−1/2; (ii) −*x*, *y*+1/2, −*z*+1/2; (iii) *x*, −*y*+1/2, *z*−1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- ---------- ---------- ----------- ------------- O1---H1*A*⋯N2^i^ 0.90 (4) 2.07 (4) 2.957 (4) 169 (4) O1---H1*B*⋯N3^ii^ 0.76 (5) 2.17 (5) 2.927 (5) 172 (5) N4---H4*N*⋯O1 0.86 1.87 2.715 (4) 169 N5---H5*N*⋯N1^iii^ 0.86 2.17 3.019 (4) 171 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.603536

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052125/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o692", "authors": [ { "first": "Yu-Hua", "last": "Ge" }, { "first": "Pei", "last": "Han" }, { "first": "Ping", "last": "Wei" }, { "first": "Ping-Kai", "last": "Ou-yang" } ] }

PMC3052126

Related literature {#sec1} ================== For a similar compound, see: Ali *et al.* (2011[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~47~H~58~N~6~O~6~*M* *~r~* = 802.99Triclinic,*a* = 19.4751 (6) Å*b* = 19.7067 (6) Å*c* = 20.6938 (7) Åα = 113.881 (3)°β = 113.983 (3)°γ = 95.343 (2)°*V* = 6311.7 (3) Å^3^*Z* = 6Mo *K*α radiationμ = 0.09 mm^−1^*T* = 100 K0.30 × 0.20 × 0.10 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb1]) *T* ~min~ = 0.975, *T* ~max~ = 0.99255060 measured reflections27973 independent reflections17926 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.044 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.070*wR*(*F* ^2^) = 0.185*S* = 1.0727973 reflections1642 parameters43 restraintsH-atom parameters constrainedΔρ~max~ = 1.01 e Å^−3^Δρ~min~ = −1.30 e Å^−3^ {#d5e402} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb1]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *X-SEED* (Barbour, 2001[@bb3]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb5]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006362/zs2091sup1.cif](http://dx.doi.org/10.1107/S1600536811006362/zs2091sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006362/zs2091Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006362/zs2091Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?zs2091&file=zs2091sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?zs2091sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?zs2091&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [ZS2091](http://scripts.iucr.org/cgi-bin/sendsup?zs2091)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= Some background on di(aryl)methane compounds having oxyacetate substituents was presented in an earlier report (Ali *et al.*, 2011). The title compound also has an N-heterocyclic substituent in the rings (Scheme I). The asymmetric unit of C~47~H~58~N~6~O~6~ consists of three molecules (Figs. 1 to 3), one of which is disordered in one *tert*-butyl group in a 1:1 ratio. For the molecule having the disordered *tert*-butyl group, the aryl rings make an angle of 115.3 (2) ° at the methylene carbon with one aryl ring aligned at 42.0 (1) ° with respect to the N-heterocyclic substituent and the other at 48.7 (1) ° with respect to its substituent. The two ordered molecules are disposed about a false center-of-inversion with the pairs of twist angles in the other two molecules different \[52.7 (1) and 61.7 (1)°; 29.1 (1) and 58.5 (1) °\]. Experimental {#experimental} ============ 6,6\'-Methylenebis(2-(2*H*-benzo\[*d*\]\[1,2,3\]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol) (0.10 g) and potassium carbonate (0.05 g) were dissolved in acetone (20 ml) at 323 K. Chloromethyl acetate (0.04 ml) was added and the reaction was stirred for 20 h. The progress of the reaction was monitored by thin layer chromatography (hexane:dichloromethane 60:40). The reaction was quenched by adding 1 M hydrochloric acid (10 ml). The aqueous phase was extracted with dichloromethane, the solvent evaporated and the crude product was recrystallized from dichloromethane (yield 80%). Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.98 Å, *U*~iso~(H) = 1.2 to 1.5*U*~eq~(C)\] and were included in the refinement in the riding model approximation. One of the *tert*-butyl groups of one of the three independent molecules is disordered over two positions; the disorder could not be refined, and was assumed to be a 1:1 type of disorder. The *C*--C~methyl~ bond distance was restrained to 1.50±0.01 and the *C*···C~methyl~ distance to 2.35±0.01 Å. The displacement parameters of the primed atoms were set to those of the unprimed ones, and the anisotropic displacement parameters were restrained to be nearly isotropic. The anisotropic displacement parameters of the O12 atom were similarly restrained as the ellipsoid was too elongated. The final difference Fourier map had a large peak 0.34 Å from H21F and a hole 0.23 Å from C23\'. One of the H-atoms of C23\' (*i.e.*, H23E) is close to an ordered H18B atom at a distance of 1.78 Å; the interaction is probably an artifact of the disorder. The \'huge\' version of *SHELXL97* was used for refining the structure. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of one of the three independent molecules of C47H58N6O6 at the 70% probability level, with hydrogen atoms drawn as spheres of arbitrary radius. The disorder in the tert-butyl group is not shown. ::: ![](e-67-0o722-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the second independent C47H58N6O6 molecule. The molecule is ordered. ::: ![](e-67-0o722-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the third independent C47H58N6O6 molecule. The molecule is ordered. ::: ![](e-67-0o722-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e201 .table-wrap} ----------------------- ---------------------------------------- C~47~H~58~N~6~O~6~ *Z* = 6 *M~r~* = 802.99 *F*(000) = 2580 Triclinic, *P*1 *D*~x~ = 1.268 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 19.4751 (6) Å Cell parameters from 12624 reflections *b* = 19.7067 (6) Å θ = 2.2--29.3° *c* = 20.6938 (7) Å µ = 0.09 mm^−1^ α = 113.881 (3)° *T* = 100 K β = 113.983 (3)° Block, colorless γ = 95.343 (2)° 0.30 × 0.20 × 0.10 mm *V* = 6311.7 (3) Å^3^ ----------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e337 .table-wrap} ------------------------------------------------------------------- --------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 27973 independent reflections Radiation source: SuperNova (Mo) X-ray Source 17926 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.044 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.2° ω scans *h* = −21→24 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −24→24 *T*~min~ = 0.975, *T*~max~ = 0.992 *l* = −26→26 55060 measured reflections ------------------------------------------------------------------- --------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e457 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.070 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.185 H-atom parameters constrained *S* = 1.07 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0603*P*)^2^ + 2.8599*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 27973 reflections (Δ/σ)~max~ = 0.001 1642 parameters Δρ~max~ = 1.01 e Å^−3^ 43 restraints Δρ~min~ = −1.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e616 .table-wrap} ------- -------------- -------------- --------------- -------------------- ------------ *x* *y* *z* *U*~iso~\*/*U*~eq~ Occ. (\<1) O1 0.73152 (10) 0.56720 (9) 0.77982 (10) 0.0207 (4) O2 0.85523 (11) 0.45200 (10) 0.82251 (11) 0.0260 (4) O3 0.81080 (14) 0.47752 (13) 0.71920 (13) 0.0428 (6) O4 0.90742 (10) 0.73822 (10) 0.70957 (10) 0.0220 (4) O5 1.05002 (10) 0.64625 (11) 0.68355 (11) 0.0276 (4) O6 1.00785 (14) 0.66968 (15) 0.77371 (14) 0.0510 (6) O7 0.39861 (9) 0.90251 (9) 0.28506 (10) 0.0199 (4) O8 0.28531 (11) 1.03092 (10) 0.32003 (11) 0.0292 (4) O9 0.30210 (12) 0.97055 (12) 0.21200 (12) 0.0371 (5) O10 0.57413 (10) 1.07394 (9) 0.21479 (10) 0.0216 (4) O11 0.48334 (11) 1.21343 (10) 0.18105 (11) 0.0278 (4) O12 0.48700 (18) 1.16101 (16) 0.25872 (17) 0.0727 (9) O13 0.75124 (10) 0.58181 (10) 0.28035 (10) 0.0217 (4) O14 0.61810 (10) 0.68267 (10) 0.31868 (11) 0.0267 (4) O15 0.67145 (16) 0.67580 (18) 0.24041 (17) 0.0712 (9) O16 0.92310 (10) 0.75874 (9) 0.21179 (10) 0.0210 (4) O17 0.80837 (11) 0.88388 (11) 0.18169 (11) 0.0305 (4) O18 0.86067 (14) 0.86029 (13) 0.28557 (12) 0.0450 (6) N1 0.62974 (12) 0.57433 (12) 0.85424 (13) 0.0223 (5) N2 0.69904 (11) 0.62930 (11) 0.91052 (12) 0.0183 (4) N3 0.72977 (12) 0.63815 (12) 0.98517 (12) 0.0212 (5) N4 0.91394 (12) 0.84301 (12) 0.63749 (12) 0.0222 (5) N5 0.85063 (11) 0.78069 (11) 0.58118 (12) 0.0183 (4) N6 0.82883 (12) 0.75881 (12) 0.50399 (12) 0.0204 (4) N7 0.40599 (12) 0.80571 (12) 0.36251 (13) 0.0227 (5) N8 0.46353 (11) 0.87336 (11) 0.41788 (12) 0.0183 (4) N9 0.47710 (12) 0.90290 (12) 0.49412 (12) 0.0211 (5) N10 0.59904 (12) 1.00301 (12) 0.01474 (12) 0.0217 (5) N11 0.62368 (12) 1.02063 (11) 0.09157 (12) 0.0193 (4) N12 0.68861 (12) 1.08076 (11) 0.14875 (13) 0.0233 (5) N13 0.74878 (12) 0.46790 (12) 0.34612 (12) 0.0211 (5) N14 0.80490 (11) 0.53557 (11) 0.40402 (12) 0.0180 (4) N15 0.81346 (12) 0.56327 (12) 0.47805 (12) 0.0204 (4) N16 1.01935 (12) 0.75529 (12) 0.13324 (13) 0.0230 (5) N17 0.95471 (12) 0.69412 (11) 0.07873 (12) 0.0184 (4) N18 0.92752 (12) 0.67388 (12) 0.00071 (12) 0.0226 (5) C1 0.61365 (15) 0.54357 (14) 0.89600 (16) 0.0216 (5) C2 0.54644 (16) 0.48354 (15) 0.86945 (18) 0.0274 (6) H2 0.5051 0.4564 0.8148 0.033\* C3 0.54465 (16) 0.46709 (15) 0.92705 (18) 0.0300 (6) H3 0.5008 0.4272 0.9118 0.036\* C4 0.60611 (16) 0.50762 (16) 1.00875 (18) 0.0294 (6) H4 0.6017 0.4943 1.0465 0.035\* C5 0.67123 (16) 0.56490 (16) 1.03508 (18) 0.0276 (6) H5 0.7121 0.5913 1.0899 0.033\* C6 0.67516 (14) 0.58322 (14) 0.97698 (15) 0.0204 (5) C7 0.73651 (14) 0.67915 (14) 0.89162 (15) 0.0178 (5) C8 0.75003 (14) 0.64661 (13) 0.82607 (15) 0.0181 (5) C9 0.78143 (14) 0.69602 (14) 0.80547 (14) 0.0185 (5) C10 0.79896 (14) 0.77637 (14) 0.85179 (15) 0.0204 (5) H10 0.8196 0.8098 0.8371 0.025\* C11 0.78746 (14) 0.80968 (14) 0.91889 (15) 0.0202 (5) C12 0.75618 (14) 0.75877 (14) 0.93844 (15) 0.0197 (5) H12 0.7484 0.7792 0.9843 0.024\* C13 0.77144 (15) 0.52843 (14) 0.82148 (15) 0.0206 (5) H13A 0.7328 0.4917 0.8211 0.025\* H13B 0.8097 0.5671 0.8785 0.025\* C14 0.81423 (15) 0.48462 (14) 0.78077 (15) 0.0217 (5) C15 0.89703 (17) 0.40463 (16) 0.78880 (18) 0.0319 (6) H15A 0.9193 0.3782 0.8199 0.048\* H15B 0.9398 0.4380 0.7914 0.048\* H15C 0.8603 0.3657 0.7322 0.048\* C16 0.81088 (16) 0.89799 (15) 0.97262 (16) 0.0260 (6) C17 0.74943 (16) 0.91726 (16) 1.00037 (17) 0.0307 (6) H17A 0.6963 0.8921 0.9532 0.046\* H17B 0.7596 0.9739 1.0273 0.046\* H17C 0.7533 0.8981 1.0382 0.046\* C18 0.8124 (3) 0.93979 (18) 0.9253 (2) 0.0612 (11) H18A 0.8562 0.9347 0.9136 0.092\* H18B 0.8195 0.9951 0.9574 0.092\* H18C 0.7624 0.9165 0.8743 0.092\* C19 0.89453 (14) 0.92226 (13) 1.04831 (15) 0.0367 (7) H19A 0.8865 0.8910 1.0734 0.044\* H19B 0.9283 0.9013 1.0251 0.044\* C20 0.94440 (15) 1.00016 (14) 1.11614 (16) 0.0381 (7) C21 0.9996 (3) 0.9840 (3) 1.1841 (2) 0.0383 (11) 0.50 H21A 1.0400 1.0329 1.2300 0.057\* 0.50 H21B 1.0252 0.9469 1.1630 0.057\* 0.50 H21C 0.9684 0.9621 1.2020 0.057\* 0.50 C22 0.9083 (3) 1.0520 (3) 1.1501 (3) 0.0340 (13) 0.50 H22A 0.9490 1.0967 1.2015 0.051\* 0.50 H22B 0.8718 1.0250 1.1598 0.051\* 0.50 H22C 0.8792 1.0703 1.1127 0.051\* 0.50 C23 1.0004 (3) 1.0347 (3) 1.0991 (3) 0.0436 (11) 0.50 H23A 1.0412 1.0808 1.1489 0.065\* 0.50 H23B 0.9724 1.0500 1.0584 0.065\* 0.50 H23C 1.0253 0.9964 1.0784 0.065\* 0.50 C21\' 1.0229 (2) 1.0038 (3) 1.1594 (3) 0.0383 (11) 0.50 H21D 1.0555 1.0585 1.1964 0.057\* 0.50 H21E 1.0422 0.9790 1.1215 0.057\* 0.50 H21F 1.0259 0.9766 1.1905 0.057\* 0.50 C22\' 0.9078 (3) 1.0294 (3) 1.1683 (3) 0.0340 (13) 0.50 H22D 0.9442 1.0788 1.2169 0.051\* 0.50 H22E 0.8963 0.9910 1.1842 0.051\* 0.50 H22F 0.8585 1.0378 1.1383 0.051\* 0.50 C23\' 0.9438 (3) 1.0593 (3) 1.0860 (3) 0.0436 (11) 0.50 H23D 0.9754 1.1115 1.1323 0.065\* 0.50 H23E 0.8894 1.0586 1.0568 0.065\* 0.50 H23F 0.9664 1.0456 1.0496 0.065\* 0.50 C24 0.80119 (15) 0.66235 (15) 0.73768 (15) 0.0232 (6) H24A 0.7768 0.6050 0.7074 0.028\* H24B 0.8592 0.6731 0.7619 0.028\* C25 0.77457 (14) 0.69317 (13) 0.67822 (14) 0.0183 (5) C26 0.82864 (14) 0.72557 (14) 0.66195 (15) 0.0188 (5) C27 0.79985 (14) 0.74635 (13) 0.60139 (14) 0.0178 (5) C28 0.72023 (14) 0.73713 (14) 0.55893 (15) 0.0196 (5) H28 0.7025 0.7510 0.5173 0.024\* C29 0.66579 (14) 0.70813 (14) 0.57598 (15) 0.0198 (5) C30 0.69503 (14) 0.68525 (14) 0.63524 (15) 0.0192 (5) H30 0.6588 0.6632 0.6467 0.023\* C31 0.95160 (14) 0.70682 (15) 0.67052 (15) 0.0219 (5) H31A 0.9835 0.7484 0.6698 0.026\* H31B 0.9153 0.6657 0.6139 0.026\* C32 1.00501 (15) 0.67286 (15) 0.71661 (15) 0.0223 (5) C33 1.10627 (16) 0.61398 (16) 0.72295 (17) 0.0292 (6) H33A 1.1392 0.6007 0.6972 0.044\* H33B 1.0779 0.5669 0.7181 0.044\* H33C 1.1399 0.6525 0.7803 0.044\* C34 0.57944 (14) 0.70691 (15) 0.53766 (15) 0.0215 (5) C35 0.56255 (16) 0.75144 (17) 0.60751 (17) 0.0317 (6) H35A 0.6016 0.8035 0.6443 0.048\* H35B 0.5659 0.7227 0.6372 0.048\* H35C 0.5094 0.7565 0.5854 0.048\* C36 0.56638 (15) 0.75121 (15) 0.49003 (16) 0.0239 (6) H36A 0.6004 0.8055 0.5264 0.036\* H36B 0.5110 0.7499 0.4665 0.036\* H36C 0.5794 0.7267 0.4466 0.036\* C37 0.52027 (15) 0.62313 (15) 0.48710 (15) 0.0245 (6) H37A 0.5399 0.5963 0.5191 0.029\* H37B 0.4697 0.6289 0.4855 0.029\* C38 0.49961 (15) 0.56603 (14) 0.39984 (16) 0.0221 (5) C39 0.45560 (16) 0.48536 (16) 0.37917 (18) 0.0327 (7) H39A 0.4910 0.4680 0.4144 0.049\* H39B 0.4380 0.4482 0.3225 0.049\* H39C 0.4096 0.4882 0.3874 0.049\* C40 0.57346 (16) 0.55975 (16) 0.39092 (17) 0.0297 (6) H40A 0.6006 0.6095 0.3995 0.045\* H40B 0.5580 0.5184 0.3364 0.045\* H40C 0.6090 0.5473 0.4311 0.045\* C41 0.44393 (16) 0.58696 (16) 0.33847 (16) 0.0296 (6) H41A 0.4725 0.6350 0.3450 0.044\* H41B 0.3991 0.5949 0.3477 0.044\* H41C 0.4246 0.5444 0.2835 0.044\* C42 0.93656 (14) 0.86362 (14) 0.59234 (16) 0.0215 (5) C43 0.99901 (16) 0.92642 (15) 0.61611 (17) 0.0272 (6) H43 1.0353 0.9616 0.6716 0.033\* C44 1.00488 (16) 0.93427 (16) 0.55597 (17) 0.0278 (6) H44 1.0463 0.9759 0.5700 0.033\* C45 0.95081 (15) 0.88207 (15) 0.47293 (17) 0.0261 (6) H45 0.9570 0.8903 0.4332 0.031\* C46 0.89053 (16) 0.82077 (15) 0.44817 (16) 0.0247 (6) H46 0.8547 0.7860 0.3925 0.030\* C47 0.88406 (14) 0.81159 (14) 0.51006 (15) 0.0191 (5) C48 0.37877 (14) 0.78967 (15) 0.40707 (15) 0.0211 (5) C49 0.31958 (15) 0.72354 (16) 0.38296 (17) 0.0256 (6) H49 0.2899 0.6832 0.3282 0.031\* C50 0.30716 (15) 0.72051 (16) 0.44238 (17) 0.0277 (6) H50 0.2682 0.6769 0.4287 0.033\* C51 0.35113 (16) 0.78092 (16) 0.52372 (18) 0.0284 (6) H51 0.3405 0.7764 0.5630 0.034\* C52 0.40800 (16) 0.84524 (16) 0.54826 (17) 0.0270 (6) H52 0.4368 0.8853 0.6032 0.032\* C53 0.42230 (15) 0.84974 (14) 0.48800 (16) 0.0213 (5) C54 0.51288 (14) 0.90783 (13) 0.39646 (15) 0.0174 (5) C55 0.47908 (14) 0.92018 (13) 0.33010 (14) 0.0176 (5) C56 0.52797 (14) 0.94924 (13) 0.30702 (14) 0.0177 (5) C57 0.60935 (14) 0.96519 (13) 0.35216 (15) 0.0190 (5) H57 0.6427 0.9839 0.3359 0.023\* C58 0.64420 (14) 0.95503 (13) 0.41988 (14) 0.0177 (5) C59 0.59371 (14) 0.92622 (13) 0.44160 (14) 0.0181 (5) H59 0.6152 0.9192 0.4879 0.022\* C60 0.36237 (15) 0.94849 (15) 0.32643 (15) 0.0227 (6) H60A 0.4035 0.9906 0.3807 0.027\* H60B 0.3276 0.9155 0.3336 0.027\* C61 0.31459 (14) 0.98341 (14) 0.27784 (15) 0.0218 (5) C62 0.23258 (16) 1.06462 (16) 0.27908 (18) 0.0327 (7) H62A 0.2064 1.0894 0.3098 0.049\* H62B 0.1927 1.0235 0.2247 0.049\* H62C 0.2629 1.1038 0.2750 0.049\* C63 0.73427 (14) 0.97618 (14) 0.47100 (15) 0.0200 (5) C64 0.77201 (15) 0.96583 (15) 0.41638 (16) 0.0246 (6) H64A 0.7442 0.9143 0.3680 0.037\* H64B 0.8277 0.9703 0.4461 0.037\* H64C 0.7681 1.0064 0.4003 0.037\* C65 0.75389 (15) 0.92045 (14) 0.50543 (16) 0.0241 (6) H65A 0.7271 0.8664 0.4614 0.036\* H65B 0.7360 0.9297 0.5453 0.036\* H65C 0.8111 0.9297 0.5316 0.036\* C66 0.76084 (14) 1.06264 (14) 0.53770 (15) 0.0214 (5) H66A 0.7497 1.0936 0.5092 0.026\* H66B 0.7245 1.0655 0.5603 0.026\* C67 0.84515 (15) 1.10735 (15) 0.61117 (16) 0.0236 (6) C68 0.86502 (17) 1.07819 (17) 0.67249 (17) 0.0359 (7) H68A 0.9133 1.1154 0.7226 0.054\* H68B 0.8731 1.0272 0.6502 0.054\* H68C 0.8214 1.0732 0.6841 0.054\* C69 0.84695 (17) 1.19215 (16) 0.65328 (18) 0.0368 (7) H69A 0.8339 1.2123 0.6150 0.055\* H69B 0.8999 1.2237 0.6994 0.055\* H69C 0.8083 1.1949 0.6724 0.055\* C70 0.91048 (16) 1.10661 (17) 0.58821 (18) 0.0341 (7) H70A 0.8980 1.1234 0.5473 0.051\* H70B 0.9144 1.0537 0.5663 0.051\* H70C 0.9609 1.1423 0.6364 0.051\* C71 0.49259 (15) 0.96613 (14) 0.23754 (14) 0.0198 (5) H71A 0.4999 1.0228 0.2599 0.024\* H71B 0.4350 0.9388 0.2057 0.024\* C72 0.52706 (14) 0.94218 (14) 0.18089 (14) 0.0174 (5) C73 0.56231 (14) 0.99634 (13) 0.16717 (14) 0.0180 (5) C74 0.58637 (14) 0.96950 (13) 0.10944 (14) 0.0176 (5) C75 0.57821 (14) 0.89075 (13) 0.06679 (14) 0.0182 (5) H75 0.5948 0.8741 0.0272 0.022\* C76 0.54607 (14) 0.83626 (14) 0.08144 (14) 0.0186 (5) C77 0.52043 (14) 0.86404 (14) 0.13834 (14) 0.0186 (5) H77 0.4972 0.8277 0.1486 0.022\* C78 0.54868 (15) 1.11972 (14) 0.17648 (15) 0.0208 (5) H78A 0.5147 1.0854 0.1174 0.025\* H78B 0.5950 1.1556 0.1858 0.025\* C79 0.50314 (16) 1.16571 (15) 0.21116 (16) 0.0250 (6) C80 0.43948 (16) 1.26189 (16) 0.20948 (17) 0.0290 (6) H80A 0.4242 1.2910 0.1799 0.044\* H80B 0.4726 1.2986 0.2675 0.044\* H80C 0.3920 1.2289 0.2003 0.044\* C81 0.54547 (15) 0.75078 (14) 0.04287 (15) 0.0200 (5) C82 0.58856 (15) 0.73806 (14) −0.00630 (16) 0.0231 (5) H82A 0.5636 0.7526 −0.0484 0.035\* H82B 0.5858 0.6830 −0.0316 0.035\* H82C 0.6440 0.7704 0.0295 0.035\* C83 0.59283 (16) 0.73531 (15) 0.11333 (16) 0.0268 (6) H83A 0.6455 0.7739 0.1487 0.040\* H83B 0.5979 0.6828 0.0915 0.040\* H83C 0.5651 0.7394 0.1444 0.040\* C84 0.46125 (15) 0.69253 (14) −0.00552 (15) 0.0228 (5) H84A 0.4676 0.6423 −0.0084 0.027\* H84B 0.4355 0.7113 0.0280 0.027\* C85 0.40164 (15) 0.67374 (15) −0.09188 (16) 0.0234 (6) C86 0.39489 (16) 0.74684 (16) −0.09990 (17) 0.0300 (6) H86A 0.4455 0.7747 −0.0901 0.045\* H86B 0.3812 0.7808 −0.0602 0.045\* H86C 0.3536 0.7319 −0.1546 0.045\* C87 0.42033 (16) 0.61839 (16) −0.15518 (16) 0.0289 (6) H87A 0.4678 0.6464 −0.1507 0.043\* H87B 0.3757 0.5991 −0.2095 0.043\* H87C 0.4295 0.5743 −0.1459 0.043\* C88 0.32046 (16) 0.63051 (16) −0.11078 (18) 0.0323 (7) H88A 0.3041 0.6655 −0.0743 0.049\* H88B 0.3238 0.5848 −0.1031 0.049\* H88C 0.2817 0.6137 −0.1670 0.049\* C89 0.65312 (15) 1.05808 (14) 0.02252 (16) 0.0222 (5) C90 0.66150 (16) 1.06765 (17) −0.03827 (18) 0.0292 (6) H90 0.6250 1.0344 −0.0941 0.035\* C91 0.72441 (17) 1.12683 (17) −0.01283 (19) 0.0330 (7) H91 0.7321 1.1346 −0.0521 0.040\* C92 0.77882 (17) 1.17726 (16) 0.07037 (19) 0.0324 (7) H92 0.8209 1.2187 0.0850 0.039\* C93 0.77294 (16) 1.16841 (15) 0.13056 (18) 0.0289 (6) H93 0.8101 1.2019 0.1862 0.035\* C94 0.70838 (15) 1.10661 (14) 0.10492 (16) 0.0230 (6) C95 0.71648 (14) 0.44991 (14) 0.38654 (15) 0.0202 (5) C96 0.65517 (15) 0.38359 (15) 0.35888 (17) 0.0262 (6) H96 0.6273 0.3438 0.3038 0.031\* C97 0.63829 (16) 0.37978 (16) 0.41544 (18) 0.0292 (6) H97 0.5974 0.3363 0.3991 0.035\* C98 0.67970 (16) 0.43859 (16) 0.49754 (18) 0.0300 (6) H98 0.6662 0.4329 0.5347 0.036\* C99 0.73827 (16) 0.50319 (15) 0.52530 (17) 0.0270 (6) H99 0.7653 0.5425 0.5806 0.032\* C100 0.75691 (15) 0.50890 (14) 0.46785 (16) 0.0213 (5) C101 0.85790 (14) 0.57377 (13) 0.38853 (14) 0.0173 (5) C102 0.83023 (14) 0.59678 (13) 0.32965 (14) 0.0179 (5) C103 0.88495 (14) 0.63311 (13) 0.31684 (14) 0.0180 (5) C104 0.96456 (14) 0.64260 (14) 0.36162 (15) 0.0196 (5) H10B 1.0013 0.6667 0.3521 0.024\* C105 0.99330 (14) 0.61855 (14) 0.41971 (15) 0.0198 (5) C106 0.93774 (14) 0.58513 (14) 0.43318 (15) 0.0202 (5) H10C 0.9549 0.5699 0.4737 0.024\* C107 0.70480 (14) 0.60898 (14) 0.31805 (15) 0.0205 (5) H10D 0.7390 0.6396 0.3775 0.025\* H10E 0.6648 0.5641 0.3056 0.025\* C108 0.66457 (15) 0.65916 (15) 0.28687 (16) 0.0240 (6) C109 0.57343 (16) 0.72991 (16) 0.29222 (17) 0.0283 (6) H10F 0.5436 0.7459 0.3212 0.042\* H10G 0.5367 0.6995 0.2339 0.042\* H10H 0.6098 0.7763 0.3037 0.042\* C110 1.08055 (14) 0.62109 (15) 0.45923 (16) 0.0232 (6) C111 1.09692 (16) 0.57357 (16) 0.38952 (17) 0.0310 (6) H11A 1.1503 0.5693 0.4122 0.047\* H11B 1.0925 0.6001 0.3575 0.047\* H11C 1.0583 0.5213 0.3547 0.047\* C112 1.09561 (15) 0.58104 (15) 0.51050 (16) 0.0250 (6) H11D 1.1517 0.5852 0.5361 0.038\* H11E 1.0639 0.5259 0.4761 0.038\* H11F 1.0809 0.6062 0.5525 0.038\* C113 1.13838 (15) 0.70448 (15) 0.50574 (16) 0.0257 (6) H11G 1.1183 0.7287 0.4711 0.031\* H11H 1.1894 0.6987 0.5087 0.031\* C114 1.15775 (16) 0.76523 (15) 0.59237 (17) 0.0269 (6) C115 1.08274 (16) 0.76919 (17) 0.59879 (18) 0.0340 (7) H11I 1.0963 0.8116 0.6521 0.051\* H11J 1.0573 0.7196 0.5918 0.051\* H11K 1.0465 0.7790 0.5565 0.051\* C116 1.19896 (17) 0.84487 (16) 0.60803 (18) 0.0326 (7) H11L 1.2170 0.8842 0.6641 0.049\* H11M 1.1618 0.8595 0.5711 0.049\* H11N 1.2444 0.8418 0.5989 0.049\* C117 1.21601 (17) 0.74909 (16) 0.65698 (17) 0.0319 (6) H11O 1.2350 0.7936 0.7108 0.048\* H11P 1.2609 0.7412 0.6478 0.048\* H11Q 1.1894 0.7021 0.6536 0.048\* C118 0.86001 (16) 0.66527 (15) 0.25868 (15) 0.0229 (6) H11R 0.8859 0.7224 0.2896 0.027\* H11S 0.8022 0.6561 0.2348 0.027\* C119 0.87942 (14) 0.63072 (14) 0.19051 (14) 0.0188 (5) C120 0.90770 (14) 0.67926 (13) 0.16729 (14) 0.0185 (5) C121 0.92115 (14) 0.64627 (14) 0.10172 (15) 0.0181 (5) C122 0.90568 (14) 0.56650 (13) 0.05851 (15) 0.0183 (5) H122 0.9137 0.5455 0.0129 0.022\* C123 0.87852 (14) 0.51687 (14) 0.08116 (15) 0.0185 (5) C124 0.86603 (14) 0.55079 (14) 0.14746 (15) 0.0199 (5) H124 0.8476 0.5179 0.1640 0.024\* C125 0.87848 (16) 0.79448 (14) 0.16965 (15) 0.0231 (6) H12D 0.8330 0.7541 0.1174 0.028\* H12E 0.9118 0.8240 0.1582 0.028\* C126 0.84944 (15) 0.84879 (14) 0.22054 (16) 0.0228 (5) C127 0.77839 (17) 0.93978 (16) 0.22430 (18) 0.0320 (7) H12F 0.7571 0.9680 0.1951 0.048\* H12G 0.8213 0.9768 0.2790 0.048\* H12H 0.7365 0.9124 0.2278 0.048\* C128 0.85950 (15) 0.42822 (14) 0.03149 (15) 0.0224 (5) C129 0.91741 (15) 0.41108 (14) −0.00175 (16) 0.0251 (6) H12I 0.9718 0.4395 0.0427 0.038\* H12J 0.9070 0.4279 −0.0425 0.038\* H12K 0.9104 0.3550 −0.0266 0.038\* C130 0.87054 (17) 0.39182 (15) 0.08632 (16) 0.0288 (6) H13C 0.9227 0.4198 0.1348 0.043\* H13D 0.8666 0.3369 0.0571 0.043\* H13E 0.8295 0.3954 0.1023 0.043\* C131 0.77218 (15) 0.40095 (14) −0.03718 (16) 0.0246 (6) H13F 0.7399 0.4126 −0.0098 0.030\* H13G 0.7700 0.4361 −0.0607 0.030\* C132 0.72797 (15) 0.31810 (15) −0.10902 (16) 0.0238 (6) C133 0.72679 (18) 0.25482 (16) −0.08463 (17) 0.0337 (7) H13H 0.7800 0.2500 −0.0620 0.051\* H13I 0.6901 0.2050 −0.1323 0.051\* H13J 0.7095 0.2688 −0.0439 0.051\* C134 0.64202 (16) 0.31588 (17) −0.15380 (18) 0.0361 (7) H13K 0.6110 0.2637 −0.2004 0.054\* H13L 0.6403 0.3544 −0.1725 0.054\* H13M 0.6199 0.3281 −0.1170 0.054\* C135 0.75888 (17) 0.29649 (16) −0.16929 (16) 0.0322 (7) H13N 0.8105 0.2890 −0.1454 0.048\* H13O 0.7643 0.3385 −0.1824 0.048\* H13P 0.7217 0.2481 −0.2188 0.048\* C136 1.03623 (15) 0.77844 (14) 0.08674 (15) 0.0210 (5) C137 1.09976 (16) 0.83920 (15) 0.10892 (18) 0.0277 (6) H137 1.1384 0.8731 0.1639 0.033\* C138 1.10304 (17) 0.84698 (16) 0.04738 (18) 0.0304 (6) H138 1.1445 0.8878 0.0600 0.036\* C139 1.04599 (17) 0.79553 (18) −0.03502 (18) 0.0339 (7) H139 1.0510 0.8028 −0.0758 0.041\* C140 0.98468 (16) 0.73641 (18) −0.05786 (18) 0.0324 (7) H140 0.9471 0.7023 −0.1132 0.039\* C141 0.97961 (15) 0.72811 (15) 0.00499 (15) 0.0221 (5) ------- -------------- -------------- --------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e5156 .table-wrap} ------- ------------- ------------- ------------- -------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0247 (9) 0.0205 (9) 0.0153 (9) 0.0093 (7) 0.0087 (8) 0.0078 (8) O2 0.0320 (10) 0.0294 (10) 0.0244 (10) 0.0183 (8) 0.0162 (9) 0.0155 (9) O3 0.0683 (16) 0.0575 (14) 0.0406 (13) 0.0451 (12) 0.0422 (13) 0.0352 (12) O4 0.0176 (9) 0.0315 (10) 0.0157 (9) 0.0107 (7) 0.0077 (8) 0.0103 (8) O5 0.0283 (10) 0.0399 (11) 0.0280 (11) 0.0207 (9) 0.0182 (9) 0.0214 (9) O6 0.0688 (16) 0.0883 (18) 0.0504 (15) 0.0602 (14) 0.0473 (14) 0.0545 (14) O7 0.0174 (9) 0.0257 (9) 0.0160 (9) 0.0088 (7) 0.0087 (8) 0.0084 (8) O8 0.0295 (10) 0.0328 (11) 0.0263 (11) 0.0179 (8) 0.0150 (9) 0.0123 (9) O9 0.0473 (13) 0.0524 (13) 0.0265 (11) 0.0323 (11) 0.0212 (10) 0.0251 (10) O10 0.0330 (10) 0.0176 (9) 0.0155 (9) 0.0111 (7) 0.0123 (8) 0.0080 (7) O11 0.0395 (11) 0.0307 (10) 0.0317 (11) 0.0222 (9) 0.0251 (10) 0.0209 (9) O12 0.137 (3) 0.096 (2) 0.094 (2) 0.0952 (19) 0.102 (2) 0.0811 (18) O13 0.0184 (9) 0.0306 (10) 0.0155 (9) 0.0113 (7) 0.0083 (8) 0.0096 (8) O14 0.0317 (10) 0.0347 (11) 0.0305 (11) 0.0217 (9) 0.0206 (9) 0.0225 (9) O15 0.094 (2) 0.133 (2) 0.103 (2) 0.096 (2) 0.0862 (19) 0.107 (2) O16 0.0269 (10) 0.0183 (9) 0.0150 (9) 0.0091 (7) 0.0080 (8) 0.0075 (7) O17 0.0409 (12) 0.0316 (11) 0.0276 (11) 0.0228 (9) 0.0182 (10) 0.0178 (9) O18 0.0670 (16) 0.0585 (14) 0.0292 (12) 0.0445 (12) 0.0306 (12) 0.0256 (11) N1 0.0236 (11) 0.0204 (11) 0.0210 (12) 0.0052 (9) 0.0131 (10) 0.0067 (9) N2 0.0188 (11) 0.0200 (11) 0.0161 (11) 0.0063 (8) 0.0097 (9) 0.0075 (9) N3 0.0223 (11) 0.0255 (11) 0.0190 (12) 0.0098 (9) 0.0112 (10) 0.0120 (10) N4 0.0182 (11) 0.0257 (12) 0.0173 (11) 0.0020 (9) 0.0063 (10) 0.0093 (10) N5 0.0164 (10) 0.0215 (11) 0.0143 (11) 0.0045 (8) 0.0058 (9) 0.0084 (9) N6 0.0246 (11) 0.0235 (11) 0.0176 (11) 0.0103 (9) 0.0128 (10) 0.0109 (9) N7 0.0208 (11) 0.0267 (12) 0.0193 (12) 0.0043 (9) 0.0095 (10) 0.0112 (10) N8 0.0188 (11) 0.0220 (11) 0.0163 (11) 0.0062 (8) 0.0091 (9) 0.0106 (9) N9 0.0274 (12) 0.0228 (11) 0.0187 (11) 0.0098 (9) 0.0147 (10) 0.0111 (9) N10 0.0247 (12) 0.0283 (12) 0.0183 (11) 0.0113 (9) 0.0121 (10) 0.0145 (10) N11 0.0240 (11) 0.0187 (11) 0.0198 (11) 0.0072 (9) 0.0130 (10) 0.0109 (9) N12 0.0285 (12) 0.0176 (11) 0.0233 (12) 0.0039 (9) 0.0148 (11) 0.0080 (10) N13 0.0182 (11) 0.0227 (11) 0.0195 (11) 0.0036 (9) 0.0072 (10) 0.0103 (9) N14 0.0200 (11) 0.0178 (10) 0.0158 (11) 0.0057 (8) 0.0085 (9) 0.0081 (9) N15 0.0233 (11) 0.0227 (11) 0.0183 (11) 0.0091 (9) 0.0128 (10) 0.0097 (9) N16 0.0258 (12) 0.0199 (11) 0.0192 (12) 0.0024 (9) 0.0111 (10) 0.0069 (9) N17 0.0199 (11) 0.0204 (11) 0.0146 (11) 0.0060 (8) 0.0078 (9) 0.0089 (9) N18 0.0225 (11) 0.0307 (12) 0.0167 (11) 0.0095 (9) 0.0102 (10) 0.0124 (10) C1 0.0237 (13) 0.0196 (13) 0.0269 (15) 0.0100 (10) 0.0164 (12) 0.0110 (11) C2 0.0268 (14) 0.0236 (14) 0.0327 (16) 0.0068 (11) 0.0180 (13) 0.0112 (12) C3 0.0332 (16) 0.0244 (14) 0.0466 (19) 0.0115 (12) 0.0284 (15) 0.0199 (14) C4 0.0368 (16) 0.0327 (15) 0.0424 (18) 0.0200 (13) 0.0291 (15) 0.0268 (14) C5 0.0299 (15) 0.0319 (15) 0.0350 (17) 0.0161 (12) 0.0197 (14) 0.0229 (13) C6 0.0204 (13) 0.0224 (13) 0.0242 (14) 0.0122 (10) 0.0123 (12) 0.0135 (11) C7 0.0163 (12) 0.0200 (12) 0.0195 (13) 0.0076 (10) 0.0090 (11) 0.0110 (11) C8 0.0172 (12) 0.0188 (12) 0.0167 (13) 0.0076 (10) 0.0075 (11) 0.0078 (10) C9 0.0172 (12) 0.0249 (13) 0.0133 (12) 0.0085 (10) 0.0065 (11) 0.0097 (11) C10 0.0205 (13) 0.0248 (13) 0.0211 (14) 0.0089 (10) 0.0109 (12) 0.0144 (11) C11 0.0193 (13) 0.0222 (13) 0.0171 (13) 0.0083 (10) 0.0069 (11) 0.0095 (11) C12 0.0214 (13) 0.0260 (13) 0.0157 (13) 0.0101 (10) 0.0117 (11) 0.0102 (11) C13 0.0271 (14) 0.0194 (13) 0.0183 (13) 0.0093 (10) 0.0118 (12) 0.0105 (11) C14 0.0231 (13) 0.0208 (13) 0.0172 (13) 0.0047 (10) 0.0088 (12) 0.0075 (11) C15 0.0319 (16) 0.0355 (16) 0.0344 (17) 0.0195 (13) 0.0188 (14) 0.0177 (14) C16 0.0336 (15) 0.0209 (13) 0.0229 (15) 0.0052 (11) 0.0159 (13) 0.0087 (12) C17 0.0257 (15) 0.0268 (15) 0.0293 (16) 0.0136 (12) 0.0084 (13) 0.0088 (13) C18 0.131 (4) 0.0254 (17) 0.053 (2) 0.028 (2) 0.061 (3) 0.0236 (17) C19 0.0235 (15) 0.0345 (16) 0.0385 (18) 0.0084 (12) 0.0163 (15) 0.0052 (14) C20 0.0406 (18) 0.0256 (15) 0.0368 (18) −0.0011 (13) 0.0236 (16) 0.0030 (13) C21 0.027 (2) 0.034 (2) 0.038 (3) 0.0084 (17) 0.0177 (19) 0.0016 (18) C22 0.0313 (18) 0.035 (3) 0.020 (2) 0.0114 (19) 0.0057 (18) 0.0071 (16) C23 0.040 (2) 0.045 (2) 0.038 (2) 0.0011 (18) 0.017 (2) 0.017 (2) C21\' 0.027 (2) 0.034 (2) 0.038 (3) 0.0084 (17) 0.0177 (19) 0.0016 (18) C22\' 0.0313 (18) 0.035 (3) 0.020 (2) 0.0114 (19) 0.0057 (18) 0.0071 (16) C23\' 0.040 (2) 0.045 (2) 0.038 (2) 0.0011 (18) 0.017 (2) 0.017 (2) C24 0.0272 (14) 0.0305 (14) 0.0214 (14) 0.0163 (11) 0.0150 (12) 0.0161 (12) C25 0.0232 (13) 0.0169 (12) 0.0160 (13) 0.0091 (10) 0.0114 (11) 0.0065 (10) C26 0.0194 (13) 0.0191 (12) 0.0152 (13) 0.0075 (10) 0.0078 (11) 0.0063 (10) C27 0.0203 (13) 0.0175 (12) 0.0166 (13) 0.0063 (10) 0.0108 (11) 0.0072 (10) C28 0.0221 (13) 0.0207 (13) 0.0157 (13) 0.0066 (10) 0.0092 (11) 0.0085 (11) C29 0.0205 (13) 0.0229 (13) 0.0167 (13) 0.0085 (10) 0.0107 (11) 0.0082 (11) C30 0.0209 (13) 0.0218 (13) 0.0198 (13) 0.0078 (10) 0.0132 (11) 0.0108 (11) C31 0.0194 (13) 0.0320 (14) 0.0186 (14) 0.0124 (11) 0.0114 (12) 0.0130 (12) C32 0.0220 (13) 0.0261 (14) 0.0190 (14) 0.0097 (11) 0.0100 (12) 0.0107 (11) C33 0.0291 (15) 0.0311 (15) 0.0329 (16) 0.0180 (12) 0.0154 (14) 0.0183 (13) C34 0.0190 (13) 0.0293 (14) 0.0197 (14) 0.0091 (11) 0.0103 (12) 0.0137 (12) C35 0.0261 (15) 0.0461 (18) 0.0264 (16) 0.0161 (13) 0.0162 (14) 0.0163 (14) C36 0.0216 (13) 0.0278 (14) 0.0240 (14) 0.0117 (11) 0.0107 (12) 0.0136 (12) C37 0.0197 (13) 0.0324 (15) 0.0240 (15) 0.0058 (11) 0.0113 (12) 0.0157 (12) C38 0.0232 (13) 0.0237 (13) 0.0230 (14) 0.0087 (11) 0.0130 (12) 0.0126 (11) C39 0.0289 (15) 0.0346 (16) 0.0366 (17) 0.0075 (12) 0.0160 (14) 0.0195 (14) C40 0.0291 (15) 0.0312 (15) 0.0334 (17) 0.0100 (12) 0.0184 (14) 0.0164 (13) C41 0.0313 (15) 0.0275 (15) 0.0224 (15) 0.0109 (12) 0.0085 (13) 0.0098 (12) C42 0.0201 (13) 0.0247 (13) 0.0241 (14) 0.0091 (10) 0.0130 (12) 0.0129 (12) C43 0.0246 (14) 0.0276 (14) 0.0256 (15) 0.0058 (11) 0.0105 (13) 0.0118 (12) C44 0.0261 (14) 0.0298 (15) 0.0358 (17) 0.0098 (12) 0.0184 (14) 0.0198 (13) C45 0.0302 (15) 0.0319 (15) 0.0326 (16) 0.0158 (12) 0.0216 (14) 0.0220 (13) C46 0.0304 (15) 0.0266 (14) 0.0236 (15) 0.0122 (11) 0.0169 (13) 0.0131 (12) C47 0.0200 (13) 0.0211 (13) 0.0232 (14) 0.0110 (10) 0.0140 (12) 0.0124 (11) C48 0.0179 (13) 0.0295 (14) 0.0226 (14) 0.0106 (11) 0.0104 (12) 0.0170 (12) C49 0.0196 (13) 0.0305 (15) 0.0313 (16) 0.0091 (11) 0.0123 (13) 0.0189 (13) C50 0.0239 (14) 0.0335 (15) 0.0413 (18) 0.0133 (12) 0.0210 (14) 0.0256 (14) C51 0.0345 (16) 0.0352 (16) 0.0379 (17) 0.0202 (13) 0.0267 (15) 0.0260 (14) C52 0.0353 (16) 0.0305 (15) 0.0299 (16) 0.0162 (12) 0.0240 (14) 0.0180 (13) C53 0.0238 (13) 0.0249 (13) 0.0242 (14) 0.0133 (11) 0.0159 (12) 0.0143 (12) C54 0.0214 (13) 0.0165 (12) 0.0190 (13) 0.0070 (10) 0.0131 (11) 0.0090 (10) C55 0.0169 (12) 0.0174 (12) 0.0164 (13) 0.0070 (9) 0.0072 (11) 0.0070 (10) C56 0.0243 (13) 0.0158 (12) 0.0146 (13) 0.0092 (10) 0.0109 (11) 0.0068 (10) C57 0.0217 (13) 0.0195 (13) 0.0189 (13) 0.0075 (10) 0.0120 (11) 0.0098 (11) C58 0.0215 (13) 0.0168 (12) 0.0157 (13) 0.0088 (10) 0.0095 (11) 0.0077 (10) C59 0.0221 (13) 0.0187 (12) 0.0150 (13) 0.0085 (10) 0.0102 (11) 0.0081 (10) C60 0.0212 (13) 0.0322 (14) 0.0192 (14) 0.0121 (11) 0.0129 (12) 0.0123 (12) C61 0.0192 (13) 0.0245 (14) 0.0176 (14) 0.0056 (10) 0.0085 (11) 0.0077 (11) C62 0.0299 (16) 0.0292 (15) 0.0354 (17) 0.0148 (12) 0.0132 (14) 0.0143 (14) C63 0.0185 (13) 0.0249 (13) 0.0185 (13) 0.0095 (10) 0.0095 (11) 0.0113 (11) C64 0.0199 (13) 0.0317 (15) 0.0234 (14) 0.0091 (11) 0.0127 (12) 0.0120 (12) C65 0.0227 (14) 0.0232 (13) 0.0261 (15) 0.0092 (11) 0.0100 (12) 0.0132 (12) C66 0.0209 (13) 0.0207 (13) 0.0188 (13) 0.0074 (10) 0.0081 (11) 0.0079 (11) C67 0.0213 (13) 0.0251 (14) 0.0198 (14) 0.0058 (11) 0.0074 (12) 0.0100 (11) C68 0.0342 (17) 0.0361 (17) 0.0224 (16) 0.0016 (13) 0.0037 (14) 0.0135 (14) C69 0.0335 (17) 0.0295 (16) 0.0305 (17) 0.0099 (13) 0.0086 (14) 0.0071 (13) C70 0.0234 (15) 0.0407 (17) 0.0293 (17) 0.0033 (12) 0.0102 (13) 0.0133 (14) C71 0.0235 (13) 0.0241 (13) 0.0158 (13) 0.0102 (10) 0.0113 (11) 0.0106 (11) C72 0.0169 (12) 0.0241 (13) 0.0131 (12) 0.0074 (10) 0.0075 (11) 0.0102 (11) C73 0.0199 (12) 0.0192 (12) 0.0141 (12) 0.0078 (10) 0.0071 (11) 0.0083 (10) C74 0.0217 (13) 0.0173 (12) 0.0186 (13) 0.0076 (10) 0.0110 (11) 0.0113 (11) C75 0.0198 (12) 0.0207 (13) 0.0140 (12) 0.0064 (10) 0.0089 (11) 0.0077 (10) C76 0.0196 (13) 0.0209 (13) 0.0147 (13) 0.0067 (10) 0.0075 (11) 0.0089 (11) C77 0.0196 (12) 0.0213 (13) 0.0177 (13) 0.0043 (10) 0.0089 (11) 0.0124 (11) C78 0.0270 (14) 0.0198 (13) 0.0197 (14) 0.0091 (10) 0.0121 (12) 0.0121 (11) C79 0.0349 (15) 0.0258 (14) 0.0199 (14) 0.0135 (12) 0.0166 (13) 0.0118 (12) C80 0.0322 (15) 0.0341 (15) 0.0317 (16) 0.0208 (12) 0.0197 (14) 0.0189 (13) C81 0.0261 (13) 0.0193 (13) 0.0165 (13) 0.0075 (10) 0.0104 (12) 0.0103 (11) C82 0.0267 (14) 0.0201 (13) 0.0233 (14) 0.0109 (11) 0.0128 (12) 0.0099 (11) C83 0.0339 (15) 0.0233 (14) 0.0250 (15) 0.0108 (12) 0.0121 (13) 0.0151 (12) C84 0.0293 (14) 0.0196 (13) 0.0227 (14) 0.0081 (11) 0.0144 (12) 0.0113 (11) C85 0.0233 (14) 0.0270 (14) 0.0203 (14) 0.0094 (11) 0.0109 (12) 0.0111 (12) C86 0.0305 (15) 0.0325 (15) 0.0309 (16) 0.0139 (12) 0.0126 (14) 0.0202 (13) C87 0.0290 (15) 0.0321 (15) 0.0194 (14) 0.0106 (12) 0.0100 (13) 0.0087 (12) C88 0.0280 (15) 0.0335 (16) 0.0345 (17) 0.0072 (12) 0.0153 (14) 0.0161 (14) C89 0.0240 (13) 0.0251 (14) 0.0303 (15) 0.0150 (11) 0.0172 (13) 0.0188 (12) C90 0.0319 (15) 0.0404 (16) 0.0337 (17) 0.0190 (13) 0.0202 (14) 0.0280 (14) C91 0.0382 (17) 0.0417 (17) 0.050 (2) 0.0229 (14) 0.0324 (16) 0.0357 (16) C92 0.0360 (16) 0.0286 (15) 0.053 (2) 0.0139 (13) 0.0324 (16) 0.0254 (15) C93 0.0311 (15) 0.0231 (14) 0.0384 (17) 0.0089 (11) 0.0216 (14) 0.0151 (13) C94 0.0287 (14) 0.0229 (13) 0.0301 (15) 0.0136 (11) 0.0211 (13) 0.0157 (12) C95 0.0170 (12) 0.0252 (13) 0.0218 (14) 0.0096 (10) 0.0097 (11) 0.0135 (11) C96 0.0205 (13) 0.0270 (14) 0.0312 (16) 0.0061 (11) 0.0100 (13) 0.0173 (13) C97 0.0260 (14) 0.0323 (15) 0.0428 (18) 0.0112 (12) 0.0202 (14) 0.0260 (14) C98 0.0353 (16) 0.0379 (16) 0.0404 (18) 0.0209 (13) 0.0279 (15) 0.0278 (15) C99 0.0370 (16) 0.0280 (14) 0.0289 (15) 0.0147 (12) 0.0237 (14) 0.0164 (13) C100 0.0231 (13) 0.0221 (13) 0.0275 (15) 0.0119 (10) 0.0151 (12) 0.0157 (12) C101 0.0184 (12) 0.0176 (12) 0.0155 (13) 0.0050 (10) 0.0091 (11) 0.0070 (10) C102 0.0190 (12) 0.0183 (12) 0.0147 (12) 0.0083 (10) 0.0083 (11) 0.0058 (10) C103 0.0250 (13) 0.0162 (12) 0.0153 (13) 0.0093 (10) 0.0124 (11) 0.0066 (10) C104 0.0215 (13) 0.0205 (13) 0.0182 (13) 0.0067 (10) 0.0111 (11) 0.0092 (11) C105 0.0204 (13) 0.0200 (13) 0.0153 (13) 0.0049 (10) 0.0089 (11) 0.0056 (10) C106 0.0239 (13) 0.0205 (13) 0.0163 (13) 0.0072 (10) 0.0098 (11) 0.0092 (11) C107 0.0208 (13) 0.0238 (13) 0.0181 (13) 0.0079 (10) 0.0109 (11) 0.0096 (11) C108 0.0230 (14) 0.0321 (15) 0.0227 (14) 0.0113 (11) 0.0128 (12) 0.0160 (12) C109 0.0339 (16) 0.0319 (15) 0.0308 (16) 0.0205 (12) 0.0187 (14) 0.0202 (13) C110 0.0186 (13) 0.0300 (14) 0.0219 (14) 0.0073 (11) 0.0106 (12) 0.0129 (12) C111 0.0258 (15) 0.0386 (16) 0.0274 (16) 0.0111 (12) 0.0153 (13) 0.0124 (13) C112 0.0221 (14) 0.0263 (14) 0.0270 (15) 0.0092 (11) 0.0115 (12) 0.0132 (12) C113 0.0194 (13) 0.0337 (15) 0.0272 (15) 0.0083 (11) 0.0118 (12) 0.0172 (13) C114 0.0281 (15) 0.0283 (14) 0.0287 (16) 0.0115 (12) 0.0163 (13) 0.0146 (13) C115 0.0328 (16) 0.0335 (16) 0.0362 (18) 0.0110 (13) 0.0209 (15) 0.0132 (14) C116 0.0336 (16) 0.0283 (15) 0.0325 (17) 0.0075 (12) 0.0154 (14) 0.0130 (13) C117 0.0343 (16) 0.0306 (15) 0.0226 (15) 0.0098 (12) 0.0101 (14) 0.0097 (13) C118 0.0304 (14) 0.0272 (14) 0.0227 (14) 0.0153 (11) 0.0185 (13) 0.0151 (12) C119 0.0169 (12) 0.0250 (13) 0.0159 (13) 0.0083 (10) 0.0079 (11) 0.0109 (11) C120 0.0193 (12) 0.0192 (13) 0.0149 (13) 0.0078 (10) 0.0072 (11) 0.0073 (10) C121 0.0163 (12) 0.0220 (13) 0.0167 (13) 0.0065 (10) 0.0061 (11) 0.0118 (11) C122 0.0190 (12) 0.0207 (13) 0.0145 (13) 0.0072 (10) 0.0086 (11) 0.0072 (10) C123 0.0160 (12) 0.0197 (12) 0.0161 (13) 0.0057 (10) 0.0051 (11) 0.0084 (10) C124 0.0193 (13) 0.0243 (13) 0.0213 (14) 0.0078 (10) 0.0100 (11) 0.0152 (11) C125 0.0321 (15) 0.0221 (13) 0.0176 (13) 0.0114 (11) 0.0117 (12) 0.0116 (11) C126 0.0243 (14) 0.0224 (13) 0.0193 (14) 0.0069 (11) 0.0091 (12) 0.0098 (11) C127 0.0327 (16) 0.0299 (15) 0.0340 (17) 0.0179 (13) 0.0167 (14) 0.0140 (13) C128 0.0266 (14) 0.0200 (13) 0.0204 (14) 0.0063 (10) 0.0129 (12) 0.0083 (11) C129 0.0249 (14) 0.0216 (13) 0.0256 (15) 0.0089 (11) 0.0119 (13) 0.0087 (12) C130 0.0374 (16) 0.0245 (14) 0.0254 (15) 0.0107 (12) 0.0148 (14) 0.0133 (12) C131 0.0247 (14) 0.0246 (14) 0.0247 (15) 0.0089 (11) 0.0119 (12) 0.0118 (12) C132 0.0235 (14) 0.0247 (14) 0.0220 (14) 0.0089 (11) 0.0114 (12) 0.0098 (12) C133 0.0415 (17) 0.0249 (15) 0.0269 (16) 0.0056 (13) 0.0136 (14) 0.0099 (13) C134 0.0290 (16) 0.0323 (16) 0.0311 (17) 0.0079 (12) 0.0096 (14) 0.0072 (14) C135 0.0294 (15) 0.0341 (16) 0.0214 (15) 0.0041 (12) 0.0108 (13) 0.0063 (13) C136 0.0259 (14) 0.0217 (13) 0.0234 (14) 0.0119 (11) 0.0165 (12) 0.0123 (11) C137 0.0305 (15) 0.0240 (14) 0.0325 (16) 0.0081 (11) 0.0199 (14) 0.0126 (12) C138 0.0322 (16) 0.0317 (15) 0.0440 (19) 0.0153 (12) 0.0278 (15) 0.0224 (14) C139 0.0342 (16) 0.0529 (19) 0.0401 (19) 0.0209 (14) 0.0264 (15) 0.0346 (16) C140 0.0288 (15) 0.0521 (19) 0.0257 (16) 0.0155 (13) 0.0162 (14) 0.0235 (15) C141 0.0224 (13) 0.0305 (14) 0.0227 (14) 0.0134 (11) 0.0141 (12) 0.0167 (12) ------- ------------- ------------- ------------- -------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e7918 .table-wrap} ------------------------- -------------- --------------------------- ------------- O1---C8 1.377 (3) C57---C58 1.394 (3) O1---C13 1.425 (3) C57---H57 0.9500 O2---C14 1.335 (3) C58---C59 1.398 (3) O2---C15 1.448 (3) C58---C63 1.539 (3) O3---C14 1.197 (3) C59---H59 0.9500 O4---C26 1.374 (3) C60---C61 1.506 (3) O4---C31 1.427 (3) C60---H60A 0.9900 O5---C32 1.339 (3) C60---H60B 0.9900 O5---C33 1.447 (3) C62---H62A 0.9800 O6---C32 1.188 (3) C62---H62B 0.9800 O7---C55 1.376 (3) C62---H62C 0.9800 O7---C60 1.426 (3) C63---C65 1.533 (3) O8---C61 1.344 (3) C63---C64 1.541 (3) O8---C62 1.445 (3) C63---C66 1.558 (3) O9---C61 1.192 (3) C64---H64A 0.9800 O10---C73 1.376 (3) C64---H64B 0.9800 O10---C78 1.425 (3) C64---H64C 0.9800 O11---C79 1.330 (3) C65---H65A 0.9800 O11---C80 1.447 (3) C65---H65B 0.9800 O12---C79 1.181 (3) C65---H65C 0.9800 O13---C102 1.375 (3) C66---C67 1.549 (3) O13---C107 1.428 (3) C66---H66A 0.9900 O14---C108 1.335 (3) C66---H66B 0.9900 O14---C109 1.449 (3) C67---C68 1.524 (4) O15---C108 1.184 (3) C67---C70 1.528 (4) O16---C120 1.383 (3) C67---C69 1.529 (4) O16---C125 1.417 (3) C68---H68A 0.9800 O17---C126 1.340 (3) C68---H68B 0.9800 O17---C127 1.443 (3) C68---H68C 0.9800 O18---C126 1.189 (3) C69---H69A 0.9800 N1---N2 1.334 (3) C69---H69B 0.9800 N1---C1 1.350 (3) C69---H69C 0.9800 N2---N3 1.336 (3) C70---H70A 0.9800 N2---C7 1.435 (3) C70---H70B 0.9800 N3---C6 1.350 (3) C70---H70C 0.9800 N4---N5 1.333 (3) C71---C72 1.516 (3) N4---C42 1.357 (3) C71---H71A 0.9900 N5---N6 1.332 (3) C71---H71B 0.9900 N5---C27 1.432 (3) C72---C77 1.391 (3) N6---C47 1.353 (3) C72---C73 1.400 (3) N7---N8 1.337 (3) C73---C74 1.384 (3) N7---C48 1.354 (3) C74---C75 1.394 (3) N8---N9 1.337 (3) C75---C76 1.389 (3) N8---C54 1.432 (3) C75---H75 0.9500 N9---C53 1.352 (3) C76---C77 1.394 (3) N10---N11 1.334 (3) C76---C81 1.541 (3) N10---C89 1.349 (3) C77---H77 0.9500 N11---N12 1.331 (3) C78---C79 1.505 (3) N11---C74 1.437 (3) C78---H78A 0.9900 N12---C94 1.361 (3) C78---H78B 0.9900 N13---N14 1.334 (3) C80---H80A 0.9800 N13---C95 1.359 (3) C80---H80B 0.9800 N14---N15 1.331 (3) C80---H80C 0.9800 N14---C101 1.433 (3) C81---C82 1.526 (3) N15---C100 1.347 (3) C81---C83 1.545 (3) N16---N17 1.331 (3) C81---C84 1.547 (3) N16---C136 1.352 (3) C82---H82A 0.9800 N17---N18 1.338 (3) C82---H82B 0.9800 N17---C121 1.430 (3) C82---H82C 0.9800 N18---C141 1.352 (3) C83---H83A 0.9800 C1---C6 1.410 (4) C83---H83B 0.9800 C1---C2 1.420 (3) C83---H83C 0.9800 C2---C3 1.368 (4) C84---C85 1.541 (4) C2---H2 0.9500 C84---H84A 0.9900 C3---C4 1.419 (4) C84---H84B 0.9900 C3---H3 0.9500 C85---C86 1.527 (4) C4---C5 1.361 (4) C85---C87 1.531 (3) C4---H4 0.9500 C85---C88 1.534 (3) C5---C6 1.415 (3) C86---H86A 0.9800 C5---H5 0.9500 C86---H86B 0.9800 C7---C12 1.379 (3) C86---H86C 0.9800 C7---C8 1.392 (3) C87---H87A 0.9800 C8---C9 1.393 (3) C87---H87B 0.9800 C9---C10 1.395 (3) C87---H87C 0.9800 C9---C24 1.513 (3) C88---H88A 0.9800 C10---C11 1.397 (3) C88---H88B 0.9800 C10---H10 0.9500 C88---H88C 0.9800 C11---C12 1.399 (3) C89---C94 1.406 (4) C11---C16 1.532 (3) C89---C90 1.413 (3) C12---H12 0.9500 C90---C91 1.360 (4) C13---C14 1.505 (3) C90---H90 0.9500 C13---H13A 0.9900 C91---C92 1.418 (4) C13---H13B 0.9900 C91---H91 0.9500 C15---H15A 0.9800 C92---C93 1.372 (4) C15---H15B 0.9800 C92---H92 0.9500 C15---H15C 0.9800 C93---C94 1.412 (3) C16---C18 1.520 (4) C93---H93 0.9500 C16---C17 1.540 (4) C95---C100 1.404 (3) C16---C19 1.584 (4) C95---C96 1.417 (3) C17---H17A 0.9800 C96---C97 1.365 (4) C17---H17B 0.9800 C96---H96 0.9500 C17---H17C 0.9800 C97---C98 1.413 (4) C18---H18A 0.9800 C97---H97 0.9500 C18---H18B 0.9800 C98---C99 1.363 (4) C18---H18C 0.9800 C98---H98 0.9500 C19---C20 1.463 (3) C99---C100 1.417 (3) C19---H19A 0.9900 C99---H99 0.9500 C19---H19B 0.9900 C101---C106 1.386 (3) C20---C21\' 1.399 (3) C101---C102 1.393 (3) C20---C22 1.408 (3) C102---C103 1.400 (3) C20---C23 1.466 (3) C103---C104 1.391 (3) C20---C22\' 1.485 (3) C103---C118 1.512 (3) C20---C23\' 1.527 (4) C104---C105 1.395 (3) C20---C21 1.560 (4) C104---H10B 0.9500 C21---H21A 0.9800 C105---C106 1.394 (3) C21---H21B 0.9800 C105---C110 1.543 (3) C21---H21C 0.9800 C106---H10C 0.9500 C22---H22A 0.9800 C107---C108 1.503 (3) C22---H22B 0.9800 C107---H10D 0.9900 C22---H22C 0.9800 C107---H10E 0.9900 C23---H23A 0.9800 C109---H10F 0.9800 C23---H23B 0.9800 C109---H10G 0.9800 C23---H23C 0.9800 C109---H10H 0.9800 C21\'---H21D 0.9800 C110---C112 1.518 (3) C21\'---H21E 0.9800 C110---C113 1.546 (3) C21\'---H21F 0.9800 C110---C111 1.548 (3) C22\'---H22D 0.9800 C111---H11A 0.9800 C22\'---H22E 0.9800 C111---H11B 0.9800 C22\'---H22F 0.9800 C111---H11C 0.9800 C23\'---H23D 0.9800 C112---H11D 0.9800 C23\'---H23E 0.9800 C112---H11E 0.9800 C23\'---H23F 0.9800 C112---H11F 0.9800 C24---C25 1.516 (3) C113---C114 1.555 (4) C24---H24A 0.9900 C113---H11G 0.9900 C24---H24B 0.9900 C113---H11H 0.9900 C25---C30 1.392 (3) C114---C115 1.526 (4) C25---C26 1.402 (3) C114---C117 1.534 (4) C26---C27 1.393 (3) C114---C116 1.535 (4) C27---C28 1.386 (3) C115---H11I 0.9800 C28---C29 1.389 (3) C115---H11J 0.9800 C28---H28 0.9500 C115---H11K 0.9800 C29---C30 1.400 (3) C116---H11L 0.9800 C29---C34 1.533 (3) C116---H11M 0.9800 C30---H30 0.9500 C116---H11N 0.9800 C31---C32 1.510 (3) C117---H11O 0.9800 C31---H31A 0.9900 C117---H11P 0.9800 C31---H31B 0.9900 C117---H11Q 0.9800 C33---H33A 0.9800 C118---C119 1.517 (3) C33---H33B 0.9800 C118---H11R 0.9900 C33---H33C 0.9800 C118---H11S 0.9900 C34---C36 1.527 (3) C119---C120 1.392 (3) C34---C35 1.543 (3) C119---C124 1.393 (3) C34---C37 1.554 (3) C120---C121 1.393 (3) C35---H35A 0.9800 C121---C122 1.384 (3) C35---H35B 0.9800 C122---C123 1.390 (3) C35---H35C 0.9800 C122---H122 0.9500 C36---H36A 0.9800 C123---C124 1.395 (3) C36---H36B 0.9800 C123---C128 1.537 (3) C36---H36C 0.9800 C124---H124 0.9500 C37---C38 1.539 (4) C125---C126 1.503 (3) C37---H37A 0.9900 C125---H12D 0.9900 C37---H37B 0.9900 C125---H12E 0.9900 C38---C39 1.531 (3) C127---H12F 0.9800 C38---C41 1.532 (4) C127---H12G 0.9800 C38---C40 1.532 (3) C127---H12H 0.9800 C39---H39A 0.9800 C128---C130 1.529 (3) C39---H39B 0.9800 C128---C129 1.540 (3) C39---H39C 0.9800 C128---C131 1.564 (4) C40---H40A 0.9800 C129---H12I 0.9800 C40---H40B 0.9800 C129---H12J 0.9800 C40---H40C 0.9800 C129---H12K 0.9800 C41---H41A 0.9800 C130---H13C 0.9800 C41---H41B 0.9800 C130---H13D 0.9800 C41---H41C 0.9800 C130---H13E 0.9800 C42---C47 1.404 (4) C131---C132 1.533 (3) C42---C43 1.412 (3) C131---H13F 0.9900 C43---C44 1.362 (4) C131---H13G 0.9900 C43---H43 0.9500 C132---C133 1.525 (4) C44---C45 1.420 (4) C132---C135 1.526 (3) C44---H44 0.9500 C132---C134 1.535 (4) C45---C46 1.359 (3) C133---H13H 0.9800 C45---H45 0.9500 C133---H13I 0.9800 C46---C47 1.415 (3) C133---H13J 0.9800 C46---H46 0.9500 C134---H13K 0.9800 C48---C53 1.407 (4) C134---H13L 0.9800 C48---C49 1.415 (3) C134---H13M 0.9800 C49---C50 1.368 (4) C135---H13N 0.9800 C49---H49 0.9500 C135---H13O 0.9800 C50---C51 1.414 (4) C135---H13P 0.9800 C50---H50 0.9500 C136---C141 1.408 (4) C51---C52 1.361 (4) C136---C137 1.412 (3) C51---H51 0.9500 C137---C138 1.368 (4) C52---C53 1.417 (3) C137---H137 0.9500 C52---H52 0.9500 C138---C139 1.421 (4) C54---C59 1.381 (3) C138---H138 0.9500 C54---C55 1.394 (3) C139---C140 1.358 (4) C55---C56 1.397 (3) C139---H139 0.9500 C56---C57 1.396 (3) C140---C141 1.415 (3) C56---C71 1.509 (3) C140---H140 0.9500 C8---O1---C13 115.89 (19) H66A---C66---H66B 106.4 C14---O2---C15 116.1 (2) C68---C67---C70 108.0 (2) C26---O4---C31 118.18 (18) C68---C67---C69 107.7 (2) C32---O5---C33 116.10 (19) C70---C67---C69 107.7 (2) C55---O7---C60 115.42 (18) C68---C67---C66 113.2 (2) C61---O8---C62 115.8 (2) C70---C67---C66 114.0 (2) C73---O10---C78 118.62 (18) C69---C67---C66 106.0 (2) C79---O11---C80 116.64 (19) C67---C68---H68A 109.5 C102---O13---C107 117.83 (18) C67---C68---H68B 109.5 C108---O14---C109 116.40 (19) H68A---C68---H68B 109.5 C120---O16---C125 116.33 (18) C67---C68---H68C 109.5 C126---O17---C127 116.0 (2) H68A---C68---H68C 109.5 N2---N1---C1 102.3 (2) H68B---C68---H68C 109.5 N1---N2---N3 117.50 (19) C67---C69---H69A 109.5 N1---N2---C7 120.6 (2) C67---C69---H69B 109.5 N3---N2---C7 121.9 (2) H69A---C69---H69B 109.5 N2---N3---C6 102.4 (2) C67---C69---H69C 109.5 N5---N4---C42 102.41 (19) H69A---C69---H69C 109.5 N6---N5---N4 117.38 (19) H69B---C69---H69C 109.5 N6---N5---C27 120.12 (19) C67---C70---H70A 109.5 N4---N5---C27 121.66 (19) C67---C70---H70B 109.5 N5---N6---C47 102.60 (19) H70A---C70---H70B 109.5 N8---N7---C48 102.3 (2) C67---C70---H70C 109.5 N9---N8---N7 117.42 (19) H70A---C70---H70C 109.5 N9---N8---C54 122.1 (2) H70B---C70---H70C 109.5 N7---N8---C54 120.21 (19) C56---C71---C72 114.9 (2) N8---N9---C53 102.43 (19) C56---C71---H71A 108.6 N11---N10---C89 102.1 (2) C72---C71---H71A 108.6 N12---N11---N10 117.80 (19) C56---C71---H71B 108.6 N12---N11---C74 121.9 (2) C72---C71---H71B 108.6 N10---N11---C74 119.8 (2) H71A---C71---H71B 107.5 N11---N12---C94 102.3 (2) C77---C72---C73 118.7 (2) N14---N13---C95 102.39 (19) C77---C72---C71 119.6 (2) N15---N14---N13 117.36 (19) C73---C72---C71 121.6 (2) N15---N14---C101 121.24 (19) O10---C73---C74 123.8 (2) N13---N14---C101 121.22 (19) O10---C73---C72 117.6 (2) N14---N15---C100 102.6 (2) C74---C73---C72 118.6 (2) N17---N16---C136 102.5 (2) C73---C74---C75 121.6 (2) N16---N17---N18 117.54 (19) C73---C74---N11 122.6 (2) N16---N17---C121 121.1 (2) C75---C74---N11 115.7 (2) N18---N17---C121 120.91 (19) C76---C75---C74 120.9 (2) N17---N18---C141 102.2 (2) C76---C75---H75 119.6 N1---C1---C6 109.0 (2) C74---C75---H75 119.6 N1---C1---C2 129.3 (3) C75---C76---C77 116.7 (2) C6---C1---C2 121.7 (2) C75---C76---C81 122.0 (2) C3---C2---C1 116.2 (3) C77---C76---C81 121.1 (2) C3---C2---H2 121.9 C72---C77---C76 123.4 (2) C1---C2---H2 121.9 C72---C77---H77 118.3 C2---C3---C4 122.2 (2) C76---C77---H77 118.3 C2---C3---H3 118.9 O10---C78---C79 108.83 (19) C4---C3---H3 118.9 O10---C78---H78A 109.9 C5---C4---C3 122.4 (2) C79---C78---H78A 109.9 C5---C4---H4 118.8 O10---C78---H78B 109.9 C3---C4---H4 118.8 C79---C78---H78B 109.9 C4---C5---C6 116.9 (3) H78A---C78---H78B 108.3 C4---C5---H5 121.6 O12---C79---O11 124.0 (2) C6---C5---H5 121.6 O12---C79---C78 125.5 (2) N3---C6---C1 108.7 (2) O11---C79---C78 110.5 (2) N3---C6---C5 130.5 (2) O11---C80---H80A 109.5 C1---C6---C5 120.7 (2) O11---C80---H80B 109.5 C12---C7---C8 121.9 (2) H80A---C80---H80B 109.5 C12---C7---N2 118.2 (2) O11---C80---H80C 109.5 C8---C7---N2 119.8 (2) H80A---C80---H80C 109.5 O1---C8---C7 122.1 (2) H80B---C80---H80C 109.5 O1---C8---C9 119.1 (2) C82---C81---C76 111.15 (19) C7---C8---C9 118.8 (2) C82---C81---C83 106.8 (2) C8---C9---C10 118.8 (2) C76---C81---C83 106.7 (2) C8---C9---C24 119.7 (2) C82---C81---C84 113.2 (2) C10---C9---C24 121.3 (2) C76---C81---C84 112.3 (2) C9---C10---C11 122.8 (2) C83---C81---C84 106.26 (19) C9---C10---H10 118.6 C81---C82---H82A 109.5 C11---C10---H10 118.6 C81---C82---H82B 109.5 C10---C11---C12 117.2 (2) H82A---C82---H82B 109.5 C10---C11---C16 122.9 (2) C81---C82---H82C 109.5 C12---C11---C16 119.8 (2) H82A---C82---H82C 109.5 C7---C12---C11 120.4 (2) H82B---C82---H82C 109.5 C7---C12---H12 119.8 C81---C83---H83A 109.5 C11---C12---H12 119.8 C81---C83---H83B 109.5 O1---C13---C14 109.56 (19) H83A---C83---H83B 109.5 O1---C13---H13A 109.8 C81---C83---H83C 109.5 C14---C13---H13A 109.8 H83A---C83---H83C 109.5 O1---C13---H13B 109.8 H83B---C83---H83C 109.5 C14---C13---H13B 109.8 C85---C84---C81 122.9 (2) H13A---C13---H13B 108.2 C85---C84---H84A 106.6 O3---C14---O2 124.4 (2) C81---C84---H84A 106.6 O3---C14---C13 126.0 (2) C85---C84---H84B 106.6 O2---C14---C13 109.5 (2) C81---C84---H84B 106.6 O2---C15---H15A 109.5 H84A---C84---H84B 106.6 O2---C15---H15B 109.5 C86---C85---C87 110.5 (2) H15A---C15---H15B 109.5 C86---C85---C88 107.6 (2) O2---C15---H15C 109.5 C87---C85---C88 106.7 (2) H15A---C15---H15C 109.5 C86---C85---C84 112.8 (2) H15B---C15---H15C 109.5 C87---C85---C84 111.8 (2) C18---C16---C11 110.3 (2) C88---C85---C84 107.1 (2) C18---C16---C17 107.8 (3) C85---C86---H86A 109.5 C11---C16---C17 109.6 (2) C85---C86---H86B 109.5 C18---C16---C19 112.5 (3) H86A---C86---H86B 109.5 C11---C16---C19 106.4 (2) C85---C86---H86C 109.5 C17---C16---C19 110.2 (2) H86A---C86---H86C 109.5 C16---C17---H17A 109.5 H86B---C86---H86C 109.5 C16---C17---H17B 109.5 C85---C87---H87A 109.5 H17A---C17---H17B 109.5 C85---C87---H87B 109.5 C16---C17---H17C 109.5 H87A---C87---H87B 109.5 H17A---C17---H17C 109.5 C85---C87---H87C 109.5 H17B---C17---H17C 109.5 H87A---C87---H87C 109.5 C16---C18---H18A 109.5 H87B---C87---H87C 109.5 C16---C18---H18B 109.5 C85---C88---H88A 109.5 H18A---C18---H18B 109.5 C85---C88---H88B 109.5 C16---C18---H18C 109.5 H88A---C88---H88B 109.5 H18A---C18---H18C 109.5 C85---C88---H88C 109.5 H18B---C18---H18C 109.5 H88A---C88---H88C 109.5 C20---C19---C16 128.6 (2) H88B---C88---H88C 109.5 C20---C19---H19A 105.1 N10---C89---C94 109.4 (2) C16---C19---H19A 105.1 N10---C89---C90 129.3 (3) C20---C19---H19B 105.1 C94---C89---C90 121.2 (2) C16---C19---H19B 105.1 C91---C90---C89 116.7 (3) H19A---C19---H19B 105.9 C91---C90---H90 121.7 C22---C20---C19 118.6 (3) C89---C90---H90 121.7 C22---C20---C23 114.0 (3) C90---C91---C92 122.2 (3) C19---C20---C23 110.2 (3) C90---C91---H91 118.9 C21\'---C20---C22\' 113.0 (3) C92---C91---H91 118.9 C19---C20---C22\' 109.9 (3) C93---C92---C91 122.4 (2) C21\'---C20---C23\' 108.2 (3) C93---C92---H92 118.8 C19---C20---C23\' 110.3 (3) C91---C92---H92 118.8 C22\'---C20---C23\' 101.6 (3) C92---C93---C94 116.0 (3) C22---C20---C21 106.2 (3) C92---C93---H93 122.0 C19---C20---C21 103.8 (2) C94---C93---H93 122.0 C23---C20---C21 102.1 (3) N12---C94---C89 108.3 (2) C20---C21---H21A 109.5 N12---C94---C93 130.1 (3) C20---C21---H21B 109.5 C89---C94---C93 121.5 (2) C20---C21---H21C 109.5 N13---C95---C100 108.5 (2) C20---C22---H22A 109.5 N13---C95---C96 130.0 (2) C20---C22---H22B 109.5 C100---C95---C96 121.4 (2) C20---C22---H22C 109.5 C97---C96---C95 116.6 (3) C20---C23---H23A 109.5 C97---C96---H96 121.7 C20---C23---H23B 109.5 C95---C96---H96 121.7 C20---C23---H23C 109.5 C96---C97---C98 122.0 (2) C20---C21\'---H21D 109.5 C96---C97---H97 119.0 C20---C21\'---H21E 109.5 C98---C97---H97 119.0 H21D---C21\'---H21E 109.5 C99---C98---C97 122.4 (2) C20---C21\'---H21F 109.5 C99---C98---H98 118.8 H21D---C21\'---H21F 109.5 C97---C98---H98 118.8 H21E---C21\'---H21F 109.5 C98---C99---C100 116.9 (3) C20---C22\'---H22D 109.5 C98---C99---H99 121.6 C20---C22\'---H22E 109.5 C100---C99---H99 121.6 H22D---C22\'---H22E 109.5 N15---C100---C95 109.1 (2) C20---C22\'---H22F 109.5 N15---C100---C99 130.1 (2) H22D---C22\'---H22F 109.5 C95---C100---C99 120.7 (2) H22E---C22\'---H22F 109.5 C106---C101---C102 121.3 (2) C20---C23\'---H23D 109.5 C106---C101---N14 117.2 (2) C20---C23\'---H23E 109.5 C102---C101---N14 121.4 (2) H23D---C23\'---H23E 109.5 O13---C102---C101 123.1 (2) C20---C23\'---H23F 109.5 O13---C102---C103 118.2 (2) H23D---C23\'---H23F 109.5 C101---C102---C103 118.7 (2) H23E---C23\'---H23F 109.5 C104---C103---C102 118.7 (2) C9---C24---C25 115.3 (2) C104---C103---C118 119.6 (2) C9---C24---H24A 108.4 C102---C103---C118 121.7 (2) C25---C24---H24A 108.4 C103---C104---C105 123.5 (2) C9---C24---H24B 108.4 C103---C104---H10B 118.3 C25---C24---H24B 108.4 C105---C104---H10B 118.3 H24A---C24---H24B 107.5 C106---C105---C104 116.5 (2) C30---C25---C26 119.0 (2) C106---C105---C110 122.5 (2) C30---C25---C24 120.2 (2) C104---C105---C110 120.7 (2) C26---C25---C24 120.7 (2) C101---C106---C105 121.3 (2) O4---C26---C27 124.0 (2) C101---C106---H10C 119.4 O4---C26---C25 117.7 (2) C105---C106---H10C 119.4 C27---C26---C25 118.3 (2) O13---C107---C108 108.92 (19) C28---C27---C26 121.5 (2) O13---C107---H10D 109.9 C28---C27---N5 116.2 (2) C108---C107---H10D 109.9 C26---C27---N5 122.3 (2) O13---C107---H10E 109.9 C27---C28---C29 121.4 (2) C108---C107---H10E 109.9 C27---C28---H28 119.3 H10D---C107---H10E 108.3 C29---C28---H28 119.3 O15---C108---O14 123.7 (2) C28---C29---C30 116.5 (2) O15---C108---C107 126.2 (2) C28---C29---C34 122.5 (2) O14---C108---C107 110.1 (2) C30---C29---C34 120.8 (2) O14---C109---H10F 109.5 C25---C30---C29 123.2 (2) O14---C109---H10G 109.5 C25---C30---H30 118.4 H10F---C109---H10G 109.5 C29---C30---H30 118.4 O14---C109---H10H 109.5 O4---C31---C32 108.40 (19) H10F---C109---H10H 109.5 O4---C31---H31A 110.0 H10G---C109---H10H 109.5 C32---C31---H31A 110.0 C112---C110---C105 111.5 (2) O4---C31---H31B 110.0 C112---C110---C113 112.7 (2) C32---C31---H31B 110.0 C105---C110---C113 112.6 (2) H31A---C31---H31B 108.4 C112---C110---C111 106.7 (2) O6---C32---O5 124.1 (2) C105---C110---C111 106.8 (2) O6---C32---C31 126.2 (2) C113---C110---C111 106.0 (2) O5---C32---C31 109.7 (2) C110---C111---H11A 109.5 O5---C33---H33A 109.5 C110---C111---H11B 109.5 O5---C33---H33B 109.5 H11A---C111---H11B 109.5 H33A---C33---H33B 109.5 C110---C111---H11C 109.5 O5---C33---H33C 109.5 H11A---C111---H11C 109.5 H33A---C33---H33C 109.5 H11B---C111---H11C 109.5 H33B---C33---H33C 109.5 C110---C112---H11D 109.5 C36---C34---C29 111.0 (2) C110---C112---H11E 109.5 C36---C34---C35 106.5 (2) H11D---C112---H11E 109.5 C29---C34---C35 107.2 (2) C110---C112---H11F 109.5 C36---C34---C37 112.8 (2) H11D---C112---H11F 109.5 C29---C34---C37 112.7 (2) H11E---C112---H11F 109.5 C35---C34---C37 106.1 (2) C110---C113---C114 122.9 (2) C34---C35---H35A 109.5 C110---C113---H11G 106.6 C34---C35---H35B 109.5 C114---C113---H11G 106.6 H35A---C35---H35B 109.5 C110---C113---H11H 106.6 C34---C35---H35C 109.5 C114---C113---H11H 106.6 H35A---C35---H35C 109.5 H11G---C113---H11H 106.6 H35B---C35---H35C 109.5 C115---C114---C117 111.3 (2) C34---C36---H36A 109.5 C115---C114---C116 108.5 (2) C34---C36---H36B 109.5 C117---C114---C116 107.1 (2) H36A---C36---H36B 109.5 C115---C114---C113 111.3 (2) C34---C36---H36C 109.5 C117---C114---C113 111.6 (2) H36A---C36---H36C 109.5 C116---C114---C113 106.7 (2) H36B---C36---H36C 109.5 C114---C115---H11I 109.5 C38---C37---C34 123.7 (2) C114---C115---H11J 109.5 C38---C37---H37A 106.4 H11I---C115---H11J 109.5 C34---C37---H37A 106.4 C114---C115---H11K 109.5 C38---C37---H37B 106.4 H11I---C115---H11K 109.5 C34---C37---H37B 106.4 H11J---C115---H11K 109.5 H37A---C37---H37B 106.5 C114---C116---H11L 109.5 C39---C38---C41 107.1 (2) C114---C116---H11M 109.5 C39---C38---C40 107.6 (2) H11L---C116---H11M 109.5 C41---C38---C40 110.3 (2) C114---C116---H11N 109.5 C39---C38---C37 107.3 (2) H11L---C116---H11N 109.5 C41---C38---C37 112.1 (2) H11M---C116---H11N 109.5 C40---C38---C37 112.2 (2) C114---C117---H11O 109.5 C38---C39---H39A 109.5 C114---C117---H11P 109.5 C38---C39---H39B 109.5 H11O---C117---H11P 109.5 H39A---C39---H39B 109.5 C114---C117---H11Q 109.5 C38---C39---H39C 109.5 H11O---C117---H11Q 109.5 H39A---C39---H39C 109.5 H11P---C117---H11Q 109.5 H39B---C39---H39C 109.5 C103---C118---C119 114.9 (2) C38---C40---H40A 109.5 C103---C118---H11R 108.5 C38---C40---H40B 109.5 C119---C118---H11R 108.5 H40A---C40---H40B 109.5 C103---C118---H11S 108.5 C38---C40---H40C 109.5 C119---C118---H11S 108.5 H40A---C40---H40C 109.5 H11R---C118---H11S 107.5 H40B---C40---H40C 109.5 C120---C119---C124 118.7 (2) C38---C41---H41A 109.5 C120---C119---C118 119.5 (2) C38---C41---H41B 109.5 C124---C119---C118 121.7 (2) H41A---C41---H41B 109.5 O16---C120---C119 118.4 (2) C38---C41---H41C 109.5 O16---C120---C121 122.7 (2) H41A---C41---H41C 109.5 C119---C120---C121 118.9 (2) H41B---C41---H41C 109.5 C122---C121---C120 121.5 (2) N4---C42---C47 108.8 (2) C122---C121---N17 117.5 (2) N4---C42---C43 130.5 (2) C120---C121---N17 121.0 (2) C47---C42---C43 120.7 (2) C121---C122---C123 120.7 (2) C44---C43---C42 117.0 (3) C121---C122---H122 119.6 C44---C43---H43 121.5 C123---C122---H122 119.6 C42---C43---H43 121.5 C122---C123---C124 117.2 (2) C43---C44---C45 121.9 (2) C122---C123---C128 120.3 (2) C43---C44---H44 119.1 C124---C123---C128 122.5 (2) C45---C44---H44 119.1 C119---C124---C123 123.0 (2) C46---C45---C44 122.5 (2) C119---C124---H124 118.5 C46---C45---H45 118.8 C123---C124---H124 118.5 C44---C45---H45 118.8 O16---C125---C126 109.18 (19) C45---C46---C47 116.2 (2) O16---C125---H12D 109.8 C45---C46---H46 121.9 C126---C125---H12D 109.8 C47---C46---H46 121.9 O16---C125---H12E 109.8 N6---C47---C42 108.8 (2) C126---C125---H12E 109.8 N6---C47---C46 129.4 (2) H12D---C125---H12E 108.3 C42---C47---C46 121.7 (2) O18---C126---O17 124.0 (2) N7---C48---C53 109.0 (2) O18---C126---C125 126.5 (2) N7---C48---C49 129.2 (2) O17---C126---C125 109.5 (2) C53---C48---C49 121.7 (2) O17---C127---H12F 109.5 C50---C49---C48 116.7 (3) O17---C127---H12G 109.5 C50---C49---H49 121.6 H12F---C127---H12G 109.5 C48---C49---H49 121.6 O17---C127---H12H 109.5 C49---C50---C51 121.4 (2) H12F---C127---H12H 109.5 C49---C50---H50 119.3 H12G---C127---H12H 109.5 C51---C50---H50 119.3 C130---C128---C123 109.4 (2) C52---C51---C50 122.9 (2) C130---C128---C129 107.8 (2) C52---C51---H51 118.5 C123---C128---C129 109.54 (19) C50---C51---H51 118.5 C130---C128---C131 113.5 (2) C51---C52---C53 116.9 (3) C123---C128---C131 104.0 (2) C51---C52---H52 121.6 C129---C128---C131 112.5 (2) C53---C52---H52 121.6 C128---C129---H12I 109.5 N9---C53---C48 108.9 (2) C128---C129---H12J 109.5 N9---C53---C52 130.6 (2) H12I---C129---H12J 109.5 C48---C53---C52 120.4 (2) C128---C129---H12K 109.5 C59---C54---C55 121.5 (2) H12I---C129---H12K 109.5 C59---C54---N8 118.4 (2) H12J---C129---H12K 109.5 C55---C54---N8 120.1 (2) C128---C130---H13C 109.5 O7---C55---C54 121.9 (2) C128---C130---H13D 109.5 O7---C55---C56 118.8 (2) H13C---C130---H13D 109.5 C54---C55---C56 119.2 (2) C128---C130---H13E 109.5 C57---C56---C55 118.2 (2) H13C---C130---H13E 109.5 C57---C56---C71 121.9 (2) H13D---C130---H13E 109.5 C55---C56---C71 119.8 (2) C132---C131---C128 124.7 (2) C58---C57---C56 123.3 (2) C132---C131---H13F 106.2 C58---C57---H57 118.4 C128---C131---H13F 106.2 C56---C57---H57 118.4 C132---C131---H13G 106.2 C57---C58---C59 117.1 (2) C128---C131---H13G 106.2 C57---C58---C63 122.5 (2) H13F---C131---H13G 106.3 C59---C58---C63 120.3 (2) C133---C132---C135 108.1 (2) C54---C59---C58 120.6 (2) C133---C132---C131 113.9 (2) C54---C59---H59 119.7 C135---C132---C131 113.6 (2) C58---C59---H59 119.7 C133---C132---C134 107.2 (2) O7---C60---C61 109.27 (19) C135---C132---C134 107.4 (2) O7---C60---H60A 109.8 C131---C132---C134 106.2 (2) C61---C60---H60A 109.8 C132---C133---H13H 109.5 O7---C60---H60B 109.8 C132---C133---H13I 109.5 C61---C60---H60B 109.8 H13H---C133---H13I 109.5 H60A---C60---H60B 108.3 C132---C133---H13J 109.5 O9---C61---O8 124.4 (2) H13H---C133---H13J 109.5 O9---C61---C60 126.9 (2) H13I---C133---H13J 109.5 O8---C61---C60 108.7 (2) C132---C134---H13K 109.5 O8---C62---H62A 109.5 C132---C134---H13L 109.5 O8---C62---H62B 109.5 H13K---C134---H13L 109.5 H62A---C62---H62B 109.5 C132---C134---H13M 109.5 O8---C62---H62C 109.5 H13K---C134---H13M 109.5 H62A---C62---H62C 109.5 H13L---C134---H13M 109.5 H62B---C62---H62C 109.5 C132---C135---H13N 109.5 C65---C63---C58 110.04 (19) C132---C135---H13O 109.5 C65---C63---C64 107.2 (2) H13N---C135---H13O 109.5 C58---C63---C64 109.2 (2) C132---C135---H13P 109.5 C65---C63---C66 113.2 (2) H13N---C135---H13P 109.5 C58---C63---C66 104.76 (18) H13O---C135---H13P 109.5 C64---C63---C66 112.4 (2) N16---C136---C141 108.7 (2) C63---C64---H64A 109.5 N16---C136---C137 130.0 (2) C63---C64---H64B 109.5 C141---C136---C137 121.2 (2) H64A---C64---H64B 109.5 C138---C137---C136 116.8 (3) C63---C64---H64C 109.5 C138---C137---H137 121.6 H64A---C64---H64C 109.5 C136---C137---H137 121.6 H64B---C64---H64C 109.5 C137---C138---C139 121.6 (2) C63---C65---H65A 109.5 C137---C138---H138 119.2 C63---C65---H65B 109.5 C139---C138---H138 119.2 H65A---C65---H65B 109.5 C140---C139---C138 122.7 (3) C63---C65---H65C 109.5 C140---C139---H139 118.7 H65A---C65---H65C 109.5 C138---C139---H139 118.7 H65B---C65---H65C 109.5 C139---C140---C141 116.6 (3) C67---C66---C63 124.4 (2) C139---C140---H140 121.7 C67---C66---H66A 106.2 C141---C140---H140 121.7 C63---C66---H66A 106.2 N18---C141---C136 109.0 (2) C67---C66---H66B 106.2 N18---C141---C140 129.8 (2) C63---C66---H66B 106.2 C136---C141---C140 121.1 (2) C1---N1---N2---N3 −0.5 (3) C59---C58---C63---C65 34.2 (3) C1---N1---N2---C7 −177.5 (2) C57---C58---C63---C64 −30.0 (3) N1---N2---N3---C6 0.2 (3) C59---C58---C63---C64 151.7 (2) C7---N2---N3---C6 177.1 (2) C57---C58---C63---C66 90.6 (3) C42---N4---N5---N6 −0.8 (3) C59---C58---C63---C66 −87.7 (3) C42---N4---N5---C27 −170.2 (2) C65---C63---C66---C67 51.6 (3) N4---N5---N6---C47 0.8 (3) C58---C63---C66---C67 171.5 (2) C27---N5---N6---C47 170.5 (2) C64---C63---C66---C67 −70.0 (3) C48---N7---N8---N9 0.5 (3) C63---C66---C67---C68 −69.6 (3) C48---N7---N8---C54 174.6 (2) C63---C66---C67---C70 54.3 (3) N7---N8---N9---C53 −0.8 (3) C63---C66---C67---C69 172.5 (2) C54---N8---N9---C53 −174.8 (2) C57---C56---C71---C72 44.2 (3) C89---N10---N11---N12 −0.8 (3) C55---C56---C71---C72 −138.9 (2) C89---N10---N11---C74 −173.0 (2) C56---C71---C72---C77 61.6 (3) N10---N11---N12---C94 1.1 (3) C56---C71---C72---C73 −121.5 (2) C74---N11---N12---C94 173.1 (2) C78---O10---C73---C74 52.5 (3) C95---N13---N14---N15 0.8 (3) C78---O10---C73---C72 −130.5 (2) C95---N13---N14---C101 176.0 (2) C77---C72---C73---O10 −174.7 (2) N13---N14---N15---C100 −0.6 (3) C71---C72---C73---O10 8.4 (3) C101---N14---N15---C100 −175.8 (2) C77---C72---C73---C74 2.5 (3) C136---N16---N17---N18 0.7 (3) C71---C72---C73---C74 −174.4 (2) C136---N16---N17---C121 173.4 (2) O10---C73---C74---C75 175.2 (2) N16---N17---N18---C141 −0.6 (3) C72---C73---C74---C75 −1.8 (4) C121---N17---N18---C141 −173.3 (2) O10---C73---C74---N11 −2.5 (4) N2---N1---C1---C6 0.6 (2) C72---C73---C74---N11 −179.5 (2) N2---N1---C1---C2 178.2 (2) N12---N11---C74---C73 55.4 (3) N1---C1---C2---C3 −176.8 (2) N10---N11---C74---C73 −132.7 (2) C6---C1---C2---C3 0.6 (4) N12---N11---C74---C75 −122.5 (2) C1---C2---C3---C4 0.2 (4) N10---N11---C74---C75 49.4 (3) C2---C3---C4---C5 −0.7 (4) C73---C74---C75---C76 −0.6 (4) C3---C4---C5---C6 0.4 (4) N11---C74---C75---C76 177.3 (2) N2---N3---C6---C1 0.2 (2) C74---C75---C76---C77 2.1 (4) N2---N3---C6---C5 −177.0 (3) C74---C75---C76---C81 −172.5 (2) N1---C1---C6---N3 −0.6 (3) C73---C72---C77---C76 −1.0 (4) C2---C1---C6---N3 −178.4 (2) C71---C72---C77---C76 176.0 (2) N1---C1---C6---C5 177.0 (2) C75---C76---C77---C72 −1.3 (4) C2---C1---C6---C5 −0.8 (4) C81---C76---C77---C72 173.3 (2) C4---C5---C6---N3 177.3 (2) C73---O10---C78---C79 132.3 (2) C4---C5---C6---C1 0.3 (4) C80---O11---C79---O12 0.1 (4) N1---N2---C7---C12 124.4 (2) C80---O11---C79---C78 −179.7 (2) N3---N2---C7---C12 −52.4 (3) O10---C78---C79---O12 −4.2 (4) N1---N2---C7---C8 −53.8 (3) O10---C78---C79---O11 175.5 (2) N3---N2---C7---C8 129.3 (2) C75---C76---C81---C82 3.8 (3) C13---O1---C8---C7 −61.1 (3) C77---C76---C81---C82 −170.6 (2) C13---O1---C8---C9 120.5 (2) C75---C76---C81---C83 119.8 (2) C12---C7---C8---O1 179.1 (2) C77---C76---C81---C83 −54.5 (3) N2---C7---C8---O1 −2.8 (3) C75---C76---C81---C84 −124.1 (2) C12---C7---C8---C9 −2.6 (4) C77---C76---C81---C84 61.5 (3) N2---C7---C8---C9 175.6 (2) C82---C81---C84---C85 −47.1 (3) O1---C8---C9---C10 179.0 (2) C76---C81---C84---C85 79.7 (3) C7---C8---C9---C10 0.7 (3) C83---C81---C84---C85 −164.0 (2) O1---C8---C9---C24 −5.3 (3) C81---C84---C85---C86 −48.2 (3) C7---C8---C9---C24 176.3 (2) C81---C84---C85---C87 77.0 (3) C8---C9---C10---C11 1.0 (4) C81---C84---C85---C88 −166.4 (2) C24---C9---C10---C11 −174.6 (2) N11---N10---C89---C94 0.1 (2) C9---C10---C11---C12 −0.7 (4) N11---N10---C89---C90 176.1 (3) C9---C10---C11---C16 176.5 (2) N10---C89---C90---C91 −176.9 (2) C8---C7---C12---C11 2.9 (4) C94---C89---C90---C91 −1.3 (4) N2---C7---C12---C11 −175.3 (2) C89---C90---C91---C92 −0.6 (4) C10---C11---C12---C7 −1.2 (4) C90---C91---C92---C93 1.9 (4) C16---C11---C12---C7 −178.5 (2) C91---C92---C93---C94 −1.1 (4) C8---O1---C13---C14 −123.9 (2) N11---N12---C94---C89 −0.9 (3) C15---O2---C14---O3 −0.6 (4) N11---N12---C94---C93 −178.6 (2) C15---O2---C14---C13 177.3 (2) N10---C89---C94---N12 0.6 (3) O1---C13---C14---O3 −5.6 (4) C90---C89---C94---N12 −175.8 (2) O1---C13---C14---O2 176.50 (19) N10---C89---C94---C93 178.5 (2) C10---C11---C16---C18 24.8 (4) C90---C89---C94---C93 2.1 (4) C12---C11---C16---C18 −158.0 (3) C92---C93---C94---N12 176.6 (3) C10---C11---C16---C17 143.4 (2) C92---C93---C94---C89 −0.9 (4) C12---C11---C16---C17 −39.5 (3) N14---N13---C95---C100 −0.6 (2) C10---C11---C16---C19 −97.5 (3) N14---N13---C95---C96 −178.1 (2) C12---C11---C16---C19 79.7 (3) N13---C95---C96---C97 176.4 (2) C18---C16---C19---C20 56.7 (4) C100---C95---C96---C97 −0.7 (4) C11---C16---C19---C20 177.6 (2) C95---C96---C97---C98 −0.2 (4) C17---C16---C19---C20 −63.7 (3) C96---C97---C98---C99 0.9 (4) C16---C19---C20---C21\' −162.5 (3) C97---C98---C99---C100 −0.6 (4) C16---C19---C20---C22 41.5 (4) N14---N15---C100---C95 0.1 (3) C16---C19---C20---C23 −92.5 (4) N14---N15---C100---C99 176.8 (3) C16---C19---C20---C22\' 70.2 (4) N13---C95---C100---N15 0.3 (3) C16---C19---C20---C23\' −41.0 (4) C96---C95---C100---N15 178.0 (2) C16---C19---C20---C21 158.9 (3) N13---C95---C100---C99 −176.7 (2) C8---C9---C24---C25 134.9 (2) C96---C95---C100---C99 1.0 (4) C10---C9---C24---C25 −49.6 (3) C98---C99---C100---N15 −176.6 (2) C9---C24---C25---C30 −58.5 (3) C98---C99---C100---C95 −0.3 (4) C9---C24---C25---C26 125.5 (2) N15---N14---C101---C106 56.3 (3) C31---O4---C26---C27 −56.1 (3) N13---N14---C101---C106 −118.7 (2) C31---O4---C26---C25 127.1 (2) N15---N14---C101---C102 −125.3 (2) C30---C25---C26---O4 175.1 (2) N13---N14---C101---C102 59.7 (3) C24---C25---C26---O4 −8.9 (3) C107---O13---C102---C101 56.3 (3) C30---C25---C26---C27 −1.9 (3) C107---O13---C102---C103 −127.3 (2) C24---C25---C26---C27 174.1 (2) C106---C101---C102---O13 175.4 (2) O4---C26---C27---C28 −175.5 (2) N14---C101---C102---O13 −2.9 (3) C25---C26---C27---C28 1.3 (3) C106---C101---C102---C103 −1.0 (3) O4---C26---C27---N5 2.4 (4) N14---C101---C102---C103 −179.3 (2) C25---C26---C27---N5 179.2 (2) O13---C102---C103---C104 −174.6 (2) N6---N5---C27---C28 −42.9 (3) C101---C102---C103---C104 2.0 (3) N4---N5---C27---C28 126.3 (2) O13---C102---C103---C118 8.2 (3) N6---N5---C27---C26 139.1 (2) C101---C102---C103---C118 −175.2 (2) N4---N5---C27---C26 −51.7 (3) C102---C103---C104---C105 −0.8 (4) C26---C27---C28---C29 1.3 (4) C118---C103---C104---C105 176.5 (2) N5---C27---C28---C29 −176.8 (2) C103---C104---C105---C106 −1.5 (4) C27---C28---C29---C30 −3.1 (3) C103---C104---C105---C110 172.0 (2) C27---C28---C29---C34 172.1 (2) C102---C101---C106---C105 −1.4 (4) C26---C25---C30---C29 0.0 (4) N14---C101---C106---C105 177.1 (2) C24---C25---C30---C29 −176.1 (2) C104---C105---C106---C101 2.5 (3) C28---C29---C30---C25 2.5 (4) C110---C105---C106---C101 −170.9 (2) C34---C29---C30---C25 −172.8 (2) C102---O13---C107---C108 124.6 (2) C26---O4---C31---C32 −138.1 (2) C109---O14---C108---O15 1.2 (4) C33---O5---C32---O6 −1.7 (4) C109---O14---C108---C107 −178.2 (2) C33---O5---C32---C31 178.2 (2) O13---C107---C108---O15 −2.0 (4) O4---C31---C32---O6 2.8 (4) O13---C107---C108---O14 177.4 (2) O4---C31---C32---O5 −177.1 (2) C106---C105---C110---C112 1.9 (3) C28---C29---C34---C36 −8.0 (3) C104---C105---C110---C112 −171.3 (2) C30---C29---C34---C36 167.0 (2) C106---C105---C110---C113 −126.0 (2) C28---C29---C34---C35 −124.0 (3) C104---C105---C110---C113 60.8 (3) C30---C29---C34---C35 51.0 (3) C106---C105---C110---C111 118.0 (3) C28---C29---C34---C37 119.7 (2) C104---C105---C110---C111 −55.1 (3) C30---C29---C34---C37 −65.3 (3) C112---C110---C113---C114 −47.2 (3) C36---C34---C37---C38 45.9 (3) C105---C110---C113---C114 80.1 (3) C29---C34---C37---C38 −80.8 (3) C111---C110---C113---C114 −163.5 (2) C35---C34---C37---C38 162.2 (2) C110---C113---C114---C115 −47.4 (3) C34---C37---C38---C39 167.0 (2) C110---C113---C114---C117 77.7 (3) C34---C37---C38---C41 −75.7 (3) C110---C113---C114---C116 −165.7 (2) C34---C37---C38---C40 49.1 (3) C104---C103---C118---C119 61.6 (3) N5---N4---C42---C47 0.4 (3) C102---C103---C118---C119 −121.2 (2) N5---N4---C42---C43 178.3 (3) C103---C118---C119---C120 −139.1 (2) N4---C42---C43---C44 −177.0 (3) C103---C118---C119---C124 44.2 (3) C47---C42---C43---C44 0.8 (4) C125---O16---C120---C119 −118.4 (2) C42---C43---C44---C45 0.1 (4) C125---O16---C120---C121 63.2 (3) C43---C44---C45---C46 −0.7 (4) C124---C119---C120---O16 −178.1 (2) C44---C45---C46---C47 0.2 (4) C118---C119---C120---O16 5.1 (3) N5---N6---C47---C42 −0.5 (2) C124---C119---C120---C121 0.4 (4) N5---N6---C47---C46 −177.0 (2) C118---C119---C120---C121 −176.5 (2) N4---C42---C47---N6 0.1 (3) O16---C120---C121---C122 179.6 (2) C43---C42---C47---N6 −178.1 (2) C119---C120---C121---C122 1.2 (4) N4---C42---C47---C46 176.9 (2) O16---C120---C121---N17 2.3 (4) C43---C42---C47---C46 −1.3 (4) C119---C120---C121---N17 −176.1 (2) C45---C46---C47---N6 176.8 (2) N16---N17---C121---C122 −128.7 (2) C45---C46---C47---C42 0.7 (4) N18---N17---C121---C122 43.7 (3) N8---N7---C48---C53 0.1 (3) N16---N17---C121---C120 48.7 (3) N8---N7---C48---C49 −177.0 (2) N18---N17---C121---C120 −138.9 (2) N7---C48---C49---C50 176.2 (2) C120---C121---C122---C123 −2.2 (4) C53---C48---C49---C50 −0.5 (4) N17---C121---C122---C123 175.3 (2) C48---C49---C50---C51 0.4 (4) C121---C122---C123---C124 1.5 (4) C49---C50---C51---C52 −0.1 (4) C121---C122---C123---C128 178.4 (2) C50---C51---C52---C53 −0.2 (4) C120---C119---C124---C123 −1.0 (4) N8---N9---C53---C48 0.7 (3) C118---C119---C124---C123 175.7 (2) N8---N9---C53---C52 176.7 (3) C122---C123---C124---C119 0.1 (4) N7---C48---C53---N9 −0.5 (3) C128---C123---C124---C119 −176.8 (2) C49---C48---C53---N9 176.8 (2) C120---O16---C125---C126 135.0 (2) N7---C48---C53---C52 −177.0 (2) C127---O17---C126---O18 1.3 (4) C49---C48---C53---C52 0.3 (4) C127---O17---C126---C125 −178.3 (2) C51---C52---C53---N9 −175.6 (3) O16---C125---C126---O18 −0.7 (4) C51---C52---C53---C48 0.1 (4) O16---C125---C126---O17 178.9 (2) N9---N8---C54---C59 48.5 (3) C122---C123---C128---C130 152.5 (2) N7---N8---C54---C59 −125.3 (2) C124---C123---C128---C130 −30.7 (3) N9---N8---C54---C55 −133.2 (2) C122---C123---C128---C129 34.6 (3) N7---N8---C54---C55 53.0 (3) C124---C123---C128---C129 −148.6 (2) C60---O7---C55---C54 66.2 (3) C122---C123---C128---C131 −85.9 (3) C60---O7---C55---C56 −115.7 (2) C124---C123---C128---C131 90.9 (3) C59---C54---C55---O7 −179.6 (2) C130---C128---C131---C132 −68.4 (3) N8---C54---C55---O7 2.2 (3) C123---C128---C131---C132 172.8 (2) C59---C54---C55---C56 2.3 (3) C129---C128---C131---C132 54.3 (3) N8---C54---C55---C56 −175.9 (2) C128---C131---C132---C133 55.0 (3) O7---C55---C56---C57 −178.5 (2) C128---C131---C132---C135 −69.4 (3) C54---C55---C56---C57 −0.3 (3) C128---C131---C132---C134 172.8 (2) O7---C55---C56---C71 4.4 (3) N17---N16---C136---C141 −0.5 (3) C54---C55---C56---C71 −177.4 (2) N17---N16---C136---C137 −177.7 (2) C55---C56---C57---C58 −1.3 (4) N16---C136---C137---C138 177.5 (3) C71---C56---C57---C58 175.7 (2) C141---C136---C137---C138 0.5 (4) C56---C57---C58---C59 1.0 (3) C136---C137---C138---C139 −1.0 (4) C56---C57---C58---C63 −177.4 (2) C137---C138---C139---C140 0.7 (4) C55---C54---C59---C58 −2.6 (4) C138---C139---C140---C141 0.2 (4) N8---C54---C59---C58 175.6 (2) N17---N18---C141---C136 0.3 (3) C57---C58---C59---C54 1.0 (3) N17---N18---C141---C140 177.2 (3) C63---C58---C59---C54 179.4 (2) N16---C136---C141---N18 0.1 (3) C55---O7---C60---C61 126.7 (2) C137---C136---C141---N18 177.7 (2) C62---O8---C61---O9 2.9 (4) N16---C136---C141---C140 −177.2 (2) C62---O8---C61---C60 −175.3 (2) C137---C136---C141---C140 0.4 (4) O7---C60---C61---O9 6.1 (4) C139---C140---C141---N18 −177.4 (3) O7---C60---C61---O8 −175.72 (19) C139---C140---C141---C136 −0.8 (4) C57---C58---C63---C65 −147.5 (2) ------------------------- -------------- --------------------------- ------------- :::

PubMed Central

2024-06-05T04:04:18.607328

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052126/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o722", "authors": [ { "first": "Tahir", "last": "Qadri" }, { "first": "Itrat", "last": "Anis" }, { "first": "M. R.", "last": "Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052127

Related literature {#sec1} ================== For general background to anthraquinones, see: Arai *et al.* (1985[@bb1]); Dalliya *et al.* (2007[@bb2]); Gatto *et al.* (1996[@bb4]); Kowalczyk *et al.* (2010[@bb6]); Mori *et al.* (1990[@bb7]); Ossowski *et al.* (2005[@bb8]); Zoń *et al.* (2003[@bb14]). For a related structure, see: Yatsenko *et al.* (2000[@bb13]). For molecular interactions, see: Hunter *et al.* (2001[@bb5]); Spek (2009[@bb11]); Takahashi *et al.* (2001[@bb12]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~13~NO~2~*M* *~r~* = 251.27Orthorhombic,*a* = 7.2823 (3) Å*b* = 11.1519 (7) Å*c* = 14.9834 (7) Å*V* = 1216.82 (11) Å^3^*Z* = 4Mo *K*α radiationμ = 0.09 mm^−1^*T* = 295 K0.45 × 0.20 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini R ULTRA Ruby CCD diffractometer4683 measured reflections1258 independent reflections918 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.033 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.037*wR*(*F* ^2^) = 0.079*S* = 0.961258 reflections174 parametersH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e498} Data collection: *CrysAlis CCD* (Oxford Diffraction, 2008[@bb9]); cell refinement: *CrysAlis RED* (Oxford Diffraction, 2008[@bb9]); data reduction: *CrysAlis RED*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb10]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb10]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb3]); software used to prepare material for publication: *SHELXL97* and *PLATON* (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006829/ng5119sup1.cif](http://dx.doi.org/10.1107/S1600536811006829/ng5119sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006829/ng5119Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006829/ng5119Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5119&file=ng5119sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5119sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5119&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5119](http://scripts.iucr.org/cgi-bin/sendsup?ng5119)). This study was financed by the State Funds for Scientific Research (grant DS/8210-4-0177-11). Comment ======= Anthraquinones, the largest group of naturally occurring quinones, present in bacteria, fungi and many higher plant families contain π-electrons, reducible *p*-quinone system and are redoxactive (Zoń *et al.*, 2003). That is the reason why those found many practical applications (Kowalczyk *et al.*, 2010; Ossowski *et al.*, 2005). Both natural and synthetic derivatives have been used as colourants in food, cosmetics, textiles and hair dyes (Mori *et al.*, 1990). In medicine they are known as antitumor drugs and antibacterial or anti-inflammatory agents (Gatto *et al.*, 1996). Among anthraquinones, the amino-derivatives, due to the possibility of their chemical modification, reveal greatest potential of application. Here, we present the crystal structure of the 1-(dimethylamino)-9,10-anthraquinone -- compound with interesting photophysical properties (Arai *et al.*, 1985; Dalliya *et al.*, 2007). In the molecule of the title compound (Fig. 1), likewise in the 1-(methyl(phenyl)amino)anthraquinone (Yatsenko *et al.*, 2000), relatively strong deviation of planarity of the anthraquinone skeleton is observed. In case of the title compound, such distortion (0.1274 (3) Å) is directly caused by the steric effect of the bulky --N(CH~3~)~2~ group (Dalliya *et al.*, 2007). The dimethylamino group is twisted at an angle of 38.4 (1)° relative to the anthracene fragment. The neighboring anthracene moieties are inclined at an angle of 59.3 (1)°, 75.7 (1)° and 76.0 (1)° in the crystal lattice. In the crystal structure, the adjacent molecules are linked by C--H···π (Table 2, Fig. 2) and π-π \[centroid-centroid distances = 3.844 (2) Å\] (Table 3, Fig. 3) contacts. All interactions demonstrated were found by *PLATON* (Spek, 2009). The C--H···π interactions should be of an attractive nature (Takahashi *et al.*, 2001), like the π-π (Hunter *et al.*, 2001) interactions. Experimental {#experimental} ============ 1-(Dimethylamino)-9,10-anthraquinone was synthesized according to the procedure described below. The solution of 40% dimethylamine in water (2,21 ml, 12.36 mmol) was added to 1-chloro-9,10-anthraquinone (1 g, 4.12 mmol) in 15 ml toluene. The mixture was stirred at 130° for 4 h. The progress of the reaction was monitored by TLC (SiO~2~, dichloromethane) until the completion of reaction. The resulting mixture was concentrated to remove the solvent and dissolved in 100 ml of dichloromethane. The solution was washed with water (100 ml), the organic phase was dried over MgSO~4~ and concentrated. The resultant solid was purified by column chromatography using dichloromethane as a solvent obtaining the title compound as a red solid (921 mg, 89%). The product was recrystallized by slow evaporation from methanol to give red crystals suitable for X-ray diffraction (m.p. 137.5--137.9°C). Spectral data: IR (KBr): 3584, 2916, 2806, 1662, 1637, 1551, 1499, 1374, 1311,1270, 1180, 1024, 935, 793, 731,704 cm^-1^; ^1^H NMR (CDCl~3~, 400 MHz): 3.03 (6*H*, s, CH~3~), 7.34--7.36 (1*H*, d, J~1~ = 8.8 Hz, H-2-Ar), 7.54--7.58 (1*H*, t, J~1~ = J~2~ = 8.0 Hz, H-3-Ar), 7.69--7.72 (1*H*, t, J~1~ = 7.6 Hz, J~1~ = 6.8 Hz, J~2~ = 7.2 Hz, H-6-Ar), 7.74--7.76 (1*H*, d, J~1~ = 7.6 Hz, H-4-Ar), 7.78--7.82 (1*H*, t, J~1~ = 7.6 Hz, J~1~ = 8.4 Hz, J~2~ = 8.0 Hz, H-7-Ar), 8.22--8.24 (1*H*, t, J~1~ = 7.2 Hz, H-8-Ar). Elemental analysis: calculated for C~16~H~13~NO~2~: C 76.48, H 5.21, N 5.57; found: C 76.52, H 5.28, N 5.51. Refinement {#refinement} ========== 1063 Friedel pairs were merged. H atoms were positioned geometrically, with C---H = 0.93 Å and 0.96 Å for the aromatic and methyl H atoms, respectively, and constrained to ride on their parent atoms with *U*~iso~(H) = *xU*~eq~(C), where *x* = 1.2 for the aromatic and *x* = 1.5 for the methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 25% probability level, and H atoms are shown as small spheres of arbitrary radius. Cg1 and Cg2 are the centroids of the C1---C4/C11/C12 and C5---C8/C13/C14 rings respectively. ::: ![](e-67-0o723-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The arrangement of the molecules in the crystal structure viewed approximately along a direction. The C--H···π interactions are represented by dotted lines. H atoms not involved in interactions have been omitted. \[Symmetry codes: (i) --x, y + 3/2, --z + 3/2; (ii) x + 3/2, --y + 1/2, --z + 1.\] ::: ![](e-67-0o723-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The arrangement of the molecules in the crystal structure viewed approximately along b direction. The π-π interactions are represented by dotted lines. H atoms have been omitted for clarity. \[Symmetry codes: (iii) x + 1, y, z; (iv) x -- 1, y + 1, z + 1.\] ::: ![](e-67-0o723-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e334 .table-wrap} ------------------------------- --------------------------------------- C~16~H~13~NO~2~ *F*(000) = 528 *M~r~* = 251.27 *D*~x~ = 1.372 Mg m^−3^ Orthorhombic, *P*2~1~2~1~2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 1944 reflections *a* = 7.2823 (3) Å θ = 3.1--29.0° *b* = 11.1519 (7) Å µ = 0.09 mm^−1^ *c* = 14.9834 (7) Å *T* = 295 K *V* = 1216.82 (11) Å^3^ Prism, red *Z* = 4 0.45 × 0.20 × 0.18 mm ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e458 .table-wrap} ----------------------------------------------------------- ------------------------------------- Oxford Diffraction Gemini R ULTRA Ruby CCD diffractometer 918 reflections with *I* \> 2σ(*I*) Radiation source: Enhance (Mo) X-ray Source *R*~int~ = 0.033 graphite θ~max~ = 25.1°, θ~min~ = 3.1° Detector resolution: 10.4002 pixels mm^-1^ *h* = −8→6 ω scans *k* = −12→13 4683 measured reflections *l* = −17→13 1258 independent reflections ----------------------------------------------------------- ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e559 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.037 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.079 H-atom parameters constrained *S* = 0.96 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0492*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 1258 reflections (Δ/σ)~max~ \< 0.001 174 parameters Δρ~max~ = 0.12 e Å^−3^ 0 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e713 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e733 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.7457 (3) 0.5675 (2) 0.53415 (14) 0.0349 (6) C2 0.8768 (3) 0.6609 (3) 0.53396 (17) 0.0437 (7) H2 0.9738 0.6578 0.4937 0.052\* C3 0.8647 (4) 0.7554 (3) 0.59116 (18) 0.0486 (7) H3 0.9530 0.8155 0.5892 0.058\* C4 0.7235 (3) 0.7630 (2) 0.65179 (17) 0.0422 (6) H4 0.7206 0.8255 0.6928 0.051\* C5 0.1522 (4) 0.6067 (3) 0.78267 (16) 0.0459 (7) H5 0.1608 0.6622 0.8288 0.055\* C6 0.0081 (4) 0.5277 (3) 0.78088 (18) 0.0487 (7) H6 −0.0795 0.5290 0.8260 0.058\* C7 −0.0067 (3) 0.4466 (3) 0.71212 (17) 0.0465 (7) H7 −0.1065 0.3946 0.7099 0.056\* C8 0.1262 (3) 0.4422 (2) 0.64640 (17) 0.0409 (6) H8 0.1164 0.3863 0.6006 0.049\* C9 0.4157 (3) 0.5148 (2) 0.57716 (15) 0.0334 (6) C10 0.4341 (4) 0.6937 (2) 0.71603 (16) 0.0394 (7) C11 0.5878 (3) 0.5814 (2) 0.58994 (14) 0.0325 (6) C12 0.5869 (3) 0.6781 (2) 0.65160 (16) 0.0335 (6) C13 0.2744 (3) 0.5206 (2) 0.64829 (15) 0.0335 (6) C14 0.2856 (3) 0.6048 (2) 0.71661 (14) 0.0354 (6) N15 0.7757 (3) 0.4671 (2) 0.48311 (13) 0.0421 (6) C16 0.7173 (4) 0.3491 (2) 0.51109 (19) 0.0528 (8) H16A 0.6745 0.3525 0.5716 0.079\* H16B 0.8189 0.2945 0.5072 0.079\* H16C 0.6198 0.3219 0.4730 0.079\* C17 0.9195 (3) 0.4667 (3) 0.41526 (17) 0.0552 (8) H17A 0.9068 0.5362 0.3780 0.083\* H17B 0.9086 0.3957 0.3794 0.083\* H17C 1.0376 0.4679 0.4437 0.083\* O18 0.3823 (2) 0.45881 (18) 0.50827 (11) 0.0484 (5) O19 0.4317 (3) 0.77920 (19) 0.76763 (15) 0.0644 (6) ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1161 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0328 (13) 0.0405 (16) 0.0315 (12) 0.0014 (14) −0.0002 (12) 0.0029 (12) C2 0.0356 (14) 0.0555 (19) 0.0400 (14) −0.0071 (15) 0.0045 (12) 0.0082 (14) C3 0.0453 (14) 0.0471 (17) 0.0532 (16) −0.0149 (15) −0.0037 (15) 0.0040 (17) C4 0.0427 (14) 0.0392 (16) 0.0448 (14) −0.0052 (14) −0.0053 (13) −0.0071 (14) C5 0.0478 (15) 0.0464 (18) 0.0435 (14) 0.0079 (15) 0.0064 (13) −0.0049 (14) C6 0.0377 (14) 0.057 (2) 0.0512 (15) 0.0046 (16) 0.0143 (12) 0.0078 (17) C7 0.0345 (14) 0.0513 (19) 0.0538 (16) −0.0061 (14) −0.0005 (13) 0.0095 (17) C8 0.0348 (13) 0.0461 (16) 0.0416 (13) −0.0012 (13) −0.0033 (12) 0.0038 (14) C9 0.0339 (12) 0.0348 (15) 0.0314 (12) 0.0014 (12) −0.0027 (11) 0.0011 (12) C10 0.0434 (15) 0.0391 (16) 0.0358 (14) 0.0024 (13) −0.0017 (13) −0.0039 (13) C11 0.0296 (12) 0.0372 (15) 0.0306 (12) 0.0010 (12) −0.0026 (11) 0.0048 (12) C12 0.0317 (12) 0.0346 (14) 0.0342 (12) 0.0011 (13) −0.0051 (12) 0.0036 (12) C13 0.0284 (12) 0.0364 (15) 0.0358 (12) 0.0050 (12) −0.0062 (11) 0.0035 (12) C14 0.0319 (13) 0.0378 (15) 0.0364 (12) 0.0035 (12) −0.0001 (12) 0.0014 (13) N15 0.0347 (11) 0.0497 (14) 0.0418 (11) −0.0001 (12) 0.0084 (10) −0.0042 (12) C16 0.0510 (16) 0.0460 (18) 0.0614 (17) 0.0072 (16) 0.0043 (15) −0.0056 (16) C17 0.0407 (14) 0.076 (2) 0.0489 (15) 0.0057 (17) 0.0081 (13) −0.0116 (16) O18 0.0404 (10) 0.0629 (12) 0.0418 (10) −0.0084 (10) 0.0001 (8) −0.0145 (10) O19 0.0661 (13) 0.0604 (14) 0.0665 (13) −0.0108 (11) 0.0160 (11) −0.0280 (13) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1546 .table-wrap} ---------------------- ------------ ----------------------- ------------- C1---N15 1.373 (3) C8---H8 0.9300 C1---C2 1.413 (4) C9---O18 1.230 (3) C1---C11 1.430 (3) C9---C11 1.469 (3) C2---C3 1.360 (4) C9---C13 1.483 (3) C2---H2 0.9300 C10---O19 1.227 (3) C3---C4 1.374 (4) C10---C14 1.467 (4) C3---H3 0.9300 C10---C12 1.483 (3) C4---C12 1.374 (3) C11---C12 1.420 (3) C4---H4 0.9300 C13---C14 1.392 (3) C5---C6 1.370 (4) N15---C16 1.446 (3) C5---C14 1.387 (3) N15---C17 1.459 (3) C5---H5 0.9300 C16---H16A 0.9600 C6---C7 1.375 (4) C16---H16B 0.9600 C6---H6 0.9300 C16---H16C 0.9600 C7---C8 1.382 (3) C17---H17A 0.9600 C7---H7 0.9300 C17---H17B 0.9600 C8---C13 1.389 (3) C17---H17C 0.9600 N15---C1---C2 119.5 (2) C14---C10---C12 118.5 (2) N15---C1---C11 122.8 (2) C12---C11---C1 117.8 (2) C2---C1---C11 117.7 (2) C12---C11---C9 117.7 (2) C3---C2---C1 121.7 (2) C1---C11---C9 123.7 (2) C3---C2---H2 119.1 C4---C12---C11 121.4 (2) C1---C2---H2 119.1 C4---C12---C10 117.5 (2) C2---C3---C4 120.8 (3) C11---C12---C10 121.1 (2) C2---C3---H3 119.6 C8---C13---C14 119.0 (2) C4---C3---H3 119.6 C8---C13---C9 119.8 (2) C12---C4---C3 119.9 (2) C14---C13---C9 121.1 (2) C12---C4---H4 120.1 C5---C14---C13 119.6 (2) C3---C4---H4 120.1 C5---C14---C10 120.7 (2) C6---C5---C14 120.9 (2) C13---C14---C10 119.7 (2) C6---C5---H5 119.6 C1---N15---C16 122.26 (19) C14---C5---H5 119.6 C1---N15---C17 120.3 (2) C5---C6---C7 119.8 (2) C16---N15---C17 114.2 (2) C5---C6---H6 120.1 N15---C16---H16A 109.5 C7---C6---H6 120.1 N15---C16---H16B 109.5 C6---C7---C8 120.2 (2) H16A---C16---H16B 109.5 C6---C7---H7 119.9 N15---C16---H16C 109.5 C8---C7---H7 119.9 H16A---C16---H16C 109.5 C7---C8---C13 120.5 (2) H16B---C16---H16C 109.5 C7---C8---H8 119.8 N15---C17---H17A 109.5 C13---C8---H8 119.8 N15---C17---H17B 109.5 O18---C9---C11 122.3 (2) H17A---C17---H17B 109.5 O18---C9---C13 119.2 (2) N15---C17---H17C 109.5 C11---C9---C13 118.4 (2) H17A---C17---H17C 109.5 O19---C10---C14 120.7 (2) H17B---C17---H17C 109.5 O19---C10---C12 120.8 (2) N15---C1---C2---C3 −172.0 (2) O19---C10---C12---C11 −178.1 (2) C11---C1---C2---C3 6.6 (3) C14---C10---C12---C11 1.8 (3) C1---C2---C3---C4 0.2 (4) C7---C8---C13---C14 −0.9 (3) C2---C3---C4---C12 −3.7 (4) C7---C8---C13---C9 −179.9 (2) C14---C5---C6---C7 −1.0 (4) O18---C9---C13---C8 14.8 (3) C5---C6---C7---C8 1.9 (4) C11---C9---C13---C8 −168.1 (2) C6---C7---C8---C13 −1.0 (4) O18---C9---C13---C14 −164.1 (2) N15---C1---C11---C12 168.8 (2) C11---C9---C13---C14 12.9 (3) C2---C1---C11---C12 −9.8 (3) C6---C5---C14---C13 −0.9 (4) N15---C1---C11---C9 −21.7 (3) C6---C5---C14---C10 176.6 (2) C2---C1---C11---C9 159.7 (2) C8---C13---C14---C5 1.9 (3) O18---C9---C11---C12 155.6 (2) C9---C13---C14---C5 −179.2 (2) C13---C9---C11---C12 −21.3 (3) C8---C13---C14---C10 −175.7 (2) O18---C9---C11---C1 −13.8 (4) C9---C13---C14---C10 3.3 (3) C13---C9---C11---C1 169.2 (2) O19---C10---C14---C5 −8.3 (4) C3---C4---C12---C11 0.2 (4) C12---C10---C14---C5 171.8 (2) C3---C4---C12---C10 −177.5 (2) O19---C10---C14---C13 169.2 (2) C1---C11---C12---C4 6.6 (3) C12---C10---C14---C13 −10.7 (3) C9---C11---C12---C4 −163.5 (2) C2---C1---N15---C16 145.7 (2) C1---C11---C12---C10 −175.8 (2) C11---C1---N15---C16 −32.9 (3) C9---C11---C12---C10 14.1 (3) C2---C1---N15---C17 −12.9 (3) O19---C10---C12---C4 −0.4 (4) C11---C1---N15---C17 168.5 (2) C14---C10---C12---C4 179.5 (2) ---------------------- ------------ ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2243 .table-wrap} ------------------------------------------------------------------------------------------------ *Cg*1 and *Cg*2 are the centroids of the C1--C4/C11/C12 and C5--C8/C13/C14 rings respectively. ------------------------------------------------------------------------------------------------ ::: ::: {#d1e2252 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C2---H2···Cg1^i^ 0.93 2.99 3.724 (3) 137 C4---H4···Cg2^ii^ 0.93 2.81 3.678 (3) 156 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*, *y*+3/2, −*z*+3/2; (ii) *x*+3/2, −*y*+1/2, −*z*+1. Table 2 π--π interactions (Å,°). {#d1e2343} ================================ ::: {#d1e2360 .table-wrap} ----- -------- --------------- ---------------- ------------- --------------- *I* *J* *CgI*···*CgJ* Dihedral angle *CgI*\_Perp Cg*I*\_Offset 1 2^iii^ 3.844 (2) 11.13 (12) 3.606 (10) 1.334 (10) 2 1^iv^ 3.844 (2) 11.13 (12) 3.606 (10) 1.334 (10) ----- -------- --------------- ---------------- ------------- --------------- ::: Symmetry codes: (iii) *x* + 1, *y*, *z*; (iv) *x* -- 1, *y* + 1, *z* + 1.Notes: *Cg*1 and *Cg*2 are the centroids of the C1-C4/C11/C12 and C5-C8/C13/C14 rings respectively. Cg*I*···Cg*J* is the distance between ring centroids. The dihedral angle is that between the planes of the rings *I* and *J*. *CgI*\_Perp is the perpendicular distance of *CgI* from ring *J*. Cg*I*\_Offset is the distance between *CgI* and perpendicular projection of *CgJ* on ring *I*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 and *Cg*2 are the centroids of the C1--C4/C11/C12 and C5--C8/C13/C14 rings respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- --------- ------- ----------- ------------- C2---H2⋯*Cg*1^i^ 0.93 2.99 3.724 (3) 137 C4---H4⋯*Cg*2^ii^ 0.93 2.81 3.678 (3) 156 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.644415

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052127/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o723", "authors": [ { "first": "Paweł", "last": "Niedziałkowski" }, { "first": "Joanna", "last": "Narloch" }, { "first": "Damian", "last": "Trzybiński" }, { "first": "Tadeusz", "last": "Ossowski" } ] }

PMC3052128

Related literature {#sec1} ================== For related structures and background, see: Lanfredi *et al.* (1975[@bb8]); Ahmad *et al.* (2010[@bb1]). For graph-set notation, see: Bernstein *et al.* (1995[@bb2]). For puckering parameters, see: Cremer & Pople (1975[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~30~H~46~O~3~*M* *~r~* = 454.67Tetragonal,*a* = 13.3167 (6) Å*c* = 31.1595 (14) Å*V* = 5525.7 (4) Å^3^*Z* = 8Mo *K*α radiationμ = 0.07 mm^−1^*T* = 296 K0.28 × 0.15 × 0.10 mm ### Data collection {#sec2.1.2} Bruker Kappa APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2005[@bb3]) *T* ~min~ = 0.935, *T* ~max~ = 0.96580888 measured reflections3012 independent reflections1936 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.103 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.061*wR*(*F* ^2^) = 0.186*S* = 1.033012 reflections306 parametersH-atom parameters constrainedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e447} Data collection: *APEX2* (Bruker, 2009[@bb4]); cell refinement: *SAINT* (Bruker, 2009[@bb4]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb9]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb6]) and *PLATON* (Spek, 2009[@bb10]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb7]) and *PLATON*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006283/bq2281sup1.cif](http://dx.doi.org/10.1107/S1600536811006283/bq2281sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006283/bq2281Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006283/bq2281Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bq2281&file=bq2281sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bq2281sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bq2281&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BQ2281](http://scripts.iucr.org/cgi-bin/sendsup?bq2281)). The authors acknowledge the provision of funds for the purchase of the diffractometer and encouragement by Dr Muhammad Akram Chaudhary, Vice Chancellor, University of Sargodha, Pakistan. Comment ======= The crystal structure of Methyl (13α,14β,20*S*,24*Z*)-3-oxo-lanosta-8,24-dien-26-oate (Lanfredi *et al.*, 1975) has been previously published which is closely related to the title compound (I. Fig. 1). This compound has been derived from the berries of *Schinus molle*. The title compound is isolated from the galls of *Pistacia integerima Stewart* which were collected from Razagran, District Dir, KPK, Pakistan. The isolated compound from the galls of *Pistacia integerima Stewart* by Ahmad *et al.*, 2010 and reported as Pisticialanstenoic acid, seems the same as (I). However their spectral studies differ a litle bit from our X-ray analysis. In (I), three six membered rings A (C1---C6), B (C5---C10) and C (C9---C14) are confirmed by different puckering parameters (Cremer & Pople, 1975). The puckering amplitude Q for the rings A, B and C have values of 0.490 (5) Å, 0.503 (4) Å and 0.540 (4) Å, θ for the rings A, B and C have values of 20.4 (6)°, 131.6 (6)° and 119.3 (4)°, φ for the rings A, B and C have values of 217.0 (17)°, 244.0 (7)° and 69.7 (5)°, respectively. The five membered ring D (C13---C17) has approximately envelop confirmation. The linear chain E (C20/C21/C22/C24) is planar with r. m. s. deviation of 0.0175 Å. The groups F (C18/C19/C25) and G (C23/O2/O3) are of course planar. The dihedral angle between E/F, E/G and F/G is 46.67 (5)°, 8.64 (1)° and 49.61 (5)°, respectively. There exist a strong intramolecular C---H···O and intermolecular O---H···O type H-bonding (Table 1, Fig. 2). Due to the inramolecular H-bonding S(6) ring motif is formed (Bernstein *et al.*, 1995). The molecules are stabilized in the form of conventional carboxylate dimers with *R*~2~^2^(8) ring motifs (Fig. 2). Experimental {#experimental} ============ The dried and crushed galls of Pistacia chinensis var integerima (5 kg) were subjected to cold extraction with methanol (MeOH). The MeOH extract (400 g) was suspended in water and successively partitioned with n-hexane, CHCl~3~, EtOAc and butanol (BuOH). The CHCl~3~ fraction (10 g) was subjected to column chromatography on silica gel. The column was first eluted with n-hexane:EtOAc (100:0 → 0:100) as solvent system. A total of 13 fractions, RF-1 to RF-13 were obtained based on TLC profiles. White crude product of fraction RF-4 was separated from the solution by decantation. This crude material was washed with acetone for several times. White crystals were obtained by re-crystallization from a mixture of n-hexane:acetone (80:20). Yield: 90 mg. Refinement {#refinement} ========== In the absence of anomalous scattering factor all of the Friedel pairs were merged. Initially all H-atoms were taken from the difference Fourier map and at the last stage these H-atoms were geometrically treated. The H-atoms were positioned geometrically (O---H = 0.82, C--H = 0.93--0.97 Å) and refined as riding with *U*~iso~(H) = x*U*~eq~(C, O), where x = 1.5 for methyl and x = 1.2 for all other H-atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title compound with the atom numbering scheme. The displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0o711-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The partial packing (PLATON; Spek, 2009) which shows that molecules form carboxylate dimers with R22(8) ring motif. ::: ![](e-67-0o711-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e172 .table-wrap} -------------------------- --------------------------------------- C~30~H~46~O~3~ *D*~x~ = 1.093 Mg m^−3^ *M~r~* = 454.67 Mo *K*α radiation, λ = 0.71073 Å Tetragonal, *P*4~3~2~1~2 Cell parameters from 1936 reflections Hall symbol: P 4nw 2abw θ = 2.0--25.5° *a* = 13.3167 (6) Å µ = 0.07 mm^−1^ *c* = 31.1595 (14) Å *T* = 296 K *V* = 5525.7 (4) Å^3^ Needle, brown *Z* = 8 0.28 × 0.15 × 0.10 mm *F*(000) = 2000 -------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e291 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker Kappa APEXII CCD diffractometer 3012 independent reflections Radiation source: fine-focus sealed tube 1936 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.103 Detector resolution: 7.50 pixels mm^-1^ θ~max~ = 25.5°, θ~min~ = 2.0° ω scans *h* = −15→15 Absorption correction: multi-scan (*SADABS*; Bruker, 2005) *k* = −15→15 *T*~min~ = 0.935, *T*~max~ = 0.965 *l* = −36→37 80888 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e411 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.061 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.186 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.086*P*)^2^ + 1.2062*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3012 reflections (Δ/σ)~max~ \< 0.001 306 parameters Δρ~max~ = 0.20 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e568 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles *etc*. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e670 .table-wrap} ------ ------------- ------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.0467 (3) 0.2309 (4) 0.45862 (16) 0.153 (3) O2 0.4258 (4) 0.3086 (4) 0.04257 (10) 0.126 (2) O3 0.4457 (3) 0.2870 (3) −0.02665 (10) 0.0945 (15) C1 0.0545 (3) 0.1086 (4) 0.40354 (12) 0.0697 (16) C2 0.0997 (4) 0.1819 (4) 0.43511 (15) 0.0853 (19) C3 0.2098 (4) 0.1923 (6) 0.43906 (16) 0.113 (3) C4 0.2651 (3) 0.1886 (4) 0.39648 (13) 0.0790 (19) C5 0.2386 (3) 0.0961 (3) 0.36929 (11) 0.0543 (11) C6 0.1235 (3) 0.0989 (3) 0.36259 (11) 0.0531 (13) C7 0.0906 (4) 0.0152 (4) 0.33306 (13) 0.090 (2) C8 0.1410 (3) 0.0268 (4) 0.28990 (12) 0.0683 (16) C9 0.2428 (3) 0.0658 (3) 0.28939 (10) 0.0519 (11) C10 0.2894 (3) 0.1031 (4) 0.32563 (11) 0.0623 (14) C11 0.4001 (3) 0.1270 (4) 0.32455 (11) 0.0750 (18) C12 0.4550 (3) 0.1281 (4) 0.28202 (11) 0.0690 (18) C13 0.3835 (3) 0.1393 (3) 0.24358 (11) 0.0512 (11) C14 0.3017 (3) 0.0559 (3) 0.24792 (11) 0.0545 (14) C15 0.2439 (3) 0.0683 (4) 0.20556 (11) 0.0664 (15) C16 0.3252 (4) 0.0930 (4) 0.17256 (12) 0.0714 (15) C17 0.4235 (3) 0.1184 (3) 0.19773 (11) 0.0587 (14) C18 0.4879 (3) 0.1963 (3) 0.17434 (12) 0.0647 (16) C19 0.5185 (4) 0.1526 (3) 0.13015 (12) 0.0750 (16) C20 0.5711 (4) 0.2247 (4) 0.10054 (12) 0.0767 (18) C21 0.5919 (3) 0.1785 (3) 0.05758 (13) 0.0670 (17) C22 0.5515 (3) 0.1957 (3) 0.01936 (12) 0.0597 (14) C23 0.4697 (3) 0.2684 (3) 0.01166 (14) 0.0667 (17) C24 0.5897 (3) 0.1425 (3) −0.02023 (13) 0.0737 (17) C25 0.5801 (4) 0.2295 (4) 0.19933 (15) 0.094 (2) C26 0.3361 (3) 0.2445 (3) 0.24457 (13) 0.0650 (16) C27 0.3455 (4) −0.0514 (3) 0.24816 (14) 0.0810 (19) C28 0.2784 (5) 0.0019 (5) 0.39218 (17) 0.112 (3) C29 0.0378 (6) 0.0107 (5) 0.42829 (18) 0.130 (3) C30 −0.0470 (4) 0.1500 (6) 0.38967 (15) 0.111 (3) H2 0.37831 0.34194 0.03369 0.1506\* H3A 0.23489 0.13882 0.45730 0.1358\* H3B 0.22476 0.25557 0.45307 0.1358\* H4A 0.33683 0.18870 0.40194 0.0946\* H4B 0.24930 0.24873 0.38024 0.0946\* H6 0.11127 0.16060 0.34627 0.0637\* H7A 0.01822 0.01725 0.32950 0.1080\* H7B 0.10831 −0.04913 0.34551 0.1080\* H8A 0.14170 −0.03851 0.27608 0.0820\* H8B 0.09968 0.07064 0.27243 0.0820\* H11A 0.43374 0.07888 0.34294 0.0902\* H11B 0.40888 0.19258 0.33758 0.0902\* H12A 0.49270 0.06612 0.27900 0.0831\* H12B 0.50259 0.18325 0.28186 0.0831\* H15A 0.20905 0.00683 0.19801 0.0794\* H15B 0.19532 0.12242 0.20762 0.0794\* H16A 0.30481 0.14991 0.15518 0.0854\* H16B 0.33623 0.03599 0.15377 0.0854\* H17 0.46301 0.05644 0.19923 0.0702\* H18 0.44620 0.25568 0.16920 0.0777\* H19A 0.56223 0.09537 0.13492 0.0898\* H19B 0.45857 0.12811 0.11589 0.0898\* H20A 0.52964 0.28396 0.09671 0.0920\* H20B 0.63392 0.24570 0.11349 0.0920\* H21 0.64161 0.12939 0.05775 0.0805\* H24A 0.63824 0.09279 −0.01204 0.1105\* H24B 0.62052 0.19041 −0.03912 0.1105\* H24C 0.53461 0.11059 −0.03468 0.1105\* H25A 0.62046 0.27268 0.18170 0.1404\* H25B 0.61863 0.17158 0.20747 0.1404\* H25C 0.55949 0.26512 0.22462 0.1404\* H26A 0.29602 0.25408 0.21928 0.0973\* H26B 0.38814 0.29424 0.24548 0.0973\* H26C 0.29438 0.25074 0.26957 0.0973\* H27A 0.38542 −0.06134 0.22286 0.1215\* H27B 0.29170 −0.09931 0.24862 0.1215\* H27C 0.38672 −0.06017 0.27316 0.1215\* H28A 0.25466 −0.05697 0.37756 0.1687\* H28B 0.25480 0.00123 0.42129 0.1687\* H28C 0.35044 0.00259 0.39196 0.1687\* H29A 0.01134 −0.03938 0.40925 0.1956\* H29B −0.00884 0.02219 0.45125 0.1956\* H29C 0.10060 −0.01211 0.43991 0.1956\* H30A −0.07966 0.10242 0.37124 0.1662\* H30B −0.03736 0.21201 0.37448 0.1662\* H30C −0.08784 0.16178 0.41454 0.1662\* ------ ------------- ------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1699 .table-wrap} ----- ----------- ----------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.090 (3) 0.218 (6) 0.152 (4) −0.011 (3) 0.022 (3) −0.121 (4) O2 0.133 (4) 0.169 (4) 0.075 (2) 0.079 (3) 0.009 (2) −0.017 (3) O3 0.122 (3) 0.100 (3) 0.0614 (18) 0.021 (2) 0.0003 (19) −0.0075 (18) C1 0.066 (3) 0.098 (3) 0.045 (2) −0.016 (3) 0.010 (2) −0.017 (2) C2 0.068 (3) 0.123 (4) 0.065 (3) −0.005 (3) 0.007 (2) −0.037 (3) C3 0.067 (3) 0.191 (7) 0.082 (3) −0.007 (4) 0.001 (3) −0.073 (4) C4 0.059 (3) 0.109 (4) 0.069 (3) −0.007 (3) −0.003 (2) −0.036 (3) C5 0.063 (2) 0.061 (2) 0.0389 (17) 0.006 (2) −0.0009 (18) −0.0028 (18) C6 0.052 (2) 0.070 (3) 0.0373 (17) −0.009 (2) 0.0011 (16) −0.0099 (18) C7 0.094 (4) 0.116 (4) 0.061 (2) −0.042 (3) 0.019 (3) −0.036 (3) C8 0.075 (3) 0.080 (3) 0.050 (2) −0.013 (2) 0.004 (2) −0.022 (2) C9 0.064 (2) 0.053 (2) 0.0388 (18) −0.0026 (19) 0.0047 (18) −0.0079 (17) C10 0.053 (2) 0.093 (3) 0.0408 (19) −0.002 (2) −0.0015 (18) −0.004 (2) C11 0.051 (3) 0.129 (4) 0.045 (2) 0.007 (3) −0.0021 (19) 0.000 (2) C12 0.057 (3) 0.101 (4) 0.049 (2) 0.006 (2) 0.002 (2) 0.001 (2) C13 0.053 (2) 0.058 (2) 0.0425 (19) 0.0116 (18) 0.0040 (17) 0.0011 (17) C14 0.068 (3) 0.051 (2) 0.0445 (19) 0.0072 (19) 0.0025 (19) −0.0040 (18) C15 0.076 (3) 0.080 (3) 0.0431 (19) −0.006 (2) 0.001 (2) −0.012 (2) C16 0.092 (3) 0.080 (3) 0.0421 (19) 0.000 (3) −0.003 (2) −0.008 (2) C17 0.067 (3) 0.058 (2) 0.051 (2) 0.018 (2) 0.011 (2) 0.0031 (18) C18 0.075 (3) 0.058 (3) 0.061 (2) 0.011 (2) 0.011 (2) 0.007 (2) C19 0.090 (3) 0.073 (3) 0.062 (2) 0.005 (3) 0.027 (2) 0.006 (2) C20 0.095 (4) 0.078 (3) 0.057 (2) −0.001 (3) 0.012 (2) 0.004 (2) C21 0.074 (3) 0.056 (3) 0.071 (3) 0.000 (2) 0.023 (2) 0.008 (2) C22 0.064 (3) 0.055 (2) 0.060 (2) −0.008 (2) 0.018 (2) −0.002 (2) C23 0.073 (3) 0.064 (3) 0.063 (3) −0.006 (2) 0.019 (2) −0.010 (2) C24 0.075 (3) 0.069 (3) 0.077 (3) −0.008 (2) 0.024 (2) −0.014 (2) C25 0.088 (4) 0.112 (4) 0.081 (3) −0.016 (3) 0.011 (3) 0.005 (3) C26 0.069 (3) 0.059 (3) 0.067 (2) 0.005 (2) 0.015 (2) −0.008 (2) C27 0.114 (4) 0.060 (3) 0.069 (3) 0.018 (3) 0.023 (3) 0.001 (2) C28 0.120 (5) 0.110 (5) 0.107 (4) 0.045 (4) 0.025 (4) 0.042 (4) C29 0.171 (7) 0.131 (5) 0.089 (4) −0.039 (5) 0.066 (4) 0.004 (4) C30 0.053 (3) 0.203 (7) 0.077 (3) −0.010 (4) 0.009 (2) −0.029 (4) ----- ----------- ----------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2330 .table-wrap} ---------------------- ------------ ----------------------- ------------ O1---C2 1.209 (7) C6---H6 0.9800 O2---C23 1.247 (6) C7---H7A 0.9700 O3---C23 1.260 (5) C7---H7B 0.9700 O2---H2 0.8200 C8---H8A 0.9700 C1---C2 1.511 (7) C8---H8B 0.9700 C1---C6 1.578 (5) C11---H11A 0.9700 C1---C30 1.522 (7) C11---H11B 0.9700 C1---C29 1.531 (8) C12---H12A 0.9700 C2---C3 1.478 (8) C12---H12B 0.9700 C3---C4 1.518 (6) C15---H15A 0.9700 C4---C5 1.536 (6) C15---H15B 0.9700 C5---C6 1.547 (6) C16---H16A 0.9700 C5---C28 1.537 (7) C16---H16B 0.9700 C5---C10 1.522 (5) C17---H17 0.9800 C6---C7 1.510 (6) C18---H18 0.9800 C7---C8 1.511 (6) C19---H19A 0.9700 C8---C9 1.452 (6) C19---H19B 0.9700 C9---C10 1.381 (5) C20---H20A 0.9700 C9---C14 1.517 (5) C20---H20B 0.9700 C10---C11 1.509 (6) C21---H21 0.9300 C11---C12 1.514 (5) C24---H24A 0.9600 C12---C13 1.537 (5) C24---H24B 0.9600 C13---C17 1.550 (5) C24---H24C 0.9600 C13---C26 1.537 (6) C25---H25A 0.9600 C13---C14 1.562 (6) C25---H25B 0.9600 C14---C15 1.537 (5) C25---H25C 0.9600 C14---C27 1.543 (6) C26---H26A 0.9600 C15---C16 1.529 (6) C26---H26B 0.9600 C16---C17 1.563 (6) C26---H26C 0.9600 C17---C18 1.531 (6) C27---H27A 0.9600 C18---C25 1.520 (6) C27---H27B 0.9600 C18---C19 1.549 (5) C27---H27C 0.9600 C19---C20 1.505 (6) C28---H28A 0.9600 C20---C21 1.499 (6) C28---H28B 0.9600 C21---C22 1.327 (6) C28---H28C 0.9600 C22---C23 1.477 (6) C29---H29A 0.9600 C22---C24 1.511 (6) C29---H29B 0.9600 C3---H3A 0.9700 C29---H29C 0.9600 C3---H3B 0.9700 C30---H30A 0.9600 C4---H4A 0.9700 C30---H30B 0.9600 C4---H4B 0.9700 C30---H30C 0.9600 O2···O3^i^ 2.645 (7) H11B···C4 2.6500 O2···C20 2.873 (7) H11B···H4A 2.2200 O3···O2^i^ 2.645 (7) H12A···C27 2.6900 O1···H30C 2.4400 H12A···H17 2.5200 O1···H30B 2.8600 H12A···H27C 2.2000 O1···H3A^ii^ 2.8900 H12B···C25 2.8400 O1···H29B 2.8900 H12B···H25C 2.2200 O2···H20A 2.2100 H12B···H26B 2.4100 O2···H2^i^ 2.7800 H15A···C8 3.0100 O2···H30A^iii^ 2.8900 H15A···H27B 2.3900 O3···H24B 2.6900 H15B···C8 2.9500 O3···H25B^iv^ 2.7800 H15B···C26 2.7400 O3···H8B^v^ 2.8000 H15B···H8B 2.4900 O3···H24C 2.6400 H15B···H26A 2.2400 O3···H2^i^ 1.8500 H15B···C21^x^ 3.0200 C10···C26 3.211 (6) H16A···C19 2.9500 C11···C27 3.441 (6) H16A···C26 3.0900 C12···C25 3.352 (6) H16A···H18 2.3900 C20···O2 2.873 (7) H16A···H19B 2.4000 C25···C26 3.548 (7) H16A···H26A 2.4300 C25···C12 3.352 (6) H16B···C19 2.9700 C26···C25 3.548 (7) H16B···H19B 2.3600 C26···C10 3.211 (6) H16B···H27A 2.6000 C27···C11 3.441 (6) H16B···C11^iv^ 3.1000 C28···C29 3.398 (10) H16B···H11A^iv^ 2.5900 C29···C28 3.398 (10) H17···C27 2.6100 C1···H28B 3.0800 H17···H12A 2.5200 C3···H29C 3.0900 H17···H19A 2.4600 C3···H28B 2.6700 H17···H25B 2.5900 C4···H11B 2.6500 H17···H27A 2.0200 C7···H29A 2.7000 H17···H24C^vi^ 2.3600 C7···H28A 2.7600 H18···C26 2.7700 C7···H30A 2.8100 H18···H16A 2.3900 C8···H27B 2.9200 H18···H20A 2.5500 C8···H15B 2.9500 H18···H26A 2.5400 C8···H15A 3.0100 H18···H26B 2.5500 C9···H6 2.7900 H18···C30^iii^ 3.0600 C9···H26C 2.6300 H18···H30C^iii^ 2.5400 C10···H26C 2.6300 H19A···H17 2.4600 C10···H27C 3.0100 H19A···H25B 2.5900 C11···H26C 2.7600 H19B···C16 2.5500 C11···H16B^vi^ 3.1000 H19B···H16A 2.4000 C11···H27C 2.9700 H19B···H16B 2.3600 C11···H4A 2.6800 H20A···O2 2.2100 C11···H28C 2.7600 H20A···C23 2.7800 C12···H27C 2.6800 H20A···H18 2.5500 C12···H25C 2.9100 H20B···C25 2.7800 C13···H25C 2.9400 H20B···H25A 2.1600 C15···H26A 2.6000 H21···H24A 2.2300 C15···H8A 2.9500 H24A···H21 2.2300 C15···H8B 2.8300 H24B···O3 2.6900 C16···H19B 2.5500 H24B···H26C^v^ 2.5200 C16···H27A 2.7100 H24C···O3 2.6400 C16···H26A 2.6200 H24C···H17^iv^ 2.3600 C17···H27A 2.5700 H25A···C20 2.6900 C18···H26A 3.0100 H25A···H20B 2.1600 C18···H26B 2.8900 H25B···H17 2.5900 C19···H16A 2.9500 H25B···H19A 2.5900 C19···H16B 2.9700 H25B···O3^vi^ 2.7800 C20···H25A 2.6900 H25C···C12 2.9100 C21···H26A^v^ 2.9800 H25C···C13 2.9400 C21···H15B^v^ 3.0200 H25C···C26 3.0500 C23···H8B^v^ 2.9500 H25C···H12B 2.2200 C23···H20A 2.7800 H25C···H26B 2.4000 C23···H2^i^ 2.6500 H26A···C15 2.6000 C24···H26C^v^ 3.0700 H26A···C16 2.6200 C25···H20B 2.7800 H26A···C18 3.0100 C25···H12B 2.8400 H26A···H15B 2.2400 C25···H26B 3.0600 H26A···H16A 2.4300 C26···H18 2.7700 H26A···H18 2.5400 C26···H15B 2.7400 H26A···C21^x^ 2.9800 C26···H16A 3.0900 H26B···C18 2.8900 C26···H25C 3.0500 H26B···C25 3.0600 C27···H17 2.6100 H26B···H12B 2.4100 C27···H8A 2.8600 H26B···H18 2.5500 C27···H12A 2.6900 H26B···H25C 2.4000 C28···H3A 2.7900 H26C···C9 2.6300 C28···H11A 2.7700 H26C···C10 2.6300 C28···H29C 2.8000 H26C···C11 2.7600 C28···H7B 2.7800 H26C···C24^x^ 3.0700 C29···H7A 3.0900 H26C···H24B^x^ 2.5200 C29···H7B 2.8600 H27A···C16 2.7100 C29···H28B 2.9000 H27A···C17 2.5700 C30···H7A 2.7200 H27A···H16B 2.6000 C30···H18^vii^ 3.0600 H27A···H17 2.0200 H2···O2^i^ 2.7800 H27B···C8 2.9200 H2···O3^i^ 1.8500 H27B···H8A 2.3200 H2···C23^i^ 2.6500 H27B···H15A 2.3900 H2···H2^i^ 2.2100 H27B···H3B^xi^ 2.4600 H3A···C28 2.7900 H27C···C10 3.0100 H3A···H28B 2.1600 H27C···C11 2.9700 H3A···O1^ii^ 2.8900 H27C···C12 2.6800 H3B···H27B^viii^ 2.4600 H27C···H12A 2.2000 H4A···C11 2.6800 H28A···C7 2.7600 H4A···H11B 2.2200 H28A···H7B 2.1900 H4A···H28C 2.5000 H28A···H4B^xi^ 2.6000 H4B···H6 2.4200 H28B···C1 3.0800 H4B···H28A^viii^ 2.6000 H28B···C3 2.6700 H6···C9 2.7900 H28B···C29 2.9000 H6···H4B 2.4200 H28B···H3A 2.1600 H6···H8B 2.6000 H28B···H29C 2.1400 H6···H30B 2.2700 H28C···C11 2.7600 H7A···C29 3.0900 H28C···H4A 2.5000 H7A···C30 2.7200 H28C···H11A 2.1400 H7A···H29A 2.6000 H29A···C7 2.7000 H7A···H30A 2.1600 H29A···H7A 2.6000 H7B···C28 2.7800 H29A···H7B 2.3700 H7B···C29 2.8600 H29A···H30A 2.5400 H7B···H28A 2.1900 H29B···O1 2.8900 H7B···H29A 2.3700 H29B···H30C 2.4200 H8A···C15 2.9500 H29C···C3 3.0900 H8A···C27 2.8600 H29C···C28 2.8000 H8A···H27B 2.3200 H29C···H28B 2.1400 H8A···H8A^ix^ 2.5300 H30A···C7 2.8100 H8B···C15 2.8300 H30A···H7A 2.1600 H8B···H6 2.6000 H30A···H29A 2.5400 H8B···H15B 2.4900 H30A···O2^vii^ 2.8900 H8B···O3^x^ 2.8000 H30B···O1 2.8600 H8B···C23^x^ 2.9500 H30B···H6 2.2700 H11A···C28 2.7700 H30C···O1 2.4400 H11A···H28C 2.1400 H30C···H29B 2.4200 H11A···H16B^vi^ 2.5900 H30C···H18^vii^ 2.5400 C23---O2---H2 109.00 H8A---C8---H8B 107.00 C2---C1---C29 106.3 (4) C10---C11---H11A 107.00 C2---C1---C30 107.7 (4) C10---C11---H11B 107.00 C2---C1---C6 110.3 (4) C12---C11---H11A 108.00 C6---C1---C30 108.5 (3) C12---C11---H11B 107.00 C29---C1---C30 108.8 (5) H11A---C11---H11B 107.00 C6---C1---C29 115.0 (4) C11---C12---H12A 109.00 O1---C2---C3 118.6 (5) C11---C12---H12B 109.00 C1---C2---C3 120.7 (5) C13---C12---H12A 109.00 O1---C2---C1 120.7 (5) C13---C12---H12B 109.00 C2---C3---C4 113.9 (4) H12A---C12---H12B 108.00 C3---C4---C5 113.4 (4) C14---C15---H15A 111.00 C4---C5---C6 106.4 (3) C14---C15---H15B 111.00 C4---C5---C10 110.0 (3) C16---C15---H15A 111.00 C6---C5---C10 108.6 (3) C16---C15---H15B 111.00 C6---C5---C28 115.1 (4) H15A---C15---H15B 109.00 C10---C5---C28 108.1 (4) C15---C16---H16A 110.00 C4---C5---C28 108.6 (4) C15---C16---H16B 110.00 C1---C6---C5 118.0 (3) C17---C16---H16A 110.00 C5---C6---C7 110.6 (3) C17---C16---H16B 110.00 C1---C6---C7 112.6 (4) H16A---C16---H16B 108.00 C6---C7---C8 109.8 (4) C13---C17---H17 107.00 C7---C8---C9 117.5 (3) C16---C17---H17 107.00 C8---C9---C14 117.5 (3) C18---C17---H17 107.00 C10---C9---C14 119.7 (3) C17---C18---H18 108.00 C8---C9---C10 122.6 (3) C19---C18---H18 108.00 C5---C10---C11 117.9 (3) C25---C18---H18 108.00 C9---C10---C11 119.8 (3) C18---C19---H19A 108.00 C5---C10---C9 120.6 (4) C18---C19---H19B 108.00 C10---C11---C12 119.6 (3) C20---C19---H19A 108.00 C11---C12---C13 112.6 (3) C20---C19---H19B 108.00 C12---C13---C17 119.2 (3) H19A---C19---H19B 107.00 C12---C13---C26 109.1 (3) C19---C20---H20A 109.00 C14---C13---C17 101.1 (3) C19---C20---H20B 109.00 C14---C13---C26 111.1 (3) C21---C20---H20A 109.00 C17---C13---C26 108.9 (3) C21---C20---H20B 109.00 C12---C13---C14 107.2 (3) H20A---C20---H20B 108.00 C9---C14---C13 111.9 (3) C20---C21---H21 115.00 C9---C14---C27 105.8 (3) C22---C21---H21 115.00 C13---C14---C15 101.5 (3) C22---C24---H24A 109.00 C13---C14---C27 113.3 (3) C22---C24---H24B 109.00 C15---C14---C27 107.0 (3) C22---C24---H24C 109.00 C9---C14---C15 117.6 (3) H24A---C24---H24B 109.00 C14---C15---C16 104.3 (3) H24A---C24---H24C 110.00 C15---C16---C17 107.6 (3) H24B---C24---H24C 109.00 C13---C17---C18 120.7 (3) C18---C25---H25A 109.00 C16---C17---C18 112.2 (3) C18---C25---H25B 109.00 C13---C17---C16 102.3 (3) C18---C25---H25C 109.00 C17---C18---C19 108.4 (3) H25A---C25---H25B 109.00 C17---C18---C25 114.0 (3) H25A---C25---H25C 110.00 C19---C18---C25 110.6 (4) H25B---C25---H25C 109.00 C18---C19---C20 115.3 (3) C13---C26---H26A 109.00 C19---C20---C21 111.8 (4) C13---C26---H26B 109.00 C20---C21---C22 131.0 (4) C13---C26---H26C 109.00 C21---C22---C24 121.0 (4) H26A---C26---H26B 110.00 C23---C22---C24 115.0 (3) H26A---C26---H26C 109.00 C21---C22---C23 123.9 (4) H26B---C26---H26C 110.00 O2---C23---C22 120.1 (4) C14---C27---H27A 109.00 O3---C23---C22 118.0 (4) C14---C27---H27B 109.00 O2---C23---O3 121.9 (4) C14---C27---H27C 109.00 C2---C3---H3A 109.00 H27A---C27---H27B 110.00 C2---C3---H3B 109.00 H27A---C27---H27C 109.00 C4---C3---H3A 109.00 H27B---C27---H27C 110.00 C4---C3---H3B 109.00 C5---C28---H28A 109.00 H3A---C3---H3B 108.00 C5---C28---H28B 109.00 C3---C4---H4A 109.00 C5---C28---H28C 109.00 C3---C4---H4B 109.00 H28A---C28---H28B 109.00 C5---C4---H4A 109.00 H28A---C28---H28C 109.00 C5---C4---H4B 109.00 H28B---C28---H28C 110.00 H4A---C4---H4B 108.00 C1---C29---H29A 109.00 C1---C6---H6 105.00 C1---C29---H29B 109.00 C5---C6---H6 105.00 C1---C29---H29C 109.00 C7---C6---H6 105.00 H29A---C29---H29B 110.00 C6---C7---H7A 110.00 H29A---C29---H29C 109.00 C6---C7---H7B 110.00 H29B---C29---H29C 109.00 C8---C7---H7A 110.00 C1---C30---H30A 109.00 C8---C7---H7B 110.00 C1---C30---H30B 109.00 H7A---C7---H7B 108.00 C1---C30---H30C 109.00 C7---C8---H8A 108.00 H30A---C30---H30B 109.00 C7---C8---H8B 108.00 H30A---C30---H30C 110.00 C9---C8---H8A 108.00 H30B---C30---H30C 109.00 C9---C8---H8B 108.00 C6---C1---C2---O1 149.9 (5) C10---C9---C14---C15 −148.9 (4) C6---C1---C2---C3 −32.5 (6) C10---C9---C14---C27 91.7 (5) C29---C1---C2---O1 −84.9 (6) C5---C10---C11---C12 176.1 (4) C29---C1---C2---C3 92.7 (6) C9---C10---C11---C12 11.1 (7) C30---C1---C2---O1 31.6 (7) C10---C11---C12---C13 19.5 (7) C30---C1---C2---C3 −150.8 (5) C11---C12---C13---C14 −52.8 (5) C2---C1---C6---C5 40.4 (5) C11---C12---C13---C17 −166.6 (4) C2---C1---C6---C7 171.2 (4) C11---C12---C13---C26 67.6 (5) C29---C1---C6---C5 −79.7 (5) C12---C13---C14---C9 59.9 (4) C29---C1---C6---C7 51.1 (5) C12---C13---C14---C15 −173.9 (3) C30---C1---C6---C5 158.2 (4) C12---C13---C14---C27 −59.6 (4) C30---C1---C6---C7 −71.0 (5) C17---C13---C14---C9 −174.6 (3) O1---C2---C3---C4 −142.5 (6) C17---C13---C14---C15 −48.4 (4) C1---C2---C3---C4 39.9 (8) C17---C13---C14---C27 65.9 (4) C2---C3---C4---C5 −52.6 (7) C26---C13---C14---C9 −59.2 (4) C3---C4---C5---C6 57.3 (5) C26---C13---C14---C15 67.0 (4) C3---C4---C5---C10 174.7 (4) C26---C13---C14---C27 −178.7 (3) C3---C4---C5---C28 −67.1 (5) C12---C13---C17---C16 156.9 (4) C4---C5---C6---C1 −52.9 (5) C12---C13---C17---C18 −77.8 (5) C4---C5---C6---C7 175.4 (3) C14---C13---C17---C16 39.9 (4) C10---C5---C6---C1 −171.3 (4) C14---C13---C17---C18 165.2 (3) C10---C5---C6---C7 57.1 (4) C26---C13---C17---C16 −77.1 (4) C28---C5---C6---C1 67.4 (5) C26---C13---C17---C18 48.2 (5) C28---C5---C6---C7 −64.2 (4) C9---C14---C15---C16 159.8 (4) C4---C5---C10---C9 −145.8 (4) C13---C14---C15---C16 37.5 (4) C4---C5---C10---C11 49.4 (5) C27---C14---C15---C16 −81.5 (4) C6---C5---C10---C9 −29.7 (6) C14---C15---C16---C17 −12.7 (5) C6---C5---C10---C11 165.4 (4) C15---C16---C17---C13 −17.3 (5) C28---C5---C10---C9 95.8 (5) C15---C16---C17---C18 −148.0 (4) C28---C5---C10---C11 −69.1 (6) C13---C17---C18---C19 178.4 (3) C1---C6---C7---C8 165.3 (4) C13---C17---C18---C25 54.8 (5) C5---C6---C7---C8 −60.3 (5) C16---C17---C18---C19 −61.0 (4) C6---C7---C8---C9 35.0 (6) C16---C17---C18---C25 175.4 (4) C7---C8---C9---C10 −7.9 (7) C17---C18---C19---C20 172.5 (4) C7---C8---C9---C14 166.7 (4) C25---C18---C19---C20 −61.9 (5) C8---C9---C10---C5 5.7 (7) C18---C19---C20---C21 −176.2 (4) C8---C9---C10---C11 170.3 (4) C19---C20---C21---C22 109.0 (5) C14---C9---C10---C5 −168.8 (4) C20---C21---C22---C23 −1.6 (7) C14---C9---C10---C11 −4.2 (7) C20---C21---C22---C24 176.6 (4) C8---C9---C14---C13 153.2 (4) C21---C22---C23---O2 −9.1 (7) C8---C9---C14---C15 36.4 (5) C21---C22---C23---O3 171.7 (4) C8---C9---C14---C27 −83.0 (4) C24---C22---C23---O2 172.6 (4) C10---C9---C14---C13 −32.1 (5) C24---C22---C23---O3 −6.7 (6) ---------------------- ------------ ----------------------- ------------ ::: Symmetry codes: (i) *y*, *x*, −*z*; (ii) *y*, *x*, −*z*+1; (iii) −*y*+1/2, *x*+1/2, *z*−1/4; (iv) −*y*+1/2, *x*−1/2, *z*−1/4; (v) *x*+1/2, −*y*+1/2, −*z*+1/4; (vi) *y*+1/2, −*x*+1/2, *z*+1/4; (vii) *y*−1/2, −*x*+1/2, *z*+1/4; (viii) −*x*+1/2, *y*+1/2, −*z*+3/4; (ix) −*y*, −*x*, −*z*+1/2; (x) *x*−1/2, −*y*+1/2, −*z*+1/4; (xi) −*x*+1/2, *y*−1/2, −*z*+3/4. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5251 .table-wrap} ----------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O2---H2···O3^i^ 0.82 1.85 2.645 (7) 162 C20---H20A···O2 0.97 2.21 2.873 (7) 125 ----------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *y*, *x*, −*z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ----------------- --------- ------- ----------- ------------- O2---H2⋯O3^i^ 0.82 1.85 2.645 (7) 162 C20---H20*A*⋯O2 0.97 2.21 2.873 (7) 125 Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.650680

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052128/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o711", "authors": [ { "first": "Mohammad", "last": "Arfan" }, { "first": "Abdur", "last": "Rauf" }, { "first": "M. Nawaz", "last": "Tahir" }, { "first": "Mumtaz", "last": "Ali" }, { "first": "Ghias", "last": "Uddin" } ] }

PMC3052129

Related literature {#sec1} ================== For background to supramolecular polymers of zinc-triad 1,1-dithiolates, including dithiocarbamates, see: Chen *et al.* (2006[@bb3]); Benson *et al.* (2007[@bb1]). For a closely related 2,2′-bipyridyl adduct, see: Song & Tiekink (2009[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cd(C~6~H~12~NS~2~)~2~(C~10~H~8~N~2~)\]*M* *~r~* = 593.16Triclinic,*a* = 10.3215 (4) Å*b* = 10.6465 (4) Å*c* = 12.4546 (5) Åα = 81.566 (3)°β = 74.790 (3)°γ = 83.641 (3)°*V* = 1302.64 (9) Å^3^*Z* = 2Mo *K*α radiationμ = 1.18 mm^−1^*T* = 150 K0.27 × 0.16 × 0.01 mm ### Data collection {#sec2.1.2} Oxford Diffraction Xcaliber Eos Gemini diffractometerAbsorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010[@bb5]) *T* ~min~ = 0.829, *T* ~max~ = 0.99015837 measured reflections5393 independent reflections4623 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.042 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.029*wR*(*F* ^2^) = 0.066*S* = 1.065393 reflections284 parametersH-atom parameters constrainedΔρ~max~ = 0.90 e Å^−3^Δρ~min~ = −0.51 e Å^−3^ {#d5e554} Data collection: *CrysAlis PRO* (Oxford Diffraction, 2010[@bb5]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb4]) and *DIAMOND* (Brandenburg, 2006[@bb2]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006878/pk2304sup1.cif](http://dx.doi.org/10.1107/S1600536811006878/pk2304sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006878/pk2304Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006878/pk2304Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?pk2304&file=pk2304sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?pk2304sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?pk2304&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [PK2304](http://scripts.iucr.org/cgi-bin/sendsup?pk2304)). We thank UKM (UKM-GUP-NBT-08--27-111 and UKM-ST-06-FRGS0092--2010), UPM and the University of Malaya for supporting this study. Comment ======= Adducts related to the title compound, (I), attract attention in crystal engineering studies (Chen *et al.*, 2006; Benson *et al.*, 2007). The Cd^II^ atom in (I) is six-coordinated, being chelated by two almost symmetrically coordinating dithiocarbamate ligands, and the N donor atoms of 2,2\'-bipyridyl ligand, Fig. 1 and Table 1. The coordination geometry is intermediate between trigonal prismatic and octahedral with a leaning towards the former. The angle between the triangular faces defined by the S1,S3,N4 and S2,S4,N3 atoms is 5.36 (9) °, and these are twisted by approximately 13 ° about the axis through them, compared to 0 ° for an an ideal trigonal prism and 60 ° for an ideal octahedron. The symmetric mode of coordination of the dithiocarbamate ligands is reflected in the associated C≐S bond distances which lie in the narrow range of 1.721 (2) to 1.733 (3) Å. The mode of coordination of the dithiocarbamate ligand, the disposition of the ligand donor set, and the intermediate coordination geometry observed for (I) matches a literature precedent (Song & Tiekink, 2009). Linear supramolecular chains along the *a* axis are formed in the crystal structure *via* C---H···S interactions, Table 2 and Fig. 2. These are consolidated into layers in the *ab* plane by π--π interactions formed between the pyridyl rings \[*Cg*(N3,C14--C18)···*Cg*(N4,C19--C23)^i^ = 3.6587 (13) Å with angle between rings = 5.35 (11) ° for *i*: 2 - *x*, 1 - *y*, 1 - *z*\]. Supramolecular layers stack along the *c* axis, Fig. 3. Experimental {#experimental} ============ The title compound was prepared using an *in situ* method. The first step was the addition of carbon disulfide (0.03 mol) to an ethanolic solution (20 ml) of butylmethylamine (0.03 mol) in ethanol (20 ml). The mixture was stirred for 1 h at 277 K. The resulting solution was added drop wise to a solution of cadmium(II) dichloride (0.015 mol) in ethanol (20 ml) followed by stirring for 4 h. A white precipitate was formed, filtered and washed with cold ethanol. The precipitate, Cd(C~6~H~12~NS~2~)~2~ (0.01 mol), and 2,2\'-bipyridyl (0.01 mol) were dissolved together in chloroform (20 ml) and stirred for 1 h. A yellowish precipitate was formed, filtered and dried in a desiccator. Crystallization was from its ethanol:chloroform (1:2) solution. Yield 86%; *M*.pt. 424--426 K. Elemental analysis. Found (calculated) for C~22~H~32~CdN~4~S~4~: C, 44.21 (44.156); H 5.32 (5.40); Cd 18.54 (18.96); N 9.23 (9.40); S 21.45 (21.63) %. UV (CHCl~3~) λ~max~ 284 (*L*(π) →*L*(π\*)). IR (KBr): ν(C---H) 2929*m*; ν(C≐N) 1485*m*; ν(N---C) 1158 s; ν(C≐S) 974 s; ν(Cd---S) 354 s cm^-1^. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.95 to 0.99 Å) and were included in the refinement in the riding model approximation, with *U*~iso~(H) set to 1.2 to 1.5*U*~equiv~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level. ::: ![](e-67-0m384-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the linear supramolecular chain along the a axis in (I) showing C---H···S contacts shown as orange dashed lines. ::: ![](e-67-0m384-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A view in projection down the b axis of the unit-cell contents for (I) showing supramolecular layers stacking along the c axis. The intermolecular C--H···S and π--π contacts are shown as orange and purple dashed lines, respectively. ::: ![](e-67-0m384-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e271 .table-wrap} ------------------------------------------ --------------------------------------- \[Cd(C~6~H~12~NS~2~)~2~(C~10~H~8~N~2~)\] *Z* = 2 *M~r~* = 593.16 *F*(000) = 608 Triclinic, *P*1 *D*~x~ = 1.512 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.3215 (4) Å Cell parameters from 8976 reflections *b* = 10.6465 (4) Å θ = 2.0--29.0° *c* = 12.4546 (5) Å µ = 1.18 mm^−1^ α = 81.566 (3)° *T* = 150 K β = 74.790 (3)° Plate, colourless γ = 83.641 (3)° 0.27 × 0.16 × 0.01 mm *V* = 1302.64 (9) Å^3^ ------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e418 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Xcaliber Eos Gemini diffractometer 5393 independent reflections Radiation source: fine-focus sealed tube 4623 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.042 Detector resolution: 16.1952 pixels mm^-1^ θ~max~ = 26.5°, θ~min~ = 2.3° ω scans *h* = −12→12 Absorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010) *k* = −13→13 *T*~min~ = 0.829, *T*~max~ = 0.990 *l* = −15→15 15837 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e538 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.029 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.066 H-atom parameters constrained *S* = 1.06 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0248*P*)^2^ + 0.0565*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5393 reflections (Δ/σ)~max~ = 0.001 284 parameters Δρ~max~ = 0.90 e Å^−3^ 0 restraints Δρ~min~ = −0.51 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e695 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e794 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cd 0.669262 (17) 0.668974 (17) 0.664886 (14) 0.02060 (7) S1 0.60096 (7) 0.69901 (6) 0.47470 (5) 0.02501 (15) S2 0.73388 (7) 0.90040 (6) 0.53865 (5) 0.02474 (15) S3 0.47202 (7) 0.54259 (7) 0.80306 (6) 0.02816 (16) S4 0.56208 (7) 0.77897 (6) 0.85175 (5) 0.02633 (15) N1 0.6294 (2) 0.93184 (19) 0.36194 (16) 0.0217 (5) N2 0.3637 (2) 0.6493 (2) 0.98885 (17) 0.0274 (5) N3 0.8838 (2) 0.62383 (19) 0.70520 (15) 0.0188 (4) N4 0.7756 (2) 0.46118 (19) 0.61699 (16) 0.0220 (5) C1 0.6525 (2) 0.8525 (2) 0.44916 (19) 0.0208 (5) C2 0.6688 (3) 1.0633 (2) 0.3422 (2) 0.0274 (6) H2A 0.6156 1.1102 0.4032 0.041\* H2B 0.6525 1.1048 0.2708 0.041\* H2C 0.7647 1.0626 0.3393 0.041\* C3 0.5565 (3) 0.9003 (2) 0.2837 (2) 0.0261 (6) H3A 0.4858 0.9693 0.2754 0.031\* H3B 0.5114 0.8209 0.3156 0.031\* C4 0.6490 (3) 0.8829 (3) 0.1684 (2) 0.0286 (6) H4A 0.5930 0.8765 0.1162 0.034\* H4B 0.7002 0.9593 0.1401 0.034\* C5 0.7477 (3) 0.7662 (3) 0.1679 (2) 0.0300 (6) H5A 0.6968 0.6893 0.1940 0.036\* H5B 0.8026 0.7713 0.2212 0.036\* C6 0.8409 (3) 0.7531 (3) 0.0524 (2) 0.0453 (8) H6A 0.7872 0.7466 −0.0006 0.068\* H6B 0.9021 0.6764 0.0565 0.068\* H6C 0.8933 0.8280 0.0269 0.068\* C7 0.4562 (2) 0.6567 (2) 0.8919 (2) 0.0232 (6) C8 0.2758 (3) 0.5432 (3) 1.0244 (2) 0.0350 (7) H8A 0.2020 0.5592 0.9870 0.053\* H8B 0.2387 0.5358 1.1058 0.053\* H8C 0.3281 0.4638 1.0041 0.053\* C9 0.3423 (3) 0.7429 (3) 1.0687 (2) 0.0329 (7) H9A 0.4118 0.8051 1.0410 0.039\* H9B 0.3536 0.6986 1.1417 0.039\* C11 0.2043 (3) 0.8137 (3) 1.0860 (2) 0.0350 (7) H11A 0.1347 0.7521 1.1166 0.042\* H11B 0.1916 0.8560 1.0128 0.042\* C12 0.1862 (3) 0.9133 (3) 1.1660 (2) 0.0400 (7) H12A 0.2177 0.8748 1.2328 0.048\* H12B 0.2427 0.9843 1.1285 0.048\* C13 0.0408 (3) 0.9657 (3) 1.2032 (3) 0.0484 (9) H13A 0.0119 1.0120 1.1383 0.073\* H13B 0.0329 1.0237 1.2592 0.073\* H13C −0.0165 0.8953 1.2361 0.073\* C14 0.9307 (3) 0.7054 (2) 0.7554 (2) 0.0249 (6) H14 0.8736 0.7775 0.7797 0.030\* C15 1.0578 (3) 0.6896 (3) 0.7734 (2) 0.0299 (6) H15 1.0872 0.7486 0.8106 0.036\* C16 1.1413 (3) 0.5869 (3) 0.7364 (2) 0.0327 (7) H16 1.2303 0.5749 0.7459 0.039\* C17 1.0942 (3) 0.5005 (2) 0.6848 (2) 0.0257 (6) H17 1.1504 0.4285 0.6590 0.031\* C18 0.9638 (2) 0.5211 (2) 0.67166 (18) 0.0185 (5) C19 0.9038 (2) 0.4298 (2) 0.62209 (19) 0.0190 (5) C20 0.9733 (3) 0.3185 (2) 0.5849 (2) 0.0243 (6) H20 1.0649 0.2995 0.5867 0.029\* C21 0.9076 (3) 0.2359 (2) 0.5453 (2) 0.0299 (6) H21 0.9535 0.1592 0.5200 0.036\* C22 0.7746 (3) 0.2662 (3) 0.5428 (2) 0.0304 (6) H22 0.7265 0.2101 0.5177 0.037\* C23 0.7136 (3) 0.3805 (3) 0.5781 (2) 0.0287 (6) H23 0.6231 0.4030 0.5744 0.034\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1595 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cd 0.01478 (10) 0.02502 (11) 0.02106 (10) 0.00349 (7) −0.00428 (8) −0.00391 (7) S1 0.0271 (4) 0.0231 (3) 0.0261 (3) −0.0007 (3) −0.0104 (3) −0.0012 (3) S2 0.0229 (3) 0.0269 (4) 0.0250 (3) 0.0008 (3) −0.0077 (3) −0.0042 (3) S3 0.0179 (3) 0.0379 (4) 0.0285 (4) −0.0019 (3) −0.0040 (3) −0.0068 (3) S4 0.0222 (3) 0.0264 (4) 0.0254 (3) 0.0025 (3) 0.0001 (3) −0.0016 (3) N1 0.0219 (12) 0.0217 (11) 0.0210 (11) 0.0041 (9) −0.0064 (9) −0.0031 (9) N2 0.0221 (12) 0.0335 (13) 0.0215 (11) −0.0001 (10) −0.0003 (10) 0.0018 (9) N3 0.0158 (11) 0.0228 (11) 0.0161 (10) −0.0001 (9) −0.0010 (9) −0.0037 (8) N4 0.0172 (11) 0.0250 (12) 0.0240 (11) −0.0005 (9) −0.0045 (9) −0.0050 (9) C1 0.0137 (12) 0.0230 (13) 0.0221 (13) 0.0065 (10) 0.0000 (10) −0.0050 (10) C2 0.0314 (15) 0.0216 (14) 0.0284 (14) 0.0027 (11) −0.0085 (12) −0.0022 (11) C3 0.0248 (14) 0.0284 (15) 0.0270 (14) 0.0011 (12) −0.0123 (12) −0.0009 (11) C4 0.0344 (16) 0.0305 (15) 0.0232 (13) −0.0031 (12) −0.0128 (13) 0.0002 (11) C5 0.0317 (16) 0.0310 (15) 0.0271 (14) −0.0011 (12) −0.0055 (13) −0.0069 (12) C6 0.048 (2) 0.054 (2) 0.0311 (16) 0.0015 (16) −0.0035 (15) −0.0122 (14) C7 0.0152 (13) 0.0302 (14) 0.0215 (13) 0.0075 (11) −0.0060 (11) 0.0014 (11) C8 0.0290 (16) 0.0405 (17) 0.0288 (15) −0.0032 (13) −0.0003 (13) 0.0053 (12) C9 0.0273 (15) 0.0460 (18) 0.0215 (13) 0.0018 (13) −0.0010 (12) −0.0041 (12) C11 0.0304 (16) 0.0350 (16) 0.0338 (16) 0.0017 (13) −0.0018 (13) −0.0003 (13) C12 0.0358 (18) 0.0343 (17) 0.0392 (17) −0.0016 (14) 0.0066 (15) −0.0009 (13) C13 0.0395 (19) 0.0323 (18) 0.061 (2) 0.0016 (15) 0.0080 (17) −0.0069 (15) C14 0.0211 (14) 0.0278 (14) 0.0253 (13) 0.0004 (11) −0.0039 (11) −0.0073 (11) C15 0.0240 (15) 0.0383 (17) 0.0312 (15) −0.0058 (13) −0.0098 (13) −0.0086 (12) C16 0.0184 (14) 0.0440 (18) 0.0383 (16) −0.0010 (13) −0.0133 (13) −0.0032 (13) C17 0.0200 (14) 0.0277 (14) 0.0282 (14) 0.0059 (11) −0.0071 (12) −0.0036 (11) C18 0.0153 (12) 0.0236 (13) 0.0136 (11) −0.0004 (10) −0.0012 (10) 0.0022 (10) C19 0.0173 (13) 0.0191 (13) 0.0172 (12) 0.0008 (10) −0.0007 (10) 0.0005 (9) C20 0.0189 (13) 0.0248 (14) 0.0242 (13) 0.0002 (11) 0.0009 (11) 0.0003 (11) C21 0.0354 (16) 0.0219 (14) 0.0283 (14) −0.0002 (12) −0.0004 (13) −0.0054 (11) C22 0.0337 (16) 0.0295 (15) 0.0290 (14) −0.0090 (13) −0.0048 (13) −0.0064 (12) C23 0.0217 (14) 0.0325 (16) 0.0325 (15) −0.0020 (12) −0.0057 (12) −0.0075 (12) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2237 .table-wrap} -------------------- -------------- ----------------------- -------------- Cd---S1 2.6104 (7) C6---H6C 0.9800 Cd---S2 2.7685 (7) C8---H8A 0.9800 Cd---S3 2.6468 (7) C8---H8B 0.9800 Cd---S4 2.6783 (7) C8---H8C 0.9800 Cd---N3 2.379 (2) C9---C11 1.514 (4) Cd---N4 2.441 (2) C9---H9A 0.9900 S1---C1 1.733 (3) C9---H9B 0.9900 S2---C1 1.721 (2) C11---C12 1.522 (4) S3---C7 1.727 (3) C11---H11A 0.9900 S4---C7 1.725 (3) C11---H11B 0.9900 N1---C1 1.332 (3) C12---C13 1.518 (4) N1---C2 1.469 (3) C12---H12A 0.9900 N1---C3 1.471 (3) C12---H12B 0.9900 N2---C7 1.327 (3) C13---H13A 0.9800 N2---C9 1.469 (3) C13---H13B 0.9800 N2---C8 1.472 (3) C13---H13C 0.9800 N3---C14 1.338 (3) C14---C15 1.377 (4) N3---C18 1.344 (3) C14---H14 0.9500 N4---C23 1.337 (3) C15---C16 1.372 (4) N4---C19 1.344 (3) C15---H15 0.9500 C2---H2A 0.9800 C16---C17 1.389 (4) C2---H2B 0.9800 C16---H16 0.9500 C2---H2C 0.9800 C17---C18 1.388 (3) C3---C4 1.526 (3) C17---H17 0.9500 C3---H3A 0.9900 C18---C19 1.489 (3) C3---H3B 0.9900 C19---C20 1.390 (3) C4---C5 1.516 (4) C20---C21 1.382 (4) C4---H4A 0.9900 C20---H20 0.9500 C4---H4B 0.9900 C21---C22 1.383 (4) C5---C6 1.522 (4) C21---H21 0.9500 C5---H5A 0.9900 C22---C23 1.383 (4) C5---H5B 0.9900 C22---H22 0.9500 C6---H6A 0.9800 C23---H23 0.9500 C6---H6B 0.9800 N3---Cd---N4 67.00 (7) N2---C7---S4 121.3 (2) N3---Cd---S1 130.89 (5) N2---C7---S3 119.9 (2) N4---Cd---S1 87.19 (5) S4---C7---S3 118.79 (14) N3---Cd---S3 115.46 (5) N2---C8---H8A 109.5 N4---Cd---S3 86.24 (5) N2---C8---H8B 109.5 S1---Cd---S3 102.91 (2) H8A---C8---H8B 109.5 N3---Cd---S4 93.32 (5) N2---C8---H8C 109.5 N4---Cd---S4 137.16 (5) H8A---C8---H8C 109.5 S1---Cd---S4 130.38 (2) H8B---C8---H8C 109.5 S3---Cd---S4 67.82 (2) N2---C9---C11 112.8 (2) N3---Cd---S2 94.02 (5) N2---C9---H9A 109.0 N4---Cd---S2 125.32 (5) C11---C9---H9A 109.0 S1---Cd---S2 67.03 (2) N2---C9---H9B 109.0 S3---Cd---S2 144.43 (2) C11---C9---H9B 109.0 S4---Cd---S2 92.26 (2) H9A---C9---H9B 107.8 C1---S1---Cd 89.21 (8) C9---C11---C12 111.9 (3) C1---S2---Cd 84.39 (8) C9---C11---H11A 109.2 C7---S3---Cd 87.18 (9) C12---C11---H11A 109.2 C7---S4---Cd 86.21 (9) C9---C11---H11B 109.2 C1---N1---C2 120.7 (2) C12---C11---H11B 109.2 C1---N1---C3 124.2 (2) H11A---C11---H11B 107.9 C2---N1---C3 114.95 (19) C13---C12---C11 112.5 (3) C7---N2---C9 123.5 (2) C13---C12---H12A 109.1 C7---N2---C8 121.3 (2) C11---C12---H12A 109.1 C9---N2---C8 115.2 (2) C13---C12---H12B 109.1 C14---N3---C18 118.6 (2) C11---C12---H12B 109.1 C14---N3---Cd 120.22 (16) H12A---C12---H12B 107.8 C18---N3---Cd 121.00 (15) C12---C13---H13A 109.5 C23---N4---C19 118.4 (2) C12---C13---H13B 109.5 C23---N4---Cd 122.04 (16) H13A---C13---H13B 109.5 C19---N4---Cd 119.35 (15) C12---C13---H13C 109.5 N1---C1---S2 120.62 (19) H13A---C13---H13C 109.5 N1---C1---S1 120.58 (19) H13B---C13---H13C 109.5 S2---C1---S1 118.80 (14) N3---C14---C15 123.0 (2) N1---C2---H2A 109.5 N3---C14---H14 118.5 N1---C2---H2B 109.5 C15---C14---H14 118.5 H2A---C2---H2B 109.5 C16---C15---C14 118.6 (2) N1---C2---H2C 109.5 C16---C15---H15 120.7 H2A---C2---H2C 109.5 C14---C15---H15 120.7 H2B---C2---H2C 109.5 C15---C16---C17 119.3 (2) N1---C3---C4 112.5 (2) C15---C16---H16 120.3 N1---C3---H3A 109.1 C17---C16---H16 120.3 C4---C3---H3A 109.1 C18---C17---C16 118.9 (2) N1---C3---H3B 109.1 C18---C17---H17 120.6 C4---C3---H3B 109.1 C16---C17---H17 120.6 H3A---C3---H3B 107.8 N3---C18---C17 121.5 (2) C5---C4---C3 113.9 (2) N3---C18---C19 116.3 (2) C5---C4---H4A 108.8 C17---C18---C19 122.1 (2) C3---C4---H4A 108.8 N4---C19---C20 121.6 (2) C5---C4---H4B 108.8 N4---C19---C18 115.3 (2) C3---C4---H4B 108.8 C20---C19---C18 123.1 (2) H4A---C4---H4B 107.7 C21---C20---C19 119.2 (2) C4---C5---C6 112.7 (2) C21---C20---H20 120.4 C4---C5---H5A 109.1 C19---C20---H20 120.4 C6---C5---H5A 109.1 C20---C21---C22 119.3 (2) C4---C5---H5B 109.1 C20---C21---H21 120.3 C6---C5---H5B 109.1 C22---C21---H21 120.3 H5A---C5---H5B 107.8 C21---C22---C23 118.0 (2) C5---C6---H6A 109.5 C21---C22---H22 121.0 C5---C6---H6B 109.5 C23---C22---H22 121.0 H6A---C6---H6B 109.5 N4---C23---C22 123.4 (2) C5---C6---H6C 109.5 N4---C23---H23 118.3 H6A---C6---H6C 109.5 C22---C23---H23 118.3 H6B---C6---H6C 109.5 N3---Cd---S1---C1 −78.98 (10) Cd---S2---C1---S1 −7.09 (13) N4---Cd---S1---C1 −134.92 (9) Cd---S1---C1---N1 −172.43 (19) S3---Cd---S1---C1 139.60 (8) Cd---S1---C1---S2 7.49 (13) S4---Cd---S1---C1 67.87 (8) C1---N1---C3---C4 −108.9 (3) S2---Cd---S1---C1 −4.42 (8) C2---N1---C3---C4 75.2 (3) N3---Cd---S2---C1 137.55 (9) N1---C3---C4---C5 68.0 (3) N4---Cd---S2---C1 73.04 (10) C3---C4---C5---C6 −178.6 (2) S1---Cd---S2---C1 4.47 (8) C9---N2---C7---S4 0.6 (3) S3---Cd---S2---C1 −75.42 (9) C8---N2---C7---S4 −178.37 (19) S4---Cd---S2---C1 −128.96 (8) C9---N2---C7---S3 −179.28 (19) N3---Cd---S3---C7 82.82 (10) C8---N2---C7---S3 1.8 (3) N4---Cd---S3---C7 145.11 (9) Cd---S4---C7---N2 −179.9 (2) S1---Cd---S3---C7 −128.65 (8) Cd---S4---C7---S3 −0.02 (13) S4---Cd---S3---C7 −0.01 (8) Cd---S3---C7---N2 179.86 (19) S2---Cd---S3---C7 −60.22 (9) Cd---S3---C7---S4 0.02 (13) N3---Cd---S4---C7 −116.17 (9) C7---N2---C9---C11 116.6 (3) N4---Cd---S4---C7 −57.04 (11) C8---N2---C9---C11 −64.4 (3) S1---Cd---S4---C7 88.29 (8) N2---C9---C11---C12 −178.0 (2) S3---Cd---S4---C7 0.01 (8) C9---C11---C12---C13 −168.1 (3) S2---Cd---S4---C7 149.67 (8) C18---N3---C14---C15 0.6 (4) N4---Cd---N3---C14 −176.21 (19) Cd---N3---C14---C15 −174.99 (19) S1---Cd---N3---C14 119.77 (16) N3---C14---C15---C16 1.2 (4) S3---Cd---N3---C14 −102.54 (17) C14---C15---C16---C17 −1.7 (4) S4---Cd---N3---C14 −35.56 (17) C15---C16---C17---C18 0.3 (4) S2---Cd---N3---C14 56.94 (17) C14---N3---C18---C17 −2.1 (3) N4---Cd---N3---C18 8.28 (16) Cd---N3---C18---C17 173.52 (17) S1---Cd---N3---C18 −55.74 (19) C14---N3---C18---C19 176.7 (2) S3---Cd---N3---C18 81.95 (17) Cd---N3---C18---C19 −7.7 (3) S4---Cd---N3---C18 148.92 (16) C16---C17---C18---N3 1.6 (4) S2---Cd---N3---C18 −118.57 (16) C16---C17---C18---C19 −177.1 (2) N3---Cd---N4---C23 176.6 (2) C23---N4---C19---C20 2.0 (3) S1---Cd---N4---C23 −46.31 (18) Cd---N4---C19---C20 −173.34 (17) S3---Cd---N4---C23 56.83 (18) C23---N4---C19---C18 −177.0 (2) S4---Cd---N4---C23 107.98 (18) Cd---N4---C19---C18 7.6 (3) S2---Cd---N4---C23 −105.41 (18) N3---C18---C19---N4 −0.2 (3) N3---Cd---N4---C19 −8.27 (16) C17---C18---C19---N4 178.6 (2) S1---Cd---N4---C19 128.86 (17) N3---C18---C19---C20 −179.2 (2) S3---Cd---N4---C19 −128.00 (17) C17---C18---C19---C20 −0.4 (4) S4---Cd---N4---C19 −76.85 (19) N4---C19---C20---C21 −2.3 (4) S2---Cd---N4---C19 69.76 (18) C18---C19---C20---C21 176.7 (2) C2---N1---C1---S2 −2.0 (3) C19---C20---C21---C22 0.4 (4) C3---N1---C1---S2 −177.74 (18) C20---C21---C22---C23 1.5 (4) C2---N1---C1---S1 177.93 (18) C19---N4---C23---C22 0.1 (4) C3---N1---C1---S1 2.2 (3) Cd---N4---C23---C22 175.32 (19) Cd---S2---C1---N1 172.83 (19) C21---C22---C23---N4 −1.9 (4) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3649 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C16---H16···S3^i^ 0.95 2.74 3.685 (3) 172 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: --------- ------------ Cd---S1 2.6104 (7) Cd---S2 2.7685 (7) Cd---S3 2.6468 (7) Cd---S4 2.6783 (7) Cd---N3 2.379 (2) Cd---N4 2.441 (2) --------- ------------ ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ----------------- --------- ------- ----------- ------------- C16---H16⋯S3^i^ 0.95 2.74 3.685 (3) 172 Symmetry code: (i) . ::: [^1]: ‡ Additional correspondence author, e-mail: aibi@ukm.my.

PubMed Central

2024-06-05T04:04:18.661222

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052129/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m384-m385", "authors": [ { "first": "Nur Amirah", "last": "Jamaluddin" }, { "first": "Ibrahim", "last": "Baba" }, { "first": "Mohamed Ibrahim", "last": "Mohamed Tahir" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }

PMC3052130

Related literature {#sec1} ================== For standard bond lengths, see: Allen *et al.* (1987[@bb1]). For hydrogen-bond motifs, see: Bernstein *et al.* (1995[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~9~BrFNO*M* *~r~* = 294.12Monoclinic,*a* = 4.4820 (2) Å*b* = 20.8088 (9) Å*c* = 12.2189 (5) Åβ = 94.570 (2)°*V* = 1135.97 (8) Å^3^*Z* = 4Mo *K*α radiationμ = 3.61 mm^−1^*T* = 296 K0.35 × 0.17 × 0.11 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2005[@bb3]) *T* ~min~ = 0.365, *T* ~max~ = 0.69210561 measured reflections2792 independent reflections1958 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.034 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.032*wR*(*F* ^2^) = 0.083*S* = 1.022792 reflections154 parametersH-atom parameters constrainedΔρ~max~ = 0.44 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e396} Data collection: *APEX2* (Bruker, 2005[@bb3]); cell refinement: *SAINT* (Bruker, 2005[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL* and *PLATON* (Spek, 2009[@bb5]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004429/jh2266sup1.cif](http://dx.doi.org/10.1107/S1600536811004429/jh2266sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004429/jh2266Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004429/jh2266Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2266&file=jh2266sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2266sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2266&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2266](http://scripts.iucr.org/cgi-bin/sendsup?jh2266)). AAA thanks the Islamic Azad University, Ardakan Branch for the research facilities (this paper was extracted from a research project supported by IAU). RK thanks the Science and Research Branch, Islamic Azad University, Tehran. HK thanks the PNU for financial support. MNT thanks Sargodha University for the research facilities. Comment ======= Schiff base ligands are one of the most prevalent systems in coordination chemistry. As part of a general study of Schiff bases, we have determined the crystal structure of the title compound. The asymmetric unit of the title compound, Fig. 1, comprises a potentially bidenate Schiff base ligand. The bond lengths (Allen *et al.,* 1987) and angles are within the normal ranges. The dihedral angle between the substituted benzene rings is 9.00 (11)Å. Strong intramolecular O---H···N hydrogen bonds generate *S(6)* ring motifs (Bernstein *et al.*, 1995). Experimental {#experimental} ============ The title compound was synthesized by adding 5-bromo-salicylaldehyde (2 mmol) to a solution of *p*-fluoroaniline (2 mmol) in ethanol (20 ml). The mixture was refluxed with stirring for half an hour. The resulting light-yellow solution was filtered. Pale-yellow single crystals suitable for *X*-ray diffraction were recrystallized from ethanol by slow evaporation of the solvents at room temperature over several days. Refinement {#refinement} ========== H atoms of the hydroxy groups were located by a rotating model and constrained to refine with the parent atoms with U~iso~(H) = 1.5 U~eq~(O), see Table 1. The remaining H atoms were positioned geometrically with C---H = 0.93 Å and included in a riding model approximation with U~iso~ (H) = 1.2 U~eq~ (C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of the title compound, showing 40% probability displacement ellipsoids and the atomic numbering. Intramolecular hydrogen bond is drawn as dashed lines. ::: ![](e-67-0o598-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram of the title compound, viewed down the c-axis. ::: ![](e-67-0o598-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e127 .table-wrap} ------------------------- --------------------------------------- C~13~H~9~BrFNO *F*(000) = 584 *M~r~* = 294.12 *D*~x~ = 1.720 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2520 reflections *a* = 4.4820 (2) Å θ = 2.5--28.5° *b* = 20.8088 (9) Å µ = 3.61 mm^−1^ *c* = 12.2189 (5) Å *T* = 296 K β = 94.570 (2)° Prism, pale-yellow *V* = 1135.97 (8) Å^3^ 0.35 × 0.17 × 0.11 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e252 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 2792 independent reflections Radiation source: fine-focus sealed tube 1958 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.034 φ and ω scans θ~max~ = 28.3°, θ~min~ = 1.9° Absorption correction: multi-scan (*SADABS*; Bruker, 2005) *h* = −5→5 *T*~min~ = 0.365, *T*~max~ = 0.692 *k* = −27→27 10561 measured reflections *l* = −16→16 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e369 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.032 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.083 H-atom parameters constrained *S* = 1.02 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0413*P*)^2^ + 0.1115*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2792 reflections (Δ/σ)~max~ = 0.001 154 parameters Δρ~max~ = 0.44 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e526 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e571 .table-wrap} ----- ------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 1.14491 (6) 0.420695 (13) 0.55664 (2) 0.06007 (13) F1 −0.3896 (4) −0.01392 (7) 0.62967 (14) 0.0714 (5) O1 0.7822 (4) 0.23124 (8) 0.89264 (12) 0.0502 (4) H1 0.6582 0.2057 0.8661 0.075\* N1 0.4202 (4) 0.17993 (8) 0.73875 (14) 0.0357 (4) C1 0.7310 (5) 0.26970 (10) 0.70681 (16) 0.0322 (5) C2 0.8605 (5) 0.27266 (11) 0.81485 (16) 0.0356 (5) C3 1.0742 (5) 0.31885 (11) 0.84342 (17) 0.0415 (5) H3 1.1617 0.3204 0.9150 0.050\* C4 1.1590 (5) 0.36250 (11) 0.76728 (18) 0.0418 (5) H4 1.3019 0.3936 0.7873 0.050\* C5 1.0300 (5) 0.35970 (10) 0.66087 (18) 0.0377 (5) C6 0.8198 (5) 0.31402 (10) 0.63019 (17) 0.0369 (5) H6 0.7360 0.3126 0.5581 0.044\* C7 0.5052 (4) 0.22206 (10) 0.67230 (17) 0.0343 (5) H7 0.4212 0.2224 0.6002 0.041\* C8 0.2060 (4) 0.13210 (10) 0.70442 (17) 0.0332 (5) C9 0.1021 (5) 0.12019 (11) 0.59655 (18) 0.0418 (5) H9 0.1690 0.1454 0.5406 0.050\* C10 −0.0999 (5) 0.07125 (11) 0.57144 (19) 0.0460 (6) H10 −0.1702 0.0633 0.4990 0.055\* C11 −0.1946 (5) 0.03478 (11) 0.6549 (2) 0.0445 (6) C12 −0.0996 (5) 0.04499 (12) 0.7619 (2) 0.0483 (6) H12 −0.1684 0.0195 0.8171 0.058\* C13 0.1021 (5) 0.09426 (12) 0.78670 (19) 0.0443 (6) H13 0.1687 0.1021 0.8595 0.053\* ----- ------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e935 .table-wrap} ----- ------------- -------------- -------------- --------------- --------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0733 (2) 0.05159 (18) 0.05448 (18) −0.01654 (13) −0.00037 (13) 0.01097 (12) F1 0.0782 (11) 0.0552 (10) 0.0788 (11) −0.0331 (9) −0.0069 (9) 0.0023 (8) O1 0.0592 (10) 0.0587 (11) 0.0313 (8) −0.0167 (8) −0.0051 (7) 0.0033 (8) N1 0.0310 (10) 0.0401 (11) 0.0354 (9) 0.0009 (8) −0.0014 (7) −0.0038 (8) C1 0.0303 (11) 0.0348 (11) 0.0312 (10) 0.0019 (9) 0.0005 (8) −0.0036 (9) C2 0.0348 (12) 0.0405 (12) 0.0315 (11) 0.0018 (9) 0.0023 (9) −0.0039 (9) C3 0.0422 (13) 0.0505 (14) 0.0305 (11) −0.0031 (11) −0.0043 (9) −0.0084 (10) C4 0.0393 (13) 0.0388 (13) 0.0467 (13) −0.0048 (10) −0.0005 (10) −0.0125 (10) C5 0.0418 (13) 0.0314 (11) 0.0402 (12) 0.0017 (10) 0.0045 (10) 0.0001 (9) C6 0.0382 (12) 0.0387 (12) 0.0327 (11) 0.0021 (10) −0.0036 (9) −0.0026 (9) C7 0.0326 (11) 0.0372 (12) 0.0322 (10) 0.0025 (9) −0.0028 (9) −0.0055 (9) C8 0.0275 (11) 0.0361 (12) 0.0357 (11) 0.0019 (9) −0.0004 (9) −0.0001 (9) C9 0.0495 (14) 0.0409 (13) 0.0344 (11) −0.0059 (11) −0.0005 (10) 0.0009 (10) C10 0.0517 (15) 0.0451 (14) 0.0397 (12) −0.0089 (11) −0.0066 (11) −0.0024 (10) C11 0.0407 (13) 0.0364 (13) 0.0554 (14) −0.0050 (10) −0.0027 (11) 0.0008 (11) C12 0.0501 (15) 0.0462 (15) 0.0492 (14) −0.0058 (12) 0.0068 (11) 0.0128 (11) C13 0.0425 (13) 0.0523 (15) 0.0370 (12) −0.0029 (11) −0.0035 (10) 0.0038 (10) ----- ------------- -------------- -------------- --------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1300 .table-wrap} -------------------- -------------- ----------------------- ------------- Br1---C5 1.898 (2) C5---C6 1.370 (3) F1---C11 1.358 (3) C6---H6 0.9300 O1---C2 1.350 (2) C7---H7 0.9300 O1---H1 0.8176 C8---C9 1.385 (3) N1---C7 1.274 (3) C8---C13 1.387 (3) N1---C8 1.423 (3) C9---C10 1.381 (3) C1---C6 1.395 (3) C9---H9 0.9300 C1---C2 1.400 (3) C10---C11 1.366 (3) C1---C7 1.455 (3) C10---H10 0.9300 C2---C3 1.382 (3) C11---C12 1.359 (3) C3---C4 1.375 (3) C12---C13 1.384 (3) C3---H3 0.9300 C12---H12 0.9300 C4---C5 1.381 (3) C13---H13 0.9300 C4---H4 0.9300 C2---O1---H1 110.1 N1---C7---H7 119.3 C7---N1---C8 121.51 (18) C1---C7---H7 119.3 C6---C1---C2 118.99 (19) C9---C8---C13 118.8 (2) C6---C1---C7 119.02 (19) C9---C8---N1 125.01 (19) C2---C1---C7 121.99 (19) C13---C8---N1 116.18 (18) O1---C2---C3 118.68 (18) C10---C9---C8 120.5 (2) O1---C2---C1 121.60 (19) C10---C9---H9 119.7 C3---C2---C1 119.7 (2) C8---C9---H9 119.7 C4---C3---C2 120.78 (19) C11---C10---C9 118.8 (2) C4---C3---H3 119.6 C11---C10---H10 120.6 C2---C3---H3 119.6 C9---C10---H10 120.6 C3---C4---C5 119.4 (2) F1---C11---C12 118.8 (2) C3---C4---H4 120.3 F1---C11---C10 118.5 (2) C5---C4---H4 120.3 C12---C11---C10 122.7 (2) C6---C5---C4 120.9 (2) C11---C12---C13 118.4 (2) C6---C5---Br1 119.87 (16) C11---C12---H12 120.8 C4---C5---Br1 119.20 (17) C13---C12---H12 120.8 C5---C6---C1 120.14 (19) C12---C13---C8 120.9 (2) C5---C6---H6 119.9 C12---C13---H13 119.6 C1---C6---H6 119.9 C8---C13---H13 119.6 N1---C7---C1 121.38 (19) C6---C1---C2---O1 179.65 (18) C6---C1---C7---N1 178.87 (18) C7---C1---C2---O1 0.1 (3) C2---C1---C7---N1 −1.6 (3) C6---C1---C2---C3 −0.4 (3) C7---N1---C8---C9 9.7 (3) C7---C1---C2---C3 180.0 (2) C7---N1---C8---C13 −171.9 (2) O1---C2---C3---C4 −179.3 (2) C13---C8---C9---C10 −0.4 (3) C1---C2---C3---C4 0.8 (3) N1---C8---C9---C10 178.1 (2) C2---C3---C4---C5 −0.5 (3) C8---C9---C10---C11 −0.2 (4) C3---C4---C5---C6 −0.2 (3) C9---C10---C11---F1 −179.0 (2) C3---C4---C5---Br1 179.31 (17) C9---C10---C11---C12 0.5 (4) C4---C5---C6---C1 0.5 (3) F1---C11---C12---C13 179.2 (2) Br1---C5---C6---C1 −179.00 (15) C10---C11---C12---C13 −0.2 (4) C2---C1---C6---C5 −0.2 (3) C11---C12---C13---C8 −0.3 (4) C7---C1---C6---C5 179.4 (2) C9---C8---C13---C12 0.6 (4) C8---N1---C7---C1 −178.11 (18) N1---C8---C13---C12 −177.9 (2) -------------------- -------------- ----------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1797 .table-wrap} --------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1···N1 0.82 1.89 2.612 (2) 146 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------- --------- ------- ----------- ------------- O1---H1⋯N1 0.82 1.89 2.612 (2) 146 :::

PubMed Central

2024-06-05T04:04:18.670011

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052130/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o598", "authors": [ { "first": "Amir Adabi", "last": "Ardakani" }, { "first": "Reza", "last": "Kia" }, { "first": "Hadi", "last": "Kargar" }, { "first": "Muhammad Nawaz", "last": "Tahir" } ] }

PMC3052131

Related literature {#sec1} ================== For the isotypic Ce analogue, see: Gao *et al.* (2011[@bb3]). For the structures and properties of lanthanide coordination compounds, see: Xiao *et al.* (2008[@bb8]); Lv *et al.* (2010[@bb4]). For bond lengths and angles in other complexes with nine-coordinate Nd^III^, see: Xiao *et al.* (2008[@bb8]); Wang *et al.* (2009[@bb6]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Nd~2~(C~10~H~8~O~4~)~3~(H~2~O)~2~\]*M* *~r~* = 901.00Triclinic,*a* = 10.4846 (13) Å*b* = 11.9660 (16) Å*c* = 12.3514 (16) Åα = 105.619 (5)°β = 97.202 (5)°γ = 92.625 (6)°*V* = 1475.5 (3) Å^3^*Z* = 2Mo *K*α radiationμ = 3.55 mm^−1^*T* = 296 K0.24 × 0.22 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 1997[@bb2]) *T* ~min~ = 0.516, *T* ~max~ = 0.5807865 measured reflections5315 independent reflections4806 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.013 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.021*wR*(*F* ^2^) = 0.054*S* = 1.035315 reflections415 parameters3 restraintsH-atom parameters constrainedΔρ~max~ = 0.64 e Å^−3^Δρ~min~ = −0.76 e Å^−3^ {#d5e579} Data collection: *SMART* (Bruker, 1997[@bb2]); cell refinement: *SAINT* (Bruker, 1997[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *XP* in *SHELXTL* (Sheldrick, 2008[@bb5]) and *DIAMOND* (Brandenburg, 2006[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb7]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006817/wm2461sup1.cif](http://dx.doi.org/10.1107/S1600536811006817/wm2461sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006817/wm2461Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006817/wm2461Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2461&file=wm2461sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2461sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2461&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2461](http://scripts.iucr.org/cgi-bin/sendsup?wm2461)). Comment ======= Lanthanide coordination polymers have shown versatile structural architectures, accompanied with desirable properties, like luminescence, magnetism, catalysis, gas adsorption and separation (Xiao *et al.*, 2008; Lv *et al.*, 2010). In order to extend our investigations in this field, we chose 1,3-phenylendiacetic acid (pda) as a functional ligand and synthesized the lanthanide coordination polymer \[Nd~2~(pda)~3~(H~2~O)~2~\]*~n~*, the structure of which is reported here. The title compound is isotypic with its Ce analogue (Gao *et al.*, 2011). The asymmetric unit of the title complex (Fig. 1) contains two crystallographically unique Nd^III^ ions, three pda ligands, and two coordinated water molecules. Both Nd1 and Nd2 are nine-coordinated within a distorted tricapped trigonal-prismatic geometry. The nine coordination sites are occupied by one O atom from a water molecule and eight O atoms from six different pda anions. The Nd---O bond lengths in the title complex are in the range 2.377 (2)--2.749 (2) Å, which is comparable to those reported for other Nd complexes with oxygen environment around the central metal (Xiao *et al*., 2008; Wang *et al.*, 2009). The pda ligands adopt two coordination modes, *viz*. *µ*~4~-hexadentate and *µ*~4~-pentadentate. Eight Nd^III^ ions and twelve pda ligands form a large \[Nd~8~(pda)~12~\] ring, whereas four Nd^III^ ions and six pda ligands form a small \[Nd~4~(pda)~6~\] ring (Fig. 2). These rings are further connected by the coordination interactions of pda ligands and Nd^III^ to generate a three-dimensional supramolecular framework (Fig. 2). Experimental {#experimental} ============ To a solution of neodymium nitrate hexahydrate (0.088 g, 0.2 mmol) in water (5 ml) was added an aqueous solution (5 ml) of the ligand (0.058 g, 0.3 mmol) and a drop of triethylamine. The reactants were sealed in a 25-ml Teflon-lined stainless-steel Parr bomb. The bomb was heated at 433 K for 3 d. Upon cooling, the solution yielded single crystals of the title complex in *ca* 75% yield. Anal./calc. for C~30~H~28~Nd~2~O~14~: C, 39.99; H, 3.13; found: C, 40.43; H, 3.47. Refinement {#refinement} ========== The H atoms of the water molecules were located in a difference Fourier map and were refined with distance constraints of O--H = 0.83 (5) Å. The C-bound H atoms were placed in geometrically idealized positions, with C--H = 0.93 and 0.97 Å for aryl and methylene H-atoms, respectively, and constrained to ride on their respective parent atoms, with *U*~iso~(H) = 1.2 *U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A drawing of the asymmetric unit in the structure of the title complex, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0m387-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Unit cell packing of the title complex showing the three-dimensional framework formed by a large \[Nd8(pda)12\] ring and a small \[Nd4(pda)6\] ring. ::: ![](e-67-0m387-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e205 .table-wrap} --------------------------------------- --------------------------------------- \[Nd~2~(C~10~H~8~O~4~)~3~(H~2~O)~2~\] *Z* = 2 *M~r~* = 901.00 *F*(000) = 880 Triclinic, *P*1 *D*~x~ = 2.028 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.4846 (13) Å Cell parameters from 5315 reflections *b* = 11.9660 (16) Å θ = 1.7--25.3° *c* = 12.3514 (16) Å µ = 3.55 mm^−1^ α = 105.619 (5)° *T* = 296 K β = 97.202 (5)° Block, colorless γ = 92.625 (6)° 0.24 × 0.22 × 0.20 mm *V* = 1475.5 (3) Å^3^ --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART CCD diffractometer 5315 independent reflections Radiation source: fine-focus sealed tube 4806 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.013 Detector resolution: 0 pixels mm^-1^ θ~max~ = 25.3°, θ~min~ = 1.7° φ and ω scans *h* = −12→12 Absorption correction: multi-scan (*SADABS*; Bruker, 1997) *k* = −12→14 *T*~min~ = 0.516, *T*~max~ = 0.580 *l* = −14→14 7865 measured reflections ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e475 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.021 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.054 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0265*P*)^2^ + 1.487*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5315 reflections (Δ/σ)~max~ = 0.001 415 parameters Δρ~max~ = 0.64 e Å^−3^ 3 restraints Δρ~min~ = −0.76 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e632 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e731 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Nd1 0.029517 (16) 0.026539 (14) 0.183517 (13) 0.01602 (6) Nd2 0.306439 (16) 0.036922 (15) 0.455279 (14) 0.01818 (6) C1 0.0706 (3) 0.8190 (3) 0.2608 (3) 0.0194 (7) C2 0.1023 (4) 0.7042 (3) 0.2819 (3) 0.0314 (9) H2A 0.1766 0.6787 0.2453 0.038\* H2B 0.1270 0.7169 0.3629 0.038\* C3 −0.0041 (4) 0.6073 (3) 0.2411 (3) 0.0244 (8) C4 −0.1173 (4) 0.6146 (3) 0.2887 (3) 0.0340 (9) H4 −0.1275 0.6802 0.3468 0.041\* C5 −0.2149 (4) 0.5267 (3) 0.2516 (4) 0.0368 (9) H5 −0.2897 0.5324 0.2853 0.044\* C6 −0.2021 (4) 0.4299 (3) 0.1643 (3) 0.0330 (9) H6 −0.2691 0.3714 0.1383 0.040\* C7 −0.0910 (4) 0.4192 (3) 0.1154 (3) 0.0265 (8) C8 0.0082 (4) 0.5078 (3) 0.1549 (3) 0.0252 (8) H8 0.0843 0.5002 0.1230 0.030\* C9 −0.0755 (4) 0.3102 (3) 0.0240 (3) 0.0326 (9) H9A −0.1557 0.2884 −0.0279 0.039\* H9B −0.0092 0.3272 −0.0188 0.039\* C10 −0.0404 (3) 0.2088 (3) 0.0679 (3) 0.0220 (7) C11 −0.2153 (3) 0.7492 (3) 0.5878 (3) 0.0243 (7) C12 −0.1546 (4) 0.6428 (3) 0.6052 (4) 0.0475 (12) H12A −0.0771 0.6353 0.5692 0.057\* H12B −0.1280 0.6558 0.6860 0.057\* C13 −0.2359 (4) 0.5289 (3) 0.5614 (3) 0.0322 (9) C14 −0.3482 (4) 0.5093 (3) 0.6035 (3) 0.0393 (10) H14 −0.3755 0.5681 0.6597 0.047\* C15 −0.4198 (4) 0.4044 (3) 0.5636 (3) 0.0334 (9) H15 −0.4955 0.3927 0.5924 0.040\* C16 −0.3801 (3) 0.3155 (3) 0.4805 (3) 0.0280 (8) H16 −0.4301 0.2449 0.4526 0.034\* C17 −0.2661 (3) 0.3315 (3) 0.4388 (3) 0.0232 (7) C18 −0.1952 (3) 0.4387 (3) 0.4794 (3) 0.0258 (8) H18 −0.1190 0.4506 0.4512 0.031\* C19 −0.2165 (3) 0.2365 (3) 0.3508 (3) 0.0257 (8) H19A −0.1419 0.2690 0.3271 0.031\* H19B −0.2825 0.2110 0.2848 0.031\* C20 −0.1792 (3) 0.1314 (3) 0.3893 (3) 0.0194 (7) C21 0.4696 (3) 0.1360 (3) −0.3232 (3) 0.0249 (8) C22 0.5520 (3) 0.2052 (3) −0.2133 (3) 0.0289 (8) H22A 0.6237 0.1609 −0.1973 0.035\* H22B 0.5873 0.2772 −0.2238 0.035\* C23 0.4804 (3) 0.2339 (3) −0.1121 (3) 0.0272 (8) C24 0.3884 (5) 0.3138 (4) −0.1054 (4) 0.0496 (12) H24 0.3733 0.3507 −0.1626 0.060\* H1W −0.2406 0.0218 0.0635 0.060\* H2W −0.2406 −0.0802 0.1125 0.060\* H4W 0.1094 0.0990 0.6110 0.060\* H3W 0.0294 0.0896 0.5035 0.060\* C25 0.3193 (5) 0.3397 (4) −0.0164 (4) 0.0574 (14) H25 0.2561 0.3919 −0.0146 0.069\* C26 0.3432 (4) 0.2885 (4) 0.0707 (3) 0.0409 (10) H26 0.2972 0.3075 0.1319 0.049\* C27 0.4349 (3) 0.2093 (3) 0.0676 (3) 0.0270 (8) C28 0.5025 (3) 0.1825 (3) −0.0248 (3) 0.0261 (8) H28 0.5641 0.1286 −0.0278 0.031\* C29 0.4652 (4) 0.1561 (4) 0.1644 (3) 0.0348 (9) H29A 0.5015 0.2183 0.2310 0.042\* H29B 0.5324 0.1040 0.1459 0.042\* C30 0.3579 (3) 0.0892 (3) 0.1978 (3) 0.0242 (7) O1 0.1566 (2) 0.9053 (2) 0.2968 (2) 0.0274 (5) O2 −0.0342 (2) 0.8302 (2) 0.2080 (2) 0.0284 (6) O3 −0.0371 (3) 0.10987 (19) −0.0009 (2) 0.0300 (6) O4 −0.0146 (3) 0.2218 (2) 0.1716 (2) 0.0346 (6) O5 −0.1595 (2) 0.84733 (19) 0.64899 (19) 0.0252 (5) O6 −0.3093 (2) 0.7452 (2) 0.5148 (2) 0.0312 (6) O7 −0.0998 (2) 0.0686 (2) 0.3388 (2) 0.0274 (5) O8 −0.2271 (3) 0.1114 (2) 0.4695 (2) 0.0365 (6) O9 0.5273 (2) 0.1006 (2) −0.41110 (18) 0.0243 (5) O10 0.3524 (3) 0.1179 (3) −0.3299 (2) 0.0445 (7) O11 0.3881 (2) 0.0619 (2) 0.2879 (2) 0.0300 (6) O12 0.2492 (2) 0.0633 (2) 0.1359 (2) 0.0308 (6) O13 −0.2057 (2) −0.0221 (2) 0.1036 (2) 0.0355 (6) O14 0.1067 (2) 0.1022 (2) 0.5416 (2) 0.0334 (6) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1777 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Nd1 0.02272 (10) 0.01120 (9) 0.01384 (9) 0.00192 (7) 0.00258 (7) 0.00292 (7) Nd2 0.02183 (10) 0.01863 (10) 0.01494 (10) 0.00167 (7) 0.00283 (7) 0.00602 (7) C1 0.0306 (18) 0.0139 (16) 0.0136 (15) 0.0028 (14) 0.0065 (14) 0.0017 (13) C2 0.043 (2) 0.0156 (18) 0.037 (2) 0.0046 (15) −0.0013 (17) 0.0105 (16) C3 0.038 (2) 0.0119 (16) 0.0242 (18) 0.0036 (14) 0.0010 (15) 0.0084 (14) C4 0.060 (3) 0.0161 (18) 0.029 (2) 0.0100 (17) 0.0159 (19) 0.0066 (15) C5 0.044 (2) 0.030 (2) 0.046 (2) 0.0107 (18) 0.0183 (19) 0.0189 (19) C6 0.041 (2) 0.0188 (19) 0.040 (2) −0.0011 (16) −0.0013 (18) 0.0131 (17) C7 0.045 (2) 0.0113 (17) 0.0229 (18) 0.0071 (15) −0.0007 (16) 0.0063 (14) C8 0.037 (2) 0.0177 (17) 0.0242 (17) 0.0095 (15) 0.0074 (15) 0.0093 (14) C9 0.057 (3) 0.0178 (18) 0.0218 (18) 0.0051 (17) 0.0011 (17) 0.0055 (15) C10 0.0297 (18) 0.0129 (17) 0.0227 (18) 0.0016 (13) 0.0054 (14) 0.0032 (14) C11 0.0265 (18) 0.0175 (18) 0.0254 (18) −0.0028 (14) 0.0044 (15) 0.0005 (14) C12 0.039 (2) 0.016 (2) 0.073 (3) 0.0030 (17) −0.018 (2) −0.0002 (19) C13 0.034 (2) 0.0155 (18) 0.041 (2) 0.0040 (15) −0.0102 (17) 0.0048 (16) C14 0.048 (3) 0.029 (2) 0.036 (2) 0.0154 (19) 0.0028 (19) −0.0006 (17) C15 0.032 (2) 0.030 (2) 0.039 (2) 0.0066 (16) 0.0131 (17) 0.0079 (17) C16 0.0314 (19) 0.0191 (18) 0.033 (2) 0.0000 (15) 0.0033 (16) 0.0077 (15) C17 0.0307 (19) 0.0192 (17) 0.0210 (17) 0.0042 (14) 0.0007 (14) 0.0087 (14) C18 0.0224 (17) 0.0199 (18) 0.035 (2) 0.0017 (14) −0.0010 (15) 0.0103 (15) C19 0.0315 (19) 0.0219 (18) 0.0252 (18) 0.0034 (15) 0.0049 (15) 0.0082 (15) C20 0.0236 (17) 0.0151 (16) 0.0167 (16) −0.0015 (13) 0.0018 (13) 0.0007 (13) C21 0.0294 (19) 0.030 (2) 0.0158 (17) 0.0037 (15) 0.0031 (14) 0.0064 (15) C22 0.0305 (19) 0.035 (2) 0.0192 (18) 0.0000 (16) 0.0027 (15) 0.0038 (16) C23 0.033 (2) 0.030 (2) 0.0161 (17) −0.0001 (15) 0.0021 (15) 0.0036 (15) C24 0.069 (3) 0.055 (3) 0.039 (2) 0.029 (2) 0.026 (2) 0.026 (2) C25 0.077 (3) 0.063 (3) 0.050 (3) 0.043 (3) 0.037 (3) 0.027 (2) C26 0.056 (3) 0.040 (2) 0.030 (2) 0.010 (2) 0.0212 (19) 0.0081 (18) C27 0.0319 (19) 0.0269 (19) 0.0227 (18) −0.0050 (15) 0.0032 (15) 0.0094 (15) C28 0.0246 (18) 0.0267 (19) 0.0253 (18) −0.0011 (14) 0.0007 (15) 0.0060 (15) C29 0.030 (2) 0.047 (2) 0.030 (2) −0.0072 (17) 0.0004 (16) 0.0188 (18) C30 0.0282 (19) 0.0257 (19) 0.0193 (17) 0.0035 (15) 0.0082 (15) 0.0046 (15) O1 0.0361 (14) 0.0165 (12) 0.0282 (13) −0.0012 (10) −0.0038 (11) 0.0079 (10) O2 0.0297 (13) 0.0205 (13) 0.0363 (14) 0.0001 (10) −0.0006 (11) 0.0126 (11) O3 0.0495 (16) 0.0138 (12) 0.0258 (13) 0.0040 (11) 0.0117 (12) 0.0010 (10) O4 0.0642 (19) 0.0190 (13) 0.0199 (13) 0.0106 (12) −0.0007 (12) 0.0060 (10) O5 0.0326 (13) 0.0158 (12) 0.0228 (12) 0.0005 (10) −0.0011 (10) 0.0001 (10) O6 0.0322 (14) 0.0198 (13) 0.0356 (14) −0.0023 (10) −0.0064 (12) 0.0035 (11) O7 0.0340 (14) 0.0250 (13) 0.0264 (13) 0.0103 (11) 0.0121 (11) 0.0080 (11) O8 0.0593 (18) 0.0261 (14) 0.0353 (15) 0.0142 (13) 0.0287 (14) 0.0160 (12) O9 0.0316 (13) 0.0260 (13) 0.0162 (11) 0.0074 (10) 0.0064 (10) 0.0050 (10) O10 0.0263 (15) 0.073 (2) 0.0265 (14) −0.0010 (14) 0.0021 (12) 0.0016 (14) O11 0.0310 (14) 0.0403 (15) 0.0247 (13) 0.0063 (11) 0.0083 (11) 0.0165 (12) O12 0.0262 (13) 0.0424 (16) 0.0236 (13) −0.0044 (11) 0.0031 (11) 0.0100 (12) O13 0.0298 (14) 0.0386 (16) 0.0362 (15) −0.0043 (12) −0.0032 (12) 0.0119 (12) O14 0.0334 (14) 0.0384 (16) 0.0316 (14) 0.0090 (12) 0.0078 (11) 0.0129 (12) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2568 .table-wrap} -------------------------- ------------- ----------------------------- -------------- Nd1---O3^i^ 2.415 (2) C15---C16 1.384 (5) Nd1---O5^ii^ 2.416 (2) C15---H15 0.9300 Nd1---O4 2.441 (2) C16---C17 1.384 (5) Nd1---O7 2.442 (2) C16---H16 0.9300 Nd1---O12 2.496 (2) C17---C18 1.387 (5) Nd1---O13 2.519 (2) C17---C19 1.508 (5) Nd1---O2^iii^ 2.520 (2) C18---H18 0.9300 Nd1---O1^iii^ 2.576 (2) C19---C20 1.510 (5) Nd1---O3 2.749 (2) C19---H19A 0.9700 Nd2---O8^iv^ 2.377 (2) C19---H19B 0.9700 Nd2---O11 2.418 (2) C20---O8 1.239 (4) Nd2---O9^v^ 2.462 (2) C20---O7 1.257 (4) Nd2---O1^iii^ 2.475 (2) C21---O10 1.227 (4) Nd2---O14 2.529 (3) C21---O9 1.290 (4) Nd2---O6^ii^ 2.531 (2) C21---C22 1.519 (5) Nd2---O10^vi^ 2.542 (3) C21---Nd2^vii^ 2.952 (3) Nd2---O5^ii^ 2.571 (2) C22---C23 1.506 (5) Nd2---O9^vi^ 2.621 (2) C22---H22A 0.9700 C1---O2 1.237 (4) C22---H22B 0.9700 C1---O1 1.282 (4) C23---C28 1.380 (5) C1---C2 1.510 (4) C23---C24 1.383 (5) C2---C3 1.506 (5) C24---C25 1.366 (6) C2---H2A 0.9700 C24---H24 0.9300 C2---H2B 0.9700 C25---C26 1.377 (6) C3---C4 1.385 (5) C25---H25 0.9300 C3---C8 1.392 (5) C26---C27 1.377 (5) C4---C5 1.374 (6) C26---H26 0.9300 C4---H4 0.9300 C27---C28 1.391 (5) C5---C6 1.378 (5) C27---C29 1.507 (5) C5---H5 0.9300 C28---H28 0.9300 C6---C7 1.373 (5) C29---C30 1.512 (5) C6---H6 0.9300 C29---H29A 0.9700 C7---C8 1.392 (5) C29---H29B 0.9700 C7---C9 1.508 (5) C30---O11 1.251 (4) C8---H8 0.9300 C30---O12 1.266 (4) C9---C10 1.499 (5) O1---Nd2^viii^ 2.475 (2) C9---H9A 0.9700 O1---Nd1^viii^ 2.576 (2) C9---H9B 0.9700 O2---Nd1^viii^ 2.520 (2) C10---O4 1.241 (4) O3---Nd1^i^ 2.415 (2) C10---O3 1.263 (4) O5---Nd1^ii^ 2.416 (2) C11---O6 1.239 (4) O5---Nd2^ii^ 2.571 (2) C11---O5 1.281 (4) O6---Nd2^ii^ 2.531 (2) C11---C12 1.503 (5) O8---Nd2^iv^ 2.377 (2) C12---C13 1.502 (5) O9---Nd2^v^ 2.462 (2) C12---H12A 0.9700 O9---Nd2^vii^ 2.621 (2) C12---H12B 0.9700 O10---Nd2^vii^ 2.542 (3) C13---C14 1.381 (6) O13---H1W 0.8758 C13---C18 1.391 (5) O13---H2W 0.8110 C14---C15 1.367 (6) O14---H4W 0.8644 C14---H14 0.9300 O14---H3W 0.8693 O3^i^---Nd1---O5^ii^ 144.23 (9) C7---C9---H9B 108.7 O3^i^---Nd1---O4 113.33 (8) H9A---C9---H9B 107.6 O5^ii^---Nd1---O4 76.46 (8) O4---C10---O3 119.9 (3) O3^i^---Nd1---O7 141.44 (8) O4---C10---C9 120.3 (3) O5^ii^---Nd1---O7 71.16 (8) O3---C10---C9 119.9 (3) O4---Nd1---O7 84.45 (8) O6---C11---O5 120.5 (3) O3^i^---Nd1---O12 74.32 (8) O6---C11---C12 123.3 (3) O5^ii^---Nd1---O12 71.68 (8) O5---C11---C12 116.0 (3) O4---Nd1---O12 88.05 (9) C13---C12---C11 117.0 (3) O7---Nd1---O12 142.83 (8) C13---C12---H12A 108.0 O3^i^---Nd1---O13 77.43 (9) C11---C12---H12A 108.0 O5^ii^---Nd1---O13 138.26 (8) C13---C12---H12B 108.0 O4---Nd1---O13 83.71 (9) C11---C12---H12B 108.0 O7---Nd1---O13 70.65 (8) H12A---C12---H12B 107.3 O12---Nd1---O13 144.46 (8) C14---C13---C18 118.6 (3) O3^i^---Nd1---O2^iii^ 75.03 (8) C14---C13---C12 121.8 (4) O5^ii^---Nd1---O2^iii^ 112.51 (8) C18---C13---C12 119.6 (4) O4---Nd1---O2^iii^ 153.02 (9) C15---C14---C13 120.8 (4) O7---Nd1---O2^iii^ 75.35 (8) C15---C14---H14 119.6 O12---Nd1---O2^iii^ 118.83 (8) C13---C14---H14 119.6 O13---Nd1---O2^iii^ 72.90 (8) C14---C15---C16 120.4 (4) O3^i^---Nd1---O1^iii^ 94.43 (8) C14---C15---H15 119.8 O5^ii^---Nd1---O1^iii^ 69.57 (8) C16---C15---H15 119.8 O4---Nd1---O1^iii^ 146.02 (8) C15---C16---C17 120.1 (3) O7---Nd1---O1^iii^ 85.44 (8) C15---C16---H16 119.9 O12---Nd1---O1^iii^ 80.76 (8) C17---C16---H16 119.9 O13---Nd1---O1^iii^ 122.85 (8) C16---C17---C18 118.8 (3) O2^iii^---Nd1---O1^iii^ 50.71 (7) C16---C17---C19 122.3 (3) O3^i^---Nd1---O3 64.78 (9) C18---C17---C19 118.9 (3) O5^ii^---Nd1---O3 119.11 (7) C17---C18---C13 121.2 (3) O4---Nd1---O3 48.91 (7) C17---C18---H18 119.4 O7---Nd1---O3 119.10 (8) C13---C18---H18 119.4 O12---Nd1---O3 80.67 (8) C17---C19---C20 115.1 (3) O13---Nd1---O3 67.92 (8) C17---C19---H19A 108.5 O2^iii^---Nd1---O3 128.34 (7) C20---C19---H19A 108.5 O1^iii^---Nd1---O3 155.25 (8) C17---C19---H19B 108.5 O8^iv^---Nd2---O11 140.87 (9) C20---C19---H19B 108.5 O8^iv^---Nd2---O9^v^ 80.82 (8) H19A---C19---H19B 107.5 O11---Nd2---O9^v^ 72.33 (8) O8---C20---O7 123.0 (3) O8^iv^---Nd2---O1^iii^ 74.90 (9) O8---C20---C19 118.7 (3) O11---Nd2---O1^iii^ 76.48 (8) O7---C20---C19 118.3 (3) O9^v^---Nd2---O1^iii^ 88.60 (8) O10---C21---O9 120.9 (3) O8^iv^---Nd2---O14 71.83 (9) O10---C21---C22 121.8 (3) O11---Nd2---O14 131.77 (8) O9---C21---C22 117.3 (3) O9^v^---Nd2---O14 152.59 (8) C23---C22---C21 114.1 (3) O1^iii^---Nd2---O14 85.98 (8) C23---C22---H22A 108.7 O8^iv^---Nd2---O6^ii^ 140.58 (9) C21---C22---H22A 108.7 O11---Nd2---O6^ii^ 77.47 (9) C23---C22---H22B 108.7 O9^v^---Nd2---O6^ii^ 132.09 (8) C21---C22---H22B 108.7 O1^iii^---Nd2---O6^ii^ 119.41 (8) H22A---C22---H22B 107.6 O14---Nd2---O6^ii^ 72.89 (9) C28---C23---C24 118.0 (3) O8^iv^---Nd2---O10^vi^ 73.99 (10) C28---C23---C22 122.3 (3) O11---Nd2---O10^vi^ 139.31 (9) C24---C23---C22 119.7 (3) O9^v^---Nd2---O10^vi^ 103.61 (8) C25---C24---C23 121.3 (4) O1^iii^---Nd2---O10^vi^ 144.10 (9) C25---C24---H24 119.4 O14---Nd2---O10^vi^ 67.60 (8) C23---C24---H24 119.4 O6^ii^---Nd2---O10^vi^ 76.78 (9) C24---C25---C26 120.1 (4) O8^iv^---Nd2---O5^ii^ 123.39 (9) C24---C25---H25 120.0 O11---Nd2---O5^ii^ 67.91 (8) C26---C25---H25 120.0 O9^v^---Nd2---O5^ii^ 137.67 (7) C25---C26---C27 120.4 (4) O1^iii^---Nd2---O5^ii^ 68.79 (7) C25---C26---H26 119.8 O14---Nd2---O5^ii^ 63.87 (8) C27---C26---H26 119.8 O6^ii^---Nd2---O5^ii^ 50.79 (7) C26---C27---C28 118.7 (3) O10^vi^---Nd2---O5^ii^ 115.78 (9) C26---C27---C29 120.8 (3) O8^iv^---Nd2---O9^vi^ 99.49 (9) C28---C27---C29 120.5 (3) O11---Nd2---O9^vi^ 94.98 (8) C23---C28---C27 121.6 (3) O9^v^---Nd2---O9^vi^ 65.88 (9) C23---C28---H28 119.2 O1^iii^---Nd2---O9^vi^ 154.47 (8) C27---C28---H28 119.2 O14---Nd2---O9^vi^ 116.39 (8) C27---C29---C30 119.0 (3) O6^ii^---Nd2---O9^vi^ 80.98 (7) C27---C29---H29A 107.6 O10^vi^---Nd2---O9^vi^ 50.17 (8) C30---C29---H29A 107.6 O5^ii^---Nd2---O9^vi^ 130.65 (7) C27---C29---H29B 107.6 O2---C1---O1 120.1 (3) C30---C29---H29B 107.6 O2---C1---C2 121.6 (3) H29A---C29---H29B 107.0 O1---C1---C2 118.3 (3) O11---C30---O12 125.0 (3) C3---C2---C1 115.8 (3) O11---C30---C29 114.2 (3) C3---C2---H2A 108.3 O12---C30---C29 120.8 (3) C1---C2---H2A 108.3 C1---O1---Nd2^viii^ 149.4 (2) C3---C2---H2B 108.3 C1---O1---Nd1^viii^ 92.21 (19) C1---C2---H2B 108.3 Nd2^viii^---O1---Nd1^viii^ 109.46 (8) H2A---C2---H2B 107.4 C1---O2---Nd1^viii^ 96.0 (2) C4---C3---C8 118.0 (3) C10---O3---Nd1^i^ 155.9 (2) C4---C3---C2 120.9 (3) C10---O3---Nd1 87.89 (19) C8---C3---C2 121.1 (3) Nd1^i^---O3---Nd1 115.22 (9) C5---C4---C3 121.1 (4) C10---O4---Nd1 103.32 (19) C5---C4---H4 119.4 C11---O5---Nd1^ii^ 153.8 (2) C3---C4---H4 119.4 C11---O5---Nd2^ii^ 92.8 (2) C4---C5---C6 120.1 (4) Nd1^ii^---O5---Nd2^ii^ 111.55 (9) C4---C5---H5 120.0 C11---O6---Nd2^ii^ 95.8 (2) C6---C5---H5 120.0 C20---O7---Nd1 147.9 (2) C7---C6---C5 120.5 (4) C20---O8---Nd2^iv^ 144.9 (2) C7---C6---H6 119.7 C21---O9---Nd2^v^ 132.8 (2) C5---C6---H6 119.7 C21---O9---Nd2^vii^ 91.54 (19) C6---C7---C8 119.0 (3) Nd2^v^---O9---Nd2^vii^ 114.12 (8) C6---C7---C9 120.0 (3) C21---O10---Nd2^vii^ 96.9 (2) C8---C7---C9 120.9 (3) C30---O11---Nd2 143.5 (2) C7---C8---C3 121.3 (3) C30---O12---Nd1 131.1 (2) C7---C8---H8 119.4 Nd1---O13---H1W 116.9 C3---C8---H8 119.4 Nd1---O13---H2W 117.1 C10---C9---C7 114.1 (3) H1W---O13---H2W 125.7 C10---C9---H9A 108.7 Nd2---O14---H4W 113.5 C7---C9---H9A 108.7 Nd2---O14---H3W 123.7 C10---C9---H9B 108.7 H4W---O14---H3W 113.8 O2---C1---C2---C3 −3.6 (5) O1^iii^---Nd1---O3---C10 −137.8 (2) O1---C1---C2---C3 178.0 (3) C1^iii^---Nd1---O3---C10 171.40 (19) C1---C2---C3---C4 −65.1 (5) O3^i^---Nd1---O3---Nd1^i^ 0.0 C1---C2---C3---C8 115.0 (4) O5^ii^---Nd1---O3---Nd1^i^ 139.84 (10) C8---C3---C4---C5 −0.4 (5) O4---Nd1---O3---Nd1^i^ 172.57 (17) C2---C3---C4---C5 179.8 (3) O7---Nd1---O3---Nd1^i^ −136.64 (10) C3---C4---C5---C6 −1.1 (6) O12---Nd1---O3---Nd1^i^ 76.98 (11) C4---C5---C6---C7 1.4 (6) O13---Nd1---O3---Nd1^i^ −86.07 (11) C5---C6---C7---C8 −0.2 (5) O2^iii^---Nd1---O3---Nd1^i^ −42.57 (15) C5---C6---C7---C9 176.9 (3) O1^iii^---Nd1---O3---Nd1^i^ 35.2 (2) C6---C7---C8---C3 −1.3 (5) C1^iii^---Nd1---O3---Nd1^i^ −15.6 (2) C9---C7---C8---C3 −178.4 (3) O3---C10---O4---Nd1 −0.8 (4) C4---C3---C8---C7 1.6 (5) C9---C10---O4---Nd1 179.2 (3) C2---C3---C8---C7 −178.6 (3) O3^i^---Nd1---O4---C10 7.8 (3) C6---C7---C9---C10 −78.4 (4) O5^ii^---Nd1---O4---C10 151.4 (2) C8---C7---C9---C10 98.7 (4) O7---Nd1---O4---C10 −136.7 (2) C7---C9---C10---O4 −6.9 (5) O12---Nd1---O4---C10 79.8 (2) C7---C9---C10---O3 173.1 (3) O13---Nd1---O4---C10 −65.6 (2) O6---C11---C12---C13 −21.0 (6) O2^iii^---Nd1---O4---C10 −95.4 (3) O5---C11---C12---C13 162.9 (4) O1^iii^---Nd1---O4---C10 150.0 (2) C11---C12---C13---C14 −62.9 (6) O3---Nd1---O4---C10 0.4 (2) C11---C12---C13---C18 119.6 (4) C1^iii^---Nd1---O4---C10 −162.0 (3) C18---C13---C14---C15 −1.6 (6) O6---C11---O5---Nd1^ii^ 156.4 (4) C12---C13---C14---C15 −179.1 (4) C12---C11---O5---Nd1^ii^ −27.5 (7) C13---C14---C15---C16 0.5 (6) O6---C11---O5---Nd2^ii^ −2.8 (3) C14---C15---C16---C17 1.3 (6) C12---C11---O5---Nd2^ii^ 173.3 (3) C15---C16---C17---C18 −1.9 (5) O5---C11---O6---Nd2^ii^ 2.9 (4) C15---C16---C17---C19 178.2 (3) C12---C11---O6---Nd2^ii^ −173.0 (4) C16---C17---C18---C13 0.8 (5) O8---C20---O7---Nd1 175.1 (3) C19---C17---C18---C13 −179.3 (3) C19---C20---O7---Nd1 −5.4 (6) C14---C13---C18---C17 0.9 (5) O3^i^---Nd1---O7---C20 −105.2 (4) C12---C13---C18---C17 178.5 (3) O5^ii^---Nd1---O7---C20 93.5 (4) C16---C17---C19---C20 −65.2 (4) O4---Nd1---O7---C20 15.9 (4) C18---C17---C19---C20 114.9 (4) O12---Nd1---O7---C20 95.2 (4) C17---C19---C20---O8 22.9 (5) O13---Nd1---O7---C20 −69.4 (4) C17---C19---C20---O7 −156.6 (3) O2^iii^---Nd1---O7---C20 −146.1 (4) O10---C21---C22---C23 8.0 (5) O1^iii^---Nd1---O7---C20 163.4 (4) O9---C21---C22---C23 −174.6 (3) O3---Nd1---O7---C20 −20.0 (4) C21---C22---C23---C28 109.6 (4) C1^iii^---Nd1---O7---C20 −170.7 (4) C21---C22---C23---C24 −70.0 (5) O7---C20---O8---Nd2^iv^ −36.4 (6) C28---C23---C24---C25 −1.3 (7) C19---C20---O8---Nd2^iv^ 144.1 (3) C22---C23---C24---C25 178.3 (4) O10---C21---O9---Nd2^v^ −118.1 (3) C23---C24---C25---C26 2.0 (8) C22---C21---O9---Nd2^v^ 64.4 (4) C24---C25---C26---C27 −1.3 (8) O10---C21---O9---Nd2^vii^ 7.5 (4) C25---C26---C27---C28 0.1 (6) C22---C21---O9---Nd2^vii^ −170.0 (3) C25---C26---C27---C29 177.8 (4) O9---C21---O10---Nd2^vii^ −7.8 (4) C24---C23---C28---C27 0.1 (6) C22---C21---O10---Nd2^vii^ 169.6 (3) C22---C23---C28---C27 −179.5 (3) O12---C30---O11---Nd2 −36.9 (6) C26---C27---C28---C23 0.5 (5) C29---C30---O11---Nd2 144.4 (3) C29---C27---C28---C23 −177.2 (3) O8^iv^---Nd2---O11---C30 100.6 (4) C26---C27---C29---C30 58.1 (5) O9^v^---Nd2---O11---C30 149.5 (4) C28---C27---C29---C30 −124.2 (4) O1^iii^---Nd2---O11---C30 56.7 (4) C27---C29---C30---O11 −170.9 (3) O14---Nd2---O11---C30 −15.2 (4) C27---C29---C30---O12 10.4 (5) O6^ii^---Nd2---O11---C30 −68.1 (4) O2---C1---O1---Nd2^viii^ 126.3 (4) O10^vi^---Nd2---O11---C30 −120.0 (4) C2---C1---O1---Nd2^viii^ −55.3 (6) O5^ii^---Nd2---O11---C30 −15.6 (4) O2---C1---O1---Nd1^viii^ −9.9 (3) O9^vi^---Nd2---O11---C30 −147.7 (4) C2---C1---O1---Nd1^viii^ 168.6 (3) C11^ii^---Nd2---O11---C30 −43.0 (4) O1---C1---O2---Nd1^viii^ 10.1 (3) C21^vi^---Nd2---O11---C30 −134.6 (4) C2---C1---O2---Nd1^viii^ −168.2 (3) O11---C30---O12---Nd1 27.9 (5) O4---C10---O3---Nd1^i^ −163.6 (4) C29---C30---O12---Nd1 −153.5 (3) C9---C10---O3---Nd1^i^ 16.4 (8) O3^i^---Nd1---O12---C30 −142.6 (3) O4---C10---O3---Nd1 0.7 (3) O5^ii^---Nd1---O12---C30 26.1 (3) C9---C10---O3---Nd1 −179.3 (3) O4---Nd1---O12---C30 102.4 (3) O3^i^---Nd1---O3---C10 −173.0 (3) O7---Nd1---O12---C30 24.3 (4) O5^ii^---Nd1---O3---C10 −33.2 (2) O13---Nd1---O12---C30 178.8 (3) O4---Nd1---O3---C10 −0.43 (19) O2^iii^---Nd1---O12---C30 −80.1 (3) O7---Nd1---O3---C10 50.4 (2) O1^iii^---Nd1---O12---C30 −45.4 (3) O12---Nd1---O3---C10 −96.0 (2) O3---Nd1---O12---C30 151.1 (3) O13---Nd1---O3---C10 100.9 (2) C1^iii^---Nd1---O12---C30 −63.8 (3) O2^iii^---Nd1---O3---C10 144.43 (19) -------------------------- ------------- ----------------------------- -------------- ::: Symmetry codes: (i) −*x*, −*y*, −*z*; (ii) −*x*, −*y*+1, −*z*+1; (iii) *x*, *y*−1, *z*; (iv) −*x*, −*y*, −*z*+1; (v) −*x*+1, −*y*, −*z*; (vi) *x*, *y*, *z*+1; (vii) *x*, *y*, *z*−1; (viii) *x*, *y*+1, *z*. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5319 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O13---H1W···O12^i^ 0.88 2.39 2.838 (3) 112 O14---H4W···O7^iv^ 0.86 2.26 2.829 (3) 124 O14---H4W···O2^ii^ 0.86 2.41 3.177 (4) 148 O14---H3W···O7 0.87 2.25 3.024 (3) 149 O14---H3W···O14^iv^ 0.87 2.53 3.100 (5) 123 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*, −*y*, −*z*; (iv) −*x*, −*y*, −*z*+1; (ii) −*x*, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- O13---H1*W*⋯O12^i^ 0.88 2.39 2.838 (3) 112 O14---H4*W*⋯O7^ii^ 0.86 2.26 2.829 (3) 124 O14---H4*W*⋯O2^iii^ 0.86 2.41 3.177 (4) 148 O14---H3*W*⋯O7 0.87 2.25 3.024 (3) 149 O14---H3*W*⋯O14^ii^ 0.87 2.53 3.100 (5) 123 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.674145

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052131/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m387", "authors": [ { "first": "Zhu-Qing", "last": "Gao" }, { "first": "Dong-Yu", "last": "Lv" }, { "first": "Hong-Ji", "last": "Li" }, { "first": "Jin-Zhong", "last": "Gu" } ] }

PMC3052132

Related literature {#sec1} ================== The title compound is a precursor for the production of hole-transporting and/or emitting materials, see: Shen *et al.* (2005[@bb6]). For a related structure, see: Bak *et al.* (1961[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~25~H~22~O*M* *~r~* = 338.43Orthorhombic,*a* = 7.5277 (13) Å*b* = 12.9969 (19) Å*c* = 18.438 (3) Å*V* = 1803.9 (5) Å^3^*Z* = 4Mo *K*α radiationμ = 0.07 mm^−1^*T* = 100 K0.2 × 0.14 × 0.08 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometer8855 measured reflections2118 independent reflections1518 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.103 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.058*wR*(*F* ^2^) = 0.146*S* = 1.032118 reflections236 parametersH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e425} Data collection: *SMART* (Bruker, 2001[@bb2]); cell refinement: *SAINT* (Bruker, 2001[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb3]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb4]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006957/rn2074sup1.cif](http://dx.doi.org/10.1107/S1600536811006957/rn2074sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006957/rn2074Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006957/rn2074Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rn2074&file=rn2074sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rn2074sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rn2074&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RN2074](http://scripts.iucr.org/cgi-bin/sendsup?rn2074)). This work was partially supported by the Institute of Chemistry, Academia Sinica, and Cardinal Tien College of Healthcare & Management. Comment ======= The title compound, (I), has been shown to be an precursor for the production of hole transporting and/or emitting materials (Shen *et al.*, 2005). A one pot synthesis of a benzofuran substituted in the 2-position has been achieved by Pd(0) complex catalyzed Sonogashira coupling reaction of 2-iodophenol with terminal alkynes, followed by cyclization of the internal alkynes formed, in high yield (see scheme 1). The molecular structure is shown in Fig. 1. The dihedral angle between the benzofuran and fluorene rings is 9.06 (6)°, and that between the two benzene rings at fluorene is 1.78 (12)°. Weak intermolecular C---H···π interactions help to stabilize the crystal structure. Experimental {#experimental} ============ The compound was synthesized by the following procedure. A two-necked round-bottomed flask was charged with PdCl~2~(PPh~3~)~2~ (100 mg), 9,9-diethyl-2-ethynyl-9*H*-fluorene (1.35 g, 5.46 mmol), CuI (30 mg), 2-iodophenol (1.00 g, 4.55 mmol), triethylamine (1.3 ml), and DMF (10 ml), and the reaction mixture stirred under nitrogen and heated at 333 K for 24 h. After cooling, the mixture was diluted with diethyl ether and the organic phase was washed with water and brine. After drying over anhydrous MgSO~4~ and removing the volatiles, the residue was purified by column chromatography using CH~2~Cl~2~/n-hexane as eluent, followed by recrystallization from CH~2~Cl~2~ and hexane to yield 0.9 g (59%) of (I) as a white solid. Crystals suitable for X-ray diffraction were grown from a CH~2~Cl~2~ solution layered with hexane at room temperature. ^1^H NMR (CDCl~3~): 7.84 (d, 2 H, J = 7.97 Hz), 7.73 (dd, 2 H, J = 7.77 Hz), 7.55 (dd, 2 H, J = 7.64 Hz), 7.35--7.31 (m, 3 H), 7.24 (tt, 2 H, J = 8.31 Hz), 7.06 (s, 1 H), 2.09 (q, 4 H, J = 7.07 Hz), 0.34 (t, 6 H, J = 6.72 Hz). FAB MS (m/e): 338.1 (*M*^+^) Anal. Calcd for C~25~H~22~O: C, 88.72; H, 6.55. Found: C, 88.92; H, 6.51. Refinement {#refinement} ========== H atoms were located geometrically and treated as riding atoms, with C---H = 0.93 Å, and with *U*~iso~(H) = 1.2*U*~eq~(C). In the absence of significant anomalous scattering effects Friedel pairs have been merged. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A molecular structure of (I) with 30% probability displacement ellipsoids, showing the atom-numbering scheme employed. H atoms are shown as small spheres of the arbitrary radii. ::: ![](e-67-0o743-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e156 .table-wrap} ------------------------------- -------------------------------------- C~25~H~22~O *F*(000) = 720 *M~r~* = 338.43 *D*~x~ = 1.246 Mg m^−3^ Orthorhombic, *P*2~1~2~1~2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2ac 2ab Cell parameters from 525 reflections *a* = 7.5277 (13) Å θ = 2.7--20.4° *b* = 12.9969 (19) Å µ = 0.07 mm^−1^ *c* = 18.438 (3) Å *T* = 100 K *V* = 1803.9 (5) Å^3^ Prism, colourless *Z* = 4 0.2 × 0.14 × 0.08 mm ------------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e278 .table-wrap} ----------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 1518 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.103 graphite θ~max~ = 26.4°, θ~min~ = 1.9° ω and φ scans *h* = −8→9 8855 measured reflections *k* = −16→16 2118 independent reflections *l* = −17→23 ----------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.058 H-atom parameters constrained *wR*(*F*^2^) = 0.146 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.03 (Δ/σ)~max~ \< 0.001 2118 reflections Δρ~max~ = 0.23 e Å^−3^ 236 parameters Δρ~min~ = −0.26 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.007 (2) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e554 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. ^1^H NMR (CDCl~3~): 7.77 (d, J = 8.2, 4H), 7.64 (d, J = 8.2, 4H). FAB MS (m/e): 462 (*M*^+^). Analysis calculated for C~18~H~8~F~6~N~2~O~4~S: C 46.76, H 1.74, N 6.06%; found: C 46.80, H 1.88, N 5.79%. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e686 .table-wrap} ------ ------------ -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O29 0.8727 (4) 0.12706 (16) 0.89298 (15) 0.0233 (6) C1 0.6113 (5) 0.4536 (2) 0.6667 (2) 0.0210 (9) C2 0.5957 (6) 0.4834 (3) 0.5267 (2) 0.0241 (9) H2 0.5355 0.5473 0.5313 0.029\* C3 0.6407 (6) 0.4451 (3) 0.4588 (2) 0.0274 (10) H3 0.6092 0.4828 0.4166 0.033\* C4 0.7307 (6) 0.3529 (2) 0.4517 (2) 0.0248 (9) H4 0.7610 0.3284 0.4048 0.030\* C5 0.7768 (6) 0.2960 (2) 0.5121 (2) 0.0250 (9) H5 0.8382 0.2325 0.5070 0.030\* C6 0.8406 (5) 0.2003 (2) 0.6748 (2) 0.0234 (9) H6 0.8885 0.1541 0.6400 0.028\* C7 0.8484 (5) 0.1773 (3) 0.7477 (2) 0.0246 (9) H7 0.9038 0.1152 0.7628 0.030\* C8 0.7765 (5) 0.2434 (2) 0.7995 (2) 0.0203 (8) C9 0.6972 (5) 0.3362 (2) 0.7766 (2) 0.0221 (9) H9 0.6485 0.3823 0.8113 0.027\* C10 0.6904 (5) 0.3599 (2) 0.7040 (2) 0.0204 (9) C11 0.6400 (5) 0.4271 (2) 0.5872 (2) 0.0197 (9) C12 0.7322 (5) 0.3329 (2) 0.5805 (2) 0.0210 (8) C13 0.7618 (5) 0.2920 (2) 0.6527 (2) 0.0211 (8) C21 0.7791 (5) 0.2166 (2) 0.8762 (2) 0.0218 (9) C22 0.7057 (6) 0.2573 (2) 0.9356 (2) 0.0236 (9) H22 0.6381 0.3189 0.9376 0.028\* C23 0.7468 (6) 0.1913 (2) 0.9960 (2) 0.0238 (9) C24 0.7066 (6) 0.1876 (3) 1.0693 (2) 0.0293 (9) H24 0.6388 0.2407 1.0914 0.035\* C25 0.7675 (6) 0.1048 (3) 1.1097 (2) 0.0311 (10) H25 0.7404 0.1012 1.1600 0.037\* C26 0.8683 (6) 0.0264 (3) 1.0779 (2) 0.0285 (10) H26 0.9081 −0.0295 1.1069 0.034\* C27 0.9113 (6) 0.0287 (3) 1.0048 (2) 0.0251 (9) H27 0.9802 −0.0238 0.9826 0.030\* C28 0.8480 (5) 0.1119 (2) 0.9661 (2) 0.0203 (9) C31 0.7154 (6) 0.5539 (2) 0.6825 (2) 0.0283 (10) H31A 0.8425 0.5409 0.6722 0.034\* H31B 0.6745 0.6072 0.6479 0.034\* C32 0.7009 (6) 0.5975 (3) 0.7583 (2) 0.0326 (10) H32A 0.7727 0.6602 0.7618 0.049\* H32B 0.7441 0.5467 0.7933 0.049\* H32C 0.5764 0.6139 0.7688 0.049\* C33 0.4142 (5) 0.4697 (3) 0.6858 (2) 0.0221 (9) H33A 0.4039 0.4798 0.7388 0.027\* H33B 0.3724 0.5336 0.6620 0.027\* C34 0.2925 (6) 0.3820 (2) 0.6635 (3) 0.0313 (10) H34A 0.1703 0.3980 0.6780 0.047\* H34B 0.3309 0.3185 0.6875 0.047\* H34C 0.2978 0.3730 0.6108 0.047\* ------ ------------ -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1306 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O29 0.0224 (15) 0.0231 (12) 0.0244 (16) 0.0027 (12) −0.0021 (14) 0.0000 (11) C1 0.021 (2) 0.0181 (16) 0.024 (2) 0.0023 (16) 0.0017 (19) −0.0008 (16) C2 0.026 (2) 0.0220 (17) 0.024 (2) 0.0022 (16) 0.000 (2) 0.0014 (16) C3 0.032 (3) 0.0265 (18) 0.024 (2) −0.0026 (18) −0.001 (2) 0.0017 (16) C4 0.027 (2) 0.0283 (17) 0.019 (2) −0.0023 (18) 0.001 (2) −0.0051 (15) C5 0.026 (2) 0.0229 (16) 0.026 (2) 0.0002 (17) 0.000 (2) −0.0015 (16) C6 0.022 (2) 0.0225 (16) 0.025 (2) 0.0038 (16) 0.0009 (19) −0.0049 (16) C7 0.027 (2) 0.0220 (17) 0.025 (2) 0.0029 (16) −0.0023 (19) −0.0009 (16) C8 0.019 (2) 0.0231 (16) 0.0194 (19) −0.0041 (17) 0.0026 (18) −0.0015 (15) C9 0.025 (2) 0.0198 (16) 0.021 (2) −0.0004 (16) 0.0024 (18) −0.0031 (15) C10 0.018 (2) 0.0212 (16) 0.022 (2) 0.0003 (16) −0.0005 (18) −0.0003 (15) C11 0.017 (2) 0.0229 (16) 0.019 (2) −0.0007 (15) 0.0025 (18) −0.0027 (15) C12 0.021 (2) 0.0201 (16) 0.022 (2) −0.0016 (16) 0.0018 (19) −0.0024 (15) C13 0.021 (2) 0.0202 (16) 0.022 (2) −0.0023 (16) −0.0017 (19) −0.0011 (15) C21 0.017 (2) 0.0174 (16) 0.031 (2) 0.0041 (16) −0.0059 (19) 0.0002 (15) C22 0.022 (2) 0.0228 (16) 0.026 (2) 0.0021 (17) 0.0021 (19) 0.0003 (16) C23 0.021 (2) 0.0260 (17) 0.025 (2) 0.0016 (17) −0.0014 (19) 0.0023 (15) C24 0.024 (2) 0.0362 (19) 0.027 (2) −0.0018 (19) 0.004 (2) −0.0003 (18) C25 0.027 (2) 0.039 (2) 0.028 (2) −0.005 (2) 0.000 (2) 0.0063 (18) C26 0.025 (2) 0.0282 (18) 0.032 (3) −0.0032 (18) −0.009 (2) 0.0078 (18) C27 0.025 (2) 0.0238 (17) 0.027 (2) −0.0008 (17) −0.0040 (19) −0.0010 (17) C28 0.022 (2) 0.0253 (17) 0.0139 (19) −0.0060 (17) −0.0019 (17) 0.0008 (15) C31 0.033 (3) 0.0232 (17) 0.029 (2) −0.0009 (18) 0.003 (2) −0.0008 (16) C32 0.034 (3) 0.0305 (19) 0.033 (3) −0.0078 (19) −0.002 (2) −0.0069 (17) C33 0.025 (2) 0.0215 (17) 0.020 (2) 0.0028 (17) 0.0031 (18) 0.0003 (15) C34 0.027 (2) 0.0326 (19) 0.034 (2) −0.0024 (19) −0.001 (2) 0.0010 (18) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1827 .table-wrap} ---------------------- ------------ ----------------------- ------------ O29---C28 1.374 (5) C12---C13 1.452 (5) O29---C21 1.395 (4) C21---C22 1.336 (5) C1---C10 1.520 (5) C22---C23 1.438 (5) C1---C11 1.521 (5) C22---H22 0.9500 C1---C33 1.539 (5) C23---C24 1.386 (6) C1---C31 1.548 (5) C23---C28 1.397 (5) C2---C11 1.375 (5) C24---C25 1.388 (5) C2---C3 1.389 (5) C24---H24 0.9500 C2---H2 0.9500 C25---C26 1.400 (5) C3---C4 1.382 (5) C25---H25 0.9500 C3---H3 0.9500 C26---C27 1.386 (6) C4---C5 1.381 (5) C26---H26 0.9500 C4---H4 0.9500 C27---C28 1.381 (5) C5---C12 1.391 (5) C27---H27 0.9500 C5---H5 0.9500 C31---C32 1.512 (6) C6---C7 1.377 (6) C31---H31A 0.9900 C6---C13 1.391 (5) C31---H31B 0.9900 C6---H6 0.9500 C32---H32A 0.9800 C7---C8 1.396 (5) C32---H32B 0.9800 C7---H7 0.9500 C32---H32C 0.9800 C8---C9 1.410 (5) C33---C34 1.519 (5) C8---C21 1.456 (5) C33---H33A 0.9900 C9---C10 1.374 (5) C33---H33B 0.9900 C9---H9 0.9500 C34---H34A 0.9800 C10---C13 1.401 (5) C34---H34B 0.9800 C11---C12 1.412 (5) C34---H34C 0.9800 C28---O29---C21 105.6 (3) C21---C22---C23 108.0 (3) C10---C1---C11 101.5 (3) C21---C22---H22 126.0 C10---C1---C33 112.6 (3) C23---C22---H22 126.0 C11---C1---C33 112.8 (3) C24---C23---C28 118.6 (3) C10---C1---C31 113.0 (3) C24---C23---C22 136.8 (4) C11---C1---C31 107.4 (3) C28---C23---C22 104.6 (3) C33---C1---C31 109.3 (3) C23---C24---C25 118.6 (4) C11---C2---C3 118.7 (3) C23---C24---H24 120.7 C11---C2---H2 120.6 C25---C24---H24 120.7 C3---C2---H2 120.6 C24---C25---C26 121.2 (4) C4---C3---C2 121.0 (4) C24---C25---H25 119.4 C4---C3---H3 119.5 C26---C25---H25 119.4 C2---C3---H3 119.5 C27---C26---C25 121.3 (4) C5---C4---C3 120.7 (4) C27---C26---H26 119.4 C5---C4---H4 119.6 C25---C26---H26 119.4 C3---C4---H4 119.6 C28---C27---C26 116.0 (4) C4---C5---C12 119.0 (3) C28---C27---H27 122.0 C4---C5---H5 120.5 C26---C27---H27 122.0 C12---C5---H5 120.5 O29---C28---C27 124.9 (3) C7---C6---C13 119.3 (3) O29---C28---C23 110.8 (3) C7---C6---H6 120.3 C27---C28---C23 124.3 (4) C13---C6---H6 120.3 C32---C31---C1 116.9 (3) C6---C7---C8 121.2 (3) C32---C31---H31A 108.1 C6---C7---H7 119.4 C1---C31---H31A 108.1 C8---C7---H7 119.4 C32---C31---H31B 108.1 C7---C8---C9 119.0 (3) C1---C31---H31B 108.1 C7---C8---C21 120.8 (3) H31A---C31---H31B 107.3 C9---C8---C21 120.1 (3) C31---C32---H32A 109.5 C10---C9---C8 120.0 (3) C31---C32---H32B 109.5 C10---C9---H9 120.0 H32A---C32---H32B 109.5 C8---C9---H9 120.0 C31---C32---H32C 109.5 C9---C10---C13 120.1 (3) H32A---C32---H32C 109.5 C9---C10---C1 129.4 (3) H32B---C32---H32C 109.5 C13---C10---C1 110.5 (3) C34---C33---C1 114.7 (3) C2---C11---C12 120.6 (4) C34---C33---H33A 108.6 C2---C11---C1 128.8 (3) C1---C33---H33A 108.6 C12---C11---C1 110.5 (3) C34---C33---H33B 108.6 C5---C12---C11 119.8 (3) C1---C33---H33B 108.6 C5---C12---C13 131.9 (3) H33A---C33---H33B 107.6 C11---C12---C13 108.3 (3) C33---C34---H34A 109.5 C6---C13---C10 120.4 (4) C33---C34---H34B 109.5 C6---C13---C12 130.4 (3) H34A---C34---H34B 109.5 C10---C13---C12 109.2 (3) C33---C34---H34C 109.5 C22---C21---O29 110.9 (3) H34A---C34---H34C 109.5 C22---C21---C8 134.1 (3) H34B---C34---H34C 109.5 O29---C21---C8 115.0 (3) C11---C2---C3---C4 −0.9 (6) C1---C10---C13---C12 −1.4 (4) C2---C3---C4---C5 0.5 (6) C5---C12---C13---C6 −2.2 (7) C3---C4---C5---C12 −0.2 (6) C11---C12---C13---C6 177.5 (4) C13---C6---C7---C8 0.9 (6) C5---C12---C13---C10 179.8 (4) C6---C7---C8---C9 −1.0 (6) C11---C12---C13---C10 −0.5 (4) C6---C7---C8---C21 177.6 (4) C28---O29---C21---C22 2.2 (4) C7---C8---C9---C10 0.5 (6) C28---O29---C21---C8 −175.7 (3) C21---C8---C9---C10 −178.1 (4) C7---C8---C21---C22 −171.3 (4) C8---C9---C10---C13 0.2 (6) C9---C8---C21---C22 7.3 (7) C8---C9---C10---C1 179.4 (4) C7---C8---C21---O29 6.0 (5) C11---C1---C10---C9 −176.8 (4) C9---C8---C21---O29 −175.4 (3) C33---C1---C10---C9 −55.9 (6) O29---C21---C22---C23 −1.4 (5) C31---C1---C10---C9 68.5 (5) C8---C21---C22---C23 175.9 (4) C11---C1---C10---C13 2.5 (4) C21---C22---C23---C24 −177.1 (5) C33---C1---C10---C13 123.3 (3) C21---C22---C23---C28 0.1 (4) C31---C1---C10---C13 −112.2 (4) C28---C23---C24---C25 −0.5 (6) C3---C2---C11---C12 1.1 (6) C22---C23---C24---C25 176.5 (4) C3---C2---C11---C1 177.8 (4) C23---C24---C25---C26 0.3 (6) C10---C1---C11---C2 −179.8 (4) C24---C25---C26---C27 0.1 (6) C33---C1---C11---C2 59.6 (5) C25---C26---C27---C28 −0.4 (6) C31---C1---C11---C2 −61.0 (5) C21---O29---C28---C27 176.8 (4) C10---C1---C11---C12 −2.8 (4) C21---O29---C28---C23 −2.1 (4) C33---C1---C11---C12 −123.5 (3) C26---C27---C28---O29 −178.5 (4) C31---C1---C11---C12 116.0 (3) C26---C27---C28---C23 0.3 (6) C4---C5---C12---C11 0.4 (6) C24---C23---C28---O29 179.1 (4) C4---C5---C12---C13 −179.9 (4) C22---C23---C28---O29 1.2 (4) C2---C11---C12---C5 −0.8 (6) C24---C23---C28---C27 0.2 (6) C1---C11---C12---C5 −178.1 (4) C22---C23---C28---C27 −177.7 (4) C2---C11---C12---C13 179.4 (4) C10---C1---C31---C32 −71.1 (5) C1---C11---C12---C13 2.1 (4) C11---C1---C31---C32 177.8 (3) C7---C6---C13---C10 −0.3 (6) C33---C1---C31---C32 55.1 (5) C7---C6---C13---C12 −178.1 (4) C10---C1---C33---C34 −61.3 (5) C9---C10---C13---C6 −0.3 (6) C11---C1---C33---C34 52.8 (4) C1---C10---C13---C6 −179.6 (3) C31---C1---C33---C34 172.2 (3) C9---C10---C13---C12 178.0 (4) ---------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2887 .table-wrap} ------------------------------------------------------------------------------------------------------------------- Cg1, Cg2, Cg3 and Cg4 are the centroids of the C23--C28, O29/C21--C23/C28 and C2--C5/C11/C12 rings, respectively. ------------------------------------------------------------------------------------------------------------------- ::: ::: {#d1e2891 .table-wrap} ---------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C2---H2···Cg1^i^ 0.95 2.99 3.643 (5) 127 C22---H22···Cg1^ii^ 0.95 2.70 3.500 (4) 143 C24---H24···Cg2^ii^ 0.95 2.85 3.569 (5) 133 C27---H27···Cg2^iii^ 0.95 2.75 3.558 (5) 143 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, *y*+1/2, −*z*+3/2; (ii) *x*−1/2, −*y*+1/2, −*z*+2; (iii) −*x*+2, *y*−1/2, −*z*+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1, *Cg*2, *Cg*3 and *Cg*4 are the centroids of the C23--C28, O29/C21--C23/C28 and C2--C5/C11/C12 rings, respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------------- --------- ------- ----------- ------------- C2---H2⋯*Cg*1^i^ 0.95 2.99 3.643 (5) 127 C22---H22⋯*Cg*1^ii^ 0.95 2.70 3.500 (4) 143 C24---H24⋯*Cg*2^ii^ 0.95 2.85 3.569 (5) 133 C27---H27⋯*Cg*2^iii^ 0.95 2.75 3.558 (5) 143 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.685120

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052132/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o743", "authors": [ { "first": "Ping-Hsin", "last": "Huang" }, { "first": "Kai-Ling", "last": "Lin" }, { "first": "Yuh-Sheng", "last": "Wen" } ] }

PMC3052133

Related literature {#sec1} ================== The starting compound, Fe(NO)~2~(CO)~2~, was prepared using a published method described by Eisch & King (1965[@bb4]). For the structures of some related dinitrosyl complexes, see: Li *et al.* (2003[@bb5]); Atkinson *et al.* (1996[@bb2]); Li Kam Wah *et al.* (1989[@bb6]); Albano *et al.* (1974[@bb1]). For general information on metal nitrosyl chemistry, see: Richter-Addo & Legzdins (1992[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Fe(NO)~2~(C~21~H~21~P)~2~\]*M* *~r~* = 724.57Triclinic,*a* = 10.240 (2) Å*b* = 19.409 (4) Å*c* = 21.040 (4) Åα = 114.508 (5)°β = 93.158 (6)°γ = 94.732 (6)°*V* = 3773.5 (13) Å^3^*Z* = 4Mo *K*α radiationμ = 0.52 mm^−1^*T* = 100 K0.34 × 0.29 × 0.29 mm ### Data collection {#sec2.1.2} Bruker APEX CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 2001[@bb8]) *T* ~min~ = 0.843, *T* ~max~ = 0.86339881 measured reflections14767 independent reflections12772 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.025 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.035*wR*(*F* ^2^) = 0.095*S* = 1.0114767 reflections883 parametersH-atom parameters constrainedΔρ~max~ = 0.47 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e394} Data collection: *SMART* (Bruker, 2007[@bb3]); cell refinement: *SAINT* (Bruker, 2007[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100465X/fk2034sup1.cif](http://dx.doi.org/10.1107/S160053681100465X/fk2034sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100465X/fk2034Isup2.hkl](http://dx.doi.org/10.1107/S160053681100465X/fk2034Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?fk2034&file=fk2034sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?fk2034sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?fk2034&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [FK2034](http://scripts.iucr.org/cgi-bin/sendsup?fk2034)). We are grateful to the US Department of Education (GAANN Fellowship to MWJ; P200A030196) and the National Science Foundation (CHE-0076640 and CHE-0911537) for funding this work. The authors thank the National Science Foundation (CHE-0130835) and the University of Oklahoma for funds to acquire the diffractometer and computers used in this work. Comment ======= The molecular structure of the title compound is shown in Fig. 1. There are two distinct molecules per asymmetric unit of the cell. Each molecule possesses a distorted tetrahedral geometry around the iron center. The irons are bound to two nitrosyl groups *via* the nitrogen atoms and to two phosphine ligands *via* the phosphorous atoms. The Fe(NO)~2~ groups are in the *attracto* conformation where the bond angles O···Fe···O \< N---Fe---N (Richter-Addo & Legzdins, 1992). The N---Fe---N bond angles for molecule 1 and molecule 2 are 129.89 (7)° and 124.29 (8)° respectively, while the interphosphine angles, P---Fe---P, are 106.00 (2)° and 105.57 (2)° respectively. The Fe---N---O bond angles range between 173.84 (15)° and 179.31 (16)°. For the structures of some related complexes, see: Li *et al.* (2003), Atkinson *et al.* (1996), Li Kam Wah *et al.* (1989), and Albano *et al.* (1974). Experimental {#experimental} ============ Dark red Fe(NO)~2~(CO)~2~ (20 µ*L*, 0.18 mmol) (Eisch & King, 1965) was added by syringe under nitrogen to a colorless toluene solution (5 ml) of P(C~6~H~4~-*p*-CH~3~)~3~ (0.111 g, 0.36 mmol) in a Schlenk tube. The mixture was stirred and heated to reflux under nitrogen for a period of \~3 h. A color change from light red to black/dark brown was observed within the first 30 min. The reaction was stopped when the infrared spectrum indicated the absence of characteristic carbonyl stretching frequencies for Fe(NO)~2~(CO)~2~ (ν~CO~ = 2090 cm^-1^ and 2040 cm^-1^). The reaction mixture was filtered through celite under N~2~ and the solvent was subsequently removed under vacuum. Isolated yield of the Fe(NO)~2~*L*~2~ compound: 31%. IR (toluene, cm^-1^): ν~NO~ = 1714 s and 1670 s. ^31^P{^1^H} NMR (CDCl~3~): δ 58.4 (*s*) referenced to 85% H~3~PO~4~. Suitable crystals for X-ray diffraction studies were grown by slow evaporation of a chloroform solution of the complex under nitrogen at ambient temperature. Refinement {#refinement} ========== Phenyl H atoms were placed using known geometry with C---H = 0.95 Å. Methyl H atoms were initially located on a difference map and their positions were refined as rigid groups maintaining C---H = 0.98 Å and C---C---H angles to be equal by refining a torsion angle for each of the rigid groups. Once refinement had converged, the additional torsion angles were removed and refinement was repeated. Displacement parameters of phenyl H atoms were set to 1.2 times the isotropic equivalent for the bonded C (1.5 for methyl H atoms). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound showing the relative orientation of the two neighboring molecules. Hydrogen atoms were omitted for clarity. The displacement ellipsoids were drawn at the 50% probability level. ::: ![](e-67-0m331-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e197 .table-wrap} ------------------------------- --------------------------------------- \[Fe(NO)~2~(C~21~H~21~P)~2~\] *Z* = 4 *M~r~* = 724.57 *F*(000) = 1520 Triclinic, *P*1 *D*~x~ = 1.275 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.240 (2) Å Cell parameters from 8062 reflections *b* = 19.409 (4) Å θ = 2.3--28.3° *c* = 21.040 (4) Å µ = 0.52 mm^−1^ α = 114.508 (5)° *T* = 100 K β = 93.158 (6)° Prism, red γ = 94.732 (6)° 0.34 × 0.29 × 0.29 mm *V* = 3773.5 (13) Å^3^ ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e334 .table-wrap} --------------------------------------------------------------- --------------------------------------- Bruker APEX CCD diffractometer 14767 independent reflections Radiation source: fine-focus sealed tube 12772 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.025 ω scans θ~max~ = 26.0°, θ~min~ = 1.9° Absorption correction: multi-scan (*SADABS*; Sheldrick, 2001) *h* = −12→12 *T*~min~ = 0.843, *T*~max~ = 0.863 *k* = −23→23 39881 measured reflections *l* = −25→25 --------------------------------------------------------------- --------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e448 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.035 Hydrogen site location: geom and difmap *wR*(*F*^2^) = 0.095 H-atom parameters constrained *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.052*P*)^2^ + 1.6*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 14767 reflections (Δ/σ)~max~ = 0.002 883 parameters Δρ~max~ = 0.47 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e607 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Fe1 0.39525 (2) 0.721825 (14) 0.379710 (13) 0.01684 (7) P11 0.28352 (4) 0.75740 (2) 0.30476 (2) 0.01665 (10) N11 0.52762 (15) 0.78538 (9) 0.40581 (8) 0.0229 (3) O11 0.62231 (14) 0.83142 (9) 0.42413 (9) 0.0423 (4) C101 0.38308 (17) 0.76140 (10) 0.23620 (9) 0.0187 (4) C102 0.50084 (18) 0.72935 (11) 0.22635 (10) 0.0243 (4) H102 0.5286 0.7048 0.2547 0.029\* C103 0.57844 (19) 0.73288 (12) 0.17537 (10) 0.0296 (4) H103 0.6592 0.7112 0.1699 0.036\* C104 0.54089 (18) 0.76711 (11) 0.13254 (10) 0.0259 (4) C105 0.42240 (19) 0.79844 (11) 0.14174 (10) 0.0272 (4) H105 0.3939 0.8216 0.1124 0.033\* C106 0.34516 (18) 0.79640 (11) 0.19310 (10) 0.0239 (4) H106 0.2654 0.8191 0.1991 0.029\* C107 0.6249 (2) 0.77143 (14) 0.07718 (11) 0.0379 (5) H10A 0.6896 0.8169 0.0982 0.057\* H10B 0.5688 0.7744 0.0393 0.057\* H10C 0.6709 0.7258 0.0581 0.057\* C108 0.23570 (18) 0.85384 (10) 0.34316 (9) 0.0200 (4) C109 0.3295 (2) 0.91604 (10) 0.35781 (10) 0.0251 (4) H109 0.4153 0.9077 0.3434 0.030\* C110 0.2992 (2) 0.98989 (11) 0.39310 (11) 0.0340 (5) H110 0.3646 1.0315 0.4027 0.041\* C111 0.1744 (2) 1.00388 (12) 0.41462 (11) 0.0393 (6) C112 0.0815 (2) 0.94192 (13) 0.40057 (10) 0.0365 (5) H112 −0.0040 0.9505 0.4154 0.044\* C113 0.11095 (19) 0.86772 (12) 0.36529 (10) 0.0269 (4) H113 0.0457 0.8262 0.3562 0.032\* C114 0.1395 (3) 1.08414 (14) 0.45209 (15) 0.0675 (10) H10D 0.0458 1.0851 0.4407 0.101\* H10E 0.1923 1.1181 0.4370 0.101\* H10F 0.1579 1.1013 0.5029 0.101\* C115 0.13121 (17) 0.69818 (10) 0.25660 (9) 0.0187 (4) C116 0.04992 (18) 0.71691 (11) 0.21226 (10) 0.0260 (4) H116 0.0735 0.7621 0.2063 0.031\* C117 −0.06413 (18) 0.67082 (11) 0.17700 (10) 0.0267 (4) H117 −0.1170 0.6841 0.1462 0.032\* C118 −0.10355 (18) 0.60487 (11) 0.18570 (10) 0.0250 (4) C119 −0.02243 (19) 0.58641 (10) 0.22993 (10) 0.0252 (4) H119 −0.0468 0.5417 0.2366 0.030\* C120 0.09349 (18) 0.63199 (10) 0.26454 (9) 0.0214 (4) H120 0.1479 0.6178 0.2941 0.026\* C121 −0.2297 (2) 0.55519 (12) 0.14826 (12) 0.0361 (5) H10G −0.3037 0.5762 0.1748 0.054\* H10H −0.2242 0.5035 0.1445 0.054\* H10I −0.2432 0.5536 0.1012 0.054\* P12 0.27399 (4) 0.74526 (2) 0.47036 (2) 0.01681 (10) N12 0.38322 (14) 0.62764 (9) 0.34965 (8) 0.0214 (3) O12 0.37303 (14) 0.56049 (7) 0.33303 (8) 0.0337 (3) C122 0.34119 (18) 0.70741 (10) 0.53047 (9) 0.0203 (4) C123 0.47703 (19) 0.71779 (12) 0.54674 (10) 0.0280 (4) H123 0.5321 0.7406 0.5242 0.034\* C124 0.5331 (2) 0.69512 (13) 0.59559 (11) 0.0352 (5) H124 0.6258 0.7039 0.6069 0.042\* C125 0.4554 (2) 0.65974 (13) 0.62823 (11) 0.0323 (5) C126 0.3199 (2) 0.64810 (11) 0.61068 (10) 0.0265 (4) H126 0.2651 0.6231 0.6316 0.032\* C127 0.26342 (18) 0.67224 (10) 0.56331 (9) 0.0222 (4) H127 0.1704 0.6647 0.5531 0.027\* C128 0.5146 (2) 0.63598 (17) 0.68217 (14) 0.0505 (7) H10J 0.4522 0.6402 0.7169 0.076\* H10K 0.5962 0.6692 0.7057 0.076\* H10L 0.5340 0.5831 0.6590 0.076\* C129 0.10421 (17) 0.70029 (10) 0.44695 (9) 0.0185 (4) C130 0.07860 (18) 0.62120 (10) 0.42010 (9) 0.0212 (4) H130 0.1489 0.5918 0.4188 0.025\* C131 −0.04789 (18) 0.58485 (11) 0.39528 (10) 0.0242 (4) H131 −0.0632 0.5309 0.3778 0.029\* C132 −0.15330 (18) 0.62621 (11) 0.39555 (10) 0.0260 (4) C133 −0.12697 (18) 0.70518 (11) 0.42229 (10) 0.0262 (4) H133 −0.1971 0.7346 0.4232 0.031\* C134 −0.00062 (18) 0.74192 (10) 0.44770 (9) 0.0218 (4) H134 0.0145 0.7959 0.4658 0.026\* C135 −0.2907 (2) 0.58681 (12) 0.36654 (12) 0.0367 (5) H10M −0.3544 0.6161 0.3968 0.055\* H10N −0.2975 0.5354 0.3649 0.055\* H10O −0.3094 0.5834 0.3191 0.055\* C136 0.26292 (17) 0.84432 (10) 0.53071 (9) 0.0185 (4) C137 0.19553 (18) 0.86158 (11) 0.59036 (9) 0.0234 (4) H137 0.1518 0.8215 0.5988 0.028\* C138 0.19201 (19) 0.93630 (11) 0.63711 (10) 0.0276 (4) H138 0.1456 0.9469 0.6774 0.033\* C139 0.25514 (18) 0.99655 (11) 0.62653 (10) 0.0258 (4) C140 0.32166 (19) 0.97939 (11) 0.56705 (10) 0.0246 (4) H140 0.3648 1.0195 0.5585 0.029\* C141 0.32592 (18) 0.90400 (10) 0.51970 (9) 0.0214 (4) H141 0.3725 0.8933 0.4794 0.026\* C142 0.2541 (2) 1.07824 (12) 0.67967 (11) 0.0372 (5) H10P 0.1701 1.0837 0.7004 0.056\* H10Q 0.2652 1.1124 0.6563 0.056\* H10R 0.3265 1.0914 0.7167 0.056\* Fe2 0.20249 (2) 0.726480 (14) 0.861160 (13) 0.01703 (7) P21 0.07337 (4) 0.78326 (2) 0.81153 (2) 0.01688 (10) N21 0.19663 (14) 0.63819 (9) 0.80051 (8) 0.0217 (3) O21 0.19345 (15) 0.57497 (8) 0.75630 (8) 0.0366 (4) C201 −0.05695 (17) 0.83832 (10) 0.85539 (9) 0.0196 (4) C202 −0.03062 (19) 0.88754 (10) 0.92638 (10) 0.0224 (4) H202 0.0550 0.8936 0.9492 0.027\* C203 −0.1274 (2) 0.92766 (10) 0.96401 (10) 0.0267 (4) H203 −0.1075 0.9607 1.0124 0.032\* C204 −0.25337 (19) 0.92016 (11) 0.93188 (11) 0.0294 (4) C205 −0.27994 (19) 0.87105 (11) 0.86129 (11) 0.0296 (4) H205 −0.3656 0.8651 0.8386 0.036\* C206 −0.18345 (18) 0.83046 (11) 0.82327 (10) 0.0245 (4) H206 −0.2038 0.7971 0.7750 0.029\* C207 −0.3572 (2) 0.96526 (12) 0.97353 (13) 0.0422 (6) H2OA −0.3894 0.9424 1.0042 0.063\* H20B −0.4305 0.9646 0.9413 0.063\* H20C −0.3189 1.0180 1.0021 0.063\* C208 −0.01124 (17) 0.71612 (10) 0.72718 (9) 0.0187 (4) C209 −0.07366 (18) 0.64768 (10) 0.72364 (10) 0.0230 (4) H209 −0.0690 0.6374 0.7641 0.028\* C210 −0.14236 (18) 0.59459 (11) 0.66173 (10) 0.0261 (4) H210 −0.1848 0.5485 0.6604 0.031\* C211 −0.15029 (18) 0.60753 (11) 0.60152 (10) 0.0264 (4) C212 −0.08842 (19) 0.67611 (11) 0.60524 (10) 0.0267 (4) H212 −0.0929 0.6863 0.5648 0.032\* C213 −0.02019 (18) 0.72984 (11) 0.66754 (10) 0.0231 (4) H213 0.0207 0.7764 0.6692 0.028\* C214 −0.2240 (2) 0.54858 (13) 0.53420 (11) 0.0407 (5) H20D −0.2704 0.5742 0.5098 0.061\* H20E −0.2878 0.5155 0.5450 0.061\* H20F −0.1615 0.5178 0.5041 0.061\* C215 0.18434 (17) 0.84965 (10) 0.79286 (9) 0.0199 (4) C216 0.1841 (2) 0.92808 (11) 0.82258 (10) 0.0267 (4) H216 0.1147 0.9503 0.8495 0.032\* C217 0.2857 (2) 0.97461 (12) 0.81311 (11) 0.0341 (5) H217 0.2855 1.0284 0.8347 0.041\* C218 0.3865 (2) 0.94394 (12) 0.77295 (11) 0.0329 (5) C219 0.38517 (19) 0.86522 (12) 0.74230 (10) 0.0286 (4) H219 0.4525 0.8430 0.7137 0.034\* C220 0.28759 (18) 0.81904 (11) 0.75285 (10) 0.0245 (4) H220 0.2902 0.7654 0.7327 0.029\* C221 0.4951 (2) 0.99342 (15) 0.76049 (14) 0.0492 (6) H20G 0.5807 0.9782 0.7694 0.074\* H20H 0.4915 1.0470 0.7923 0.074\* H20I 0.4834 0.9871 0.7118 0.074\* P22 0.09066 (4) 0.71480 (3) 0.94568 (2) 0.01739 (10) N22 0.34007 (15) 0.78364 (9) 0.89869 (8) 0.0247 (3) O22 0.44468 (15) 0.81869 (9) 0.92377 (10) 0.0486 (4) C222 0.16869 (17) 0.65324 (10) 0.97918 (9) 0.0192 (4) C223 0.30279 (17) 0.64885 (10) 0.97346 (9) 0.0207 (4) H223 0.3474 0.6720 0.9476 0.025\* C224 0.37193 (18) 0.61113 (10) 1.00497 (10) 0.0227 (4) H224 0.4634 0.6088 1.0004 0.027\* C225 0.31008 (19) 0.57673 (10) 1.04306 (10) 0.0244 (4) C226 0.1750 (2) 0.57987 (12) 1.04768 (11) 0.0305 (5) H226 0.1303 0.5558 1.0728 0.037\* C227 0.10521 (19) 0.61749 (11) 1.01627 (10) 0.0274 (4) H227 0.0134 0.6190 1.0200 0.033\* C228 0.3873 (2) 0.53776 (12) 1.07865 (11) 0.0337 (5) H20J 0.3826 0.5632 1.1295 0.051\* H20K 0.4794 0.5404 1.0686 0.051\* H20L 0.3501 0.4843 1.0611 0.051\* C229 0.08260 (17) 0.79809 (10) 1.02850 (9) 0.0197 (4) C230 0.17595 (18) 0.86123 (10) 1.04769 (10) 0.0224 (4) H230 0.2380 0.8623 1.0161 0.027\* C231 0.17944 (19) 0.92279 (11) 1.11262 (10) 0.0256 (4) H231 0.2442 0.9654 1.1248 0.031\* C232 0.09016 (19) 0.92330 (11) 1.16006 (10) 0.0262 (4) C233 −0.0038 (2) 0.86033 (12) 1.14066 (10) 0.0282 (4) H233 −0.0663 0.8597 1.1722 0.034\* C234 −0.00769 (19) 0.79843 (11) 1.07609 (10) 0.0247 (4) H234 −0.0723 0.7559 1.0641 0.030\* C235 0.0974 (2) 0.98930 (13) 1.23171 (11) 0.0366 (5) H20M 0.0089 0.9947 1.2474 0.055\* H20N 0.1329 1.0363 1.2289 0.055\* H20O 0.1549 0.9796 1.2651 0.055\* C236 −0.07859 (17) 0.67165 (10) 0.91595 (9) 0.0189 (4) C237 −0.10360 (18) 0.59358 (10) 0.87334 (10) 0.0221 (4) H237 −0.0339 0.5626 0.8666 0.027\* C238 −0.22833 (18) 0.56068 (11) 0.84085 (10) 0.0231 (4) H238 −0.2427 0.5075 0.8116 0.028\* C239 −0.33384 (17) 0.60460 (11) 0.85051 (9) 0.0217 (4) C240 −0.30823 (18) 0.68238 (11) 0.89178 (10) 0.0227 (4) H240 −0.3779 0.7134 0.8982 0.027\* C241 −0.18260 (17) 0.71601 (10) 0.92405 (9) 0.0211 (4) H241 −0.1675 0.7695 0.9518 0.025\* C242 −0.47141 (18) 0.56809 (12) 0.81872 (10) 0.0277 (4) H20P −0.5091 0.5424 0.8461 0.042\* H20Q −0.4685 0.5308 0.7702 0.042\* H20R −0.5261 0.6074 0.8192 0.042\* ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2971 .table-wrap} ------ -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Fe1 0.01472 (13) 0.01709 (13) 0.01718 (13) 0.00358 (10) 0.00093 (9) 0.00549 (10) P11 0.0145 (2) 0.0170 (2) 0.0172 (2) 0.00310 (17) 0.00163 (17) 0.00579 (18) N11 0.0184 (8) 0.0240 (8) 0.0253 (8) 0.0039 (6) −0.0006 (6) 0.0094 (7) O11 0.0236 (8) 0.0363 (9) 0.0614 (11) −0.0091 (7) −0.0071 (7) 0.0188 (8) C101 0.0159 (8) 0.0178 (9) 0.0177 (8) 0.0002 (7) 0.0020 (7) 0.0030 (7) C102 0.0231 (10) 0.0258 (10) 0.0245 (10) 0.0072 (8) 0.0043 (8) 0.0100 (8) C103 0.0206 (10) 0.0356 (11) 0.0297 (11) 0.0088 (8) 0.0081 (8) 0.0091 (9) C104 0.0221 (10) 0.0282 (10) 0.0197 (9) −0.0035 (8) 0.0035 (7) 0.0036 (8) C105 0.0248 (10) 0.0333 (11) 0.0235 (10) 0.0012 (8) 0.0026 (8) 0.0123 (8) C106 0.0193 (9) 0.0298 (10) 0.0235 (9) 0.0059 (8) 0.0041 (7) 0.0113 (8) C107 0.0297 (11) 0.0493 (14) 0.0320 (11) 0.0007 (10) 0.0116 (9) 0.0142 (10) C108 0.0239 (9) 0.0213 (9) 0.0142 (8) 0.0079 (7) 0.0008 (7) 0.0060 (7) C109 0.0281 (10) 0.0224 (10) 0.0231 (9) 0.0049 (8) −0.0005 (8) 0.0079 (8) C110 0.0476 (13) 0.0210 (10) 0.0280 (11) 0.0041 (9) −0.0114 (9) 0.0067 (8) C111 0.0509 (14) 0.0289 (11) 0.0260 (11) 0.0215 (10) −0.0137 (10) −0.0013 (9) C112 0.0356 (12) 0.0434 (13) 0.0231 (10) 0.0248 (10) 0.0002 (9) 0.0033 (9) C113 0.0255 (10) 0.0318 (11) 0.0218 (9) 0.0103 (8) 0.0018 (8) 0.0085 (8) C114 0.076 (2) 0.0357 (14) 0.0576 (17) 0.0335 (14) −0.0298 (15) −0.0138 (12) C115 0.0154 (8) 0.0198 (9) 0.0180 (8) 0.0030 (7) 0.0031 (7) 0.0048 (7) C116 0.0215 (10) 0.0324 (11) 0.0285 (10) 0.0000 (8) −0.0004 (8) 0.0181 (9) C117 0.0184 (9) 0.0369 (11) 0.0257 (10) 0.0035 (8) −0.0026 (8) 0.0147 (9) C118 0.0186 (9) 0.0241 (10) 0.0232 (9) 0.0020 (7) 0.0001 (7) 0.0013 (8) C119 0.0266 (10) 0.0172 (9) 0.0268 (10) 0.0011 (7) 0.0010 (8) 0.0049 (8) C120 0.0214 (9) 0.0201 (9) 0.0200 (9) 0.0042 (7) −0.0003 (7) 0.0057 (7) C121 0.0278 (11) 0.0294 (11) 0.0399 (12) −0.0030 (9) −0.0094 (9) 0.0062 (9) P12 0.0159 (2) 0.0166 (2) 0.0169 (2) 0.00352 (17) 0.00099 (17) 0.00579 (18) N12 0.0178 (8) 0.0222 (8) 0.0214 (8) 0.0061 (6) 0.0023 (6) 0.0056 (6) O12 0.0325 (8) 0.0175 (7) 0.0456 (9) 0.0052 (6) 0.0036 (7) 0.0075 (6) C122 0.0228 (9) 0.0187 (9) 0.0191 (9) 0.0061 (7) 0.0019 (7) 0.0068 (7) C123 0.0219 (10) 0.0391 (12) 0.0298 (10) 0.0061 (8) 0.0038 (8) 0.0206 (9) C124 0.0230 (10) 0.0535 (14) 0.0369 (12) 0.0113 (10) 0.0022 (9) 0.0257 (11) C125 0.0337 (11) 0.0419 (12) 0.0284 (11) 0.0155 (9) 0.0040 (9) 0.0197 (10) C126 0.0311 (11) 0.0267 (10) 0.0247 (10) 0.0067 (8) 0.0069 (8) 0.0128 (8) C127 0.0222 (9) 0.0225 (9) 0.0205 (9) 0.0040 (7) 0.0021 (7) 0.0073 (8) C128 0.0413 (14) 0.083 (2) 0.0514 (15) 0.0225 (13) 0.0079 (11) 0.0486 (15) C129 0.0169 (9) 0.0206 (9) 0.0172 (8) 0.0032 (7) 0.0028 (7) 0.0068 (7) C130 0.0191 (9) 0.0218 (9) 0.0229 (9) 0.0069 (7) 0.0026 (7) 0.0087 (8) C131 0.0239 (10) 0.0200 (9) 0.0239 (9) 0.0014 (7) 0.0014 (8) 0.0046 (8) C132 0.0192 (9) 0.0279 (10) 0.0244 (10) 0.0031 (8) 0.0003 (7) 0.0049 (8) C133 0.0182 (9) 0.0287 (10) 0.0282 (10) 0.0089 (8) −0.0002 (8) 0.0076 (8) C134 0.0232 (9) 0.0190 (9) 0.0207 (9) 0.0058 (7) 0.0016 (7) 0.0054 (7) C135 0.0212 (10) 0.0334 (12) 0.0433 (13) 0.0006 (9) −0.0037 (9) 0.0054 (10) C136 0.0164 (8) 0.0191 (9) 0.0173 (8) 0.0046 (7) −0.0013 (7) 0.0049 (7) C137 0.0231 (10) 0.0237 (10) 0.0213 (9) 0.0024 (7) 0.0023 (7) 0.0075 (8) C138 0.0255 (10) 0.0309 (11) 0.0194 (9) 0.0043 (8) 0.0042 (8) 0.0031 (8) C139 0.0229 (10) 0.0233 (10) 0.0227 (9) 0.0048 (8) −0.0031 (8) 0.0017 (8) C140 0.0258 (10) 0.0203 (9) 0.0246 (10) 0.0002 (7) −0.0030 (8) 0.0076 (8) C141 0.0225 (9) 0.0219 (9) 0.0170 (9) 0.0035 (7) 0.0005 (7) 0.0054 (7) C142 0.0373 (12) 0.0256 (11) 0.0342 (12) 0.0048 (9) 0.0022 (9) −0.0019 (9) Fe2 0.01515 (13) 0.01775 (13) 0.01839 (13) 0.00327 (10) 0.00339 (10) 0.00735 (10) P21 0.0166 (2) 0.0161 (2) 0.0176 (2) 0.00260 (17) 0.00314 (17) 0.00653 (18) N21 0.0187 (8) 0.0225 (8) 0.0254 (8) 0.0051 (6) 0.0041 (6) 0.0108 (7) O21 0.0392 (9) 0.0199 (7) 0.0389 (8) 0.0069 (6) 0.0010 (7) 0.0004 (6) C201 0.0201 (9) 0.0175 (9) 0.0241 (9) 0.0033 (7) 0.0065 (7) 0.0107 (7) C202 0.0248 (10) 0.0186 (9) 0.0242 (9) 0.0035 (7) 0.0036 (7) 0.0092 (8) C203 0.0320 (11) 0.0187 (9) 0.0275 (10) 0.0030 (8) 0.0101 (8) 0.0071 (8) C204 0.0262 (10) 0.0190 (9) 0.0419 (12) 0.0051 (8) 0.0146 (9) 0.0099 (9) C205 0.0187 (10) 0.0265 (10) 0.0430 (12) 0.0047 (8) 0.0056 (8) 0.0132 (9) C206 0.0221 (10) 0.0235 (10) 0.0270 (10) 0.0039 (8) 0.0035 (8) 0.0095 (8) C207 0.0299 (12) 0.0288 (11) 0.0598 (15) 0.0077 (9) 0.0216 (11) 0.0079 (11) C208 0.0154 (8) 0.0184 (9) 0.0197 (9) 0.0036 (7) 0.0029 (7) 0.0049 (7) C209 0.0223 (9) 0.0224 (9) 0.0246 (9) 0.0044 (7) 0.0017 (7) 0.0099 (8) C210 0.0232 (10) 0.0199 (9) 0.0322 (10) 0.0019 (7) 0.0008 (8) 0.0084 (8) C211 0.0217 (10) 0.0269 (10) 0.0238 (10) 0.0029 (8) 0.0004 (8) 0.0043 (8) C212 0.0255 (10) 0.0332 (11) 0.0206 (9) 0.0022 (8) 0.0025 (8) 0.0108 (8) C213 0.0214 (9) 0.0231 (9) 0.0250 (9) 0.0004 (7) 0.0038 (7) 0.0104 (8) C214 0.0450 (14) 0.0353 (12) 0.0289 (11) −0.0050 (10) −0.0072 (10) 0.0041 (10) C215 0.0198 (9) 0.0215 (9) 0.0189 (9) −0.0006 (7) 0.0001 (7) 0.0097 (7) C216 0.0342 (11) 0.0234 (10) 0.0218 (9) 0.0031 (8) 0.0036 (8) 0.0087 (8) C217 0.0476 (13) 0.0205 (10) 0.0307 (11) −0.0071 (9) −0.0012 (10) 0.0098 (9) C218 0.0303 (11) 0.0382 (12) 0.0308 (11) −0.0124 (9) −0.0062 (9) 0.0192 (10) C219 0.0219 (10) 0.0405 (12) 0.0275 (10) 0.0012 (8) 0.0022 (8) 0.0190 (9) C220 0.0244 (10) 0.0249 (10) 0.0253 (10) 0.0033 (8) 0.0035 (8) 0.0114 (8) C221 0.0409 (14) 0.0538 (15) 0.0561 (16) −0.0189 (12) −0.0036 (12) 0.0317 (13) P22 0.0158 (2) 0.0186 (2) 0.0188 (2) 0.00351 (17) 0.00334 (17) 0.00850 (18) N22 0.0202 (8) 0.0242 (8) 0.0302 (9) 0.0030 (7) 0.0046 (7) 0.0117 (7) O22 0.0238 (8) 0.0433 (10) 0.0653 (11) −0.0094 (7) 0.0005 (8) 0.0124 (9) C222 0.0207 (9) 0.0175 (9) 0.0186 (9) 0.0038 (7) 0.0016 (7) 0.0065 (7) C223 0.0204 (9) 0.0183 (9) 0.0228 (9) 0.0016 (7) 0.0025 (7) 0.0080 (7) C224 0.0185 (9) 0.0212 (9) 0.0253 (9) 0.0026 (7) −0.0001 (7) 0.0070 (8) C225 0.0285 (10) 0.0213 (9) 0.0232 (9) 0.0041 (8) −0.0006 (8) 0.0092 (8) C226 0.0328 (11) 0.0348 (11) 0.0355 (11) 0.0083 (9) 0.0095 (9) 0.0248 (10) C227 0.0217 (10) 0.0325 (11) 0.0344 (11) 0.0063 (8) 0.0073 (8) 0.0193 (9) C228 0.0348 (12) 0.0356 (12) 0.0376 (12) 0.0076 (9) 0.0021 (9) 0.0218 (10) C229 0.0197 (9) 0.0225 (9) 0.0190 (9) 0.0075 (7) 0.0021 (7) 0.0099 (7) C230 0.0210 (9) 0.0253 (10) 0.0224 (9) 0.0051 (7) 0.0027 (7) 0.0109 (8) C231 0.0241 (10) 0.0254 (10) 0.0245 (10) 0.0020 (8) −0.0040 (8) 0.0089 (8) C232 0.0287 (10) 0.0299 (10) 0.0189 (9) 0.0123 (8) 0.0002 (8) 0.0078 (8) C233 0.0292 (11) 0.0362 (11) 0.0226 (10) 0.0119 (9) 0.0083 (8) 0.0137 (9) C234 0.0250 (10) 0.0273 (10) 0.0236 (9) 0.0054 (8) 0.0048 (8) 0.0118 (8) C235 0.0402 (13) 0.0377 (12) 0.0244 (10) 0.0127 (10) 0.0035 (9) 0.0042 (9) C236 0.0170 (9) 0.0235 (9) 0.0195 (9) 0.0028 (7) 0.0045 (7) 0.0118 (7) C237 0.0183 (9) 0.0241 (9) 0.0263 (10) 0.0058 (7) 0.0054 (7) 0.0120 (8) C238 0.0230 (9) 0.0218 (9) 0.0239 (9) 0.0003 (7) 0.0034 (7) 0.0092 (8) C239 0.0185 (9) 0.0303 (10) 0.0198 (9) 0.0020 (7) 0.0024 (7) 0.0141 (8) C240 0.0186 (9) 0.0300 (10) 0.0250 (9) 0.0073 (7) 0.0056 (7) 0.0160 (8) C241 0.0217 (9) 0.0221 (9) 0.0217 (9) 0.0041 (7) 0.0060 (7) 0.0105 (8) C242 0.0206 (10) 0.0366 (11) 0.0271 (10) 0.0009 (8) −0.0002 (8) 0.0154 (9) ------ -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e4563 .table-wrap} --------------------------- -------------- --------------------------- -------------- Fe1---N11 1.6555 (16) Fe2---N21 1.6519 (16) Fe1---N12 1.6590 (16) Fe2---N22 1.6529 (16) Fe1---P12 2.2407 (6) Fe2---P22 2.2451 (6) Fe1---P11 2.2600 (6) Fe2---P21 2.2574 (6) P11---C108 1.8266 (18) P21---C208 1.8232 (18) P11---C115 1.8288 (18) P21---C201 1.8242 (18) P11---C101 1.8352 (18) P21---C215 1.8259 (18) N11---O11 1.191 (2) N21---O21 1.190 (2) C101---C102 1.389 (3) C201---C206 1.394 (3) C101---C106 1.397 (3) C201---C202 1.395 (3) C102---C103 1.390 (3) C202---C203 1.385 (3) C102---H102 0.9500 C202---H202 0.9500 C103---C104 1.379 (3) C203---C204 1.390 (3) C103---H103 0.9500 C203---H203 0.9500 C104---C105 1.389 (3) C204---C205 1.388 (3) C104---C107 1.511 (3) C204---C207 1.511 (3) C105---C106 1.385 (3) C205---C206 1.389 (3) C105---H105 0.9500 C205---H205 0.9500 C106---H106 0.9500 C206---H206 0.9500 C107---H10A 0.9800 C207---H2OA 0.9799 C107---H10B 0.9798 C207---H20B 0.9800 C107---H10C 0.9801 C207---H20C 0.9800 C108---C113 1.393 (3) C208---C213 1.386 (3) C108---C109 1.394 (3) C208---C209 1.397 (3) C109---C110 1.385 (3) C209---C210 1.385 (3) C109---H109 0.9500 C209---H209 0.9500 C110---C111 1.390 (3) C210---C211 1.390 (3) C110---H110 0.9500 C210---H210 0.9500 C111---C112 1.387 (3) C211---C212 1.396 (3) C111---C114 1.510 (3) C211---C214 1.510 (3) C112---C113 1.388 (3) C212---C213 1.392 (3) C112---H112 0.9500 C212---H212 0.9500 C113---H113 0.9500 C213---H213 0.9500 C114---H10D 0.9800 C214---H20D 0.9798 C114---H10E 0.9800 C214---H20E 0.9801 C114---H10F 0.9798 C214---H20F 0.9800 C115---C120 1.390 (3) C215---C216 1.385 (3) C115---C116 1.393 (3) C215---C220 1.402 (3) C116---C117 1.377 (3) C216---C217 1.398 (3) C116---H116 0.9500 C216---H216 0.9500 C117---C118 1.397 (3) C217---C218 1.384 (3) C117---H117 0.9500 C217---H217 0.9500 C118---C119 1.387 (3) C218---C219 1.389 (3) C118---C121 1.507 (3) C218---C221 1.514 (3) C119---C120 1.385 (3) C219---C220 1.376 (3) C119---H119 0.9500 C219---H219 0.9500 C120---H120 0.9500 C220---H220 0.9500 C121---H10G 0.9800 C221---H20G 0.9801 C121---H10H 0.9799 C221---H20H 0.9800 C121---H10I 0.9800 C221---H20I 0.9802 P12---C129 1.8237 (18) P22---C236 1.8174 (18) P12---C136 1.8298 (18) P22---C229 1.8323 (18) P12---C122 1.8361 (18) P22---C222 1.8323 (18) N12---O12 1.195 (2) N22---O22 1.187 (2) C122---C123 1.392 (3) C222---C223 1.392 (3) C122---C127 1.393 (3) C222---C227 1.394 (3) C123---C124 1.390 (3) C223---C224 1.383 (3) C123---H123 0.9500 C223---H223 0.9500 C124---C125 1.392 (3) C224---C225 1.385 (3) C124---H124 0.9500 C224---H224 0.9500 C125---C126 1.391 (3) C225---C226 1.397 (3) C125---C128 1.508 (3) C225---C228 1.504 (3) C126---C127 1.384 (3) C226---C227 1.384 (3) C126---H126 0.9500 C226---H226 0.9500 C127---H127 0.9500 C227---H227 0.9500 C128---H10J 0.9801 C228---H20J 0.9801 C128---H10K 0.9799 C228---H20K 0.9800 C128---H10L 0.9800 C228---H20L 0.9800 C129---C134 1.393 (2) C229---C230 1.390 (3) C129---C130 1.394 (2) C229---C234 1.398 (3) C130---C131 1.385 (3) C230---C231 1.389 (3) C130---H130 0.9500 C230---H230 0.9500 C131---C132 1.396 (3) C231---C232 1.388 (3) C131---H131 0.9500 C231---H231 0.9500 C132---C133 1.392 (3) C232---C233 1.391 (3) C132---C135 1.509 (3) C232---C235 1.513 (3) C133---C134 1.387 (3) C233---C234 1.386 (3) C133---H133 0.9500 C233---H233 0.9500 C134---H134 0.9500 C234---H234 0.9500 C135---H10M 0.9800 C235---H20M 0.9800 C135---H10N 0.9800 C235---H20N 0.9800 C135---H10O 0.9798 C235---H20O 0.9799 C136---C141 1.388 (3) C236---C237 1.396 (3) C136---C137 1.396 (3) C236---C241 1.398 (2) C137---C138 1.379 (3) C237---C238 1.383 (3) C137---H137 0.9500 C237---H237 0.9500 C138---C139 1.394 (3) C238---C239 1.403 (3) C138---H138 0.9500 C238---H238 0.9500 C139---C140 1.388 (3) C239---C240 1.387 (3) C139---C142 1.516 (3) C239---C242 1.507 (3) C140---C141 1.393 (3) C240---C241 1.393 (3) C140---H140 0.9500 C240---H240 0.9500 C141---H141 0.9500 C241---H241 0.9500 C142---H10P 0.9800 C242---H20P 0.9800 C142---H10Q 0.9800 C242---H20Q 0.9800 C142---H10R 0.9800 C242---H20R 0.9799 N11---Fe1---N12 129.89 (7) N21---Fe2---N22 124.29 (8) N11---Fe1---P12 108.61 (6) N21---Fe2---P22 104.14 (6) N12---Fe1---P12 98.23 (5) N22---Fe2---P22 108.24 (6) N11---Fe1---P11 101.15 (6) N21---Fe2---P21 104.17 (6) N12---Fe1---P11 111.19 (5) N22---Fe2---P21 108.98 (6) P12---Fe1---P11 106.00 (2) P22---Fe2---P21 105.57 (2) C108---P11---C115 103.82 (8) C208---P21---C201 102.89 (8) C108---P11---C101 101.42 (8) C208---P21---C215 106.11 (8) C115---P11---C101 104.38 (8) C201---P21---C215 105.07 (8) C108---P11---Fe1 115.61 (6) C208---P21---Fe2 112.38 (6) C115---P11---Fe1 117.49 (6) C201---P21---Fe2 123.08 (6) C101---P11---Fe1 112.28 (6) C215---P21---Fe2 106.05 (6) O11---N11---Fe1 179.31 (16) O21---N21---Fe2 179.10 (16) C102---C101---C106 117.99 (16) C206---C201---C202 118.24 (17) C102---C101---P11 119.80 (14) C206---C201---P21 123.77 (14) C106---C101---P11 122.21 (13) C202---C201---P21 117.86 (14) C101---C102---C103 120.56 (18) C203---C202---C201 120.95 (18) C101---C102---H102 119.7 C203---C202---H202 119.5 C103---C102---H102 119.7 C201---C202---H202 119.5 C104---C103---C102 121.55 (18) C202---C203---C204 120.81 (18) C104---C103---H103 119.2 C202---C203---H203 119.6 C102---C103---H103 119.2 C204---C203---H203 119.6 C103---C104---C105 118.00 (17) C205---C204---C203 118.35 (18) C103---C104---C107 121.88 (19) C205---C204---C207 121.6 (2) C105---C104---C107 120.12 (19) C203---C204---C207 120.06 (19) C106---C105---C104 121.03 (18) C204---C205---C206 121.15 (19) C106---C105---H105 119.5 C204---C205---H205 119.4 C104---C105---H105 119.5 C206---C205---H205 119.4 C105---C106---C101 120.86 (17) C205---C206---C201 120.49 (18) C105---C106---H106 119.6 C205---C206---H206 119.8 C101---C106---H106 119.6 C201---C206---H206 119.8 C104---C107---H10A 109.5 C204---C207---H2OA 109.5 C104---C107---H10B 109.5 C204---C207---H20B 109.5 H10A---C107---H10B 109.5 H2OA---C207---H20B 109.5 C104---C107---H10C 109.5 C204---C207---H20C 109.5 H10A---C107---H10C 109.5 H2OA---C207---H20C 109.5 H10B---C107---H10C 109.5 H20B---C207---H20C 109.5 C113---C108---C109 118.39 (17) C213---C208---C209 118.54 (16) C113---C108---P11 121.57 (15) C213---C208---P21 124.11 (14) C109---C108---P11 119.68 (14) C209---C208---P21 117.32 (14) C110---C109---C108 120.86 (19) C210---C209---C208 120.63 (18) C110---C109---H109 119.6 C210---C209---H209 119.7 C108---C109---H109 119.6 C208---C209---H209 119.7 C109---C110---C111 120.8 (2) C209---C210---C211 121.13 (18) C109---C110---H110 119.6 C209---C210---H210 119.4 C111---C110---H110 119.6 C211---C210---H210 119.4 C112---C111---C110 118.27 (19) C210---C211---C212 118.17 (17) C112---C111---C114 120.4 (2) C210---C211---C214 120.45 (18) C110---C111---C114 121.4 (2) C212---C211---C214 121.38 (18) C111---C112---C113 121.3 (2) C213---C212---C211 120.82 (18) C111---C112---H112 119.4 C213---C212---H212 119.6 C113---C112---H112 119.4 C211---C212---H212 119.6 C112---C113---C108 120.4 (2) C208---C213---C212 120.70 (17) C112---C113---H113 119.8 C208---C213---H213 119.7 C108---C113---H113 119.8 C212---C213---H213 119.7 C111---C114---H10D 109.5 C211---C214---H20D 109.5 C111---C114---H10E 109.5 C211---C214---H20E 109.5 H10D---C114---H10E 109.5 H20D---C214---H20E 109.5 C111---C114---H10F 109.5 C211---C214---H20F 109.5 H10D---C114---H10F 109.5 H20D---C214---H20F 109.5 H10E---C114---H10F 109.5 H20E---C214---H20F 109.5 C120---C115---C116 118.13 (16) C216---C215---C220 118.19 (17) C120---C115---P11 119.21 (13) C216---C215---P21 124.84 (14) C116---C115---P11 122.66 (14) C220---C215---P21 116.40 (14) C117---C116---C115 120.86 (18) C215---C216---C217 120.13 (19) C117---C116---H116 119.6 C215---C216---H216 119.9 C115---C116---H116 119.6 C217---C216---H216 119.9 C116---C117---C118 121.21 (18) C218---C217---C216 121.34 (19) C116---C117---H117 119.4 C218---C217---H217 119.3 C118---C117---H117 119.4 C216---C217---H217 119.3 C119---C118---C117 117.77 (17) C217---C218---C219 118.31 (18) C119---C118---C121 120.96 (18) C217---C218---C221 122.0 (2) C117---C118---C121 121.28 (18) C219---C218---C221 119.7 (2) C120---C119---C118 121.14 (18) C220---C219---C218 120.81 (19) C120---C119---H119 119.4 C220---C219---H219 119.6 C118---C119---H119 119.4 C218---C219---H219 119.6 C119---C120---C115 120.88 (17) C219---C220---C215 121.18 (18) C119---C120---H120 119.6 C219---C220---H220 119.4 C115---C120---H120 119.6 C215---C220---H220 119.4 C118---C121---H10G 109.5 C218---C221---H20G 109.5 C118---C121---H10H 109.5 C218---C221---H20H 109.5 H10G---C121---H10H 109.5 H20G---C221---H20H 109.5 C118---C121---H10I 109.5 C218---C221---H20I 109.5 H10G---C121---H10I 109.5 H20G---C221---H20I 109.5 H10H---C121---H10I 109.5 H20H---C221---H20I 109.5 C129---P12---C136 105.07 (8) C236---P22---C229 105.45 (8) C129---P12---C122 103.58 (8) C236---P22---C222 105.88 (8) C136---P12---C122 101.37 (8) C229---P22---C222 99.71 (8) C129---P12---Fe1 115.06 (6) C236---P22---Fe2 113.70 (6) C136---P12---Fe1 118.82 (6) C229---P22---Fe2 120.17 (6) C122---P12---Fe1 111.08 (6) C222---P22---Fe2 110.27 (6) O12---N12---Fe1 175.05 (15) O22---N22---Fe2 173.84 (15) C123---C122---C127 118.20 (17) C223---C222---C227 118.43 (17) C123---C122---P12 118.11 (14) C223---C222---P22 117.38 (13) C127---C122---P12 123.62 (14) C227---C222---P22 123.83 (14) C124---C123---C122 120.77 (18) C224---C223---C222 120.75 (17) C124---C123---H123 119.6 C224---C223---H223 119.6 C122---C123---H123 119.6 C222---C223---H223 119.6 C123---C124---C125 121.02 (19) C223---C224---C225 121.15 (17) C123---C124---H124 119.5 C223---C224---H224 119.4 C125---C124---H124 119.5 C225---C224---H224 119.4 C126---C125---C124 117.95 (18) C224---C225---C226 118.11 (17) C126---C125---C128 120.5 (2) C224---C225---C228 120.54 (18) C124---C125---C128 121.6 (2) C226---C225---C228 121.34 (18) C127---C126---C125 121.20 (18) C227---C226---C225 121.02 (18) C127---C126---H126 119.4 C227---C226---H226 119.5 C125---C126---H126 119.4 C225---C226---H226 119.5 C126---C127---C122 120.83 (18) C226---C227---C222 120.50 (18) C126---C127---H127 119.6 C226---C227---H227 119.7 C122---C127---H127 119.6 C222---C227---H227 119.7 C125---C128---H10J 109.5 C225---C228---H20J 109.5 C125---C128---H10K 109.5 C225---C228---H20K 109.5 H10J---C128---H10K 109.5 H20J---C228---H20K 109.5 C125---C128---H10L 109.5 C225---C228---H20L 109.5 H10J---C128---H10L 109.5 H20J---C228---H20L 109.5 H10K---C128---H10L 109.5 H20K---C228---H20L 109.5 C134---C129---C130 118.29 (16) C230---C229---C234 118.28 (17) C134---C129---P12 121.71 (14) C230---C229---P22 119.14 (14) C130---C129---P12 119.61 (13) C234---C229---P22 122.39 (14) C131---C130---C129 120.95 (17) C231---C230---C229 120.67 (18) C131---C130---H130 119.5 C231---C230---H230 119.7 C129---C130---H130 119.5 C229---C230---H230 119.7 C130---C131---C132 121.04 (17) C232---C231---C230 121.23 (18) C130---C131---H131 119.5 C232---C231---H231 119.4 C132---C131---H131 119.5 C230---C231---H231 119.4 C133---C132---C131 117.70 (17) C231---C232---C233 118.07 (18) C133---C132---C135 120.95 (17) C231---C232---C235 121.01 (19) C131---C132---C135 121.34 (18) C233---C232---C235 120.89 (18) C134---C133---C132 121.49 (17) C234---C233---C232 121.15 (18) C134---C133---H133 119.3 C234---C233---H233 119.4 C132---C133---H133 119.3 C232---C233---H233 119.4 C133---C134---C129 120.52 (17) C233---C234---C229 120.60 (18) C133---C134---H134 119.7 C233---C234---H234 119.7 C129---C134---H134 119.7 C229---C234---H234 119.7 C132---C135---H10M 109.5 C232---C235---H20M 109.5 C132---C135---H10N 109.5 C232---C235---H20N 109.5 H10M---C135---H10N 109.5 H20M---C235---H20N 109.5 C132---C135---H10O 109.5 C232---C235---H20O 109.5 H10M---C135---H10O 109.5 H20M---C235---H20O 109.5 H10N---C135---H10O 109.5 H20N---C235---H20O 109.5 C141---C136---C137 118.48 (16) C237---C236---C241 118.21 (16) C141---C136---P12 120.68 (13) C237---C236---P22 119.27 (13) C137---C136---P12 120.79 (14) C241---C236---P22 121.57 (14) C138---C137---C136 120.50 (18) C238---C237---C236 121.00 (17) C138---C137---H137 119.7 C238---C237---H237 119.5 C136---C137---H137 119.7 C236---C237---H237 119.5 C137---C138---C139 121.40 (18) C237---C238---C239 120.98 (17) C137---C138---H138 119.3 C237---C238---H238 119.5 C139---C138---H138 119.3 C239---C238---H238 119.5 C140---C139---C138 118.09 (17) C240---C239---C238 117.90 (17) C140---C139---C142 121.17 (19) C240---C239---C242 121.04 (17) C138---C139---C142 120.72 (18) C238---C239---C242 121.04 (17) C139---C140---C141 120.80 (18) C239---C240---C241 121.39 (17) C139---C140---H140 119.6 C239---C240---H240 119.3 C141---C140---H140 119.6 C241---C240---H240 119.3 C136---C141---C140 120.72 (17) C240---C241---C236 120.48 (17) C136---C141---H141 119.6 C240---C241---H241 119.8 C140---C141---H141 119.6 C236---C241---H241 119.8 C139---C142---H10P 109.5 C239---C242---H20P 109.5 C139---C142---H10Q 109.5 C239---C242---H20Q 109.5 H10P---C142---H10Q 109.5 H20P---C242---H20Q 109.5 C139---C142---H10R 109.5 C239---C242---H20R 109.5 H10P---C142---H10R 109.5 H20P---C242---H20R 109.5 H10Q---C142---H10R 109.5 H20Q---C242---H20R 109.5 N11---Fe1---P11---C108 −61.00 (9) N22---Fe2---P21---C208 140.90 (8) N12---Fe1---P11---C108 157.97 (9) P22---Fe2---P21---C208 −103.03 (6) P12---Fe1---P11---C108 52.26 (7) N21---Fe2---P21---C201 130.16 (9) N11---Fe1---P11---C115 175.76 (8) N22---Fe2---P21---C201 −95.31 (9) N12---Fe1---P11---C115 34.73 (9) P22---Fe2---P21---C201 20.77 (7) P12---Fe1---P11---C115 −70.98 (7) N21---Fe2---P21---C215 −109.16 (8) N11---Fe1---P11---C101 54.71 (8) N22---Fe2---P21---C215 25.38 (8) N12---Fe1---P11---C101 −86.32 (8) P22---Fe2---P21---C215 141.45 (6) P12---Fe1---P11---C101 167.97 (6) N22---Fe2---N21---O21 −53 (11) N12---Fe1---N11---O11 130 (19) P22---Fe2---N21---O21 −178 (100) P12---Fe1---N11---O11 −112 (19) P21---Fe2---N21---O21 72 (11) C108---P11---C101---C102 136.85 (15) C208---P21---C201---C206 −5.77 (17) C115---P11---C101---C102 −115.49 (15) C215---P21---C201---C206 105.11 (16) Fe1---P11---C101---C102 12.83 (16) Fe2---P21---C201---C206 −133.75 (14) C108---P11---C101---C106 −42.70 (16) C208---P21---C201---C202 170.03 (14) C115---P11---C101---C106 64.96 (16) C215---P21---C201---C202 −79.08 (15) Fe1---P11---C101---C106 −166.71 (13) Fe2---P21---C201---C202 42.06 (16) C106---C101---C102---C103 0.5 (3) C206---C201---C202---C203 −0.1 (3) P11---C101---C102---C103 −179.03 (15) P21---C201---C202---C203 −176.12 (14) C101---C102---C103---C104 −0.9 (3) C201---C202---C203---C204 −0.3 (3) C102---C103---C104---C105 0.1 (3) C202---C203---C204---C205 0.5 (3) C102---C103---C104---C107 179.78 (18) C202---C203---C204---C207 −179.12 (18) C103---C104---C105---C106 0.9 (3) C203---C204---C205---C206 −0.3 (3) C107---C104---C105---C106 −178.73 (18) C207---C204---C205---C206 179.30 (19) C104---C105---C106---C101 −1.3 (3) C204---C205---C206---C201 −0.1 (3) C102---C101---C106---C105 0.5 (3) C202---C201---C206---C205 0.3 (3) P11---C101---C106---C105 −179.94 (14) P21---C201---C206---C205 176.06 (15) C115---P11---C108---C113 33.99 (17) C201---P21---C208---C213 90.85 (16) C101---P11---C108---C113 142.08 (15) C215---P21---C208---C213 −19.25 (18) Fe1---P11---C108---C113 −96.19 (15) Fe2---P21---C208---C213 −134.73 (14) C115---P11---C108---C109 −152.98 (14) C201---P21---C208---C209 −87.29 (15) C101---P11---C108---C109 −44.89 (16) C215---P21---C208---C209 162.61 (14) Fe1---P11---C108---C109 76.84 (15) Fe2---P21---C208---C209 47.13 (15) C113---C108---C109---C110 −0.4 (3) C213---C208---C209---C210 0.3 (3) P11---C108---C109---C110 −173.66 (15) P21---C208---C209---C210 178.59 (14) C108---C109---C110---C111 −0.2 (3) C208---C209---C210---C211 0.5 (3) C109---C110---C111---C112 0.8 (3) C209---C210---C211---C212 −0.8 (3) C109---C110---C111---C114 −179.0 (2) C209---C210---C211---C214 179.14 (19) C110---C111---C112---C113 −0.7 (3) C210---C211---C212---C213 0.3 (3) C114---C111---C112---C113 179.0 (2) C214---C211---C212---C213 −179.66 (19) C111---C112---C113---C108 0.1 (3) C209---C208---C213---C212 −0.9 (3) C109---C108---C113---C112 0.5 (3) P21---C208---C213---C212 −178.98 (14) P11---C108---C113---C112 173.58 (15) C211---C212---C213---C208 0.6 (3) C108---P11---C115---C120 −132.53 (14) C208---P21---C215---C216 123.32 (16) C101---P11---C115---C120 121.59 (15) C201---P21---C215---C216 14.76 (18) Fe1---P11---C115---C120 −3.49 (16) Fe2---P21---C215---C216 −116.98 (16) C108---P11---C115---C116 46.96 (17) C208---P21---C215---C220 −65.58 (16) C101---P11---C115---C116 −58.92 (17) C201---P21---C215---C220 −174.14 (14) Fe1---P11---C115---C116 176.00 (13) Fe2---P21---C215---C220 54.13 (15) C120---C115---C116---C117 −0.4 (3) C220---C215---C216---C217 −0.8 (3) P11---C115---C116---C117 −179.90 (15) P21---C215---C216---C217 170.19 (15) C115---C116---C117---C118 1.5 (3) C215---C216---C217---C218 1.5 (3) C116---C117---C118---C119 −1.4 (3) C216---C217---C218---C219 −0.4 (3) C116---C117---C118---C121 178.78 (19) C216---C217---C218---C221 178.2 (2) C117---C118---C119---C120 0.3 (3) C217---C218---C219---C220 −1.3 (3) C121---C118---C119---C120 −179.88 (18) C221---C218---C219---C220 179.96 (19) C118---C119---C120---C115 0.8 (3) C218---C219---C220---C215 2.1 (3) C116---C115---C120---C119 −0.7 (3) C216---C215---C220---C219 −1.0 (3) P11---C115---C120---C119 178.82 (14) P21---C215---C220---C219 −172.70 (15) N11---Fe1---P12---C129 163.18 (8) N21---Fe2---P22---C236 −59.05 (8) N12---Fe1---P12---C129 −59.73 (8) N22---Fe2---P22---C236 166.94 (8) P11---Fe1---P12---C129 55.19 (7) P21---Fe2---P22---C236 50.36 (7) N11---Fe1---P12---C136 37.38 (9) N21---Fe2---P22---C229 174.68 (8) N12---Fe1---P12---C136 174.47 (8) N22---Fe2---P22---C229 40.67 (9) P11---Fe1---P12---C136 −70.61 (7) P21---Fe2---P22---C229 −75.91 (7) N11---Fe1---P12---C122 −79.57 (9) N21---Fe2---P22---C222 59.68 (8) N12---Fe1---P12---C122 57.52 (8) N22---Fe2---P22---C222 −74.34 (9) P11---Fe1---P12---C122 172.44 (6) P21---Fe2---P22---C222 169.09 (6) N11---Fe1---N12---O12 97.0 (16) N21---Fe2---N22---O22 −21.2 (15) P12---Fe1---N12---O12 −25.7 (16) P22---Fe2---N22---O22 101.2 (15) P11---Fe1---N12---O12 −136.5 (16) P21---Fe2---N22---O22 −144.4 (15) C129---P12---C122---C123 166.66 (15) C236---P22---C222---C223 149.46 (14) C136---P12---C122---C123 −84.59 (16) C229---P22---C222---C223 −101.29 (15) Fe1---P12---C122---C123 42.60 (16) Fe2---P22---C222---C223 26.06 (15) C129---P12---C122---C127 −16.60 (17) C236---P22---C222---C227 −37.58 (18) C136---P12---C122---C127 92.15 (16) C229---P22---C222---C227 71.67 (17) Fe1---P12---C122---C127 −140.65 (14) Fe2---P22---C222---C227 −160.98 (15) C127---C122---C123---C124 −1.4 (3) C227---C222---C223---C224 −1.2 (3) P12---C122---C123---C124 175.54 (16) P22---C222---C223---C224 172.13 (14) C122---C123---C124---C125 1.6 (3) C222---C223---C224---C225 0.0 (3) C123---C124---C125---C126 −0.3 (3) C223---C224---C225---C226 1.2 (3) C123---C124---C125---C128 −179.0 (2) C223---C224---C225---C228 −178.34 (18) C124---C125---C126---C127 −1.3 (3) C224---C225---C226---C227 −1.2 (3) C128---C125---C126---C127 177.5 (2) C228---C225---C226---C227 178.35 (19) C125---C126---C127---C122 1.5 (3) C225---C226---C227---C222 0.0 (3) C123---C122---C127---C126 −0.2 (3) C223---C222---C227---C226 1.2 (3) P12---C122---C127---C126 −176.92 (14) P22---C222---C227---C226 −171.66 (16) C136---P12---C129---C134 27.42 (17) C236---P22---C229---C230 −149.74 (14) C122---P12---C129---C134 133.38 (15) C222---P22---C229---C230 100.68 (15) Fe1---P12---C129---C134 −105.20 (14) Fe2---P22---C229---C230 −19.72 (17) C136---P12---C129---C130 −159.89 (14) C236---P22---C229---C234 35.53 (17) C122---P12---C129---C130 −53.92 (16) C222---P22---C229---C234 −74.06 (16) Fe1---P12---C129---C130 67.50 (15) Fe2---P22---C229---C234 165.54 (13) C134---C129---C130---C131 −0.5 (3) C234---C229---C230---C231 0.3 (3) P12---C129---C130---C131 −173.45 (14) P22---C229---C230---C231 −174.69 (14) C129---C130---C131---C132 0.8 (3) C229---C230---C231---C232 −0.2 (3) C130---C131---C132---C133 −0.7 (3) C230---C231---C232---C233 −0.3 (3) C130---C131---C132---C135 178.10 (19) C230---C231---C232---C235 177.86 (18) C131---C132---C133---C134 0.2 (3) C231---C232---C233---C234 0.6 (3) C135---C132---C133---C134 −178.60 (19) C235---C232---C233---C234 −177.55 (18) C132---C133---C134---C129 0.1 (3) C232---C233---C234---C229 −0.5 (3) C130---C129---C134---C133 0.0 (3) C230---C229---C234---C233 0.0 (3) P12---C129---C134---C133 172.80 (14) P22---C229---C234---C233 174.83 (14) C129---P12---C136---C141 −128.97 (15) C229---P22---C236---C237 −153.01 (14) C122---P12---C136---C141 123.45 (15) C222---P22---C236---C237 −47.90 (16) Fe1---P12---C136---C141 1.49 (17) Fe2---P22---C236---C237 73.31 (15) C129---P12---C136---C137 53.68 (16) C229---P22---C236---C241 38.41 (16) C122---P12---C136---C137 −53.91 (16) C222---P22---C236---C241 143.52 (15) Fe1---P12---C136---C137 −175.87 (12) Fe2---P22---C236---C241 −95.27 (14) C141---C136---C137---C138 0.0 (3) C241---C236---C237---C238 −1.0 (3) P12---C136---C137---C138 177.39 (14) P22---C236---C237---C238 −169.96 (14) C136---C137---C138---C139 −0.1 (3) C236---C237---C238---C239 −0.9 (3) C137---C138---C139---C140 0.4 (3) C237---C238---C239---C240 2.1 (3) C137---C138---C139---C142 −177.94 (18) C237---C238---C239---C242 −176.25 (17) C138---C139---C140---C141 −0.5 (3) C238---C239---C240---C241 −1.4 (3) C142---C139---C140---C141 177.75 (18) C242---C239---C240---C241 176.92 (16) C137---C136---C141---C140 −0.2 (3) C239---C240---C241---C236 −0.5 (3) P12---C136---C141---C140 −177.58 (14) C237---C236---C241---C240 1.7 (3) C139---C140---C141---C136 0.4 (3) P22---C236---C241---C240 170.36 (13) N21---Fe2---P21---C208 6.36 (8) --------------------------- -------------- --------------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.692323

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052133/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m331", "authors": [ { "first": "Myron W.", "last": "Jones" }, { "first": "Douglas R.", "last": "Powell" }, { "first": "George B.", "last": "Richter-Addo" } ] }

PMC3052134

Related literature {#sec1} ================== For the synthesis of related compounds, see: Contreras *et al.* (2001[@bb4]); Capuano *et al.* (2002[@bb3]). For their use as intermediates in the synthesis of anti-inflammatory agents or CCR1 antagonists, see: Rolland & Duhault (1989[@bb7]); Kaufmann (2005[@bb6]); Tanikawa *et al.* (1995[@bb9]); Xie *et al.* (2007[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~16~ClFN~2~O*M* *~r~* = 270.73Orthorhombic,*a* = 7.9350 (5) Å*b* = 8.4610 (4) Å*c* = 19.0040 (11) Å*V* = 1275.89 (12) Å^3^*Z* = 4Mo *K*α radiationμ = 0.30 mm^−1^*T* = 291 K0.30 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2001[@bb1]) *T* ~min~ = 0.566, *T* ~max~ = 0.71612886 measured reflections3001 independent reflections2550 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.033 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.035*wR*(*F* ^2^) = 0.085*S* = 1.013001 reflections165 parametersH-atom parameters constrainedΔρ~max~ = 0.33 e Å^−3^Δρ~min~ = −0.18 e Å^−3^Absolute structure: Flack (1983[@bb5]), 1255 Friedel pairsFlack parameter: 0.03 (7) {#d5e372} Data collection: *APEX2* (Bruker, 2003[@bb2]); cell refinement: *SAINT* (Bruker, 2001[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *DIAMOND* (Brandenburg, 1999)[@bb11]; software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006180/si2316sup1.cif](http://dx.doi.org/10.1107/S1600536811006180/si2316sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006180/si2316Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006180/si2316Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2316&file=si2316sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2316sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2316&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2316](http://scripts.iucr.org/cgi-bin/sendsup?si2316)). The authors would like to thank the Ministry of Science and Technology of China (2007AA02Z160, 2009ZX09501--004) and the Chinese National Natural Science Foundation (20872077, 90813013) for financial support. Comment ======= Piperazine derivatives similar to the title compound are well known as being useful for a variety of pharmaceutical indication, particularly as cardiotonic, neurotropic or anti-inflammatory agents (Kaufmann, 2005). The synthesis of related pyridazine compounds and their medicinal and pharmaceutical activity were reported (Contreras *et al.*, 2001; Capuano *et al.*, 2002). The use of related compounds as intermediates in the synthesis of antiinflammatory agents or CCRI antagonists can be studied in various patents (Rolland & Duhault, 1989; Kaufmann, 2005; Tanikawa *et al.*, 1995) and medicinal journal (Xie *et al.*, 2007). Moreover, we recently identified a series of compounds bearing various substituted benzylpiperazine moiety with potent antitumor activity by virtual screening approach (paper was being revised). Herein, we report the synthesis of the title compound as one important representative of piperazine derivatives and its X-ray crystal structure. The molecule of (I) is shown in Fig. 1. The bond lengths and angles are within normal ranges. The piperazine ring in the molecule adopts a chair conformation. The dihedral angle between the fluorophenyl ring and the four planar C atoms (r.m.s. = 0.0055 Å) of the piperazine chair is 78.27 (7)°. Whereas the dihedral angle between the four planar C atoms of the piperazine chair and the ethanone plane is 55.21 (9)Å with the Cl atom about 1.589 (2) Å out of plane. In the crystal, there are no strong intermolecular hydrogen bonds to link the molecules. Experimental {#experimental} ============ All chemicals and solvents were obtained from commercial supplies and used without purification. To a solution of chloroacetic chloride (0.58 ml, 7.15 mmol) in CH~2~Cl~2~ (10 ml) was added, at 0 °C, 1-(2-fluorobenzyl)piperazine(II) (1.15 g, 5.90 mmol) dissolved in CH~2~Cl~2~ (20 ml) which was prepared from the reaction of anhydrous piperazine(III) and 1-(chloromethyl)-2-fluorobenzene(IV). The reaction mixture was stirred at room temperature for about 30 min until no 1-(2-fluorobenzyl)piperazine remained, as monitored by TLC. The mixture was poured into cold H~2~O (50 ml) and rendered alkaline with a 10% NaHCO~3~ aqueous solution and separated. The organic layer, dried over Na~2~SO~4~, was evaporated under reduced pressure to give 1.44 g of pure title compound as a yellow oil. Yield 90%; ^1^H NMR (400 MHz, CDCl~3~) δ 7.35 (dd, *J* = 7.4, 1.4 Hz, 1H), δ 7.23--7.29 (m, 1H), δ 7.12 (t, *J* = 7.2 Hz, 1H), δ 7.04 (t, *J* = 9.2 Hz, 1H), δ 4.05 (s, 2H), δ 3.64 (d, *J* = 5.2 Hz, 2H), δ 3.62 (d, *J* = 4.4 Hz, 2H), 3.52 (t, *J* = 5.0 Hz, 2H), δ 2.51 (dt, *J* = 15.6, 4.8 Hz, 4H); ^13^C NMR (100.6 MHz, CDCl~3~) δ 161.16, 131.24, 128.88, 123.88, 123.75, 115.27, 115.05, 54.87, 52.41, 52.00, 46.06, 41.93, 40.67. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding model approximation with distances C---H = 0.93 Å for the benzene ring and 0.97 Å for C~sp3~ carbon atoms and *U*~iso~(H) = 1.2 times *U*~eq~(C). The absolute structure was determined by using the Flack parameter refinement with the TWIN/BASF instruction, and the coordinates of all atoms were inverted by instruction MOVE 1 1 1 - 1 in the final refinement with *SHELXL97*. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound showing displacement ellipsoids at the 30% probability level. ::: ![](e-67-0o708-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Synthesis of the title compound ::: ![](e-67-0o708-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e213 .table-wrap} ------------------------------- ------------------------------------- C~13~H~16~ClFN~2~O *F*(000) = 568 *M~r~* = 270.73 *D*~x~ = 1.409 Mg m^−3^ Orthorhombic, *P*2~1~2~1~2~1~ Mo *K*α radiation, λ = 0.71069 Å Hall symbol: P 2ac 2ab Cell parameters from 25 reflections *a* = 7.9350 (5) Å θ = 7.5--15° *b* = 8.4610 (4) Å µ = 0.30 mm^−1^ *c* = 19.0040 (11) Å *T* = 291 K *V* = 1275.89 (12) Å^3^ Block, colorless *Z* = 4 0.30 × 0.30 × 0.20 mm ------------------------------- ------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e338 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 3001 independent reflections Radiation source: fine-focus sealed tube 2550 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.033 ω scans θ~max~ = 28.4°, θ~min~ = 3.2° Absorption correction: multi-scan (*SADABS*; Bruker, 2001) *h* = −10→10 *T*~min~ = 0.566, *T*~max~ = 0.716 *k* = −10→10 12886 measured reflections *l* = −25→25 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e452 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Hydrogen site location: inferred from neighbouring sites Least-squares matrix: full H-atom parameters constrained *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.035 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.028*P*)^2^ + 0.4*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *wR*(*F*^2^) = 0.085 (Δ/σ)~max~ \< 0.001 *S* = 1.01 Δρ~max~ = 0.33 e Å^−3^ 3001 reflections Δρ~min~ = −0.18 e Å^−3^ 165 parameters Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ 0 restraints Extinction coefficient: 0.077 (3) Primary atom site location: structure-invariant direct methods Absolute structure: Flack (1983), 1255 Friedel pairs Secondary atom site location: difference Fourier map Flack parameter: 0.03 (7) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e638 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e737 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 1.51486 (16) 0.40256 (17) 0.67832 (8) 0.0512 (3) Cl1 1.23456 (9) 0.09826 (6) 0.64207 (3) 0.06647 (19) F1 0.6313 (2) 0.88072 (19) 0.64912 (8) 0.0801 (4) N1 0.96049 (18) 0.62572 (16) 0.64509 (8) 0.0378 (3) N2 1.2433 (2) 0.46187 (17) 0.70180 (8) 0.0437 (4) C1 0.8356 (2) 0.8253 (2) 0.56706 (9) 0.0415 (4) C2 0.7317 (3) 0.9332 (2) 0.59859 (10) 0.0492 (5) C3 0.7224 (3) 1.0901 (3) 0.58058 (12) 0.0622 (6) H3 0.6497 1.1582 0.6041 0.075\* C4 0.8215 (3) 1.1433 (3) 0.52783 (12) 0.0623 (6) H4 0.8177 1.2491 0.5146 0.075\* C5 0.9276 (3) 1.0405 (3) 0.49380 (12) 0.0588 (6) H5 0.9960 1.0766 0.4574 0.071\* C6 0.9328 (3) 0.8832 (3) 0.51363 (10) 0.0524 (5) H6 1.0047 0.8148 0.4898 0.063\* C7 0.8427 (2) 0.6546 (2) 0.58860 (10) 0.0459 (4) H7A 0.7312 0.6211 0.6034 0.055\* H7B 0.8746 0.5912 0.5482 0.055\* C8 1.1333 (2) 0.6613 (2) 0.62433 (10) 0.0424 (4) H8A 1.1409 0.7723 0.6118 0.051\* H8B 1.1613 0.6000 0.5828 0.051\* C9 1.2590 (2) 0.6266 (2) 0.68052 (10) 0.0459 (4) H9A 1.3719 0.6464 0.6631 0.055\* H9B 1.2395 0.6951 0.7207 0.055\* C10 1.0718 (2) 0.4225 (3) 0.72213 (11) 0.0500 (5) H10A 1.0413 0.4821 0.7638 0.060\* H10B 1.0655 0.3109 0.7336 0.060\* C11 0.9506 (2) 0.4583 (2) 0.66487 (11) 0.0460 (5) H11A 0.9758 0.3931 0.6242 0.055\* H11B 0.8372 0.4337 0.6804 0.055\* C12 1.3729 (2) 0.3613 (2) 0.69620 (9) 0.0388 (4) C13 1.3417 (3) 0.1882 (2) 0.71208 (10) 0.0476 (5) H13A 1.2753 0.1787 0.7547 0.057\* H13B 1.4484 0.1351 0.7197 0.057\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1184 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0326 (7) 0.0537 (8) 0.0671 (9) 0.0000 (6) −0.0001 (6) 0.0034 (7) Cl1 0.0760 (4) 0.0506 (3) 0.0729 (3) −0.0109 (3) −0.0059 (3) −0.0099 (3) F1 0.0805 (10) 0.0910 (10) 0.0688 (8) 0.0264 (8) 0.0272 (8) 0.0187 (8) N1 0.0326 (7) 0.0339 (7) 0.0471 (8) 0.0024 (6) −0.0027 (6) 0.0003 (6) N2 0.0343 (8) 0.0416 (7) 0.0552 (9) 0.0042 (7) 0.0010 (8) 0.0090 (6) C1 0.0373 (9) 0.0480 (10) 0.0393 (9) 0.0030 (8) −0.0091 (7) −0.0007 (8) C2 0.0465 (11) 0.0587 (12) 0.0423 (9) 0.0063 (10) −0.0002 (9) 0.0045 (8) C3 0.0751 (15) 0.0544 (11) 0.0573 (12) 0.0190 (12) 0.0006 (12) −0.0014 (10) C4 0.0801 (17) 0.0479 (12) 0.0590 (13) −0.0008 (11) −0.0167 (11) 0.0099 (10) C5 0.0596 (14) 0.0677 (14) 0.0492 (11) −0.0068 (11) −0.0017 (10) 0.0128 (10) C6 0.0502 (11) 0.0624 (13) 0.0447 (10) 0.0049 (10) −0.0006 (9) −0.0006 (10) C7 0.0400 (10) 0.0464 (10) 0.0512 (10) −0.0017 (8) −0.0089 (9) −0.0047 (9) C8 0.0363 (9) 0.0337 (8) 0.0570 (11) −0.0023 (7) −0.0006 (8) 0.0053 (8) C9 0.0370 (9) 0.0362 (9) 0.0645 (11) −0.0006 (8) −0.0076 (9) 0.0016 (8) C10 0.0393 (11) 0.0497 (11) 0.0610 (12) 0.0068 (8) 0.0094 (9) 0.0158 (10) C11 0.0328 (9) 0.0397 (9) 0.0656 (13) −0.0015 (8) 0.0056 (9) 0.0061 (9) C12 0.0364 (9) 0.0433 (9) 0.0366 (8) 0.0023 (8) −0.0050 (7) −0.0010 (7) C13 0.0479 (11) 0.0442 (11) 0.0506 (11) 0.0067 (9) −0.0049 (9) 0.0071 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1552 .table-wrap} -------------------- -------------- ---------------------- -------------- O1---C12 1.228 (2) C5---H5 0.9300 Cl1---C13 1.753 (2) C6---H6 0.9300 F1---C2 1.324 (2) C7---H7A 0.9700 N1---C7 1.444 (2) C7---H7B 0.9700 N1---C8 1.459 (2) C8---C9 1.490 (3) N1---C11 1.467 (2) C8---H8A 0.9700 N2---C12 1.339 (2) C8---H8B 0.9700 N2---C10 1.454 (2) C9---H9A 0.9700 N2---C9 1.457 (2) C9---H9B 0.9700 C1---C6 1.366 (3) C10---C11 1.483 (3) C1---C2 1.369 (3) C10---H10A 0.9700 C1---C7 1.502 (3) C10---H10B 0.9700 C2---C3 1.373 (3) C11---H11A 0.9700 C3---C4 1.351 (3) C11---H11B 0.9700 C3---H3 0.9300 C12---C13 1.515 (3) C4---C5 1.373 (3) C13---H13A 0.9700 C4---H4 0.9300 C13---H13B 0.9700 C5---C6 1.384 (3) C7---N1---C8 111.87 (15) C9---C8---H8A 108.9 C7---N1---C11 108.62 (14) N1---C8---H8B 108.9 C8---N1---C11 108.59 (13) C9---C8---H8B 108.9 C12---N2---C10 126.45 (15) H8A---C8---H8B 107.7 C12---N2---C9 121.38 (16) N2---C9---C8 109.27 (15) C10---N2---C9 111.92 (15) N2---C9---H9A 109.8 C6---C1---C2 115.21 (18) C8---C9---H9A 109.8 C6---C1---C7 121.77 (18) N2---C9---H9B 109.8 C2---C1---C7 123.02 (18) C8---C9---H9B 109.8 F1---C2---C1 117.11 (18) H9A---C9---H9B 108.3 F1---C2---C3 118.22 (19) N2---C10---C11 111.40 (16) C1---C2---C3 124.7 (2) N2---C10---H10A 109.3 C4---C3---C2 118.4 (2) C11---C10---H10A 109.3 C4---C3---H3 120.8 N2---C10---H10B 109.3 C2---C3---H3 120.8 C11---C10---H10B 109.3 C3---C4---C5 119.7 (2) H10A---C10---H10B 108.0 C3---C4---H4 120.2 N1---C11---C10 110.55 (16) C5---C4---H4 120.2 N1---C11---H11A 109.5 C4---C5---C6 120.0 (2) C10---C11---H11A 109.5 C4---C5---H5 120.0 N1---C11---H11B 109.5 C6---C5---H5 120.0 C10---C11---H11B 109.5 C1---C6---C5 122.1 (2) H11A---C11---H11B 108.1 C1---C6---H6 119.0 O1---C12---N2 123.07 (18) C5---C6---H6 119.0 O1---C12---C13 118.68 (17) N1---C7---C1 112.92 (15) N2---C12---C13 118.24 (17) N1---C7---H7A 109.0 C12---C13---Cl1 110.34 (13) C1---C7---H7A 109.0 C12---C13---H13A 109.6 N1---C7---H7B 109.0 Cl1---C13---H13A 109.6 C1---C7---H7B 109.0 C12---C13---H13B 109.6 H7A---C7---H7B 107.8 Cl1---C13---H13B 109.6 N1---C8---C9 113.25 (16) H13A---C13---H13B 108.1 N1---C8---H8A 108.9 C6---C1---C2---F1 177.86 (18) C11---N1---C8---C9 −57.8 (2) C7---C1---C2---F1 −1.6 (3) C12---N2---C9---C8 120.59 (19) C6---C1---C2---C3 −0.9 (3) C10---N2---C9---C8 −54.0 (2) C7---C1---C2---C3 179.7 (2) N1---C8---C9---N2 56.1 (2) F1---C2---C3---C4 −178.3 (2) C12---N2---C10---C11 −118.1 (2) C1---C2---C3---C4 0.4 (3) C9---N2---C10---C11 56.2 (2) C2---C3---C4---C5 0.1 (3) C7---N1---C11---C10 179.10 (16) C3---C4---C5---C6 0.0 (3) C8---N1---C11---C10 57.2 (2) C2---C1---C6---C5 0.9 (3) N2---C10---C11---N1 −57.6 (2) C7---C1---C6---C5 −179.60 (19) C10---N2---C12---O1 179.59 (18) C4---C5---C6---C1 −0.5 (3) C9---N2---C12---O1 5.8 (3) C8---N1---C7---C1 −63.4 (2) C10---N2---C12---C13 0.2 (3) C11---N1---C7---C1 176.72 (16) C9---N2---C12---C13 −173.64 (16) C6---C1---C7---N1 93.1 (2) O1---C12---C13---Cl1 −103.48 (18) C2---C1---C7---N1 −87.4 (2) N2---C12---C13---Cl1 75.97 (19) C7---N1---C8---C9 −177.68 (15) -------------------- -------------- ---------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.708768

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052134/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o708", "authors": [ { "first": "Cunlong", "last": "Zhang" }, { "first": "Xin", "last": "Zhai" }, { "first": "Furen", "last": "Wan" }, { "first": "Ping", "last": "Gong" }, { "first": "Yuyang", "last": "Jiang" } ] }

PMC3052135

Related literature {#sec1} ================== For background to supramolecular coordination polymers of zinc-triad 1,1-dithiolates, see: Tiekink (2003[@bb10]). For the use of steric effects to control supramolecular aggregation patterns, see: Chen *et al.* (2006[@bb4]). For structural studies on hydroxyl-substituted dithiocarbamate ligands, see Benson *et al.* (2007[@bb1]); Song & Tiekink (2009[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cd(C~6~H~12~NOS~2~)~2~(C~12~H~10~N~4~)~2~\]*M* *~r~* = 889.45Triclinic,*a* = 8.532 (3) Å*b* = 10.951 (4) Å*c* = 11.184 (5) Åα = 79.59 (3)°β = 88.06 (3)°γ = 78.23 (2)°*V* = 1006.2 (7) Å^3^*Z* = 1Mo *K*α radiationμ = 0.80 mm^−1^*T* = 98 K0.25 × 0.16 × 0.04 mm ### Data collection {#sec2.1.2} Rigaku AFC12/SATURN724 CCD diffractometerAbsorption correction: multi-scan (*ABSCOR*; Higashi, 1995[@bb5]) *T* ~min~ = 0.719, *T* ~max~ = 110677 measured reflections4150 independent reflections4009 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.023 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.025*wR*(*F* ^2^) = 0.062*S* = 1.084150 reflections245 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.40 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e576} Data collection: *CrystalClear* (Molecular Structure Corporation & Rigaku, 2005[@bb7]); cell refinement: *CrystalClear*; data reduction: *CrystalClear*; program(s) used to solve structure: PATTY in *DIRDIF* (Beurskens *et al.*, 1992[@bb2]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *ORTEPII* (Johnson, 1976[@bb6]) and *DIAMOND* (Brandenburg, 2006[@bb3]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004508/hb5795sup1.cif](http://dx.doi.org/10.1107/S1600536811004508/hb5795sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004508/hb5795Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004508/hb5795Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5795&file=hb5795sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5795sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5795&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5795](http://scripts.iucr.org/cgi-bin/sendsup?hb5795)). Comment ======= Interest in the title compound, (I), relates to controlling supramolecular aggregation patterns in the zinc-triad 1,1-thiolates (Tiekink, 2003; Chen *et al.*, 2006). With functionalized dithiocarbamate ligands carrying hydrogen bonding potential, smaller aggregates can be linked into 2-D and 3-D architectures (Benson *et al.*, 2007; Song & Tiekink, 2009). In (I), the cadmium atom is located on a centre of inversion and is chelated by symmetrically coordinating dithiocarbamate ligands, Table 1 and Fig. 1. The octahedral N~2~S~4~ donor set is completed by two pyridine-N atoms derived from two monodentate 4-pyridinealdazine ligands. The monomeric molecules are connected into a supramolecular chain *via* O--H···N hydrogen bonds, Table 2, that lead to the formation of 40-membered \[CdSCNC~2~OH···NC~4~N~2~C~4~N\]~2~ synthons, Fig. 2. These chains are linked into layers *via* C--H···O interactions, Table 1, which that stack along \[1 0 1\]; consolidation of these layers into a 3-D array is afforded by C---H···N~azo~ contacts, Table 2 and Fig. 3. Experimental {#experimental} ============ Compound (I) was prepared following the standard literature procedure (Song & Tiekink, 2009) from the reaction of Cd\[S~2~CN(CH~2~CH~2~OH)(nPr)\]~2~ and 4-\[(1*E*)-\[(*E*)-2-(pyridin-4-ylmethylidene)hydrazin-1-ylidene\]methyl\]pyridine (Sigma Aldrich). Yellow plates of (I) were obtained from the slow evaporation of a chloroform/acetonitrile (3/1) solution. Refinement {#refinement} ========== C-bound H-atoms were placed in calculated positions (C--H 0.95--0.99 Å) and were included in the refinement in the riding model approximation with *U*~iso~(H) set to 1.2--1.5*U*~eq~(C). The O-bound H-atom was located in a difference Fourier map and refined with an O--H restraint of 0.84±0.01 Å, and with *U*~iso~(H) = 1.5*U*~eq~(O). The reflection (81 2) was removed from the final refinement owing to poor agreement. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of (I) showing displacement ellipsoids at the 70% probability level. The Cd atom is located on a centre of inversion and i = 1 - x, 1 - y, 1 - z. ::: ![](e-67-0m320-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Supramolecular chain in (I) mediated by O--H···N (orange dashed lines) hydrogen bonds. Colour code: Cd, orange; S, yellow; O, red; N, blue; C, grey; and H, green. ::: ![](e-67-0m320-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Unit-cell contents in (I) viewed in projection down the a axis. ::: ![](e-67-0m320-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e201 .table-wrap} ----------------------------------------------- --------------------------------------- \[Cd(C~6~H~12~NOS~2~)~2~(C~12~H~10~N~4~)~2~\] *Z* = 1 *M~r~* = 889.45 *F*(000) = 458 Triclinic, *P*1 *D*~x~ = 1.468 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71070 Å *a* = 8.532 (3) Å Cell parameters from 3485 reflections *b* = 10.951 (4) Å θ = 2.4--30.3° *c* = 11.184 (5) Å µ = 0.80 mm^−1^ α = 79.59 (3)° *T* = 98 K β = 88.06 (3)° Plate, yellow γ = 78.23 (2)° 0.25 × 0.16 × 0.04 mm *V* = 1006.2 (7) Å^3^ ----------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e351 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku AFC12K/SATURN724 CCD diffractometer 4150 independent reflections Radiation source: fine-focus sealed tube 4009 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.023 ω scans θ~max~ = 26.5°, θ~min~ = 2.4° Absorption correction: multi-scan (*ABSCOR*; Higashi, 1995) *h* = −10→10 *T*~min~ = 0.719, *T*~max~ = 1 *k* = −13→12 10677 measured reflections *l* = −14→14 ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e465 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.062 H atoms treated by a mixture of independent and constrained refinement *S* = 1.08 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0288*P*)^2^ + 0.6008*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4150 reflections (Δ/σ)~max~ \< 0.001 245 parameters Δρ~max~ = 0.40 e Å^−3^ 1 restraint Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e622 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e721 .table-wrap} ----- --------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cd 0.5000 0.5000 0.5000 0.01706 (6) S1 0.67567 (5) 0.26992 (4) 0.55937 (3) 0.01562 (9) S2 0.48740 (5) 0.36286 (4) 0.32801 (4) 0.01587 (9) O1 0.88422 (15) 0.05660 (12) 0.17754 (11) 0.0223 (3) H1o 0.954 (2) 0.094 (2) 0.1432 (19) 0.033\* N1 0.67484 (15) 0.13324 (12) 0.38469 (11) 0.0120 (3) N2 0.26143 (17) 0.42763 (14) 0.61140 (13) 0.0192 (3) N3 −0.25800 (17) 0.36129 (14) 0.82625 (13) 0.0194 (3) N4 −0.37162 (17) 0.28924 (14) 0.87834 (12) 0.0191 (3) N5 −0.88990 (18) 0.19365 (15) 1.06431 (14) 0.0245 (3) C1 0.61822 (18) 0.24449 (15) 0.41986 (14) 0.0135 (3) C2 0.62455 (19) 0.10536 (15) 0.26935 (14) 0.0156 (3) H2A 0.5139 0.1526 0.2501 0.019\* H2B 0.6239 0.0138 0.2796 0.019\* C3 0.7325 (2) 0.14035 (16) 0.16368 (15) 0.0196 (3) H3A 0.6824 0.1356 0.0866 0.024\* H3B 0.7465 0.2285 0.1601 0.024\* C4 0.79259 (19) 0.03218 (15) 0.45840 (14) 0.0150 (3) H4A 0.8604 0.0717 0.5037 0.018\* H4B 0.8630 −0.0158 0.4033 0.018\* C5 0.7154 (2) −0.05962 (16) 0.54826 (15) 0.0185 (3) H5A 0.6421 −0.0957 0.5043 0.022\* H5B 0.6517 −0.0137 0.6080 0.022\* C6 0.8430 (2) −0.16666 (17) 0.61485 (17) 0.0239 (4) H6A 0.7911 −0.2254 0.6715 0.036\* H6B 0.9137 −0.1311 0.6602 0.036\* H6C 0.9059 −0.2121 0.5557 0.036\* C7 0.1257 (2) 0.50814 (17) 0.63223 (18) 0.0254 (4) H7 0.1197 0.5963 0.6049 0.031\* C8 −0.0057 (2) 0.46933 (17) 0.69130 (17) 0.0238 (4) H8 −0.0989 0.5297 0.7041 0.029\* C9 0.0008 (2) 0.34018 (16) 0.73174 (14) 0.0169 (3) C10 0.1403 (2) 0.25663 (16) 0.70970 (16) 0.0203 (3) H10 0.1493 0.1679 0.7352 0.024\* C11 0.2661 (2) 0.30418 (16) 0.65018 (16) 0.0205 (3) H11 0.3608 0.2458 0.6362 0.025\* C12 −0.1326 (2) 0.28869 (16) 0.79403 (14) 0.0177 (3) H12 −0.1255 0.1995 0.8107 0.021\* C13 −0.5012 (2) 0.35972 (17) 0.90688 (15) 0.0200 (3) H13 −0.5119 0.4492 0.8929 0.024\* C14 −0.6338 (2) 0.30118 (17) 0.96168 (14) 0.0188 (3) C15 −0.7640 (2) 0.37321 (18) 1.01209 (17) 0.0248 (4) H15 −0.7681 0.4604 1.0127 0.030\* C16 −0.8877 (2) 0.31554 (19) 1.06143 (17) 0.0269 (4) H16 −0.9762 0.3659 1.0952 0.032\* C17 −0.7628 (2) 0.12403 (18) 1.01712 (16) 0.0247 (4) H17 −0.7612 0.0367 1.0192 0.030\* C18 −0.6341 (2) 0.17338 (18) 0.96559 (16) 0.0228 (4) H18 −0.5468 0.1206 0.9332 0.027\* ----- --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1401 .table-wrap} ----- -------------- -------------- -------------- --------------- --------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cd 0.01757 (10) 0.01303 (10) 0.02083 (10) −0.00255 (7) 0.00354 (7) −0.00493 (7) S1 0.0170 (2) 0.01481 (19) 0.01487 (19) −0.00153 (15) −0.00065 (15) −0.00389 (15) S2 0.0170 (2) 0.01234 (19) 0.0169 (2) −0.00014 (15) −0.00203 (15) −0.00179 (15) O1 0.0183 (6) 0.0224 (6) 0.0251 (6) −0.0043 (5) 0.0080 (5) −0.0026 (5) N1 0.0114 (6) 0.0119 (6) 0.0122 (6) −0.0014 (5) −0.0004 (5) −0.0016 (5) N2 0.0185 (7) 0.0181 (7) 0.0218 (7) −0.0050 (6) 0.0034 (6) −0.0048 (6) N3 0.0178 (7) 0.0218 (7) 0.0184 (7) −0.0064 (6) 0.0024 (5) −0.0007 (6) N4 0.0188 (7) 0.0228 (7) 0.0161 (7) −0.0080 (6) 0.0024 (5) −0.0003 (6) N5 0.0222 (8) 0.0305 (9) 0.0219 (8) −0.0094 (7) 0.0047 (6) −0.0035 (6) C1 0.0114 (7) 0.0144 (8) 0.0147 (7) −0.0042 (6) 0.0032 (6) −0.0014 (6) C2 0.0165 (8) 0.0145 (8) 0.0158 (8) −0.0018 (6) 0.0002 (6) −0.0037 (6) C3 0.0222 (9) 0.0195 (8) 0.0156 (8) −0.0012 (7) 0.0027 (6) −0.0030 (6) C4 0.0127 (7) 0.0138 (8) 0.0169 (8) 0.0004 (6) −0.0007 (6) −0.0020 (6) C5 0.0167 (8) 0.0168 (8) 0.0210 (8) −0.0043 (7) 0.0009 (6) −0.0003 (6) C6 0.0224 (9) 0.0202 (9) 0.0266 (9) −0.0051 (7) −0.0034 (7) 0.0044 (7) C7 0.0230 (9) 0.0162 (8) 0.0348 (10) −0.0033 (7) 0.0087 (8) −0.0008 (7) C8 0.0174 (9) 0.0198 (9) 0.0320 (10) −0.0012 (7) 0.0055 (7) −0.0023 (7) C9 0.0168 (8) 0.0207 (8) 0.0146 (8) −0.0062 (7) 0.0003 (6) −0.0039 (6) C10 0.0217 (9) 0.0158 (8) 0.0245 (9) −0.0048 (7) 0.0021 (7) −0.0055 (7) C11 0.0193 (8) 0.0175 (8) 0.0259 (9) −0.0031 (7) 0.0036 (7) −0.0083 (7) C12 0.0181 (8) 0.0198 (8) 0.0153 (8) −0.0055 (7) −0.0024 (6) −0.0015 (6) C13 0.0198 (9) 0.0213 (9) 0.0178 (8) −0.0049 (7) 0.0006 (6) 0.0003 (7) C14 0.0171 (8) 0.0241 (9) 0.0146 (8) −0.0054 (7) 0.0000 (6) −0.0003 (6) C15 0.0238 (9) 0.0215 (9) 0.0283 (9) −0.0043 (7) 0.0040 (7) −0.0039 (7) C16 0.0206 (9) 0.0304 (10) 0.0290 (10) −0.0037 (8) 0.0076 (7) −0.0062 (8) C17 0.0255 (9) 0.0246 (9) 0.0260 (9) −0.0096 (8) 0.0052 (7) −0.0056 (7) C18 0.0216 (9) 0.0248 (9) 0.0229 (9) −0.0054 (7) 0.0045 (7) −0.0067 (7) ----- -------------- -------------- -------------- --------------- --------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1967 .table-wrap} ----------------------- -------------- ----------------------- -------------- Cd---S1 2.6379 (10) C4---H4B 0.9900 Cd---S2 2.6626 (10) C5---C6 1.527 (2) Cd---N2 2.5403 (17) C5---H5A 0.9900 Cd---S1^i^ 2.6379 (10) C5---H5B 0.9900 Cd---S2^i^ 2.6626 (10) C6---H6A 0.9800 Cd---N2^i^ 2.5403 (17) C6---H6B 0.9800 S1---C1 1.7369 (17) C6---H6C 0.9800 S2---C1 1.7286 (18) C7---C8 1.385 (2) O1---C3 1.421 (2) C7---H7 0.9500 O1---H1o 0.835 (10) C8---C9 1.395 (2) N1---C1 1.339 (2) C8---H8 0.9500 N1---C2 1.475 (2) C9---C10 1.390 (2) N1---C4 1.479 (2) C9---C12 1.471 (2) N2---C11 1.336 (2) C10---C11 1.386 (2) N2---C7 1.347 (2) C10---H10 0.9500 N3---C12 1.280 (2) C11---H11 0.9500 N3---N4 1.418 (2) C12---H12 0.9500 N4---C13 1.279 (2) C13---C14 1.475 (2) N5---C16 1.333 (3) C13---H13 0.9500 N5---C17 1.344 (2) C14---C15 1.391 (2) C2---C3 1.516 (2) C14---C18 1.393 (3) C2---H2A 0.9900 C15---C16 1.388 (3) C2---H2B 0.9900 C15---H15 0.9500 C3---H3A 0.9900 C16---H16 0.9500 C3---H3B 0.9900 C17---C18 1.385 (2) C4---C5 1.521 (2) C17---H17 0.9500 C4---H4A 0.9900 C18---H18 0.9500 N2^i^---Cd---N2 180 C4---C5---C6 110.58 (14) N2^i^---Cd---S1 89.42 (4) C4---C5---H5A 109.5 N2---Cd---S1 90.58 (4) C6---C5---H5A 109.5 N2^i^---Cd---S1^i^ 90.58 (4) C4---C5---H5B 109.5 N2---Cd---S1^i^ 89.42 (4) C6---C5---H5B 109.5 S1---Cd---S1^i^ 180 H5A---C5---H5B 108.1 N2^i^---Cd---S2 87.62 (4) C5---C6---H6A 109.5 N2---Cd---S2 92.38 (4) C5---C6---H6B 109.5 S1---Cd---S2 68.83 (3) H6A---C6---H6B 109.5 S1^i^---Cd---S2 111.17 (3) C5---C6---H6C 109.5 N2^i^---Cd---S2^i^ 92.38 (4) H6A---C6---H6C 109.5 N2---Cd---S2^i^ 87.62 (4) H6B---C6---H6C 109.5 S1---Cd---S2^i^ 111.17 (3) N2---C7---C8 123.52 (17) S1^i^---Cd---S2^i^ 68.83 (3) N2---C7---H7 118.2 S2---Cd---S2^i^ 180 C8---C7---H7 118.2 C1---S1---Cd 86.05 (6) C7---C8---C9 119.02 (16) C1---S2---Cd 85.43 (6) C7---C8---H8 120.5 C3---O1---H1o 109.5 (16) C9---C8---H8 120.5 C1---N1---C2 121.74 (13) C10---C9---C8 117.67 (15) C1---N1---C4 121.96 (13) C10---C9---C12 118.88 (15) C2---N1---C4 116.29 (13) C8---C9---C12 123.44 (16) C11---N2---C7 116.95 (15) C11---C10---C9 119.30 (16) C11---N2---Cd 119.88 (11) C11---C10---H10 120.3 C7---N2---Cd 123.16 (11) C9---C10---H10 120.3 C12---N3---N4 110.47 (14) N2---C11---C10 123.54 (16) C13---N4---N3 111.93 (14) N2---C11---H11 118.2 C16---N5---C17 116.98 (16) C10---C11---H11 118.2 N1---C1---S2 120.59 (12) N3---C12---C9 121.48 (16) N1---C1---S1 119.77 (12) N3---C12---H12 119.3 S2---C1---S1 119.64 (10) C9---C12---H12 119.3 N1---C2---C3 113.01 (13) N4---C13---C14 119.59 (16) N1---C2---H2A 109.0 N4---C13---H13 120.2 C3---C2---H2A 109.0 C14---C13---H13 120.2 N1---C2---H2B 109.0 C15---C14---C18 117.63 (16) C3---C2---H2B 109.0 C15---C14---C13 120.38 (16) H2A---C2---H2B 107.8 C18---C14---C13 121.99 (16) O1---C3---C2 110.27 (14) C16---C15---C14 118.89 (17) O1---C3---H3A 109.6 C16---C15---H15 120.6 C2---C3---H3A 109.6 C14---C15---H15 120.6 O1---C3---H3B 109.6 N5---C16---C15 123.90 (17) C2---C3---H3B 109.6 N5---C16---H16 118.0 H3A---C3---H3B 108.1 C15---C16---H16 118.0 N1---C4---C5 113.22 (13) N5---C17---C18 123.21 (17) N1---C4---H4A 108.9 N5---C17---H17 118.4 C5---C4---H4A 108.9 C18---C17---H17 118.4 N1---C4---H4B 108.9 C17---C18---C14 119.38 (17) C5---C4---H4B 108.9 C17---C18---H18 120.3 H4A---C4---H4B 107.7 C14---C18---H18 120.3 N2^i^---Cd---S1---C1 −86.27 (7) C4---N1---C2---C3 −87.99 (17) N2---Cd---S1---C1 93.73 (7) N1---C2---C3---O1 70.19 (17) S1^i^---Cd---S1---C1 95 (100) C1---N1---C4---C5 90.95 (18) S2---Cd---S1---C1 1.40 (5) C2---N1---C4---C5 −89.78 (16) S2^i^---Cd---S1---C1 −178.60 (5) N1---C4---C5---C6 175.96 (13) N2^i^---Cd---S2---C1 88.89 (7) C11---N2---C7---C8 0.3 (3) N2---Cd---S2---C1 −91.11 (7) Cd---N2---C7---C8 179.02 (14) S1---Cd---S2---C1 −1.41 (5) N2---C7---C8---C9 −0.1 (3) S1^i^---Cd---S2---C1 178.59 (5) C7---C8---C9---C10 −0.3 (3) S2^i^---Cd---S2---C1 −29 (100) C7---C8---C9---C12 −179.20 (17) N2^i^---Cd---N2---C11 −146 (100) C8---C9---C10---C11 0.5 (2) S1---Cd---N2---C11 −10.78 (13) C12---C9---C10---C11 179.47 (15) S1^i^---Cd---N2---C11 169.22 (13) C7---N2---C11---C10 −0.1 (3) S2---Cd---N2---C11 58.06 (13) Cd---N2---C11---C10 −178.83 (13) S2^i^---Cd---N2---C11 −121.94 (13) C9---C10---C11---N2 −0.3 (3) N2^i^---Cd---N2---C7 35 (100) N4---N3---C12---C9 176.90 (14) S1---Cd---N2---C7 170.58 (14) C10---C9---C12---N3 173.70 (15) S1^i^---Cd---N2---C7 −9.42 (14) C8---C9---C12---N3 −7.4 (3) S2---Cd---N2---C7 −120.58 (14) N3---N4---C13---C14 179.61 (14) S2^i^---Cd---N2---C7 59.42 (14) N4---C13---C14---C15 169.03 (16) C12---N3---N4---C13 −177.28 (14) N4---C13---C14---C18 −10.7 (3) C2---N1---C1---S2 −2.1 (2) C18---C14---C15---C16 −1.1 (3) C4---N1---C1---S2 177.14 (10) C13---C14---C15---C16 179.14 (16) C2---N1---C1---S1 177.52 (10) C17---N5---C16---C15 0.6 (3) C4---N1---C1---S1 −3.2 (2) C14---C15---C16---N5 0.4 (3) Cd---S2---C1---N1 −178.09 (12) C16---N5---C17---C18 −0.8 (3) Cd---S2---C1---S1 2.29 (8) N5---C17---C18---C14 0.1 (3) Cd---S1---C1---N1 178.07 (12) C15---C14---C18---C17 0.9 (3) Cd---S1---C1---S2 −2.31 (8) C13---C14---C18---C17 −179.34 (16) C1---N1---C2---C3 91.28 (18) ----------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*+1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3093 .table-wrap} --------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1o···N5^ii^ 0.84 (2) 1.98 (2) 2.810 (2) 176 (2) C10---H10···O1^iii^ 0.95 2.55 3.480 (3) 168 C3---H3a···N4^iv^ 0.99 2.61 3.369 (3) 134 --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (ii) *x*+2, *y*, *z*−1; (iii) −*x*+1, −*y*, −*z*+1; (iv) *x*+1, *y*, *z*−1. Table 1 ::: {.caption} ###### Selected geometric parameters (Å, °) ::: ::: {#d32e574 .table-wrap} --------- ------------- Cd---S1 2.6379 (10) Cd---S2 2.6626 (10) Cd---N2 2.5403 (17) --------- ------------- ::: ::: {#d32e592 .table-wrap} -------------- ----------- S1---Cd---S2 68.83 (3) -------------- ----------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ ---------- ---------- ----------- ------------- O1---H1*o*⋯N5^i^ 0.84 (2) 1.98 (2) 2.810 (2) 176 (2) C10---H10⋯O1^ii^ 0.95 2.55 3.480 (3) 168 C3---H3a⋯N4^iii^ 0.99 2.61 3.369 (3) 134 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.714569

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052135/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m320-m321", "authors": [ { "first": "Grant A.", "last": "Broker" }, { "first": "Edward R. T.", "last": "Tiekink" } ] }

PMC3052136

Related literature {#sec1} ================== For structural data on isonipecotamide salts, see: Smith *et al.* (2010[@bb11]); Smith & Wermuth (2010*a* [@bb6],*b* [@bb7],*c* [@bb8],*d* [@bb9], 2011[@bb10]). For the crystal structure of *o*-phthalic acid, see: Ermer (1981[@bb1]). For hydrogen-bonding graph-set analysis, see: Etter *et al.* (1990[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~6~H~13~N~2~O^+^·C~8~H~5~O~4~ ^−^·C~8~H~6~O~4~*M* *~r~* = 460.43Triclinic,*a* = 8.7857 (4) Å*b* = 11.7907 (6) Å*c* = 12.3188 (6) Åα = 62.496 (5)°β = 85.916 (4)°γ = 82.604 (4)°*V* = 1122.36 (11) Å^3^*Z* = 2Mo *K*α radiationμ = 0.11 mm^−1^*T* = 200 K0.40 × 0.30 × 0.18 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini-S CCD-detector diffractometerAbsorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010[@bb4]) *T* ~min~ = 0.923, *T* ~max~ = 0.98013586 measured reflections4401 independent reflections3444 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.024 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.037*wR*(*F* ^2^) = 0.094*S* = 1.074401 reflections326 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e690} Data collection: *CrysAlis PRO* (Oxford Diffraction, 2010[@bb4]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]) within *WinGX* (Farrugia, 1999[@bb3]); molecular graphics: *PLATON* (Spek, 2009[@bb12]); software used to prepare material for publication: *PLATON*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003825/wn2419sup1.cif](http://dx.doi.org/10.1107/S1600536811003825/wn2419sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003825/wn2419Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003825/wn2419Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wn2419&file=wn2419sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wn2419sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wn2419&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WN2419](http://scripts.iucr.org/cgi-bin/sendsup?wn2419)). The authors acknowledge financial support from the Australian Research Council, the Faculty of Science and Technology and the University Library, Queensland University of Technology and the School of Biomolecular and Physical Sciences, Griffith University. Comment ======= The amide piperidine-4-carboxamide (isonipecotamide, INIPA) has provided the structures of proton-transfer compounds with a range of organic acids, mainly aromatic (Smith & Wermuth, 2010*a*,*b*,*c*,*d*, 2011; Smith *et al.*, 2010). The title compound, the salt adduct, C~6~H~13~N~2~O^+^ C~8~H~5~O~4~^-^ . C~8~H~6~O~4~, was obtained from the 1:1 stoichiometric reaction of phthalic acid with INIPA in methanol and the crystal structure is reported here; it represents the first example of a salt--adduct of INIPA. The asymmetric unit (Fig. 1) comprises an isonipecotamide cation, (*C*), a hydrogen phthalate anion (*B*) and a phthalic acid adduct molecule (*A*), which together form a two-dimensional hydrogen-bonded network through head-to-tail cation--anion--adduct molecule interactions (Table 1). These include a cyclic heteromolecular amide--carboxylate motif \[graph set R~2~^2^(8) (Etter *et al.*, 1990)\], conjoint cyclic R~2~^2^(6) and R~3~^3^(10) piperidinium N---H···O~carboxyl~ associations, as well as strong carboxylic acid O---H···O~carboxyl~ hydrogen bonds (Fig. 2). There is no occurrence of the cyclic homomolecular amide--amide dimer motif association, such as is found in the INIPA salts of the 2-nitro-, 4-nitro- and 3,5-dinitrobenzoic acids (Smith & Wermuth, 2010*b*) or of biphenyl-4,4\'-disulfonic acid (Smith *et al.*, 2010). In the hydrogen phthalate anion (*B*) and the phthalic acid adduct molecule (*A*), the carboxyl substituent groups are rotated by differing degrees out of the planes of the benzene rings \[torsion angles C1---C2---C21---O22 and C2---C1---C11---O11: -147.67 (6) and 52.9 (2)° \[for *B*)\] and -117.75 (15) and -157.57 (14)° \[for *A*)\], which compare with 20.3 (1)° for the parent acid molecule which has two-fold rotational symmetry (Ermer, 1981). Experimental {#experimental} ============ The title compound was synthesized by heating together under reflux for 10 minutes, 1 mmol quantities of piperidine-4-carboxamide (isonipecotamide) and phthalic acid in 50 ml of methanol. After concentration to *ca* 30 ml, partial room temperature evaporation of the hot-filtered solution gave colourless plates of the title compound, from which a specimen was cleaved for the X-ray crystallographic analysis. Refinement {#refinement} ========== Hydrogen atoms involved in hydrogen-bonding interactions were located by difference methods and their positional and isotropic displacement parameters were refined. Other H-atoms were included in the refinement at calculated positions using a riding-model approximation \[C---H = 0.93--0.98 Å\] and with *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular conformation for the INIPA cation (C), the hydrogen phthalate anion (B) and the phthalic acid adduct molecule (A) in the asymmetric unit. The inter-species hydrogen bonds are shown as dashed lines and displacement ellipsoids are drawn at the 40% probability level. Hydrogen atoms are shown as spheres of arbitrary radius. ::: ![](e-67-0o566-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The hydrogen-bonded chain structure, showing the cyclic R22(8) amide--carboxyl and R22(6) piperidinium--carboxyl cation--anion associations. Non-associative H atoms have been omitted and hydrogen bonds are shown as dashed lines. For symmetry codes, see Table 1. ::: ![](e-67-0o566-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e237 .table-wrap} ------------------------------------------------ --------------------------------------- C~6~H~13~N~2~O^+^·C~8~H~5~O~4~^−^·C~8~H~6~O~4~ *Z* = 2 *M~r~* = 460.43 *F*(000) = 484 Triclinic, *P*1 *D*~x~ = 1.362 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.7857 (4) Å Cell parameters from 6939 reflections *b* = 11.7907 (6) Å θ = 3.2--28.7° *c* = 12.3188 (6) Å µ = 0.11 mm^−1^ α = 62.496 (5)° *T* = 200 K β = 85.916 (4)° Plate, colourless γ = 82.604 (4)° 0.40 × 0.30 × 0.18 mm *V* = 1122.36 (11) Å^3^ ------------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e395 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Gemini-S CCD-detector diffractometer 4401 independent reflections Radiation source: Enhance (Mo) X-ray source 3444 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.024 Detector resolution: 16.077 pixels mm^-1^ θ~max~ = 26.0°, θ~min~ = 3.3° ω scans *h* = −10→10 Absorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010) *k* = −14→14 *T*~min~ = 0.923, *T*~max~ = 0.980 *l* = −15→15 13586 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e515 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.037 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.094 H atoms treated by a mixture of independent and constrained refinement *S* = 1.07 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0531*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4401 reflections (Δ/σ)~max~ = 0.001 326 parameters Δρ~max~ = 0.25 e Å^−3^ 0 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e669 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles *etc*. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e771 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O41C 0.74423 (12) 0.61632 (11) −0.02736 (9) 0.0416 (3) N1C 1.00683 (14) 0.42772 (13) 0.35653 (11) 0.0325 (4) N41C 0.52124 (15) 0.58014 (14) 0.08017 (12) 0.0383 (4) C2C 0.85240 (17) 0.48482 (14) 0.37702 (12) 0.0316 (5) C3C 0.77366 (16) 0.56671 (13) 0.25569 (12) 0.0279 (4) C4C 0.75894 (15) 0.48525 (13) 0.19015 (12) 0.0255 (4) C5C 0.91666 (17) 0.42485 (15) 0.17252 (13) 0.0352 (5) C6C 0.99655 (17) 0.34593 (15) 0.29489 (13) 0.0355 (5) C41C 0.67380 (16) 0.56532 (14) 0.07155 (12) 0.0287 (4) O11A 0.80799 (12) 0.85845 (10) 0.30180 (10) 0.0382 (3) O12A 1.01504 (12) 0.71996 (11) 0.38418 (9) 0.0457 (4) O21A 1.15402 (13) 0.64611 (10) 0.19609 (10) 0.0428 (4) O22A 1.34884 (12) 0.66738 (10) 0.28975 (10) 0.0350 (3) C1A 1.04746 (16) 0.90657 (13) 0.19787 (11) 0.0257 (4) C2A 1.18683 (15) 0.85461 (13) 0.16830 (12) 0.0273 (4) C3A 1.28238 (18) 0.93696 (15) 0.07974 (14) 0.0388 (5) C4A 1.2394 (2) 1.06857 (16) 0.02235 (15) 0.0456 (5) C5A 1.10150 (19) 1.11900 (15) 0.05043 (14) 0.0402 (5) C6A 1.00445 (17) 1.03847 (13) 0.13774 (12) 0.0321 (4) C11A 0.95520 (16) 0.81938 (13) 0.30320 (12) 0.0270 (4) C21A 1.22700 (16) 0.71181 (14) 0.22139 (12) 0.0285 (4) O11B 0.55460 (12) 0.56551 (9) 0.65124 (9) 0.0375 (3) O12B 0.70819 (11) 0.67951 (10) 0.49932 (9) 0.0365 (3) O21B 0.62518 (11) 0.72888 (11) 0.75928 (9) 0.0380 (3) O22B 0.39403 (12) 0.75761 (11) 0.83676 (9) 0.0443 (4) C1B 0.47554 (15) 0.78671 (12) 0.53468 (12) 0.0234 (4) C2B 0.41733 (15) 0.82601 (12) 0.62266 (12) 0.0250 (4) C3B 0.30225 (17) 0.92762 (14) 0.59082 (14) 0.0332 (5) C4B 0.24536 (18) 0.99166 (14) 0.47329 (15) 0.0400 (5) C5B 0.30399 (18) 0.95471 (14) 0.38598 (14) 0.0380 (5) C6B 0.41770 (17) 0.85304 (13) 0.41663 (13) 0.0309 (4) C11B 0.58924 (15) 0.66926 (13) 0.56461 (12) 0.0251 (4) C21B 0.47720 (16) 0.76662 (13) 0.75001 (12) 0.0282 (4) H4C 0.69780 0.41540 0.24300 0.0310\* H11C 1.068 (2) 0.4933 (17) 0.3102 (16) 0.051 (5)\* H12C 1.0542 (19) 0.3761 (16) 0.4339 (16) 0.048 (5)\* H21C 0.86350 0.53720 0.41730 0.0380\* H22C 0.79060 0.41670 0.42960 0.0380\* H31C 0.83260 0.63760 0.20490 0.0330\* H32C 0.67250 0.60230 0.26930 0.0330\* H41C 0.461 (2) 0.6370 (17) 0.0071 (17) 0.058 (5)\* H42C 0.475 (2) 0.5356 (17) 0.1562 (17) 0.054 (5)\* H51C 0.90570 0.36990 0.13500 0.0420\* H52C 0.97860 0.49200 0.11810 0.0420\* H61C 0.93950 0.27400 0.34670 0.0430\* H62C 1.09880 0.31190 0.28190 0.0430\* H3A 1.37520 0.90370 0.05900 0.0470\* H4A 1.30450 1.12320 −0.03570 0.0550\* H5A 1.07320 1.20730 0.01080 0.0480\* H6A 0.91060 1.07260 0.15610 0.0380\* H11A 0.762 (2) 0.793 (2) 0.3786 (19) 0.078 (6)\* H22A 1.374 (2) 0.583 (2) 0.3154 (18) 0.072 (6)\* H3B 0.26280 0.95300 0.64920 0.0400\* H4B 0.16780 1.05940 0.45310 0.0480\* H5B 0.26690 0.99830 0.30660 0.0460\* H6B 0.45630 0.82850 0.35750 0.0370\* H21B 0.664 (2) 0.691 (2) 0.844 (2) 0.081 (7)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1500 .table-wrap} ------ ------------- ------------ ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O41C 0.0306 (6) 0.0590 (7) 0.0233 (5) −0.0098 (5) 0.0002 (4) −0.0077 (5) N1C 0.0310 (7) 0.0316 (7) 0.0255 (6) −0.0079 (6) −0.0069 (6) −0.0032 (6) N41C 0.0285 (7) 0.0545 (9) 0.0257 (7) −0.0019 (6) −0.0009 (6) −0.0138 (7) C2C 0.0382 (9) 0.0315 (8) 0.0255 (7) −0.0033 (7) −0.0024 (6) −0.0133 (6) C3C 0.0290 (8) 0.0272 (7) 0.0255 (7) −0.0033 (6) −0.0021 (6) −0.0101 (6) C4C 0.0256 (7) 0.0278 (7) 0.0216 (7) −0.0058 (6) 0.0004 (5) −0.0093 (6) C5C 0.0340 (8) 0.0430 (9) 0.0282 (8) 0.0018 (7) −0.0001 (6) −0.0175 (7) C6C 0.0301 (8) 0.0360 (9) 0.0356 (8) 0.0038 (7) −0.0007 (6) −0.0141 (7) C41C 0.0280 (8) 0.0351 (8) 0.0256 (7) −0.0061 (6) −0.0006 (6) −0.0155 (6) O11A 0.0307 (6) 0.0306 (6) 0.0376 (6) 0.0049 (5) 0.0092 (5) −0.0057 (5) O12A 0.0312 (6) 0.0454 (7) 0.0307 (6) 0.0011 (5) 0.0005 (5) 0.0063 (5) O21A 0.0453 (7) 0.0335 (6) 0.0459 (6) −0.0133 (5) −0.0085 (5) −0.0116 (5) O22A 0.0294 (6) 0.0271 (6) 0.0485 (6) 0.0029 (5) −0.0075 (5) −0.0178 (5) C1A 0.0279 (7) 0.0259 (7) 0.0211 (7) −0.0046 (6) −0.0022 (6) −0.0083 (6) C2A 0.0253 (7) 0.0283 (8) 0.0249 (7) −0.0062 (6) −0.0011 (6) −0.0083 (6) C3A 0.0290 (8) 0.0378 (9) 0.0386 (8) −0.0059 (7) 0.0051 (7) −0.0083 (7) C4A 0.0402 (10) 0.0367 (9) 0.0403 (9) −0.0137 (8) 0.0060 (7) 0.0005 (8) C5A 0.0446 (10) 0.0242 (8) 0.0376 (8) −0.0041 (7) −0.0045 (7) −0.0016 (7) C6A 0.0342 (8) 0.0277 (8) 0.0289 (7) 0.0005 (7) −0.0034 (6) −0.0089 (6) C11A 0.0287 (8) 0.0271 (8) 0.0237 (7) −0.0024 (6) −0.0004 (6) −0.0106 (6) C21A 0.0242 (7) 0.0302 (8) 0.0282 (7) −0.0058 (6) 0.0049 (6) −0.0110 (6) O11B 0.0377 (6) 0.0231 (5) 0.0381 (6) 0.0013 (5) 0.0143 (5) −0.0056 (5) O12B 0.0278 (6) 0.0373 (6) 0.0324 (5) 0.0012 (5) 0.0100 (4) −0.0083 (5) O21B 0.0281 (6) 0.0522 (7) 0.0244 (5) −0.0004 (5) −0.0019 (4) −0.0104 (5) O22B 0.0407 (7) 0.0563 (8) 0.0295 (6) 0.0060 (6) 0.0030 (5) −0.0175 (5) C1B 0.0209 (7) 0.0206 (7) 0.0265 (7) −0.0045 (6) 0.0001 (5) −0.0085 (6) C2B 0.0244 (7) 0.0214 (7) 0.0281 (7) −0.0050 (6) 0.0007 (6) −0.0099 (6) C3B 0.0347 (8) 0.0274 (8) 0.0377 (8) 0.0014 (7) 0.0010 (7) −0.0165 (7) C4B 0.0372 (9) 0.0265 (8) 0.0493 (10) 0.0096 (7) −0.0118 (7) −0.0132 (7) C5B 0.0420 (9) 0.0306 (8) 0.0355 (8) 0.0016 (7) −0.0176 (7) −0.0092 (7) C6B 0.0345 (8) 0.0299 (8) 0.0292 (7) −0.0024 (7) −0.0057 (6) −0.0139 (6) C11B 0.0238 (7) 0.0266 (7) 0.0232 (7) −0.0022 (6) 0.0017 (6) −0.0103 (6) C21B 0.0308 (8) 0.0245 (7) 0.0273 (7) −0.0033 (6) 0.0017 (6) −0.0103 (6) ------ ------------- ------------ ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2183 .table-wrap} ------------------------- -------------- ------------------------- -------------- O41C---C41C 1.2413 (17) C5C---H51C 0.9700 O11A---C11A 1.3144 (18) C5C---H52C 0.9700 O12A---C11A 1.2172 (19) C6C---H61C 0.9700 O21A---C21A 1.220 (2) C6C---H62C 0.9700 O22A---C21A 1.3062 (18) C1A---C11A 1.4934 (19) O11A---H11A 1.00 (2) C1A---C2A 1.399 (2) O22A---H22A 0.90 (2) C1A---C6A 1.391 (2) O11B---C11B 1.2537 (18) C2A---C21A 1.500 (2) O12B---C11B 1.2557 (17) C2A---C3A 1.392 (2) O21B---C21B 1.3140 (18) C3A---C4A 1.387 (3) O22B---C21B 1.2211 (17) C4A---C5A 1.373 (3) O21B---H21B 0.99 (2) C5A---C6A 1.386 (2) N1C---C6C 1.491 (2) C3A---H3A 0.9300 N1C---C2C 1.494 (2) C4A---H4A 0.9300 N41C---C41C 1.332 (2) C5A---H5A 0.9300 N1C---H12C 0.953 (18) C6A---H6A 0.9300 N1C---H11C 0.932 (19) C1B---C2B 1.405 (2) N41C---H42C 0.930 (18) C1B---C11B 1.509 (2) N41C---H41C 0.979 (19) C1B---C6B 1.3918 (19) C2C---C3C 1.5123 (19) C2B---C3B 1.386 (2) C3C---C4C 1.534 (2) C2B---C21B 1.4954 (19) C4C---C5C 1.523 (2) C3B---C4B 1.383 (2) C4C---C41C 1.5117 (19) C4B---C5B 1.381 (2) C5C---C6C 1.523 (2) C5B---C6B 1.380 (2) C2C---H21C 0.9700 C3B---H3B 0.9300 C2C---H22C 0.9700 C4B---H4B 0.9300 C3C---H31C 0.9700 C5B---H5B 0.9300 C3C---H32C 0.9700 C6B---H6B 0.9300 C4C---H4C 0.9800 C11A---O11A---H11A 106.6 (12) C2A---C1A---C11A 118.40 (13) C21A---O22A---H22A 112.4 (12) C3A---C2A---C21A 119.76 (14) C21B---O21B---H21B 113.9 (11) C1A---C2A---C3A 119.05 (15) C2C---N1C---C6C 112.01 (12) C1A---C2A---C21A 120.92 (12) H11C---N1C---H12C 107.8 (15) C2A---C3A---C4A 120.14 (16) C6C---N1C---H11C 110.2 (12) C3A---C4A---C5A 120.62 (16) C2C---N1C---H11C 109.5 (12) C4A---C5A---C6A 120.06 (17) C2C---N1C---H12C 108.5 (11) C1A---C6A---C5A 119.96 (15) C6C---N1C---H12C 108.8 (13) O12A---C11A---C1A 121.18 (13) H41C---N41C---H42C 121.8 (16) O11A---C11A---O12A 123.45 (13) C41C---N41C---H42C 118.5 (11) O11A---C11A---C1A 115.38 (13) C41C---N41C---H41C 119.7 (11) O22A---C21A---C2A 114.51 (14) N1C---C2C---C3C 109.73 (11) O21A---C21A---C2A 121.23 (13) C2C---C3C---C4C 110.03 (13) O21A---C21A---O22A 124.16 (16) C5C---C4C---C41C 113.04 (12) C2A---C3A---H3A 120.00 C3C---C4C---C5C 110.14 (12) C4A---C3A---H3A 120.00 C3C---C4C---C41C 110.15 (13) C5A---C4A---H4A 120.00 C4C---C5C---C6C 110.52 (12) C3A---C4A---H4A 120.00 N1C---C6C---C5C 110.09 (14) C4A---C5A---H5A 120.00 O41C---C41C---C4C 120.98 (13) C6A---C5A---H5A 120.00 N41C---C41C---C4C 116.38 (12) C5A---C6A---H6A 120.00 O41C---C41C---N41C 122.62 (13) C1A---C6A---H6A 120.00 N1C---C2C---H21C 110.00 C2B---C1B---C6B 118.78 (14) H21C---C2C---H22C 108.00 C6B---C1B---C11B 118.11 (13) C3C---C2C---H21C 110.00 C2B---C1B---C11B 122.94 (12) C3C---C2C---H22C 110.00 C1B---C2B---C21B 123.27 (13) N1C---C2C---H22C 110.00 C3B---C2B---C21B 117.17 (13) C4C---C3C---H31C 110.00 C1B---C2B---C3B 119.52 (13) C2C---C3C---H32C 110.00 C2B---C3B---C4B 120.84 (15) H31C---C3C---H32C 108.00 C3B---C4B---C5B 119.83 (16) C4C---C3C---H32C 110.00 C4B---C5B---C6B 119.96 (14) C2C---C3C---H31C 110.00 C1B---C6B---C5B 121.06 (14) C41C---C4C---H4C 108.00 O11B---C11B---C1B 116.96 (12) C5C---C4C---H4C 108.00 O12B---C11B---C1B 118.86 (13) C3C---C4C---H4C 108.00 O11B---C11B---O12B 124.11 (15) C4C---C5C---H51C 110.00 O21B---C21B---C2B 114.59 (12) C4C---C5C---H52C 110.00 O22B---C21B---C2B 121.76 (13) C6C---C5C---H51C 110.00 O21B---C21B---O22B 123.64 (13) C6C---C5C---H52C 110.00 C2B---C3B---H3B 120.00 H51C---C5C---H52C 108.00 C4B---C3B---H3B 120.00 C5C---C6C---H61C 110.00 C3B---C4B---H4B 120.00 H61C---C6C---H62C 108.00 C5B---C4B---H4B 120.00 C5C---C6C---H62C 110.00 C4B---C5B---H5B 120.00 N1C---C6C---H61C 110.00 C6B---C5B---H5B 120.00 N1C---C6C---H62C 110.00 C1B---C6B---H6B 119.00 C2A---C1A---C6A 120.16 (13) C5B---C6B---H6B 119.00 C6A---C1A---C11A 121.15 (13) C6C---N1C---C2C---C3C −59.45 (17) C1A---C2A---C21A---O22A −117.75 (15) C2C---N1C---C6C---C5C 58.30 (15) C3A---C2A---C21A---O21A −108.28 (17) N1C---C2C---C3C---C4C 58.11 (16) C3A---C2A---C21A---O22A 68.28 (18) C2C---C3C---C4C---C5C −57.23 (15) C2A---C3A---C4A---C5A −1.1 (3) C2C---C3C---C4C---C41C 177.41 (11) C3A---C4A---C5A---C6A 0.7 (3) C3C---C4C---C5C---C6C 56.17 (17) C4A---C5A---C6A---C1A 0.7 (2) C41C---C4C---C5C---C6C 179.86 (14) C6B---C1B---C2B---C3B 1.3 (2) C3C---C4C---C41C---O41C 97.27 (18) C6B---C1B---C2B---C21B −176.43 (14) C3C---C4C---C41C---N41C −81.09 (18) C11B---C1B---C2B---C3B −173.80 (14) C5C---C4C---C41C---O41C −26.4 (2) C11B---C1B---C2B---C21B 8.5 (2) C5C---C4C---C41C---N41C 155.23 (16) C2B---C1B---C6B---C5B −0.8 (2) C4C---C5C---C6C---N1C −56.27 (17) C11B---C1B---C6B---C5B 174.56 (14) C6A---C1A---C2A---C3A 1.1 (2) C2B---C1B---C11B---O11B 52.9 (2) C6A---C1A---C2A---C21A −172.89 (13) C2B---C1B---C11B---O12B −130.04 (15) C11A---C1A---C2A---C3A −172.71 (14) C6B---C1B---C11B---O11B −122.25 (15) C11A---C1A---C2A---C21A 13.3 (2) C6B---C1B---C11B---O12B 54.86 (19) C2A---C1A---C6A---C5A −1.6 (2) C1B---C2B---C3B---C4B −0.8 (2) C11A---C1A---C6A---C5A 172.11 (14) C21B---C2B---C3B---C4B 177.07 (14) C2A---C1A---C11A---O11A −157.57 (14) C1B---C2B---C21B---O21B 34.0 (2) C2A---C1A---C11A---O12A 23.0 (2) C1B---C2B---C21B---O22B −147.67 (16) C6A---C1A---C11A---O11A 28.7 (2) C3B---C2B---C21B---O21B −143.76 (15) C6A---C1A---C11A---O12A −150.80 (15) C3B---C2B---C21B---O22B 34.6 (2) C1A---C2A---C3A---C4A 0.2 (2) C2B---C3B---C4B---C5B −0.3 (2) C21A---C2A---C3A---C4A 174.29 (15) C3B---C4B---C5B---C6B 0.8 (3) C1A---C2A---C21A---O21A 65.69 (19) C4B---C5B---C6B---C1B −0.3 (2) ------------------------- -------------- ------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3169 .table-wrap} ------------------------- ------------ ------------ ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1C---H11C···O21A 0.932 (19) 1.911 (19) 2.8287 (18) 167.7 (16) N1C---H12C···O12A^i^ 0.953 (18) 2.077 (17) 2.8519 (16) 137.4 (14) N1C---H12C···O12B^i^ 0.953 (18) 2.204 (17) 2.9606 (16) 135.6 (14) N41C---H41C···O22B^ii^ 0.979 (19) 1.994 (19) 2.9494 (17) 164.5 (16) N41C---H42C···O11B^iii^ 0.930 (18) 2.120 (19) 3.0122 (17) 160.3 (16) O11A---H11A···O12B 1.00 (2) 1.57 (2) 2.5635 (15) 173 (2) O21B---H21B···O41C^iv^ 0.99 (2) 1.58 (2) 2.5644 (14) 171 (2) O22A---H22A···O11B^i^ 0.90 (2) 1.65 (2) 2.5363 (17) 170.8 (18) C3B---H3B···O11A^v^ 0.93 2.55 3.365 (2) 146 C4C---H4C···O11B^iii^ 0.98 2.53 3.2159 (17) 127 C2C---H21C···O12A 0.97 2.54 3.317 (2) 137 C2C---H21C···O12B 0.97 2.55 3.364 (2) 142 C6C---H62C···O21B^i^ 0.97 2.47 3.4265 (19) 168 ------------------------- ------------ ------------ ------------- --------------- ::: Symmetry codes: (i) −*x*+2, −*y*+1, −*z*+1; (ii) *x*, *y*, *z*−1; (iii) −*x*+1, −*y*+1, −*z*+1; (iv) *x*, *y*, *z*+1; (v) −*x*+1, −*y*+2, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ----------------------------- ------------ ------------ ------------- ------------- N1*C*---H11*C*⋯O21*A* 0.932 (19) 1.911 (19) 2.8287 (18) 167.7 (16) N1*C*---H12*C*⋯O12*A*^i^ 0.953 (18) 2.077 (17) 2.8519 (16) 137.4 (14) N1*C*---H12*C*⋯O12*B*^i^ 0.953 (18) 2.204 (17) 2.9606 (16) 135.6 (14) N41*C*---H41*C*⋯O22*B*^ii^ 0.979 (19) 1.994 (19) 2.9494 (17) 164.5 (16) N41*C*---H42*C*⋯O11*B*^iii^ 0.930 (18) 2.120 (19) 3.0122 (17) 160.3 (16) O11*A*---H11*A*⋯O12*B* 1.00 (2) 1.57 (2) 2.5635 (15) 173 (2) O21*B*---H21*B*⋯O41*C*^iv^ 0.99 (2) 1.58 (2) 2.5644 (14) 171 (2) O22*A*---H22*A*⋯O11*B*^i^ 0.90 (2) 1.65 (2) 2.5363 (17) 170.8 (18) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::

PubMed Central

2024-06-05T04:04:18.720666

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052136/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o566", "authors": [ { "first": "Graham", "last": "Smith" }, { "first": "Urs D.", "last": "Wermuth" } ] }

PMC3052137

Related literature {#sec1} ================== For general background to metal complexes with 4,4′-bi-1,3-thiazole ligands, see: Baker & Goodwin (1985[@bb6]); Mahjoub & Morsali (2001[@bb17], 2002*a* [@bb18],*b* [@bb19]). For related structures, see: Al-Hashemi *et al.* (2009[@bb1]); Ali & Al-Far (2007[@bb2]); Amani *et al.* (2007*a* [@bb3],*b* [@bb4], 2009[@bb5]); Craig *et al.* (1988[@bb9]); Figgis *et al.* (1983[@bb11]); Jia *et al.* (2006[@bb13]); Khavasi *et al.* (2008[@bb14]); Kulkarni *et al.* (1998[@bb15]); Notash *et al.* (2008[@bb21], 2009[@bb20]); Rahimi *et al.* (2009[@bb22]); Safari *et al.* (2009[@bb23]). For the synthesis of the ligand, see: Erlenmeyer & Ueberwasser (1939[@bb10]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Fe(C~6~H~4~N~2~S~2~)~3~\]\[FeBr~4~\]Br*M* *~r~* = 1015.95Trigonal,*a* = 12.0638 (7) Å*c* = 17.6907 (13) Å*V* = 2229.7 (2) Å^3^*Z* = 3Mo *K*α radiationμ = 8.14 mm^−1^*T* = 100 K0.45 × 0.35 × 0.30 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2001[@bb7]) *T* ~min~ = 0.031, *T* ~max~ = 0.0868430 measured reflections2508 independent reflections2427 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.099 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.036*wR*(*F* ^2^) = 0.085*S* = 1.012508 reflections112 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.93 e Å^−3^Δρ~min~ = −0.78 e Å^−3^Absolute structure: Flack (1983[@bb12]), 1195 Friedel pairsFlack parameter: 0.021 (9) {#d5e561} Data collection: *APEX2* (Bruker, 2007[@bb8]); cell refinement: *SAINT* (Bruker, 2007[@bb8]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb24]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb24]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb24]) and *Mercury* (Macrae *et al.*, 2006[@bb16]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004181/hy2404sup1.cif](http://dx.doi.org/10.1107/S1600536811004181/hy2404sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004181/hy2404Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004181/hy2404Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hy2404&file=hy2404sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hy2404sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hy2404&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HY2404](http://scripts.iucr.org/cgi-bin/sendsup?hy2404)). We thank the Graduate Study Councils of the Islamic Azad University, North Tehran Branch, and Shahid Beheshti University for financial support. Comment ======= Erlenmeyer & Ueberwasser (1939) first reported the synthesis of 4,4\'-bi-1,3-thiazole (4,4\'-bit) and Craig *et al.* (1988) determined the structure of this compound. Although 4,4\'-bit is a good bidentate ligand, a few of its metal complexes have been prepared, such as those of nickel and iron (Baker & Goodwin, 1985), lead (Mahjoub & Morsali, 2001, 2002*a*) and bismuth (Mahjoub & Morsali, 2002*b*). We recently introduced the coordination chemistry of 2,2\'-dimethyl-4,4\'-bi-1,3-thiazole with copper (Al-Hashemi *et al.*, 2009), zinc and mercury (Khavasi *et al.*, 2008; Safari *et al.*, 2009), cadmium (Notash *et al.*, 2009) and thallium (Notash *et al.*, 2008). We report here the synthesis and crystal structure of the title compound. The asymmetric unit of the title compound (Fig. 1), contains one third of an \[Fe(4,4\'-bit)~3~\]^2+^ cation, one third of an \[FeBr~4~\]^-^ anion and one third of a Br^-^ anion. In the \[Fe(4,4\'-bit)~3~\]^2+^ cation, the Fe^II^ atom (3 symmetry) is six-coordinated in a distorted octahedral geometry by six N atoms from three 4,4\'-bit ligands. The Fe---N bond lengths are 1.962 (3) and 1.974 (3) Å (Table 1). The average Fe---N bond distances in high-spin iron(II) and (III) complexes with phenanthroline and bipyridine are around 2.2 Å. However, for low-spin iron(II) and (III) complexes, the Fe---N distances less than 2.0 Å have been reported (Amani *et al.*, 2007*a*,b, 2009; Figgis *et al.*, 1983; Kulkarni *et al.*, 1998; Rahimi *et al.*, 2009). Therefore, in the \[Fe(4,4\'-bit)~3~\]^2+^ cation, the Fe---N bond distances are unambiguous in accord with low-spin iron(II). The N---Fe---N bond angles are in the range of 82.00 (14) to 171.87 (14)°. The bond angles and distances are in good agreement to those of \[Fe(4,4\'-bit)~3~\]^2+^ cations, which have been found in other structures (Baker & Goodwin, 1985). In the \[FeBr~4~\]^-^ anion, the Fe^III^ atom (3 symmetry) is four-coordinated in a distorted tetrahedral geometry by four Br atoms. The Fe---Br bond lengths are 2.3348 (5) and 2.3370 (12) Å. The Br---Fe---Br angles, in turn, span the ranges of 108.64 (3) to 110.29 (3)°, and the bond angles and distances are in good agreement to those of \[FeBr~4~\]^-^ anions, which have been found in other structures (Ali & Al-Far 2007; Jia *et al.*, 2006). Fig. 2 shows significant intermolecular C---H···Br hydrogen bonds in the title compound (Table 2). The hydrogen bonds cause the formation of a supramolecular architecture, best described as built up by Br(thiazol)~9~ supramolecular synthons (Fig. 2) assembled *via* C---H···Br hydrogen bonds, where nine thiazole groups surround one (central) uncoordinated bromide ion. These synthons are further connected into an adamantoid-like network that extends into a three-dimensional structure. The discrete \[FeBr~4~\]^-^ anions occupy the cavities that result from the three-dimensional assembly of the Br(thiazol)~9~ entities. There also exist intermolecular Br···π interactions between the \[FeBr~4~\]^-^ anions and thiazole rings in the crystal structure (Fig. 3), with Br1···*Cg*1 = 3.562 (3) and Br1^i^···*Cg*2 = 3.765 (2) Å \[*Cg*1 and *Cg*2 are the centroids of C1, C2, C3, N2, S2 ring and C4, C5, C6, N1, S1 ring. Symmetry code: (i) 1-x+y, 2-x, z\]. The hydrogen bonds and Br···π interactions link the cations and anions, which may be effective in the stabilization of the structure. Experimental {#experimental} ============ 4,4\'-bi-1,3-thiazole (0.11 g, 0.63 mmol) in CH~3~OH (20 ml) was added to a solution of FeBr~3~ (0.06 g, 0.21 mmol) in CH~3~OH (10 ml) and the resulting red solution was stirred at 313 K for 1 h. The red colored precipitated product was recrystallized from CH~3~CN/CH~3~OH (v/v 2:1). After two weeks, dark-red prismatic crystals of the title compound were isolated (yield: 0.08 g, 75.0%; m.p. 464 K). Refinement {#refinement} ========== All H atoms were positioned geometrically and refined as riding atoms, with C---H = 0.93 Å and with *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level. \[Symmetry codes: (i) 1-x+y, 2-x, z; (ii) 2-y, 1+x-y, z; (iii) 1-y, 1+x-y, z; (iv) -x+y, 1-x, z.\] ::: ![](e-67-0m311-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing diagram for the title compound. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0m311-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Intermolecular Br···π interactions (dashed lines) in the title compound. \[Symmetry code: (i) 1-x+y, 2-x, z.\] ::: ![](e-67-0m311-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e275 .table-wrap} ------------------------------------------ --------------------------------------- \[Fe(C~6~H~4~N~2~S~2~)~3~\]\[FeBr~4~\]Br *D*~x~ = 2.270 Mg m^−3^ *M~r~* = 1015.95 Mo *K*α radiation, λ = 0.71073 Å Trigonal, *R*3 Cell parameters from 1635 reflections Hall symbol: R 3 θ = 3.0--28.0° *a* = 12.0638 (7) Å µ = 8.14 mm^−1^ *c* = 17.6907 (13) Å *T* = 100 K *V* = 2229.7 (2) Å^3^ Prism, dark-red *Z* = 3 0.45 × 0.35 × 0.30 mm *F*(000) = 1455 ------------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e399 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2508 independent reflections Radiation source: fine-focus sealed tube 2427 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.099 φ and ω scans θ~max~ = 28.9°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Bruker, 2001) *h* = −16→16 *T*~min~ = 0.031, *T*~max~ = 0.086 *k* = −16→16 8430 measured reflections *l* = −24→23 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e516 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.036 H-atom parameters constrained *wR*(*F*^2^) = 0.085 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0485*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.01 (Δ/σ)~max~ \< 0.001 2508 reflections Δρ~max~ = 0.93 e Å^−3^ 112 parameters Δρ~min~ = −0.78 e Å^−3^ 1 restraint Absolute structure: Flack (1983), 1195 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.021 (9) ---------------------------------------------------------------- ------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e677 .table-wrap} ----- -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.53314 (4) 0.70585 (5) 0.46767 (3) 0.02946 (13) Br2 0.3333 0.6667 0.64196 (3) 0.01401 (14) Br3 1.6667 1.3333 0.53208 (4) 0.01483 (14) Fe1 1.0000 1.0000 0.48640 (5) 0.00941 (17) Fe2 0.3333 0.6667 0.50986 (6) 0.01351 (18) S1 1.25908 (10) 1.31480 (10) 0.64504 (6) 0.0182 (2) S2 1.33303 (9) 1.07879 (10) 0.33584 (6) 0.01552 (19) N1 1.1247 (3) 1.1426 (3) 0.54875 (19) 0.0120 (6) N2 1.1543 (3) 1.0443 (3) 0.42603 (19) 0.0121 (6) C1 1.1756 (4) 1.0038 (4) 0.3613 (2) 0.0141 (7) H1A 1.1107 0.9401 0.3323 0.017\* C2 1.3758 (4) 1.1697 (4) 0.4169 (2) 0.0161 (7) H2A 1.4589 1.2296 0.4310 0.019\* C3 1.2677 (4) 1.1394 (4) 0.4572 (2) 0.0132 (7) C4 1.2524 (4) 1.1950 (4) 0.5268 (2) 0.0127 (7) C5 1.3381 (4) 1.2906 (4) 0.5716 (3) 0.0185 (8) H5A 1.4262 1.3361 0.5639 0.022\* C6 1.1159 (4) 1.1969 (4) 0.6109 (2) 0.0154 (7) H6A 1.0383 1.1732 0.6345 0.019\* ----- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e942 .table-wrap} ----- -------------- -------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0213 (2) 0.0518 (3) 0.0176 (2) 0.0201 (2) 0.00229 (16) −0.0064 (2) Br2 0.01593 (18) 0.01593 (18) 0.0102 (3) 0.00796 (9) 0.000 0.000 Br3 0.01604 (19) 0.01604 (19) 0.0124 (3) 0.00802 (9) 0.000 0.000 Fe1 0.0096 (2) 0.0096 (2) 0.0090 (4) 0.00479 (11) 0.000 0.000 Fe2 0.0153 (3) 0.0153 (3) 0.0099 (4) 0.00764 (13) 0.000 0.000 S1 0.0184 (4) 0.0170 (4) 0.0170 (5) 0.0072 (4) −0.0042 (4) −0.0073 (4) S2 0.0162 (4) 0.0198 (4) 0.0128 (4) 0.0107 (3) 0.0037 (3) 0.0013 (3) N1 0.0113 (13) 0.0118 (14) 0.0122 (14) 0.0052 (12) 0.0016 (11) 0.0003 (11) N2 0.0143 (14) 0.0143 (14) 0.0102 (13) 0.0090 (12) 0.0021 (12) 0.0016 (12) C1 0.0135 (16) 0.0138 (16) 0.0157 (17) 0.0074 (14) 0.0000 (13) −0.0008 (13) C2 0.0161 (16) 0.0175 (17) 0.0139 (18) 0.0078 (14) 0.0027 (14) 0.0035 (14) C3 0.0173 (17) 0.0131 (15) 0.0134 (16) 0.0106 (14) 0.0009 (13) 0.0036 (13) C4 0.0156 (16) 0.0101 (15) 0.0126 (16) 0.0065 (13) 0.0010 (13) 0.0001 (12) C5 0.0168 (17) 0.0198 (19) 0.0192 (19) 0.0092 (15) −0.0020 (14) −0.0002 (15) C6 0.0135 (16) 0.0148 (17) 0.0151 (17) 0.0048 (13) −0.0024 (14) −0.0020 (13) ----- -------------- -------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1228 .table-wrap} -------------------------- ------------- -------------------- ------------ Fe1---N1 1.962 (3) N2---C1 1.320 (5) Fe1---N2 1.974 (3) N2---C3 1.385 (5) Fe2---Br1 2.3348 (5) C1---H1A 0.9300 Fe2---Br2 2.3370 (12) C2---C3 1.366 (6) S1---C6 1.706 (4) C2---H2A 0.9300 S1---C5 1.721 (4) C3---C4 1.458 (5) S2---C1 1.706 (4) C4---C5 1.355 (6) S2---C2 1.720 (4) C5---H5A 0.9300 N1---C6 1.312 (5) C6---H6A 0.9300 N1---C4 1.396 (5) N1---Fe1---N1^i^ 91.50 (14) C6---N1---Fe1 133.8 (3) N1---Fe1---N1^ii^ 91.50 (14) C4---N1---Fe1 115.4 (3) N1^i^---Fe1---N1^ii^ 91.50 (14) C1---N2---C3 111.0 (3) N1---Fe1---N2^i^ 171.87 (13) C1---N2---Fe1 134.5 (3) N1^i^---Fe1---N2^i^ 82.00 (14) C3---N2---Fe1 114.6 (3) N1^ii^---Fe1---N2^i^ 93.53 (13) N2---C1---S2 113.8 (3) N1---Fe1---N2 82.00 (14) N2---C1---H1A 123.1 N1^i^---Fe1---N2 93.53 (13) S2---C1---H1A 123.1 N1^ii^---Fe1---N2 171.87 (13) C3---C2---S2 108.8 (3) N2^i^---Fe1---N2 93.49 (14) C3---C2---H2A 125.6 N1---Fe1---N2^ii^ 93.53 (13) S2---C2---H2A 125.6 N1^i^---Fe1---N2^ii^ 171.87 (14) C2---C3---N2 115.4 (3) N1^ii^---Fe1---N2^ii^ 82.00 (14) C2---C3---C4 129.9 (4) N2^i^---Fe1---N2^ii^ 93.49 (14) N2---C3---C4 114.7 (3) N2---Fe1---N2^ii^ 93.49 (14) C5---C4---N1 115.0 (4) Br1^iii^---Fe2---Br1^iv^ 110.29 (3) C5---C4---C3 131.9 (4) Br1^iii^---Fe2---Br1 110.29 (3) N1---C4---C3 113.0 (3) Br1^iv^---Fe2---Br1 110.29 (3) C4---C5---S1 109.5 (3) Br1^iii^---Fe2---Br2 108.64 (3) C4---C5---H5A 125.2 Br1^iv^---Fe2---Br2 108.64 (3) S1---C5---H5A 125.2 Br1---Fe2---Br2 108.64 (3) N1---C6---S1 114.3 (3) C6---S1---C5 90.4 (2) N1---C6---H6A 122.8 C1---S2---C2 91.01 (19) S1---C6---H6A 122.8 C6---N1---C4 110.7 (3) N1^i^---Fe1---N1---C6 −86.9 (3) S2---C2---C3---N2 1.7 (4) N1^ii^---Fe1---N1---C6 4.6 (4) S2---C2---C3---C4 −175.8 (3) N2---Fe1---N1---C6 179.8 (4) C1---N2---C3---C2 −1.2 (5) N2^ii^---Fe1---N1---C6 86.7 (4) Fe1---N2---C3---C2 178.8 (3) N1^i^---Fe1---N1---C4 88.3 (3) C1---N2---C3---C4 176.7 (3) N1^ii^---Fe1---N1---C4 179.8 (3) Fe1---N2---C3---C4 −3.3 (4) N2---Fe1---N1---C4 −5.1 (3) C6---N1---C4---C5 −1.7 (5) N2^ii^---Fe1---N1---C4 −98.1 (3) Fe1---N1---C4---C5 −178.0 (3) N1---Fe1---N2---C1 −175.5 (4) C6---N1---C4---C3 −179.1 (3) N1^i^---Fe1---N2---C1 93.5 (4) Fe1---N1---C4---C3 4.7 (4) N2^i^---Fe1---N2---C1 11.3 (4) C2---C3---C4---C5 −0.2 (7) N2^ii^---Fe1---N2---C1 −82.4 (3) N2---C3---C4---C5 −177.7 (4) N1---Fe1---N2---C3 4.6 (3) C2---C3---C4---N1 176.7 (4) N1^i^---Fe1---N2---C3 −86.5 (3) N2---C3---C4---N1 −0.8 (5) N2^i^---Fe1---N2---C3 −168.6 (3) N1---C4---C5---S1 1.4 (5) N2^ii^---Fe1---N2---C3 97.6 (3) C3---C4---C5---S1 178.2 (3) C3---N2---C1---S2 0.0 (4) C6---S1---C5---C4 −0.6 (3) Fe1---N2---C1---S2 −180.0 (2) C4---N1---C6---S1 1.2 (4) C2---S2---C1---N2 0.8 (3) Fe1---N1---C6---S1 176.5 (2) C1---S2---C2---C3 −1.4 (3) C5---S1---C6---N1 −0.3 (3) -------------------------- ------------- -------------------- ------------ ::: Symmetry codes: (i) −*x*+*y*+1, −*x*+2, *z*; (ii) −*y*+2, *x*−*y*+1, *z*; (iii) −*y*+1, *x*−*y*+1, *z*; (iv) −*x*+*y*, −*x*+1, *z*. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1938 .table-wrap} ---------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C2---H2A···Br3 0.93 2.81 3.665 (5) 153 C5---H5A···Br3 0.93 2.97 3.798 (5) 149 ---------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: ----------- ------------- Fe1---N1 1.962 (3) Fe1---N2 1.974 (3) Fe2---Br1 2.3348 (5) Fe2---Br2 2.3370 (12) ----------- ------------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- C2---H2*A*⋯Br3 0.93 2.81 3.665 (5) 153 C5---H5*A*⋯Br3 0.93 2.97 3.798 (5) 149 :::

PubMed Central

2024-06-05T04:04:18.726397

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052137/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m311-m312", "authors": [ { "first": "Anita", "last": "Abedi" }, { "first": "Vahid", "last": "Amani" }, { "first": "Nasser", "last": "Safari" } ] }

PMC3052138

Related literature {#sec1} ================== For the appications of phthalimides and *N*-substituted phthalimides, see: Lima *et al.* (2002[@bb3]). For a related structure, see: Liang (2008[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~4~H~14~N~2~ ^2+^·2C~9~H~7~O~4~ ^−^·2H~2~O*M* *~r~* = 484.50Monoclinic,*a* = 14.0344 (15) Å*b* = 8.6746 (9) Å*c* = 10.2304 (11) Åβ = 95.620 (1)°*V* = 1239.5 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 0.10 mm^−1^*T* = 298 K0.50 × 0.48 × 0.47 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 1997[@bb1]) *T* ~min~ = 0.950, *T* ~max~ = 0.9536001 measured reflections2178 independent reflections1601 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.037 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.043*wR*(*F* ^2^) = 0.123*S* = 1.072178 reflections157 parametersH-atom parameters constrainedΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e503} Data collection: *SMART* (Bruker, 1997[@bb1]); cell refinement: *SAINT* (Bruker, 1997[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb4]) and *PLATON* (Spek, 2009[@bb5]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003618/lh5202sup1.cif](http://dx.doi.org/10.1107/S1600536811003618/lh5202sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003618/lh5202Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003618/lh5202Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5202&file=lh5202sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5202sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5202&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5202](http://scripts.iucr.org/cgi-bin/sendsup?lh5202)). The author thanks the Shandong Provincial Natural Science Foundation, China (ZR2009BL027). Comment ======= Phthalimides and N-substituted phthalimides are animportant class of compounds because of their interesting biological activities (Lima *et al.*, 2002). 2-(Methoxycarbonyl)benzoic acid is an intermediate in the preparation of N-substituted phthalimides. In this paper, the structure of the title compound is reported. The asymmetric unit of the title compound (I) contains one half a butane-1,4-diaminium cation, a 2-(methoxycarbonyl)benzoate anion and a solvent water molecule (Fig. 1). The bond lengths and angles agree with those in ethane-1,2-diaminium 2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate methanol solvate (Liang, 2008). In the crystal, intermolecular N---H···O and O---H···O hydrogen bonds link the components of the structure into two-dimensional layers parallel to (100) (Fig. 2 and Table 1). Addtional stabilization within these layers is provided by weak intermolecular C---H···O hydrogen bonds. Experimental {#experimental} ============ A mixture of phthalic anhydride (1.52 g, 0.01 mol) and methanol (15 ml) was refluxed for 0.5 h. 1,4-Butanediamine (0.44 g, 0.005 mol) was added to the above solution and mixed for 10 min at room temperature. The solution was kept at room temperature for 5 d. Natural evaporation gave colourless single crystals of the title compound, suitable for X-ray analysis. Refinement {#refinement} ========== H atoms were initially located in difference maps and then refined in a riding-model approximation with C---H = 0.93--0.97 Å, N---H = 0.89 Å, O---H = 0.82Å and *U*~iso~(H) = 1.2*U*~eq~(C, O) or 1.5*U*~eq~(N, methyl C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of (I), drawn with 30% probability ellipsoids. ::: ![](e-67-0o587-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure of the title compound with hydrogen bonds shown as dashed lines. Only H atoms involved in hydrogen bonds are shown. ::: ![](e-67-0o587-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e113 .table-wrap} ------------------------------------------- --------------------------------------- C~4~H~14~N~2~^2+^·2C~9~H~7~O~4~^−^·2H~2~O *F*(000) = 516 *M~r~* = 484.50 *D*~x~ = 1.298 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 2198 reflections *a* = 14.0344 (15) Å θ = 2.8--27.5° *b* = 8.6746 (9) Å µ = 0.10 mm^−1^ *c* = 10.2304 (11) Å *T* = 298 K β = 95.620 (1)° Block, colorless *V* = 1239.5 (2) Å^3^ 0.50 × 0.48 × 0.47 mm *Z* = 2 ------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e259 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART CCD diffractometer 2178 independent reflections Radiation source: fine-focus sealed tube 1601 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.037 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.8° Absorption correction: multi-scan (*SADABS*; Bruker, 1997) *h* = −12→16 *T*~min~ = 0.950, *T*~max~ = 0.953 *k* = −10→10 6001 measured reflections *l* = −10→12 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e376 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.043 H-atom parameters constrained *wR*(*F*^2^) = 0.123 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0556*P*)^2^ + 0.314*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.07 (Δ/σ)~max~ \< 0.001 2178 reflections Δρ~max~ = 0.17 e Å^−3^ 157 parameters Δρ~min~ = −0.20 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.118 (8) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e557 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e656 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ N1 0.44862 (11) 0.25834 (17) 0.79462 (15) 0.0369 (4) H1A 0.5061 0.2597 0.7647 0.055\* H1B 0.4252 0.3537 0.7944 0.055\* H1C 0.4094 0.1986 0.7432 0.055\* O1 0.13265 (10) 0.39089 (19) 0.54038 (16) 0.0622 (5) O2 0.28346 (10) 0.43510 (19) 0.61583 (16) 0.0596 (5) O3 0.37929 (10) 0.54277 (15) 0.88018 (14) 0.0458 (4) O4 0.35667 (9) 0.74614 (15) 0.74950 (14) 0.0479 (4) O5 0.33244 (12) 0.04093 (17) 0.63792 (15) 0.0628 (5) H5C 0.3453 0.0256 0.5595 0.075\* H5D 0.3382 −0.0443 0.6790 0.075\* C1 0.19982 (14) 0.4525 (2) 0.62583 (19) 0.0376 (5) C2 0.32751 (13) 0.6373 (2) 0.81441 (18) 0.0342 (4) C3 0.15919 (12) 0.5400 (2) 0.73169 (18) 0.0351 (5) C4 0.22064 (13) 0.6245 (2) 0.82091 (18) 0.0344 (5) C5 0.18168 (15) 0.7007 (2) 0.9231 (2) 0.0490 (6) H5 0.2216 0.7570 0.9833 0.059\* C6 0.08535 (16) 0.6941 (3) 0.9366 (2) 0.0587 (6) H6 0.0608 0.7457 1.0056 0.070\* C7 0.02511 (16) 0.6117 (3) 0.8485 (2) 0.0565 (6) H7 −0.0401 0.6075 0.8579 0.068\* C8 0.06155 (14) 0.5354 (2) 0.7462 (2) 0.0469 (5) H8 0.0206 0.4804 0.6863 0.056\* C9 0.16701 (18) 0.2992 (4) 0.4371 (3) 0.0783 (9) H9A 0.2048 0.3625 0.3851 0.117\* H9B 0.1135 0.2580 0.3825 0.117\* H9C 0.2055 0.2161 0.4751 0.117\* C10 0.45726 (13) 0.1967 (2) 0.93045 (17) 0.0337 (4) H10A 0.3955 0.2014 0.9654 0.040\* H10B 0.5020 0.2592 0.9860 0.040\* C11 0.49175 (14) 0.0324 (2) 0.93138 (17) 0.0353 (5) H11A 0.5510 0.0274 0.8901 0.042\* H11B 0.4447 −0.0306 0.8801 0.042\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1097 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ N1 0.0428 (9) 0.0320 (8) 0.0361 (9) 0.0064 (7) 0.0048 (7) 0.0075 (7) O1 0.0412 (8) 0.0820 (12) 0.0614 (11) −0.0001 (8) −0.0048 (7) −0.0318 (9) O2 0.0391 (9) 0.0752 (11) 0.0644 (11) −0.0021 (7) 0.0052 (7) −0.0322 (9) O3 0.0441 (8) 0.0439 (8) 0.0481 (9) 0.0115 (6) −0.0026 (6) 0.0025 (7) O4 0.0462 (9) 0.0374 (8) 0.0612 (10) −0.0023 (6) 0.0106 (7) 0.0063 (7) O5 0.0936 (13) 0.0428 (8) 0.0488 (10) −0.0037 (8) −0.0094 (8) 0.0011 (7) C1 0.0365 (11) 0.0357 (10) 0.0398 (11) −0.0011 (8) 0.0001 (8) −0.0013 (8) C2 0.0391 (10) 0.0279 (9) 0.0351 (10) 0.0004 (8) 0.0008 (8) −0.0071 (8) C3 0.0352 (10) 0.0325 (10) 0.0374 (11) 0.0026 (8) 0.0023 (8) 0.0043 (8) C4 0.0382 (10) 0.0275 (9) 0.0372 (11) 0.0038 (8) 0.0024 (8) 0.0037 (8) C5 0.0479 (13) 0.0505 (12) 0.0486 (13) 0.0046 (10) 0.0041 (10) −0.0111 (10) C6 0.0530 (14) 0.0701 (15) 0.0548 (15) 0.0104 (12) 0.0146 (11) −0.0149 (12) C7 0.0386 (12) 0.0694 (15) 0.0634 (15) 0.0079 (11) 0.0144 (10) −0.0010 (13) C8 0.0378 (11) 0.0493 (12) 0.0530 (14) −0.0004 (9) 0.0014 (9) 0.0017 (10) C9 0.0604 (16) 0.101 (2) 0.0702 (19) 0.0054 (14) −0.0111 (13) −0.0481 (16) C10 0.0425 (11) 0.0302 (9) 0.0286 (10) 0.0033 (8) 0.0044 (8) 0.0020 (8) C11 0.0457 (11) 0.0307 (9) 0.0295 (10) 0.0041 (8) 0.0035 (8) 0.0007 (8) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1434 .table-wrap} ------------------- -------------- ------------------------- ------------- N1---C10 1.483 (2) C5---C6 1.373 (3) N1---H1A 0.8900 C5---H5 0.9300 N1---H1B 0.8900 C6---C7 1.374 (3) N1---H1C 0.8900 C6---H6 0.9300 O1---C1 1.333 (2) C7---C8 1.378 (3) O1---C9 1.443 (3) C7---H7 0.9300 O2---C1 1.198 (2) C8---H8 0.9300 O3---C2 1.248 (2) C9---H9A 0.9600 O4---C2 1.246 (2) C9---H9B 0.9600 O5---H5C 0.8500 C9---H9C 0.9600 O5---H5D 0.8500 C10---C11 1.505 (2) C1---C3 1.481 (3) C10---H10A 0.9700 C2---C4 1.512 (3) C10---H10B 0.9700 C3---C8 1.393 (3) C11---C11^i^ 1.509 (3) C3---C4 1.400 (3) C11---H11A 0.9700 C4---C5 1.393 (3) C11---H11B 0.9700 C10---N1---H1A 109.5 C7---C6---H6 119.9 C10---N1---H1B 109.5 C6---C7---C8 119.8 (2) H1A---N1---H1B 109.5 C6---C7---H7 120.1 C10---N1---H1C 109.5 C8---C7---H7 120.1 H1A---N1---H1C 109.5 C7---C8---C3 120.6 (2) H1B---N1---H1C 109.5 C7---C8---H8 119.7 C1---O1---C9 115.83 (17) C3---C8---H8 119.7 H5C---O5---H5D 108.2 O1---C9---H9A 109.5 O2---C1---O1 121.97 (18) O1---C9---H9B 109.5 O2---C1---C3 125.28 (17) H9A---C9---H9B 109.5 O1---C1---C3 112.75 (16) O1---C9---H9C 109.5 O4---C2---O3 125.51 (18) H9A---C9---H9C 109.5 O4---C2---C4 117.28 (16) H9B---C9---H9C 109.5 O3---C2---C4 117.10 (16) N1---C10---C11 110.12 (14) C8---C3---C4 119.66 (18) N1---C10---H10A 109.6 C8---C3---C1 121.09 (17) C11---C10---H10A 109.6 C4---C3---C1 119.22 (16) N1---C10---H10B 109.6 C5---C4---C3 118.40 (17) C11---C10---H10B 109.6 C5---C4---C2 117.51 (17) H10A---C10---H10B 108.2 C3---C4---C2 124.08 (16) C10---C11---C11^i^ 112.22 (19) C6---C5---C4 121.2 (2) C10---C11---H11A 109.2 C6---C5---H5 119.4 C11^i^---C11---H11A 109.2 C4---C5---H5 119.4 C10---C11---H11B 109.2 C5---C6---C7 120.3 (2) C11^i^---C11---H11B 109.2 C5---C6---H6 119.9 H11A---C11---H11B 107.9 C9---O1---C1---O2 1.4 (3) O3---C2---C4---C5 86.2 (2) C9---O1---C1---C3 −177.8 (2) O4---C2---C4---C3 90.4 (2) O2---C1---C3---C8 −170.6 (2) O3---C2---C4---C3 −93.2 (2) O1---C1---C3---C8 8.6 (3) C3---C4---C5---C6 −0.2 (3) O2---C1---C3---C4 7.4 (3) C2---C4---C5---C6 −179.6 (2) O1---C1---C3---C4 −173.44 (17) C4---C5---C6---C7 −0.1 (4) C8---C3---C4---C5 0.7 (3) C5---C6---C7---C8 0.0 (4) C1---C3---C4---C5 −177.31 (17) C6---C7---C8---C3 0.5 (3) C8---C3---C4---C2 −179.96 (17) C4---C3---C8---C7 −0.8 (3) C1---C3---C4---C2 2.1 (3) C1---C3---C8---C7 177.12 (19) O4---C2---C4---C5 −90.2 (2) N1---C10---C11---C11^i^ 176.08 (19) ------------------- -------------- ------------------------- ------------- ::: Symmetry codes: (i) −*x*+1, −*y*, −*z*+2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1979 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···O4^ii^ 0.89 1.95 2.815 (2) 164 N1---H1B···O3 0.89 2.00 2.823 (2) 154 N1---H1C···O5 0.89 1.99 2.876 (2) 172 O5---H5C···O3^iii^ 0.85 2.03 2.873 (2) 172 O5---H5D···O4^iv^ 0.85 1.96 2.808 (2) 172 C11---H11A···O2^ii^ 0.97 2.46 3.346 (2) 151 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −*x*+1, *y*−1/2, −*z*+3/2; (iii) *x*, −*y*+1/2, *z*−1/2; (iv) *x*, *y*−1, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- --------- ------- ----------- ------------- N1---H1*A*⋯O4^i^ 0.89 1.95 2.815 (2) 164 N1---H1*B*⋯O3 0.89 2.00 2.823 (2) 154 N1---H1*C*⋯O5 0.89 1.99 2.876 (2) 172 O5---H5*C*⋯O3^ii^ 0.85 2.03 2.873 (2) 172 O5---H5*D*⋯O4^iii^ 0.85 1.96 2.808 (2) 172 C11---H11*A*⋯O2^i^ 0.97 2.46 3.346 (2) 151 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.731207

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052138/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o587", "authors": [ { "first": "Jian", "last": "Li" } ] }

PMC3052139

Related literature {#sec1} ================== For the related [l]{.smallcaps}-serine methyl ester hydrochloride, see: Schouten & Lutz (2009[@bb6]). For the theory of twin formation, see: Cahn (1954[@bb1]). Twin integration is based on Schreurs *et al.* (2010[@bb8]) and the twin refinement on Herbst-Irmer & Sheldrick (2002[@bb3]). The methods of Flack (1983[@bb2]) and Hooft *et al.* (2008[@bb4]) were used for the absolute structure determination. Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~4~H~10~NO~2~ ^+^·Cl^−^·H~2~O*M* *~r~* = 157.60Triclinic,*a* = 4.9461 (4) Å*b* = 6.0134 (4) Å*c* = 6.6853 (5) Åα = 101.833 (4)°β = 93.533 (3)°γ = 92.112 (4)°*V* = 194.00 (2) Å^3^*Z* = 1Mo *K*α radiationμ = 0.44 mm^−1^*T* = 110 K0.39 × 0.29 × 0.12 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (*TWINABS-2008/4*; Sheldrick, 2008*a* [@bb9]) *T* ~min~ = 0.69, *T* ~max~ = 0.7511388 measured reflections3213 independent reflections3180 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.019 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.015*wR*(*F* ^2^) = 0.043*S* = 1.053213 reflections133 parameters3 restraintsAll H-atom parameters refinedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.13 e Å^−3^ {#d5e520} Data collection: *COLLECT* (Nonius, 1999[@bb5]); cell refinement: *PEAKREF* (Schreurs, 2008[@bb7]); data reduction: *Eval15* (Schreurs *et al.*, 2010[@bb8]) and *TWINABS-2008/4* (Sheldrick, 2008*a* [@bb9]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008*b* [@bb10]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008*b* [@bb10]); molecular graphics: *PLATON* (Spek, 2009[@bb11]); software used to prepare material for publication: manual editing of *SHELXL* CIF file. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100420X/ez2229sup1.cif](http://dx.doi.org/10.1107/S160053681100420X/ez2229sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100420X/ez2229Isup2.hkl](http://dx.doi.org/10.1107/S160053681100420X/ez2229Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2229&file=ez2229sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2229sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2229&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2229](http://scripts.iucr.org/cgi-bin/sendsup?ez2229)). Comment ======= In the context of our ongoing studies of absolute structure determinations of hydrochlorides of amino acid esters, we determined the structure of the title compound (I). The related L-serine methyl ester hydrochloride (Schouten & Lutz, 2009) has an extended backbone with O--C--C--N and C--O--C--C torsion angles of -175.99 (7) and 179.72 (7)°, respectively. In (I), the O--C--C--N torsion angle is 155.83 (6)° indicating a significant deviation from an extended backbone. The C--O--C--C torsion angle of 177.22 (6)° is again close to a *trans* conformation (Fig. 1). Two H atoms of the ammonium moiety are involved in hydrogen bonds with chloride anions as acceptors. This results in a one-dimensional chain in the a-direction. These two hydrogen bonds have significantly different lengths: the N1···Cl1 distance is 3.3007 (7) Å, while the N1···Cl1 (*x* - 1, *y*, *z*) distance is 3.1665 (6) Å. The third ammonium H atom is hydrogen bonded to the co-crystallized lattice water molecule, which itself donates two hydrogen bonds to chlorides. The water thus links the one-dimensional chains into a two-dimensional network, which is parallel to the *a*,*c*-plane (Fig. 2). In the *b*-direction the hydrogen bonded layers of the ammonium moieties, chloride anions and lattice water molecules are alternating with the organic part of the alanine methyl ester. The O atoms of the ester functionality are not involved in strong intermolecular interactions, but there is a weak C---H···O bond with the ester O2 as acceptor (Table 1). The crystal of (I) appeared to be twinned with a twofold rotation about *hkl*=(0,0,1) as twin operation. This twin relation was taken into account during the intensity integration with Eval15 (Schreurs *et al.*, 2010) and the refinement (Herbst-Irmer & Sheldrick, 2002). As can easily be verified in Fig. 2, the twinning operation results in reversed stacking of the two-dimensional hydrogen bonded networks. At the twinning boundaries the polar and ionic groups involved in the hydrogen bonds must approach each other in the direction of the *b* axis and the alternation of polar and apolar moieties is broken. These stacking faults might be accompanied by shifts of the layers for a better structural fit. Such dislocations often depend on the way the twin was generated (Cahn, 1954), which has not been investigated in the present study of (I). In the macroscopic shape of the crystal of (I), faces *hkl*=(0,0,1) and (0,0,1) have the smallest dimensions. For the determination of the absolute structure, reflections with inverted indices were introduced into the dataset using the TWINABS software (Sheldrick, 2008*a*). Thus there were in total four twin domains included in the refinement. The corresponding twin fractions refined to 0.86 (2) and 0.104 (4) for the non-merohedral domains, and 0.03 (2) and 0.005 (4) for the corresponding inverted domains. The latter values are very close to zero and we can consider the enantiopurity as proven, but it should be noted that the two twin fractions of the inverted domains are in the least-squares refinement highly correlated with each other (correlation -0.999). Because of this correlation we also performed a single-crystal refinement only on the non-overlapping reflections of the major twin domain. This dataset has a completeness of 82% (1447 unique reflections) and the coverage of Bijvoet pairs is 80% (712 pairs). Here, the Flack parameter (Flack, 1983) refined to a value of *x*=0.04 (3). On these data also an analysis according to Hooft *et al.* (2008) was performed. Assuming a Gaussian distribution of σ(I) the absolute structure parameter was calculated as *y*=0.044 (9). A plot of the Bijvoet differences is shown in Fig. 3. Experimental {#experimental} ============ Crystalline L-alanine methyl ester (Aldrich) was dissolved in technical ethanol. Evaporation at room temperature resulted in a viscous liquid. Crystallization was initiated by adding a seed crystal of the crystalline starting material. Refinement {#refinement} ========== The data set in HKLF-5 format (Herbst-Irmer & Sheldrick, 2002) contains non-overlapping reflections of both twin components, respectively, together with the overlapping reflections. Equivalent reflections were merged with TWINABS (Sheldrick, 2008*a*) prior to the least-squares refinement. The same software was used to introduce the inverted reflections for the absolute structure determination. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms. ::: ![](e-67-0o586-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Formation of two-dimensional sheets parallel to (010) by hydrogen bonding in (I). Hydrogen bonds are drawn as dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o586-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Bijvoet pairs in the non-overlapping reflections of the major twin component in (I). Scatter plot prepared by PLATON (Spek, 2009). 622 pairs are shown with Δobs \> 0.25σ(Δobs). 534 Reflections confirming the absolute structure are drawn in black. 88 Reflections with the wrong sign are shown in red. ::: ![](e-67-0o586-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e177 .table-wrap} ------------------------------- --------------------------------------- C~4~H~10~NO~2~^+^·Cl^−^·H~2~O *Z* = 1 *M~r~* = 157.60 *F*(000) = 84 Triclinic, *P*1 *D*~x~ = 1.349 Mg m^−3^ Hall symbol: P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 4.9461 (4) Å Cell parameters from 5169 reflections *b* = 6.0134 (4) Å θ = 3.5--27.5° *c* = 6.6853 (5) Å µ = 0.44 mm^−1^ α = 101.833 (4)° *T* = 110 K β = 93.533 (3)° Plate, colourless γ = 92.112 (4)° 0.39 × 0.29 × 0.12 mm *V* = 194.00 (2) Å^3^ ------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e319 .table-wrap} ------------------------------------------------------------------------ -------------------------------------- Nonius KappaCCD diffractometer 3213 independent reflections Radiation source: rotating anode 3180 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.019 φ and ω scans θ~max~ = 27.7°, θ~min~ = 3.1° Absorption correction: multi-scan (TWINABS-2008/4; Sheldrick, 2008*a*) *h* = −6→6 *T*~min~ = 0.69, *T*~max~ = 0.75 *k* = −7→7 11388 measured reflections *l* = −8→8 ------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e436 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.015 Hydrogen site location: difference Fourier map *wR*(*F*^2^) = 0.043 All H-atom parameters refined *S* = 1.05 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0283*P*)^2^ + 0.0041*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3213 reflections (Δ/σ)~max~ = 0.005 133 parameters Δρ~max~ = 0.20 e Å^−3^ 3 restraints Δρ~min~ = −0.13 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e593 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e692 .table-wrap} ----- --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.52552 (12) 0.30665 (9) 0.60201 (9) 0.01877 (12) O2 0.74232 (12) 0.64013 (9) 0.59202 (9) 0.01863 (12) N1 0.29086 (13) 0.79507 (11) 0.43187 (9) 0.01456 (12) H1N 0.447 (2) 0.8444 (16) 0.3859 (16) 0.018 (2)\* H2N 0.143 (2) 0.8271 (19) 0.3614 (17) 0.021 (3)\* H3N 0.284 (2) 0.8560 (18) 0.5673 (18) 0.021 (2)\* C1 0.54988 (14) 0.50654 (11) 0.54561 (10) 0.01343 (14) C2 0.30541 (15) 0.54425 (12) 0.41118 (12) 0.01473 (14) H2 0.150 (2) 0.4952 (16) 0.4556 (15) 0.016 (2)\* C3 0.3288 (2) 0.42892 (16) 0.18812 (15) 0.02366 (18) H3A 0.171 (3) 0.452 (2) 0.110 (2) 0.047 (4)\* H3B 0.494 (4) 0.489 (3) 0.146 (3) 0.060 (5)\* H3C 0.331 (2) 0.273 (2) 0.1796 (19) 0.031 (3)\* C4 0.75776 (19) 0.25176 (15) 0.72382 (14) 0.02231 (18) H4A 0.909 (3) 0.225 (2) 0.644 (2) 0.040 (3)\* H4B 0.695 (4) 0.118 (3) 0.779 (3) 0.064 (4)\* H4C 0.819 (4) 0.360 (3) 0.821 (3) 0.052 (4)\* Cl1 0.793162 (15) 0.934964 (15) 0.171315 (15) 0.01891 (5) O3 0.26844 (13) 0.86392 (12) 0.85023 (9) 0.02491 (13) H1O 0.415 (4) 0.880 (3) 0.930 (3) 0.057 (5)\* H2O 0.133 (3) 0.878 (2) 0.912 (2) 0.044 (4)\* ----- --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e981 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0167 (3) 0.0218 (3) 0.0201 (3) −0.0007 (2) −0.0021 (2) 0.0111 (2) O2 0.0107 (3) 0.0205 (3) 0.0253 (3) 0.0016 (2) −0.0013 (2) 0.0067 (2) N1 0.0123 (3) 0.0188 (3) 0.0132 (3) 0.0052 (2) 0.0008 (2) 0.0038 (2) C1 0.0107 (4) 0.0182 (3) 0.0123 (3) 0.0038 (3) 0.0042 (3) 0.0038 (3) C2 0.0098 (3) 0.0180 (3) 0.0176 (3) 0.0008 (2) 0.0007 (3) 0.0066 (3) C3 0.0296 (6) 0.0195 (3) 0.0186 (4) 0.0036 (3) −0.0074 (4) −0.0013 (3) C4 0.0195 (4) 0.0277 (4) 0.0231 (4) 0.0026 (3) −0.0034 (4) 0.0143 (3) Cl1 0.01091 (8) 0.03258 (8) 0.01630 (8) 0.00378 (5) 0.00140 (5) 0.01156 (6) O3 0.0129 (3) 0.0475 (4) 0.0132 (3) 0.0008 (3) 0.0011 (2) 0.0038 (2) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1173 .table-wrap} ------------------- ------------- ------------------- ------------ O1---C1 1.3351 (8) C2---H2 0.901 (11) O1---C4 1.4541 (10) C3---H3A 0.939 (14) O2---C1 1.2052 (9) C3---H3B 0.961 (18) N1---C2 1.4909 (9) C3---H3C 0.930 (12) N1---H1N 0.909 (11) C4---H4A 0.947 (14) N1---H2N 0.895 (12) C4---H4B 1.001 (17) N1---H3N 0.908 (12) C4---H4C 0.854 (18) C1---C2 1.5137 (10) O3---H1O 0.860 (18) C2---C3 1.5236 (12) O3---H2O 0.808 (17) C1---O1---C4 115.00 (6) C3---C2---H2 109.9 (6) C2---N1---H1N 106.5 (6) C2---C3---H3A 109.1 (9) C2---N1---H2N 110.3 (7) C2---C3---H3B 107.1 (10) H1N---N1---H2N 112.5 (10) H3A---C3---H3B 114.5 (13) C2---N1---H3N 107.0 (7) C2---C3---H3C 108.4 (8) H1N---N1---H3N 110.0 (10) H3A---C3---H3C 105.7 (11) H2N---N1---H3N 110.2 (10) H3B---C3---H3C 111.9 (12) O2---C1---O1 125.01 (7) O1---C4---H4A 110.8 (9) O2---C1---C2 123.63 (6) O1---C4---H4B 105.5 (10) O1---C1---C2 111.36 (6) H4A---C4---H4B 113.8 (13) N1---C2---C1 106.75 (6) O1---C4---H4C 114.3 (11) N1---C2---C3 110.50 (6) H4A---C4---H4C 102.3 (14) C1---C2---C3 111.57 (6) H4B---C4---H4C 110.4 (15) N1---C2---H2 106.5 (6) H1O---O3---H2O 112.9 (15) C1---C2---H2 111.5 (6) C4---O1---C1---O2 −1.75 (11) O1---C1---C2---N1 155.83 (6) C4---O1---C1---C2 177.22 (6) O2---C1---C2---C3 95.64 (9) O2---C1---C2---N1 −25.18 (9) O1---C1---C2---C3 −83.35 (8) ------------------- ------------- ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1448 .table-wrap} --------------------- ------------ ------------ ------------ --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1N···Cl1 0.909 (11) 2.418 (11) 3.3007 (7) 163.9 (9) N1---H2N···Cl1^i^ 0.895 (12) 2.275 (12) 3.1665 (6) 174.2 (10) N1---H3N···O3 0.908 (12) 1.888 (12) 2.7519 (9) 158.2 (9) O3---H1O···Cl1^ii^ 0.860 (18) 2.364 (18) 3.2220 (7) 175.1 (15) O3---H2O···Cl1^iii^ 0.808 (17) 2.470 (17) 3.2613 (7) 166.9 (14) C2---H2···O2^i^ 0.901 (11) 2.385 (10) 3.1302 (9) 140.0 (8) --------------------- ------------ ------------ ------------ --------------- ::: Symmetry codes: (i) *x*−1, *y*, *z*; (ii) *x*, *y*, *z*+1; (iii) *x*−1, *y*, *z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- ------------ ------------ ------------ ------------- N1---H1*N*⋯Cl1 0.909 (11) 2.418 (11) 3.3007 (7) 163.9 (9) N1---H2*N*⋯Cl1^i^ 0.895 (12) 2.275 (12) 3.1665 (6) 174.2 (10) N1---H3*N*⋯O3 0.908 (12) 1.888 (12) 2.7519 (9) 158.2 (9) O3---H1*O*⋯Cl1^ii^ 0.860 (18) 2.364 (18) 3.2220 (7) 175.1 (15) O3---H2*O*⋯Cl1^iii^ 0.808 (17) 2.470 (17) 3.2613 (7) 166.9 (14) C2---H2⋯O2^i^ 0.901 (11) 2.385 (10) 3.1302 (9) 140.0 (8) Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.735791

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052139/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o586", "authors": [ { "first": "Martin", "last": "Lutz" }, { "first": "Arie", "last": "Schouten" } ] }

PMC3052140

Related literature {#sec1} ================== For the crystal structure of the tetradecyl-substituted analog, see: Dardouri *et al.* (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~21~H~20~ClN~3~O~3~*M* *~r~* = 397.85Triclinic,*a* = 8.1821 (1) Å*b* = 9.0741 (1) Å*c* = 13.3792 (2) Åα = 79.748 (1)°β = 80.142 (1)°γ = 85.910 (1)°*V* = 962.19 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 0.23 mm^−1^*T* = 295 K0.40 × 0.30 × 0.20 mm ### Data collection {#sec2.1.2} Bruker X8 APEXII diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb4]) *T* ~min~ = 0.915, *T* ~max~ = 0.95619243 measured reflections4383 independent reflections4056 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.020 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.066*wR*(*F* ^2^) = 0.184*S* = 1.034383 reflections256 parametersH-atom parameters constrainedΔρ~max~ = 0.83 e Å^−3^Δρ~min~ = −0.44 e Å^−3^ {#d5e375} Data collection: *APEX2* (Bruker, 2008[@bb2]); cell refinement: *SAINT* (Bruker, 2008[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *X-SEED* (Barbour, 2001[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100657X/bt5479sup1.cif](http://dx.doi.org/10.1107/S160053681100657X/bt5479sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100657X/bt5479Isup2.hkl](http://dx.doi.org/10.1107/S160053681100657X/bt5479Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5479&file=bt5479sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5479sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5479&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5479](http://scripts.iucr.org/cgi-bin/sendsup?bt5479)). We thank Université Mohammed V-Agdal and the University of Malaya for supporting this study. Comment ======= The methylene part of 1,5-dimethyl-1,5-benzodiazepine-2,4-dione is relatively acidic, and one proton can be abstracted by using potassium *t*-butoxide; the resulting carbanion can undergo a nucleophlilic subsitution with a dibromoalkane to form 3-substituted derivatives. In a previous study, the compound was reacted with bromotetradecane to give the tetradecyl substitued derivative (Dardouri *et al.*, 2011). The title compound was obtained by using *p*-chlorobenzaldoxime to react with the ally group to furnish the title isoxazolinyl derivative (Scheme I, Fig. 1). The seven-membered ring of C~21~H~20~ClN~3~O~3~ adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methine C atom as the prow). The substituent at the 3-position occupies an equatorial position. Experimental {#experimental} ============ To a solution of 3-allyl-1,5-dimethyl-1,5-benzodiazepine-2,4-dione (0.25 g, 1 mmol) and *p*-chlorobenzaldoxime (0.2 g, 1.3 mmol) in chloroform (10 ml) was added to a 4%solution of sodium hypochlorite solution (commerical bleach) (4 ml) at 273 K. Stirring was continued for 4 h. The organic layer was dried and the solvent evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel by using a mixture of hexane and ethyl acetate (1/1) as eluent. Colorless crystals were isolated when the solvent was allowed to evaporate. Refinement {#refinement} ========== H-atoms were placed in calculated positions (C---H 0.93--0.97 Å) and were included in the refinement in the riding model approximation, with *U*(H) set to 1.2--1.5*U*~eq~(C). Omitted from the refinements were the following reflections because of being obscured by the beam stop and/or bad agreement between observed and calculated structure factors: (0 1 0), (1 1 0), (0 2 0), (2 3 0), (0 0 1), (1 1 1), (-1 1 2), (0 1 2) and (1 1 2). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of C21H20ClN3O3 at the 50% probability level; hydrogen atoms are drawn as arbitrary radius. ::: ![](e-67-0o720-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e135 .table-wrap} ----------------------- --------------------------------------- C~21~H~20~ClN~3~O~3~ *Z* = 2 *M~r~* = 397.85 *F*(000) = 416 Triclinic, *P*1 *D*~x~ = 1.373 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.1821 (1) Å Cell parameters from 9887 reflections *b* = 9.0741 (1) Å θ = 3.0--30.7° *c* = 13.3792 (2) Å µ = 0.23 mm^−1^ α = 79.748 (1)° *T* = 295 K β = 80.142 (1)° Block, colorless γ = 85.910 (1)° 0.40 × 0.30 × 0.20 mm *V* = 962.19 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e271 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker X8 APEXII diffractometer 4383 independent reflections Radiation source: fine-focus sealed tube 4056 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.020 φ and ω scans θ~max~ = 27.5°, θ~min~ = 3.0° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −10→10 *T*~min~ = 0.915, *T*~max~ = 0.956 *k* = −11→11 19243 measured reflections *l* = −17→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.066 H-atom parameters constrained *wR*(*F*^2^) = 0.184 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.1062*P*)^2^ + 0.889*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.03 (Δ/σ)~max~ = 0.001 4383 reflections Δρ~max~ = 0.83 e Å^−3^ 256 parameters Δρ~min~ = −0.44 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.046 (8) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e571 .table-wrap} ------ ------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cl1 0.00333 (8) 0.14321 (7) 1.07254 (5) 0.0471 (2) O1 0.2880 (2) 1.2329 (2) 0.66476 (13) 0.0428 (4) O2 0.6469 (2) 1.2468 (2) 0.82002 (12) 0.0430 (4) O3 0.6108 (2) 0.79540 (18) 0.76659 (12) 0.0400 (4) N1 0.5122 (2) 1.2697 (2) 0.53908 (14) 0.0337 (4) N2 0.7763 (2) 1.2907 (2) 0.65440 (13) 0.0310 (4) N3 0.5112 (2) 0.6671 (2) 0.78978 (14) 0.0353 (4) C1 0.6816 (3) 1.2379 (2) 0.50002 (15) 0.0309 (4) C2 0.7216 (3) 1.2001 (3) 0.40171 (18) 0.0452 (6) H2 0.6374 1.1910 0.3647 0.054\* C3 0.8856 (4) 1.1760 (4) 0.35894 (19) 0.0504 (7) H3 0.9109 1.1522 0.2931 0.060\* C4 1.0116 (3) 1.1870 (3) 0.4132 (2) 0.0448 (6) H4 1.1216 1.1710 0.3839 0.054\* C5 0.9744 (3) 1.2219 (3) 0.51136 (18) 0.0360 (5) H5 1.0596 1.2275 0.5483 0.043\* C6 0.8100 (3) 1.2487 (2) 0.55536 (15) 0.0284 (4) C7 0.4069 (3) 1.3563 (3) 0.46807 (19) 0.0449 (6) H7A 0.3220 1.4127 0.5059 0.067\* H7B 0.3563 1.2889 0.4359 0.067\* H7C 0.4739 1.4237 0.4163 0.067\* C8 0.4365 (3) 1.2097 (2) 0.63486 (16) 0.0313 (4) C9 0.5486 (3) 1.1145 (2) 0.70220 (15) 0.0293 (4) H9 0.6178 1.0465 0.6616 0.035\* C10 0.6618 (3) 1.2213 (2) 0.73248 (15) 0.0301 (4) C11 0.8826 (3) 1.3976 (3) 0.6799 (2) 0.0437 (6) H11A 0.8160 1.4626 0.7216 0.065\* H11B 0.9365 1.4563 0.6177 0.065\* H11C 0.9648 1.3438 0.7173 0.065\* C12 0.4489 (3) 1.0212 (2) 0.79575 (16) 0.0307 (4) H12A 0.4059 1.0846 0.8463 0.037\* H12B 0.3551 0.9814 0.7752 0.037\* C13 0.5550 (3) 0.8928 (2) 0.84372 (16) 0.0326 (4) H13 0.6499 0.9304 0.8659 0.039\* C14 0.4547 (3) 0.7892 (2) 0.93283 (15) 0.0317 (4) H14A 0.5181 0.7544 0.9881 0.038\* H14B 0.3515 0.8382 0.9599 0.038\* C15 0.4243 (3) 0.6634 (2) 0.87944 (15) 0.0301 (4) C16 0.3142 (2) 0.5391 (2) 0.92464 (15) 0.0290 (4) C17 0.2745 (3) 0.4381 (3) 0.86525 (16) 0.0352 (5) H17 0.3144 0.4520 0.7950 0.042\* C18 0.1772 (3) 0.3186 (3) 0.90967 (18) 0.0367 (5) H18 0.1508 0.2523 0.8698 0.044\* C19 0.1190 (3) 0.2982 (2) 1.01501 (17) 0.0330 (4) C20 0.1526 (3) 0.3979 (2) 1.07529 (16) 0.0310 (4) H20 0.1109 0.3840 1.1453 0.037\* C21 0.2496 (3) 0.5188 (2) 1.02965 (15) 0.0291 (4) H21 0.2718 0.5871 1.0693 0.035\* ------ ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1187 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cl1 0.0506 (4) 0.0392 (3) 0.0554 (4) −0.0106 (2) −0.0094 (3) −0.0145 (3) O1 0.0328 (8) 0.0558 (11) 0.0374 (9) 0.0037 (7) −0.0019 (6) −0.0071 (7) O2 0.0561 (10) 0.0510 (10) 0.0238 (7) −0.0044 (8) −0.0058 (7) −0.0114 (7) O3 0.0490 (9) 0.0360 (8) 0.0274 (7) 0.0054 (7) 0.0083 (6) −0.0011 (6) N1 0.0331 (9) 0.0421 (10) 0.0258 (8) −0.0033 (7) −0.0058 (7) −0.0037 (7) N2 0.0381 (9) 0.0322 (9) 0.0248 (8) −0.0041 (7) −0.0079 (7) −0.0063 (7) N3 0.0432 (10) 0.0348 (9) 0.0241 (8) 0.0085 (8) −0.0014 (7) −0.0026 (7) C1 0.0339 (10) 0.0360 (10) 0.0220 (9) −0.0061 (8) −0.0025 (7) −0.0030 (7) C2 0.0481 (13) 0.0640 (16) 0.0256 (10) −0.0096 (11) −0.0045 (9) −0.0121 (10) C3 0.0542 (15) 0.0698 (18) 0.0267 (11) −0.0104 (13) 0.0074 (10) −0.0166 (11) C4 0.0384 (12) 0.0523 (14) 0.0400 (12) −0.0074 (10) 0.0093 (10) −0.0104 (11) C5 0.0338 (11) 0.0379 (11) 0.0356 (11) −0.0038 (8) −0.0045 (8) −0.0042 (9) C6 0.0346 (10) 0.0284 (9) 0.0214 (9) −0.0045 (7) −0.0037 (7) −0.0018 (7) C7 0.0408 (12) 0.0581 (15) 0.0366 (12) −0.0014 (11) −0.0149 (10) −0.0020 (11) C8 0.0338 (10) 0.0339 (10) 0.0271 (10) −0.0031 (8) −0.0027 (8) −0.0091 (8) C9 0.0326 (10) 0.0301 (9) 0.0235 (9) −0.0002 (7) −0.0005 (7) −0.0045 (7) C10 0.0370 (10) 0.0306 (10) 0.0224 (9) 0.0026 (8) −0.0059 (7) −0.0042 (7) C11 0.0472 (13) 0.0469 (13) 0.0433 (13) −0.0099 (10) −0.0154 (10) −0.0137 (10) C12 0.0292 (9) 0.0346 (10) 0.0267 (9) −0.0003 (8) −0.0023 (7) −0.0030 (8) C13 0.0309 (10) 0.0381 (11) 0.0263 (9) 0.0005 (8) −0.0025 (7) −0.0016 (8) C14 0.0391 (11) 0.0322 (10) 0.0211 (9) −0.0001 (8) −0.0008 (8) −0.0015 (7) C15 0.0358 (10) 0.0327 (10) 0.0202 (8) 0.0085 (8) −0.0057 (7) −0.0033 (7) C16 0.0311 (10) 0.0328 (10) 0.0237 (9) 0.0069 (8) −0.0067 (7) −0.0075 (7) C17 0.0383 (11) 0.0450 (12) 0.0250 (9) 0.0090 (9) −0.0086 (8) −0.0145 (8) C18 0.0383 (11) 0.0415 (12) 0.0374 (11) 0.0085 (9) −0.0143 (9) −0.0216 (9) C19 0.0306 (10) 0.0337 (10) 0.0376 (11) 0.0033 (8) −0.0095 (8) −0.0116 (8) C20 0.0337 (10) 0.0336 (10) 0.0267 (9) 0.0002 (8) −0.0044 (8) −0.0094 (8) C21 0.0349 (10) 0.0304 (10) 0.0231 (9) 0.0029 (8) −0.0056 (7) −0.0085 (7) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1791 .table-wrap} --------------------- -------------- ----------------------- -------------- Cl1---C19 1.738 (2) C9---C12 1.523 (3) O1---C8 1.228 (3) C9---C10 1.536 (3) O2---C10 1.218 (3) C9---H9 0.9800 O3---N3 1.427 (3) C11---H11A 0.9600 O3---C13 1.470 (3) C11---H11B 0.9600 N1---C8 1.360 (3) C11---H11C 0.9600 N1---C1 1.423 (3) C12---C13 1.518 (3) N1---C7 1.477 (3) C12---H12A 0.9700 N2---C10 1.371 (3) C12---H12B 0.9700 N2---C6 1.420 (3) C13---C14 1.534 (3) N2---C11 1.467 (3) C13---H13 0.9800 N3---C15 1.282 (3) C14---C15 1.506 (3) C1---C2 1.397 (3) C14---H14A 0.9700 C1---C6 1.403 (3) C14---H14B 0.9700 C2---C3 1.384 (4) C15---C16 1.471 (3) C2---H2 0.9300 C16---C21 1.398 (3) C3---C4 1.378 (4) C16---C17 1.403 (3) C3---H3 0.9300 C17---C18 1.376 (4) C4---C5 1.383 (3) C17---H17 0.9300 C4---H4 0.9300 C18---C19 1.392 (3) C5---C6 1.396 (3) C18---H18 0.9300 C5---H5 0.9300 C19---C20 1.384 (3) C7---H7A 0.9600 C20---C21 1.388 (3) C7---H7B 0.9600 C20---H20 0.9300 C7---H7C 0.9600 C21---H21 0.9300 C8---C9 1.514 (3) N3---O3---C13 109.02 (15) N2---C11---H11B 109.5 C8---N1---C1 123.46 (18) H11A---C11---H11B 109.5 C8---N1---C7 117.58 (19) N2---C11---H11C 109.5 C1---N1---C7 118.47 (18) H11A---C11---H11C 109.5 C10---N2---C6 122.62 (17) H11B---C11---H11C 109.5 C10---N2---C11 117.51 (18) C13---C12---C9 111.22 (17) C6---N2---C11 119.31 (18) C13---C12---H12A 109.4 C15---N3---O3 109.03 (18) C9---C12---H12A 109.4 C2---C1---C6 119.0 (2) C13---C12---H12B 109.4 C2---C1---N1 118.8 (2) C9---C12---H12B 109.4 C6---C1---N1 122.17 (18) H12A---C12---H12B 108.0 C3---C2---C1 120.5 (2) O3---C13---C12 107.78 (17) C3---C2---H2 119.8 O3---C13---C14 103.57 (17) C1---C2---H2 119.8 C12---C13---C14 112.48 (17) C4---C3---C2 120.5 (2) O3---C13---H13 110.9 C4---C3---H3 119.8 C12---C13---H13 110.9 C2---C3---H3 119.8 C14---C13---H13 110.9 C3---C4---C5 119.9 (2) C15---C14---C13 100.88 (16) C3---C4---H4 120.0 C15---C14---H14A 111.6 C5---C4---H4 120.0 C13---C14---H14A 111.6 C4---C5---C6 120.5 (2) C15---C14---H14B 111.6 C4---C5---H5 119.7 C13---C14---H14B 111.6 C6---C5---H5 119.7 H14A---C14---H14B 109.4 C5---C6---C1 119.58 (19) N3---C15---C16 120.6 (2) C5---C6---N2 119.19 (19) N3---C15---C14 114.1 (2) C1---C6---N2 121.20 (18) C16---C15---C14 125.22 (17) N1---C7---H7A 109.5 C21---C16---C17 118.9 (2) N1---C7---H7B 109.5 C21---C16---C15 119.55 (19) H7A---C7---H7B 109.5 C17---C16---C15 121.59 (19) N1---C7---H7C 109.5 C18---C17---C16 120.8 (2) H7A---C7---H7C 109.5 C18---C17---H17 119.6 H7B---C7---H7C 109.5 C16---C17---H17 119.6 O1---C8---N1 122.1 (2) C17---C18---C19 119.1 (2) O1---C8---C9 122.53 (19) C17---C18---H18 120.4 N1---C8---C9 115.32 (18) C19---C18---H18 120.4 C8---C9---C12 111.58 (17) C20---C19---C18 121.4 (2) C8---C9---C10 107.09 (17) C20---C19---Cl1 119.19 (17) C12---C9---C10 112.23 (17) C18---C19---Cl1 119.38 (17) C8---C9---H9 108.6 C21---C20---C19 119.01 (19) C12---C9---H9 108.6 C21---C20---H20 120.5 C10---C9---H9 108.6 C19---C20---H20 120.5 O2---C10---N2 122.0 (2) C20---C21---C16 120.69 (19) O2---C10---C9 121.92 (19) C20---C21---H21 119.7 N2---C10---C9 116.09 (17) C16---C21---H21 119.7 N2---C11---H11A 109.5 C13---O3---N3---C15 −11.1 (2) C11---N2---C10---C9 177.93 (19) C8---N1---C1---C2 132.2 (2) C8---C9---C10---O2 109.6 (2) C7---N1---C1---C2 −39.5 (3) C12---C9---C10---O2 −13.1 (3) C8---N1---C1---C6 −50.2 (3) C8---C9---C10---N2 −68.0 (2) C7---N1---C1---C6 138.0 (2) C12---C9---C10---N2 169.27 (17) C6---C1---C2---C3 −1.0 (4) C8---C9---C12---C13 162.03 (18) N1---C1---C2---C3 176.6 (2) C10---C9---C12---C13 −77.8 (2) C1---C2---C3---C4 0.9 (4) N3---O3---C13---C12 −101.45 (18) C2---C3---C4---C5 0.2 (4) N3---O3---C13---C14 17.9 (2) C3---C4---C5---C6 −1.1 (4) C9---C12---C13---O3 −61.8 (2) C4---C5---C6---C1 1.0 (3) C9---C12---C13---C14 −175.36 (17) C4---C5---C6---N2 −177.2 (2) O3---C13---C14---C15 −17.1 (2) C2---C1---C6---C5 0.1 (3) C12---C13---C14---C15 99.0 (2) N1---C1---C6---C5 −177.46 (19) O3---N3---C15---C16 −177.74 (17) C2---C1---C6---N2 178.3 (2) O3---N3---C15---C14 −1.2 (2) N1---C1---C6---N2 0.7 (3) C13---C14---C15---N3 12.0 (2) C10---N2---C6---C5 −130.1 (2) C13---C14---C15---C16 −171.60 (18) C11---N2---C6---C5 41.1 (3) N3---C15---C16---C21 165.85 (19) C10---N2---C6---C1 51.7 (3) C14---C15---C16---C21 −10.3 (3) C11---N2---C6---C1 −137.1 (2) N3---C15---C16---C17 −13.0 (3) C1---N1---C8---O1 −176.2 (2) C14---C15---C16---C17 170.9 (2) C7---N1---C8---O1 −4.3 (3) C21---C16---C17---C18 −1.7 (3) C1---N1---C8---C9 4.7 (3) C15---C16---C17---C18 177.11 (19) C7---N1---C8---C9 176.56 (19) C16---C17---C18---C19 −0.4 (3) O1---C8---C9---C12 15.3 (3) C17---C18---C19---C20 2.0 (3) N1---C8---C9---C12 −165.63 (18) C17---C18---C19---Cl1 −177.34 (16) O1---C8---C9---C10 −107.9 (2) C18---C19---C20---C21 −1.4 (3) N1---C8---C9---C10 71.2 (2) Cl1---C19---C20---C21 177.92 (15) C6---N2---C10---O2 171.7 (2) C19---C20---C21---C16 −0.8 (3) C11---N2---C10---O2 0.3 (3) C17---C16---C21---C20 2.3 (3) C6---N2---C10---C9 −10.7 (3) C15---C16---C21---C20 −176.55 (18) --------------------- -------------- ----------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.738749

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052140/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o720", "authors": [ { "first": "Rachida", "last": "Dardouri" }, { "first": "Youssef Kandri", "last": "Rodi" }, { "first": "Sonia", "last": "Ladeira" }, { "first": "El Mokhtar", "last": "Essassi" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052141

Related literature {#sec1} ================== For similar structures, see: Adriaanse *et al.* (2009[@bb1]); Salas *et al.* (1999[@bb5]); Caballero *et al.* (2010[@bb3]). For a description of the geometry of tetrahedrally coordinated metal atoms, see: Yang *et al.* (2007[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(NCO)~2~(C~7~H~8~N~4~)~2~\]*M* *~r~* = 445.76Triclinic,*a* = 10.0023 (15) Å*b* = 10.8168 (16) Å*c* = 11.1094 (16) Åα = 116.772 (2)°β = 107.226 (2)°γ = 98.557 (2)°*V* = 967.2 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 1.31 mm^−1^*T* = 293 K0.25 × 0.14 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD system diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb6]) *T* ~min~ = 0.773, *T* ~max~ = 0.88111387 measured reflections4403 independent reflections3580 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.025 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.039*wR*(*F* ^2^) = 0.106*S* = 1.014403 reflections266 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.22 e Å^−3^ {#d5e398} Data collection: *SMART* (Bruker, 2007[@bb2]); cell refinement: *SAINT* (Bruker, 2007[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: Xtal\_GX (Hall *et al.*, 1999[@bb4]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005769/su2253sup1.cif](http://dx.doi.org/10.1107/S1600536811005769/su2253sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005769/su2253Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005769/su2253Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?su2253&file=su2253sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?su2253sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?su2253&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SU2253](http://scripts.iucr.org/cgi-bin/sendsup?su2253)). Financial support from the Junta de Andalucia (FQM-3705 and FQM-4228) and the Spanish Ministry of Education (FPU fellowship of Ana B. Caballero) is gratefully acknowledged. Comment ======= The coordination chemistry of 1,2,4-triazolo\[1,5-*a*\]pyrimidine derivatives displays great versatility, binding metal ions in several different ways, either in a monodentate (usually through the N atom in position 3) or in a bidentate fashion, bridging metal atoms and leading to dinuclear or polynuclear species with interesting metal-metal interactions (Salas *et al.*, 1999). Some zinc(II) complexes containing these derivatives together with secondary bridging ligands have been described, for example with the thiocyanate anion (Salas *et al.*, 1999; Adriaanse *et al.*, 2009). In most of these metal complexes, both ligands display monodentate binding leading to mononuclear species with either octahedral or tetrahedral coordination geometries. The title compound continues our studies on a series of triazolopyrimidine and pseudohalide-based metal complexes (Caballero *et al.*, 2010). This zinc(II) complex, together with the analogous complex with the unsubstituted triazolopyrimidine ligand (Caballero *et al.*, 2010), are the only ones that have been obtained with the cyanate anion. The title compound exhibits a distorted tetrahedral coordination geometry (τ~4~ = 0.924, Yang *et al.*, 2007) made of two dmtp ligands (dmtp = 5,7-dimethyl-1,2,4-triazolo\[1,5-*a*\]pyrimidine) interacting through their more usual coordination position, N3, and two cyanate anions bound through their N atom (Fig. 1). The Zn---N3 bond distances, 2.022 (2) and 2.043 (2) Å, are in the typical range for triazolopyrimidine ligands. In the crystal the stacking interactions between the pyrimidine ring of two triazolopyrimidine aromatic systems leads to the formation of supramolecular centrosymmetric dimers (Fig. 2); the centroid-to-centroid distance, involving ring (N4A,C3A,N8A,C7A,C6A,C5A) and that related by an inversion center \[symmetry code: 1-x, -y, -z\], is 3.5444 (18) Å. Experimental {#experimental} ============ A 10 ml volume of an aqueous solution containing 1 mmol of NaNCO (0.068 g) was slowly added to a 10 ml aqueous solution containing 0.5 mmol of Zn(NO)~3~.4H~2~O (0.131 g) and 1 mmol of dmtp ligand (0.148 g). Immediately after adding NaNCO, a yellow turbidity gradually appeared. The mixture was stirred at 353 K for 15 min. and the precipitate was then filtered off. The resulting clear yellow solution was left to stand for a week at room temperature and yellow crystals of the title compound were collected and used for X-ray diffraction studies. Refinement {#refinement} ========== The pyrimidine H atoms were positioned geometrically and treated as riding with C---H = 0.93 Å (methine) and 0.96 Å (methyl), and with *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the molecular structure of the title molecule with displacement ellipsoids drawn at the 50% probability level. H atoms are represented as spheres of arbitrary radii. ::: ![](e-67-0m345-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view along c axis of the crystal packing of the title compound, showing the formation of the dimers by π···π interactions (dashed lines) involing pyrimidine ring (N4A, C3A, N8A, C7A, C6A, C5A) and that related by an inversion center. ::: ![](e-67-0m345-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e155 .table-wrap} --------------------------------- --------------------------------------- \[Zn(NCO)~2~(C~7~H~8~N~4~)~2~\] *Z* = 2 *M~r~* = 445.76 *F*(000) = 456 Triclinic, *P*1 *D*~x~ = 1.531 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71069 Å *a* = 10.0023 (15) Å Cell parameters from 3345 reflections *b* = 10.8168 (16) Å θ = 2.2--23.4° *c* = 11.1094 (16) Å µ = 1.31 mm^−1^ α = 116.772 (2)° *T* = 293 K β = 107.226 (2)° Prismatic, colourless γ = 98.557 (2)° 0.25 × 0.14 × 0.10 mm *V* = 967.2 (2) Å^3^ --------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e295 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD system diffractometer 4403 independent reflections Radiation source: fine-focus sealed tube 3580 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.025 Detector resolution: 8.26 pixels mm^-1^ θ~max~ = 28.4°, θ~min~ = 2.2° φ and ω scans *h* = −13→12 Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *k* = −13→14 *T*~min~ = 0.773, *T*~max~ = 0.881 *l* = −14→14 11387 measured reflections --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e418 .table-wrap} ------------------------------------- ----------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: heavy-atom method Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.039 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.106 H-atom parameters constrained *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.060*P*)^2^ + 0.060*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4403 reflections (Δ/σ)~max~ = 0.001 266 parameters Δρ~max~ = 0.37 e Å^−3^ 0 restraints Δρ~min~ = −0.22 e Å^−3^ ------------------------------------- ----------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e575 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e674 .table-wrap} ------ ------------- ------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Zn 0.36171 (3) 0.27490 (3) 0.25442 (3) 0.04810 (12) N1A 0.7252 (2) 0.5596 (2) 0.2847 (2) 0.0566 (5) C2A 0.6371 (3) 0.5067 (3) 0.3287 (3) 0.0552 (6) H2A 0.6552 0.5497 0.4282 0.066\* N3A 0.5182 (2) 0.3860 (2) 0.2224 (2) 0.0477 (4) C3AA 0.5321 (2) 0.3589 (2) 0.0970 (2) 0.0429 (5) N4A 0.4440 (2) 0.2520 (2) −0.0413 (2) 0.0485 (5) C5A 0.4853 (3) 0.2523 (3) −0.1441 (3) 0.0528 (6) C51A 0.3895 (4) 0.1323 (3) −0.3011 (3) 0.0776 (9) H51A 0.4437 0.0690 −0.3384 0.093\* H52A 0.3611 0.1745 −0.3605 0.093\* H53A 0.3022 0.0766 −0.3053 0.093\* C6A 0.6140 (3) 0.3580 (3) −0.1100 (3) 0.0578 (6) H6A 0.6388 0.3529 −0.1861 0.069\* C7A 0.7020 (3) 0.4665 (3) 0.0310 (3) 0.0514 (6) C71A 0.8386 (3) 0.5868 (3) 0.0821 (4) 0.0715 (8) H71A 0.8597 0.5736 −0.0010 0.086\* H72A 0.9207 0.5851 0.1522 0.086\* H73A 0.8231 0.6795 0.1281 0.086\* N8A 0.6577 (2) 0.4640 (2) 0.1343 (2) 0.0455 (4) N1B 0.2927 (2) −0.1274 (2) −0.1076 (3) 0.0627 (6) C2B 0.3459 (3) −0.0230 (3) 0.0314 (3) 0.0560 (6) H2B 0.4302 −0.0160 0.1018 0.067\* N3B 0.2735 (2) 0.0740 (2) 0.0676 (2) 0.0463 (4) C3AB 0.1626 (2) 0.0281 (2) −0.0619 (2) 0.0436 (5) N4B 0.0575 (2) 0.0863 (2) −0.0882 (2) 0.0522 (5) C5B −0.0380 (3) 0.0186 (3) −0.2292 (3) 0.0580 (6) C51B −0.1560 (3) 0.0829 (4) −0.2625 (4) 0.0837 (10) H51B −0.1447 0.1672 −0.1727 0.100\* H52B −0.2519 0.0113 −0.3059 0.100\* H53B −0.1470 0.1118 −0.3305 0.100\* C6B −0.0299 (3) −0.1076 (3) −0.3424 (3) 0.0645 (7) H6B −0.0992 −0.1512 −0.4393 0.077\* C7B 0.0770 (3) −0.1662 (3) −0.3123 (3) 0.0598 (7) C71B 0.0991 (4) −0.2982 (3) −0.4201 (3) 0.0881 (10) H71B 0.1921 −0.2690 −0.4245 0.106\* H72B 0.0200 −0.3420 −0.5161 0.106\* H73B 0.0995 −0.3682 −0.3894 0.106\* N8B 0.1732 (2) −0.0941 (2) −0.1680 (2) 0.0484 (4) N1C 0.2232 (3) 0.3742 (3) 0.2904 (3) 0.0697 (6) C1C 0.1135 (4) 0.3882 (3) 0.2404 (4) 0.0699 (8) O1C −0.0024 (3) 0.4026 (4) 0.1929 (4) 0.1284 (11) N1D 0.4708 (3) 0.2496 (3) 0.4110 (3) 0.0750 (7) C1D 0.5648 (3) 0.2391 (3) 0.4912 (3) 0.0589 (6) O1D 0.6598 (3) 0.2288 (3) 0.5767 (3) 0.0985 (8) ------ ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1342 .table-wrap} ------ -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Zn 0.05173 (19) 0.05143 (19) 0.03623 (16) 0.01493 (13) 0.01566 (13) 0.02134 (13) N1A 0.0559 (12) 0.0492 (12) 0.0424 (11) 0.0070 (9) 0.0145 (10) 0.0137 (9) C2A 0.0582 (15) 0.0539 (14) 0.0382 (12) 0.0137 (12) 0.0182 (11) 0.0150 (11) N3A 0.0519 (11) 0.0467 (11) 0.0359 (10) 0.0134 (9) 0.0181 (9) 0.0159 (9) C3AA 0.0468 (12) 0.0404 (11) 0.0395 (11) 0.0166 (10) 0.0168 (10) 0.0195 (10) N4A 0.0568 (12) 0.0427 (10) 0.0376 (10) 0.0131 (9) 0.0154 (9) 0.0182 (9) C5A 0.0708 (16) 0.0491 (14) 0.0399 (13) 0.0256 (12) 0.0209 (12) 0.0238 (11) C51A 0.102 (2) 0.0684 (19) 0.0408 (15) 0.0189 (17) 0.0195 (15) 0.0212 (14) C6A 0.0741 (17) 0.0644 (16) 0.0534 (15) 0.0314 (14) 0.0354 (14) 0.0368 (14) C7A 0.0539 (14) 0.0562 (14) 0.0579 (15) 0.0245 (12) 0.0265 (12) 0.0362 (13) C71A 0.0649 (18) 0.0762 (19) 0.083 (2) 0.0181 (15) 0.0344 (16) 0.0484 (18) N8A 0.0488 (11) 0.0420 (10) 0.0424 (10) 0.0163 (9) 0.0177 (9) 0.0198 (9) N1B 0.0521 (12) 0.0550 (13) 0.0588 (14) 0.0194 (10) 0.0156 (11) 0.0169 (11) C2B 0.0480 (13) 0.0550 (15) 0.0550 (15) 0.0175 (11) 0.0122 (12) 0.0266 (13) N3B 0.0467 (10) 0.0454 (10) 0.0398 (10) 0.0134 (8) 0.0117 (8) 0.0213 (9) C3AB 0.0428 (12) 0.0406 (12) 0.0401 (12) 0.0076 (9) 0.0123 (9) 0.0204 (10) N4B 0.0487 (11) 0.0485 (11) 0.0544 (12) 0.0142 (9) 0.0135 (10) 0.0285 (10) C5B 0.0471 (14) 0.0557 (15) 0.0606 (16) 0.0056 (11) 0.0058 (12) 0.0359 (14) C51B 0.0582 (18) 0.083 (2) 0.090 (2) 0.0150 (16) −0.0003 (16) 0.0516 (19) C6B 0.0555 (16) 0.0666 (17) 0.0458 (14) −0.0007 (13) 0.0016 (12) 0.0281 (13) C7B 0.0543 (15) 0.0522 (14) 0.0448 (14) −0.0028 (12) 0.0137 (12) 0.0143 (12) C71B 0.081 (2) 0.074 (2) 0.0547 (18) 0.0086 (17) 0.0222 (16) 0.0010 (15) N8B 0.0459 (11) 0.0431 (10) 0.0429 (11) 0.0093 (8) 0.0131 (9) 0.0173 (9) N1C 0.0721 (16) 0.0717 (15) 0.0620 (15) 0.0335 (13) 0.0318 (13) 0.0272 (13) C1C 0.077 (2) 0.0734 (19) 0.073 (2) 0.0326 (17) 0.0411 (18) 0.0403 (17) O1C 0.100 (2) 0.172 (3) 0.157 (3) 0.085 (2) 0.059 (2) 0.103 (3) N1D 0.0783 (17) 0.0876 (18) 0.0526 (14) 0.0202 (14) 0.0111 (13) 0.0437 (14) C1D 0.0783 (19) 0.0609 (16) 0.0416 (13) 0.0249 (14) 0.0291 (14) 0.0266 (12) O1D 0.115 (2) 0.136 (2) 0.0756 (15) 0.0763 (18) 0.0359 (14) 0.0712 (16) ------ -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1830 .table-wrap} -------------------- ------------- -------------------- ------------- Zn---N1C 1.902 (2) N1B---C2B 1.306 (3) Zn---N1D 1.919 (2) N1B---N8B 1.370 (3) Zn---N3B 2.0223 (19) C2B---N3B 1.344 (3) Zn---N3A 2.0430 (19) C2B---H2B 0.9300 N1A---C2A 1.304 (3) N3B---C3AB 1.339 (3) N1A---N8A 1.372 (3) C3AB---N4B 1.329 (3) C2A---N3A 1.353 (3) C3AB---N8B 1.365 (3) C2A---H2A 0.9300 N4B---C5B 1.332 (3) N3A---C3AA 1.344 (3) C5B---C6B 1.414 (4) C3AA---N4A 1.330 (3) C5B---C51B 1.494 (4) C3AA---N8A 1.373 (3) C51B---H51B 0.9600 N4A---C5A 1.326 (3) C51B---H52B 0.9600 C5A---C6A 1.411 (4) C51B---H53B 0.9601 C5A---C51A 1.498 (4) C6B---C7B 1.356 (4) C51A---H51A 0.9603 C6B---H6B 0.9300 C51A---H52A 0.9604 C7B---N8B 1.357 (3) C51A---H53A 0.9604 C7B---C71B 1.494 (4) C6A---C7A 1.351 (4) C71B---H71B 0.9602 C6A---H6A 0.9300 C71B---H72B 0.9602 C7A---N8A 1.357 (3) C71B---H73B 0.9602 C7A---C71A 1.493 (4) N1C---C1C 1.140 (4) C71A---H71A 0.9601 C1C---O1C 1.188 (4) C71A---H72A 0.9601 N1D---C1D 1.148 (3) C71A---H73A 0.9601 C1D---O1D 1.188 (3) N1C---Zn---N1D 115.09 (11) N1A---N8A---C3AA 110.40 (18) N1C---Zn---N3B 114.59 (9) C2B---N1B---N8B 101.30 (19) N1D---Zn---N3B 106.30 (9) N1B---C2B---N3B 116.8 (2) N1C---Zn---N3A 111.07 (9) N1B---C2B---H2B 121.5 N1D---Zn---N3A 105.50 (10) N3B---C2B---H2B 121.6 N3B---Zn---N3A 103.25 (8) C3AB---N3B---C2B 103.40 (19) C2A---N1A---N8A 101.70 (19) C3AB---N3B---Zn 128.57 (15) N1A---C2A---N3A 116.7 (2) C2B---N3B---Zn 124.47 (16) N1A---C2A---H2A 121.6 N4B---C3AB---N3B 128.1 (2) N3A---C2A---H2A 121.6 N4B---C3AB---N8B 124.0 (2) C3AA---N3A---C2A 103.34 (19) N3B---C3AB---N8B 107.9 (2) C3AA---N3A---Zn 130.18 (16) C3AB---N4B---C5B 115.2 (2) C2A---N3A---Zn 126.47 (16) N4B---C5B---C6B 122.5 (2) N4A---C3AA---N3A 128.6 (2) N4B---C5B---C51B 116.4 (3) N4A---C3AA---N8A 123.6 (2) C6B---C5B---C51B 121.1 (3) N3A---C3AA---N8A 107.82 (19) C5B---C51B---H51B 109.6 C5A---N4A---C3AA 115.4 (2) C5B---C51B---H52B 109.7 N4A---C5A---C6A 122.6 (2) H51B---C51B---H52B 109.5 N4A---C5A---C51A 116.8 (2) C5B---C51B---H53B 109.2 C6A---C5A---C51A 120.5 (2) H51B---C51B---H53B 109.5 C5A---C51A---H51A 109.6 H52B---C51B---H53B 109.5 C5A---C51A---H52A 109.5 C7B---C6B---C5B 121.2 (2) H51A---C51A---H52A 109.4 C7B---C6B---H6B 119.4 C5A---C51A---H53A 109.5 C5B---C6B---H6B 119.4 H51A---C51A---H53A 109.4 C6B---C7B---N8B 114.9 (2) H52A---C51A---H53A 109.4 C6B---C7B---C71B 127.0 (3) C7A---C6A---C5A 121.3 (2) N8B---C7B---C71B 118.1 (3) C7A---C6A---H6A 119.3 C7B---C71B---H71B 109.2 C5A---C6A---H6A 119.3 C7B---C71B---H72B 109.3 C6A---C7A---N8A 115.0 (2) H71B---C71B---H72B 109.5 C6A---C7A---C71A 126.8 (2) C7B---C71B---H73B 109.9 N8A---C7A---C71A 118.1 (2) H71B---C71B---H73B 109.5 C7A---C71A---H71A 109.7 H72B---C71B---H73B 109.4 C7A---C71A---H72A 109.5 C7B---N8B---C3AB 122.2 (2) H71A---C71A---H72A 109.5 C7B---N8B---N1B 127.2 (2) C7A---C71A---H73A 109.3 C3AB---N8B---N1B 110.57 (19) H71A---C71A---H73A 109.5 C1C---N1C---Zn 146.6 (2) H72A---C71A---H73A 109.5 N1C---C1C---O1C 177.2 (4) C7A---N8A---N1A 127.6 (2) C1D---N1D---Zn 161.5 (3) C7A---N8A---C3AA 122.0 (2) N1D---C1D---O1D 178.1 (3) -------------------- ------------- -------------------- ------------- :::

PubMed Central

2024-06-05T04:04:18.744564

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052141/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m345", "authors": [ { "first": "Ana B.", "last": "Caballero" }, { "first": "Miguel", "last": "Quirós" }, { "first": "Antonio", "last": "Rodríguez-Diéguez" }, { "first": "Juan M.", "last": "Salas" } ] }

PMC3052142

Related literature {#sec1} ================== For structures and properties of luminescent lanthanide coordination compounds, see: Kustaryono *et al.* (2010[@bb7]); He *et al.* (2010[@bb6]); Li *et al.* (2008[@bb8]); Luo *et al.* (2008[@bb9]). For the use of multi-carboxylate and heterocyclic acids in coordination chemistry, see: Li *et al.* (2008[@bb8]); Luo *et al.* (2008[@bb9]). For the dicarboxylate ligand 4-oxido-pyridine-2,6-dicarboxylate, see: Gao *et al.* (2008[@bb5]). For the isotypic structures of the Dy and Eu analogues, see: Gao *et al.* (2006[@bb4]) and Lv *et al.* (2010[@bb10]), respectively. For bond lengths and angles in other complexes with eight-coordinate Tb^III^, see: Chen *et al.* (2008[@bb3]); Ramya *et al.* (2010[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]·H~2~O*M* *~r~* = 411.08Monoclinic,*a* = 9.953 (2) Å*b* = 7.5454 (16) Å*c* = 15.461 (3) Åβ = 105.126 (2)°*V* = 1120.9 (4) Å^3^*Z* = 4Mo *K*α radiationμ = 6.35 mm^−1^*T* = 293 K0.30 × 0.25 × 0.22 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2004[@bb2]) *T* ~min~ = 0.162, *T* ~max~ = 0.2477828 measured reflections2080 independent reflections1929 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.032 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.019*wR*(*F* ^2^) = 0.051*S* = 1.102080 reflections196 parameters12 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 1.34 e Å^−3^Δρ~min~ = −0.60 e Å^−3^ {#d5e721} Data collection: *APEX2* (Bruker, 2004[@bb2]); cell refinement: *SAINT* (Bruker, 2004[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb12]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb12]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb12]) and *DIAMOND* (Brandenburg & Putz, 2005[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb13]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005447/wm2449sup1.cif](http://dx.doi.org/10.1107/S1600536811005447/wm2449sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005447/wm2449Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005447/wm2449Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?wm2449&file=wm2449sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?wm2449sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?wm2449&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [WM2449](http://scripts.iucr.org/cgi-bin/sendsup?wm2449)). Comment ======= The design and synthesis of luminescent lanthanide coordination polymers have achieved great progress during the last years owing to their potential applications in biomedical imaging, as luminescent sensors or as fluorescent probes (Kustaryono *et al.*, 2010; He *et al.*, 2010). Eu and Tb are the most useful lanthanides due to their good fluorescence properties (Li *et al.*, 2008; Luo *et al.*, 2008). Many multi-carboxylate or heterocylic carboxylic acids are used for designing such materials (Li *et al.*, 2008; Luo *et al.*, 2008). For lanthanide coordination polymers, 4-hydroxy-pyridine-2,6-dicarboxylic acid is an excellent bridging pyridine dicarboxylate ligand (Lv *et al.*, 2010; Gao *et al.*, 2008), which can provide at most one nitrogen atom and five O coordination sites. In order to extend the investigation in this field, we synthesized the lanthanide coordination polymer {\[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]^.^H~2~O}, and report its structure here. The title compound is isotypic with its Dy (Gao *et al.*, 2006) and Eu (Lv *et al.*, 2010) analogues. As shown in Fig.1, the asymmetric unit contains one Tb(III) ion, one 4-oxidopyridine-2,6-dicarboxylate anion, three coordinated water molecules, and one water molecule of crystallisation. The Tb atom is eight-coordinated by seven oxygen atoms from three anions and three coordinated water molecules and by one nitrogen atom from one tridentate anion (the other two anions are monodentate), forming a distorted bicapped trigonal-prismatic coordination environment. Important bond distances and angles are presented in Table 1. The Tb---O bond lengths \[2.3035 (19) to 2.424 (2) Å\] are shorter than the Tb---N bond length \[2.471 (2) Å\], which is in agreement with the bond lengths observed in other Tb(III) complexes (Chen *et al.*, 2008; Ramya *et al.*, 2010). The anion adopts a *µ*~3~-pentadentate coordination mode, as shown in Fig. 1. The anions bridge adjacent Tb^III^ ions to form infinite double chains (Fig. 2). Adjacent chains are further connected by the coordination of the anions and Tb(III) ions into a two-dimensional sheet parallel to (101) (Fig. 3), which are further extended into a three-dimensional framework through O---H···O hydrogen-bonding interactions including both coordinated and uncoordinated water molecules (Table 2). Experimental {#experimental} ============ To a solution of terbium(III) nitrate hexahydrate (0.136 g, 0.3 mmol) in water (5 ml) was added an aqueous solution (5 ml) of the ligand (0.060 g, 0.3 mmol) and a drop of triethylamine. The reactants were sealed in a 25-ml Teflon-lined stainless-steel Parr bomb. The bomb was heated at 433 K for 3 days. The cool solution contained single crystals in *ca* 60% yield. Anal. Calcd for C~7~H~10~TbNO~9~: C, 20.45; H, 2.45; N, 3.41. Found: C, 20.16; H, 2.17; N, 3.74. Refinement {#refinement} ========== The coordinated water H atoms were located in a different Fourier map and refined with distance constraints of O--H = 0.83 (3) Å. The free water H atoms were placed at calculated positions and refined with a riding model, considering the position of oxygen atoms and the quantity of H atoms. The carbon-bound H atoms were placed in geometrically idealized positions, with C---H = 0.93 Å and constrained to ride on their respective parent atoms, with *U*iso(H) = 1.2 *U*eq(C). The two highest remaining electron denstity peaks greater than one electron per Å^3^ are located at (0.4907 0.8249 0.2004) and (0.5006 0.8231 0.3054), repectively. The corresponding distances to the nearest atom (heavy atom Tb1) are *ca* 0.80 Å. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Drawing of the asymmetric unit of the title compound, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. ::: ![](e-67-0m357-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### View along the b axis of the title compound, showing the double chain. ::: ![](e-67-0m357-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### View approximately along the a axis, showing the sheet structure of {\[Tb(C7H2NO5)(H2O)3\].H2O}. ::: ![](e-67-0m357-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e228 .table-wrap} --------------------------------------- --------------------------------------- \[Tb(C~7~H~2~NO~5~)(H~2~O)~3~\]·H~2~O *F*(000) = 784 *M~r~* = 411.08 *D*~x~ = 2.436 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 5700 reflections *a* = 9.953 (2) Å θ = 2.2--28.3° *b* = 7.5454 (16) Å µ = 6.35 mm^−1^ *c* = 15.461 (3) Å *T* = 293 K β = 105.126 (2)° Block, colorless *V* = 1120.9 (4) Å^3^ 0.30 × 0.25 × 0.22 mm *Z* = 4 --------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e366 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD diffractometer 2080 independent reflections Radiation source: fine-focus sealed tube 1929 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.032 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.2° Absorption correction: multi-scan (*SADABS*; Bruker, 2004) *h* = −12→11 *T*~min~ = 0.162, *T*~max~ = 0.247 *k* = −9→8 7828 measured reflections *l* = −18→18 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e483 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.019 H atoms treated by a mixture of independent and constrained refinement *wR*(*F*^2^) = 0.051 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0227*P*)^2^ + 0.941*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.10 (Δ/σ)~max~ = 0.001 2080 reflections Δρ~max~ = 1.34 e Å^−3^ 196 parameters Δρ~min~ = −0.60 e Å^−3^ 12 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.0244 (6) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e664 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e763 .table-wrap} ----- --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Tb1 0.499147 (11) 0.823001 (18) 0.253250 (7) 0.01168 (10) C1 0.5913 (3) 0.8297 (4) 0.06235 (18) 0.0145 (6) C2 0.4542 (3) 0.7331 (4) 0.03360 (17) 0.0137 (6) C3 0.3928 (3) 0.6833 (4) −0.05345 (18) 0.0157 (6) H3 0.4367 0.7069 −0.0984 0.019\* C4 0.2628 (3) 0.5961 (4) −0.07393 (17) 0.0150 (6) C5 0.2059 (3) 0.5615 (4) −0.00148 (17) 0.0166 (6) H5 0.1218 0.5012 −0.0109 0.020\* C6 0.2739 (3) 0.6163 (4) 0.08284 (17) 0.0149 (6) C7 0.2160 (3) 0.5940 (4) 0.16200 (17) 0.0176 (6) H1W 0.685 (3) 0.519 (5) 0.3081 (14) 0.033 (10)\* H2W 0.678 (4) 0.555 (5) 0.2179 (17) 0.049 (12)\* H3W 0.507 (4) 0.547 (2) 0.394 (2) 0.049 (13)\* H4W 0.477 (4) 0.706 (4) 0.433 (2) 0.039 (12)\* H5W 0.378 (3) 1.090 (5) 0.1149 (12) 0.032 (10)\* H6W 0.339 (4) 1.121 (5) 0.196 (2) 0.051 (13)\* H7W 0.348 (2) 0.664 (5) 0.544 (3) 0.051 (14)\* H8W 0.457 (5) 0.756 (7) 0.608 (3) 0.11 (2)\* N1 0.3970 (3) 0.7017 (3) 0.10190 (15) 0.0144 (5) O1 0.6315 (2) 0.8714 (3) 0.14414 (12) 0.0198 (5) O2 0.6576 (2) 0.8598 (3) 0.00587 (13) 0.0232 (5) O3 0.2780 (2) 0.6745 (3) 0.23225 (14) 0.0273 (6) O4 0.1088 (2) 0.5009 (3) 0.15414 (12) 0.0222 (5) O5 0.1971 (2) 0.5510 (3) −0.15625 (12) 0.0191 (5) O6 0.6360 (2) 0.5619 (3) 0.25964 (14) 0.0286 (5) O7 0.5014 (3) 0.6624 (3) 0.38879 (14) 0.0254 (5) O8 0.3974 (3) 1.0761 (3) 0.17129 (14) 0.0294 (6) O9 0.4360 (3) 0.6777 (3) 0.5670 (2) 0.0376 (6) ----- --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1149 .table-wrap} ----- -------------- -------------- -------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Tb1 0.00900 (13) 0.01520 (14) 0.01068 (12) −0.00006 (5) 0.00229 (7) −0.00069 (4) C1 0.0132 (15) 0.0153 (15) 0.0153 (13) 0.0025 (11) 0.0043 (11) 0.0017 (10) C2 0.0126 (15) 0.0137 (14) 0.0153 (12) 0.0009 (12) 0.0044 (11) 0.0017 (11) C3 0.0146 (16) 0.0195 (16) 0.0137 (13) 0.0016 (11) 0.0047 (11) 0.0008 (10) C4 0.0133 (15) 0.0159 (15) 0.0145 (12) 0.0045 (12) 0.0013 (10) −0.0021 (10) C5 0.0121 (15) 0.0184 (15) 0.0186 (13) −0.0034 (12) 0.0030 (11) −0.0012 (11) C6 0.0113 (14) 0.0165 (15) 0.0168 (13) −0.0007 (12) 0.0036 (11) 0.0023 (11) C7 0.0136 (15) 0.0219 (16) 0.0170 (13) 0.0004 (13) 0.0035 (11) 0.0018 (11) N1 0.0099 (13) 0.0182 (13) 0.0148 (11) −0.0016 (10) 0.0027 (9) −0.0013 (9) O1 0.0145 (11) 0.0288 (12) 0.0164 (10) −0.0054 (9) 0.0048 (8) −0.0030 (8) O2 0.0189 (12) 0.0352 (13) 0.0178 (10) −0.0049 (10) 0.0087 (8) 0.0022 (9) O3 0.0229 (13) 0.0446 (16) 0.0165 (10) −0.0167 (10) 0.0087 (9) −0.0084 (9) O4 0.0184 (12) 0.0307 (13) 0.0178 (9) −0.0134 (10) 0.0050 (8) −0.0016 (8) O5 0.0155 (11) 0.0272 (12) 0.0126 (9) 0.0033 (9) −0.0001 (8) −0.0052 (8) O6 0.0329 (14) 0.0328 (14) 0.0226 (11) 0.0189 (11) 0.0118 (10) 0.0066 (10) O7 0.0338 (15) 0.0226 (14) 0.0218 (11) 0.0025 (10) 0.0107 (10) 0.0009 (9) O8 0.0394 (15) 0.0339 (14) 0.0198 (11) 0.0178 (11) 0.0163 (10) 0.0098 (10) O9 0.0222 (15) 0.0273 (15) 0.0595 (18) 0.0038 (11) 0.0041 (13) 0.0031 (12) ----- -------------- -------------- -------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1499 .table-wrap} ---------------------- ------------- -------------------- ------------- Tb1---O5^i^ 2.3035 (19) C5---C6 1.367 (4) Tb1---O8 2.368 (2) C5---H5 0.9300 Tb1---O6 2.383 (2) C6---N1 1.347 (4) Tb1---O4^ii^ 2.4106 (19) C6---C7 1.492 (4) Tb1---O3 2.415 (2) C7---O4 1.256 (3) Tb1---O7 2.416 (2) C7---O3 1.257 (3) Tb1---O1 2.424 (2) O4---Tb1^iii^ 2.4106 (19) Tb1---N1 2.471 (2) O5---Tb1^iv^ 2.3035 (19) C1---O2 1.245 (3) O6---H1W 0.85 (4) C1---O1 1.263 (3) O6---H2W 0.86 (4) C1---C2 1.508 (4) O7---H3W 0.875 (16) C2---N1 1.345 (4) O7---H4W 0.85 (4) C2---C3 1.377 (4) O8---H5W 0.849 (16) C3---C4 1.412 (4) O8---H6W 0.85 (4) C3---H3 0.9300 O9---H7W 0.86 (4) C4---O5 1.315 (3) O9---H8W 0.85 (4) C4---C5 1.405 (4) O5^i^---Tb1---O8 99.83 (8) C3---C2---C1 123.8 (2) O5^i^---Tb1---O6 85.81 (8) C2---C3---C4 119.5 (3) O8---Tb1---O6 148.11 (7) C2---C3---H3 120.2 O5^i^---Tb1---O4^ii^ 81.52 (7) C4---C3---H3 120.2 O8---Tb1---O4^ii^ 70.97 (7) O5---C4---C5 121.4 (3) O6---Tb1---O4^ii^ 140.77 (7) O5---C4---C3 122.2 (2) O5^i^---Tb1---O3 151.44 (7) C5---C4---C3 116.4 (2) O8---Tb1---O3 93.13 (9) C6---C5---C4 120.1 (3) O6---Tb1---O3 96.50 (8) C6---C5---H5 120.0 O4^ii^---Tb1---O3 78.83 (7) C4---C5---H5 120.0 O5^i^---Tb1---O7 82.37 (8) N1---C6---C5 123.3 (3) O8---Tb1---O7 140.75 (8) N1---C6---C7 113.5 (2) O6---Tb1---O7 70.95 (8) C5---C6---C7 123.2 (3) O4^ii^---Tb1---O7 70.65 (7) O4---C7---O3 124.5 (3) O3---Tb1---O7 71.68 (8) O4---C7---C6 118.9 (2) O5^i^---Tb1---O1 80.00 (7) O3---C7---C6 116.5 (3) O8---Tb1---O1 74.95 (7) C2---N1---C6 117.4 (2) O6---Tb1---O1 75.22 (8) C2---N1---Tb1 121.61 (19) O4^ii^---Tb1---O1 137.48 (7) C6---N1---Tb1 120.69 (18) O3---Tb1---O1 128.19 (7) C1---O1---Tb1 124.88 (18) O7---Tb1---O1 142.73 (8) C7---O3---Tb1 124.41 (18) O5^i^---Tb1---N1 143.47 (8) C7---O4---Tb1^iii^ 138.84 (17) O8---Tb1---N1 77.25 (8) C4---O5---Tb1^iv^ 127.69 (17) O6---Tb1---N1 79.77 (8) Tb1---O6---H1W 123 (2) O4^ii^---Tb1---N1 129.18 (8) Tb1---O6---H2W 114 (3) O3---Tb1---N1 64.24 (7) H1W---O6---H2W 112 (3) O7---Tb1---N1 122.96 (8) Tb1---O7---H3W 124 (2) O1---Tb1---N1 63.95 (7) Tb1---O7---H4W 125 (2) O2---C1---O1 124.7 (3) H3W---O7---H4W 110 (3) O2---C1---C2 119.1 (2) Tb1---O8---H5W 127 (2) O1---C1---C2 116.2 (2) Tb1---O8---H6W 109 (3) N1---C2---C3 123.2 (3) H5W---O8---H6W 115 (3) N1---C2---C1 112.9 (2) H7W---O9---H8W 114 (3) ---------------------- ------------- -------------------- ------------- ::: Symmetry codes: (i) *x*+1/2, −*y*+3/2, *z*+1/2; (ii) −*x*+1/2, *y*+1/2, −*z*+1/2; (iii) −*x*+1/2, *y*−1/2, −*z*+1/2; (iv) *x*−1/2, −*y*+3/2, *z*−1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2065 .table-wrap} --------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O6---H1W···O1^v^ 0.85 (4) 2.10 (3) 2.799 (3) 139 (3) O6---H2W···O5^vi^ 0.86 (4) 1.93 (3) 2.725 (3) 154 (3) O7---H3W···O9^vii^ 0.88 (2) 1.84 (2) 2.687 (3) 162 (4) O7---H4W···O9 0.85 (4) 2.23 (3) 2.995 (4) 151 (3) O8---H5W···O2^viii^ 0.85 (2) 1.85 (2) 2.693 (3) 175 (4) O8---H6W···O3^ii^ 0.85 (4) 1.85 (4) 2.680 (3) 167 (4) O9---H7W···O2^ix^ 0.86 (4) 1.84 (2) 2.699 (3) 175 (4) O9---H8W···O4^i^ 0.85 (4) 2.37 (4) 3.073 (4) 141 (5) --------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (v) −*x*+3/2, *y*−1/2, −*z*+1/2; (vi) −*x*+1, −*y*+1, −*z*; (vii) −*x*+1, −*y*+1, −*z*+1; (viii) −*x*+1, −*y*+2, −*z*; (ii) −*x*+1/2, *y*+1/2, −*z*+1/2; (ix) *x*−1/2, −*y*+3/2, *z*+1/2; (i) *x*+1/2, −*y*+3/2, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: -------------- ------------- Tb1---O5^i^ 2.3035 (19) Tb1---O8 2.368 (2) Tb1---O6 2.383 (2) Tb1---O4^ii^ 2.4106 (19) Tb1---O3 2.415 (2) Tb1---O7 2.416 (2) Tb1---O1 2.424 (2) Tb1---N1 2.471 (2) -------------- ------------- Symmetry codes: (i) ; (ii) . ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- ---------- ---------- ----------- ------------- O6---H1*W*⋯O1^iii^ 0.85 (4) 2.10 (3) 2.799 (3) 139 (3) O6---H2*W*⋯O5^iv^ 0.86 (4) 1.93 (3) 2.725 (3) 154 (3) O7---H3*W*⋯O9^v^ 0.88 (2) 1.84 (2) 2.687 (3) 162 (4) O7---H4*W*⋯O9 0.85 (4) 2.23 (3) 2.995 (4) 151 (3) O8---H5*W*⋯O2^vi^ 0.85 (2) 1.85 (2) 2.693 (3) 175 (4) O8---H6*W*⋯O3^ii^ 0.85 (4) 1.85 (4) 2.680 (3) 167 (4) O9---H7*W*⋯O2^vii^ 0.86 (4) 1.84 (2) 2.699 (3) 175 (4) O9---H8*W*⋯O4^i^ 0.85 (4) 2.37 (4) 3.073 (4) 141 (5) Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) . :::

PubMed Central

2024-06-05T04:04:18.749239

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052142/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m357-m358", "authors": [ { "first": "Dong-Yu", "last": "Lv" }, { "first": "Zhu-Qing", "last": "Gao" }, { "first": "Jin-Zhong", "last": "Gu" } ] }

PMC3052143

Related literature {#sec1} ================== For related structures and background references, see: Al-abbasi *et al.* (2010[@bb1]); Hung *et al.* (2010[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~16~H~16~N~2~OS*M* *~r~* = 284.37Triclinic,*a* = 7.735 (2) Å*b* = 8.013 (2) Å*c* = 12.540 (3) Åα = 101.837 (5)°β = 96.908 (5)°γ = 94.205 (6)°*V* = 751.3 (4) Å^3^*Z* = 2Mo *K*α radiationμ = 0.21 mm^−1^*T* = 298 K0.53 × 0.38 × 0.19 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2000[@bb2]) *T* ~min~ = 0.908, *T* ~max~ = 0.9617829 measured reflections2648 independent reflections2329 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.023 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.054*wR*(*F* ^2^) = 0.144*S* = 1.062648 reflections189 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.30 e Å^−3^ {#d5e388} Data collection: *SMART* (Bruker, 2000[@bb2]); cell refinement: *SAINT* (Bruker, 2000[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb5]); software used to prepare material for publication: *SHELXTL*, *PARST* (Nardelli, 1995[@bb4]) and *PLATON* (Spek, 2009[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004326/gk2345sup1.cif](http://dx.doi.org/10.1107/S1600536811004326/gk2345sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004326/gk2345Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004326/gk2345Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2345&file=gk2345sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2345sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2345&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2345](http://scripts.iucr.org/cgi-bin/sendsup?gk2345)). The authors thank Universiti Kebangsaan Malaysia for providing the facilities and grants (UKM-GUP-BTT-07--30--190 & UKMST-06-FRGS0111--2009) and the Libyan Government and Sabha University, Libya, for providing a scholarship for AA. Comment ======= The ethyl group and S-atom are in *cis-*configuration with respect to the N2---C8 bond, however, the N2-phenyl and benzoyl groups are *trans* to S-atom with respect to both C---N thiourea bonds (Fig. 1). The benzene ring \[C1/C2/C3/C4/C5/C6/C7\] (A), phenyl ring \[N2/C9/C10/C11/C12/C13/C14\] (B) and the thiourea \[(S1/N1/N2/C8/\] (C) fragment are essentially planar. The dihedral angle between the plane A and the plane B is 75.93 (15)° whereas, the dihedral angle between thiourea plane (C) and both planes (A, B) are 87.99 (11) and 62.44 (16)°, respectively. Furthermore, the amide group \[N2/C9/C10/C11/C12/C13/C14\] (D) is twisted relative to the thiourea fragment (C) forming a dihedral angle of 62.44 (16)°. In addition, the molecules are linked by N1---H···S1 hydrogen bonds (Table 1, Fig. 2) to form centrosymmetric dimers. Experimental {#experimental} ============ The reaction scheme involved a reaction of benzoyl chloride (10 mmol) with ammonium thiocyanate (10 mmol) in acetone. The product, benzoyl isothiocyanate was reacted with *N*-ethylaniline (10 mmol) to give the title compound with 80% yield. A slow evaporation of the reaction mixture give light yellow crystals suitable for X-ray analysis. Refinement {#refinement} ========== Positions of C-bound H atoms were calculated. These H atoms were refined using a riding model with U~iso~=1.5U~eq~(C~methyl~ ) and U~iso~=1.5U~eq~(C) for the remaining H atoms. The amide-group H atom was located in a diffrence Fourier map and freely refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title molecule with displacement ellipsods drawn at the 50% probability level. ::: ![](e-67-0o611-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing viewed down the a-axis. Hydrogen bonds are drawn as dashed lines. ::: ![](e-67-0o611-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e126 .table-wrap} ---------------------- --------------------------------------- C~16~H~16~N~2~OS *Z* = 2 *M~r~* = 284.37 *F*(000) = 300 Triclinic, *P*1 *D*~x~ = 1.257 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 7.735 (2) Å Cell parameters from 4273 reflections *b* = 8.013 (2) Å θ = 1.7--25.0° *c* = 12.540 (3) Å µ = 0.21 mm^−1^ α = 101.837 (5)° *T* = 298 K β = 96.908 (5)° Blok, colorless γ = 94.205 (6)° 0.53 × 0.38 × 0.19 mm *V* = 751.3 (4) Å^3^ ---------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e260 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEX CCD area-detector diffractometer 2648 independent reflections Radiation source: fine-focus sealed tube 2329 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.023 ω scan θ~max~ = 25.0°, θ~min~ = 1.7° Absorption correction: multi-scan (*SADABS*; Bruker, 2000) *h* = −9→9 *T*~min~ = 0.908, *T*~max~ = 0.961 *k* = −9→9 7829 measured reflections *l* = −14→14 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e374 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.054 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.144 H atoms treated by a mixture of independent and constrained refinement *S* = 1.06 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0752*P*)^2^ + 0.3013*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2648 reflections (Δ/σ)~max~ \< 0.001 189 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.30 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e531 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e630 .table-wrap} ------ ------------- ------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ S1 0.23483 (8) 1.04861 (8) 0.44047 (5) 0.0590 (2) O1 0.2723 (2) 0.5506 (2) 0.26763 (17) 0.0716 (5) N1 0.4237 (2) 0.8089 (2) 0.34962 (15) 0.0467 (4) N2 0.2081 (3) 0.8877 (3) 0.23101 (16) 0.0663 (6) C1 0.5519 (4) 0.3888 (3) 0.3646 (2) 0.0629 (6) H1B 0.4418 0.3356 0.3670 0.076\* C2 0.6996 (6) 0.3080 (4) 0.3850 (2) 0.0855 (10) H2A 0.6892 0.2010 0.4029 0.103\* C3 0.8618 (5) 0.3839 (5) 0.3793 (2) 0.0900 (11) H3A 0.9606 0.3276 0.3922 0.108\* C4 0.8789 (4) 0.5418 (5) 0.3545 (2) 0.0821 (9) H4A 0.9892 0.5925 0.3502 0.099\* C5 0.7326 (3) 0.6268 (3) 0.33594 (19) 0.0567 (6) H5A 0.7447 0.7354 0.3204 0.068\* C6 0.5686 (3) 0.5503 (3) 0.34046 (16) 0.0453 (5) C7 0.4073 (3) 0.6313 (3) 0.31503 (18) 0.0475 (5) C8 0.2875 (3) 0.9101 (3) 0.33425 (18) 0.0497 (5) C9 0.2909 (5) 0.8135 (4) 0.1373 (2) 0.0757 (9) C10 0.4569 (5) 0.8773 (4) 0.1275 (2) 0.0858 (9) H10A 0.5164 0.9661 0.1822 0.103\* C11 0.5366 (7) 0.8103 (6) 0.0365 (3) 0.1170 (15) H11A 0.6502 0.8520 0.0317 0.140\* C12 0.4498 (11) 0.6856 (8) −0.0443 (4) 0.146 (2) H12A 0.5042 0.6398 −0.1044 0.175\* C13 0.2835 (10) 0.6260 (7) −0.0388 (3) 0.146 (2) H13A 0.2219 0.5451 −0.0975 0.175\* C14 0.2019 (7) 0.6853 (6) 0.0554 (3) 0.1116 (15) H14A 0.092 (4) 0.660 (4) 0.063 (2) 0.067 (10)\* C15 0.0405 (4) 0.9631 (4) 0.2081 (3) 0.0865 (9) H15A −0.0407 0.8796 0.1550 0.104\* H15B −0.0115 0.9914 0.2754 0.104\* C16 0.0708 (5) 1.1179 (5) 0.1650 (3) 0.1049 (11) H16A −0.0382 1.1650 0.1512 0.157\* H16B 0.1200 1.0893 0.0976 0.157\* H16C 0.1506 1.2009 0.2178 0.157\* H1A 0.499 (3) 0.850 (3) 0.403 (2) 0.050 (6)\* ------ ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1115 .table-wrap} ----- ------------- ------------- ------------- ------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ S1 0.0635 (4) 0.0613 (4) 0.0516 (4) 0.0281 (3) 0.0083 (3) 0.0032 (3) O1 0.0501 (9) 0.0559 (10) 0.1014 (14) 0.0015 (8) 0.0001 (9) 0.0070 (9) N1 0.0474 (10) 0.0455 (10) 0.0438 (10) 0.0136 (8) −0.0009 (8) 0.0026 (8) N2 0.0700 (13) 0.0692 (13) 0.0521 (11) 0.0319 (10) −0.0102 (9) −0.0027 (9) C1 0.0841 (17) 0.0513 (13) 0.0569 (14) 0.0164 (12) 0.0139 (12) 0.0139 (11) C2 0.134 (3) 0.0642 (17) 0.0625 (17) 0.0491 (19) 0.0039 (17) 0.0151 (13) C3 0.099 (2) 0.097 (2) 0.0681 (18) 0.062 (2) −0.0074 (16) −0.0040 (16) C4 0.0544 (15) 0.103 (2) 0.0796 (19) 0.0283 (15) 0.0084 (13) −0.0085 (17) C5 0.0528 (13) 0.0592 (13) 0.0578 (13) 0.0148 (10) 0.0140 (10) 0.0049 (11) C6 0.0545 (12) 0.0439 (11) 0.0376 (10) 0.0146 (9) 0.0101 (8) 0.0036 (8) C7 0.0476 (12) 0.0452 (11) 0.0505 (12) 0.0088 (9) 0.0110 (9) 0.0086 (9) C8 0.0499 (11) 0.0465 (11) 0.0509 (12) 0.0119 (9) 0.0031 (9) 0.0061 (9) C9 0.109 (2) 0.0675 (16) 0.0456 (13) 0.0460 (16) −0.0089 (14) 0.0000 (12) C10 0.130 (3) 0.0819 (19) 0.0523 (15) 0.043 (2) 0.0186 (16) 0.0165 (14) C11 0.183 (4) 0.120 (3) 0.070 (2) 0.074 (3) 0.049 (2) 0.033 (2) C12 0.262 (7) 0.135 (4) 0.056 (2) 0.116 (5) 0.027 (4) 0.020 (3) C13 0.245 (6) 0.110 (3) 0.060 (2) 0.085 (4) −0.032 (3) −0.029 (2) C14 0.139 (4) 0.103 (3) 0.071 (2) 0.045 (3) −0.023 (2) −0.0209 (19) C15 0.089 (2) 0.084 (2) 0.0754 (18) 0.0332 (16) −0.0183 (15) 0.0005 (15) C16 0.119 (3) 0.104 (3) 0.096 (2) 0.046 (2) 0.007 (2) 0.024 (2) ----- ------------- ------------- ------------- ------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1485 .table-wrap} -------------------- -------------- ----------------------- ------------ S1---C8 1.662 (2) C6---C7 1.479 (3) O1---C7 1.207 (3) C9---C14 1.370 (5) N1---C7 1.392 (3) C9---C10 1.375 (5) N1---C8 1.394 (3) C10---C11 1.392 (4) N1---H1A 0.83 (2) C10---H10A 0.9300 N2---C8 1.335 (3) C11---C12 1.341 (7) N2---C9 1.448 (3) C11---H11A 0.9300 N2---C15 1.491 (3) C12---C13 1.354 (8) C1---C2 1.377 (4) C12---H12A 0.9300 C1---C6 1.389 (3) C13---C14 1.418 (7) C1---H1B 0.9300 C13---H13A 0.9300 C2---C3 1.370 (5) C14---H14A 0.88 (3) C2---H2A 0.9300 C15---C16 1.467 (5) C3---C4 1.364 (5) C15---H15A 0.9700 C3---H3A 0.9300 C15---H15B 0.9700 C4---C5 1.383 (4) C16---H16A 0.9600 C4---H4A 0.9300 C16---H16B 0.9600 C5---C6 1.380 (3) C16---H16C 0.9600 C5---H5A 0.9300 C7---N1---C8 123.84 (19) C14---C9---C10 119.6 (4) C7---N1---H1A 116.1 (17) C14---C9---N2 120.4 (4) C8---N1---H1A 114.8 (16) C10---C9---N2 120.0 (3) C8---N2---C9 122.1 (2) C9---C10---C11 120.7 (4) C8---N2---C15 120.0 (2) C9---C10---H10A 119.7 C9---N2---C15 117.2 (2) C11---C10---H10A 119.7 C2---C1---C6 119.4 (3) C12---C11---C10 120.0 (5) C2---C1---H1B 120.3 C12---C11---H11A 120.0 C6---C1---H1B 120.3 C10---C11---H11A 120.0 C3---C2---C1 120.6 (3) C11---C12---C13 120.3 (5) C3---C2---H2A 119.7 C11---C12---H12A 119.8 C1---C2---H2A 119.7 C13---C12---H12A 119.8 C4---C3---C2 120.2 (3) C12---C13---C14 120.9 (5) C4---C3---H3A 119.9 C12---C13---H13A 119.5 C2---C3---H3A 119.9 C14---C13---H13A 119.5 C3---C4---C5 120.2 (3) C9---C14---C13 118.3 (6) C3---C4---H4A 119.9 C9---C14---H14A 115 (2) C5---C4---H4A 119.9 C13---C14---H14A 126 (2) C6---C5---C4 119.9 (3) C16---C15---N2 110.7 (3) C6---C5---H5A 120.0 C16---C15---H15A 109.5 C4---C5---H5A 120.0 N2---C15---H15A 109.5 C5---C6---C1 119.7 (2) C16---C15---H15B 109.5 C5---C6---C7 122.05 (19) N2---C15---H15B 109.5 C1---C6---C7 118.2 (2) H15A---C15---H15B 108.1 O1---C7---N1 122.5 (2) C15---C16---H16A 109.5 O1---C7---C6 122.96 (19) C15---C16---H16B 109.5 N1---C7---C6 114.58 (18) H16A---C16---H16B 109.5 N2---C8---N1 115.58 (19) C15---C16---H16C 109.5 N2---C8---S1 124.27 (16) H16A---C16---H16C 109.5 N1---C8---S1 120.15 (16) H16B---C16---H16C 109.5 C6---C1---C2---C3 −1.5 (4) C15---N2---C8---S1 −12.3 (4) C1---C2---C3---C4 0.8 (4) C7---N1---C8---N2 −53.4 (3) C2---C3---C4---C5 0.5 (4) C7---N1---C8---S1 127.2 (2) C3---C4---C5---C6 −1.2 (4) C8---N2---C9---C14 132.1 (3) C4---C5---C6---C1 0.5 (3) C15---N2---C9---C14 −57.0 (4) C4---C5---C6---C7 −176.4 (2) C8---N2---C9---C10 −51.0 (4) C2---C1---C6---C5 0.8 (3) C15---N2---C9---C10 120.0 (3) C2---C1---C6---C7 177.9 (2) C14---C9---C10---C11 −1.4 (5) C8---N1---C7---O1 0.6 (3) N2---C9---C10---C11 −178.4 (3) C8---N1---C7---C6 −179.73 (19) C9---C10---C11---C12 1.9 (5) C5---C6---C7---O1 143.2 (2) C10---C11---C12---C13 1.0 (7) C1---C6---C7---O1 −33.8 (3) C11---C12---C13---C14 −4.3 (8) C5---C6---C7---N1 −36.4 (3) C10---C9---C14---C13 −1.8 (5) C1---C6---C7---N1 146.6 (2) N2---C9---C14---C13 175.2 (3) C9---N2---C8---N1 −21.0 (4) C12---C13---C14---C9 4.7 (7) C15---N2---C8---N1 168.3 (2) C8---N2---C15---C16 102.9 (3) C9---N2---C8---S1 158.4 (2) C9---N2---C15---C16 −68.3 (3) -------------------- -------------- ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2141 .table-wrap} ------------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···S1^i^ 0.83 (2) 2.62 (2) 3.444 (2) 172 (2) C4---H4A···O1^ii^ 0.93 2.55 3.354 (4) 145 ------------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+2, −*z*+1; (ii) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ ---------- ---------- ----------- ------------- N1---H1*A*⋯S1^i^ 0.83 (2) 2.62 (2) 3.444 (2) 172 (2) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.753835

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052143/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o611", "authors": [ { "first": "Aisha A.", "last": "Al-abbasi" }, { "first": "Mohammad B.", "last": "Kassim" } ] }

PMC3052144

Related literature {#sec1} ================== For the structures of Schiff bases and their complexes, see: Ali *et al.* (2008[@bb1]); Eltayeb *et al.* (2007[@bb4]); Datta *et al.* (2009[@bb3]); Zhao *et al.* (2010[@bb9]); Temel *et al.* (2010[@bb8]); Naveenkumar *et al.* (2010[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Zn(C~13~H~10~ClN~2~O)I(CH~4~O)\]*M* *~r~* = 469.99Monoclinic,*a* = 7.0769 (9) Å*b* = 12.7212 (16) Å*c* = 18.225 (2) Åβ = 98.994 (1)°*V* = 1620.5 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 3.59 mm^−1^*T* = 298 K0.20 × 0.20 × 0.18 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb6]) *T* ~min~ = 0.534, *T* ~max~ = 0.5649273 measured reflections3522 independent reflections2947 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.021 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.025*wR*(*F* ^2^) = 0.058*S* = 1.043522 reflections195 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.91 e Å^−3^ {#d5e413} Data collection: *SMART* (Bruker, 1998[@bb2]); cell refinement: *SAINT* (Bruker, 1998[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb7]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100417X/rz2553sup1.cif](http://dx.doi.org/10.1107/S160053681100417X/rz2553sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100417X/rz2553Isup2.hkl](http://dx.doi.org/10.1107/S160053681100417X/rz2553Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2553&file=rz2553sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2553sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2553&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2553](http://scripts.iucr.org/cgi-bin/sendsup?rz2553)). This work was supported by Yichun University. Comment ======= Schiff bases and their complexes have attracted much attention for their interesting structures (Ali *et al.*, 2008; Eltayeb *et al.*, 2007; Datta *et al.*, 2009; Zhao *et al.*, 2010; Temel *et al.*, 2010; Naveenkumar *et al.*, 2010). In this paper, the title new Schiff base zinc(II) complex, Fig. 1, is reported. The Zn atom in the complex is five-coordinated by one phenolate O atom, one imine and one pyridine N atoms of the Schiff base ligand, one methanol O atom, and one iodide atom to form a distorted square pyramidal geometry. The dihedral angle between the benzene and the pyridine rings is 22.9 (2)°. In the crystal structure (Fig. 2), centrosymmetrically related molecules are linked through intermolecular O---H···N hydrogen bonds (Table 1) to form dimers. Experimental {#experimental} ============ Equimolar quantities (0.1 mmol each) of 5-chlorosalicylaldehyde, 2-aminomethylpyridine, and zinc iodide were mixed and stirred in methanol for 30 min at reflux. After keeping the filtrate in air for a few days, colourless block crystals suitable for X-ray analysis were formed. Refinement {#refinement} ========== H2 attached to O2 was located from a difference Fourier map, and refined with the O--H distance restrained to 0.85 (1) Å, and with *U*~iso~ restrained to 0.08 Å^2^. The remaining H atoms were placed in calculated positions and constrained to ride on their parent atoms, with C---H distances of 0.93--0.97 Å, and with *U*~iso~(H) = 1.2*U*~eq~(C) or 1.5*U*~eq~(C) for methyl H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, with 30% displacements ellipsoids. ::: ![](e-67-0m313-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular packing of the title compound, viewed along the c axis. Hydrogen atoms not involved in hydrogen bonds (dashed lines) are omitted for clarity. ::: ![](e-67-0m313-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------------------ --------------------------------------- \[Zn(C~13~H~10~ClN~2~O)I(CH~4~O)\] *F*(000) = 912 *M~r~* = 469.99 *D*~x~ = 1.926 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 3746 reflections *a* = 7.0769 (9) Å θ = 2.7--27.8° *b* = 12.7212 (16) Å µ = 3.59 mm^−1^ *c* = 18.225 (2) Å *T* = 298 K β = 98.994 (1)° Block, colorless *V* = 1620.5 (3) Å^3^ 0.20 × 0.20 × 0.18 mm *Z* = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e274 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3522 independent reflections Radiation source: fine-focus sealed tube 2947 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.021 ω scans θ~max~ = 27.0°, θ~min~ = 2.0° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −9→8 *T*~min~ = 0.534, *T*~max~ = 0.564 *k* = −16→15 9273 measured reflections *l* = −23→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e388 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.058 H atoms treated by a mixture of independent and constrained refinement *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0266*P*)^2^ + 0.3654*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3522 reflections (Δ/σ)~max~ = 0.003 195 parameters Δρ~max~ = 0.37 e Å^−3^ 1 restraint Δρ~min~ = −0.91 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e545 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e644 .table-wrap} ------ -------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Zn1 0.56550 (5) 1.00055 (2) 0.370141 (16) 0.03411 (9) Cl1 0.80941 (15) 0.43991 (6) 0.42899 (5) 0.0673 (3) I1 0.20664 (3) 1.054046 (16) 0.337917 (10) 0.04454 (7) O1 0.5675 (3) 0.87992 (14) 0.44157 (10) 0.0428 (5) O2 0.6619 (3) 1.10027 (17) 0.45789 (11) 0.0461 (5) N1 0.6673 (3) 0.89862 (17) 0.29675 (11) 0.0343 (5) N2 0.6831 (3) 1.10583 (17) 0.29614 (12) 0.0353 (5) C1 0.6966 (4) 0.7424 (2) 0.37342 (14) 0.0331 (6) C2 0.6271 (4) 0.7827 (2) 0.43675 (14) 0.0350 (6) C3 0.6226 (5) 0.7138 (2) 0.49658 (16) 0.0502 (8) H3 0.5819 0.7388 0.5394 0.060\* C4 0.6768 (5) 0.6104 (2) 0.49358 (17) 0.0517 (8) H4 0.6702 0.5664 0.5338 0.062\* C5 0.7407 (5) 0.5715 (2) 0.43160 (17) 0.0443 (7) C6 0.7511 (4) 0.6356 (2) 0.37262 (16) 0.0394 (6) H6 0.7951 0.6086 0.3310 0.047\* C7 0.7123 (4) 0.8024 (2) 0.30781 (15) 0.0357 (6) H7 0.7599 0.7676 0.2697 0.043\* C8 0.6893 (5) 0.9462 (2) 0.22567 (15) 0.0450 (7) H8A 0.5762 0.9319 0.1896 0.054\* H8B 0.7983 0.9150 0.2076 0.054\* C9 0.7177 (4) 1.0624 (2) 0.23317 (15) 0.0364 (6) C10 0.7742 (4) 1.1230 (3) 0.17688 (15) 0.0451 (7) H10 0.7966 1.0917 0.1329 0.054\* C11 0.7966 (4) 1.2294 (3) 0.18702 (17) 0.0492 (8) H11 0.8336 1.2712 0.1499 0.059\* C12 0.7637 (4) 1.2735 (2) 0.25260 (17) 0.0480 (7) H12 0.7803 1.3452 0.2610 0.058\* C13 0.7061 (4) 1.2099 (2) 0.30520 (17) 0.0437 (7) H13 0.6817 1.2400 0.3493 0.052\* C14 0.8502 (5) 1.1310 (3) 0.48795 (17) 0.0548 (8) H14A 0.8972 1.0869 0.5296 0.082\* H14B 0.8498 1.2029 0.5040 0.082\* H14C 0.9315 1.1240 0.4507 0.082\* H2 0.585 (4) 1.104 (2) 0.4897 (14) 0.055 (9)\* ------ -------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1103 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Zn1 0.03959 (19) 0.03446 (17) 0.03043 (16) 0.00566 (13) 0.01222 (13) 0.00098 (12) Cl1 0.0921 (7) 0.0349 (4) 0.0725 (6) 0.0165 (4) 0.0054 (5) −0.0032 (4) I1 0.03836 (12) 0.05586 (13) 0.04069 (12) 0.01147 (9) 0.01019 (8) 0.00744 (8) O1 0.0617 (13) 0.0352 (10) 0.0351 (10) 0.0147 (9) 0.0191 (9) 0.0028 (8) O2 0.0553 (14) 0.0511 (12) 0.0363 (11) −0.0032 (10) 0.0210 (10) −0.0105 (9) N1 0.0387 (13) 0.0371 (12) 0.0285 (11) 0.0009 (10) 0.0102 (9) −0.0023 (9) N2 0.0354 (13) 0.0385 (12) 0.0333 (12) 0.0014 (10) 0.0096 (10) 0.0029 (10) C1 0.0311 (14) 0.0365 (14) 0.0320 (13) 0.0031 (11) 0.0055 (11) −0.0022 (11) C2 0.0359 (15) 0.0360 (14) 0.0327 (14) 0.0056 (11) 0.0045 (11) −0.0002 (11) C3 0.072 (2) 0.0460 (17) 0.0355 (15) 0.0140 (16) 0.0157 (15) 0.0035 (13) C4 0.072 (2) 0.0411 (16) 0.0431 (17) 0.0130 (16) 0.0112 (15) 0.0108 (14) C5 0.0494 (18) 0.0337 (14) 0.0481 (17) 0.0080 (13) 0.0023 (14) −0.0022 (12) C6 0.0381 (16) 0.0379 (15) 0.0421 (16) 0.0038 (12) 0.0063 (12) −0.0065 (12) C7 0.0356 (15) 0.0401 (15) 0.0330 (14) 0.0003 (12) 0.0104 (11) −0.0102 (12) C8 0.061 (2) 0.0469 (17) 0.0299 (14) 0.0002 (14) 0.0149 (14) −0.0022 (12) C9 0.0304 (15) 0.0473 (16) 0.0323 (14) 0.0017 (12) 0.0079 (11) 0.0051 (12) C10 0.0418 (17) 0.061 (2) 0.0338 (15) 0.0001 (14) 0.0104 (13) 0.0063 (13) C11 0.0449 (18) 0.0580 (19) 0.0461 (17) −0.0019 (14) 0.0111 (14) 0.0198 (15) C12 0.0471 (18) 0.0418 (16) 0.0557 (19) 0.0003 (14) 0.0101 (15) 0.0103 (14) C13 0.0485 (18) 0.0404 (16) 0.0433 (16) 0.0046 (13) 0.0108 (13) 0.0030 (13) C14 0.057 (2) 0.066 (2) 0.0415 (17) −0.0016 (17) 0.0095 (15) 0.0005 (15) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1488 .table-wrap} ---------------- ------------- ------------------- ----------- Zn1---O1 2.0111 (18) C4---C5 1.373 (4) Zn1---N1 2.071 (2) C4---H4 0.9300 Zn1---O2 2.071 (2) C5---C6 1.361 (4) Zn1---N2 2.158 (2) C6---H6 0.9300 Zn1---I1 2.6060 (5) C7---H7 0.9300 Cl1---C5 1.746 (3) C8---C9 1.496 (4) O1---C2 1.314 (3) C8---H8A 0.9700 O2---C14 1.415 (4) C8---H8B 0.9700 O2---H2 0.86 (3) C9---C10 1.391 (4) N1---C7 1.272 (3) C10---C11 1.372 (4) N1---C8 1.460 (3) C10---H10 0.9300 N2---C9 1.330 (3) C11---C12 1.372 (4) N2---C13 1.340 (3) C11---H11 0.9300 C1---C6 1.412 (4) C12---C13 1.365 (4) C1---C2 1.419 (3) C12---H12 0.9300 C1---C7 1.438 (4) C13---H13 0.9300 C2---C3 1.403 (4) C14---H14A 0.9600 C3---C4 1.373 (4) C14---H14B 0.9600 C3---H3 0.9300 C14---H14C 0.9600 O1---Zn1---N1 88.42 (8) C4---C5---Cl1 119.8 (2) O1---Zn1---O2 89.96 (8) C5---C6---C1 121.3 (3) N1---Zn1---O2 140.91 (9) C5---C6---H6 119.4 O1---Zn1---N2 156.05 (8) C1---C6---H6 119.4 N1---Zn1---N2 77.17 (8) N1---C7---C1 126.4 (2) O2---Zn1---N2 89.42 (8) N1---C7---H7 116.8 O1---Zn1---I1 104.65 (6) C1---C7---H7 116.8 N1---Zn1---I1 116.29 (6) N1---C8---C9 111.1 (2) O2---Zn1---I1 101.87 (6) N1---C8---H8A 109.4 N2---Zn1---I1 98.90 (6) C9---C8---H8A 109.4 C2---O1---Zn1 130.13 (16) N1---C8---H8B 109.4 C14---O2---Zn1 130.14 (18) C9---C8---H8B 109.4 C14---O2---H2 112 (2) H8A---C8---H8B 108.0 Zn1---O2---H2 113 (2) N2---C9---C10 121.3 (3) C7---N1---C8 118.7 (2) N2---C9---C8 116.7 (2) C7---N1---Zn1 127.11 (18) C10---C9---C8 122.0 (2) C8---N1---Zn1 114.18 (16) C11---C10---C9 119.2 (3) C9---N2---C13 118.8 (2) C11---C10---H10 120.4 C9---N2---Zn1 115.00 (17) C9---C10---H10 120.4 C13---N2---Zn1 125.93 (18) C12---C11---C10 119.2 (3) C6---C1---C2 119.1 (2) C12---C11---H11 120.4 C6---C1---C7 116.5 (2) C10---C11---H11 120.4 C2---C1---C7 124.4 (2) C13---C12---C11 118.7 (3) O1---C2---C3 119.3 (2) C13---C12---H12 120.7 O1---C2---C1 123.4 (2) C11---C12---H12 120.7 C3---C2---C1 117.3 (2) N2---C13---C12 122.9 (3) C4---C3---C2 121.8 (3) N2---C13---H13 118.6 C4---C3---H3 119.1 C12---C13---H13 118.6 C2---C3---H3 119.1 O2---C14---H14A 109.5 C5---C4---C3 120.5 (3) O2---C14---H14B 109.5 C5---C4---H4 119.7 H14A---C14---H14B 109.5 C3---C4---H4 119.7 O2---C14---H14C 109.5 C6---C5---C4 120.0 (3) H14A---C14---H14C 109.5 C6---C5---Cl1 120.2 (2) H14B---C14---H14C 109.5 ---------------- ------------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1990 .table-wrap} ----------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O2---H2···O1^i^ 0.86 (3) 1.79 (3) 2.643 (3) 176 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+2, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- ---------- ---------- ----------- ------------- O2---H2⋯O1^i^ 0.86 (3) 1.79 (3) 2.643 (3) 176 (3) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.759110

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052144/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):m313", "authors": [ { "first": "Hong-Wei", "last": "Huang" } ] }

PMC3052145

Related literature {#sec1} ================== For the pharmacological applications of 7-oxabicyclo\[2.2.1\]hept-5-ene-2,3-dicarboxylic anhydride and its derivatives, see: Deng & Hu (2007[@bb2]); Hart *et al.* (2004[@bb4]). For related structures, see: Li (2010*a* [@bb5],*b* [@bb6]); Goh *et al.* (2008[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~12~N~2~O~3~*M* *~r~* = 256.26Orthorhombic,*a* = 10.4457 (11) Å*b* = 8.8245 (9) Å*c* = 13.2114 (15) Å*V* = 1217.8 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 0.10 mm^−1^*T* = 298 K0.38 × 0.33 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 1997[@bb1]) *T* ~min~ = 0.963, *T* ~max~ = 0.9805021 measured reflections1131 independent reflections827 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.061 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.041*wR*(*F* ^2^) = 0.084*S* = 1.011131 reflections173 parameters1 restraintH-atom parameters constrainedΔρ~max~ = 0.14 e Å^−3^Δρ~min~ = −0.12 e Å^−3^ {#d5e408} Data collection: *SMART* (Bruker, 1997[@bb1]); cell refinement: *SAINT* (Bruker, 1997[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb7]) and *PLATON* (Spek, 2009[@bb8]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100362X/lh5200sup1.cif](http://dx.doi.org/10.1107/S160053681100362X/lh5200sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100362X/lh5200Isup2.hkl](http://dx.doi.org/10.1107/S160053681100362X/lh5200Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5200&file=lh5200sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5200sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5200&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5200](http://scripts.iucr.org/cgi-bin/sendsup?lh5200)). The author thanks the Shandong Provincial Natural Science Foundation, China (ZR2009BL027). Comment ======= 7-Oxa-bicyclo\[2,2,1\]hept-5-ene-2,3-dicarboxylic anhydride has been widely employed in clinical practice, as it has low toxicity and is relatively easy to synthesize (Deng & Hu, 2007). Its derivatives are pharmacologically active (Hart *et al.*, 2004). In this paper, the structure of the title compound, (I), is reported. The molecular structure of (I) is shown in Fig. 1. The bond lengths and bond angles are as expected and they are comparable to those in similar compounds (Li, 2010*a*,*b*; Goh, *et al.*, 2008). The essentially planar pyrrole ring (maximum deviation = 0.037 (4)Å for atom C2) and the benzene ring form a dihedral angle of 69.5 (2) °. In the crystal, intermolecular N---H···O hydrogen bonds connect molecules into one-dimensional chains along \[001\]. Additional stabilization is provided by weak intermolecular C---H···O hydrogen bonds. Experimental {#experimental} ============ A mixture of *exo*-7-oxa-bicyclo\[2,2,1\]hept-5-ene-2,3-dicarboxylic anhydride (0.332 g, 2 mmol) and benzene-1,2-diamine (0.216 g, 2 mmol) in methanol (5 ml) was stirred for 5 h at room temperature, and then refluxed for 1 h. After cooling the precipitate was filtered and dried, the title compound was obtained. The crude product of 20 mg was dissolved in methanol of 10 ml. The solution was filtered to remove impurities, and then the filtrate was left for crystallization at room temperature. The single-crystal suitable for X-ray determination was obtained by evaporation of a methanol solution of the title compound after 5 days. Refinement {#refinement} ========== In the absence of significant anomalous dispersion effects the Friedel pairs were merged. H atoms were initially located in difference maps and then refined in a riding-model approximation with C---H = 0.93--0.98 Å, N---H = 0.86Å and *U*~iso~(H) = 1.2*U*~eq~(C,N). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I), with displacement ellipsoide drawn at the 30% probability level. ::: ![](e-67-0o588-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Part of the crystal structure with hydrogen bonds shown as dashed lines. ::: ![](e-67-0o588-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e120 .table-wrap} ------------------------- -------------------------------------- C~14~H~12~N~2~O~3~ *F*(000) = 536 *M~r~* = 256.26 *D*~x~ = 1.398 Mg m^−3^ Orthorhombic, *Pca*2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2c -2ac Cell parameters from 975 reflections *a* = 10.4457 (11) Å θ = 3.1--20.1° *b* = 8.8245 (9) Å µ = 0.10 mm^−1^ *c* = 13.2114 (15) Å *T* = 298 K *V* = 1217.8 (2) Å^3^ Block, pale yellow *Z* = 4 0.38 × 0.33 × 0.20 mm ------------------------- -------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e245 .table-wrap} ------------------------------------------------------------ ------------------------------------- Bruker SMART CCD diffractometer 1131 independent reflections Radiation source: fine-focus sealed tube 827 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.061 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Bruker, 1997) *h* = −12→11 *T*~min~ = 0.963, *T*~max~ = 0.980 *k* = −10→10 5021 measured reflections *l* = −15→12 ------------------------------------------------------------ ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e362 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.084 H-atom parameters constrained *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0348*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 1131 reflections (Δ/σ)~max~ \< 0.001 173 parameters Δρ~max~ = 0.14 e Å^−3^ 1 restraint Δρ~min~ = −0.12 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e516 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e615 .table-wrap} ----- ------------- ------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ N1 0.0406 (3) 0.1444 (3) 0.0863 (2) 0.0401 (7) N2 0.2069 (3) 0.1868 (4) 0.2520 (3) 0.0729 (11) H2A 0.2110 0.1054 0.2164 0.087\* H2B 0.2577 0.1992 0.3025 0.087\* O1 −0.0454 (3) −0.0189 (3) 0.20351 (18) 0.0680 (9) O2 0.1232 (3) 0.2521 (3) −0.0577 (2) 0.0671 (9) O3 0.2418 (2) −0.1090 (3) 0.03190 (19) 0.0562 (7) C1 −0.0025 (4) 0.0040 (4) 0.1192 (3) 0.0467 (9) C2 0.0207 (4) −0.1091 (4) 0.0363 (3) 0.0476 (9) H2 −0.0560 −0.1684 0.0201 0.057\* C3 0.0677 (3) −0.0159 (4) −0.0536 (3) 0.0469 (10) H3 0.0115 −0.0229 −0.1128 0.056\* C4 0.0818 (3) 0.1439 (5) −0.0139 (3) 0.0462 (10) C5 0.0363 (4) 0.2805 (4) 0.1474 (3) 0.0442 (9) C6 0.1193 (4) 0.2968 (4) 0.2282 (3) 0.0490 (10) C7 0.1108 (5) 0.4281 (5) 0.2857 (3) 0.0709 (14) H7 0.1657 0.4417 0.3404 0.085\* C8 0.0224 (6) 0.5379 (5) 0.2631 (4) 0.0818 (16) H8 0.0173 0.6247 0.3029 0.098\* C9 −0.0598 (5) 0.5204 (5) 0.1810 (4) 0.0783 (14) H9 −0.1187 0.5958 0.1652 0.094\* C10 −0.0533 (4) 0.3914 (5) 0.1239 (3) 0.0588 (11) H10 −0.1087 0.3780 0.0695 0.071\* C11 0.1408 (4) −0.2123 (4) 0.0576 (3) 0.0555 (11) H11 0.1455 −0.2562 0.1256 0.067\* C12 0.1452 (4) −0.3243 (5) −0.0286 (3) 0.0640 (12) H12 0.1251 −0.4269 −0.0259 0.077\* C13 0.1827 (4) −0.2477 (5) −0.1075 (3) 0.0629 (13) H13 0.1946 −0.2846 −0.1728 0.075\* C14 0.2030 (4) −0.0868 (4) −0.0717 (3) 0.0548 (11) H14 0.2615 −0.0259 −0.1130 0.066\* ----- ------------- ------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1087 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ N1 0.0467 (17) 0.0387 (18) 0.0349 (15) −0.0027 (15) 0.0028 (13) 0.0024 (14) N2 0.076 (3) 0.068 (2) 0.075 (3) −0.004 (2) −0.025 (2) 0.004 (2) O1 0.094 (2) 0.066 (2) 0.0437 (16) −0.0215 (16) 0.0186 (16) 0.0025 (14) O2 0.093 (2) 0.0526 (19) 0.0561 (17) −0.0006 (16) 0.0217 (16) 0.0131 (14) O3 0.0502 (17) 0.0539 (16) 0.0644 (17) −0.0025 (15) −0.0137 (14) −0.0007 (13) C1 0.051 (2) 0.049 (2) 0.040 (2) −0.008 (2) −0.0003 (18) −0.0011 (17) C2 0.052 (2) 0.048 (2) 0.0433 (19) −0.009 (2) 0.0000 (18) −0.0039 (19) C3 0.051 (2) 0.051 (2) 0.038 (2) 0.005 (2) −0.0063 (17) 0.0006 (18) C4 0.047 (2) 0.050 (3) 0.042 (2) 0.006 (2) 0.0011 (18) 0.009 (2) C5 0.046 (2) 0.042 (2) 0.045 (2) 0.002 (2) 0.0095 (18) 0.0005 (18) C6 0.053 (3) 0.049 (2) 0.045 (2) −0.004 (2) 0.0000 (19) −0.0003 (19) C7 0.086 (4) 0.065 (3) 0.062 (3) −0.027 (3) 0.014 (2) −0.019 (2) C8 0.095 (4) 0.053 (3) 0.097 (4) −0.012 (3) 0.049 (3) −0.028 (3) C9 0.068 (4) 0.051 (3) 0.115 (4) 0.016 (3) 0.027 (3) 0.003 (3) C10 0.055 (3) 0.047 (2) 0.075 (3) 0.003 (2) 0.008 (2) 0.004 (2) C11 0.067 (3) 0.050 (2) 0.050 (2) −0.003 (2) −0.006 (2) 0.0055 (18) C12 0.076 (3) 0.046 (3) 0.070 (3) 0.005 (2) 0.001 (2) −0.008 (2) C13 0.069 (3) 0.061 (3) 0.059 (3) 0.014 (2) 0.002 (2) −0.013 (2) C14 0.056 (3) 0.061 (3) 0.047 (2) 0.006 (2) 0.0046 (19) 0.003 (2) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1466 .table-wrap} --------------------- ------------ ----------------------- ------------ N1---C1 1.388 (4) C5---C6 1.383 (5) N1---C4 1.392 (4) C5---C10 1.390 (5) N1---C5 1.447 (4) C6---C7 1.388 (5) N2---C6 1.370 (5) C7---C8 1.372 (7) N2---H2A 0.8600 C7---H7 0.9300 N2---H2B 0.8600 C8---C9 1.392 (7) O1---C1 1.217 (4) C8---H8 0.9300 O2---C4 1.198 (4) C9---C10 1.367 (6) O3---C11 1.434 (4) C9---H9 0.9300 O3---C14 1.440 (4) C10---H10 0.9300 C1---C2 1.502 (5) C11---C12 1.508 (5) C2---C3 1.525 (5) C11---H11 0.9800 C2---C11 1.576 (5) C12---C13 1.303 (6) C2---H2 0.9800 C12---H12 0.9300 C3---C4 1.512 (5) C13---C14 1.512 (5) C3---C14 1.564 (5) C13---H13 0.9300 C3---H3 0.9800 C14---H14 0.9800 C1---N1---C4 113.3 (3) C8---C7---C6 120.9 (5) C1---N1---C5 123.8 (3) C8---C7---H7 119.5 C4---N1---C5 122.9 (3) C6---C7---H7 119.5 C6---N2---H2A 120.0 C7---C8---C9 120.4 (4) C6---N2---H2B 120.0 C7---C8---H8 119.8 H2A---N2---H2B 120.0 C9---C8---H8 119.8 C11---O3---C14 96.0 (3) C10---C9---C8 119.5 (4) O1---C1---N1 123.6 (3) C10---C9---H9 120.3 O1---C1---C2 128.1 (4) C8---C9---H9 120.3 N1---C1---C2 108.2 (3) C9---C10---C5 119.8 (4) C1---C2---C3 105.2 (3) C9---C10---H10 120.1 C1---C2---C11 112.4 (3) C5---C10---H10 120.1 C3---C2---C11 101.2 (3) O3---C11---C12 102.5 (3) C1---C2---H2 112.4 O3---C11---C2 100.2 (3) C3---C2---H2 112.4 C12---C11---C2 105.5 (3) C11---C2---H2 112.4 O3---C11---H11 115.6 C4---C3---C2 105.3 (3) C12---C11---H11 115.6 C4---C3---C14 109.8 (3) C2---C11---H11 115.6 C2---C3---C14 101.2 (3) C13---C12---C11 105.9 (4) C4---C3---H3 113.2 C13---C12---H12 127.1 C2---C3---H3 113.2 C11---C12---H12 127.1 C14---C3---H3 113.2 C12---C13---C14 106.1 (4) O2---C4---N1 124.7 (4) C12---C13---H13 126.9 O2---C4---C3 127.7 (4) C14---C13---H13 126.9 N1---C4---C3 107.6 (3) O3---C14---C13 102.1 (3) C6---C5---C10 121.4 (3) O3---C14---C3 99.4 (3) C6---C5---N1 119.9 (3) C13---C14---C3 107.3 (3) C10---C5---N1 118.7 (3) O3---C14---H14 115.4 N2---C6---C5 121.4 (3) C13---C14---H14 115.4 N2---C6---C7 120.6 (4) C3---C14---H14 115.4 C5---C6---C7 118.0 (4) C4---N1---C1---O1 −178.2 (4) C10---C5---C6---C7 0.0 (5) C5---N1---C1---O1 −1.7 (5) N1---C5---C6---C7 −179.1 (3) C4---N1---C1---C2 4.9 (4) N2---C6---C7---C8 −179.2 (4) C5---N1---C1---C2 −178.6 (3) C5---C6---C7---C8 0.1 (6) O1---C1---C2---C3 176.8 (4) C6---C7---C8---C9 −0.7 (7) N1---C1---C2---C3 −6.4 (4) C7---C8---C9---C10 1.1 (7) O1---C1---C2---C11 −73.9 (5) C8---C9---C10---C5 −0.9 (6) N1---C1---C2---C11 102.8 (3) C6---C5---C10---C9 0.4 (6) C1---C2---C3---C4 5.6 (4) N1---C5---C10---C9 179.5 (3) C11---C2---C3---C4 −111.6 (3) C14---O3---C11---C12 48.6 (3) C1---C2---C3---C14 119.9 (3) C14---O3---C11---C2 −59.9 (3) C11---C2---C3---C14 2.7 (3) C1---C2---C11---O3 −77.4 (3) C1---N1---C4---O2 −179.7 (4) C3---C2---C11---O3 34.3 (3) C5---N1---C4---O2 3.7 (6) C1---C2---C11---C12 176.5 (3) C1---N1---C4---C3 −1.1 (4) C3---C2---C11---C12 −71.8 (4) C5---N1---C4---C3 −177.7 (3) O3---C11---C12---C13 −31.7 (4) C2---C3---C4---O2 175.5 (4) C2---C11---C12---C13 72.7 (4) C14---C3---C4---O2 67.3 (5) C11---C12---C13---C14 0.3 (5) C2---C3---C4---N1 −3.0 (4) C11---O3---C14---C13 −48.3 (3) C14---C3---C4---N1 −111.2 (3) C11---O3---C14---C3 61.8 (3) C1---N1---C5---C6 72.1 (4) C12---C13---C14---O3 31.1 (4) C4---N1---C5---C6 −111.7 (4) C12---C13---C14---C3 −72.9 (4) C1---N1---C5---C10 −107.0 (4) C4---C3---C14---O3 72.1 (3) C4---N1---C5---C10 69.2 (5) C2---C3---C14---O3 −38.9 (3) C10---C5---C6---N2 179.4 (3) C4---C3---C14---C13 178.0 (3) N1---C5---C6---N2 0.3 (5) C2---C3---C14---C13 67.0 (3) --------------------- ------------ ----------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2210 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N2---H2B···O2^i^ 0.86 2.28 3.131 (5) 174 C3---H3···O1^ii^ 0.98 2.48 3.232 (5) 133 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1/2, *y*, *z*+1/2; (ii) −*x*, −*y*, *z*−1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ --------- ------- ----------- ------------- N2---H2*B*⋯O2^i^ 0.86 2.28 3.131 (5) 174 C3---H3⋯O1^ii^ 0.98 2.48 3.232 (5) 133 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.763029

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052145/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o588", "authors": [ { "first": "Jian", "last": "Li" } ] }

PMC3052146

Related literature {#sec1} ================== For the structure of 4,4′-bis(prop-2-ynyloxy)biphenyl, see: Zhang *et al.* (2008[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~14~I~4~O~2~*M* *~r~* = 769.89Triclinic,*a* = 10.0470 (4) Å*b* = 10.2267 (4) Å*c* = 11.3581 (4) Åα = 105.760 (4)°β = 101.433 (3)°γ = 108.211 (4)°*V* = 1014.45 (7) Å^3^*Z* = 2Mo *K*α radiationμ = 6.15 mm^−1^*T* = 100 K0.20 × 0.10 × 0.05 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb1]) *T* ~min~ = 0.467, *T* ~max~ = 1.0008121 measured reflections4502 independent reflections4118 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.026 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.030*wR*(*F* ^2^) = 0.079*S* = 1.044502 reflections217 parametersH-atom parameters constrainedΔρ~max~ = 3.38 e Å^−3^Δρ~min~ = −1.69 e Å^−3^ {#d5e353} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb1]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb3]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb3]); molecular graphics: *X-SEED* (Barbour, 2001[@bb2]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb4]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003874/jh2264sup1.cif](http://dx.doi.org/10.1107/S1600536811003874/jh2264sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003874/jh2264Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003874/jh2264Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?jh2264&file=jh2264sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?jh2264sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?jh2264&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [JH2264](http://scripts.iucr.org/cgi-bin/sendsup?jh2264)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= We have intended to activate the triple bond of 4,4\'-bis(prop-2-ynyloxy)biphenyl (Zhang *et al.*, 2008) in order to polymerize the compound by using a cuprous iodide/iodine catalytic system. The attempt yielded instead the iodinated title compound (Scheme I, Fig. 1). The aromatic rings are twisted 37.8 (2) °. Experimental {#experimental} ============ Potassium carbonate (3 g, 1 mmol) and biphenyl-4,4\'-diol (1 g, 5.3 mmol) were dissolved in ethanol (30 ml). The solution was heated for 1 h. This was followed by the addition propargyl bromide (1.5 ml, 17 mmol). The mixture was heated for another 8 h. The solvent was removed and the residue dissolved in a mixture of water (30 ml) and dichloromethane (30 ml). The aqueous layer was extracted three times with dichloromethane. Slow evaporation of dichloromethane gave colorless crystals (70%) of 4,4\'-bis(prop-2-ynyloxy)biphenyl. This compound (1 g, 3.8 mmol) was dissolved an ethanol solution of cuprous iodide and iodine in an attempt to activate the triple bond. Slow evaporation of the solvent yielded the iodinated product in 80% yield. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 to 0.99 Å, *U*~iso~(H) 1.2*U*~eq~(C)\] and were included in the refinement in the riding model approximation. The final difference Fourier map had a peak at 0.96 Å from I2 and a hole at 0.60 Å from the same atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C18H14I4O4 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o568-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e115 .table-wrap} ------------------------ --------------------------------------- C~18~H~14~I~4~O~2~ *Z* = 2 *M~r~* = 769.89 *F*(000) = 700 Triclinic, *P*1 *D*~x~ = 2.520 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.0470 (4) Å Cell parameters from 5987 reflections *b* = 10.2267 (4) Å θ = 2.4--29.2° *c* = 11.3581 (4) Å µ = 6.15 mm^−1^ α = 105.760 (4)° *T* = 100 K β = 101.433 (3)° Prism, colorless γ = 108.211 (4)° 0.20 × 0.10 × 0.05 mm *V* = 1014.45 (7) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e251 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 4502 independent reflections Radiation source: SuperNova (Mo) X-ray Source 4118 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.026 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.4° ω scans *h* = −12→9 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −13→13 *T*~min~ = 0.467, *T*~max~ = 1.000 *l* = −9→14 8121 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e371 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.030 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.079 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0391*P*)^2^ + 2.8781*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4502 reflections (Δ/σ)~max~ = 0.001 217 parameters Δρ~max~ = 3.38 e Å^−3^ 0 restraints Δρ~min~ = −1.69 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e530 .table-wrap} ------ ------------- -------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ I1 0.52321 (3) 0.89339 (3) 0.77411 (3) 0.02006 (8) I2 0.05784 (3) 0.47289 (3) 0.70014 (3) 0.02903 (10) I3 0.69630 (3) −0.38925 (3) 0.56256 (3) 0.02370 (9) I4 1.15769 (3) −0.03766 (3) 0.91544 (3) 0.02524 (9) O1 0.5470 (4) 0.7096 (3) 0.9645 (3) 0.0202 (6) O2 0.8521 (4) −0.0703 (3) 0.5344 (3) 0.0200 (6) C1 0.2354 (5) 0.6460 (5) 0.6979 (5) 0.0207 (9) H1 0.2259 0.6735 0.6242 0.025\* C2 0.3610 (5) 0.7193 (5) 0.7945 (4) 0.0181 (9) C3 0.3993 (5) 0.7013 (5) 0.9214 (4) 0.0194 (9) H3A 0.3862 0.7788 0.9867 0.023\* H3B 0.3297 0.6046 0.9150 0.023\* C4 0.5783 (5) 0.5922 (5) 0.9042 (4) 0.0177 (9) C5 0.7224 (5) 0.6043 (5) 0.9543 (4) 0.0182 (9) H5 0.7893 0.6881 1.0270 0.022\* C6 0.7679 (5) 0.4940 (5) 0.8981 (4) 0.0184 (9) H6 0.8666 0.5044 0.9316 0.022\* C7 0.6700 (5) 0.3677 (5) 0.7927 (4) 0.0167 (8) C8 0.5257 (5) 0.3563 (5) 0.7479 (4) 0.0193 (9) H8 0.4568 0.2704 0.6782 0.023\* C9 0.4797 (5) 0.4667 (5) 0.8023 (4) 0.0194 (9) H9 0.3806 0.4559 0.7696 0.023\* C10 0.7198 (5) 0.2529 (5) 0.7296 (4) 0.0160 (8) C11 0.6679 (5) 0.1820 (5) 0.5947 (4) 0.0189 (9) H11 0.5995 0.2077 0.5448 0.023\* C12 0.7143 (5) 0.0756 (5) 0.5334 (4) 0.0191 (9) H12 0.6784 0.0294 0.4424 0.023\* C13 0.8144 (5) 0.0367 (4) 0.6066 (4) 0.0163 (8) C14 0.8670 (5) 0.1041 (5) 0.7393 (4) 0.0181 (9) H14 0.9346 0.0775 0.7891 0.022\* C15 0.8192 (5) 0.2116 (5) 0.7992 (4) 0.0172 (8) H15 0.8558 0.2579 0.8902 0.021\* C16 0.9582 (5) −0.1128 (5) 0.6013 (4) 0.0192 (9) H16A 1.0423 −0.0230 0.6631 0.023\* H16B 0.9961 −0.1666 0.5386 0.023\* C17 0.8964 (5) −0.2085 (5) 0.6726 (4) 0.0172 (8) C18 0.9551 (5) −0.1992 (5) 0.7908 (4) 0.0201 (9) H18 0.9018 −0.2705 0.8211 0.024\* ------ ------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1043 .table-wrap} ----- -------------- -------------- -------------- -------------- --------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ I1 0.01788 (15) 0.02009 (15) 0.01828 (15) 0.00200 (11) 0.00372 (11) 0.00864 (12) I2 0.01896 (17) 0.01891 (16) 0.0441 (2) 0.00325 (12) 0.01327 (14) 0.00592 (14) I3 0.01724 (16) 0.02002 (16) 0.02533 (16) 0.00179 (12) 0.00369 (12) 0.00383 (13) I4 0.02077 (16) 0.02426 (17) 0.02344 (16) 0.01197 (13) −0.00226 (12) 0.00046 (13) O1 0.0246 (17) 0.0183 (15) 0.0189 (15) 0.0112 (13) 0.0053 (13) 0.0061 (13) O2 0.0263 (17) 0.0199 (16) 0.0201 (15) 0.0149 (13) 0.0081 (13) 0.0091 (13) C1 0.014 (2) 0.014 (2) 0.031 (2) 0.0025 (17) 0.0072 (18) 0.0052 (19) C2 0.016 (2) 0.014 (2) 0.025 (2) 0.0055 (16) 0.0100 (18) 0.0060 (18) C3 0.025 (2) 0.019 (2) 0.020 (2) 0.0116 (18) 0.0126 (18) 0.0093 (18) C4 0.024 (2) 0.016 (2) 0.019 (2) 0.0100 (17) 0.0108 (18) 0.0092 (17) C5 0.022 (2) 0.014 (2) 0.018 (2) 0.0051 (17) 0.0054 (17) 0.0076 (17) C6 0.016 (2) 0.020 (2) 0.020 (2) 0.0060 (17) 0.0037 (17) 0.0105 (18) C7 0.020 (2) 0.016 (2) 0.018 (2) 0.0073 (17) 0.0059 (17) 0.0100 (17) C8 0.019 (2) 0.018 (2) 0.021 (2) 0.0078 (18) 0.0058 (17) 0.0058 (18) C9 0.018 (2) 0.021 (2) 0.022 (2) 0.0095 (18) 0.0062 (18) 0.0090 (19) C10 0.016 (2) 0.014 (2) 0.018 (2) 0.0027 (16) 0.0060 (16) 0.0086 (17) C11 0.017 (2) 0.020 (2) 0.021 (2) 0.0087 (18) 0.0041 (17) 0.0096 (18) C12 0.021 (2) 0.019 (2) 0.017 (2) 0.0074 (18) 0.0055 (17) 0.0070 (18) C13 0.017 (2) 0.0123 (19) 0.022 (2) 0.0045 (16) 0.0078 (17) 0.0088 (17) C14 0.019 (2) 0.016 (2) 0.021 (2) 0.0067 (17) 0.0061 (17) 0.0113 (18) C15 0.016 (2) 0.014 (2) 0.018 (2) 0.0037 (16) 0.0021 (16) 0.0054 (17) C16 0.020 (2) 0.019 (2) 0.025 (2) 0.0107 (18) 0.0099 (18) 0.0131 (19) C17 0.014 (2) 0.014 (2) 0.021 (2) 0.0053 (16) 0.0051 (17) 0.0041 (17) C18 0.019 (2) 0.017 (2) 0.023 (2) 0.0063 (17) 0.0042 (18) 0.0077 (18) ----- -------------- -------------- -------------- -------------- --------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1451 .table-wrap} --------------------- -------------- ----------------------- ------------ I1---C2 2.107 (4) C7---C10 1.482 (6) I2---C1 2.094 (4) C8---C9 1.389 (6) I3---C17 2.109 (4) C8---H8 0.9500 I4---C18 2.089 (5) C9---H9 0.9500 O1---C4 1.372 (5) C10---C15 1.390 (6) O1---C3 1.435 (6) C10---C11 1.410 (6) O2---C13 1.381 (5) C11---C12 1.386 (6) O2---C16 1.432 (5) C11---H11 0.9500 C1---C2 1.331 (7) C12---C13 1.400 (6) C1---H1 0.9500 C12---H12 0.9500 C2---C3 1.493 (6) C13---C14 1.386 (6) C3---H3A 0.9900 C14---C15 1.398 (6) C3---H3B 0.9900 C14---H14 0.9500 C4---C9 1.383 (6) C15---H15 0.9500 C4---C5 1.399 (6) C16---C17 1.500 (6) C5---C6 1.392 (6) C16---H16A 0.9900 C5---H5 0.9500 C16---H16B 0.9900 C6---C7 1.403 (6) C17---C18 1.319 (6) C6---H6 0.9500 C18---H18 0.9500 C7---C8 1.395 (6) C4---O1---C3 118.0 (3) C8---C9---H9 120.1 C13---O2---C16 117.6 (3) C15---C10---C11 117.5 (4) C2---C1---I2 123.3 (4) C15---C10---C7 122.1 (4) C2---C1---H1 118.3 C11---C10---C7 120.4 (4) I2---C1---H1 118.3 C12---C11---C10 121.5 (4) C1---C2---C3 128.2 (4) C12---C11---H11 119.3 C1---C2---I1 117.0 (3) C10---C11---H11 119.3 C3---C2---I1 114.7 (3) C11---C12---C13 119.5 (4) O1---C3---C2 113.8 (4) C11---C12---H12 120.2 O1---C3---H3A 108.8 C13---C12---H12 120.2 C2---C3---H3A 108.8 C14---C13---O2 125.7 (4) O1---C3---H3B 108.8 C14---C13---C12 120.3 (4) C2---C3---H3B 108.8 O2---C13---C12 114.0 (4) H3A---C3---H3B 107.7 C13---C14---C15 119.2 (4) O1---C4---C9 125.3 (4) C13---C14---H14 120.4 O1---C4---C5 115.2 (4) C15---C14---H14 120.4 C9---C4---C5 119.5 (4) C10---C15---C14 122.0 (4) C6---C5---C4 120.2 (4) C10---C15---H15 119.0 C6---C5---H5 119.9 C14---C15---H15 119.0 C4---C5---H5 119.9 O2---C16---C17 113.0 (4) C5---C6---C7 120.9 (4) O2---C16---H16A 109.0 C5---C6---H6 119.5 C17---C16---H16A 109.0 C7---C6---H6 119.5 O2---C16---H16B 109.0 C8---C7---C6 117.5 (4) C17---C16---H16B 109.0 C8---C7---C10 121.5 (4) H16A---C16---H16B 107.8 C6---C7---C10 121.0 (4) C18---C17---C16 128.5 (4) C9---C8---C7 122.0 (4) C18---C17---I3 116.8 (3) C9---C8---H8 119.0 C16---C17---I3 114.6 (3) C7---C8---H8 119.0 C17---C18---I4 124.2 (4) C4---C9---C8 119.8 (4) C17---C18---H18 117.9 C4---C9---H9 120.1 I4---C18---H18 117.9 I2---C1---C2---C3 −3.1 (7) C8---C7---C10---C11 37.3 (6) I2---C1---C2---I1 −178.41 (19) C6---C7---C10---C11 −141.2 (4) C4---O1---C3---C2 −73.4 (5) C15---C10---C11---C12 −0.3 (7) C1---C2---C3---O1 139.5 (5) C7---C10---C11---C12 179.2 (4) I1---C2---C3---O1 −45.1 (4) C10---C11---C12---C13 0.3 (7) C3---O1---C4---C9 1.6 (6) C16---O2---C13---C14 −2.1 (6) C3---O1---C4---C5 −177.3 (4) C16---O2---C13---C12 177.8 (4) O1---C4---C5---C6 −177.9 (4) C11---C12---C13---C14 −0.1 (7) C9---C4---C5---C6 3.1 (6) C11---C12---C13---O2 −179.9 (4) C4---C5---C6---C7 −1.5 (7) O2---C13---C14---C15 179.6 (4) C5---C6---C7---C8 −0.9 (6) C12---C13---C14---C15 −0.2 (6) C5---C6---C7---C10 177.6 (4) C11---C10---C15---C14 0.0 (6) C6---C7---C8---C9 1.8 (7) C7---C10---C15---C14 −179.5 (4) C10---C7---C8---C9 −176.8 (4) C13---C14---C15---C10 0.3 (7) O1---C4---C9---C8 178.9 (4) C13---O2---C16---C17 74.9 (5) C5---C4---C9---C8 −2.3 (7) O2---C16---C17---C18 −135.0 (5) C7---C8---C9---C4 −0.2 (7) O2---C16---C17---I3 49.6 (4) C8---C7---C10---C15 −143.3 (4) C16---C17---C18---I4 1.3 (7) C6---C7---C10---C15 38.2 (6) I3---C17---C18---I4 176.6 (2) --------------------- -------------- ----------------------- ------------ :::

PubMed Central

2024-06-05T04:04:18.767551

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052146/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o568", "authors": [ { "first": "Kiramat", "last": "Shah" }, { "first": "M.", "last": "Raza Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052147

Related literature {#sec1} ================== For the structure of 2-bromonitrobenzene, see: Fronczek (2006[@bb4]). For the structure of 3-bromonitrobenzene, see: Charlton & Trotter (1963[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~6~H~4~BrNO~2~*M* *~r~* = 202.01Triclinic,*a* = 6.3676 (6) Å*b* = 7.3635 (7) Å*c* = 7.6798 (7) Åα = 65.554 (9)°β = 87.705 (8)°γ = 88.884 (8)°*V* = 327.54 (5) Å^3^*Z* = 2Mo *K*α radiationμ = 6.20 mm^−1^*T* = 100 K0.20 × 0.10 × 0.05 mm ### Data collection {#sec2.1.2} Agilent SuperNova Dual diffractometer with an Atlas detectorAbsorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010[@bb1]) *T* ~min~ = 0.414, *T* ~max~ = 1.0002142 measured reflections1443 independent reflections1365 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.052 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.045*wR*(*F* ^2^) = 0.119*S* = 1.071443 reflections92 parametersH-atom parameters constrainedΔρ~max~ = 0.91 e Å^−3^Δρ~min~ = −1.58 e Å^−3^ {#d5e407} Data collection: *CrysAlis PRO* (Agilent, 2010[@bb1]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *X-SEED* (Barbour, 2001[@bb2]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003394/xu5150sup1.cif](http://dx.doi.org/10.1107/S1600536811003394/xu5150sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003394/xu5150Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003394/xu5150Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?xu5150&file=xu5150sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?xu5150sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?xu5150&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [XU5150](http://scripts.iucr.org/cgi-bin/sendsup?xu5150)). We thank the Higher Education Commission of Pakistan and the University of Malaya for supporting this study. Comment ======= 4-Bromo-1-nitrobenzene (Scheme I) was synthesized as a precursor that will be used in the synthesis of 4,4\'-bis(aminophenoxy)biphenyl (the compound is also commercially available: http://www.chemindustry.com/chemicals/815494.html). The molecule is flat (Fig. 1) as the nitro substituent is co-planar with the aromatic ring. π-π stacking occrs between parallel benzene rings of adjacent molecules, centroids distance between C1-ring and C1^i^-ring (symmetry code: (i) 1-x, -5, 1-z) is 3.643 (3) Å and that between C1-ring and C1^ii^-ring (symmetry code: (ii) 1-x, 1-y, 1-z) is 3.741 (3) Å. Intermolecular weak C---H···O hydrogen bonding (Table 1) and the short Br···O contacts \[3.227 (4), 3.401 (4) Å\] are observed in the crystal structure. Experimental {#experimental} ============ The nitrating mixture cosisted of 5 ml conc. HNO~3~ and 5 ml conc. H~2~SO~4~ kept at 273 K. Bromobenzene (2.6 ml) was added. The temperature was then raised to about 333 K for 3 h. The mixture was added to water (200 ml); the organic compound was extracted by using dichloromethane. The solvent was dried and then alllowed to evaporate to yield the product in 70% yield. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C---H 0.95 Å, *U*~iso~(H) 1.2*U*~eq~(C)\] and were included in the refinement in the riding model approximation. The crystal is a non-merohedral twin; the separation of the two domains was effected by *CrysAlis PRO* (Agilent, 2010). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of C6H4BrNO2 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o548-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e133 .table-wrap} ----------------------- --------------------------------------- C~6~H~4~BrNO~2~ *Z* = 2 *M~r~* = 202.01 *F*(000) = 196 Triclinic, *P*1 *D*~x~ = 2.048 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 6.3676 (6) Å Cell parameters from 1590 reflections *b* = 7.3635 (7) Å θ = 2.9--28.3° *c* = 7.6798 (7) Å µ = 6.20 mm^−1^ α = 65.554 (9)° *T* = 100 K β = 87.705 (8)° Block, colorless γ = 88.884 (8)° 0.20 × 0.10 × 0.05 mm *V* = 327.54 (5) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e266 .table-wrap} ------------------------------------------------------------------- -------------------------------------- Agilent SuperNova Dual diffractometer with an Atlas detector 1443 independent reflections Radiation source: SuperNova (Mo) X-ray Source 1365 reflections with *I* \> 2σ(*I*) Mirror *R*~int~ = 0.052 Detector resolution: 10.4041 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.9° ω scans *h* = −8→8 Absorption correction: multi-scan (*CrysAlis PRO*; Agilent, 2010) *k* = −9→9 *T*~min~ = 0.414, *T*~max~ = 1.000 *l* = −9→9 2142 measured reflections ------------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e386 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.045 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.119 H-atom parameters constrained *S* = 1.07 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0671*P*)^2^ + 0.4717*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 1443 reflections (Δ/σ)~max~ = 0.001 92 parameters Δρ~max~ = 0.91 e Å^−3^ 0 restraints Δρ~min~ = −1.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e545 .table-wrap} ----- ------------- ------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 0.83556 (7) 0.24763 (7) 0.14671 (6) 0.01978 (19) O1 0.0573 (5) 0.3167 (6) 0.7390 (5) 0.0238 (8) O2 0.3071 (6) 0.2117 (6) 0.9389 (5) 0.0245 (8) N1 0.2383 (6) 0.2623 (6) 0.7787 (5) 0.0151 (7) C6 0.7151 (7) 0.1751 (7) 0.5288 (7) 0.0173 (9) H6 0.8526 0.1212 0.5575 0.021\* C5 0.5810 (7) 0.1811 (7) 0.6722 (6) 0.0146 (9) H5 0.6251 0.1326 0.8004 0.018\* C2 0.4465 (7) 0.3256 (7) 0.2969 (7) 0.0173 (9) H2 0.4024 0.3750 0.1687 0.021\* C3 0.3121 (7) 0.3291 (7) 0.4408 (6) 0.0159 (9) H3 0.1731 0.3792 0.4130 0.019\* C1 0.6478 (7) 0.2483 (6) 0.3429 (6) 0.0157 (9) C4 0.3809 (7) 0.2594 (6) 0.6254 (6) 0.0125 (8) ----- ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e750 .table-wrap} ----- ------------- ------------- ------------- --------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.0204 (3) 0.0213 (3) 0.0206 (3) −0.00244 (19) 0.00662 (18) −0.0122 (2) O1 0.0149 (16) 0.038 (2) 0.0232 (18) 0.0024 (15) 0.0001 (13) −0.0174 (16) O2 0.0299 (19) 0.032 (2) 0.0131 (16) 0.0028 (16) −0.0003 (14) −0.0107 (15) N1 0.0173 (18) 0.0152 (18) 0.0156 (18) −0.0013 (14) 0.0010 (14) −0.0093 (15) C6 0.015 (2) 0.017 (2) 0.021 (2) −0.0008 (17) 0.0000 (17) −0.0089 (19) C5 0.016 (2) 0.015 (2) 0.014 (2) 0.0014 (16) −0.0023 (16) −0.0076 (17) C2 0.020 (2) 0.018 (2) 0.016 (2) −0.0004 (18) 0.0001 (17) −0.0094 (18) C3 0.018 (2) 0.016 (2) 0.015 (2) 0.0020 (17) −0.0041 (17) −0.0072 (17) C1 0.019 (2) 0.014 (2) 0.019 (2) −0.0005 (18) 0.0015 (18) −0.0113 (19) C4 0.0133 (19) 0.015 (2) 0.012 (2) −0.0005 (16) 0.0005 (15) −0.0090 (17) ----- ------------- ------------- ------------- --------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e982 .table-wrap} -------------------- ------------ ------------------- ------------ Br1---C1 1.887 (4) C5---C4 1.387 (6) O1---N1 1.220 (5) C5---H5 0.9500 O2---N1 1.226 (5) C2---C3 1.379 (6) N1---C4 1.464 (5) C2---C1 1.390 (6) C6---C1 1.384 (6) C2---H2 0.9500 C6---C5 1.381 (6) C3---C4 1.380 (6) C6---H6 0.9500 C3---H3 0.9500 O1---N1---O2 123.6 (4) C1---C2---H2 120.6 O1---N1---C4 117.9 (4) C4---C3---C2 119.6 (4) O2---N1---C4 118.4 (4) C4---C3---H3 120.2 C1---C6---C5 119.5 (4) C2---C3---H3 120.2 C1---C6---H6 120.2 C6---C1---C2 121.5 (4) C5---C6---H6 120.2 C6---C1---Br1 119.2 (3) C4---C5---C6 118.7 (4) C2---C1---Br1 119.3 (3) C4---C5---H5 120.6 C3---C4---C5 121.8 (4) C6---C5---H5 120.6 C3---C4---N1 119.7 (4) C3---C2---C1 118.8 (4) C5---C4---N1 118.4 (4) C3---C2---H2 120.6 C1---C6---C5---C4 0.5 (7) C2---C3---C4---N1 −179.8 (4) C1---C2---C3---C4 1.1 (7) C6---C5---C4---C3 0.7 (7) C5---C6---C1---C2 −0.9 (7) C6---C5---C4---N1 179.0 (4) C5---C6---C1---Br1 177.9 (3) O1---N1---C4---C3 4.1 (6) C3---C2---C1---C6 0.1 (7) O2---N1---C4---C3 −175.3 (4) C3---C2---C1---Br1 −178.7 (3) O1---N1---C4---C5 −174.3 (4) C2---C3---C4---C5 −1.5 (7) O2---N1---C4---C5 6.3 (6) -------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1246 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C3---H3···O1^i^ 0.95 2.52 3.359 (6) 147 C5---H5···O2^ii^ 0.95 2.54 3.276 (6) 135 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*, −*y*+1, −*z*+1; (ii) −*x*+1, −*y*, −*z*+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- C3---H3⋯O1^i^ 0.95 2.52 3.359 (6) 147 C5---H5⋯O2^ii^ 0.95 2.54 3.276 (6) 135 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.772362

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052147/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o548", "authors": [ { "first": "Qamar", "last": "Ali" }, { "first": "M.", "last": "Raza Shah" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052148

Related literature {#sec1} ================== For general background to the method proposed by our group for obtaining 2-oxa-6-azabenzobicyclononanes using commercially available dibenzyl ketone, salicylic aldehyde and ammonium acetate as starting materials, see: Baliah *et al.* (1983[@bb1]); Soldatenkov *et al.* (1996[@bb7]); Le Tuan Anh *et al.* (2008[@bb4]). For related compounds, see: Soldatenkov *et al.* (2002[@bb8], 2010[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~36~H~31~N~2~O~3~ ^+^·C~2~H~3~O~2~ ^−^·2C~2~H~6~O*M* *~r~* = 690.81Monoclinic,*a* = 13.5464 (10) Å*b* = 20.1124 (15) Å*c* = 14.2535 (11) Åβ = 105.118 (2)°*V* = 3749.0 (5) Å^3^*Z* = 4Mo *K*α radiationμ = 0.08 mm^−1^*T* = 100 K0.28 × 0.15 × 0.13 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 2003[@bb5]) *T* ~min~ = 0.977, *T* ~max~ = 0.98935569 measured reflections7399 independent reflections4951 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.062 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.044*wR*(*F* ^2^) = 0.107*S* = 1.017399 reflections463 parametersH-atom parameters constrainedΔρ~max~ = 0.23 e Å^−3^Δρ~min~ = −0.24 e Å^−3^ {#d5e582} Data collection: *APEX2* (Bruker, 2005[@bb3]); cell refinement: *SAINT-Plus* (Bruker, 2001[@bb2]); data reduction: *SAINT-Plus*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S160053681100376X/rk2264sup1.cif](http://dx.doi.org/10.1107/S160053681100376X/rk2264sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100376X/rk2264Isup2.hkl](http://dx.doi.org/10.1107/S160053681100376X/rk2264Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rk2264&file=rk2264sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rk2264sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rk2264&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RK2264](http://scripts.iucr.org/cgi-bin/sendsup?rk2264)). Comment ======= Recently our group has found an efficient method of the one-step synthesis of potentially bioactive substances having oxazocine skeletal structure. These molecules are formed by domino condensation from commercially available dibenzyl ketone, salicylic aldehyde and ammonium acetate as starting materials (Soldatenkov *et al.*, 2010). The key step of this condensation is Petrenko--Kritchenko reaction (Baliah *et al.*, 1983) leading to the formation of the substituted γ-piperidone (Le Tuan Anh *et al.*, 2008), which then reacts with the excess of ammonium acetate and aldehyde. This work reports the structural characterization of a product of such reaction - 2-oxa-6-aza-3,4-benzobicyclo\[3.3.1^1,5^\]nonan-6-ium acetate (I). Compound I crystallizes as diethanol solvate, *i.e.*, C~38~H~34~N~2~O~5~^.^2(C~2~H~6~O). The cation of the salt I comprises a fused tricyclic system containing three six-membered rings (piperidine, dihydro-2*H*-pyran and benzene) (Fig. 1). The piperidine ring has the usual *chair* conformation, while the dihydropyran ring adopts the slightly distorted *sofa* conformation (the C13 carbon atom deviates from the plane passed through the other atoms of the ring by 0.691 (2) Å). The phenyl substituents at the C10 and C11 carbon atoms occupy the sterically favorable equatorial positions, whereas the phenyl substituent at the C13 carbon atom is axially disposed. The cation of I possesses four asymmetric centers at the C1, C10, C11, and C13 carbon atoms and can have potentially numerous diastereomers. The crystal of I is racemic and consists of enantiomeric pairs with the following relative configuration of the centers: *rac*-1*S\**,10*R\**,11*S\**, 13*S\**. In the crystal, there are six (one intra- and five intermolecular) independent hydrogen bonding interactions (Table 1). The intermolecular hydrogen bonds link the cations and anions of I and ethanol solvate molecules into ribbons along the direction \[0 0 1\] (Fig. 2). The crystal packing of the ribbons is stacked along the *a* axis. Experimental {#experimental} ============ Ammonium acetate (4.0 g, 52 mmol) was added to a solution of dibenzyl ketone (2.1 g, 10 mmol) and salicylic aldehyde (3.66 g, 30 mmol) in ethanol (50 ml) (Fig. 3). The reaction mixture was stirred for 96 h at 293 K (monitoring by *TLC* until disappearance of the starting ketone spot). At the end of the reaction, the formed precipitate was filtered off, one half of the mother liquid solvent removed under reduced pressure and the residue was cooled to give 1.45 g of light-yellow crystals of I. Yield is 21%. *M*.p. = 451--453 K. IR (KBr), ν/cm^-1^: 1623, 1748, 3405, 3460. ^1^H NMR (DMSO-*d*~6~, 400 MHz, 300 K): δ = 1.08 (t, 6H, CH~3~CH~2~O, J = 6.8), 3.30 (s, 3H, CH~3~CO), 3.47 (q, 4H, CH~3~CH~2~O, J = 6.8), 3.77 (d, 1H, H8, J~7.8~ = 9.0), 4.23 (d, 1H, H9, J~5,9~ = 1.5), 4.32 (d, 1H, H7, J~7,8~= 9.0), 4.41 (br, 4H, 2(*Alk*)OH, ^+^NH~2~), 4.48 (d, 1H, H5, J~5,9~ = 1.5), 6.41--7.50 (br m, 22H, H~arom~), 7.94 (s, 1H, N=CH), 10.63 (br, 1H, (*Ar*)OH), 12.48 (s, 1H, (*Ar*)OH). Anal. Calcd. for C~42~H~46~N~2~O~7~: C, 73.04; H, 6.67; N, 4.06. Found: C, 73.13; H, 6.79; N, 4.23. Refinement {#refinement} ========== The hydrogen atoms of the hydroxy and amino groups were localized in the difference Fourier map and included in the refinement with fixed positional and isotropic displacement parameters \[*U*~iso~(H) = 1.5*U*~eq~(O) and 1.2*U*~eq~(N)\]. The other hydrogen atoms were placed in calculated positions with C---H = 0.95--1.00Å and refined in the riding model with fixed isotropic displacement parameters \[*U*~iso~(H) = 1.5*U*~eq~(C) for CH~3~-groups and *U*~iso~(H) = 1.2*U*~eq~(C) for the other groups\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of I with the atom numbering scheme. Displacement ellipsoids are shown at the 50% probability level. H atoms are presented as a small spheres of arbitrary radius. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o560-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing of I. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o560-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Domino condensation of dibenzyl ketone with salicylic aldehyde and ammonium acetate. ::: ![](e-67-0o560-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e338 .table-wrap} -------------------------------------------------- --------------------------------------- C~36~H~31~N~2~O~3~^+^·C~2~H~3~O~2~^−^·2C~2~H~6~O *F*(000) = 1472 *M~r~* = 690.81 *D*~x~ = 1.224 Mg m^−3^ Monoclinic, *P*2~1~/*c* Melting point = 451--453 K Hall symbol: -P 2ybc Mo *K*α radiation, λ = 0.71073 Å *a* = 13.5464 (10) Å Cell parameters from 4349 reflections *b* = 20.1124 (15) Å θ = 2.5--23.7° *c* = 14.2535 (11) Å µ = 0.08 mm^−1^ β = 105.118 (2)° *T* = 100 K *V* = 3749.0 (5) Å^3^ Prism, light-yellow *Z* = 4 0.28 × 0.15 × 0.13 mm -------------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e491 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 7399 independent reflections Radiation source: fine-focus sealed tube 4951 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.062 φ and ω scans θ~max~ = 26.1°, θ~min~ = 1.6° Absorption correction: multi-scan (*SADABS*; Sheldrick, 2003) *h* = −16→16 *T*~min~ = 0.977, *T*~max~ = 0.989 *k* = −24→24 35569 measured reflections *l* = −17→17 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e608 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.044 Hydrogen site location: difference Fourier map *wR*(*F*^2^) = 0.107 H-atom parameters constrained *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.044*P*)^2^ + 0.8*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 7399 reflections (Δ/σ)~max~ = 0.001 463 parameters Δρ~max~ = 0.23 e Å^−3^ 0 restraints Δρ~min~ = −0.24 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e765 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor w*R* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*-factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e864 .table-wrap} ------ --------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.31447 (13) 0.45725 (9) 0.26034 (13) 0.0241 (4) H1 0.3562 0.4309 0.3162 0.029\* C2 0.27020 (13) 0.41161 (8) 0.17702 (13) 0.0238 (4) C3 0.31983 (14) 0.35414 (9) 0.15984 (14) 0.0286 (4) H3 0.3835 0.3423 0.2031 0.034\* C4 0.27796 (14) 0.31398 (9) 0.08085 (15) 0.0332 (5) H4 0.3128 0.2749 0.0698 0.040\* C5 0.18468 (14) 0.33100 (9) 0.01773 (14) 0.0308 (4) H5 0.1562 0.3036 −0.0370 0.037\* C6 0.13298 (13) 0.38735 (8) 0.03375 (13) 0.0253 (4) H6 0.0687 0.3985 −0.0089 0.030\* C7 0.17631 (13) 0.42725 (8) 0.11278 (12) 0.0224 (4) O8 0.11919 (8) 0.48161 (5) 0.12638 (8) 0.0223 (3) C9 0.16377 (13) 0.52919 (8) 0.20072 (12) 0.0218 (4) C10 0.22947 (12) 0.58026 (8) 0.16205 (13) 0.0229 (4) H10 0.2529 0.6143 0.2143 0.027\* C11 0.32643 (12) 0.54871 (8) 0.14383 (12) 0.0222 (4) H11 0.3046 0.5182 0.0867 0.027\* N12 0.38139 (10) 0.50797 (7) 0.22941 (10) 0.0226 (3) H12A 0.4342 0.4854 0.2119 0.027\* H12B 0.4088 0.5347 0.2840 0.027\* C13 0.23087 (12) 0.49527 (8) 0.29266 (12) 0.0235 (4) H13 0.2660 0.5317 0.3365 0.028\* N1 0.08334 (10) 0.56563 (7) 0.22658 (10) 0.0232 (3) C14 −0.00930 (13) 0.54651 (9) 0.20077 (13) 0.0256 (4) H14 −0.0258 0.5075 0.1623 0.031\* C15 −0.09103 (13) 0.58249 (9) 0.22817 (13) 0.0260 (4) C16 −0.07164 (14) 0.64102 (10) 0.28307 (14) 0.0335 (5) O1 0.02500 (10) 0.66495 (7) 0.31689 (12) 0.0508 (4) H1O 0.0648 0.6343 0.2931 0.076\* C17 −0.15130 (15) 0.67540 (10) 0.30517 (16) 0.0420 (5) H17 −0.1381 0.7155 0.3416 0.050\* C18 −0.24953 (15) 0.65141 (11) 0.27434 (15) 0.0411 (5) H18 −0.3037 0.6752 0.2899 0.049\* C19 −0.27084 (15) 0.59328 (10) 0.22123 (15) 0.0392 (5) H19 −0.3388 0.5768 0.2012 0.047\* C20 −0.19200 (14) 0.55965 (10) 0.19783 (14) 0.0333 (5) H20 −0.2064 0.5201 0.1603 0.040\* C21 0.16999 (12) 0.61709 (8) 0.07242 (13) 0.0239 (4) C22 0.15273 (13) 0.58968 (9) −0.01999 (13) 0.0264 (4) H22 0.1762 0.5460 −0.0273 0.032\* C23 0.10186 (13) 0.62515 (9) −0.10155 (14) 0.0301 (4) H23 0.0917 0.6059 −0.1642 0.036\* C24 0.06575 (14) 0.68840 (10) −0.09224 (15) 0.0347 (5) H24 0.0309 0.7127 −0.1482 0.042\* C25 0.08082 (14) 0.71584 (9) −0.00093 (16) 0.0366 (5) H25 0.0554 0.7591 0.0060 0.044\* C26 0.13278 (13) 0.68080 (9) 0.08103 (15) 0.0298 (4) H26 0.1431 0.7004 0.1435 0.036\* C27 0.39849 (12) 0.59989 (9) 0.12015 (13) 0.0241 (4) C28 0.43138 (13) 0.59222 (9) 0.03550 (13) 0.0257 (4) O2 0.39434 (9) 0.54015 (6) −0.02342 (9) 0.0311 (3) H2O 0.4183 0.5416 −0.0816 0.047\* C29 0.49980 (14) 0.63804 (10) 0.01430 (14) 0.0340 (5) H29 0.5235 0.6326 −0.0423 0.041\* C30 0.53299 (15) 0.69114 (10) 0.07520 (16) 0.0394 (5) H30 0.5798 0.7220 0.0603 0.047\* C31 0.49895 (15) 0.70016 (10) 0.15790 (15) 0.0361 (5) H31 0.5206 0.7376 0.1988 0.043\* C32 0.43302 (13) 0.65386 (9) 0.18001 (14) 0.0293 (4) H32 0.4109 0.6592 0.2376 0.035\* C33 0.17145 (13) 0.45525 (9) 0.35001 (13) 0.0268 (4) C34 0.12157 (14) 0.39565 (10) 0.31830 (14) 0.0332 (5) H34 0.1256 0.3769 0.2582 0.040\* C35 0.06608 (16) 0.36341 (11) 0.37368 (15) 0.0427 (5) H35 0.0325 0.3227 0.3513 0.051\* C36 0.05916 (17) 0.39003 (12) 0.46139 (16) 0.0477 (6) H36 0.0200 0.3682 0.4987 0.057\* C37 0.10967 (17) 0.44863 (11) 0.49416 (16) 0.0464 (6) H37 0.1066 0.4667 0.5549 0.056\* C38 0.16484 (15) 0.48112 (10) 0.43867 (14) 0.0357 (5) H38 0.1986 0.5217 0.4615 0.043\* O5 0.46371 (10) 0.57558 (7) 0.39577 (9) 0.0374 (3) H5O 0.4207 0.5946 0.4335 0.056\* C41 0.56962 (14) 0.57329 (10) 0.44520 (15) 0.0351 (5) H41A 0.6090 0.5584 0.3995 0.042\* H41B 0.5804 0.5405 0.4987 0.042\* C42 0.60860 (16) 0.63970 (10) 0.48591 (17) 0.0454 (6) H42A 0.6826 0.6371 0.5146 0.068\* H42B 0.5747 0.6526 0.5360 0.068\* H42C 0.5941 0.6729 0.4338 0.068\* O6 0.66244 (10) 0.37980 (6) 0.50427 (10) 0.0369 (3) H6O 0.6265 0.3937 0.4387 0.055\* C43 0.70231 (18) 0.31419 (11) 0.50708 (16) 0.0468 (6) H43A 0.7738 0.3162 0.5021 0.056\* H43B 0.6617 0.2886 0.4508 0.056\* C44 0.69941 (17) 0.27955 (11) 0.59883 (16) 0.0474 (6) H44A 0.7292 0.2351 0.5997 0.071\* H44B 0.6284 0.2757 0.6024 0.071\* H44C 0.7388 0.3051 0.6546 0.071\* C39 0.59166 (14) 0.42003 (10) 0.25775 (14) 0.0321 (4) C40 0.69533 (16) 0.39181 (13) 0.25958 (17) 0.0524 (6) H40A 0.7006 0.3464 0.2854 0.079\* H40B 0.7487 0.4195 0.3010 0.079\* H40C 0.7040 0.3911 0.1934 0.079\* O3 0.54470 (9) 0.45292 (6) 0.18438 (9) 0.0316 (3) O4 0.55567 (10) 0.41052 (8) 0.32869 (10) 0.0459 (4) ------ --------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2120 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0223 (9) 0.0253 (9) 0.0253 (10) −0.0004 (7) 0.0072 (7) 0.0040 (8) C2 0.0242 (9) 0.0216 (9) 0.0288 (10) −0.0005 (7) 0.0125 (8) 0.0047 (7) C3 0.0266 (10) 0.0247 (10) 0.0386 (11) 0.0017 (7) 0.0159 (8) 0.0058 (8) C4 0.0349 (11) 0.0221 (10) 0.0505 (13) −0.0001 (8) 0.0252 (10) −0.0016 (9) C5 0.0350 (11) 0.0241 (10) 0.0391 (11) −0.0062 (8) 0.0200 (9) −0.0069 (8) C6 0.0261 (10) 0.0251 (10) 0.0277 (10) −0.0021 (7) 0.0125 (8) −0.0005 (8) C7 0.0257 (9) 0.0186 (9) 0.0282 (10) −0.0005 (7) 0.0161 (8) 0.0007 (7) O8 0.0229 (6) 0.0206 (6) 0.0247 (7) 0.0012 (5) 0.0084 (5) −0.0030 (5) C9 0.0227 (9) 0.0214 (9) 0.0232 (9) 0.0003 (7) 0.0092 (7) −0.0042 (7) C10 0.0204 (9) 0.0220 (9) 0.0281 (10) −0.0014 (7) 0.0095 (7) −0.0032 (7) C11 0.0217 (9) 0.0233 (9) 0.0223 (9) 0.0008 (7) 0.0070 (7) 0.0004 (7) N12 0.0196 (7) 0.0264 (8) 0.0233 (8) 0.0020 (6) 0.0082 (6) 0.0002 (6) C13 0.0232 (9) 0.0252 (9) 0.0231 (9) −0.0017 (7) 0.0077 (7) −0.0021 (7) N1 0.0222 (8) 0.0225 (8) 0.0281 (8) −0.0005 (6) 0.0122 (6) −0.0022 (6) C14 0.0298 (10) 0.0239 (9) 0.0257 (10) −0.0014 (8) 0.0117 (8) −0.0019 (8) C15 0.0266 (10) 0.0263 (10) 0.0271 (10) 0.0006 (7) 0.0103 (8) 0.0003 (8) C16 0.0303 (11) 0.0330 (11) 0.0398 (12) −0.0020 (8) 0.0138 (9) −0.0090 (9) O1 0.0290 (8) 0.0438 (9) 0.0836 (12) −0.0086 (6) 0.0216 (8) −0.0343 (8) C17 0.0369 (12) 0.0369 (12) 0.0552 (14) 0.0023 (9) 0.0178 (10) −0.0153 (10) C18 0.0308 (11) 0.0492 (13) 0.0459 (13) 0.0067 (9) 0.0145 (10) −0.0095 (11) C19 0.0261 (11) 0.0481 (13) 0.0455 (13) −0.0007 (9) 0.0130 (9) −0.0105 (10) C20 0.0295 (11) 0.0368 (11) 0.0352 (11) −0.0037 (8) 0.0115 (9) −0.0082 (9) C21 0.0168 (9) 0.0237 (9) 0.0329 (10) −0.0022 (7) 0.0095 (7) 0.0018 (8) C22 0.0222 (9) 0.0248 (10) 0.0334 (11) 0.0013 (7) 0.0093 (8) 0.0024 (8) C23 0.0260 (10) 0.0335 (11) 0.0321 (11) −0.0022 (8) 0.0098 (8) 0.0061 (9) C24 0.0261 (10) 0.0317 (11) 0.0447 (13) −0.0012 (8) 0.0066 (9) 0.0136 (9) C25 0.0313 (11) 0.0211 (10) 0.0584 (15) 0.0014 (8) 0.0134 (10) 0.0061 (9) C26 0.0266 (10) 0.0234 (10) 0.0414 (12) −0.0015 (8) 0.0125 (9) −0.0015 (8) C27 0.0191 (9) 0.0246 (9) 0.0293 (10) 0.0007 (7) 0.0073 (7) 0.0024 (8) C28 0.0211 (9) 0.0276 (10) 0.0281 (10) 0.0017 (7) 0.0062 (8) 0.0022 (8) O2 0.0320 (7) 0.0357 (8) 0.0297 (7) −0.0059 (6) 0.0151 (6) −0.0045 (6) C29 0.0336 (11) 0.0381 (12) 0.0342 (11) −0.0049 (9) 0.0156 (9) 0.0045 (9) C30 0.0366 (12) 0.0350 (12) 0.0502 (13) −0.0092 (9) 0.0179 (10) 0.0060 (10) C31 0.0329 (11) 0.0288 (10) 0.0461 (13) −0.0074 (8) 0.0094 (9) −0.0046 (9) C32 0.0253 (10) 0.0318 (11) 0.0322 (11) −0.0015 (8) 0.0099 (8) −0.0021 (8) C33 0.0237 (9) 0.0326 (10) 0.0248 (10) −0.0006 (8) 0.0075 (8) 0.0018 (8) C34 0.0349 (11) 0.0405 (12) 0.0261 (10) −0.0098 (9) 0.0113 (8) −0.0003 (9) C35 0.0465 (13) 0.0471 (13) 0.0373 (12) −0.0188 (10) 0.0163 (10) −0.0013 (10) C36 0.0536 (14) 0.0591 (15) 0.0381 (13) −0.0189 (11) 0.0259 (11) 0.0012 (11) C37 0.0578 (14) 0.0557 (15) 0.0352 (12) −0.0153 (11) 0.0289 (11) −0.0087 (11) C38 0.0383 (11) 0.0382 (12) 0.0351 (11) −0.0071 (9) 0.0178 (9) −0.0051 (9) O5 0.0285 (7) 0.0497 (9) 0.0331 (8) −0.0006 (6) 0.0064 (6) −0.0104 (7) C41 0.0284 (10) 0.0357 (11) 0.0389 (12) −0.0008 (8) 0.0045 (9) −0.0025 (9) C42 0.0394 (12) 0.0343 (12) 0.0590 (15) −0.0062 (9) 0.0067 (11) 0.0009 (11) O6 0.0375 (8) 0.0375 (8) 0.0361 (8) 0.0077 (6) 0.0102 (6) −0.0005 (6) C43 0.0541 (14) 0.0419 (13) 0.0465 (14) 0.0159 (11) 0.0171 (11) 0.0013 (11) C44 0.0503 (14) 0.0439 (13) 0.0507 (14) 0.0129 (10) 0.0177 (11) 0.0050 (11) C39 0.0282 (10) 0.0365 (11) 0.0344 (11) 0.0031 (8) 0.0133 (9) 0.0011 (9) C40 0.0419 (13) 0.0696 (17) 0.0522 (15) 0.0227 (12) 0.0238 (11) 0.0142 (12) O3 0.0268 (7) 0.0401 (8) 0.0302 (7) 0.0057 (6) 0.0117 (6) 0.0035 (6) O4 0.0382 (8) 0.0664 (11) 0.0376 (9) 0.0189 (7) 0.0181 (7) 0.0160 (7) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3050 .table-wrap} ----------------------- -------------- ----------------------- -------------- C1---C2 1.497 (2) C24---C25 1.379 (3) C1---N12 1.505 (2) C24---H24 0.9500 C1---C13 1.533 (2) C25---C26 1.388 (3) C1---H1 1.0000 C25---H25 0.9500 C2---C3 1.391 (2) C26---H26 0.9500 C2---C7 1.396 (2) C27---C32 1.384 (2) C3---C4 1.382 (3) C27---C28 1.400 (2) C3---H3 0.9500 C28---O2 1.354 (2) C4---C5 1.389 (3) C28---C29 1.395 (2) C4---H4 0.9500 O2---H2O 0.9659 C5---C6 1.382 (2) C29---C30 1.376 (3) C5---H5 0.9500 C29---H29 0.9500 C6---C7 1.383 (2) C30---C31 1.385 (3) C6---H6 0.9500 C30---H30 0.9500 C7---O8 1.3820 (19) C31---C32 1.382 (3) O8---C9 1.438 (2) C31---H31 0.9500 C9---N1 1.439 (2) C32---H32 0.9500 C9---C13 1.545 (2) C33---C38 1.391 (3) C9---C10 1.551 (2) C33---C34 1.392 (3) C10---C21 1.514 (2) C34---C35 1.385 (3) C10---C11 1.541 (2) C34---H34 0.9500 C10---H10 1.0000 C35---C36 1.385 (3) C11---N12 1.497 (2) C35---H35 0.9500 C11---C27 1.516 (2) C36---C37 1.382 (3) C11---H11 1.0000 C36---H36 0.9500 N12---H12A 0.9347 C37---C38 1.386 (3) N12---H12B 0.9381 C37---H37 0.9500 C13---C33 1.519 (2) C38---H38 0.9500 C13---H13 1.0000 O5---C41 1.425 (2) N1---C14 1.272 (2) O5---H5O 0.9692 C14---C15 1.459 (2) C41---C42 1.497 (3) C14---H14 0.9500 C41---H41A 0.9900 C15---C16 1.400 (3) C41---H41B 0.9900 C15---C20 1.400 (3) C42---H42A 0.9800 C16---O1 1.360 (2) C42---H42B 0.9800 C16---C17 1.385 (3) C42---H42C 0.9800 O1---H1O 0.9389 O6---C43 1.422 (2) C17---C18 1.375 (3) O6---H6O 0.9752 C17---H17 0.9500 C43---C44 1.491 (3) C18---C19 1.382 (3) C43---H43A 0.9900 C18---H18 0.9500 C43---H43B 0.9900 C19---C20 1.377 (3) C44---H44A 0.9800 C19---H19 0.9500 C44---H44B 0.9800 C20---H20 0.9500 C44---H44C 0.9800 C21---C22 1.390 (3) C39---O4 1.246 (2) C21---C26 1.394 (2) C39---O3 1.261 (2) C22---C23 1.385 (2) C39---C40 1.509 (3) C22---H22 0.9500 C40---H40A 0.9800 C23---C24 1.382 (3) C40---H40B 0.9800 C23---H23 0.9500 C40---H40C 0.9800 C2---C1---N12 109.30 (14) C24---C23---C22 120.32 (19) C2---C1---C13 111.69 (14) C24---C23---H23 119.8 N12---C1---C13 107.37 (13) C22---C23---H23 119.8 C2---C1---H1 109.5 C25---C24---C23 119.36 (18) N12---C1---H1 109.5 C25---C24---H24 120.3 C13---C1---H1 109.5 C23---C24---H24 120.3 C3---C2---C7 118.13 (16) C24---C25---C26 120.58 (18) C3---C2---C1 122.50 (16) C24---C25---H25 119.7 C7---C2---C1 119.36 (15) C26---C25---H25 119.7 C4---C3---C2 120.99 (18) C25---C26---C21 120.53 (18) C4---C3---H3 119.5 C25---C26---H26 119.7 C2---C3---H3 119.5 C21---C26---H26 119.7 C3---C4---C5 119.63 (17) C32---C27---C28 119.04 (16) C3---C4---H4 120.2 C32---C27---C11 121.92 (16) C5---C4---H4 120.2 C28---C27---C11 119.03 (15) C6---C5---C4 120.63 (18) O2---C28---C29 122.43 (16) C6---C5---H5 119.7 O2---C28---C27 118.04 (15) C4---C5---H5 119.7 C29---C28---C27 119.53 (17) C5---C6---C7 118.99 (17) C28---O2---H2O 110.8 C5---C6---H6 120.5 C30---C29---C28 120.17 (18) C7---C6---H6 120.5 C30---C29---H29 119.9 O8---C7---C6 116.05 (15) C28---C29---H29 119.9 O8---C7---C2 122.28 (15) C29---C30---C31 120.79 (18) C6---C7---C2 121.61 (16) C29---C30---H30 119.6 C7---O8---C9 119.13 (13) C31---C30---H30 119.6 O8---C9---N1 109.09 (13) C32---C31---C30 118.95 (18) O8---C9---C13 111.85 (13) C32---C31---H31 120.5 N1---C9---C13 108.96 (13) C30---C31---H31 120.5 O8---C9---C10 110.38 (13) C31---C32---C27 121.48 (18) N1---C9---C10 107.26 (13) C31---C32---H32 119.3 C13---C9---C10 109.18 (13) C27---C32---H32 119.3 C21---C10---C11 110.40 (14) C38---C33---C34 118.44 (17) C21---C10---C9 113.29 (14) C38---C33---C13 117.35 (16) C11---C10---C9 112.37 (14) C34---C33---C13 124.20 (16) C21---C10---H10 106.8 C35---C34---C33 120.51 (18) C11---C10---H10 106.8 C35---C34---H34 119.7 C9---C10---H10 106.8 C33---C34---H34 119.7 N12---C11---C27 109.93 (13) C34---C35---C36 120.53 (19) N12---C11---C10 110.66 (13) C34---C35---H35 119.7 C27---C11---C10 112.63 (14) C36---C35---H35 119.7 N12---C11---H11 107.8 C37---C36---C35 119.38 (19) C27---C11---H11 107.8 C37---C36---H36 120.3 C10---C11---H11 107.8 C35---C36---H36 120.3 C11---N12---C1 113.59 (13) C36---C37---C38 120.18 (19) C11---N12---H12A 107.5 C36---C37---H37 119.9 C1---N12---H12A 108.1 C38---C37---H37 119.9 C11---N12---H12B 111.5 C37---C38---C33 120.95 (19) C1---N12---H12B 106.5 C37---C38---H38 119.5 H12A---N12---H12B 109.5 C33---C38---H38 119.5 C33---C13---C1 115.72 (14) C41---O5---H5O 114.3 C33---C13---C9 114.42 (14) O5---C41---C42 111.77 (16) C1---C13---C9 106.41 (13) O5---C41---H41A 109.3 C33---C13---H13 106.6 C42---C41---H41A 109.3 C1---C13---H13 106.6 O5---C41---H41B 109.3 C9---C13---H13 106.6 C42---C41---H41B 109.3 C14---N1---C9 121.86 (15) H41A---C41---H41B 107.9 N1---C14---C15 122.22 (16) C41---C42---H42A 109.5 N1---C14---H14 118.9 C41---C42---H42B 109.5 C15---C14---H14 118.9 H42A---C42---H42B 109.5 C16---C15---C20 118.30 (17) C41---C42---H42C 109.5 C16---C15---C14 121.47 (16) H42A---C42---H42C 109.5 C20---C15---C14 120.21 (16) H42B---C42---H42C 109.5 O1---C16---C17 118.54 (17) C43---O6---H6O 112.5 O1---C16---C15 121.25 (16) O6---C43---C44 111.19 (17) C17---C16---C15 120.21 (18) O6---C43---H43A 109.4 C16---O1---H1O 103.3 C44---C43---H43A 109.4 C18---C17---C16 119.89 (19) O6---C43---H43B 109.4 C18---C17---H17 120.1 C44---C43---H43B 109.4 C16---C17---H17 120.1 H43A---C43---H43B 108.0 C17---C18---C19 121.22 (18) C43---C44---H44A 109.5 C17---C18---H18 119.4 C43---C44---H44B 109.5 C19---C18---H18 119.4 H44A---C44---H44B 109.5 C20---C19---C18 118.95 (18) C43---C44---H44C 109.5 C20---C19---H19 120.5 H44A---C44---H44C 109.5 C18---C19---H19 120.5 H44B---C44---H44C 109.5 C19---C20---C15 121.41 (18) O4---C39---O3 122.28 (17) C19---C20---H20 119.3 O4---C39---C40 119.18 (18) C15---C20---H20 119.3 O3---C39---C40 118.54 (17) C22---C21---C26 118.20 (17) C39---C40---H40A 109.5 C22---C21---C10 121.76 (15) C39---C40---H40B 109.5 C26---C21---C10 120.03 (16) H40A---C40---H40B 109.5 C23---C22---C21 121.00 (17) C39---C40---H40C 109.5 C23---C22---H22 119.5 H40A---C40---H40C 109.5 C21---C22---H22 119.5 H40B---C40---H40C 109.5 N12---C1---C2---C3 88.45 (19) C20---C15---C16---O1 178.30 (18) C13---C1---C2---C3 −152.89 (16) C14---C15---C16---O1 −3.1 (3) N12---C1---C2---C7 −90.60 (18) C20---C15---C16---C17 −0.8 (3) C13---C1---C2---C7 28.1 (2) C14---C15---C16---C17 177.75 (18) C7---C2---C3---C4 0.7 (3) O1---C16---C17---C18 −178.2 (2) C1---C2---C3---C4 −178.39 (16) C15---C16---C17---C18 1.0 (3) C2---C3---C4---C5 −0.3 (3) C16---C17---C18---C19 −0.1 (3) C3---C4---C5---C6 −0.6 (3) C17---C18---C19---C20 −1.0 (3) C4---C5---C6---C7 1.1 (3) C18---C19---C20---C15 1.2 (3) C5---C6---C7---O8 −178.01 (15) C16---C15---C20---C19 −0.3 (3) C5---C6---C7---C2 −0.6 (3) C14---C15---C20---C19 −178.86 (18) C3---C2---C7---O8 176.98 (15) C11---C10---C21---C22 44.7 (2) C1---C2---C7---O8 −3.9 (2) C9---C10---C21---C22 −82.32 (19) C3---C2---C7---C6 −0.2 (2) C11---C10---C21---C26 −133.91 (16) C1---C2---C7---C6 178.88 (15) C9---C10---C21---C26 99.07 (18) C6---C7---O8---C9 −173.46 (14) C26---C21---C22---C23 1.3 (2) C2---C7---O8---C9 9.2 (2) C10---C21---C22---C23 −177.29 (16) C7---O8---C9---N1 −158.67 (13) C21---C22---C23---C24 −1.0 (3) C7---O8---C9---C13 −38.05 (18) C22---C23---C24---C25 0.0 (3) C7---O8---C9---C10 83.72 (17) C23---C24---C25---C26 0.8 (3) O8---C9---C10---C21 57.51 (18) C24---C25---C26---C21 −0.4 (3) N1---C9---C10---C21 −61.23 (18) C22---C21---C26---C25 −0.6 (3) C13---C9---C10---C21 −179.16 (14) C10---C21---C26---C25 178.05 (16) O8---C9---C10---C11 −68.47 (17) N12---C11---C27---C32 −70.3 (2) N1---C9---C10---C11 172.79 (13) C10---C11---C27---C32 53.6 (2) C13---C9---C10---C11 54.86 (18) N12---C11---C27---C28 109.50 (17) C21---C10---C11---N12 −175.72 (13) C10---C11---C27---C28 −126.60 (17) C9---C10---C11---N12 −48.19 (18) C32---C27---C28---O2 −178.12 (15) C21---C10---C11---C27 60.78 (18) C11---C27---C28---O2 2.1 (2) C9---C10---C11---C27 −171.69 (14) C32---C27---C28---C29 1.5 (3) C27---C11---N12---C1 177.98 (13) C11---C27---C28---C29 −178.31 (16) C10---C11---N12---C1 52.95 (18) O2---C28---C29---C30 178.19 (17) C2---C1---N12---C11 58.31 (18) C27---C28---C29---C30 −1.4 (3) C13---C1---N12---C11 −63.00 (17) C28---C29---C30---C31 −0.3 (3) C2---C1---C13---C33 74.96 (19) C29---C30---C31---C32 1.8 (3) N12---C1---C13---C33 −165.24 (14) C30---C31---C32---C27 −1.7 (3) C2---C1---C13---C9 −53.37 (18) C28---C27---C32---C31 0.1 (3) N12---C1---C13---C9 66.44 (16) C11---C27---C32---C31 179.82 (17) O8---C9---C13---C33 −69.97 (18) C1---C13---C33---C38 127.54 (18) N1---C9---C13---C33 50.72 (19) C9---C13---C33---C38 −108.19 (18) C10---C9---C13---C33 167.57 (14) C1---C13---C33---C34 −54.1 (2) O8---C9---C13---C1 59.12 (16) C9---C13---C33---C34 70.1 (2) N1---C9---C13---C1 179.81 (13) C38---C33---C34---C35 0.5 (3) C10---C9---C13---C1 −63.34 (16) C13---C33---C34---C35 −177.78 (18) O8---C9---N1---C14 13.6 (2) C33---C34---C35---C36 0.1 (3) C13---C9---N1---C14 −108.74 (18) C34---C35---C36---C37 −1.1 (4) C10---C9---N1---C14 133.19 (16) C35---C36---C37---C38 1.4 (4) C9---N1---C14---C15 178.85 (16) C36---C37---C38---C33 −0.7 (3) N1---C14---C15---C16 1.3 (3) C34---C33---C38---C37 −0.2 (3) N1---C14---C15---C20 179.83 (17) C13---C33---C38---C37 178.19 (19) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4848 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1O···N1 0.94 1.73 2.608 (2) 154 O2---H2O···O3^i^ 0.97 1.67 2.637 (2) 177 O5---H5O···O6^ii^ 0.97 1.69 2.651 (2) 174 O6---H6O···O4 0.98 1.65 2.617 (2) 173 N12---H12A···O3 0.93 1.77 2.697 (2) 172 N12---H12B···O5 0.94 1.77 2.709 (2) 173 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*; (ii) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- --------- ------- ----------- ------------- O1---H1*O*⋯N1 0.94 1.73 2.608 (2) 154 O2---H2*O*⋯O3^i^ 0.97 1.67 2.637 (2) 177 O5---H5*O*⋯O6^ii^ 0.97 1.69 2.651 (2) 174 O6---H6*O*⋯O4 0.98 1.65 2.617 (2) 173 N12---H12*A*⋯O3 0.93 1.77 2.697 (2) 172 N12---H12*B*⋯O5 0.94 1.77 2.709 (2) 173 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.774870

2011-2-05

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052148/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 5; 67(Pt 3):o560-o561", "authors": [ { "first": "Le Tuan", "last": "Anh" }, { "first": "Truong Hong", "last": "Hieu" }, { "first": "Anatoly T.", "last": "Soldatenkov" }, { "first": "Svetlana A.", "last": "Soldatova" }, { "first": "Victor N.", "last": "Khrustalev" } ] }

PMC3052149

Related literature {#sec1} ================== For tripodal Schiff base ligands, see: Kanesato *et al.* (2000[@bb5]) and for azo compounds, see: Butcher *et al.* (2005[@bb3]). For further synthetic details, see: Dinçalp *et al.* (2007[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~48~H~48~N~10~O~6~*M* *~r~* = 860.96Triclinic,*a* = 10.5613 (9) Å*b* = 12.1234 (5) Å*c* = 17.2107 (9) Åα = 86.418 (3)°β = 89.308 (2)°γ = 88.084 (3)°*V* = 2198.0 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 0.09 mm^−1^*T* = 150 K0.22 × 0.20 × 0.16 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: multi-scan (*SORTAV*; Blessing, 1995[@bb2]) *T* ~min~ = 0.827, *T* ~max~ = 0.99019855 measured reflections9781 independent reflections4152 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.071 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.062*wR*(*F* ^2^) = 0.187*S* = 0.999781 reflections589 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.23 e Å^−3^ {#d5e447} Data collection: *COLLECT* (Nonius, 2002[@bb6]); cell refinement: *DENZO-SMN* (Otwinowski & Minor, 1997[@bb7]); data reduction: *DENZO-SMN*; program(s) used to solve structure: *SIR92* (Altomare *et al.*, 1994[@bb1]); program(s) used to refine structure: *SHELXTL* (Sheldrick, 2008[@bb8]); molecular graphics: *PLATON* (Spek, 2009[@bb9]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004405/hb5798sup1.cif](http://dx.doi.org/10.1107/S1600536811004405/hb5798sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004405/hb5798Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004405/hb5798Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hb5798&file=hb5798sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hb5798sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hb5798&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HB5798](http://scripts.iucr.org/cgi-bin/sendsup?hb5798)). We are grateful to Bu-Ali Sina University for financial support. Comment ======= Herein, we report the synthesis and X-ray crystal structure of the title compound, (I), (Fig. 1), a tripodal Schiff base ligand containing three azo groups. For tripodal Schiff base ligands see: Kanesato *et al.* (2000) and for azo compounds see: Butcher *et al.* (2005). The title compound adopts a cage-like conformation in the solid state. The geometry around the bridghead N atom of the compound is approximately pyramidal, since the angles C1--N1--C33, C1--N1--C17 and C33--N1--C17 have values of 112.3 (2), 113.5 (2) and 112.8 (2)°, respectively. The average of N═N bond lengths\[1.25 (3) Å\] is in the expected range and is in good agreement with values found in other similar compounds. Interestingly the hydrogen atom of one of three OH groups has transferred to one of three imine groups through intramolecular hydrogen bonding producing a zwitterionic compound. Three arms of tripodal ligand are located close to each other and in all of them there is an intramolecularhydrogen bonding (table 1). Experimental {#experimental} ============ Azo dye (5-(4-methoxyphenylazo)salicylaldehyde) was synthesized according to the literature procedure (Dinçalp *et al.*, 2007). Then to a solution of above aldehyde (3 mmol) in ethanol (70 ml) was added tren (1 mmol) in the same solvent (10 ml) (see Scheme I). The solution was stirred for 12 h at 40°C. The resulting orange precipitate was filtered and dried in vacuum. Orange blocks of (I) were obtained by slow evaporation from a acetonitril solution at room temperature after 24 h. Refinement {#refinement} ========== The H(C) atom positions were calculated and refined in isotropic approximatiom within riding model with the *U*~iso~(H) parameters equal to 1.2 *U*~eq~(Ci) where U(Ci) is the equivalent thermal parameters of the carbon atoms to which corresponding H atoms are bonded. \'H atoms bonded to C atoms were placed in calculated positions with C-H distances in the range 0.95-0.99 Å and were included in the refinement in a riding-model approximation with U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(C~methyl~). H atoms bonded to O and N atoms were refined independently with isotropic displacement parameters. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A view of the structure of (I), with displacement ellipsoids drawn at the 50% probability level. All C-bonded H atoms omitted for clarity. ::: ![](e-67-0o606-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e125 .table-wrap} ----------------------- --------------------------------------- C~48~H~48~N~10~O~6~ *Z* = 2 *M~r~* = 860.96 *F*(000) = 908 Triclinic, *P*1 *D*~x~ = 1.301 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.5613 (9) Å Cell parameters from 7794 reflections *b* = 12.1234 (5) Å θ = 2.6--27.5° *c* = 17.2107 (9) Å µ = 0.09 mm^−1^ α = 86.418 (3)° *T* = 150 K β = 89.308 (2)° Block, orange γ = 88.084 (3)° 0.22 × 0.20 × 0.16 mm *V* = 2198.0 (2) Å^3^ ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e261 .table-wrap} -------------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 9781 independent reflections Radiation source: fine-focus sealed tube 4152 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.071 Detector resolution: 9 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 2.6° φ scans and ω scans with κ offsets *h* = −13→13 Absorption correction: multi-scan (*SORTAV*; Blessing, 1995) *k* = −15→15 *T*~min~ = 0.827, *T*~max~ = 0.990 *l* = −22→22 19855 measured reflections -------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e387 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.062 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.187 H atoms treated by a mixture of independent and constrained refinement *S* = 0.99 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0768*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 9781 reflections (Δ/σ)~max~ = 0.001 589 parameters Δρ~max~ = 0.37 e Å^−3^ 2 restraints Δρ~min~ = −0.23 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e541 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e640 .table-wrap} ------ --------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.2448 (2) 0.82743 (16) 0.82789 (12) 0.0474 (6) O2 0.43622 (18) 0.45882 (17) 0.57762 (12) 0.0495 (6) O3 −0.0630 (2) 0.8117 (2) 0.50993 (12) 0.0576 (6) O4 −0.1109 (2) −0.08081 (19) 0.91613 (15) 0.0776 (8) O5 −0.47340 (19) −0.00203 (17) 0.79102 (13) 0.0582 (6) O6 −0.57085 (19) 0.29892 (18) 1.01599 (12) 0.0571 (6) N1 0.3726 (2) 0.8543 (2) 0.56017 (14) 0.0444 (6) N2 0.3882 (2) 0.74854 (19) 0.72451 (13) 0.0403 (6) N3 0.3183 (3) 0.6273 (2) 0.50901 (14) 0.0431 (6) N4 0.0959 (2) 0.8958 (2) 0.59704 (14) 0.0438 (6) N5 0.0284 (2) 0.4183 (2) 0.88438 (14) 0.0460 (6) N6 0.0856 (2) 0.3371 (2) 0.85796 (14) 0.0427 (6) N7 −0.0348 (2) 0.3043 (2) 0.66786 (13) 0.0418 (6) N8 −0.0348 (2) 0.2007 (2) 0.68282 (13) 0.0425 (6) N9 −0.2363 (2) 0.5682 (2) 0.77249 (14) 0.0457 (6) N10 −0.3386 (2) 0.5194 (2) 0.76315 (14) 0.0475 (7) C1 0.4720 (3) 0.8657 (2) 0.61690 (17) 0.0468 (8) H1A 0.4489 0.9278 0.6495 0.056\* H1B 0.5521 0.8835 0.5891 0.056\* C2 0.4926 (3) 0.7609 (2) 0.66887 (17) 0.0439 (8) H2A 0.4983 0.6961 0.6366 0.053\* H2B 0.5733 0.7644 0.6972 0.053\* C3 0.3336 (3) 0.6552 (2) 0.73432 (15) 0.0368 (7) H3A 0.3584 0.5963 0.7029 0.044\* C4 0.2343 (2) 0.6388 (2) 0.79291 (15) 0.0355 (7) C5 0.1799 (3) 0.5360 (2) 0.80621 (16) 0.0393 (7) H5A 0.2052 0.4766 0.7754 0.047\* C6 0.0884 (3) 0.5204 (3) 0.86465 (17) 0.0422 (7) C7 0.0480 (3) 0.6087 (3) 0.90776 (17) 0.0476 (8) H7A −0.0164 0.5984 0.9463 0.057\* C8 0.1006 (3) 0.7108 (3) 0.89495 (16) 0.0459 (8) H8A 0.0728 0.7705 0.9248 0.055\* C9 0.1939 (3) 0.7264 (2) 0.83858 (16) 0.0384 (7) C10 0.0247 (3) 0.2334 (2) 0.87651 (16) 0.0405 (7) C11 0.0921 (3) 0.1410 (3) 0.85677 (18) 0.0494 (8) H11A 0.1733 0.1485 0.8330 0.059\* C12 0.0447 (3) 0.0371 (3) 0.87057 (19) 0.0574 (9) H12A 0.0926 −0.0264 0.8564 0.069\* C13 −0.0730 (3) 0.0262 (3) 0.90515 (19) 0.0508 (8) C14 −0.1426 (3) 0.1186 (3) 0.92557 (17) 0.0520 (9) H14A −0.2237 0.1114 0.9495 0.062\* C15 −0.0925 (3) 0.2223 (3) 0.91061 (16) 0.0468 (8) H15A −0.1399 0.2863 0.9242 0.056\* C16 −0.2313 (4) −0.0982 (3) 0.9522 (2) 0.0927 (15) H16A −0.2475 −0.1775 0.9563 0.139\* H16B −0.2974 −0.0590 0.9208 0.139\* H16C −0.2318 −0.0701 1.0044 0.139\* C17 0.4180 (3) 0.8058 (3) 0.48855 (17) 0.0487 (8) H17A 0.4997 0.7654 0.4989 0.058\* H17B 0.4333 0.8659 0.4482 0.058\* C18 0.3250 (3) 0.7275 (2) 0.45807 (17) 0.0489 (8) H18A 0.2401 0.7645 0.4544 0.059\* H18B 0.3515 0.7080 0.4052 0.059\* C19 0.2148 (3) 0.5907 (2) 0.54053 (16) 0.0422 (7) H19A 0.1382 0.6330 0.5325 0.051\* C20 0.2118 (3) 0.4892 (2) 0.58677 (16) 0.0391 (7) C21 0.0946 (3) 0.4468 (2) 0.61236 (16) 0.0392 (7) H21A 0.0193 0.4910 0.6044 0.047\* C22 0.0871 (3) 0.3435 (2) 0.64833 (16) 0.0397 (7) C23 0.2004 (3) 0.2813 (2) 0.66447 (16) 0.0411 (7) H23A 0.1959 0.2101 0.6906 0.049\* C24 0.3155 (3) 0.3206 (2) 0.64355 (15) 0.0413 (7) H24A 0.3897 0.2777 0.6573 0.050\* C25 0.3276 (3) 0.4250 (2) 0.60136 (16) 0.0393 (7) C26 −0.1541 (3) 0.1589 (2) 0.70770 (16) 0.0404 (7) C27 −0.1660 (3) 0.0458 (3) 0.7050 (2) 0.0548 (9) H27A −0.0983 0.0027 0.6844 0.066\* C28 −0.2738 (3) −0.0052 (3) 0.7316 (2) 0.0573 (9) H28A −0.2810 −0.0826 0.7283 0.069\* C29 −0.3711 (3) 0.0563 (3) 0.76274 (18) 0.0453 (8) C30 −0.3613 (3) 0.1697 (2) 0.76609 (16) 0.0430 (8) H30A −0.4288 0.2125 0.7873 0.052\* C31 −0.2526 (3) 0.2202 (2) 0.73831 (16) 0.0413 (7) H31A −0.2459 0.2979 0.7404 0.050\* C32 −0.5733 (3) 0.0585 (3) 0.8261 (2) 0.0722 (11) H32A −0.6401 0.0081 0.8435 0.108\* H32B −0.6081 0.1147 0.7881 0.108\* H32C −0.5410 0.0945 0.8709 0.108\* C33 0.2976 (3) 0.9573 (3) 0.54508 (19) 0.0515 (9) H33A 0.2576 0.9564 0.4934 0.062\* H33B 0.3547 1.0206 0.5436 0.062\* C34 0.1956 (3) 0.9737 (3) 0.60625 (18) 0.0497 (8) H34A 0.2325 0.9617 0.6588 0.060\* H34B 0.1600 1.0503 0.6006 0.060\* C35 0.0569 (3) 0.8342 (2) 0.65497 (18) 0.0420 (7) H35A 0.0957 0.8376 0.7042 0.050\* C36 −0.0453 (3) 0.7596 (2) 0.64655 (17) 0.0379 (7) C37 −0.0930 (3) 0.6951 (2) 0.71012 (17) 0.0413 (7) H37A −0.0565 0.7003 0.7599 0.050\* C38 −0.1911 (3) 0.6244 (2) 0.70259 (17) 0.0412 (7) C39 −0.2429 (3) 0.6148 (3) 0.62893 (18) 0.0484 (8) H39A −0.3081 0.5641 0.6225 0.058\* C40 −0.1999 (3) 0.6784 (3) 0.56589 (18) 0.0491 (8) H40A −0.2370 0.6725 0.5164 0.059\* C41 −0.1031 (3) 0.7508 (3) 0.57366 (17) 0.0436 (8) C42 −0.3878 (3) 0.4641 (2) 0.83188 (18) 0.0424 (7) C43 −0.3285 (3) 0.4523 (2) 0.90327 (18) 0.0476 (8) H43A −0.2474 0.4822 0.9091 0.057\* C44 −0.3864 (3) 0.3974 (2) 0.96617 (19) 0.0484 (8) H44A −0.3451 0.3892 1.0150 0.058\* C45 −0.5053 (3) 0.3540 (2) 0.95763 (18) 0.0437 (8) C46 −0.5658 (3) 0.3664 (2) 0.88634 (18) 0.0466 (8) H46A −0.6480 0.3384 0.8807 0.056\* C47 −0.5060 (3) 0.4197 (2) 0.82372 (18) 0.0445 (8) H47A −0.5461 0.4260 0.7745 0.053\* C48 −0.5098 (3) 0.2782 (3) 1.08894 (19) 0.0662 (10) H48A −0.5668 0.2386 1.1255 0.099\* H48B −0.4884 0.3486 1.1097 0.099\* H48C −0.4322 0.2331 1.0819 0.099\* H1 0.308 (4) 0.816 (3) 0.787 (2) 0.103 (14)\* H2 0.392 (4) 0.573 (3) 0.519 (2) 0.100 (14)\* H3 0.005 (4) 0.867 (3) 0.529 (2) 0.103 (13)\* ------ --------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2158 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0573 (14) 0.0363 (13) 0.0490 (14) −0.0036 (11) 0.0010 (11) −0.0046 (10) O2 0.0392 (12) 0.0557 (14) 0.0529 (13) −0.0072 (11) 0.0028 (10) 0.0031 (11) O3 0.0633 (15) 0.0720 (16) 0.0368 (13) −0.0080 (13) −0.0009 (11) 0.0047 (11) O4 0.0704 (17) 0.0500 (15) 0.110 (2) −0.0222 (14) −0.0129 (15) 0.0250 (14) O5 0.0429 (13) 0.0481 (14) 0.0844 (17) −0.0111 (11) 0.0115 (12) −0.0067 (12) O6 0.0515 (13) 0.0604 (15) 0.0587 (15) −0.0159 (12) −0.0064 (11) 0.0113 (12) N1 0.0423 (14) 0.0430 (16) 0.0467 (16) −0.0039 (13) 0.0005 (12) 0.0069 (12) N2 0.0393 (14) 0.0391 (15) 0.0419 (15) −0.0059 (12) −0.0013 (11) 0.0052 (12) N3 0.0450 (16) 0.0394 (16) 0.0443 (16) −0.0041 (14) −0.0011 (12) 0.0046 (12) N4 0.0435 (15) 0.0435 (16) 0.0435 (16) −0.0001 (13) 0.0017 (12) 0.0037 (13) N5 0.0510 (16) 0.0430 (15) 0.0435 (16) −0.0004 (13) 0.0029 (12) 0.0005 (13) N6 0.0430 (14) 0.0414 (16) 0.0436 (16) 0.0015 (13) −0.0007 (12) −0.0027 (13) N7 0.0406 (15) 0.0424 (16) 0.0421 (15) −0.0036 (13) −0.0012 (11) 0.0010 (12) N8 0.0380 (14) 0.0400 (16) 0.0494 (16) −0.0053 (12) 0.0022 (11) 0.0001 (12) N9 0.0362 (14) 0.0437 (16) 0.0563 (17) 0.0001 (13) 0.0005 (12) 0.0020 (13) N10 0.0423 (15) 0.0434 (16) 0.0563 (17) −0.0005 (13) 0.0014 (13) −0.0011 (13) C1 0.0449 (18) 0.0451 (19) 0.0500 (19) −0.0146 (16) 0.0008 (15) 0.0068 (15) C2 0.0349 (16) 0.0456 (19) 0.0502 (19) −0.0052 (15) 0.0028 (14) 0.0069 (15) C3 0.0391 (16) 0.0346 (17) 0.0362 (17) −0.0026 (14) −0.0023 (13) 0.0011 (13) C4 0.0361 (16) 0.0338 (17) 0.0363 (17) −0.0036 (14) −0.0021 (13) 0.0022 (14) C5 0.0417 (17) 0.0373 (18) 0.0386 (17) −0.0049 (14) −0.0070 (14) 0.0043 (14) C6 0.0416 (17) 0.0457 (18) 0.0383 (17) −0.0076 (15) −0.0042 (14) 0.0091 (15) C7 0.0518 (19) 0.053 (2) 0.0372 (18) 0.0022 (17) 0.0066 (15) 0.0029 (16) C8 0.058 (2) 0.0410 (19) 0.0384 (18) −0.0017 (16) 0.0006 (15) −0.0017 (15) C9 0.0428 (17) 0.0359 (18) 0.0363 (17) −0.0045 (15) −0.0029 (14) 0.0027 (14) C10 0.0433 (18) 0.0397 (19) 0.0377 (18) −0.0064 (16) −0.0026 (14) 0.0071 (14) C11 0.0462 (19) 0.043 (2) 0.058 (2) 0.0001 (17) 0.0081 (16) −0.0002 (16) C12 0.060 (2) 0.037 (2) 0.075 (2) −0.0009 (17) 0.0048 (19) −0.0001 (17) C13 0.054 (2) 0.043 (2) 0.054 (2) −0.0083 (18) −0.0071 (16) 0.0164 (16) C14 0.0422 (18) 0.068 (2) 0.044 (2) −0.0058 (19) 0.0040 (15) 0.0052 (17) C15 0.0526 (19) 0.045 (2) 0.0428 (19) −0.0007 (16) −0.0025 (15) −0.0013 (15) C16 0.070 (3) 0.095 (3) 0.110 (3) −0.047 (3) −0.019 (2) 0.045 (3) C17 0.0464 (18) 0.052 (2) 0.046 (2) −0.0053 (16) 0.0106 (15) 0.0057 (16) C18 0.0484 (18) 0.053 (2) 0.0441 (19) −0.0024 (17) −0.0008 (15) 0.0067 (16) C19 0.0408 (17) 0.0424 (17) 0.0440 (18) −0.0059 (15) 0.0021 (14) −0.0053 (13) C20 0.0423 (17) 0.0392 (16) 0.0362 (17) −0.0047 (15) 0.0038 (13) −0.0053 (12) C21 0.0374 (17) 0.0362 (18) 0.0443 (18) 0.0005 (14) 0.0031 (13) −0.0066 (14) C22 0.0361 (17) 0.0387 (18) 0.0442 (18) −0.0038 (15) 0.0024 (14) −0.0021 (14) C23 0.0442 (18) 0.0394 (18) 0.0398 (18) −0.0033 (15) −0.0009 (14) −0.0015 (14) C24 0.0404 (17) 0.0441 (19) 0.0394 (18) 0.0001 (15) −0.0052 (14) −0.0016 (15) C25 0.0413 (18) 0.0425 (19) 0.0350 (17) −0.0046 (15) −0.0008 (13) −0.0070 (14) C26 0.0352 (17) 0.0413 (19) 0.0447 (18) −0.0060 (15) 0.0000 (14) 0.0003 (15) C27 0.0396 (18) 0.041 (2) 0.084 (3) −0.0007 (16) 0.0092 (17) −0.0078 (18) C28 0.0412 (19) 0.040 (2) 0.092 (3) −0.0058 (17) 0.0081 (18) −0.0106 (18) C29 0.0367 (17) 0.043 (2) 0.056 (2) −0.0108 (16) 0.0003 (15) −0.0011 (16) C30 0.0397 (17) 0.0408 (19) 0.0478 (19) 0.0021 (15) 0.0069 (14) −0.0010 (15) C31 0.0443 (18) 0.0352 (17) 0.0441 (18) −0.0046 (15) 0.0001 (14) 0.0022 (14) C32 0.054 (2) 0.062 (3) 0.100 (3) −0.010 (2) 0.029 (2) −0.003 (2) C33 0.052 (2) 0.044 (2) 0.057 (2) −0.0073 (17) −0.0002 (16) 0.0115 (16) C34 0.0513 (19) 0.0378 (19) 0.059 (2) 0.0016 (16) −0.0034 (16) 0.0024 (16) C35 0.0391 (17) 0.0427 (19) 0.0432 (19) 0.0066 (15) −0.0024 (14) 0.0002 (15) C36 0.0352 (16) 0.0368 (17) 0.0410 (18) 0.0071 (14) 0.0008 (13) −0.0004 (14) C37 0.0365 (16) 0.0456 (19) 0.0416 (18) 0.0012 (15) −0.0070 (13) 0.0000 (15) C38 0.0345 (16) 0.0414 (18) 0.0465 (19) 0.0064 (15) 0.0035 (14) 0.0016 (15) C39 0.0434 (18) 0.048 (2) 0.055 (2) −0.0021 (16) 0.0027 (16) −0.0147 (17) C40 0.0484 (19) 0.061 (2) 0.0383 (18) 0.0025 (17) −0.0013 (15) −0.0097 (16) C41 0.0406 (17) 0.050 (2) 0.0397 (19) 0.0070 (16) 0.0021 (14) −0.0007 (15) C42 0.0376 (17) 0.0347 (18) 0.054 (2) 0.0017 (14) 0.0000 (15) 0.0007 (15) C43 0.0365 (17) 0.0442 (19) 0.062 (2) 0.0005 (15) −0.0075 (16) 0.0000 (16) C44 0.0391 (18) 0.051 (2) 0.055 (2) −0.0069 (16) −0.0086 (15) 0.0059 (16) C45 0.0391 (17) 0.0350 (18) 0.057 (2) −0.0041 (15) 0.0034 (15) 0.0004 (15) C46 0.0372 (17) 0.0437 (19) 0.059 (2) −0.0045 (15) −0.0053 (16) −0.0011 (16) C47 0.0399 (17) 0.0423 (19) 0.051 (2) 0.0005 (15) −0.0059 (15) −0.0035 (15) C48 0.066 (2) 0.072 (3) 0.060 (2) −0.018 (2) −0.0120 (19) 0.0141 (19) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3374 .table-wrap} ------------------- ----------- ------------------- ----------- O1---C9 1.355 (3) C17---C18 1.509 (4) O1---H1 0.98 (4) C17---H17A 0.9900 O2---C25 1.284 (3) C17---H17B 0.9900 O3---C41 1.355 (3) C18---H18A 0.9900 O3---H3 1.07 (4) C18---H18B 0.9900 O4---C13 1.371 (3) C19---C20 1.424 (4) O4---C16 1.425 (4) C19---H19A 0.9500 O5---C29 1.378 (3) C20---C21 1.411 (4) O5---C32 1.416 (4) C20---C25 1.444 (4) O6---C45 1.366 (3) C21---C22 1.366 (4) O6---C48 1.423 (3) C21---H21A 0.9500 N1---C1 1.459 (3) C22---C23 1.414 (4) N1---C33 1.467 (4) C23---C24 1.357 (4) N1---C17 1.467 (4) C23---H23A 0.9500 N2---C3 1.288 (3) C24---C25 1.428 (4) N2---C2 1.457 (3) C24---H24A 0.9500 N3---C19 1.294 (3) C26---C31 1.377 (4) N3---C18 1.457 (4) C26---C27 1.385 (4) N3---H2 1.02 (4) C27---C28 1.373 (4) N4---C35 1.281 (3) C27---H27A 0.9500 N4---C34 1.454 (3) C28---C29 1.372 (4) N5---N6 1.245 (3) C28---H28A 0.9500 N5---C6 1.429 (3) C29---C30 1.388 (4) N6---C10 1.447 (3) C30---C31 1.385 (4) N7---N8 1.266 (3) C30---H30A 0.9500 N7---C22 1.417 (3) C31---H31A 0.9500 N8---C26 1.425 (3) C32---H32A 0.9800 N9---N10 1.266 (3) C32---H32B 0.9800 N9---C38 1.430 (4) C32---H32C 0.9800 N10---C42 1.424 (4) C33---C34 1.514 (4) C1---C2 1.518 (4) C33---H33A 0.9900 C1---H1A 0.9900 C33---H33B 0.9900 C1---H1B 0.9900 C34---H34A 0.9900 C2---H2A 0.9900 C34---H34B 0.9900 C2---H2B 0.9900 C35---C36 1.445 (4) C3---C4 1.456 (4) C35---H35A 0.9500 C3---H3A 0.9500 C36---C37 1.403 (4) C4---C5 1.395 (3) C36---C41 1.414 (4) C4---C9 1.412 (4) C37---C38 1.380 (4) C5---C6 1.395 (4) C37---H37A 0.9500 C5---H5A 0.9500 C38---C39 1.400 (4) C6---C7 1.393 (4) C39---C40 1.373 (4) C7---C8 1.378 (4) C39---H39A 0.9500 C7---H7A 0.9500 C40---C41 1.382 (4) C8---C9 1.384 (4) C40---H40A 0.9500 C8---H8A 0.9500 C42---C43 1.383 (4) C10---C11 1.366 (4) C42---C47 1.388 (4) C10---C15 1.371 (4) C43---C44 1.382 (4) C11---C12 1.376 (4) C43---H43A 0.9500 C11---H11A 0.9500 C44---C45 1.390 (4) C12---C13 1.379 (4) C44---H44A 0.9500 C12---H12A 0.9500 C45---C46 1.388 (4) C13---C14 1.381 (4) C46---C47 1.379 (4) C14---C15 1.388 (4) C46---H46A 0.9500 C14---H14A 0.9500 C47---H47A 0.9500 C15---H15A 0.9500 C48---H48A 0.9800 C16---H16A 0.9800 C48---H48B 0.9800 C16---H16B 0.9800 C48---H48C 0.9800 C16---H16C 0.9800 C9---O1---H1 102 (2) C22---C21---H21A 119.3 C41---O3---H3 107 (2) C20---C21---H21A 119.3 C13---O4---C16 117.4 (3) C21---C22---C23 118.8 (3) C29---O5---C32 117.3 (2) C21---C22---N7 117.9 (3) C45---O6---C48 117.7 (2) C23---C22---N7 123.2 (3) C1---N1---C33 112.3 (2) C24---C23---C22 121.7 (3) C1---N1---C17 113.5 (2) C24---C23---H23A 119.2 C33---N1---C17 112.8 (2) C22---C23---H23A 119.2 C3---N2---C2 119.8 (3) C23---C24---C25 121.5 (3) C19---N3---C18 124.2 (3) C23---C24---H24A 119.2 C19---N3---H2 111 (2) C25---C24---H24A 119.2 C18---N3---H2 124 (2) O2---C25---C24 121.2 (3) C35---N4---C34 120.9 (3) O2---C25---C20 122.4 (3) N6---N5---C6 113.1 (2) C24---C25---C20 116.4 (3) N5---N6---C10 113.6 (2) C31---C26---C27 118.7 (3) N8---N7---C22 113.0 (3) C31---C26---N8 125.4 (3) N7---N8---C26 114.7 (3) C27---C26---N8 115.8 (3) N10---N9---C38 113.0 (2) C28---C27---C26 121.3 (3) N9---N10---C42 114.6 (2) C28---C27---H27A 119.4 N1---C1---C2 111.9 (2) C26---C27---H27A 119.4 N1---C1---H1A 109.2 C29---C28---C27 119.7 (3) C2---C1---H1A 109.2 C29---C28---H28A 120.1 N1---C1---H1B 109.2 C27---C28---H28A 120.1 C2---C1---H1B 109.2 C28---C29---O5 116.0 (3) H1A---C1---H1B 107.9 C28---C29---C30 120.1 (3) N2---C2---C1 110.1 (2) O5---C29---C30 123.9 (3) N2---C2---H2A 109.6 C31---C30---C29 119.6 (3) C1---C2---H2A 109.6 C31---C30---H30A 120.2 N2---C2---H2B 109.6 C29---C30---H30A 120.2 C1---C2---H2B 109.6 C26---C31---C30 120.7 (3) H2A---C2---H2B 108.2 C26---C31---H31A 119.7 N2---C3---C4 120.8 (3) C30---C31---H31A 119.7 N2---C3---H3A 119.6 O5---C32---H32A 109.5 C4---C3---H3A 119.6 O5---C32---H32B 109.5 C5---C4---C9 119.0 (2) H32A---C32---H32B 109.5 C5---C4---C3 120.7 (3) O5---C32---H32C 109.5 C9---C4---C3 120.3 (2) H32A---C32---H32C 109.5 C4---C5---C6 120.1 (3) H32B---C32---H32C 109.5 C4---C5---H5A 120.0 N1---C33---C34 112.5 (2) C6---C5---H5A 120.0 N1---C33---H33A 109.1 C7---C6---C5 119.9 (3) C34---C33---H33A 109.1 C7---C6---N5 115.3 (3) N1---C33---H33B 109.1 C5---C6---N5 124.9 (3) C34---C33---H33B 109.1 C8---C7---C6 120.6 (3) H33A---C33---H33B 107.8 C8---C7---H7A 119.7 N4---C34---C33 109.4 (2) C6---C7---H7A 119.7 N4---C34---H34A 109.8 C7---C8---C9 120.0 (3) C33---C34---H34A 109.8 C7---C8---H8A 120.0 N4---C34---H34B 109.8 C9---C8---H8A 120.0 C33---C34---H34B 109.8 O1---C9---C8 118.7 (3) H34A---C34---H34B 108.2 O1---C9---C4 120.9 (2) N4---C35---C36 121.0 (3) C8---C9---C4 120.5 (3) N4---C35---H35A 119.5 C11---C10---C15 119.3 (3) C36---C35---H35A 119.5 C11---C10---N6 115.4 (3) C37---C36---C41 117.3 (3) C15---C10---N6 125.4 (3) C37---C36---C35 121.8 (3) C10---C11---C12 121.3 (3) C41---C36---C35 120.9 (3) C10---C11---H11A 119.3 C38---C37---C36 122.0 (3) C12---C11---H11A 119.3 C38---C37---H37A 119.0 C11---C12---C13 119.3 (3) C36---C37---H37A 119.0 C11---C12---H12A 120.4 C37---C38---C39 119.0 (3) C13---C12---H12A 120.4 C37---C38---N9 116.7 (3) O4---C13---C12 114.4 (3) C39---C38---N9 124.2 (3) O4---C13---C14 125.3 (3) C40---C39---C38 120.3 (3) C12---C13---C14 120.3 (3) C40---C39---H39A 119.9 C13---C14---C15 119.1 (3) C38---C39---H39A 119.9 C13---C14---H14A 120.5 C39---C40---C41 120.7 (3) C15---C14---H14A 120.5 C39---C40---H40A 119.6 C10---C15---C14 120.8 (3) C41---C40---H40A 119.6 C10---C15---H15A 119.6 O3---C41---C40 118.9 (3) C14---C15---H15A 119.6 O3---C41---C36 120.5 (3) O4---C16---H16A 109.5 C40---C41---C36 120.6 (3) O4---C16---H16B 109.5 C43---C42---C47 119.4 (3) H16A---C16---H16B 109.5 C43---C42---N10 125.8 (3) O4---C16---H16C 109.5 C47---C42---N10 114.8 (3) H16A---C16---H16C 109.5 C44---C43---C42 120.5 (3) H16B---C16---H16C 109.5 C44---C43---H43A 119.8 N1---C17---C18 112.3 (2) C42---C43---H43A 119.8 N1---C17---H17A 109.1 C43---C44---C45 119.7 (3) C18---C17---H17A 109.1 C43---C44---H44A 120.1 N1---C17---H17B 109.1 C45---C44---H44A 120.1 C18---C17---H17B 109.1 O6---C45---C46 115.5 (2) H17A---C17---H17B 107.9 O6---C45---C44 124.4 (3) N3---C18---C17 110.9 (2) C46---C45---C44 120.1 (3) N3---C18---H18A 109.5 C47---C46---C45 119.5 (3) C17---C18---H18A 109.5 C47---C46---H46A 120.2 N3---C18---H18B 109.5 C45---C46---H46A 120.2 C17---C18---H18B 109.5 C46---C47---C42 120.7 (3) H18A---C18---H18B 108.1 C46---C47---H47A 119.6 N3---C19---C20 122.2 (3) C42---C47---H47A 119.6 N3---C19---H19A 118.9 O6---C48---H48A 109.5 C20---C19---H19A 118.9 O6---C48---H48B 109.5 C21---C20---C19 120.0 (3) H48A---C48---H48B 109.5 C21---C20---C25 120.0 (3) O6---C48---H48C 109.5 C19---C20---C25 119.8 (3) H48A---C48---H48C 109.5 C22---C21---C20 121.4 (3) H48B---C48---H48C 109.5 ------------------- ----------- ------------------- ----------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4793 .table-wrap} ----------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O3---H3···N4 1.07 (4) 1.58 (4) 2.543 (3) 146 (3) O1---H1···N2 0.98 (4) 1.61 (4) 2.534 (3) 157 (3) N3---H2···O2 1.02 (4) 1.71 (4) 2.585 (3) 142 (3) N3---H2···O2^i^ 1.02 (4) 2.48 (4) 3.155 (3) 123 (3) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- ---------- ---------- ----------- ------------- O3---H3⋯N4 1.07 (4) 1.58 (4) 2.543 (3) 146 (3) O1---H1⋯N2 0.98 (4) 1.61 (4) 2.534 (3) 157 (3) N3---H2⋯O2 1.02 (4) 1.71 (4) 2.585 (3) 142 (3) N3---H2⋯O2^i^ 1.02 (4) 2.48 (4) 3.155 (3) 123 (3) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.785910

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052149/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o606", "authors": [ { "first": "Sadegh", "last": "Salehzadeh" }, { "first": "Mahsa", "last": "Mahdavian" }, { "first": "Mehdi", "last": "Khalaj" } ] }

PMC3052150

Related literature {#sec1} ================== For general background to aroylhydrazines and their metal complexes, see: Cariati *et al.* (2002[@bb2]); Chen *et al.* (2010[@bb4]); Fun *et al.* (1996[@bb5]); Liao *et al.* (2000[@bb7]); Liu & Gao (1998[@bb8]); Lu *et al.* (1996[@bb9]); Tai *et al.* (2003[@bb13]); Xue & Liu (2006[@bb16]); Yang & Pan (2004[@bb17]). For related structures, see: Chen & Liu (2006[@bb3]); Tan *et al.* (2010[@bb14]); Wu & Liu (2004[@bb15]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Co(C~15~H~12~N~3~O~4~)~2~Cl(C~6~H~7~N)\]*M* *~r~* = 784.06Triclinic,*a* = 10.530 (2) Å*b* = 14.028 (3) Å*c* = 14.794 (3) Åα = 62.203 (3)°β = 85.669 (3)°γ = 72.275 (3)°*V* = 1835.6 (7) Å^3^*Z* = 2Mo *K*α radiationμ = 0.60 mm^−1^*T* = 293 K0.12 × 0.10 × 0.08 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID diffractometerAbsorption correction: multi-scan (*ABSCOR*; Higashi, 1995[@bb6]) *T* ~min~ = 0.931, *T* ~max~ = 0.95412688 measured reflections6308 independent reflections3144 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.064 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.063*wR*(*F* ^2^) = 0.157*S* = 0.946308 reflections478 parametersH-atom parameters constrainedΔρ~max~ = 0.73 e Å^−3^Δρ~min~ = −0.29 e Å^−3^ {#d5e483} Data collection: *RAPID-AUTO* (Rigaku, 1998[@bb10]); cell refinement: *RAPID-AUTO*; data reduction: *CrystalStructure* (Rigaku/MSC, 2002[@bb11]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb12]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb12]); molecular graphics: *DIAMOND* (Brandenburg, 1999[@bb1]); software used to prepare material for publication: *SHELXTL* (Sheldrick, 2008[@bb12]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811003321/hy2400sup1.cif](http://dx.doi.org/10.1107/S1600536811003321/hy2400sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003321/hy2400Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003321/hy2400Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hy2400&file=hy2400sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hy2400sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hy2400&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HY2400](http://scripts.iucr.org/cgi-bin/sendsup?hy2400)). The authors acknowledge financial support from the Young Teachers' Foundation of Fujian Agriculture and Forest University (grant No. 08B10). Comment ======= Recently, much attention has been paid to the chemistry of aroylhydrazines and their complexes with metal ions (Cariati *et al.*, 2002; Chen *et al.*, 2010; Liu & Gao 1998; Tai *et al.*, 2003; Xue & Liu, 2006). These compounds can serve as potential chelating agents (Fun *et al.*, 1996; Lu *et al.*, 1996) and possess biological activity (Liao *et al.*, 2000; Yang & Pan, 2004). Here we report the synthesis and crystal structure of the title compound. As shown in Fig. 1, the Co^III^ ion exists in a distorted octahedral N~3~O~2~Cl coordination geometry. The equatorial plane is defined by three donor atoms (O3, O7 and N3) from two hydrazine ligands and N7 atom from a 4-methylpyridine ligand, with an r.m.s. deviation of 0.0305 Å from the mean plane. The axial sites are occupied by N6 of one hydrazine ligand and Cl1. The Co^III^ ion is displaced towards the axial Cl1 atom by 0.038 (2)Å from the equatorial plane. Bond distances (Table 1) and bond angles around Co1 atom are compared with those in the reported cobalt complexes (Chen & Liu, 2006; Tan *et al.*, 2010; Wu & Liu, 2004). Experimental {#experimental} ============ The hydrazine ligand (HL) was prepared by the reaction of *o*-methoxybenzaldehyde and *p*-nitrobenzoylhydrazine in a molar ratio of 1:1 under reflux in ethanol for 3 h. The yellow product obtained on cooling was recrystallized from methanol. To HL (1 mmol) in DMF (5 ml) was added an equimolar amount of CoCl~2~ in methanol (5 ml). After stirring for 15 min, 0.2 ml *p*-methylpyridine was added to the solution. The resulting mixture was stirred at room temperature for an additional period of 1 h and then filtered. Brown prism-shaped crystals were obtained from the solution after two weeks. Analysis, calculated for C~36~H~31~ClCoN~7~O~8~: C 54.98, H 4.01, N 12.43%; found: C 55.10, H 3.95, N 12.50%. Refinement {#refinement} ========== H atoms were placed at calculated positions and treated as riding on their parent atoms, with C---H = 0.93 (CH) and 0.96 (CH~3~) Å and with *U*~iso~(H) = 1.2(1.5 for methyl)*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids. ::: ![](e-67-0m293-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e162 .table-wrap} -------------------------------------------- --------------------------------------- \[Co(C~15~H~12~N~3~O~4~)~2~Cl(C~6~H~7~N)\] *Z* = 2 *M~r~* = 784.06 *F*(000) = 808 Triclinic, *P*1 *D*~x~ = 1.419 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.530 (2) Å Cell parameters from 3144 reflections *b* = 14.028 (3) Å θ = 2.0--25.0° *c* = 14.794 (3) Å µ = 0.60 mm^−1^ α = 62.203 (3)° *T* = 293 K β = 85.669 (3)° Prism, brown γ = 72.275 (3)° 0.12 × 0.10 × 0.08 mm *V* = 1835.6 (7) Å^3^ -------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e309 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID diffractometer 6308 independent reflections Radiation source: rotation anode 3144 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.064 ω scans θ~max~ = 25.0°, θ~min~ = 2.0° Absorption correction: multi-scan (*ABSCOR*; Higashi, 1995) *h* = −12→12 *T*~min~ = 0.931, *T*~max~ = 0.954 *k* = −16→14 12688 measured reflections *l* = −17→17 ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e423 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.063 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.157 H-atom parameters constrained *S* = 0.94 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0697*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 6308 reflections (Δ/σ)~max~ = 0.001 478 parameters Δρ~max~ = 0.73 e Å^−3^ 0 restraints Δρ~min~ = −0.29 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e579 .table-wrap} ------ -------------- --------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Co1 0.37392 (7) 0.10485 (6) 0.26462 (5) 0.0404 (2) Cl1 0.56482 (14) −0.04002 (12) 0.31714 (10) 0.0594 (4) O1 0.7244 (6) 0.5110 (5) 0.4349 (4) 0.128 (2) O2 0.6499 (5) 0.4123 (4) 0.5748 (4) 0.1036 (16) O3 0.4228 (3) 0.1646 (3) 0.3428 (2) 0.0454 (9) O4 0.4954 (4) 0.2019 (3) −0.1040 (3) 0.0698 (11) O5 −0.0960 (7) 0.1461 (6) −0.2398 (5) 0.145 (3) O6 0.0849 (7) 0.0090 (6) −0.2185 (5) 0.134 (2) O7 0.3203 (3) 0.0612 (3) 0.1748 (2) 0.0427 (8) O8 0.1019 (4) 0.4428 (4) 0.3188 (4) 0.0871 (14) N1 0.6684 (6) 0.4408 (5) 0.4845 (4) 0.0769 (16) N2 0.5113 (4) 0.2641 (4) 0.1940 (3) 0.0493 (11) N3 0.4654 (4) 0.2001 (3) 0.1626 (3) 0.0439 (10) N4 0.0158 (9) 0.0820 (8) −0.1975 (5) 0.103 (2) N5 0.1387 (4) 0.2219 (4) 0.1352 (3) 0.0468 (11) N6 0.2066 (4) 0.2250 (4) 0.2103 (3) 0.0435 (11) N7 0.2841 (4) 0.0135 (3) 0.3809 (3) 0.0409 (10) C1 0.5279 (5) 0.2942 (4) 0.3384 (4) 0.0439 (13) C2 0.4979 (5) 0.2702 (4) 0.4383 (4) 0.0496 (14) H2B 0.4478 0.2211 0.4725 0.060\* C3 0.5420 (5) 0.3184 (5) 0.4871 (4) 0.0558 (15) H3A 0.5225 0.3027 0.5540 0.067\* C4 0.6163 (6) 0.3909 (5) 0.4334 (4) 0.0527 (14) C5 0.6444 (6) 0.4179 (5) 0.3343 (4) 0.0570 (15) H5B 0.6917 0.4693 0.2996 0.068\* C6 0.6020 (5) 0.3684 (5) 0.2872 (4) 0.0543 (15) H6A 0.6227 0.3843 0.2204 0.065\* C7 0.4835 (5) 0.2372 (4) 0.2892 (4) 0.0425 (12) C8 0.4890 (5) 0.2082 (4) 0.0719 (3) 0.0481 (14) H8A 0.4581 0.1616 0.0565 0.058\* C9 0.5563 (5) 0.2793 (5) −0.0091 (4) 0.0532 (14) C10 0.5598 (6) 0.2723 (5) −0.1022 (4) 0.0565 (15) C11 0.6177 (6) 0.3369 (6) −0.1841 (4) 0.0749 (19) H11A 0.6169 0.3330 −0.2450 0.090\* C12 0.6774 (7) 0.4083 (7) −0.1765 (5) 0.090 (2) H12A 0.7174 0.4516 −0.2324 0.108\* C13 0.6782 (7) 0.4160 (6) −0.0861 (5) 0.091 (2) H13A 0.7186 0.4641 −0.0813 0.109\* C14 0.6187 (7) 0.3515 (6) −0.0040 (4) 0.0764 (19) H14A 0.6200 0.3562 0.0566 0.092\* C15 0.4867 (8) 0.1978 (6) −0.1990 (5) 0.100 (2) H15A 0.4389 0.1461 −0.1904 0.151\* H15B 0.5752 0.1726 −0.2179 0.151\* H15C 0.4403 0.2718 −0.2520 0.151\* C16 0.1556 (6) 0.1187 (4) 0.0397 (4) 0.0505 (14) C17 0.2401 (6) 0.0517 (5) 0.0012 (4) 0.0685 (17) H17A 0.3286 0.0142 0.0279 0.082\* C18 0.1936 (7) 0.0404 (6) −0.0764 (5) 0.0777 (19) H18A 0.2501 −0.0052 −0.1019 0.093\* C19 0.0650 (8) 0.0960 (6) −0.1154 (5) 0.0727 (19) C20 −0.0214 (7) 0.1636 (6) −0.0792 (5) 0.0756 (19) H20A −0.1092 0.2016 −0.1075 0.091\* C21 0.0238 (6) 0.1743 (5) −0.0009 (4) 0.0667 (17) H21A −0.0339 0.2189 0.0250 0.080\* C22 0.2089 (6) 0.1335 (5) 0.1225 (4) 0.0441 (13) C23 0.1556 (6) 0.3046 (5) 0.2358 (4) 0.0490 (14) H23A 0.2047 0.2987 0.2888 0.059\* C24 0.0358 (5) 0.4014 (5) 0.1967 (4) 0.0472 (13) C25 0.0126 (7) 0.4728 (5) 0.2425 (5) 0.0591 (16) C26 −0.0976 (8) 0.5700 (6) 0.2070 (6) 0.077 (2) H26A −0.1120 0.6183 0.2359 0.093\* C27 −0.1858 (7) 0.5946 (6) 0.1285 (6) 0.0777 (19) H27A −0.2587 0.6600 0.1049 0.093\* C28 −0.1675 (7) 0.5250 (6) 0.0855 (5) 0.0713 (18) H28A −0.2287 0.5417 0.0341 0.086\* C29 −0.0568 (6) 0.4283 (5) 0.1188 (4) 0.0626 (16) H29A −0.0442 0.3811 0.0888 0.075\* C30 0.0780 (8) 0.5059 (8) 0.3742 (7) 0.133 (3) H30A 0.1499 0.4739 0.4260 0.199\* H30B −0.0047 0.5033 0.4059 0.199\* H30C 0.0728 0.5831 0.3280 0.199\* C31 0.2877 (5) 0.0132 (5) 0.4712 (4) 0.0539 (15) H31A 0.3369 0.0541 0.4792 0.065\* C32 0.2223 (5) −0.0445 (5) 0.5528 (4) 0.0597 (16) H32A 0.2257 −0.0399 0.6133 0.072\* C33 0.1520 (5) −0.1088 (5) 0.5453 (5) 0.0617 (16) C34 0.1506 (6) −0.1112 (5) 0.4531 (5) 0.0687 (18) H34A 0.1052 −0.1541 0.4445 0.082\* C35 0.2171 (6) −0.0495 (5) 0.3735 (4) 0.0632 (16) H35A 0.2149 −0.0522 0.3121 0.076\* C36 0.0757 (6) −0.1717 (5) 0.6334 (5) 0.088 (2) H36A 0.0882 −0.1598 0.6905 0.131\* H36B 0.1087 −0.2512 0.6534 0.131\* H36C −0.0178 −0.1439 0.6116 0.131\* ------ -------------- --------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1730 .table-wrap} ----- ------------ ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Co1 0.0446 (5) 0.0485 (5) 0.0383 (4) −0.0235 (4) 0.0059 (3) −0.0229 (3) Cl1 0.0574 (9) 0.0657 (10) 0.0590 (9) −0.0195 (8) 0.0010 (7) −0.0313 (8) O1 0.187 (6) 0.188 (6) 0.110 (4) −0.154 (5) 0.063 (4) −0.097 (4) O2 0.162 (5) 0.130 (4) 0.067 (3) −0.087 (4) 0.019 (3) −0.060 (3) O3 0.053 (2) 0.058 (2) 0.0385 (19) −0.032 (2) 0.0124 (16) −0.0246 (17) O4 0.097 (3) 0.080 (3) 0.047 (2) −0.029 (3) 0.009 (2) −0.041 (2) O5 0.149 (6) 0.187 (6) 0.124 (5) −0.029 (5) −0.057 (4) −0.095 (5) O6 0.157 (6) 0.192 (7) 0.131 (5) −0.073 (5) 0.017 (4) −0.127 (5) O7 0.045 (2) 0.047 (2) 0.043 (2) −0.0155 (19) −0.0015 (17) −0.0251 (17) O8 0.073 (3) 0.118 (4) 0.117 (4) −0.027 (3) 0.008 (3) −0.094 (3) N1 0.102 (4) 0.101 (4) 0.063 (4) −0.055 (4) 0.018 (3) −0.054 (3) N2 0.065 (3) 0.057 (3) 0.044 (3) −0.035 (3) 0.014 (2) −0.030 (2) N3 0.055 (3) 0.047 (3) 0.039 (2) −0.022 (2) 0.005 (2) −0.024 (2) N4 0.125 (7) 0.135 (7) 0.074 (4) −0.060 (6) −0.016 (4) −0.053 (5) N5 0.048 (3) 0.050 (3) 0.047 (3) −0.015 (2) −0.001 (2) −0.026 (2) N6 0.049 (3) 0.048 (3) 0.037 (2) −0.021 (2) 0.005 (2) −0.019 (2) N7 0.040 (3) 0.045 (3) 0.040 (2) −0.018 (2) 0.0019 (19) −0.018 (2) C1 0.048 (3) 0.051 (3) 0.042 (3) −0.024 (3) 0.007 (2) −0.025 (3) C2 0.063 (4) 0.050 (3) 0.045 (3) −0.031 (3) 0.016 (3) −0.023 (3) C3 0.079 (4) 0.072 (4) 0.042 (3) −0.040 (3) 0.018 (3) −0.038 (3) C4 0.072 (4) 0.060 (4) 0.045 (3) −0.035 (3) 0.007 (3) −0.031 (3) C5 0.075 (4) 0.067 (4) 0.048 (3) −0.043 (3) 0.016 (3) −0.030 (3) C6 0.070 (4) 0.068 (4) 0.046 (3) −0.041 (3) 0.018 (3) −0.034 (3) C7 0.050 (3) 0.045 (3) 0.035 (3) −0.022 (3) 0.009 (2) −0.018 (2) C8 0.055 (3) 0.061 (4) 0.036 (3) −0.024 (3) 0.009 (3) −0.026 (3) C9 0.062 (4) 0.061 (4) 0.038 (3) −0.020 (3) 0.009 (3) −0.024 (3) C10 0.057 (4) 0.060 (4) 0.041 (3) −0.008 (3) 0.003 (3) −0.020 (3) C11 0.075 (5) 0.103 (5) 0.041 (4) −0.026 (4) 0.016 (3) −0.030 (4) C12 0.078 (5) 0.113 (6) 0.055 (4) −0.041 (5) 0.027 (4) −0.017 (4) C13 0.111 (6) 0.111 (6) 0.073 (5) −0.074 (5) 0.036 (4) −0.041 (4) C14 0.111 (5) 0.099 (5) 0.053 (4) −0.076 (5) 0.030 (3) −0.038 (4) C15 0.139 (7) 0.122 (6) 0.057 (4) −0.037 (5) 0.004 (4) −0.057 (4) C16 0.065 (4) 0.047 (3) 0.046 (3) −0.024 (3) −0.006 (3) −0.021 (3) C17 0.064 (4) 0.084 (5) 0.072 (4) −0.010 (4) −0.011 (3) −0.053 (4) C18 0.082 (5) 0.094 (5) 0.082 (5) −0.027 (4) 0.004 (4) −0.062 (4) C19 0.084 (5) 0.098 (5) 0.056 (4) −0.044 (5) −0.004 (4) −0.040 (4) C20 0.073 (5) 0.086 (5) 0.083 (5) −0.028 (4) −0.017 (4) −0.046 (4) C21 0.060 (4) 0.076 (5) 0.073 (4) −0.021 (4) −0.011 (3) −0.040 (4) C22 0.049 (4) 0.052 (4) 0.038 (3) −0.028 (3) 0.007 (3) −0.020 (3) C23 0.063 (4) 0.052 (4) 0.045 (3) −0.027 (3) 0.013 (3) −0.029 (3) C24 0.047 (4) 0.043 (3) 0.054 (3) −0.020 (3) 0.011 (3) −0.023 (3) C25 0.064 (4) 0.058 (4) 0.074 (4) −0.033 (4) 0.023 (4) −0.039 (4) C26 0.085 (5) 0.062 (5) 0.103 (6) −0.034 (4) 0.040 (5) −0.051 (4) C27 0.075 (5) 0.059 (5) 0.084 (5) −0.015 (4) 0.021 (4) −0.027 (4) C28 0.075 (5) 0.066 (5) 0.061 (4) −0.011 (4) 0.000 (3) −0.026 (4) C29 0.073 (4) 0.051 (4) 0.060 (4) −0.012 (4) 0.003 (3) −0.025 (3) C30 0.099 (6) 0.204 (9) 0.186 (9) −0.052 (6) 0.032 (6) −0.163 (8) C31 0.054 (4) 0.067 (4) 0.046 (3) −0.032 (3) 0.009 (3) −0.023 (3) C32 0.068 (4) 0.063 (4) 0.046 (3) −0.032 (4) 0.014 (3) −0.019 (3) C33 0.048 (4) 0.057 (4) 0.060 (4) −0.016 (3) 0.007 (3) −0.012 (3) C34 0.065 (4) 0.069 (4) 0.072 (4) −0.042 (4) 0.007 (3) −0.020 (4) C35 0.069 (4) 0.071 (4) 0.056 (4) −0.034 (4) −0.002 (3) −0.026 (3) C36 0.064 (4) 0.073 (5) 0.081 (4) −0.026 (4) 0.024 (3) −0.001 (4) ----- ------------ ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2805 .table-wrap} ---------------------- ------------- ----------------------- ------------ Co1---O3 1.887 (3) C12---H12A 0.9300 Co1---O7 1.882 (3) C13---C14 1.375 (7) Co1---N3 1.917 (4) C13---H13A 0.9300 Co1---N6 1.932 (4) C14---H14A 0.9300 Co1---N7 1.983 (4) C15---H15A 0.9600 Co1---Cl1 2.2472 (17) C15---H15B 0.9600 O1---N1 1.213 (6) C15---H15C 0.9600 O2---N1 1.221 (6) C16---C17 1.384 (7) O3---C7 1.281 (5) C16---C21 1.387 (7) O4---C10 1.367 (7) C16---C22 1.507 (7) O4---C15 1.445 (6) C17---C18 1.371 (7) O5---N4 1.235 (8) C17---H17A 0.9300 O6---N4 1.218 (8) C18---C19 1.353 (8) O7---C22 1.298 (6) C18---H18A 0.9300 O8---C25 1.346 (7) C19---C20 1.374 (9) O8---C30 1.424 (8) C20---C21 1.371 (7) N1---C4 1.467 (7) C20---H20A 0.9300 N2---C7 1.311 (6) C21---H21A 0.9300 N2---N3 1.395 (5) C23---C24 1.450 (7) N3---C8 1.304 (5) C23---H23A 0.9300 N4---C19 1.470 (8) C24---C29 1.400 (7) N5---C22 1.326 (6) C24---C25 1.408 (7) N5---N6 1.390 (5) C25---C26 1.393 (8) N6---C23 1.294 (6) C26---C27 1.387 (8) N7---C35 1.332 (6) C26---H26A 0.9300 N7---C31 1.336 (6) C27---C28 1.357 (9) C1---C2 1.388 (6) C27---H27A 0.9300 C1---C6 1.392 (6) C28---C29 1.394 (7) C1---C7 1.487 (7) C28---H28A 0.9300 C2---C3 1.374 (6) C29---H29A 0.9300 C2---H2B 0.9300 C30---H30A 0.9600 C3---C4 1.385 (7) C30---H30B 0.9600 C3---H3A 0.9300 C30---H30C 0.9600 C4---C5 1.365 (7) C31---C32 1.374 (6) C5---C6 1.362 (7) C31---H31A 0.9300 C5---H5B 0.9300 C32---C33 1.374 (7) C6---H6A 0.9300 C32---H32A 0.9300 C8---C9 1.456 (7) C33---C34 1.381 (8) C8---H8A 0.9300 C33---C36 1.524 (7) C9---C14 1.395 (7) C34---C35 1.385 (7) C9---C10 1.424 (7) C34---H34A 0.9300 C10---C11 1.364 (8) C35---H35A 0.9300 C11---C12 1.381 (9) C36---H36A 0.9600 C11---H11A 0.9300 C36---H36B 0.9600 C12---C13 1.393 (9) C36---H36C 0.9600 O7---Co1---O3 173.83 (15) C9---C14---H14A 119.1 O7---Co1---N3 93.09 (15) O4---C15---H15A 109.5 O3---Co1---N3 82.36 (15) O4---C15---H15B 109.5 O7---Co1---N6 82.64 (17) H15A---C15---H15B 109.5 O3---Co1---N6 93.15 (17) O4---C15---H15C 109.5 N3---Co1---N6 90.00 (16) H15A---C15---H15C 109.5 O7---Co1---N7 93.80 (15) H15B---C15---H15C 109.5 O3---Co1---N7 90.72 (15) C17---C16---C21 119.4 (5) N3---Co1---N7 173.07 (18) C17---C16---C22 119.7 (5) N6---Co1---N7 90.18 (16) C21---C16---C22 120.9 (5) O7---Co1---Cl1 91.96 (12) C18---C17---C16 120.2 (6) O3---Co1---Cl1 92.19 (11) C18---C17---H17A 119.9 N3---Co1---Cl1 89.84 (13) C16---C17---H17A 119.9 N6---Co1---Cl1 174.59 (14) C19---C18---C17 119.5 (6) N7---Co1---Cl1 90.63 (12) C19---C18---H18A 120.2 C7---O3---Co1 110.7 (3) C17---C18---H18A 120.2 C10---O4---C15 117.6 (5) C18---C19---C20 121.8 (6) C22---O7---Co1 110.5 (3) C18---C19---N4 119.1 (7) C25---O8---C30 119.5 (6) C20---C19---N4 119.2 (7) O1---N1---O2 122.7 (5) C21---C20---C19 119.1 (6) O1---N1---C4 118.8 (5) C21---C20---H20A 120.5 O2---N1---C4 118.4 (5) C19---C20---H20A 120.5 C7---N2---N3 108.7 (4) C20---C21---C16 120.1 (6) C8---N3---N2 119.5 (4) C20---C21---H21A 120.0 C8---N3---Co1 127.2 (4) C16---C21---H21A 120.0 N2---N3---Co1 113.3 (3) O7---C22---N5 124.6 (5) O6---N4---O5 124.6 (7) O7---C22---C16 118.5 (5) O6---N4---C19 119.2 (8) N5---C22---C16 116.9 (5) O5---N4---C19 116.2 (8) N6---C23---C24 131.7 (5) C22---N5---N6 108.6 (4) N6---C23---H23A 114.1 C23---N6---N5 119.3 (5) C24---C23---H23A 114.1 C23---N6---Co1 127.2 (4) C29---C24---C25 118.4 (6) N5---N6---Co1 113.5 (3) C29---C24---C23 125.6 (5) C35---N7---C31 116.7 (4) C25---C24---C23 116.0 (5) C35---N7---Co1 122.3 (4) O8---C25---C26 123.5 (6) C31---N7---Co1 121.0 (3) O8---C25---C24 116.7 (6) C2---C1---C6 119.7 (5) C26---C25---C24 119.8 (6) C2---C1---C7 119.2 (4) C27---C26---C25 120.0 (6) C6---C1---C7 121.2 (4) C27---C26---H26A 120.0 C3---C2---C1 120.4 (5) C25---C26---H26A 120.0 C3---C2---H2B 119.8 C28---C27---C26 121.1 (7) C1---C2---H2B 119.8 C28---C27---H27A 119.5 C2---C3---C4 117.9 (5) C26---C27---H27A 119.5 C2---C3---H3A 121.1 C27---C28---C29 119.8 (6) C4---C3---H3A 121.1 C27---C28---H28A 120.1 C5---C4---C3 122.8 (5) C29---C28---H28A 120.1 C5---C4---N1 118.1 (5) C28---C29---C24 120.9 (6) C3---C4---N1 119.1 (5) C28---C29---H29A 119.6 C6---C5---C4 118.9 (5) C24---C29---H29A 119.6 C6---C5---H5B 120.6 O8---C30---H30A 109.5 C4---C5---H5B 120.6 O8---C30---H30B 109.5 C5---C6---C1 120.4 (5) H30A---C30---H30B 109.5 C5---C6---H6A 119.8 O8---C30---H30C 109.5 C1---C6---H6A 119.8 H30A---C30---H30C 109.5 O3---C7---N2 124.8 (5) H30B---C30---H30C 109.5 O3---C7---C1 118.0 (4) N7---C31---C32 123.4 (5) N2---C7---C1 117.2 (4) N7---C31---H31A 118.3 N3---C8---C9 129.8 (5) C32---C31---H31A 118.3 N3---C8---H8A 115.1 C33---C32---C31 120.1 (5) C9---C8---H8A 115.1 C33---C32---H32A 119.9 C14---C9---C10 117.3 (5) C31---C32---H32A 119.9 C14---C9---C8 126.8 (5) C32---C33---C34 116.8 (5) C10---C9---C8 115.9 (5) C32---C33---C36 121.6 (6) C11---C10---O4 123.9 (6) C34---C33---C36 121.6 (6) C11---C10---C9 121.0 (6) C33---C34---C35 119.9 (6) O4---C10---C9 115.0 (5) C33---C34---H34A 120.1 C10---C11---C12 120.1 (6) C35---C34---H34A 120.1 C10---C11---H11A 120.0 N7---C35---C34 123.0 (5) C12---C11---H11A 120.0 N7---C35---H35A 118.5 C11---C12---C13 120.6 (6) C34---C35---H35A 118.5 C11---C12---H12A 119.7 C33---C36---H36A 109.5 C13---C12---H12A 119.7 C33---C36---H36B 109.5 C14---C13---C12 119.2 (6) H36A---C36---H36B 109.5 C14---C13---H13A 120.4 C33---C36---H36C 109.5 C12---C13---H13A 120.4 H36A---C36---H36C 109.5 C13---C14---C9 121.8 (6) H36B---C36---H36C 109.5 C13---C14---H14A 119.1 N3---Co1---O3---C7 2.5 (3) C15---O4---C10---C9 175.4 (5) N6---Co1---O3---C7 −87.1 (3) C14---C9---C10---C11 −2.3 (8) N7---Co1---O3---C7 −177.3 (3) C8---C9---C10---C11 178.5 (5) Cl1---Co1---O3---C7 92.1 (3) C14---C9---C10---O4 −178.9 (5) N3---Co1---O7---C22 −86.5 (3) C8---C9---C10---O4 2.0 (7) N6---Co1---O7---C22 3.1 (3) O4---C10---C11---C12 178.1 (6) N7---Co1---O7---C22 92.8 (3) C9---C10---C11---C12 1.8 (9) Cl1---Co1---O7---C22 −176.4 (3) C10---C11---C12---C13 −0.6 (10) C7---N2---N3---C8 −176.1 (4) C11---C12---C13---C14 0.0 (11) C7---N2---N3---Co1 2.8 (5) C12---C13---C14---C9 −0.6 (11) O7---Co1---N3---C8 −8.4 (4) C10---C9---C14---C13 1.7 (9) O3---Co1---N3---C8 175.8 (4) C8---C9---C14---C13 −179.3 (6) N6---Co1---N3---C8 −91.0 (4) C21---C16---C17---C18 −0.1 (9) Cl1---Co1---N3---C8 83.6 (4) C22---C16---C17---C18 −178.0 (5) O7---Co1---N3---N2 172.8 (3) C16---C17---C18---C19 0.6 (9) O3---Co1---N3---N2 −3.0 (3) C17---C18---C19---C20 −0.3 (10) Cl1---Co1---N3---N2 −95.2 (3) C17---C18---C19---N4 −179.2 (6) C22---N5---N6---C23 −179.7 (4) O6---N4---C19---C18 10.4 (10) C22---N5---N6---Co1 1.0 (4) O5---N4---C19---C18 −170.5 (7) O7---Co1---N6---C23 178.4 (4) O6---N4---C19---C20 −168.5 (7) O3---Co1---N6---C23 −6.1 (4) O5---N4---C19---C20 10.6 (10) N3---Co1---N6---C23 −88.5 (4) C18---C19---C20---C21 −0.5 (10) N7---Co1---N6---C23 84.6 (4) N4---C19---C20---C21 178.4 (5) O7---Co1---N6---N5 −2.3 (3) C19---C20---C21---C16 1.0 (9) O3---Co1---N6---N5 173.1 (3) C17---C16---C21---C20 −0.7 (8) N3---Co1---N6---N5 90.8 (3) C22---C16---C21---C20 177.2 (5) N7---Co1---N6---N5 −96.1 (3) Co1---O7---C22---N5 −3.8 (5) O7---Co1---N7---C35 0.5 (4) Co1---O7---C22---C16 174.8 (3) O3---Co1---N7---C35 176.3 (4) N6---N5---C22---O7 1.9 (6) N6---Co1---N7---C35 83.1 (4) N6---N5---C22---C16 −176.8 (4) Cl1---Co1---N7---C35 −91.5 (4) C17---C16---C22---O7 −18.2 (7) O7---Co1---N7---C31 −179.1 (4) C21---C16---C22---O7 163.9 (5) O3---Co1---N7---C31 −3.3 (4) C17---C16---C22---N5 160.5 (5) N6---Co1---N7---C31 −96.5 (4) C21---C16---C22---N5 −17.4 (7) Cl1---Co1---N7---C31 88.9 (4) N5---N6---C23---C24 −3.0 (7) C6---C1---C2---C3 −0.5 (8) Co1---N6---C23---C24 176.2 (4) C7---C1---C2---C3 177.6 (5) N6---C23---C24---C29 1.5 (8) C1---C2---C3---C4 0.0 (8) N6---C23---C24---C25 −178.8 (5) C2---C3---C4---C5 1.5 (9) C30---O8---C25---C26 6.5 (9) C2---C3---C4---N1 −178.0 (5) C30---O8---C25---C24 −174.6 (6) O1---N1---C4---C5 6.1 (9) C29---C24---C25---O8 178.4 (5) O2---N1---C4---C5 −176.1 (6) C23---C24---C25---O8 −1.3 (7) O1---N1---C4---C3 −174.3 (6) C29---C24---C25---C26 −2.6 (7) O2---N1---C4---C3 3.5 (9) C23---C24---C25---C26 177.7 (5) C3---C4---C5---C6 −2.5 (9) O8---C25---C26---C27 −179.5 (5) N1---C4---C5---C6 177.1 (5) C24---C25---C26---C27 1.6 (8) C4---C5---C6---C1 1.9 (8) C25---C26---C27---C28 0.5 (9) C2---C1---C6---C5 −0.4 (8) C26---C27---C28---C29 −1.5 (9) C7---C1---C6---C5 −178.5 (5) C27---C28---C29---C24 0.5 (8) Co1---O3---C7---N2 −1.8 (6) C25---C24---C29---C28 1.6 (7) Co1---O3---C7---C1 179.2 (3) C23---C24---C29---C28 −178.7 (5) N3---N2---C7---O3 −0.7 (7) C35---N7---C31---C32 −2.6 (8) N3---N2---C7---C1 178.4 (4) Co1---N7---C31---C32 177.0 (4) C2---C1---C7---O3 −2.3 (7) N7---C31---C32---C33 2.1 (8) C6---C1---C7---O3 175.7 (5) C31---C32---C33---C34 −0.4 (8) C2---C1---C7---N2 178.6 (5) C31---C32---C33---C36 −178.6 (5) C6---C1---C7---N2 −3.4 (7) C32---C33---C34---C35 −0.7 (8) N2---N3---C8---C9 −1.9 (8) C36---C33---C34---C35 177.6 (5) Co1---N3---C8---C9 179.3 (4) C31---N7---C35---C34 1.5 (8) N3---C8---C9---C14 4.1 (10) Co1---N7---C35---C34 −178.1 (4) N3---C8---C9---C10 −176.9 (5) C33---C34---C35---N7 0.1 (9) C15---O4---C10---C11 −1.0 (8) ---------------------- ------------- ----------------------- ------------ ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond lengths (Å) ::: ----------- ------------- Co1---O3 1.887 (3) Co1---O7 1.882 (3) Co1---N3 1.917 (4) Co1---N6 1.932 (4) Co1---N7 1.983 (4) Co1---Cl1 2.2472 (17) ----------- ------------- :::

PubMed Central

2024-06-05T04:04:18.797767

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052150/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):m293", "authors": [ { "first": "Qiong-Jie", "last": "Wu" }, { "first": "Xiao-Hua", "last": "Chen" }, { "first": "Jiang", "last": "Jiang" }, { "first": "Bi-Qiong", "last": "Cai" }, { "first": "Yong-Ping", "last": "Xie" } ] }

PMC3052151

Related literature {#sec1} ================== For the pharmacological effects, biological activity and synthesis of 3(2*H*)-pyridazinones, see: Şüküroğlu *et al.* 2006[@bb10]; Brogden 1986[@bb3]. For bond-length data, see: Allen *et al.* (1987[@bb1]). For ring conformational analysis, see: Cremer & Pople (1975[@bb4]). For the quantum mechanical *CNDO*/2 approximation, see: Pople & Beveridge (1970[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~26~H~28~FN~5~O~3~*M* *~r~* = 477.53Triclinic,*a* = 8.9168 (5) Å*b* = 10.7106 (6) Å*c* = 13.5147 (8) Åα = 73.489 (4)°β = 71.309 (4)°γ = 83.486 (4)°*V* = 1171.87 (12) Å^3^*Z* = 2Mo *K*α radiationμ = 0.10 mm^−1^*T* = 296 K0.60 × 0.49 × 0.20 mm ### Data collection {#sec2.1.2} STOE IPDS 2 diffractometerAbsorption correction: integration (*X-RED32*; Stoe & Cie, 2002[@bb9]) *T* ~min~ = 0.945, *T* ~max~ = 0.98113273 measured reflections4861 independent reflections3479 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.029 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.036*wR*(*F* ^2^) = 0.091*S* = 1.034861 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.12 e Å^−3^Δρ~min~ = −0.14 e Å^−3^ {#d5e525} Data collection: *X-AREA* (Stoe & Cie, 2002[@bb9]); cell refinement: *X-AREA*; data reduction: *X-RED32* (Stoe & Cie, 2002[@bb9]); program(s) used to solve structure: *SIR97* (Altomare *et al.*, 1999[@bb2]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb5]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005071/ez2227sup1.cif](http://dx.doi.org/10.1107/S1600536811005071/ez2227sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005071/ez2227Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005071/ez2227Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ez2227&file=ez2227sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ez2227sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ez2227&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [EZ2227](http://scripts.iucr.org/cgi-bin/sendsup?ez2227)). The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund). Comment ======= In recent years, the 3(2*H*)-pyridazinone system has aroused a great deal of attention due to its structural relationship to pyrazolone derivatives such as aminopyrine and dipyrone in view of the ring enlargement of pyrazolone to pyridazinone. These drugs possess analgesic and anti-inflammatory activities although they have limitations for their clinical use due to serious side effects such as blood dyscrasias (Şüküroğlu *et al.*, 2006; Brogden, 1986). A series of 6-morpholino-4-aryl-3(2*H*)-pyridazinone alkanoic acids, their ester and amide derivatives were prepared and tested for their *in vivo* analgesic activity by using the *p*-benzoquinone-induced writhing test. The title compound, C~26~H~28~FN~5~O~3~, generally showed higher activity but caused gastric ulceration in the animals (Şüküroğlu *et al.*, 2006). In the title molecule (I), Fig. 1, the morpholine ring (N3/O2/C11--C14) adopts a chair conformation. The piperazine ring (N4/N5/C17--C20) is puckered. The conformation of this ring is described by three puckering parameters: Q~T~ = 0.5437 (15) Å, θ = 8.89 (15) ° and, φ = 357.2 (11) ° (Cremer & Pople, 1975). The 1,6-dihydropyridazine ring (N1/N2/C7--C10) makes dihedral angles of 28.03 (7) and 77.46 (7) ° with the C1--C6 phenyl and C21--C26 benzene rings, respectively. The phenyl and benzene rings make a dihedral angle of 50.17 (8) ° with each other. In the crystal structure, molecules are linked along the *c*-axis direction and are flattened parallel to the plane containing the a and c axes. Furthermore, C--H···π interactions contribute to the stability of the structure (Table 1). Fig. 2 shows the packing diagram of (I) down the *b* axis. Theoretical calculations were carried out using the semiempirical quantum-mechanical *CNDO*/2 (Complete Neglect of Differential Overlap) method (Pople and Beveridge, 1970). The spatial view of the single molecule calculated as closed-shell in a vacuum is shown in Fig. 3 with atomic labels. The calculated dipole moment of (I) is about 2.795 Debye. The *HOMO* and *LUMO* energy levels are -10.013 and 0.832 eV, respectively. According to the theoretical *CNDO/2* and experimental X-ray structural results, the values of the geometric parameters of (I) are almost comparable within the experimental error interval (Allen *et al.*, 1987). The 1,6-dihydropyridazine ring (N1/N2/C7--C10) forms dihedral angles of 2.24 and 60.48° with the C1--C6 phenyl and C21--C26 benzene rings, respectively. The dihedral angle between the phenyl and benzene rings is 62.62°. The orientations of the planes of the rings are however, slightly different in the *CNDO*/2 and X-ray results. That is, intermolecular interactions play an important role in determining the crystal state conformation of (I). Experimental {#experimental} ============ A reaction mixture containing 2-\[4-phenyl-6-(morpholin-4-yl)-3(2*H*)- pyridazinone-2-yl\]acetic acid (0.01 mole) and triethylamine (0.011 mole) in 20 ml dichloromethane at 273 K (ice-bath) was treated with ethyl chloroformate (0,01 mole). After stirring the reaction mixture at 273 K for 15 min, 0.011 mole of 4-(4-fluorophenyl)-piperazine derivative was added to this solution. The final mixture was stirred at room temperature for 24 h and evaporated to dryness and then acetone was added. All undissolved salts were filtered off, the filtrate was evaporated to dryness and the residue was recrystallized from acetone-water (1:1) to yield 62%, \[m.p.: 457 K\]. ^1^H-NMR (CDCl~3~), δ 7.75 (m, 2H, phenyl-H2, H6), 7.43 (m, 3H, phenyl-H3, H4, H5), 7.23 (s, 1H, pyridazinone-H5), 6.99 (m, 4H, 4-fluorophenyl-H2, H3, H5, H6), 4.98 (s, 2H, N---CH~2~---CO), 3.82 (m, 6H, morpholine-H2, H6, piperazine- H2(6)), 3.71 (m, 2H, piperazine-H6(2)), 3.31 (t, 8H, morpholine-H3, H5), 3.15 (m, 4H, piperazine-H3, H5) p.p.m.. IR *v*~max~ cm^-1^ (KBr): 2845, 1661, 1643. Anal. C, H, N (C~26~H~28~FN~5~O~3~) (Şüküroğlu *et al.*, 2006). Elemental analysis: C~26~H~28~FN~5~O~3~, Calc.(%) / Found (%): C: 65.39/65.54, H: 5.91/5.49, N: 14.67/14.28. Refinement {#refinement} ========== All H atoms were positioned geometrically and refined using a riding model with C---H = 0.93 and 0.97 Å, and *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### View of the title molecule with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level. ::: ![](e-67-0o666-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing and hydrogen bonding interactions of (I) down the b axis. H atoms not participating in hydrogen bonding have been omitted for clarity. ::: ![](e-67-0o666-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The spatial view of the title molecule (I), calculated by the CNDO/2 aproximation. ::: ![](e-67-0o666-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e262 .table-wrap} ------------------------- ---------------------------------------- C~26~H~28~FN~5~O~3~ *Z* = 2 *M~r~* = 477.53 *F*(000) = 504 Triclinic, *P*1 *D*~x~ = 1.353 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.9168 (5) Å Cell parameters from 19046 reflections *b* = 10.7106 (6) Å θ = 1.7--28.2° *c* = 13.5147 (8) Å µ = 0.10 mm^−1^ α = 73.489 (4)° *T* = 296 K β = 71.309 (4)° Prism, yellow γ = 83.486 (4)° 0.60 × 0.49 × 0.20 mm *V* = 1171.87 (12) Å^3^ ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e398 .table-wrap} ------------------------------------------------------------------ -------------------------------------- STOE IPDS 2 diffractometer 4861 independent reflections Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus 3479 reflections with *I* \> 2σ(*I*) plane graphite *R*~int~ = 0.029 Detector resolution: 6.67 pixels mm^-1^ θ~max~ = 26.5°, θ~min~ = 1.7° ω scans *h* = −11→11 Absorption correction: integration (*X-RED32*; Stoe & Cie, 2002) *k* = −13→13 *T*~min~ = 0.945, *T*~max~ = 0.981 *l* = −16→16 13273 measured reflections ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e518 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.036 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.091 H-atom parameters constrained *S* = 1.03 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0469*P*)^2^ + 0.0141*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4861 reflections (Δ/σ)~max~ \< 0.001 316 parameters Δρ~max~ = 0.12 e Å^−3^ 0 restraints Δρ~min~ = −0.14 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e675 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. Bond distances, angles *etc*. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on *F*^2^ for ALL reflections except those flagged by the user for potential systematic errors. Weighted *R*-factors *wR* and all goodnesses of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The observed criterion of *F*^2^ \> σ(*F*^2^) is used only for calculating -*R*-factor-obs *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*-factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e777 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ F1 1.31808 (14) 0.32221 (10) 1.12298 (8) 0.0875 (4) O1 0.65668 (12) 0.66791 (10) 0.43998 (8) 0.0635 (4) O2 0.02122 (12) 1.05391 (10) 0.84902 (8) 0.0626 (3) O3 0.84333 (12) 0.78850 (9) 0.56875 (9) 0.0627 (3) N1 0.44450 (12) 0.78805 (9) 0.66593 (8) 0.0437 (3) N2 0.54428 (12) 0.72130 (10) 0.59688 (8) 0.0438 (3) N3 0.25440 (13) 0.94880 (10) 0.69277 (8) 0.0471 (3) N4 0.93182 (13) 0.58003 (10) 0.61148 (9) 0.0473 (4) N5 1.09333 (13) 0.46726 (10) 0.76728 (8) 0.0459 (3) C1 0.43486 (15) 0.84428 (12) 0.33963 (10) 0.0425 (4) C2 0.38220 (17) 0.96206 (13) 0.28338 (11) 0.0530 (5) C3 0.3712 (2) 0.97650 (17) 0.18124 (13) 0.0668 (6) C4 0.4089 (2) 0.87442 (18) 0.13408 (12) 0.0671 (6) C5 0.46053 (19) 0.75785 (16) 0.18863 (12) 0.0622 (6) C6 0.47474 (17) 0.74228 (13) 0.29017 (11) 0.0523 (5) C7 0.44320 (14) 0.82808 (11) 0.45042 (10) 0.0402 (4) C8 0.55601 (15) 0.73397 (12) 0.49132 (10) 0.0445 (4) C9 0.35078 (14) 0.87626 (11) 0.62510 (10) 0.0406 (4) C10 0.34782 (15) 0.89739 (11) 0.51700 (10) 0.0429 (4) C11 0.10441 (17) 1.00413 (13) 0.67498 (11) 0.0546 (5) C12 0.04171 (18) 1.10537 (13) 0.73676 (12) 0.0615 (5) C13 0.17058 (19) 1.00733 (16) 0.86405 (13) 0.0641 (6) C14 0.24172 (18) 0.90257 (14) 0.80774 (11) 0.0533 (5) C15 0.64791 (15) 0.62509 (12) 0.64412 (11) 0.0462 (4) C16 0.81643 (16) 0.67228 (12) 0.60443 (10) 0.0444 (4) C17 1.09342 (16) 0.61613 (15) 0.59093 (11) 0.0578 (5) C18 1.12789 (17) 0.59830 (13) 0.69637 (12) 0.0553 (5) C19 0.93822 (16) 0.42227 (12) 0.78027 (11) 0.0460 (4) C20 0.90918 (17) 0.44392 (12) 0.67254 (11) 0.0484 (4) C21 1.14574 (15) 0.43318 (12) 0.85944 (10) 0.0446 (4) C22 1.24267 (18) 0.51424 (13) 0.87566 (12) 0.0532 (5) C23 1.2999 (2) 0.47658 (15) 0.96358 (13) 0.0611 (6) C24 1.26051 (19) 0.35931 (15) 1.03610 (12) 0.0599 (5) C25 1.16453 (19) 0.27695 (15) 1.02480 (12) 0.0596 (5) C26 1.10713 (17) 0.31386 (13) 0.93713 (11) 0.0530 (5) H2 0.35420 1.03140 0.31490 0.0640\* H3 0.33800 1.05620 0.14380 0.0800\* H4 0.39940 0.88440 0.06570 0.0810\* H5 0.48620 0.68860 0.15690 0.0750\* H6 0.51130 0.66300 0.32590 0.0630\* H10 0.27860 0.96040 0.49140 0.0510\* H11A 0.02810 0.93570 0.69910 0.0660\* H11B 0.12070 1.04350 0.59830 0.0660\* H12A 0.11470 1.17670 0.70830 0.0740\* H12B −0.05910 1.13980 0.72630 0.0740\* H13A 0.15730 0.97320 0.94090 0.0770\* H13B 0.24260 1.07930 0.83630 0.0770\* H14A 0.34600 0.87750 0.81590 0.0640\* H14B 0.17600 0.82650 0.84070 0.0640\* H15A 0.64680 0.54450 0.62510 0.0550\* H15B 0.60890 0.60740 0.72240 0.0550\* H17A 1.10820 0.70640 0.54920 0.0690\* H17B 1.16660 0.56240 0.54900 0.0690\* H18A 1.23860 0.61530 0.68140 0.0660\* H18B 1.06480 0.66110 0.73320 0.0660\* H19A 0.85690 0.46850 0.82480 0.0550\* H19B 0.93100 0.33020 0.81730 0.0550\* H20A 0.98170 0.38910 0.63140 0.0580\* H20B 0.80200 0.41990 0.68420 0.0580\* H22 1.26910 0.59500 0.82640 0.0640\* H23 1.36500 0.53130 0.97310 0.0730\* H25 1.13830 0.19710 1.07550 0.0720\* H26 1.04120 0.25820 0.92940 0.0630\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1576 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ F1 0.1156 (9) 0.0924 (7) 0.0722 (6) 0.0160 (6) −0.0589 (6) −0.0215 (5) O1 0.0598 (7) 0.0678 (6) 0.0611 (6) 0.0271 (5) −0.0168 (5) −0.0268 (5) O2 0.0534 (6) 0.0630 (6) 0.0617 (6) 0.0020 (5) 0.0024 (5) −0.0255 (5) O3 0.0606 (6) 0.0408 (5) 0.0794 (7) −0.0021 (4) −0.0271 (5) 0.0026 (5) N1 0.0414 (6) 0.0417 (5) 0.0441 (6) 0.0032 (4) −0.0094 (5) −0.0111 (5) N2 0.0391 (6) 0.0427 (5) 0.0463 (6) 0.0082 (4) −0.0124 (5) −0.0108 (5) N3 0.0453 (6) 0.0442 (6) 0.0463 (6) 0.0071 (5) −0.0075 (5) −0.0140 (5) N4 0.0395 (6) 0.0438 (6) 0.0548 (7) 0.0038 (5) −0.0182 (5) −0.0045 (5) N5 0.0445 (6) 0.0450 (6) 0.0459 (6) −0.0017 (5) −0.0163 (5) −0.0053 (5) C1 0.0356 (7) 0.0440 (7) 0.0459 (7) −0.0017 (5) −0.0097 (5) −0.0114 (5) C2 0.0543 (9) 0.0500 (8) 0.0552 (8) 0.0054 (6) −0.0206 (7) −0.0127 (6) C3 0.0701 (11) 0.0693 (10) 0.0592 (9) 0.0068 (8) −0.0283 (8) −0.0077 (8) C4 0.0657 (11) 0.0914 (12) 0.0465 (8) −0.0052 (9) −0.0193 (7) −0.0179 (8) C5 0.0626 (10) 0.0713 (10) 0.0561 (9) −0.0032 (8) −0.0116 (7) −0.0288 (8) C6 0.0543 (9) 0.0508 (8) 0.0516 (8) 0.0003 (6) −0.0137 (6) −0.0166 (6) C7 0.0357 (7) 0.0375 (6) 0.0452 (7) −0.0016 (5) −0.0101 (5) −0.0095 (5) C8 0.0389 (7) 0.0434 (7) 0.0497 (7) 0.0048 (5) −0.0112 (6) −0.0145 (6) C9 0.0371 (7) 0.0360 (6) 0.0450 (7) −0.0004 (5) −0.0082 (5) −0.0100 (5) C10 0.0388 (7) 0.0386 (6) 0.0492 (7) 0.0048 (5) −0.0136 (5) −0.0102 (5) C11 0.0529 (9) 0.0497 (7) 0.0521 (8) 0.0148 (6) −0.0100 (6) −0.0122 (6) C12 0.0565 (9) 0.0448 (7) 0.0671 (10) 0.0079 (6) −0.0004 (7) −0.0142 (7) C13 0.0578 (10) 0.0736 (10) 0.0607 (9) −0.0014 (8) −0.0060 (7) −0.0310 (8) C14 0.0518 (8) 0.0563 (8) 0.0478 (8) 0.0018 (6) −0.0088 (6) −0.0158 (6) C15 0.0420 (7) 0.0415 (6) 0.0503 (7) 0.0058 (5) −0.0156 (6) −0.0057 (6) C16 0.0471 (8) 0.0411 (7) 0.0432 (7) 0.0035 (5) −0.0178 (6) −0.0053 (5) C17 0.0400 (8) 0.0661 (9) 0.0545 (8) −0.0036 (6) −0.0137 (6) 0.0039 (7) C18 0.0478 (8) 0.0533 (8) 0.0591 (9) −0.0096 (6) −0.0200 (7) 0.0015 (7) C19 0.0476 (8) 0.0372 (6) 0.0512 (7) 0.0004 (5) −0.0142 (6) −0.0100 (5) C20 0.0513 (8) 0.0384 (6) 0.0588 (8) 0.0083 (5) −0.0240 (6) −0.0131 (6) C21 0.0442 (7) 0.0434 (7) 0.0448 (7) 0.0072 (5) −0.0134 (6) −0.0126 (5) C22 0.0596 (9) 0.0455 (7) 0.0574 (8) 0.0032 (6) −0.0224 (7) −0.0144 (6) C23 0.0685 (10) 0.0594 (9) 0.0690 (10) 0.0083 (7) −0.0328 (8) −0.0282 (8) C24 0.0682 (10) 0.0666 (9) 0.0525 (8) 0.0179 (8) −0.0302 (7) −0.0213 (7) C25 0.0634 (10) 0.0571 (8) 0.0518 (8) 0.0062 (7) −0.0197 (7) −0.0045 (7) C26 0.0534 (9) 0.0490 (7) 0.0551 (8) 0.0000 (6) −0.0203 (7) −0.0077 (6) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2301 .table-wrap} ---------------------- -------------- ----------------------- -------------- F1---C24 1.369 (2) C21---C26 1.3999 (19) O1---C8 1.2343 (17) C22---C23 1.380 (2) O2---C12 1.4173 (18) C23---C24 1.357 (2) O2---C13 1.424 (2) C24---C25 1.366 (2) O3---C16 1.2215 (17) C25---C26 1.378 (2) N1---N2 1.3698 (15) C2---H2 0.9300 N1---C9 1.3098 (17) C3---H3 0.9300 N2---C8 1.3646 (16) C4---H4 0.9300 N2---C15 1.4531 (18) C5---H5 0.9300 N3---C9 1.3883 (16) C6---H6 0.9300 N3---C11 1.464 (2) C10---H10 0.9300 N3---C14 1.4612 (17) C11---H11A 0.9700 N4---C16 1.3501 (18) C11---H11B 0.9700 N4---C17 1.4532 (19) C12---H12A 0.9700 N4---C20 1.4571 (17) C12---H12B 0.9700 N5---C18 1.4586 (18) C13---H13A 0.9700 N5---C19 1.4572 (19) C13---H13B 0.9700 N5---C21 1.4067 (17) C14---H14A 0.9700 C1---C2 1.393 (2) C14---H14B 0.9700 C1---C6 1.3933 (19) C15---H15A 0.9700 C1---C7 1.4827 (18) C15---H15B 0.9700 C2---C3 1.379 (2) C17---H17A 0.9700 C3---C4 1.375 (3) C17---H17B 0.9700 C4---C5 1.371 (3) C18---H18A 0.9700 C5---C6 1.380 (2) C18---H18B 0.9700 C7---C8 1.4639 (19) C19---H19A 0.9700 C7---C10 1.3528 (18) C19---H19B 0.9700 C9---C10 1.4219 (18) C20---H20A 0.9700 C11---C12 1.504 (2) C20---H20B 0.9700 C13---C14 1.502 (2) C22---H22 0.9300 C15---C16 1.518 (2) C23---H23 0.9300 C17---C18 1.508 (2) C25---H25 0.9300 C19---C20 1.509 (2) C26---H26 0.9300 C21---C22 1.396 (2) F1···H3^i^ 2.7700 H2···H10 2.1900 F1···H15B^ii^ 2.6900 H2···O3^iii^ 2.9100 F1···H19A^ii^ 2.7100 H2···N1^iii^ 2.9000 O1···C6 2.8742 (19) H3···F1^xii^ 2.7700 O1···C16 3.0123 (18) H3···C25^xii^ 3.0300 O2···N3 2.8383 (15) H3···H25^xii^ 2.4400 O3···N2 2.7209 (16) H5···C22^iv^ 3.0700 O3···C11^iii^ 3.3306 (18) H5···C23^iv^ 2.8800 O3···C8 3.2257 (18) H5···C24^iv^ 2.9800 O1···H12A^iii^ 2.6800 H6···O1 2.3200 O1···H15A 2.4500 H6···C8 2.7100 O1···H6 2.3200 H6···H15A^xi^ 2.5800 O1···H17B^iv^ 2.7700 H10···C2 2.6600 O2···H13A^v^ 2.7200 H10···C11 2.6100 O2···H26^vi^ 2.7500 H10···H2 2.1900 O3···H17A 2.3800 H10···H11B 2.0000 O3···H2^iii^ 2.9100 H10···O3^iii^ 2.7800 O3···H10^iii^ 2.7800 H11B···C10 2.5700 O3···H11B^iii^ 2.4100 H11B···H10 2.0000 N2···O3 2.7209 (16) H11B···O3^iii^ 2.4100 N3···O2 2.8383 (15) H12A···H13B 2.3100 N4···N5 2.8407 (16) H12A···H20A^vi^ 2.5500 N5···N4 2.8407 (16) H12A···O1^iii^ 2.6800 N1···H22^vii^ 2.7300 H12B···C3^x^ 2.9200 N1···H2^iii^ 2.9000 H12B···C4^x^ 3.0800 N1···H18A^vii^ 2.6700 H13A···O2^v^ 2.7200 N1···H14A 2.3600 H13B···H12A 2.3100 N1···H14B 2.8600 H13B···C6^iii^ 3.0700 N2···H18A^vii^ 2.8300 H14A···N1 2.3600 C2···C14^iii^ 3.508 (2) H14A···C2^iii^ 2.8600 C6···O1 2.8742 (19) H14B···N1 2.8600 C7···C9^iii^ 3.5673 (18) H14B···H22^vii^ 2.5600 C8···O3 3.2257 (18) H15A···O1 2.4500 C9···C7^iii^ 3.5673 (18) H15A···C20 2.6500 C9···C18^vii^ 3.497 (2) H15A···H20B 2.0000 C9···C10^iii^ 3.5089 (18) H15A···H6^xi^ 2.5800 C10···C9^iii^ 3.5089 (18) H15B···C20 3.0200 C10···C10^iii^ 3.5197 (19) H15B···H20B 2.5500 C11···O3^iii^ 3.3306 (18) H15B···F1^ii^ 2.6900 C12···C19^vi^ 3.577 (2) H17A···O3 2.3800 C14···C2^iii^ 3.508 (2) H17A···C10^viii^ 2.9700 C16···O1 3.0123 (18) H17B···H20A 2.4000 C18···C9^viii^ 3.497 (2) H17B···O1^iv^ 2.7700 C19···C12^ix^ 3.577 (2) H18A···N1^viii^ 2.6700 C2···H14A^iii^ 2.8600 H18A···N2^viii^ 2.8300 C2···H10 2.6600 H18A···C9^viii^ 2.8900 C3···H12B^x^ 2.9200 H18A···C22 2.5500 C4···H12B^x^ 3.0800 H18A···H22 2.0100 C5···H20B^xi^ 2.9400 H18B···C22 2.8900 C6···H20B^xi^ 3.0500 H18B···H22 2.4700 C6···H13B^iii^ 3.0700 H19A···F1^ii^ 2.7100 C8···H6 2.7100 H19A···C23^ii^ 2.9500 C9···H18A^vii^ 2.8900 H19A···C24^ii^ 2.8800 C10···H17A^vii^ 2.9700 H19B···C12^ix^ 2.8700 C10···H2 2.6900 H19B···C26 2.5500 C10···H11B 2.5700 H19B···H26 1.9900 C11···H10 2.6100 H20A···C12^ix^ 3.0300 C12···H20A^vi^ 3.0300 H20A···H12A^ix^ 2.5500 C12···H19B^vi^ 2.8700 H20A···H17B 2.4000 C13···H26^vi^ 3.0500 H20B···C15 2.4800 C15···H20B 2.4800 H20B···H15A 2.0000 C18···H22 2.4600 H20B···H15B 2.5500 C19···H26 2.6100 H20B···C5^xi^ 2.9400 C20···H15A 2.6500 H20B···C6^xi^ 3.0500 C20···H15B 3.0200 H22···N1^viii^ 2.7300 C22···H18A 2.5500 H22···C18 2.4600 C22···H18B 2.8900 H22···H14B^viii^ 2.5600 C22···H5^iv^ 3.0700 H22···H18A 2.0100 C23···H5^iv^ 2.8800 H22···H18B 2.4700 C23···H19A^ii^ 2.9500 H25···H3^i^ 2.4400 C24···H5^iv^ 2.9800 H26···O2^ix^ 2.7500 C24···H19A^ii^ 2.8800 H26···C13^ix^ 3.0500 C25···H3^i^ 3.0300 H26···C19 2.6100 C26···H19B 2.5500 H26···H19B 1.9900 H2···C10 2.6900 C12---O2---C13 108.95 (12) C4---C5---H5 120.00 N2---N1---C9 116.01 (10) C6---C5---H5 120.00 N1---N2---C8 127.91 (11) C1---C6---H6 120.00 N1---N2---C15 114.75 (10) C5---C6---H6 120.00 C8---N2---C15 117.34 (11) C7---C10---H10 119.00 C9---N3---C11 119.14 (11) C9---C10---H10 119.00 C9---N3---C14 117.13 (11) N3---C11---H11A 110.00 C11---N3---C14 112.25 (11) N3---C11---H11B 110.00 C16---N4---C17 120.60 (12) C12---C11---H11A 110.00 C16---N4---C20 126.08 (12) C12---C11---H11B 110.00 C17---N4---C20 110.06 (12) H11A---C11---H11B 108.00 C18---N5---C19 114.00 (11) O2---C12---H12A 109.00 C18---N5---C21 116.78 (11) O2---C12---H12B 109.00 C19---N5---C21 117.13 (10) C11---C12---H12A 109.00 C2---C1---C6 118.22 (12) C11---C12---H12B 109.00 C2---C1---C7 120.29 (12) H12A---C12---H12B 108.00 C6---C1---C7 121.46 (12) O2---C13---H13A 109.00 C1---C2---C3 120.40 (14) O2---C13---H13B 109.00 C2---C3---C4 120.71 (16) C14---C13---H13A 109.00 C3---C4---C5 119.50 (15) C14---C13---H13B 109.00 C4---C5---C6 120.59 (15) H13A---C13---H13B 108.00 C1---C6---C5 120.57 (14) N3---C14---H14A 110.00 C1---C7---C8 120.11 (11) N3---C14---H14B 110.00 C1---C7---C10 122.01 (12) C13---C14---H14A 110.00 C8---C7---C10 117.88 (11) C13---C14---H14B 110.00 O1---C8---N2 119.12 (12) H14A---C14---H14B 108.00 O1---C8---C7 126.40 (12) N2---C15---H15A 109.00 N2---C8---C7 114.49 (11) N2---C15---H15B 109.00 N1---C9---N3 116.54 (11) C16---C15---H15A 109.00 N1---C9---C10 121.96 (11) C16---C15---H15B 109.00 N3---C9---C10 121.49 (11) H15A---C15---H15B 108.00 C7---C10---C9 121.60 (12) N4---C17---H17A 110.00 N3---C11---C12 109.61 (12) N4---C17---H17B 110.00 O2---C12---C11 112.03 (12) C18---C17---H17A 110.00 O2---C13---C14 112.09 (14) C18---C17---H17B 110.00 N3---C14---C13 110.40 (12) H17A---C17---H17B 108.00 N2---C15---C16 111.27 (11) N5---C18---H18A 109.00 O3---C16---N4 122.80 (14) N5---C18---H18B 109.00 O3---C16---C15 120.54 (13) C17---C18---H18A 109.00 N4---C16---C15 116.67 (11) C17---C18---H18B 109.00 N4---C17---C18 110.23 (12) H18A---C18---H18B 108.00 N5---C18---C17 112.17 (12) N5---C19---H19A 109.00 N5---C19---C20 111.62 (11) N5---C19---H19B 109.00 N4---C20---C19 110.40 (11) C20---C19---H19A 109.00 N5---C21---C22 121.73 (12) C20---C19---H19B 109.00 N5---C21---C26 121.14 (12) H19A---C19---H19B 108.00 C22---C21---C26 117.10 (13) N4---C20---H20A 110.00 C21---C22---C23 121.10 (14) N4---C20---H20B 110.00 C22---C23---C24 119.61 (16) C19---C20---H20A 110.00 F1---C24---C23 119.38 (15) C19---C20---H20B 110.00 F1---C24---C25 118.95 (14) H20A---C20---H20B 108.00 C23---C24---C25 121.67 (15) C21---C22---H22 119.00 C24---C25---C26 119.02 (14) C23---C22---H22 119.00 C21---C26---C25 121.49 (14) C22---C23---H23 120.00 C1---C2---H2 120.00 C24---C23---H23 120.00 C3---C2---H2 120.00 C24---C25---H25 121.00 C2---C3---H3 120.00 C26---C25---H25 120.00 C4---C3---H3 120.00 C21---C26---H26 119.00 C3---C4---H4 120.00 C25---C26---H26 119.00 C5---C4---H4 120.00 C13---O2---C12---C11 60.78 (16) C6---C1---C7---C10 −151.12 (14) C12---O2---C13---C14 −59.74 (16) C6---C1---C7---C8 28.3 (2) C9---N1---N2---C8 −1.23 (19) C6---C1---C2---C3 −0.4 (2) N2---N1---C9---C10 2.71 (18) C7---C1---C2---C3 −178.64 (14) C9---N1---N2---C15 179.39 (11) C2---C1---C7---C8 −153.52 (13) N2---N1---C9---N3 −177.06 (11) C2---C1---C6---C5 −0.7 (2) C15---N2---C8---O1 −2.74 (19) C7---C1---C6---C5 177.56 (14) N1---N2---C8---C7 −2.13 (19) C2---C1---C7---C10 27.1 (2) C15---N2---C8---C7 177.24 (11) C1---C2---C3---C4 1.3 (3) N1---N2---C15---C16 −105.23 (12) C2---C3---C4---C5 −1.1 (3) C8---N2---C15---C16 75.32 (14) C3---C4---C5---C6 0.1 (3) N1---N2---C8---O1 177.89 (12) C4---C5---C6---C1 0.9 (3) C14---N3---C11---C12 52.25 (15) C1---C7---C10---C9 176.59 (12) C14---N3---C9---N1 −12.56 (18) C8---C7---C10---C9 −2.82 (19) C14---N3---C9---C10 167.66 (13) C1---C7---C8---O1 4.6 (2) C9---N3---C14---C13 165.09 (13) C10---C7---C8---N2 3.99 (18) C11---N3---C14---C13 −51.70 (16) C1---C7---C8---N2 −175.43 (12) C9---N3---C11---C12 −165.36 (11) C10---C7---C8---O1 −176.03 (14) C11---N3---C9---N1 −153.17 (12) N1---C9---C10---C7 −0.7 (2) C11---N3---C9---C10 27.06 (18) N3---C9---C10---C7 179.07 (12) C16---N4---C20---C19 −98.68 (16) N3---C11---C12---O2 −57.26 (16) C17---N4---C16---O3 8.9 (2) O2---C13---C14---N3 55.52 (17) C17---N4---C16---C15 −170.73 (11) N2---C15---C16---N4 −158.32 (11) C20---N4---C16---C15 −13.24 (19) N2---C15---C16---O3 22.07 (17) C20---N4---C17---C18 −60.28 (15) N4---C17---C18---N5 53.86 (16) C16---N4---C17---C18 100.50 (15) N5---C19---C20---N4 −54.43 (15) C20---N4---C16---O3 166.37 (13) N5---C21---C22---C23 −176.61 (14) C17---N4---C20---C19 60.79 (15) C26---C21---C22---C23 1.2 (2) C19---N5---C18---C17 −48.75 (16) N5---C21---C26---C25 176.70 (14) C21---N5---C19---C20 −169.67 (11) C22---C21---C26---C25 −1.1 (2) C19---N5---C21---C26 34.26 (18) C21---C22---C23---C24 −0.5 (2) C18---N5---C19---C20 48.87 (15) C22---C23---C24---F1 179.76 (15) C18---N5---C21---C26 174.65 (13) C22---C23---C24---C25 −0.3 (3) C18---N5---C21---C22 −7.63 (19) F1---C24---C25---C26 −179.68 (14) C21---N5---C18---C17 169.65 (12) C23---C24---C25---C26 0.4 (3) C19---N5---C21---C22 −148.02 (13) C24---C25---C26---C21 0.4 (2) ---------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) *x*+1, *y*−1, *z*+1; (ii) −*x*+2, −*y*+1, −*z*+2; (iii) −*x*+1, −*y*+2, −*z*+1; (iv) −*x*+2, −*y*+1, −*z*+1; (v) −*x*, −*y*+2, −*z*+2; (vi) *x*−1, *y*+1, *z*; (vii) *x*−1, *y*, *z*; (viii) *x*+1, *y*, *z*; (ix) *x*+1, *y*−1, *z*; (x) −*x*, −*y*+2, −*z*+1; (xi) −*x*+1, −*y*+1, −*z*+1; (xii) *x*−1, *y*+1, *z*−1. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e4545 .table-wrap} --------------------------------------------------------------------------------------------------- Cg2, Cg4 and Cg5 are the centroids of the N1/N2/C7--C10, C1--C6 and C21--C26 rings, respectively. --------------------------------------------------------------------------------------------------- ::: ::: {#d1e4549 .table-wrap} ------------------------ --------- --------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C6---H6···O1 0.93 2.32 2.8742 (19) 117 C11---H11B···O3^iii^ 0.97 2.41 3.3306 (18) 159 C17---H17A···O3 0.97 2.38 2.7660 (19) 103 C5---H5···Cg5^iv^ 0.93 2.86 3.4941 (18) 127 C13---H13B···Cg4^iii^ 0.97 2.92 3.7395 (19) 143 C18---H18A···Cg2^viii^ 0.97 2.73 3.5079 (16) 138 ------------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (iii) −*x*+1, −*y*+2, −*z*+1; (iv) −*x*+2, −*y*+1, −*z*+1; (viii) *x*+1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*2, *Cg*4 and *Cg*5 are the centroids of the N1/N2/C7--C10, C1--C6 and C21--C26 rings, respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------------- --------- ------- ------------- ------------- C11---H11*B*⋯O3^i^ 0.97 2.41 3.3306 (18) 159 C5---H5⋯*Cg*5^ii^ 0.93 2.86 3.4941 (18) 127 C13---H13*B*⋯*Cg*4^i^ 0.97 2.92 3.7395 (19) 143 C18---H18*A*⋯*Cg*2^iii^ 0.97 2.73 3.5079 (16) 138 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.808558

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052151/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o666-o667", "authors": [ { "first": "Abdullah", "last": "Aydın" }, { "first": "Murat", "last": "Şüküroğlu" }, { "first": "Mehmet", "last": "Akkurt" }, { "first": "Orhan", "last": "Büyükgüngör" } ] }

PMC3052152

Related literature {#sec1} ================== For the biological activity of sydnones, see: Holla *et al.* (1986[@bb6], 1987[@bb7], 1992[@bb8]); Rai *et al.* (2008[@bb9]). For related structures, see: Fun *et al.* (2010[@bb4], 2011[@bb5]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986[@bb3]). For bond-length data, see: Allen *et al.* (1987[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~9~Br~2~NO~4~*M* *~r~* = 403.03Triclinic,*a* = 8.6939 (7) Å*b* = 8.7834 (8) Å*c* = 10.4722 (9) Åα = 89.334 (2)°β = 69.846 (2)°γ = 68.114 (2)°*V* = 690.32 (10) Å^3^*Z* = 2Mo *K*α radiationμ = 5.88 mm^−1^*T* = 100 K0.28 × 0.18 × 0.08 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2009[@bb2]) *T* ~min~ = 0.292, *T* ~max~ = 0.64410644 measured reflections4015 independent reflections3390 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.030 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.043*wR*(*F* ^2^) = 0.100*S* = 1.334015 reflections216 parametersH-atom parameters constrainedΔρ~max~ = 0.71 e Å^−3^Δρ~min~ = −0.60 e Å^−3^ {#d5e457} Data collection: *APEX2* (Bruker, 2009[@bb2]); cell refinement: *SAINT* (Bruker, 2009[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb10]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL* and *PLATON* (Spek, 2009[@bb11]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003552/sj5095sup1.cif](http://dx.doi.org/10.1107/S1600536811003552/sj5095sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003552/sj5095Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003552/sj5095Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?sj5095&file=sj5095sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?sj5095sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?sj5095&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SJ5095](http://scripts.iucr.org/cgi-bin/sendsup?sj5095)). HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSH also thanks USM for the award of a research fellowship. Comment ======= Nitrofurans belong to a class of synthetic compounds characterized by the presence of the 5-nitro-2-furyl group. The presence of a nitro group at the 5-position of the molecule conferred antibacterial activity (Holla *et al.*1986). A large number of nitrofurans have attained commercial utility as antibacterial agents in humans and in veterinary medicine because of their broad spectrum of activity (Holla & Kalluraya *et al.*1992; Holla *et al.* 1987). Dibromopropanones were obtained by the bromination of 1-aryl-3-(5-nitro-2-furyl)-2-propen-1-ones. Acid-catalysed condensation of acetophenones with nitrofural diacetate in acetic acid yielded the required 1-aryl-3-(5-nitro-2-furyl)-2-propen-1-ones known as chalcones (Rai *et al.*, 2008). The title compound, C~13~H~9~Br~2~NO~4~, (Fig. 1), consist of phenyl (C1--C6) and 2-nitrofuran (C10--C13/O2--O4/N1) rings linked by a 2,3-dibromopropanal group (O1/C7--C9/Br1/Br2). Six atoms (C8--C10/Br1/Br2/O2) of this linking group including a furyl C atom are disordered over two positions with a site-occupancy ratio of 0.733 (11): 0.267 (11). The dihedral angle between the furan (C11--C13/O2/C10) (maximum deviation of 0.028 (4) Å of at atom C12) and phenyl rings in the major component is 16.9 (3)°. In the minor component, the corresponding values are 0.87 (4) Å at atom C12 and 23.3 (5)°. Bond lengths (Allen *et al.*, 1987) and angles are normal and comparable to those in related structures (Fun *et al.*, 2010, 2011). In the crystal packing (Fig. 2), intermolecular C9A---H9AA···O1 and C4---H4A···O4 hydrogen bonds (Table 1) link the molecules into two-dimensional arrays parallel to the *ab* plane. Experimental {#experimental} ============ 1-Phenyl-3-(5-nitro-2-furyl)-2-propen-1-one (0.01 mol) was dissolved in glacial acetic acid (25 ml) by gentle warming. A solution of bromine in glacial acetic acid (30% *w*/*v*) was added to it with constant stirring till the yellow color of the bromine persisted. The reaction mixture was kept aside at room temperature for overnight. Crystals of dibromopropanone that separated out were collected by filtration and washed with petroleum ether and dried. They were then recrystallized from glacial acetic acid. Crystals suitable for X-ray analysis were obtained from 1:2 mixtures of DMF and ethanol by slow evaporation. Refinement {#refinement} ========== All the H atoms were positioned geometrically \[C--H = 0.9300 or 0.9800 Å\] and were refined using a riding model, with *U*~iso~(H) = 1.2 *U*~eq~ (C). Six atoms are disordered over two positions with a refined occupany ratio of 0.733 (11):0.267 (11). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme. Both major and minor components are shown with bonds to atoms of the minor component drawn as open lines. ::: ![](e-67-0o546-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound, viewed along the c axis. Only the major disordered component is shown. ::: ![](e-67-0o546-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e152 .table-wrap} ------------------------ --------------------------------------- C~13~H~9~Br~2~NO~4~ *Z* = 2 *M~r~* = 403.03 *F*(000) = 392 Triclinic, *P*1 *D*~x~ = 1.939 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.6939 (7) Å Cell parameters from 4381 reflections *b* = 8.7834 (8) Å θ = 2.7--29.9° *c* = 10.4722 (9) Å µ = 5.88 mm^−1^ α = 89.334 (2)° *T* = 100 K β = 69.846 (2)° Block, colourless γ = 68.114 (2)° 0.28 × 0.18 × 0.08 mm *V* = 690.32 (10) Å^3^ ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e288 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 4015 independent reflections Radiation source: fine-focus sealed tube 3390 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.030 φ and ω scans θ~max~ = 30.1°, θ~min~ = 2.1° Absorption correction: multi-scan (*SADABS*; Bruker, 2009) *h* = −12→12 *T*~min~ = 0.292, *T*~max~ = 0.644 *k* = −12→12 10644 measured reflections *l* = −14→14 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e405 .table-wrap} ------------------------------------- --------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.100 H-atom parameters constrained *S* = 1.33 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.*P*)^2^ + 1.8339*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4015 reflections (Δ/σ)~max~ = 0.004 216 parameters Δρ~max~ = 0.71 e Å^−3^ 0 restraints Δρ~min~ = −0.60 e Å^−3^ ------------------------------------- --------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e562 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e667 .table-wrap} ------ ------------- -------------- ------------- -------------------- ------------ *x* *y* *z* *U*~iso~\*/*U*~eq~ Occ. (\<1) Br1A 0.5867 (5) −0.0270 (6) 0.3027 (5) 0.0390 (6) 0.733 (11) Br2A 0.3391 (5) 0.3650 (6) 0.0580 (4) 0.0351 (7) 0.733 (11) Br1B 0.3448 (12) 0.3749 (13) 0.0447 (8) 0.0197 (10) 0.267 (11) Br2B 0.5581 (11) −0.0069 (17) 0.3178 (13) 0.0296 (14) 0.267 (11) O1 0.2667 (4) 0.0406 (4) 0.1625 (3) 0.0338 (7) O2A 0.6226 (6) 0.3610 (7) 0.2085 (5) 0.0189 (9) 0.733 (11) O2B 0.6469 (19) 0.3223 (18) 0.2302 (15) 0.018 (3)\* 0.267 (11) O3 0.6434 (4) 0.5677 (4) 0.3755 (3) 0.0325 (6) O4 0.8888 (4) 0.5635 (4) 0.2207 (3) 0.0415 (8) N1 0.7672 (4) 0.5148 (4) 0.2642 (3) 0.0249 (6) C1 −0.0571 (5) 0.1488 (5) 0.3829 (4) 0.0212 (7) H1A −0.0479 0.0924 0.3043 0.025\* C2 −0.2122 (5) 0.1970 (5) 0.4979 (4) 0.0253 (7) H2A −0.3084 0.1755 0.4960 0.030\* C3 −0.2236 (5) 0.2777 (5) 0.6167 (4) 0.0294 (8) H3A −0.3274 0.3095 0.6943 0.035\* C4 −0.0827 (5) 0.3104 (6) 0.6197 (4) 0.0323 (9) H4A −0.0907 0.3625 0.7000 0.039\* C5 0.0721 (5) 0.2667 (5) 0.5041 (4) 0.0292 (8) H5A 0.1662 0.2918 0.5062 0.035\* C6 0.0856 (5) 0.1849 (5) 0.3846 (4) 0.0228 (7) C7 0.2483 (5) 0.1296 (5) 0.2579 (4) 0.0247 (7) C8A 0.4061 (7) 0.1730 (7) 0.2557 (5) 0.0216 (12) 0.733 (11) H8AA 0.3645 0.2723 0.3204 0.026\* 0.733 (11) C9A 0.5127 (6) 0.1929 (6) 0.1129 (5) 0.0193 (12) 0.733 (11) H9AA 0.5601 0.0895 0.0515 0.023\* 0.733 (11) C10A 0.6591 (8) 0.2419 (8) 0.1058 (6) 0.0203 (11) 0.733 (11) C8B 0.3734 (19) 0.229 (2) 0.2179 (16) 0.021 (3)\* 0.267 (11) H8BA 0.3511 0.3022 0.2981 0.025\* 0.267 (11) C9B 0.5672 (17) 0.1115 (16) 0.1590 (13) 0.018 (3)\* 0.267 (11) H9BA 0.5921 0.0391 0.0776 0.022\* 0.267 (11) C10B 0.688 (2) 0.200 (2) 0.1295 (18) 0.019 (4)\* 0.267 (11) C11 0.8299 (5) 0.1960 (5) 0.0144 (4) 0.0253 (8) H11A 0.8883 0.1133 −0.0605 0.030\* C12 0.9001 (5) 0.2992 (5) 0.0562 (4) 0.0240 (7) H12A 1.0104 0.3042 0.0109 0.029\* C13 0.7741 (5) 0.3889 (5) 0.1753 (4) 0.0214 (7) ------ ------------- -------------- ------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1189 .table-wrap} ------ ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1A 0.0594 (17) 0.0360 (9) 0.0387 (12) −0.0285 (13) −0.0276 (13) 0.0186 (8) Br2A 0.0317 (11) 0.0294 (7) 0.0539 (16) −0.0122 (6) −0.0269 (10) 0.0123 (8) Br1B 0.0144 (15) 0.026 (2) 0.0159 (13) −0.0064 (14) −0.0040 (10) 0.0003 (13) Br2B 0.0210 (13) 0.049 (4) 0.0275 (18) −0.0201 (15) −0.0118 (11) 0.017 (2) O1 0.0328 (15) 0.0468 (19) 0.0237 (14) −0.0266 (14) 0.0000 (12) −0.0101 (12) O2A 0.0164 (18) 0.022 (2) 0.018 (2) −0.0095 (17) −0.0035 (16) −0.0004 (17) O3 0.0296 (14) 0.0340 (16) 0.0319 (15) −0.0137 (13) −0.0073 (12) −0.0056 (12) O4 0.0337 (16) 0.053 (2) 0.0443 (18) −0.0308 (16) −0.0064 (14) −0.0062 (15) N1 0.0224 (14) 0.0256 (16) 0.0300 (17) −0.0107 (13) −0.0117 (13) 0.0014 (13) C1 0.0196 (15) 0.0248 (18) 0.0199 (16) −0.0109 (14) −0.0055 (13) 0.0004 (13) C2 0.0197 (16) 0.029 (2) 0.0276 (19) −0.0124 (15) −0.0056 (14) 0.0034 (15) C3 0.0229 (18) 0.034 (2) 0.029 (2) −0.0116 (16) −0.0062 (15) −0.0009 (16) C4 0.0281 (19) 0.042 (2) 0.0228 (19) −0.0168 (18) −0.0010 (15) −0.0096 (16) C5 0.0233 (17) 0.039 (2) 0.0235 (18) −0.0166 (17) −0.0010 (14) −0.0095 (16) C6 0.0211 (16) 0.0255 (18) 0.0207 (17) −0.0118 (14) −0.0033 (13) −0.0018 (13) C7 0.0212 (16) 0.0291 (19) 0.0222 (17) −0.0146 (15) −0.0008 (14) −0.0042 (14) C8A 0.020 (2) 0.024 (3) 0.022 (2) −0.012 (2) −0.0047 (19) 0.001 (2) C9A 0.018 (2) 0.021 (3) 0.018 (2) −0.0080 (18) −0.0042 (17) −0.0023 (17) C10A 0.022 (3) 0.019 (3) 0.021 (3) −0.008 (2) −0.008 (2) 0.002 (2) C11 0.0210 (17) 0.029 (2) 0.0205 (17) −0.0097 (15) −0.0014 (14) −0.0038 (14) C12 0.0154 (15) 0.029 (2) 0.0251 (18) −0.0089 (14) −0.0039 (13) 0.0019 (14) C13 0.0183 (15) 0.0254 (18) 0.0239 (17) −0.0126 (14) −0.0074 (13) 0.0026 (13) ------ ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1674 .table-wrap} ------------------------- ------------- ------------------------- ------------- Br1A---C8A 2.061 (7) C4---H4A 0.9300 Br2A---C9A 1.942 (7) C5---C6 1.398 (5) Br1B---C8B 2.24 (2) C5---H5A 0.9300 Br2B---C9B 1.944 (18) C6---C7 1.485 (5) O1---C7 1.205 (5) C7---C8A 1.547 (6) O2A---C13 1.356 (5) C7---C8B 1.586 (15) O2A---C10A 1.376 (7) C8A---C9A 1.512 (7) O2B---C10B 1.37 (2) C8A---H8AA 0.9800 O2B---C13 1.390 (15) C9A---C10A 1.468 (7) O3---N1 1.228 (4) C9A---H9AA 0.9800 O4---N1 1.229 (4) C10A---C11 1.366 (6) N1---C13 1.424 (5) C8B---C9B 1.513 (19) C1---C2 1.384 (5) C8B---H8BA 0.9800 C1---C6 1.396 (5) C9B---C10B 1.48 (2) C1---H1A 0.9300 C9B---H9BA 0.9800 C2---C3 1.394 (6) C10B---C11 1.382 (17) C2---H2A 0.9300 C11---C12 1.411 (5) C3---C4 1.369 (6) C11---H11A 0.9300 C3---H3A 0.9300 C12---C13 1.347 (5) C4---C5 1.388 (5) C12---H12A 0.9300 C13---O2A---C10A 104.7 (4) C8A---C9A---Br2A 104.1 (3) C10B---O2B---C13 103.9 (12) C10A---C9A---H9AA 109.5 O3---N1---O4 124.8 (3) C8A---C9A---H9AA 109.5 O3---N1---C13 119.5 (3) Br2A---C9A---H9AA 109.5 O4---N1---C13 115.7 (3) C11---C10A---O2A 110.5 (4) C2---C1---C6 120.1 (3) C11---C10A---C9A 133.2 (5) C2---C1---H1A 119.9 O2A---C10A---C9A 116.3 (4) C6---C1---H1A 119.9 C9B---C8B---C7 110.4 (11) C1---C2---C3 119.8 (3) C9B---C8B---Br1B 102.2 (9) C1---C2---H2A 120.1 C7---C8B---Br1B 112.9 (9) C3---C2---H2A 120.1 C9B---C8B---H8BA 110.4 C4---C3---C2 120.3 (4) C7---C8B---H8BA 110.4 C4---C3---H3A 119.8 Br1B---C8B---H8BA 110.4 C2---C3---H3A 119.8 C10B---C9B---C8B 111.8 (12) C3---C4---C5 120.7 (4) C10B---C9B---Br2B 114.8 (11) C3---C4---H4A 119.7 C8B---C9B---Br2B 95.2 (9) C5---C4---H4A 119.7 C10B---C9B---H9BA 111.3 C4---C5---C6 119.6 (4) C8B---C9B---H9BA 111.3 C4---C5---H5A 120.2 Br2B---C9B---H9BA 111.3 C6---C5---H5A 120.2 O2B---C10B---C11 111.1 (14) C1---C6---C5 119.6 (3) O2B---C10B---C9B 115.5 (14) C1---C6---C7 117.5 (3) C11---C10B---C9B 133.2 (15) C5---C6---C7 123.0 (3) C10A---C11---C10B 20.1 (6) O1---C7---C6 122.0 (3) C10A---C11---C12 106.3 (4) O1---C7---C8A 119.2 (3) C10B---C11---C12 105.3 (8) C6---C7---C8A 118.5 (3) C10A---C11---H11A 126.8 O1---C7---C8B 113.5 (6) C10B---C11---H11A 124.3 C6---C7---C8B 121.2 (6) C12---C11---H11A 126.8 C8A---C7---C8B 24.7 (5) C13---C12---C11 105.7 (3) C9A---C8A---C7 111.9 (4) C13---C12---H12A 127.1 C9A---C8A---Br1A 103.2 (3) C11---C12---H12A 127.1 C7---C8A---Br1A 108.7 (4) C12---C13---O2A 112.5 (4) C9A---C8A---H8AA 110.9 C12---C13---O2B 111.5 (7) C7---C8A---H8AA 110.9 O2A---C13---O2B 18.2 (5) Br1A---C8A---H8AA 110.9 C12---C13---N1 131.7 (3) C10A---C9A---C8A 114.2 (4) O2A---C13---N1 115.6 (3) C10A---C9A---Br2A 109.9 (4) O2B---C13---N1 115.6 (7) C6---C1---C2---C3 −1.7 (6) C7---C8B---C9B---C10B −176.0 (12) C1---C2---C3---C4 0.4 (6) Br1B---C8B---C9B---C10B 63.7 (13) C2---C3---C4---C5 1.2 (7) C7---C8B---C9B---Br2B −56.6 (11) C3---C4---C5---C6 −1.6 (7) Br1B---C8B---C9B---Br2B −176.9 (7) C2---C1---C6---C5 1.3 (6) C13---O2B---C10B---C11 −2.7 (15) C2---C1---C6---C7 179.9 (4) C13---O2B---C10B---C9B −177.7 (12) C4---C5---C6---C1 0.3 (6) C8B---C9B---C10B---O2B 45.3 (18) C4---C5---C6---C7 −178.2 (4) Br2B---C9B---C10B---O2B −61.8 (16) C1---C6---C7---O1 −8.5 (6) C8B---C9B---C10B---C11 −128.2 (19) C5---C6---C7---O1 170.0 (4) Br2B---C9B---C10B---C11 124.7 (17) C1---C6---C7---C8A 178.1 (4) O2A---C10A---C11---C10B 86 (3) C5---C6---C7---C8A −3.4 (6) C9A---C10A---C11---C10B −96 (3) C1---C6---C7---C8B 149.7 (8) O2A---C10A---C11---C12 −4.1 (7) C5---C6---C7---C8B −31.8 (9) C9A---C10A---C11---C12 174.2 (7) O1---C7---C8A---C9A 36.3 (6) O2B---C10B---C11---C10A −84 (3) C6---C7---C8A---C9A −150.1 (4) C9B---C10B---C11---C10A 89 (3) C8B---C7---C8A---C9A −46.6 (14) O2B---C10B---C11---C12 11.5 (14) O1---C7---C8A---Br1A −77.1 (5) C9B---C10B---C11---C12 −174.8 (16) C6---C7---C8A---Br1A 96.5 (4) C10A---C11---C12---C13 5.3 (5) C8B---C7---C8A---Br1A −159.9 (15) C10B---C11---C12---C13 −15.6 (9) C7---C8A---C9A---C10A 177.2 (5) C11---C12---C13---O2A −4.7 (5) Br1A---C8A---C9A---C10A −66.1 (5) C11---C12---C13---O2B 14.9 (7) C7---C8A---C9A---Br2A 57.4 (5) C11---C12---C13---N1 −178.8 (4) Br1A---C8A---C9A---Br2A 174.0 (3) C10A---O2A---C13---C12 2.2 (6) C13---O2A---C10A---C11 1.3 (7) C10A---O2A---C13---O2B −88 (3) C13---O2A---C10A---C9A −177.3 (5) C10A---O2A---C13---N1 177.3 (4) C8A---C9A---C10A---C11 139.8 (8) C10B---O2B---C13---C12 −7.8 (12) Br2A---C9A---C10A---C11 −103.6 (8) C10B---O2B---C13---O2A 89 (3) C8A---C9A---C10A---O2A −41.9 (7) C10B---O2B---C13---N1 −176.6 (9) Br2A---C9A---C10A---O2A 74.7 (6) O3---N1---C13---C12 −172.8 (4) O1---C7---C8B---C9B −59.4 (13) O4---N1---C13---C12 7.9 (6) C6---C7---C8B---C9B 140.8 (9) O3---N1---C13---O2A 13.3 (6) C8A---C7---C8B---C9B 49.9 (13) O4---N1---C13---O2A −166.0 (4) O1---C7---C8B---Br1B 54.3 (9) O3---N1---C13---O2B −6.9 (8) C6---C7---C8B---Br1B −105.5 (7) O4---N1---C13---O2B 173.8 (7) C8A---C7---C8B---Br1B 163.6 (19) ------------------------- ------------- ------------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2615 .table-wrap} -------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C9A---H9AA···O1^i^ 0.98 2.25 3.098 (6) 145 C4---H4A···O4^ii^ 0.93 2.46 3.200 (6) 136 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*, −*z*; (ii) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------------- --------- ------- ----------- ------------- C9*A*---H9*AA*⋯O1^i^ 0.98 2.25 3.098 (6) 145 C4---H4*A*⋯O4^ii^ 0.93 2.46 3.200 (6) 136 Symmetry codes: (i) ; (ii) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009.

PubMed Central

2024-06-05T04:04:18.818219

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052152/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o546", "authors": [ { "first": "Tara", "last": "Shahani" }, { "first": "Hoong-Kun", "last": "Fun" }, { "first": null, "last": "Nithinchandra" }, { "first": "Balakrishna", "last": "Kalluraya" } ] }

PMC3052153

Related literature {#sec1} ================== For the structures of CuCl~2~ complexes with similar ligands, see: Saleh Salga *et al.* (2010[@bb4]); Wang *et al.* (2009[@bb7]). For the structure of a CdCl~2~ complex with the same Schiff base ligand, see: Ikmal Hisham *et al.* (2010[@bb3]). For a description of the geometry of complexes with a five-coordinate metal atom, see: Addison *et al.* (1984[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[CuCl~2~(C~13~H~19~N~3~O)\]·H~2~O*M* *~r~* = 385.77Monoclinic,*a* = 7.9194 (8) Å*b* = 8.5793 (8) Å*c* = 22.925 (2) Åβ = 91.981 (1)°*V* = 1556.6 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 1.75 mm^−1^*T* = 100 K0.18 × 0.16 × 0.09 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb5]) *T* ~min~ = 0.743, *T* ~max~ = 0.8589634 measured reflections3348 independent reflections2948 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.023 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.025*wR*(*F* ^2^) = 0.060*S* = 1.053348 reflections197 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.34 e Å^−3^ {#d5e573} Data collection: *APEX2* (Bruker, 2007[@bb2]); cell refinement: *SAINT* (Bruker, 2007[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *X-SEED* (Barbour, 2001)[@bb9]; software used to prepare material for publication: *SHELXL97* and *publCIF* (Westrip, 2010[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004892/is2674sup1.cif](http://dx.doi.org/10.1107/S1600536811004892/is2674sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004892/is2674Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004892/is2674Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2674&file=is2674sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2674sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2674&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2674](http://scripts.iucr.org/cgi-bin/sendsup?is2674)). The authors thank University of Malaya for funding this study (FRGS grant No. FP004/2010B). Comment ======= The asymmetric unit of the title compound consists of a copper(II) complex and one molecule of water. Like the CdCl~2~ complex of the Schiff base, 2-morpholino-*N*-\[1-(2-pyridyl)ethylidene\]ethanamine, (Ikmal Hisham *et al.*, 2010) the metal ion in the present structure is five-coordinated by the *N,N\',N\"*-tridentate Schiff base ligand and two Cl atoms in a distorted square-pyramidal geometry, the τ value (Addison *et al.*,1984) being 0.15. The Cu---Cl and Cu---N interatomic distances are comparable to the values reported in the literature (Saleh Salga *et al.*, 2010; Wang *et al.*, 2009). In the crystal, the adjacent metal complexes and water molecules are linked into a three-dimensional network *via* O---H···Cl, C---H···Cl and C---H···O interactions. In addition, intramolecular C---H···Cl hydrogen bonding is observed. Experimental {#experimental} ============ A mixture of 2-acetylpyridine (0.20 g, 1.65 mmol) and 4-(2-aminoethyl)morpholine (0.21 g, 1.65 mmol) in ethanol (20 ml) was refluxed. After 2 hr a solution of copper(II) chloride dihydrate (0.28 g, 1.65 mmol) in a minimum amount of ethanol was added and the resulting solution was refluxed for 30 min, then set aside at room temperature. The crystals of the title complex were obtained after a few days. Refinement {#refinement} ========== The C-bound hydrogen atoms were placed at calculated positions (C---H 0.95--0.99 Å) and were treated as riding on their parent atoms. The O-bound H atoms were placed in a difference Fourier map, and were refined with distance restraint of O---H 0.84 (2) Å. For all hydrogen atoms *U*~iso~(H) were set to 1.2--1.5 times *U*~eq~(carrier atom). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Displacement ellipsoid plot of the title compound at the 50% probability level. Hydrogen atoms are drawn as spheres of arbitrary radii. ::: ![](e-67-0m334-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e126 .table-wrap} ------------------------------------ --------------------------------------- \[CuCl~2~(C~13~H~19~N~3~O)\]·H~2~O *F*(000) = 796 *M~r~* = 385.77 *D*~x~ = 1.646 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 4229 reflections *a* = 7.9194 (8) Å θ = 2.5--28.2° *b* = 8.5793 (8) Å µ = 1.75 mm^−1^ *c* = 22.925 (2) Å *T* = 100 K β = 91.981 (1)° Block, green *V* = 1556.6 (3) Å^3^ 0.18 × 0.16 × 0.09 mm *Z* = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e260 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker APEXII CCD diffractometer 3348 independent reflections Radiation source: fine-focus sealed tube 2948 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.023 φ and ω scans θ~max~ = 27.0°, θ~min~ = 2.5° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −10→10 *T*~min~ = 0.743, *T*~max~ = 0.858 *k* = −10→10 9634 measured reflections *l* = −29→28 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e377 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.025 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.060 H atoms treated by a mixture of independent and constrained refinement *S* = 1.05 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0258*P*)^2^ + 0.893*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3348 reflections (Δ/σ)~max~ = 0.001 197 parameters Δρ~max~ = 0.37 e Å^−3^ 2 restraints Δρ~min~ = −0.34 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e534 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e633 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cu1 0.60251 (3) 0.86379 (2) 0.122328 (9) 0.01099 (7) Cl1 0.49087 (6) 0.62132 (5) 0.11931 (2) 0.01873 (11) Cl2 0.90458 (6) 0.85029 (5) 0.15951 (2) 0.01773 (11) O1 0.32231 (17) 0.82636 (16) 0.30317 (6) 0.0183 (3) N1 0.68558 (19) 0.86674 (17) 0.03959 (7) 0.0129 (3) N2 0.60269 (19) 1.09006 (17) 0.10733 (7) 0.0119 (3) N3 0.51025 (18) 0.92685 (17) 0.20213 (6) 0.0114 (3) C1 0.7350 (2) 0.7448 (2) 0.00826 (8) 0.0159 (4) H1 0.7128 0.6427 0.0221 0.019\* C2 0.8177 (2) 0.7617 (2) −0.04381 (8) 0.0167 (4) H2 0.8513 0.6729 −0.0653 0.020\* C3 0.8501 (2) 0.9106 (2) −0.06373 (8) 0.0156 (4) H3 0.9077 0.9254 −0.0990 0.019\* C4 0.7975 (2) 1.0386 (2) −0.03157 (8) 0.0147 (4) H4 0.8168 1.1417 −0.0449 0.018\* C5 0.7169 (2) 1.0126 (2) 0.01989 (8) 0.0121 (4) C6 0.6645 (2) 1.1396 (2) 0.05987 (8) 0.0127 (4) C7 0.6910 (2) 1.3055 (2) 0.04320 (8) 0.0172 (4) H7A 0.6395 1.3737 0.0719 0.026\* H7B 0.6385 1.3247 0.0045 0.026\* H7C 0.8124 1.3271 0.0422 0.026\* C8 0.5483 (2) 1.1856 (2) 0.15617 (8) 0.0127 (4) H8A 0.4272 1.2127 0.1510 0.015\* H8B 0.6148 1.2832 0.1587 0.015\* C9 0.5779 (2) 1.0881 (2) 0.21117 (8) 0.0132 (4) H9A 0.7005 1.0830 0.2210 0.016\* H9B 0.5212 1.1379 0.2442 0.016\* C10 0.5778 (2) 0.8179 (2) 0.24813 (8) 0.0139 (4) H10A 0.7017 0.8316 0.2522 0.017\* H10B 0.5557 0.7094 0.2353 0.017\* C11 0.5017 (2) 0.8419 (2) 0.30720 (8) 0.0174 (4) H11A 0.5492 0.7642 0.3352 0.021\* H11B 0.5316 0.9471 0.3221 0.021\* C12 0.2547 (2) 0.9419 (2) 0.26393 (8) 0.0171 (4) H12A 0.2853 1.0468 0.2789 0.021\* H12B 0.1299 0.9340 0.2620 0.021\* C13 0.3217 (2) 0.9220 (2) 0.20293 (8) 0.0130 (4) H13A 0.2818 0.8210 0.1867 0.016\* H13B 0.2749 1.0057 0.1774 0.016\* O2 0.0878 (2) 0.59912 (18) 0.08146 (7) 0.0273 (3) H2A 0.035 (3) 0.659 (3) 0.1032 (10) 0.033\* H2B 0.183 (2) 0.602 (3) 0.0978 (11) 0.033\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1188 .table-wrap} ----- -------------- -------------- -------------- --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cu1 0.01348 (12) 0.00927 (11) 0.01044 (12) 0.00023 (8) 0.00364 (8) 0.00007 (8) Cl1 0.0256 (3) 0.0112 (2) 0.0200 (2) −0.00334 (17) 0.00966 (19) −0.00245 (17) Cl2 0.0123 (2) 0.0245 (2) 0.0165 (2) 0.00191 (17) 0.00273 (17) 0.00437 (18) O1 0.0157 (7) 0.0231 (7) 0.0165 (7) −0.0002 (5) 0.0050 (5) 0.0047 (6) N1 0.0131 (7) 0.0133 (7) 0.0124 (8) 0.0007 (6) 0.0013 (6) 0.0005 (6) N2 0.0124 (7) 0.0112 (7) 0.0120 (8) 0.0006 (6) 0.0008 (6) −0.0010 (6) N3 0.0109 (7) 0.0114 (7) 0.0120 (8) −0.0005 (6) 0.0013 (6) −0.0006 (6) C1 0.0190 (10) 0.0125 (9) 0.0162 (10) 0.0001 (7) 0.0019 (8) −0.0010 (7) C2 0.0175 (9) 0.0177 (9) 0.0151 (10) 0.0032 (7) 0.0029 (7) −0.0031 (7) C3 0.0142 (9) 0.0215 (10) 0.0113 (9) 0.0014 (7) 0.0017 (7) 0.0002 (7) C4 0.0145 (9) 0.0155 (9) 0.0142 (9) 0.0001 (7) 0.0004 (7) 0.0017 (7) C5 0.0127 (9) 0.0130 (8) 0.0107 (9) 0.0010 (7) 0.0003 (7) −0.0004 (7) C6 0.0108 (8) 0.0141 (9) 0.0130 (9) 0.0002 (7) 0.0003 (7) 0.0008 (7) C7 0.0229 (10) 0.0124 (9) 0.0169 (10) 0.0016 (7) 0.0070 (8) 0.0016 (7) C8 0.0150 (9) 0.0109 (8) 0.0124 (9) −0.0008 (7) 0.0031 (7) −0.0010 (7) C9 0.0145 (9) 0.0126 (9) 0.0126 (9) −0.0025 (7) 0.0007 (7) −0.0029 (7) C10 0.0127 (9) 0.0155 (9) 0.0134 (9) 0.0024 (7) 0.0007 (7) 0.0033 (7) C11 0.0160 (9) 0.0228 (10) 0.0134 (9) 0.0002 (8) 0.0021 (7) 0.0025 (8) C12 0.0152 (9) 0.0194 (9) 0.0171 (10) 0.0013 (7) 0.0056 (8) −0.0004 (8) C13 0.0099 (8) 0.0144 (9) 0.0148 (9) −0.0005 (7) 0.0009 (7) 0.0000 (7) O2 0.0307 (9) 0.0231 (8) 0.0285 (9) 0.0035 (7) 0.0053 (7) −0.0013 (7) ----- -------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1581 .table-wrap} ----------------- -------------- ------------------- ------------- Cu1---N2 1.9715 (15) C5---C6 1.491 (2) Cu1---N1 2.0290 (15) C6---C7 1.490 (2) Cu1---N3 2.0654 (15) C7---H7A 0.9800 Cu1---Cl1 2.2604 (5) C7---H7B 0.9800 Cu1---Cl2 2.5143 (5) C7---H7C 0.9800 O1---C11 1.427 (2) C8---C9 1.524 (2) O1---C12 1.430 (2) C8---H8A 0.9900 N1---C1 1.336 (2) C8---H8B 0.9900 N1---C5 1.356 (2) C9---H9A 0.9900 N2---C6 1.281 (2) C9---H9B 0.9900 N2---C8 1.464 (2) C10---C11 1.515 (3) N3---C10 1.494 (2) C10---H10A 0.9900 N3---C13 1.495 (2) C10---H10B 0.9900 N3---C9 1.495 (2) C11---H11A 0.9900 C1---C2 1.389 (3) C11---H11B 0.9900 C1---H1 0.9500 C12---C13 1.522 (3) C2---C3 1.383 (3) C12---H12A 0.9900 C2---H2 0.9500 C12---H12B 0.9900 C3---C4 1.395 (3) C13---H13A 0.9900 C3---H3 0.9500 C13---H13B 0.9900 C4---C5 1.379 (3) O2---H2A 0.837 (16) C4---H4 0.9500 O2---H2B 0.831 (16) N2---Cu1---N1 79.77 (6) C6---C7---H7B 109.5 N2---Cu1---N3 84.20 (6) H7A---C7---H7B 109.5 N1---Cu1---N3 163.90 (6) C6---C7---H7C 109.5 N2---Cu1---Cl1 154.62 (5) H7A---C7---H7C 109.5 N1---Cu1---Cl1 97.01 (4) H7B---C7---H7C 109.5 N3---Cu1---Cl1 96.79 (4) N2---C8---C9 106.53 (14) N2---Cu1---Cl2 95.63 (5) N2---C8---H8A 110.4 N1---Cu1---Cl2 88.97 (5) C9---C8---H8A 110.4 N3---Cu1---Cl2 94.20 (4) N2---C8---H8B 110.4 Cl1---Cu1---Cl2 109.544 (19) C9---C8---H8B 110.4 C11---O1---C12 109.02 (14) H8A---C8---H8B 108.6 C1---N1---C5 118.92 (16) N3---C9---C8 110.42 (14) C1---N1---Cu1 127.12 (12) N3---C9---H9A 109.6 C5---N1---Cu1 113.06 (12) C8---C9---H9A 109.6 C6---N2---C8 126.51 (15) N3---C9---H9B 109.6 C6---N2---Cu1 118.51 (13) C8---C9---H9B 109.6 C8---N2---Cu1 114.57 (11) H9A---C9---H9B 108.1 C10---N3---C13 107.88 (14) N3---C10---C11 113.72 (15) C10---N3---C9 111.29 (14) N3---C10---H10A 108.8 C13---N3---C9 112.19 (14) C11---C10---H10A 108.8 C10---N3---Cu1 109.42 (11) N3---C10---H10B 108.8 C13---N3---Cu1 112.81 (11) C11---C10---H10B 108.8 C9---N3---Cu1 103.24 (10) H10A---C10---H10B 107.7 N1---C1---C2 122.40 (17) O1---C11---C10 110.79 (15) N1---C1---H1 118.8 O1---C11---H11A 109.5 C2---C1---H1 118.8 C10---C11---H11A 109.5 C3---C2---C1 118.62 (17) O1---C11---H11B 109.5 C3---C2---H2 120.7 C10---C11---H11B 109.5 C1---C2---H2 120.7 H11A---C11---H11B 108.1 C2---C3---C4 119.35 (17) O1---C12---C13 111.41 (15) C2---C3---H3 120.3 O1---C12---H12A 109.3 C4---C3---H3 120.3 C13---C12---H12A 109.3 C5---C4---C3 118.75 (17) O1---C12---H12B 109.3 C5---C4---H4 120.6 C13---C12---H12B 109.3 C3---C4---H4 120.6 H12A---C12---H12B 108.0 N1---C5---C4 121.95 (16) N3---C13---C12 112.83 (15) N1---C5---C6 114.30 (15) N3---C13---H13A 109.0 C4---C5---C6 123.69 (16) C12---C13---H13A 109.0 N2---C6---C7 126.57 (17) N3---C13---H13B 109.0 N2---C6---C5 113.71 (16) C12---C13---H13B 109.0 C7---C6---C5 119.70 (16) H13A---C13---H13B 107.8 C6---C7---H7A 109.5 H2A---O2---H2B 101 (2) ----------------- -------------- ------------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2183 .table-wrap} -------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O2---H2A···Cl2^i^ 0.84 (2) 2.35 (2) 3.1829 (16) 173 (2) O2---H2B···Cl1 0.83 (2) 2.48 (2) 3.2841 (18) 164 (2) C2---H2···O2^ii^ 0.95 2.41 3.307 (2) 156 C3---H3···Cl2^iii^ 0.95 2.82 3.619 (2) 142 C4---H4···O2^iv^ 0.95 2.50 3.445 (2) 172 C7---H7A···Cl1^v^ 0.98 2.68 3.6179 (19) 161 C8---H8A···O1^vi^ 0.99 2.47 3.336 (2) 146 C10---H10B···Cl1 0.99 2.79 3.4496 (19) 124 C10---H10A···Cl2 0.99 2.71 3.3566 (19) 123 -------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) *x*−1, *y*, *z*; (ii) −*x*+1, −*y*+1, −*z*; (iii) −*x*+2, −*y*+2, −*z*; (iv) −*x*+1, −*y*+2, −*z*; (v) *x*, *y*+1, *z*; (vi) −*x*+1/2, *y*+1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------- ---------- ---------- ------------- ------------- O2---H2*A*⋯Cl2^i^ 0.84 (2) 2.35 (2) 3.1829 (16) 173 (2) O2---H2*B*⋯Cl1 0.83 (2) 2.48 (2) 3.2841 (18) 164 (2) C2---H2⋯O2^ii^ 0.95 2.41 3.307 (2) 156 C3---H3⋯Cl2^iii^ 0.95 2.82 3.619 (2) 142 C4---H4⋯O2^iv^ 0.95 2.50 3.445 (2) 172 C7---H7*A*⋯Cl1^v^ 0.98 2.68 3.6179 (19) 161 C8---H8*A*⋯O1^vi^ 0.99 2.47 3.336 (2) 146 C10---H10*B*⋯Cl1 0.99 2.79 3.4496 (19) 124 C10---H10*A*⋯Cl2 0.99 2.71 3.3566 (19) 123 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) . :::

PubMed Central

2024-06-05T04:04:18.824821

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052153/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m334", "authors": [ { "first": "Nura", "last": "Suleiman Gwaram" }, { "first": "Hamid", "last": "Khaledi" }, { "first": "Hapipah", "last": "Mohd Ali" } ] }

PMC3052154

Related literature {#sec1} ================== For the synthesis of the starting material, see: Tolmachev *et al.* (2006[@bb6]). For a related structure, see: Ha *et al.* (2009[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~17~N~3~*M* *~r~* = 275.35Monoclinic,*a* = 11.5580 (7) Å*b* = 9.9179 (6) Å*c* = 13.9268 (7) Åβ = 105.707 (2)°*V* = 1536.83 (15) Å^3^*Z* = 4Mo *K*α radiationμ = 0.07 mm^−1^*T* = 100 K0.5 × 0.4 × 0.2 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID II-S diffractometerAbsorption correction: multi-scan (*RAPID-AUTO*; Rigaku, 2008[@bb4]) *T* ~min~ = 0.966, *T* ~max~ = 0.98613505 measured reflections3185 independent reflections2321 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.077 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.049*wR*(*F* ^2^) = 0.134*S* = 1.073185 reflections193 parametersH-atom parameters constrainedΔρ~max~ = 0.22 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e330} Data collection: *RAPID-AUTO* (Rigaku, 2008[@bb4]); cell refinement: *RAPID-AUTO*; data reduction: *RAPID-AUTO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb1]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb2]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005587/bq2278sup1.cif](http://dx.doi.org/10.1107/S1600536811005587/bq2278sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005587/bq2278Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005587/bq2278Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bq2278&file=bq2278sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bq2278sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bq2278&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BQ2278](http://scripts.iucr.org/cgi-bin/sendsup?bq2278)). This study was supported financially by Chonnam National University. CHK thanks the RIC, Sunchon National University, for financial support. Comment ======= Recently we have reported the structure of 2-(1-propyl-2,6-distyryl-1,4-pyridin-4-ylidene)malononitrile as a fluorescent dye (Ha *et al.*, 2009). Continuing our study on the (1,4-pyridin-4-ylidene)malononitrile derivatives, the title compound was synthesized and its structure was confirmed by ^1^H NMR and X-ray crystal analysis. In the title compound, C~18~H~17~N~3~, the dihedral angles between the central pyridine and phenyl ring is 72.57 (5)° and that between the pyridine ring and malonitrile plane (N2 C13 C12 C14 N3 plane) is 5.19 (20)°. The bond distances of C---C bonds in the pyridine ring are considerably shorter than those of normal single bonds (D(C1---C2) = D(C1---C5) = 1.413 (3) Å). These results suggest that the electrons on the pyridine ring including non-bonding electrons of N1 are delocalized on the ring (Fig. 1). Experimental {#experimental} ============ A mixture of 2-(2-methyl-6-phenyl-4*H*-pyran-4-ylidene)malononitrile (1.5 g, 6.4 mmol) and *n*-propylamine (20 ml) was heated at 150 °C for 3 h. The mixture was cooled and concentrated under vacuum. Crude product was recrystallized from MeOH to give crystals suitable for X-ray analysis (1.20 g, 68%). Mp 166--167 °C. ^1^H NMR (300 MHz, CDCl~3~) δ 7.52--7.26 (m, 5H, Ph), 6.79 (d, 1H, J = 2.5 Hz, C---C*H*=C---N), 6.70 (d, 1H, J = 2.5 Hz), 3.75 (t, 2H, J = 8.1 Hz, NC*H*~2~CH~2~CH~3~), 2.50 (s, 3H, C*H*~3~), 1.52 (m, 2H, NCH~2~C*H*~2~CH~3~), 0.70 (t, 3H, J = 7.4 Hz, NCH~2~CH~2~C*H*~3~) Refinement {#refinement} ========== H atoms were positioned geometrically and allowed to ride on their respective parent atoms \[C---H = 0.93 (CH, *sp*^2^), 0.96 (CH~3~), 0.97Å (CH~2~), respectively and *U*~iso~(H) = 1.2*U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The structure of the title compound with displacement ellipsoids drawn at the 50% probability level for non-H atoms. ::: ![](e-67-0o670-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e186 .table-wrap} ------------------------- ---------------------------------------- C~18~H~17~N~3~ *F*(000) = 584 *M~r~* = 275.35 Z = 4 Monoclinic, *P*2~1~/*c* *D*~x~ = 1.190 Mg m^−3^ Hall symbol: -P 2ybc Mo *K*α radiation, λ = 0.71073 Å *a* = 11.5580 (7) Å Cell parameters from 15051 reflections *b* = 9.9179 (6) Å θ = 27.5--3.0° *c* = 13.9268 (7) Å µ = 0.07 mm^−1^ β = 105.707 (2)° *T* = 100 K *V* = 1536.83 (15) Å^3^ Block, yellow *Z* = 4 0.5 × 0.4 × 0.2 mm ------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e314 .table-wrap} ---------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID II-S diffractometer 3185 independent reflections Radiation source: fine-focus sealed tube 2321 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.077 ω scans θ~max~ = 26.5°, θ~min~ = 3.0° Absorption correction: multi-scan (*RAPID-AUTO*; Rigaku, 2008) *h* = −14→14 *T*~min~ = 0.966, *T*~max~ = 0.986 *k* = −12→12 13505 measured reflections *l* = −16→17 ---------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e428 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.049 H-atom parameters constrained *wR*(*F*^2^) = 0.134 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0522*P*)^2^ + 0.3213*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.07 (Δ/σ)~max~ \< 0.001 3185 reflections Δρ~max~ = 0.22 e Å^−3^ 193 parameters Δρ~min~ = −0.20 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.013 (3) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e609 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e708 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.86513 (14) 0.37654 (15) 0.41005 (10) 0.0322 (4) C2 0.94627 (14) 0.43142 (16) 0.36078 (11) 0.0350 (4) H2 1.0277 0.4120 0.3851 0.042\* C3 0.90918 (14) 0.51234 (16) 0.27834 (11) 0.0345 (4) C4 0.70719 (14) 0.49082 (15) 0.28609 (10) 0.0311 (4) C5 0.74344 (14) 0.41302 (16) 0.36931 (11) 0.0332 (4) H5 0.6864 0.3829 0.4004 0.040\* C6 0.57636 (14) 0.51915 (15) 0.24329 (11) 0.0325 (4) C7 0.51068 (15) 0.45459 (18) 0.15657 (12) 0.0402 (4) H7 0.5498 0.3993 0.1214 0.048\* C8 0.38795 (16) 0.4724 (2) 0.12290 (13) 0.0466 (4) H8 0.3443 0.4281 0.0657 0.056\* C9 0.32989 (16) 0.55609 (19) 0.17404 (13) 0.0467 (5) H9 0.2473 0.5686 0.1506 0.056\* C10 0.39303 (17) 0.62090 (19) 0.25902 (14) 0.0478 (5) H10 0.3534 0.6773 0.2931 0.057\* C11 0.51660 (15) 0.60193 (18) 0.29407 (12) 0.0409 (4) H11 0.5594 0.6452 0.3521 0.049\* C12 0.90262 (14) 0.28936 (16) 0.49335 (11) 0.0357 (4) C13 0.82087 (16) 0.24072 (17) 0.54461 (12) 0.0399 (4) C14 1.02361 (17) 0.24658 (18) 0.52802 (12) 0.0436 (4) C15 0.74831 (15) 0.63071 (16) 0.15180 (11) 0.0366 (4) H15A 0.6704 0.5997 0.1122 0.044\* H15B 0.8041 0.6235 0.1110 0.044\* C16 0.73834 (19) 0.77697 (18) 0.17897 (12) 0.0481 (5) H16A 0.8174 0.8115 0.2129 0.058\* H16B 0.6877 0.7844 0.2241 0.058\* C17 0.6847 (2) 0.8605 (2) 0.08532 (15) 0.0669 (6) H17A 0.6826 0.9537 0.1032 0.100\* H17B 0.6045 0.8298 0.0542 0.100\* H17C 0.7333 0.8503 0.0397 0.100\* C18 0.99893 (17) 0.5697 (2) 0.22903 (14) 0.0500 (5) H18A 0.9884 0.6655 0.2224 0.075\* H18B 0.9869 0.5300 0.1642 0.075\* H18C 1.0788 0.5500 0.2690 0.075\* N1 0.78979 (11) 0.54168 (13) 0.24021 (9) 0.0320 (3) N2 0.75433 (16) 0.20179 (18) 0.58685 (12) 0.0569 (5) N3 1.12223 (16) 0.2122 (2) 0.55469 (12) 0.0672 (5) ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1203 .table-wrap} ----- ------------- ------------- ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0369 (9) 0.0294 (8) 0.0286 (7) −0.0009 (7) 0.0057 (6) −0.0046 (6) C2 0.0321 (8) 0.0349 (9) 0.0361 (8) 0.0006 (7) 0.0058 (6) −0.0010 (6) C3 0.0334 (9) 0.0337 (9) 0.0367 (8) −0.0020 (7) 0.0100 (6) −0.0031 (6) C4 0.0342 (9) 0.0282 (8) 0.0299 (7) −0.0015 (6) 0.0069 (6) −0.0038 (6) C5 0.0332 (8) 0.0354 (8) 0.0303 (8) −0.0013 (7) 0.0073 (6) −0.0003 (6) C6 0.0333 (8) 0.0324 (8) 0.0306 (7) 0.0024 (7) 0.0068 (6) 0.0039 (6) C7 0.0382 (9) 0.0434 (10) 0.0372 (8) 0.0010 (7) 0.0070 (7) −0.0041 (7) C8 0.0399 (10) 0.0557 (11) 0.0386 (9) −0.0008 (8) 0.0012 (7) 0.0013 (8) C9 0.0350 (10) 0.0525 (11) 0.0496 (10) 0.0065 (8) 0.0063 (8) 0.0144 (8) C10 0.0476 (11) 0.0480 (11) 0.0518 (10) 0.0119 (9) 0.0204 (8) 0.0050 (8) C11 0.0431 (10) 0.0425 (10) 0.0364 (8) 0.0032 (8) 0.0097 (7) −0.0027 (7) C12 0.0371 (9) 0.0361 (9) 0.0320 (8) 0.0022 (7) 0.0062 (6) 0.0017 (6) C13 0.0469 (10) 0.0386 (9) 0.0326 (8) 0.0038 (8) 0.0081 (7) 0.0025 (7) C14 0.0484 (11) 0.0502 (11) 0.0321 (8) 0.0099 (9) 0.0105 (7) 0.0071 (7) C15 0.0431 (9) 0.0387 (9) 0.0276 (7) 0.0021 (7) 0.0091 (7) 0.0022 (6) C16 0.0662 (13) 0.0414 (10) 0.0380 (9) 0.0068 (9) 0.0163 (8) 0.0044 (7) C17 0.0989 (18) 0.0518 (12) 0.0534 (11) 0.0250 (12) 0.0265 (11) 0.0160 (9) C18 0.0451 (11) 0.0524 (11) 0.0554 (11) −0.0005 (8) 0.0185 (8) 0.0122 (9) N1 0.0356 (7) 0.0310 (7) 0.0287 (6) 0.0000 (5) 0.0075 (5) 0.0001 (5) N2 0.0670 (11) 0.0572 (11) 0.0521 (9) 0.0020 (9) 0.0258 (9) 0.0113 (8) N3 0.0545 (11) 0.0899 (14) 0.0562 (10) 0.0296 (10) 0.0130 (8) 0.0229 (9) ----- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1590 .table-wrap} --------------------- -------------- ---------------------- -------------- C1---C2 1.412 (2) C10---H10 0.9300 C1---C5 1.414 (2) C11---H11 0.9300 C1---C12 1.417 (2) C12---C13 1.414 (2) C2---C3 1.371 (2) C12---C14 1.415 (2) C2---H2 0.9300 C13---N2 1.154 (2) C3---N1 1.369 (2) C14---N3 1.151 (2) C3---C18 1.502 (2) C15---N1 1.4852 (18) C4---C5 1.361 (2) C15---C16 1.511 (2) C4---N1 1.3801 (19) C15---H15A 0.9700 C4---C6 1.494 (2) C15---H15B 0.9700 C5---H5 0.9300 C16---C17 1.527 (2) C6---C11 1.384 (2) C16---H16A 0.9700 C6---C7 1.396 (2) C16---H16B 0.9700 C7---C8 1.380 (2) C17---H17A 0.9600 C7---H7 0.9300 C17---H17B 0.9600 C8---C9 1.380 (3) C17---H17C 0.9600 C8---H8 0.9300 C18---H18A 0.9600 C9---C10 1.371 (3) C18---H18B 0.9600 C9---H9 0.9300 C18---H18C 0.9600 C10---C11 1.391 (2) C2---C1---C5 115.20 (13) C13---C12---C14 117.32 (14) C2---C1---C12 122.45 (14) C13---C12---C1 121.55 (14) C5---C1---C12 122.34 (14) C14---C12---C1 121.13 (15) C3---C2---C1 122.29 (15) N2---C13---C12 179.5 (2) C3---C2---H2 118.9 N3---C14---C12 178.88 (18) C1---C2---H2 118.9 N1---C15---C16 113.11 (12) N1---C3---C2 120.21 (14) N1---C15---H15A 109.0 N1---C3---C18 119.37 (14) C16---C15---H15A 109.0 C2---C3---C18 120.42 (15) N1---C15---H15B 109.0 C5---C4---N1 120.64 (14) C16---C15---H15B 109.0 C5---C4---C6 119.44 (13) H15A---C15---H15B 107.8 N1---C4---C6 119.92 (12) C15---C16---C17 110.33 (14) C4---C5---C1 122.03 (14) C15---C16---H16A 109.6 C4---C5---H5 119.0 C17---C16---H16A 109.6 C1---C5---H5 119.0 C15---C16---H16B 109.6 C11---C6---C7 118.97 (15) C17---C16---H16B 109.6 C11---C6---C4 119.92 (14) H16A---C16---H16B 108.1 C7---C6---C4 120.90 (14) C16---C17---H17A 109.5 C8---C7---C6 120.24 (16) C16---C17---H17B 109.5 C8---C7---H7 119.9 H17A---C17---H17B 109.5 C6---C7---H7 119.9 C16---C17---H17C 109.5 C7---C8---C9 120.04 (16) H17A---C17---H17C 109.5 C7---C8---H8 120.0 H17B---C17---H17C 109.5 C9---C8---H8 120.0 C3---C18---H18A 109.5 C10---C9---C8 120.53 (17) C3---C18---H18B 109.5 C10---C9---H9 119.7 H18A---C18---H18B 109.5 C8---C9---H9 119.7 C3---C18---H18C 109.5 C9---C10---C11 119.70 (16) H18A---C18---H18C 109.5 C9---C10---H10 120.1 H18B---C18---H18C 109.5 C11---C10---H10 120.1 C3---N1---C4 119.59 (12) C6---C11---C10 120.52 (15) C3---N1---C15 120.88 (13) C6---C11---H11 119.7 C4---N1---C15 119.51 (13) C10---C11---H11 119.7 C5---C1---C2---C3 −1.1 (2) C4---C6---C11---C10 −175.04 (15) C12---C1---C2---C3 177.93 (14) C9---C10---C11---C6 0.6 (3) C1---C2---C3---N1 −0.6 (2) C2---C1---C12---C13 176.88 (15) C1---C2---C3---C18 179.35 (15) C5---C1---C12---C13 −4.2 (2) N1---C4---C5---C1 −2.5 (2) C2---C1---C12---C14 −3.7 (2) C6---C4---C5---C1 176.43 (14) C5---C1---C12---C14 175.28 (15) C2---C1---C5---C4 2.6 (2) N1---C15---C16---C17 −174.92 (16) C12---C1---C5---C4 −176.36 (14) C2---C3---N1---C4 0.9 (2) C5---C4---C6---C11 69.6 (2) C18---C3---N1---C4 −179.09 (15) N1---C4---C6---C11 −111.43 (17) C2---C3---N1---C15 179.15 (14) C5---C4---C6---C7 −105.08 (17) C18---C3---N1---C15 −0.8 (2) N1---C4---C6---C7 73.9 (2) C5---C4---N1---C3 0.7 (2) C11---C6---C7---C8 −0.6 (2) C6---C4---N1---C3 −178.28 (13) C4---C6---C7---C8 174.15 (15) C5---C4---N1---C15 −177.62 (13) C6---C7---C8---C9 1.1 (3) C6---C4---N1---C15 3.4 (2) C7---C8---C9---C10 −0.7 (3) C16---C15---N1---C3 −93.10 (18) C8---C9---C10---C11 −0.1 (3) C16---C15---N1---C4 85.16 (18) C7---C6---C11---C10 −0.2 (2) --------------------- -------------- ---------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.829911

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052154/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o670", "authors": [ { "first": "Young Hyun", "last": "Kim" }, { "first": "Hyung Jin", "last": "Kim" }, { "first": "Enkhzul", "last": "Otgonbaatar" }, { "first": "Chee-Hun", "last": "Kwak" } ] }

PMC3052155

Related literature {#sec1} ================== For crystalline metal complexes of styphnic acid, see: Cui *et al.* (2008**a*[@bb3],b* [@bb4]); Orbovic & Codoceo (2008[@bb7]); Zheng *et al.* (2006*a* [@bb12],*b* [@bb13]); Zhu & Xiao (2009[@bb14]). For crystalline adducts of styphnic acid with organic bases, see: Abashev *et al.* (2001[@bb1]); Liu *et al.* (2008[@bb6]); Tenishev *et al.* (2002[@bb10]); For related molecular salts, see: Kalaivani & Malarvizhi (2010[@bb5]); Vogel (1978[@bb11]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~7~H~10~NO^+^·C~6~H~2~N~3~O~8~ ^−^*M* *~r~* = 368.27Monoclinic,*a* = 10.6957 (4) Å*b* = 17.8368 (5) Å*c* = 8.0527 (3) Åβ = 91.991 (2)°*V* = 1535.34 (9) Å^3^*Z* = 4Mo *K*α radiationμ = 0.14 mm^−1^*T* = 293 K0.22 × 0.18 × 0.12 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2008[@bb2]) *T* ~min~ = 0.978, *T* ~max~ = 0.98819208 measured reflections4930 independent reflections3539 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.028 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.050*wR*(*F* ^2^) = 0.142*S* = 1.044930 reflections238 parametersH-atom parameters constrainedΔρ~max~ = 0.45 e Å^−3^Δρ~min~ = −0.40 e Å^−3^ {#d5e585} Data collection: *APEX2* (Bruker, 2008[@bb2]); cell refinement: *SAINT* (Bruker, 2008[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]); molecular graphics: *PLATON* (Spek, 2009[@bb9]); software used to prepare material for publication: *PLATON*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005708/bv2174sup1.cif](http://dx.doi.org/10.1107/S1600536811005708/bv2174sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005708/bv2174Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005708/bv2174Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bv2174&file=bv2174sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bv2174sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bv2174&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BV2174](http://scripts.iucr.org/cgi-bin/sendsup?bv2174)). The authors thank the DST-India (FIST programme) for the use of the Bruker SMART APEXII diffractometer at the School of Chemistry, Bharathidasan University. Comment ======= In spite of the fact that many crystalline complexes have been derived from styphnic acid and metals in recent years \[(Cui *et al.*, 2008**a*,* 2008*b*), (Orbovic *et al.*, 2008), (Zheng *et al.*, 2006*a*, 2006*b*), (Zhu & Xiao, 2009)\], only a few crystalline complexes are known from styphnic acid and organic molecules \[(Abashev *et al.*, 2001), (Liu *et al.*, 2008), (Tenishev *et al.*, 2002)\]. It has also been pointed out that aromatic hydrocarbons (and also some amines) form 1:1 adducts with styphnic acid and these derivatives do not crystallize as well as the corresponding picrates (Vogel, 1978). In the present work an elegant method has been proposed to prepare a crystalline molecular salt from 2-methoxyaniline and styphnic acid. The title compound (I), is shown in Fig 1. The adduct formation between styphnic acid and 2-methoxyaniline may involve two important types of charge-transfer interactions (i) π-π^\*^ transition and (ii) proton transfer. A view of the crystal packing is shown in Fig 2. The proton transfer from phenolic OH to amino group is the main contributing factor which stabilizes the title molecular salt. The same observation has been reported by us in a related molecular salt (Kalaivani & Malarvizhi, 2010). The 3-hydroxy-2,4,6-trinitrophenolate ions self-assemble *via* O---H···O hydrogen bonds to from a supramolecular chain the *b* axis, with the graph-set notation C(9); this is shown in Fig. 3. Experimental {#experimental} ============ 2,4,6-Trinitro-1,3-benzenediol (styphnic acid: 2.45 g, 0.01 mol) was dissolved in the minimum quantity of dimethyl sulphoxide. 2-Methoxyaniline (1.23 g, 0.01 mol) dissolved in the minimum amount of dimethyl sulphoxide was added to styphnic acid solution. The mixture was stirred well for 3 h and kept as such for another 12 h. The mixture was then poured into ice cold water with stirring. The molecular salt (adduct) formed was filtered and washed first with water and then with alcohol and dried. The dried adduct was washed several times with ether and recrystallized from ethanol (yield 70--75%, mp.455 K). Good pale yellow crystals of the molecular salt were obtained by slow evaporation of ethanol at room temperature. The same molecular salt was obtained when styphnic acid (0.01 mol) was mixed with excess of 2-methoxyaniline (0.03 mol). Refinement {#refinement} ========== All hydrogen atoms were positioned geometrically and were refined using a riding model. The C---H, O---H and N---H bond lengths are 0.93--0.96, 0.82 and 0.89 Å, respectively \[*U*~iso~ (H)=1.2 *U*~eq~(parent atom)\]. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The asymmetric unit of (I), showing 50% probability displacement ellipsoids. Dashed lines indicate hydrogen bonds. ::: ![](e-67-0o686-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing view of 2-methoxyanilinium 3-hydroxy- 2,4,6-trinitrophenolate.Dashed lines indicate hydrogen bonds H atoms not involved in hydrogen bonding have been omitted \[symmetry codes: (i) x, -y + 1/2, z + 1/2; (vi) -x + 1, y - 1/2, -z + 1/2\]. ::: ![](e-67-0o686-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### Hydrogen-bonding patterns in the supramolecular chain in compound (I). Dashed lines indicate hydrogen bonds H atoms not involved in hydrogen bonding have been omitted \[symmetry codes: (vi) -x + 1, y - 1/2, -z + 1/2\]. ::: ![](e-67-0o686-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e189 .table-wrap} ------------------------------------ --------------------------------------- C~7~H~10~NO^+^·C~6~H~2~N~3~O~8~^−^ *F*(000) = 760 *M~r~* = 368.27 *D*~x~ = 1.593 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 4930 reflections *a* = 10.6957 (4) Å θ = 1.9--31.8° *b* = 17.8368 (5) Å µ = 0.14 mm^−1^ *c* = 8.0527 (3) Å *T* = 293 K β = 91.991 (2)° Prism, colourless *V* = 1535.34 (9) Å^3^ 0.22 × 0.18 × 0.12 mm *Z* = 4 ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e332 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII CCD area-detector diffractometer 4930 independent reflections Radiation source: fine-focus sealed tube 3539 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.028 φ and ω scans θ~max~ = 31.8°, θ~min~ = 1.9° Absorption correction: multi-scan (*SADABS*; Bruker, 2008) *h* = −15→15 *T*~min~ = 0.978, *T*~max~ = 0.988 *k* = −25→26 19208 measured reflections *l* = −11→11 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e449 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.050 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.142 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0626*P*)^2^ + 0.4547*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4930 reflections (Δ/σ)~max~ \< 0.001 238 parameters Δρ~max~ = 0.45 e Å^−3^ 0 restraints Δρ~min~ = −0.40 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e606 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Geometry. Bond distances, angles *etc*. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on *F*^2^ for ALL reflections except those flagged by the user for potential systematic errors. Weighted *R*-factors *wR* and all goodnesses of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The observed criterion of *F*^2^ \> σ(*F*^2^) is used only for calculating -*R*-factor-obs *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*-factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e708 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 −0.00430 (12) 0.14533 (7) 0.45345 (16) 0.0536 (4) N1 0.18296 (12) 0.21738 (7) 0.59909 (15) 0.0366 (3) C1 0.08388 (13) 0.26071 (8) 0.51522 (17) 0.0344 (4) C2 −0.01386 (14) 0.22085 (9) 0.43872 (19) 0.0400 (4) C3 −0.10912 (16) 0.26008 (12) 0.3561 (2) 0.0529 (6) C4 −0.10434 (19) 0.33740 (12) 0.3498 (3) 0.0592 (6) C5 −0.0059 (2) 0.37645 (11) 0.4229 (3) 0.0580 (6) C6 0.08921 (16) 0.33785 (9) 0.5076 (2) 0.0450 (5) C7 −0.1013 (2) 0.10034 (13) 0.3781 (3) 0.0712 (8) O2 0.30956 (10) 0.18764 (5) 0.31638 (13) 0.0372 (3) O3 0.18239 (12) 0.01420 (9) 0.30014 (18) 0.0662 (5) O4 0.26170 (13) 0.05325 (8) 0.53302 (15) 0.0569 (4) O5 0.43465 (12) −0.06180 (6) 0.30043 (17) 0.0508 (4) O6 0.64034 (12) −0.08887 (6) 0.14078 (16) 0.0519 (4) O7 0.76246 (12) 0.00182 (7) 0.07391 (18) 0.0585 (4) O8 0.63270 (16) 0.25143 (8) 0.0819 (3) 0.0929 (7) O9 0.46083 (14) 0.28678 (7) 0.1770 (3) 0.0813 (7) N2 0.26692 (12) 0.04141 (7) 0.38421 (16) 0.0376 (4) N3 0.66485 (12) −0.02118 (7) 0.12862 (16) 0.0405 (4) N4 0.53537 (12) 0.23793 (7) 0.14816 (19) 0.0428 (4) C8 0.39391 (12) 0.14238 (7) 0.27345 (16) 0.0299 (3) C9 0.38107 (13) 0.06399 (7) 0.30251 (17) 0.0323 (4) C10 0.46368 (14) 0.00851 (7) 0.26041 (18) 0.0346 (4) C11 0.57235 (13) 0.03198 (8) 0.17977 (18) 0.0346 (4) C12 0.59200 (13) 0.10722 (8) 0.14638 (18) 0.0353 (4) C13 0.50678 (13) 0.16065 (7) 0.19047 (17) 0.0326 (4) H1A 0.23360 0.19870 0.52400 0.0550\* H1B 0.14930 0.18000 0.65560 0.0550\* H1C 0.22640 0.24700 0.66890 0.0550\* H3 −0.17580 0.23450 0.30530 0.0630\* H4 −0.16870 0.36360 0.29510 0.0710\* H5A −0.00330 0.42850 0.41560 0.0700\* H6 0.15570 0.36370 0.55850 0.0540\* H7A −0.17980 0.11290 0.42510 0.1070\* H7B −0.08320 0.04830 0.39790 0.1070\* H7C −0.10580 0.10960 0.26060 0.1070\* H5 0.49030 −0.09010 0.27160 0.0760\* H12 0.66400 0.12170 0.09330 0.0420\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1235 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0559 (7) 0.0422 (6) 0.0617 (8) −0.0173 (5) −0.0108 (6) −0.0007 (5) N1 0.0394 (6) 0.0344 (6) 0.0360 (6) −0.0046 (5) 0.0009 (5) −0.0036 (5) C1 0.0349 (7) 0.0371 (7) 0.0316 (6) −0.0025 (5) 0.0071 (5) −0.0028 (5) C2 0.0382 (7) 0.0448 (8) 0.0372 (7) −0.0080 (6) 0.0054 (6) −0.0011 (6) C3 0.0390 (8) 0.0708 (12) 0.0487 (9) −0.0041 (8) −0.0011 (7) 0.0013 (8) C4 0.0530 (10) 0.0678 (12) 0.0567 (11) 0.0164 (9) 0.0010 (9) 0.0078 (9) C5 0.0692 (12) 0.0435 (9) 0.0616 (11) 0.0104 (8) 0.0064 (10) 0.0029 (8) C6 0.0491 (9) 0.0380 (8) 0.0484 (9) −0.0038 (6) 0.0070 (7) −0.0043 (6) C7 0.0722 (13) 0.0657 (12) 0.0750 (14) −0.0377 (11) −0.0093 (11) −0.0021 (10) O2 0.0427 (5) 0.0302 (5) 0.0391 (5) 0.0093 (4) 0.0059 (4) 0.0036 (4) O3 0.0518 (7) 0.0849 (10) 0.0619 (9) −0.0254 (7) 0.0013 (6) −0.0089 (7) O4 0.0685 (8) 0.0630 (8) 0.0397 (6) −0.0072 (6) 0.0112 (6) 0.0038 (5) O5 0.0551 (7) 0.0250 (5) 0.0729 (8) 0.0048 (5) 0.0093 (6) 0.0032 (5) O6 0.0591 (7) 0.0340 (6) 0.0626 (8) 0.0103 (5) 0.0011 (6) −0.0118 (5) O7 0.0470 (7) 0.0551 (7) 0.0744 (9) 0.0086 (6) 0.0155 (6) −0.0091 (6) O8 0.0737 (10) 0.0508 (8) 0.1580 (18) −0.0022 (7) 0.0568 (11) 0.0234 (10) O9 0.0604 (8) 0.0281 (6) 0.1575 (17) 0.0013 (6) 0.0329 (10) 0.0079 (8) N2 0.0429 (7) 0.0294 (5) 0.0407 (7) −0.0008 (5) 0.0036 (5) 0.0046 (5) N3 0.0436 (7) 0.0376 (6) 0.0400 (7) 0.0088 (5) −0.0023 (5) −0.0090 (5) N4 0.0378 (6) 0.0310 (6) 0.0595 (8) −0.0029 (5) 0.0004 (6) 0.0055 (5) C8 0.0339 (6) 0.0269 (6) 0.0286 (6) 0.0017 (5) −0.0021 (5) −0.0003 (4) C9 0.0346 (6) 0.0269 (6) 0.0353 (7) 0.0002 (5) 0.0018 (5) 0.0003 (5) C10 0.0407 (7) 0.0257 (6) 0.0371 (7) 0.0021 (5) −0.0037 (6) −0.0022 (5) C11 0.0355 (7) 0.0317 (6) 0.0363 (7) 0.0059 (5) −0.0017 (5) −0.0052 (5) C12 0.0326 (6) 0.0359 (7) 0.0373 (7) 0.0010 (5) −0.0003 (5) −0.0026 (5) C13 0.0338 (6) 0.0262 (6) 0.0375 (7) −0.0012 (5) −0.0020 (5) 0.0002 (5) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1744 .table-wrap} --------------------- -------------- ----------------------- -------------- O1---C2 1.356 (2) C1---C6 1.379 (2) O1---C7 1.430 (3) C2---C3 1.387 (2) O2---C8 1.2676 (16) C3---C4 1.381 (3) O3---N2 1.2119 (19) C4---C5 1.377 (3) O4---N2 1.2200 (18) C5---C6 1.388 (3) O5---C10 1.3342 (17) C3---H3 0.9300 O6---N3 1.2401 (17) C4---H4 0.9300 O7---N3 1.2183 (18) C5---H5A 0.9300 O8---N4 1.210 (2) C6---H6 0.9300 O9---N4 1.2090 (19) C7---H7C 0.9600 O5---H5 0.8200 C7---H7A 0.9600 N1---C1 1.4583 (19) C7---H7B 0.9600 N1---H1C 0.8900 C8---C13 1.4374 (19) N1---H1A 0.8900 C8---C9 1.4251 (18) N1---H1B 0.8900 C9---C10 1.3769 (19) N2---C9 1.4634 (19) C10---C11 1.414 (2) N3---C11 1.4408 (19) C11---C12 1.386 (2) N4---C13 1.4550 (18) C12---C13 1.3739 (19) C1---C2 1.390 (2) C12---H12 0.9300 O1···N1 2.6221 (18) N3···C10^iii^ 3.3846 (19) O1···C4^i^ 3.415 (3) N4···O2 2.9496 (17) O2···C1 3.2183 (17) N3···H5 2.5400 O2···N1^ii^ 2.7569 (16) C1···O2 3.2183 (17) O2···C6^ii^ 3.397 (2) C1···C3^i^ 3.511 (2) O2···O4 3.0189 (17) C2···C3^i^ 3.562 (2) O2···O9 2.6703 (19) C3···C2^ii^ 3.562 (2) O2···N1 2.7408 (16) C3···O8^xi^ 3.365 (3) O2···N2 2.7068 (15) C3···C1^ii^ 3.511 (2) O2···N4 2.9496 (17) C4···O1^ii^ 3.415 (3) O3···O5 3.0194 (18) C6···O7^ix^ 3.402 (2) O3···O7^iii^ 3.103 (2) C6···O2^i^ 3.397 (2) O4···N1 3.0974 (19) C7···O7^xii^ 3.311 (3) O4···O2 3.0189 (17) C7···O4^v^ 3.324 (3) O4···C11^iv^ 3.2443 (19) C10···N3^iii^ 3.3846 (19) O4···C7^v^ 3.324 (3) C11···C11^iii^ 3.431 (2) O4···N3^iv^ 2.8670 (18) C11···O4^iv^ 3.2443 (19) O4···O6^iv^ 2.8654 (18) C12···O6^iii^ 3.3512 (19) O5···N3 2.9560 (18) C13···O6^iii^ 3.3074 (19) O5···O6 2.6311 (18) C3···H7C 2.7900 O5···O9^vi^ 2.9263 (17) C3···H7A 2.7900 O5···N2 2.6733 (17) C5···H7C^i^ 2.9700 O5···O3 3.0194 (18) C5···H1B^ii^ 2.9400 O6···O9^vi^ 2.890 (2) C6···H1B^ii^ 2.9500 O6···C13^iii^ 3.3074 (19) C7···H3 2.5800 O6···C12^iii^ 3.3512 (19) C8···H6^ii^ 3.0300 O6···O5 2.6311 (18) C8···H1A 2.8700 O6···O4^iv^ 2.8654 (18) C8···H1C^ii^ 2.7800 O7···C6^vi^ 3.402 (2) H1A···O1 2.7600 O7···O3^iii^ 3.103 (2) H1A···O9^i^ 2.7000 O7···C7^vii^ 3.311 (3) H1A···O2 1.8900 O8···C3^viii^ 3.365 (3) H1A···O4 2.6100 O9···O6^ix^ 2.890 (2) H1A···C8 2.8700 O9···O5^ix^ 2.9263 (17) H1B···C5^i^ 2.9400 O9···N1^ii^ 3.017 (2) H1B···C6^i^ 2.9500 O9···O2 2.6703 (19) H1B···O4 2.7600 O1···H1A 2.7600 H1B···O1 2.3500 O1···H1B 2.3500 H1C···H6 2.3800 O2···H1C^ii^ 1.8700 H1C···O9^i^ 2.5800 O2···H1A 1.8900 H1C···C8^i^ 2.7800 O2···H6^ii^ 2.7600 H1C···O2^i^ 1.8700 O3···H7B^v^ 2.9100 H3···H7A 2.3700 O3···H4^x^ 2.8000 H3···H7C 2.3800 O4···H1B 2.7600 H3···O8^xii^ 2.7000 O4···H7B^v^ 2.7000 H3···C7 2.5800 O4···H1A 2.6100 H4···O3^xiii^ 2.8000 O6···H6^vi^ 2.8800 H5···N3 2.5400 O6···H5 1.9500 H5···O9^vi^ 2.2900 O7···H7C^vii^ 2.7900 H5···O6 1.9500 O7···H12 2.3900 H5A···O7^ix^ 2.8900 O7···H6^vi^ 2.8400 H6···H1C 2.3800 O7···H5A^vi^ 2.8900 H6···O6^ix^ 2.8800 O8···H3^vii^ 2.7000 H6···O7^ix^ 2.8400 O8···H12 2.3400 H6···O2^i^ 2.7600 O9···H1A^ii^ 2.7000 H6···C8^i^ 3.0300 O9···H5^ix^ 2.2900 H7A···H3 2.3700 O9···H1C^ii^ 2.5800 H7A···C3 2.7900 N1···O9^i^ 3.017 (2) H7B···O4^v^ 2.7000 N1···O2 2.7408 (16) H7B···O3^v^ 2.9100 N1···O1 2.6221 (18) H7C···O7^xii^ 2.7900 N1···O4 3.0974 (19) H7C···H3 2.3800 N1···O2^i^ 2.7569 (16) H7C···C5^ii^ 2.9700 N2···O5 2.6733 (17) H7C···C3 2.7900 N2···O2 2.7068 (15) H12···O7 2.3900 N3···O4^iv^ 2.8670 (18) H12···O8 2.3400 N3···O5 2.9560 (18) C2---O1---C7 117.97 (14) C5---C4---H4 119.00 C10---O5---H5 109.00 C6---C5---H5A 120.00 H1B---N1---H1C 109.00 C4---C5---H5A 120.00 C1---N1---H1B 109.00 C5---C6---H6 120.00 C1---N1---H1A 109.00 C1---C6---H6 120.00 H1A---N1---H1C 110.00 O1---C7---H7C 109.00 C1---N1---H1C 109.00 O1---C7---H7B 109.00 H1A---N1---H1B 109.00 H7B---C7---H7C 109.00 O4---N2---C9 117.47 (13) H7A---C7---H7B 110.00 O3---N2---C9 118.49 (13) H7A---C7---H7C 110.00 O3---N2---O4 124.01 (14) O1---C7---H7A 109.00 O6---N3---C11 117.97 (12) O2---C8---C9 120.43 (12) O7---N3---C11 119.17 (12) C9---C8---C13 112.71 (11) O6---N3---O7 122.86 (13) O2---C8---C13 126.84 (12) O8---N4---O9 121.62 (15) N2---C9---C10 117.74 (12) O9---N4---C13 119.50 (14) C8---C9---C10 126.76 (13) O8---N4---C13 118.86 (13) N2---C9---C8 115.50 (11) C2---C1---C6 121.49 (14) O5---C10---C11 126.23 (13) N1---C1---C6 121.27 (13) C9---C10---C11 116.42 (12) N1---C1---C2 117.21 (13) O5---C10---C9 117.35 (13) C1---C2---C3 118.89 (15) N3---C11---C12 118.13 (12) O1---C2---C1 114.58 (13) C10---C11---C12 120.54 (13) O1---C2---C3 126.53 (15) N3---C11---C10 121.33 (12) C2---C3---C4 119.60 (17) C11---C12---C13 121.00 (13) C3---C4---C5 121.20 (19) N4---C13---C12 116.74 (12) C4---C5---C6 119.71 (18) C8---C13---C12 122.57 (12) C1---C6---C5 119.10 (16) N4---C13---C8 120.69 (12) C4---C3---H3 120.00 C11---C12---H12 119.00 C2---C3---H3 120.00 C13---C12---H12 120.00 C3---C4---H4 119.00 C7---O1---C2---C1 179.98 (15) C3---C4---C5---C6 −1.4 (3) C7---O1---C2---C3 −0.4 (2) C4---C5---C6---C1 0.8 (3) O4---N2---C9---C10 105.00 (16) O2---C8---C9---C10 178.89 (14) O3---N2---C9---C8 102.38 (16) C13---C8---C9---C10 0.3 (2) O4---N2---C9---C8 −75.60 (17) O2---C8---C13---N4 0.7 (2) O3---N2---C9---C10 −77.02 (18) C9---C8---C13---N4 179.16 (13) O7---N3---C11---C10 −173.12 (14) C13---C8---C9---N2 −179.01 (12) O6---N3---C11---C12 −171.69 (14) O2---C8---C13---C12 −178.89 (14) O7---N3---C11---C12 7.5 (2) C9---C8---C13---C12 −0.44 (19) O6---N3---C11---C10 7.7 (2) O2---C8---C9---N2 −0.45 (19) O8---N4---C13---C8 178.25 (17) N2---C9---C10---O5 −1.3 (2) O9---N4---C13---C8 −3.1 (2) C8---C9---C10---C11 −0.1 (2) O8---N4---C13---C12 −2.1 (2) N2---C9---C10---C11 179.24 (12) O9---N4---C13---C12 176.54 (18) C8---C9---C10---O5 179.33 (14) N1---C1---C6---C5 178.46 (16) C9---C10---C11---N3 −179.46 (13) C2---C1---C6---C5 0.6 (2) C9---C10---C11---C12 −0.1 (2) N1---C1---C2---C3 −179.29 (13) O5---C10---C11---C12 −179.44 (15) C6---C1---C2---O1 178.32 (14) O5---C10---C11---N3 1.2 (2) N1---C1---C2---O1 0.41 (19) C10---C11---C12---C13 0.0 (2) C6---C1---C2---C3 −1.4 (2) N3---C11---C12---C13 179.36 (13) C1---C2---C3---C4 0.8 (2) C11---C12---C13---N4 −179.30 (13) O1---C2---C3---C4 −178.90 (17) C11---C12---C13---C8 0.3 (2) C2---C3---C4---C5 0.6 (3) --------------------- -------------- ----------------------- -------------- ::: Symmetry codes: (i) *x*, −*y*+1/2, *z*+1/2; (ii) *x*, −*y*+1/2, *z*−1/2; (iii) −*x*+1, −*y*, −*z*; (iv) −*x*+1, −*y*, −*z*+1; (v) −*x*, −*y*, −*z*+1; (vi) −*x*+1, *y*−1/2, −*z*+1/2; (vii) *x*+1, *y*, *z*; (viii) *x*+1, −*y*+1/2, *z*−1/2; (ix) −*x*+1, *y*+1/2, −*z*+1/2; (x) −*x*, *y*−1/2, −*z*+1/2; (xi) *x*−1, −*y*+1/2, *z*+1/2; (xii) *x*−1, *y*, *z*; (xiii) −*x*, *y*+1/2, −*z*+1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3342 .table-wrap} ------------------ --------- --------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···O2 0.89 1.89 2.7408 (16) 158 N1---H1C···O2^i^ 0.89 1.87 2.7569 (16) 177 N1---H1C···O9^i^ 0.89 2.58 3.017 (2) 111 O5---H5···O6 0.82 1.95 2.6311 (18) 140 O5---H5···N3 0.82 2.54 2.9560 (18) 112 O5---H5···O9^vi^ 0.82 2.29 2.9263 (17) 135 C12---H12···O8 0.93 2.34 2.663 (2) 100 ------------------ --------- --------- ------------- --------------- ::: Symmetry codes: (i) *x*, −*y*+1/2, *z*+1/2; (vi) −*x*+1, *y*−1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ --------- ------- ------------- ------------- N1---H1*A*⋯O2 0.89 1.89 2.7408 (16) 158 N1---H1*C*⋯O2^i^ 0.89 1.87 2.7569 (16) 177 O5---H5⋯O6 0.82 1.95 2.6311 (18) 140 O5---H5⋯O9^ii^ 0.82 2.29 2.9263 (17) 135 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.834810

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052155/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o686", "authors": [ { "first": "Doraisamyraja", "last": "Kalaivani" }, { "first": "Rangasamy", "last": "Malarvizhi" }, { "first": "Kaliyaperumal", "last": "Thanigaimani" }, { "first": "Packianathan Thomas", "last": "Muthiah" } ] }

PMC3052156

Related literature {#sec1} ================== For the preparation of 1,2-dihydroquinoline, see: Edwards *et al.* (1998[@bb5]); Yan *et al.* (2004[@bb27]); Petasis & Butkevich (2009[@bb19]); Johnson *et al.* (1989[@bb13]); Gültekin *et al.* (2010[@bb9]); Waldmann *et al.* (2008[@bb26]). For the biological activity of dihydroquinolines, see: Elmore *et al.* (2001[@bb6]); Dillard *et al.* (1973[@bb4]); Muren & Weissman (1971[@bb18]). For the preparation of quinolines, see: Dauphinee & Forrest (1978[@bb3]); Yan *et al.* (2004[@bb27]); Tom & Ruel (2001[@bb25]); Tokuyama *et al.* (2001[@bb24]); Sarma & Prajapati (2008[@bb21]); Martinez *et al.* (2008[@bb17]); Huang *et al.* (2009[@bb12]); Katritzky *et al.* (1996[@bb14]). For the biological activity of quinolines, see: Hamann *et al.* (1998[@bb10]); He *et al.* (2003[@bb11]); LaMontagne *et al.* (1989[@bb15]). For hydorgen-bond motifs, see: Bernstein *et al.* (1995[@bb1]). For ring puckering parameters, see: Cremer & Pople (1975[@bb2]). For the melting point, see: Rueping & Gültekin (2009[@bb20]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~14~H~15~NO~4~*M* *~r~* = 261.27Monoclinic,*a* = 7.9917 (12) Å*b* = 8.8886 (11) Å*c* = 18.9855 (18) Åβ = 99.194 (9)°*V* = 1331.3 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 0.10 mm^−1^*T* = 294 K0.6 × 0.6 × 0.5 mm ### Data collection {#sec2.1.2} Nicolet P3 diffractometer4144 measured reflections3890 independent reflections3097 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.0533 standard reflections every 50 reflections intensity decay: 1% ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.052*wR*(*F* ^2^) = 0.159*S* = 1.053890 reflections180 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e523} Data collection: *XSCANS* (Siemens, 1996[@bb23]); cell refinement: *XSCANS*; data reduction: *SHELXTL* (Sheldrick, 2008[@bb22]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb22]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb22]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb7]) and *Mercury* (Macrae *et al.*, 2006[@bb16]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005605/bv2176sup1.cif](http://dx.doi.org/10.1107/S1600536811005605/bv2176sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005605/bv2176Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005605/bv2176Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bv2176&file=bv2176sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bv2176sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bv2176&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BV2176](http://scripts.iucr.org/cgi-bin/sendsup?bv2176)). This research was carried out at RWTH Aachen University. The authors thank Professor Magnus Rueping of RWTH Aachen University, Germany, for helpful discussions. Comment ======= Dihydroquinolines have been widely studied and found to be an important structural unit in synthetic organic and medicinal chemistry (Elmore *et al.*, 2001; Dillard *et al.*, 1973; Muren & Weissman, 1971). Many dihydroquinoline derivatives have been reported in the literature (Edwards *et al.*, 1998; Yan *et al.*, 2004; Petasis & Butkevich, 2009; Gültekin *et al.*, 2010) and some of them have biological effects. For example, 2,2,4-substituted 1,2-dihydroquinolines have been shown to possess antibacterial activities (Johnson *et al.*, 1989). They are also important intermediates for the preparation of quinolines (Dauphinee & Forrest, 1978; Yan *et al.*, 2004; Tom & Ruel, 2001; Tokuyama *et al.*, 2001) and 1,2,3,4-tetrahydroquinolines (Katritzky *et al.*, 1996). Many synthetic methods have been developed for the preparation of quinolines (Sarma & Prajapati, 2008; Martinez *et al.*, 2008; Huang *et al.*, 2009; Waldmann *et al.*, 2008) and many quinolines display biological effects (Hamann *et al.*, 1998; He *et al.*, 2003; LaMontagne *et al.*, 1989; Muren & Weissman, 1971). In the title compound, (I), (Fig. 1), the ring A (C1-C4/C9/N1) is not planar with the puckering parameters (Cremer & Pople, 1975) Q~T~ = 0.364 (2) Å, φ = -143.4 (3)° and θ = 113.9 (2)°. In the crystal structure, intermolecular N-H···O hydrogen bonds (Table 1) link the molecules into centrosymmetric R~2~^2^(10) dimers (Bernstein *et al.*, 1995). These dimers are further connected *via* intermolecular C-H···O hydrogen bonds (Table 1) to form a three-dimensional network (Fig. 2). Experimental {#experimental} ============ The title compound was synthesized by the literature method (Waldmann *et al.*, 2008). Aniline (100 mg, 1 eq) was dissolved in chloroform (1.5 ml) in a screw-capped test tube and Bi(OTf)~3~ (5 mol%, 0.05 eq) was added to the mixture. The mixture was stirred at room temperature for 4h until the starting material was completely consumed as monitored by TLC. The resultant residue was directly purified by flash chromatography on silica (EtOAc:Cylohexane 2:98) gave in 63% yield as a yellow solid. Recrystallized over pentane and ethyl acetate (70:30) gave yellow crystalline solid R~f~ 0.53 (2:1 Cyclohexane/EtOAc) mp 346 K (Rueping & Gültekin, 2009). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o672-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A partial packing diagram viewed down the b-axis. Hydrogen bonds are shown as dashed lines. ::: ![](e-67-0o672-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e163 .table-wrap} ------------------------- ------------------------------------- C~14~H~15~NO~4~ *F*(000) = 552 *M~r~* = 261.27 *D*~x~ = 1.304 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 49 reflections *a* = 7.9917 (12) Å θ = 17--18° *b* = 8.8886 (11) Å µ = 0.10 mm^−1^ *c* = 18.9855 (18) Å *T* = 294 K β = 99.194 (9)° Block, colourless *V* = 1331.3 (3) Å^3^ 0.6 × 0.6 × 0.5 mm *Z* = 4 ------------------------- ------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e290 .table-wrap} ------------------------------------------ --------------------------------------------- Nicolet P3 diffractometer *R*~int~ = 0.053 Radiation source: fine-focus sealed tube θ~max~ = 30.0°, θ~min~ = 2.2° graphite *h* = 0→11 Wyckoff--Scan scans *k* = 0→12 4144 measured reflections *l* = −26→26 3890 independent reflections 3 standard reflections every 50 reflections 3097 reflections with *I* \> 2σ(*I*) intensity decay: 1% ------------------------------------------ --------------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e382 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.052 H atoms treated by a mixture of independent and constrained refinement *wR*(*F*^2^) = 0.159 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0757*P*)^2^ + 0.2951*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.05 (Δ/σ)~max~ \< 0.001 3890 reflections Δρ~max~ = 0.24 e Å^−3^ 180 parameters Δρ~min~ = −0.18 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.076 (5) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e563 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e608 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.16885 (15) 0.61815 (14) 0.96958 (6) 0.0632 (3) O2 0.15641 (17) 0.84306 (14) 0.91740 (6) 0.0671 (4) O3 −0.04420 (19) 0.60887 (14) 0.63398 (6) 0.0688 (4) O4 0.00900 (15) 0.83447 (13) 0.68455 (5) 0.0538 (3) N1 −0.12790 (17) 0.52602 (16) 0.88407 (7) 0.0527 (3) H1 −0.137 (3) 0.491 (3) 0.9282 (12) 0.080 (6)\* C1 −0.08128 (18) 0.68333 (17) 0.88397 (7) 0.0447 (3) C2 −0.07661 (18) 0.73116 (16) 0.80816 (7) 0.0441 (3) H2 −0.1036 0.8299 0.7946 0.053\* C3 −0.03445 (17) 0.63452 (15) 0.76014 (7) 0.0411 (3) C4 −0.00240 (17) 0.47523 (15) 0.77879 (7) 0.0439 (3) C5 0.0730 (2) 0.37209 (18) 0.73815 (9) 0.0551 (4) H5 0.1104 0.4042 0.6967 0.066\* C6 0.0929 (2) 0.22295 (19) 0.75842 (11) 0.0675 (5) H6 0.1440 0.1557 0.7309 0.081\* C7 0.0370 (3) 0.17430 (19) 0.81939 (12) 0.0723 (5) H7 0.0479 0.0734 0.8323 0.087\* C8 −0.0351 (2) 0.27357 (19) 0.86154 (10) 0.0630 (4) H8 −0.0718 0.2393 0.9028 0.076\* C9 −0.05340 (17) 0.42528 (16) 0.84272 (8) 0.0468 (3) C10 −0.2084 (2) 0.7764 (2) 0.91791 (10) 0.0689 (5) H10A −0.2112 0.7408 0.9654 0.103\* H10B −0.3191 0.7667 0.8899 0.103\* H10C −0.1749 0.8802 0.9197 0.103\* C11 0.09548 (18) 0.70811 (16) 0.92869 (6) 0.0432 (3) C12 0.3182 (3) 0.8827 (3) 0.95860 (10) 0.0782 (6) H12A 0.3519 0.9801 0.9441 0.117\* H12B 0.4015 0.8094 0.9507 0.117\* H12C 0.3087 0.8848 1.0084 0.117\* C13 −0.02495 (18) 0.68793 (17) 0.68624 (7) 0.0455 (3) C14 0.0372 (3) 0.8942 (2) 0.61686 (9) 0.0639 (4) H14A 0.0545 1.0009 0.6209 0.096\* H14B −0.0598 0.8739 0.5813 0.096\* H14C 0.1355 0.8477 0.6032 0.096\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1089 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0643 (7) 0.0639 (7) 0.0556 (6) −0.0034 (5) −0.0082 (5) 0.0187 (5) O2 0.0860 (9) 0.0569 (7) 0.0495 (6) −0.0208 (6) −0.0163 (6) 0.0115 (5) O3 0.1070 (10) 0.0603 (7) 0.0347 (5) 0.0046 (7) −0.0018 (6) −0.0064 (5) O4 0.0706 (7) 0.0516 (6) 0.0369 (5) −0.0038 (5) 0.0014 (4) 0.0041 (4) N1 0.0563 (7) 0.0561 (7) 0.0457 (6) −0.0088 (6) 0.0077 (5) 0.0054 (5) C1 0.0484 (7) 0.0491 (7) 0.0360 (6) 0.0029 (6) 0.0048 (5) 0.0012 (5) C2 0.0518 (7) 0.0421 (6) 0.0356 (6) 0.0049 (5) −0.0014 (5) 0.0021 (5) C3 0.0438 (6) 0.0423 (6) 0.0340 (5) 0.0002 (5) −0.0033 (5) 0.0004 (5) C4 0.0449 (6) 0.0411 (6) 0.0415 (6) −0.0011 (5) −0.0056 (5) −0.0011 (5) C5 0.0600 (9) 0.0502 (8) 0.0507 (8) 0.0060 (7) −0.0046 (6) −0.0072 (6) C6 0.0735 (11) 0.0476 (8) 0.0732 (11) 0.0094 (8) −0.0133 (9) −0.0119 (8) C7 0.0816 (12) 0.0385 (8) 0.0861 (13) −0.0058 (8) −0.0198 (10) 0.0041 (8) C8 0.0688 (10) 0.0475 (8) 0.0666 (10) −0.0150 (7) −0.0081 (8) 0.0117 (7) C9 0.0450 (7) 0.0444 (7) 0.0470 (7) −0.0092 (5) −0.0054 (5) 0.0037 (5) C10 0.0674 (10) 0.0854 (13) 0.0559 (9) 0.0197 (9) 0.0157 (8) −0.0024 (9) C11 0.0522 (7) 0.0478 (7) 0.0296 (5) −0.0014 (5) 0.0063 (5) 0.0015 (5) C12 0.0917 (13) 0.0891 (14) 0.0472 (9) −0.0413 (12) −0.0086 (8) 0.0045 (9) C13 0.0498 (7) 0.0487 (7) 0.0343 (6) 0.0046 (6) −0.0042 (5) −0.0008 (5) C14 0.0774 (11) 0.0698 (11) 0.0430 (8) −0.0016 (8) 0.0053 (7) 0.0141 (7) ----- ------------- ------------- ------------- -------------- -------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1480 .table-wrap} --------------------- -------------- -------------------- -------------- O1---C11 1.2001 (17) C5---C6 1.382 (2) O2---C11 1.3249 (18) C5---H5 0.9300 O2---C12 1.443 (2) C6---C7 1.376 (3) O3---C13 1.2055 (17) C6---H6 0.9300 O4---C13 1.3319 (19) C7---C8 1.377 (3) O4---C14 1.4410 (18) C7---H7 0.9300 N1---C1 1.447 (2) C8---C9 1.397 (2) N1---C9 1.386 (2) C8---H8 0.9300 N1---H1 0.91 (2) C10---H10A 0.9600 C1---C2 1.5070 (18) C10---H10B 0.9600 C1---C10 1.530 (2) C10---H10C 0.9600 C1---C11 1.5432 (19) C12---H12A 0.9600 C2---C3 1.3344 (19) C12---H12B 0.9600 C2---H2 0.9300 C12---H12C 0.9600 C3---C4 1.4720 (19) C14---H14A 0.9600 C3---C13 1.4944 (18) C14---H14B 0.9600 C4---C5 1.395 (2) C14---H14C 0.9600 C4---C9 1.412 (2) C11---O2---C12 116.97 (13) C7---C8---H8 119.8 C13---O4---C14 116.33 (13) C9---C8---H8 119.8 C1---N1---H1 112.9 (15) N1---C9---C4 119.52 (13) C9---N1---C1 119.30 (12) N1---C9---C8 121.05 (15) C9---N1---H1 114.2 (14) C8---C9---C4 119.37 (15) N1---C1---C2 108.63 (12) C1---C10---H10A 109.5 N1---C1---C10 109.48 (14) C1---C10---H10B 109.5 N1---C1---C11 110.51 (12) C1---C10---H10C 109.5 C2---C1---C10 111.66 (13) H10A---C10---H10B 109.5 C2---C1---C11 108.97 (11) H10A---C10---H10C 109.5 C10---C1---C11 107.59 (13) H10B---C10---H10C 109.5 C1---C2---H2 119.4 O1---C11---O2 123.62 (14) C3---C2---C1 121.23 (12) O1---C11---C1 124.78 (13) C3---C2---H2 119.4 O2---C11---C1 111.59 (12) C2---C3---C4 120.53 (12) O2---C12---H12A 109.5 C2---C3---C13 119.55 (12) O2---C12---H12B 109.5 C4---C3---C13 119.90 (12) O2---C12---H12C 109.5 C5---C4---C3 124.94 (13) H12A---C12---H12B 109.5 C5---C4---C9 118.56 (14) H12A---C12---H12C 109.5 C9---C4---C3 116.50 (13) H12B---C12---H12C 109.5 C4---C5---H5 119.4 O3---C13---O4 123.36 (14) C6---C5---C4 121.12 (17) O3---C13---C3 124.65 (14) C6---C5---H5 119.4 O4---C13---C3 111.99 (11) C5---C6---H6 120.1 O4---C14---H14A 109.5 C7---C6---C5 119.82 (18) O4---C14---H14B 109.5 C7---C6---H6 120.1 O4---C14---H14C 109.5 C6---C7---C8 120.64 (16) H14A---C14---H14B 109.5 C6---C7---H7 119.7 H14A---C14---H14C 109.5 C8---C7---H7 119.7 H14B---C14---H14C 109.5 C7---C8---C9 120.43 (18) C12---O2---C11---O1 −1.7 (2) C2---C3---C4---C5 −167.06 (14) C12---O2---C11---C1 177.32 (15) C2---C3---C4---C9 13.20 (19) C14---O4---C13---O3 −5.3 (2) C13---C3---C4---C5 14.8 (2) C14---O4---C13---C3 174.17 (13) C13---C3---C4---C9 −164.94 (12) C9---N1---C1---C2 44.10 (17) C2---C3---C13---O3 −154.18 (16) C9---N1---C1---C10 166.27 (14) C2---C3---C13---O4 26.33 (18) C9---N1---C1---C11 −75.40 (16) C4---C3---C13---O3 24.0 (2) C1---N1---C9---C4 −30.23 (19) C4---C3---C13---O4 −155.51 (12) C1---N1---C9---C8 152.77 (14) C3---C4---C5---C6 −177.69 (14) N1---C1---C2---C3 −31.14 (18) C9---C4---C5---C6 2.0 (2) C10---C1---C2---C3 −151.98 (15) C3---C4---C9---N1 −0.52 (18) C11---C1---C2---C3 89.32 (16) C3---C4---C9---C8 176.53 (13) N1---C1---C11---O1 −14.36 (19) C5---C4---C9---N1 179.73 (13) N1---C1---C11---O2 166.68 (12) C5---C4---C9---C8 −3.2 (2) C2---C1---C11---O1 −133.65 (15) C4---C5---C6---C7 0.4 (3) C2---C1---C11---O2 47.38 (16) C5---C6---C7---C8 −1.6 (3) C10---C1---C11---O1 105.13 (18) C6---C7---C8---C9 0.4 (3) C10---C1---C11---O2 −73.84 (16) C7---C8---C9---N1 179.06 (15) C1---C2---C3---C4 4.2 (2) C7---C8---C9---C4 2.1 (2) C1---C2---C3---C13 −177.68 (12) --------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2154 .table-wrap} ---------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1···O1^i^ 0.91 (2) 2.22 (2) 3.1241 (18) 174 (2) C12---H12A···O3^ii^ 0.96 2.57 3.377 (3) 142 C12---H12C···O3^iii^ 0.96 2.49 3.336 (2) 148 ---------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −*x*, −*y*+1, −*z*+2; (ii) −*x*+1/2, *y*+1/2, −*z*+3/2; (iii) *x*+1/2, −*y*+3/2, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------------- ---------- ---------- ------------- ------------- N1---H1⋯O1^i^ 0.91 (2) 2.22 (2) 3.1241 (18) 174 (2) C12---H12*A*⋯O3^ii^ 0.96 2.57 3.377 (3) 142 C12---H12*C*⋯O3^iii^ 0.96 2.49 3.336 (2) 148 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.841734

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052156/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o672-o673", "authors": [ { "first": "Zeynep", "last": "Gültekin" }, { "first": "Wolfgang", "last": "Frey" }, { "first": "Barış", "last": "Tercan" }, { "first": "Tuncer", "last": "Hökelek" } ] }

PMC3052157

Related literature {#sec1} ================== For general background to inorganic--organic hybrid compounds, see: Zhang *et al.* (2009[@bb7]); Descalzo *et al.* (2006[@bb2]); Li *et al.* (2007[@bb3]), Sanchez *et al.* (2005[@bb4]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~8~H~10~NO~2~)~4~\[SnCl~6~\]Cl~2~*M* *~r~* = 1010.97Monoclinic,*a* = 30.748 (3) Å*b* = 7.1172 (8) Å*c* = 22.113 (2) Åβ = 119.424 (2)°*V* = 4215.0 (7) Å^3^*Z* = 4Mo *K*α radiationμ = 1.16 mm^−1^*T* = 298 K0.50 × 0.46 × 0.46 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb5]) *T* ~min~ = 0.594, *T* ~max~ = 0.61710221 measured reflections3719 independent reflections2969 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.035 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.031*wR*(*F* ^2^) = 0.090*S* = 1.013719 reflections245 parametersH-atom parameters constrainedΔρ~max~ = 0.51 e Å^−3^Δρ~min~ = −0.44 e Å^−3^ {#d5e550} Data collection: *SMART* (Bruker, 2007[@bb1]); cell refinement: *SAINT* (Bruker, 2007[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *XP* in *SHELXTL* (Sheldrick, 2008[@bb6]); software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003692/cv5035sup1.cif](http://dx.doi.org/10.1107/S1600536811003692/cv5035sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003692/cv5035Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003692/cv5035Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?cv5035&file=cv5035sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?cv5035sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?cv5035&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [CV5035](http://scripts.iucr.org/cgi-bin/sendsup?cv5035)). The authors acknowledge the financial support of the National Science Foundation of China (grant Nos. 50672090 and 50702053). Comment ======= Considerable attention has been devoted to inorganic-organic hybrid materials over recent years (Zhang *et al.*, 2009). These hybrid materials have potential applications in many areas including gas storage, separation, catalysis, magnetism, optics as well as electrical conductivity (Descalzo *et al.*, 2006; Li *et al.*, 2007; Sanchez *et al.*, 2005\]. Herein we report the structure of the title compound (Fig.1.), This title compound contains SnCl~6~ inorganic anions, organic cations and dissociated chloride anions. The SnCl~6~ inorganic anion adopts a regular octahedron geometry, with average Sn---Cl distance of 2.4262 Å. In the organic cation, the dihedral angle between the ester group and the phenyl ring is 14.86(0.19)°. In the crystal structure, intermolecular N---H···Cl and C---H···O hydrogen bonds (Table 1) link cations and anions into layers with alternating inorganic and organic species. Experimental {#experimental} ============ 4-Aminobenzoic acid (10 mmol) was dissolved to acid methanol solution (10 ml). Ten minutes later, a methanol solution (10 ml) of tin tetrachloride(5 mmol) was added with stirring. The mixture was stirred for 4 h. Crystals of the title compound suitable for X-ray analysis were grown from the saturation ethanol solution after about two weeks. Refinement {#refinement} ========== All H-atoms were positioned geometrically and refined using a riding model, with C---H = 0.96 Å (methyl), 0.93 Å (aromatic), N---H =0.89 Å (ammonium) and *U*~iso~(H) =1.5*U*~eq~(C), *U*~iso~(H) =1.2*U*~eq~(C),*U*~iso~(H) =1.5*U*~eq~(N) Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A portion of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme in asymmetric unit \[symmetry code (A): -x, y, -z + 1/2\]. Dashed lines denote N---H···Cl hydrogen bonds. ::: ![](e-67-0m297-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e150 .table-wrap} ------------------------------------- --------------------------------------- (C~8~H~10~NO~2~)~4~\[SnCl~6~\]Cl~2~ *F*(000) = 2040 *M~r~* = 1010.97 *D*~x~ = 1.593 Mg m^−3^ Monoclinic, *C*2/*c* Mo *K*α radiation, λ = 0.71073 Å *a* = 30.748 (3) Å Cell parameters from 4623 reflections *b* = 7.1172 (8) Å θ = 2.7--27.7° *c* = 22.113 (2) Å µ = 1.16 mm^−1^ β = 119.424 (2)° *T* = 298 K *V* = 4215.0 (7) Å^3^ Block, yellow *Z* = 4 0.50 × 0.46 × 0.46 mm ------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e280 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3719 independent reflections Radiation source: fine-focus sealed tube 2969 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.035 φ and ω scans θ~max~ = 25.0°, θ~min~ = 1.5° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −29→36 *T*~min~ = 0.594, *T*~max~ = 0.617 *k* = −7→8 10221 measured reflections *l* = −26→25 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e397 .table-wrap} ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.031 H-atom parameters constrained *wR*(*F*^2^) = 0.090 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.045*P*)^2^ + 5.2918*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 1.01 (Δ/σ)~max~ \< 0.001 3719 reflections Δρ~max~ = 0.51 e Å^−3^ 245 parameters Δρ~min~ = −0.44 e Å^−3^ 0 restraints Extinction correction: *SHELXL97* (Sheldrick, 2008), Fc^\*^=kFc\[1+0.001xFc^2^λ^3^/sin(2θ)\]^-1/4^ Primary atom site location: structure-invariant direct methods Extinction coefficient: 0.00204 (13) ---------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e578 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e677 .table-wrap} ------ --------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Sn1 0.0000 0.88525 (4) 0.2500 0.03147 (14) Cl1 0.05414 (3) 1.12542 (12) 0.24657 (5) 0.0448 (2) Cl2 0.04668 (3) 0.88401 (13) 0.37614 (4) 0.0446 (2) Cl3 0.05329 (3) 0.64043 (12) 0.24497 (5) 0.0452 (2) Cl4 0.01937 (4) 0.27991 (19) 0.05504 (6) 0.0745 (4) N1 0.05296 (13) 0.8682 (5) 0.09640 (19) 0.0681 (11) H1A 0.0488 0.8145 0.1295 0.102\* H1B 0.0354 0.8058 0.0568 0.102\* H1C 0.0425 0.9868 0.0908 0.102\* O1 0.28945 (11) 0.8266 (5) 0.23899 (19) 0.0801 (9) O2 0.27319 (15) 0.8654 (6) 0.1308 (2) 0.1100 (15) C1 0.25910 (17) 0.8534 (6) 0.1724 (3) 0.0614 (12) C2 0.20539 (15) 0.8609 (5) 0.1534 (2) 0.0488 (9) C3 0.19023 (15) 0.8011 (7) 0.1997 (2) 0.0596 (11) H3 0.2138 0.7596 0.2437 0.071\* C4 0.14066 (15) 0.8028 (7) 0.1808 (2) 0.0627 (12) H4 0.1305 0.7621 0.2119 0.075\* C5 0.10627 (15) 0.8642 (5) 0.1165 (2) 0.0510 (10) C6 0.12064 (16) 0.9276 (6) 0.0699 (2) 0.0563 (10) H6 0.0971 0.9721 0.0265 0.068\* C7 0.17023 (16) 0.9236 (6) 0.0889 (2) 0.0571 (11) H7 0.1803 0.9640 0.0577 0.069\* C8 0.34155 (17) 0.8066 (9) 0.2610 (3) 0.0977 (18) H8A 0.3466 0.6959 0.2404 0.146\* H8B 0.3601 0.7958 0.3107 0.146\* H8C 0.3528 0.9148 0.2467 0.146\* N2 −0.04641 (12) 0.3799 (4) 0.12080 (17) 0.0549 (8) H2A −0.0469 0.2835 0.1461 0.082\* H2B −0.0329 0.4794 0.1481 0.082\* H2C −0.0284 0.3495 0.1008 0.082\* O3 −0.27704 (11) 0.5652 (5) −0.06223 (17) 0.0754 (9) O4 −0.25318 (15) 0.6482 (7) −0.1379 (2) 0.1235 (17) C9 −0.24390 (17) 0.5845 (7) −0.0834 (2) 0.0649 (12) C10 −0.19295 (13) 0.5235 (6) −0.03008 (18) 0.0475 (9) C11 −0.15324 (15) 0.5639 (6) −0.0409 (2) 0.0530 (10) H11 −0.1591 0.6244 −0.0814 0.064\* C12 −0.10518 (13) 0.5155 (5) 0.00777 (19) 0.0460 (9) H12 −0.0785 0.5435 0.0007 0.055\* C13 −0.09772 (13) 0.4248 (5) 0.06700 (18) 0.0412 (8) C14 −0.13659 (14) 0.3806 (5) 0.07820 (19) 0.0484 (9) H14 −0.1306 0.3179 0.1185 0.058\* C15 −0.18453 (14) 0.4296 (6) 0.0293 (2) 0.0538 (10) H15 −0.2112 0.3995 0.0363 0.065\* C16 −0.32747 (17) 0.6233 (8) −0.1111 (3) 0.100 (2) H16A −0.3402 0.5467 −0.1521 0.150\* H16B −0.3274 0.7526 −0.1234 0.150\* H16C −0.3483 0.6091 −0.0903 0.150\* ------ --------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1343 .table-wrap} ----- ------------- ------------ ------------ -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Sn1 0.0315 (2) 0.0292 (2) 0.0350 (2) 0.000 0.01734 (15) 0.000 Cl1 0.0388 (5) 0.0417 (5) 0.0498 (5) −0.0108 (4) 0.0187 (4) 0.0027 (4) Cl2 0.0430 (5) 0.0531 (6) 0.0319 (5) 0.0061 (4) 0.0138 (4) 0.0043 (4) Cl3 0.0441 (5) 0.0385 (5) 0.0611 (6) 0.0090 (4) 0.0322 (5) 0.0006 (4) Cl4 0.0609 (7) 0.0948 (9) 0.0812 (8) 0.0232 (6) 0.0452 (6) 0.0309 (7) N1 0.054 (2) 0.094 (3) 0.063 (2) 0.0182 (18) 0.0344 (19) 0.021 (2) O1 0.0490 (18) 0.115 (3) 0.080 (2) 0.0101 (17) 0.0348 (18) −0.003 (2) O2 0.084 (3) 0.174 (4) 0.107 (3) 0.001 (2) 0.074 (3) 0.016 (3) C1 0.063 (3) 0.055 (3) 0.086 (4) −0.006 (2) 0.052 (3) −0.008 (2) C2 0.056 (2) 0.045 (2) 0.060 (3) 0.0003 (17) 0.040 (2) −0.0021 (18) C3 0.051 (2) 0.083 (3) 0.052 (2) 0.013 (2) 0.031 (2) 0.017 (2) C4 0.056 (3) 0.091 (3) 0.056 (3) 0.019 (2) 0.038 (2) 0.028 (2) C5 0.052 (2) 0.056 (3) 0.055 (2) 0.0110 (18) 0.034 (2) 0.0093 (19) C6 0.063 (3) 0.065 (3) 0.047 (2) 0.009 (2) 0.032 (2) 0.0141 (19) C7 0.072 (3) 0.062 (3) 0.056 (3) 0.003 (2) 0.046 (2) 0.008 (2) C8 0.053 (3) 0.114 (4) 0.128 (5) 0.012 (3) 0.046 (3) −0.002 (4) N2 0.0470 (19) 0.057 (2) 0.052 (2) 0.0027 (15) 0.0173 (16) −0.0006 (16) O3 0.0418 (16) 0.094 (2) 0.075 (2) 0.0087 (16) 0.0164 (16) −0.0012 (18) O4 0.081 (3) 0.201 (5) 0.063 (2) 0.034 (3) 0.015 (2) 0.051 (3) C9 0.055 (3) 0.073 (3) 0.047 (3) 0.008 (2) 0.010 (2) −0.002 (2) C10 0.046 (2) 0.053 (2) 0.039 (2) 0.0024 (17) 0.0163 (18) −0.0014 (18) C11 0.063 (3) 0.055 (2) 0.041 (2) 0.0008 (19) 0.025 (2) 0.0055 (18) C12 0.046 (2) 0.046 (2) 0.051 (2) −0.0042 (17) 0.0277 (19) 0.0003 (18) C13 0.040 (2) 0.042 (2) 0.038 (2) 0.0015 (15) 0.0161 (16) −0.0023 (16) C14 0.048 (2) 0.056 (2) 0.040 (2) 0.0017 (18) 0.0207 (18) 0.0097 (17) C15 0.042 (2) 0.070 (3) 0.048 (2) −0.0043 (19) 0.0216 (19) 0.004 (2) C16 0.039 (3) 0.114 (5) 0.103 (4) 0.013 (3) 0.002 (3) −0.023 (3) ----- ------------- ------------ ------------ -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1823 .table-wrap} ----------------------- ------------ ------------------- ----------- Sn1---Cl1 2.4131 (8) C8---H8A 0.9600 Sn1---Cl1^i^ 2.4131 (8) C8---H8B 0.9600 Sn1---Cl2^i^ 2.4305 (9) C8---H8C 0.9600 Sn1---Cl2 2.4305 (9) N2---C13 1.471 (4) Sn1---Cl3 2.4315 (8) N2---H2A 0.8900 Sn1---Cl3^i^ 2.4315 (8) N2---H2B 0.8900 N1---C5 1.473 (5) N2---H2C 0.8900 N1---H1A 0.8900 O3---C9 1.320 (5) N1---H1B 0.8900 O3---C16 1.448 (5) N1---H1C 0.8900 O4---C9 1.185 (5) O1---C1 1.314 (6) C9---C10 1.489 (5) O1---C8 1.434 (5) C10---C15 1.380 (5) O2---C1 1.197 (5) C10---C11 1.384 (5) C1---C2 1.492 (5) C11---C12 1.377 (5) C2---C7 1.373 (6) C11---H11 0.9300 C2---C3 1.384 (5) C12---C13 1.375 (5) C3---C4 1.368 (5) C12---H12 0.9300 C3---H3 0.9300 C13---C14 1.371 (5) C4---C5 1.362 (5) C14---C15 1.378 (5) C4---H4 0.9300 C14---H14 0.9300 C5---C6 1.380 (5) C15---H15 0.9300 C6---C7 1.369 (5) C16---H16A 0.9600 C6---H6 0.9300 C16---H16B 0.9600 C7---H7 0.9300 C16---H16C 0.9600 Cl1---Sn1---Cl1^i^ 89.79 (5) C2---C7---H7 119.5 Cl1---Sn1---Cl2^i^ 89.66 (3) O1---C8---H8A 109.5 Cl1^i^---Sn1---Cl2^i^ 90.63 (3) O1---C8---H8B 109.5 Cl1---Sn1---Cl2 90.63 (3) H8A---C8---H8B 109.5 Cl1^i^---Sn1---Cl2 89.66 (3) O1---C8---H8C 109.5 Cl2^i^---Sn1---Cl2 179.58 (4) H8A---C8---H8C 109.5 Cl1---Sn1---Cl3 90.88 (3) H8B---C8---H8C 109.5 Cl1^i^---Sn1---Cl3 179.00 (3) C13---N2---H2A 109.5 Cl2^i^---Sn1---Cl3 88.64 (3) C13---N2---H2B 109.5 Cl2---Sn1---Cl3 91.06 (3) H2A---N2---H2B 109.5 Cl1---Sn1---Cl3^i^ 179.00 (3) C13---N2---H2C 109.5 Cl1^i^---Sn1---Cl3^i^ 90.88 (3) H2A---N2---H2C 109.5 Cl2^i^---Sn1---Cl3^i^ 91.06 (3) H2B---N2---H2C 109.5 Cl2---Sn1---Cl3^i^ 88.64 (3) C9---O3---C16 115.8 (4) Cl3---Sn1---Cl3^i^ 88.45 (4) O4---C9---O3 124.0 (4) C5---N1---H1A 109.5 O4---C9---C10 123.4 (5) C5---N1---H1B 109.5 O3---C9---C10 112.6 (4) H1A---N1---H1B 109.5 C15---C10---C11 119.7 (3) C5---N1---H1C 109.5 C15---C10---C9 121.8 (4) H1A---N1---H1C 109.5 C11---C10---C9 118.5 (4) H1B---N1---H1C 109.5 C12---C11---C10 120.8 (4) C1---O1---C8 117.0 (4) C12---C11---H11 119.6 O2---C1---O1 123.1 (4) C10---C11---H11 119.6 O2---C1---C2 123.4 (5) C13---C12---C11 118.3 (3) O1---C1---C2 113.5 (4) C13---C12---H12 120.9 C7---C2---C3 119.2 (4) C11---C12---H12 120.9 C7---C2---C1 120.1 (4) C14---C13---C12 121.8 (3) C3---C2---C1 120.6 (4) C14---C13---N2 119.2 (3) C4---C3---C2 120.1 (4) C12---C13---N2 118.9 (3) C4---C3---H3 120.0 C13---C14---C15 119.5 (4) C2---C3---H3 120.0 C13---C14---H14 120.3 C5---C4---C3 119.9 (4) C15---C14---H14 120.3 C5---C4---H4 120.0 C14---C15---C10 119.8 (4) C3---C4---H4 120.0 C14---C15---H15 120.1 C4---C5---C6 121.0 (4) C10---C15---H15 120.1 C4---C5---N1 119.9 (3) O3---C16---H16A 109.5 C6---C5---N1 119.0 (4) O3---C16---H16B 109.5 C7---C6---C5 118.8 (4) H16A---C16---H16B 109.5 C7---C6---H6 120.6 O3---C16---H16C 109.5 C5---C6---H6 120.6 H16A---C16---H16C 109.5 C6---C7---C2 121.0 (3) H16B---C16---H16C 109.5 C6---C7---H7 119.5 ----------------------- ------------ ------------------- ----------- ::: Symmetry codes: (i) −*x*, *y*, −*z*+1/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2498 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···Cl3 0.89 2.78 3.659 (4) 170 N2---H2B···Cl3 0.89 2.71 3.479 (3) 145 N2---H2C···Cl4 0.89 2.21 3.098 (4) 177 N1---H1B···Cl4^ii^ 0.89 2.29 3.155 (4) 165 N1---H1C···Cl4^iii^ 0.89 2.22 3.092 (4) 166 N2---H2A···Cl1^iv^ 0.89 3.01 3.482 (3) 115 C3---H3···O4^v^ 0.93 2.39 3.148 (6) 139 C15---H15···O2^vi^ 0.93 2.38 3.130 (5) 138 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −*x*, −*y*+1, −*z*; (iii) *x*, *y*+1, *z*; (iv) *x*, *y*−1, *z*; (v) *x*+1/2, −*y*+3/2, *z*+1/2; (vi) *x*−1/2, *y*−1/2, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- N1---H1*A*⋯Cl3 0.89 2.78 3.659 (4) 170 N2---H2*B*⋯Cl3 0.89 2.71 3.479 (3) 145 N2---H2*C*⋯Cl4 0.89 2.21 3.098 (4) 177 N1---H1*B*⋯Cl4^i^ 0.89 2.29 3.155 (4) 165 N1---H1*C*⋯Cl4^ii^ 0.89 2.22 3.092 (4) 166 N2---H2*A*⋯Cl1^iii^ 0.89 3.01 3.482 (3) 115 C3---H3⋯O4^iv^ 0.93 2.39 3.148 (6) 139 C15---H15⋯O2^v^ 0.93 2.38 3.130 (5) 138 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) . :::

PubMed Central

2024-06-05T04:04:18.847055

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052157/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):m297", "authors": [ { "first": "Wenzhi", "last": "Xiao" }, { "first": "Ruiting", "last": "Xue" }, { "first": "Yansheng", "last": "Yin" } ] }

PMC3052158

Related literature {#sec1} ================== For general background to the synthesis of thiophene-based conjugated polymers, see: Cheng *et al.* (2009[@bb4]). For the synthesis of the title compound, see: Brzezinski & Reynolds (2002[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~9~H~4~I~2~OS~2~*M* *~r~* = 446.04Monoclinic,*a* = 10.1908 (9) Å*b* = 11.4832 (10) Å*c* = 10.9083 (10) Åβ = 107.600 (1)°*V* = 1216.77 (19) Å^3^*Z* = 4Mo *K*α radiationμ = 5.48 mm^−1^*T* = 298 K0.16 × 0.12 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb5]) *T* ~min~ = 0.474, *T* ~max~ = 0.6108022 measured reflections3003 independent reflections2541 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.084 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.043*wR*(*F* ^2^) = 0.103*S* = 1.113003 reflections127 parametersH-atom parameters constrainedΔρ~max~ = 1.08 e Å^−3^Δρ~min~ = −0.67 e Å^−3^ {#d5e387} Data collection: *SMART* (Bruker, 2001[@bb2]); cell refinement: *SAINT* (Bruker, 1999[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb6]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb6]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb6]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005472/cv5050sup1.cif](http://dx.doi.org/10.1107/S1600536811005472/cv5050sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005472/cv5050Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005472/cv5050Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?cv5050&file=cv5050sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?cv5050sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?cv5050&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [CV5050](http://scripts.iucr.org/cgi-bin/sendsup?cv5050)). The author acknowledges financial support from Xiangfan University. Comment ======= The title compound, (I), is an important organic intermediate for the synthesis of conjugated polymers for organic solar cell applications (Brzezinski & Reynolds, 2002; Cheng *et al.*, 2009). In (I) (Fig. 1), two five-membered rings form a dihedral angle of 64.2 (2)°. Weak intermolecular C---H···O hydrogen bonds link the molecules into layers parallel to *ab* plane. The crystal packing exhibits short C···I contacts of 3.442 (5) Å between the molecules from the neighbouring layers. Experimental {#experimental} ============ The title compound was synthesized according to the reported method by Brzezinski & Reynolds (2002). After being dissolved in the mixture of MeOH-Hexane (1:3) for seversal days, colourless crystals suitable for single-crystal X-ray diffraction were obtained. Refinement {#refinement} ========== All hydrogen atoms were positioned geometrically (C---H = 0.93 Å) and allowed to ride on their parent atoms, with *U*~iso~(H) = 1.2 *U*~eq~(C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The title molecule with the atom-numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o691-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e104 .table-wrap} ------------------------- --------------------------------------- C~9~H~4~I~2~OS~2~ *F*(000) = 816 *M~r~* = 446.04 *D*~x~ = 2.435 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 2906 reflections *a* = 10.1908 (9) Å θ = 2.4--26.9° *b* = 11.4832 (10) Å µ = 5.48 mm^−1^ *c* = 10.9083 (10) Å *T* = 298 K β = 107.600 (1)° Block, colourless *V* = 1216.77 (19) Å^3^ 0.16 × 0.12 × 0.10 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e234 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART CCD area-detector diffractometer 3003 independent reflections Radiation source: fine-focus sealed tube 2541 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.084 φ and ω scans θ~max~ = 28.2°, θ~min~ = 2.4° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −13→7 *T*~min~ = 0.474, *T*~max~ = 0.610 *k* = −15→12 8022 measured reflections *l* = −14→14 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e351 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.103 H-atom parameters constrained *S* = 1.11 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0342*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3003 reflections (Δ/σ)~max~ = 0.001 127 parameters Δρ~max~ = 1.08 e Å^−3^ 0 restraints Δρ~min~ = −0.67 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e505 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e604 .table-wrap} ---- -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.7428 (5) 0.3871 (4) 0.9017 (5) 0.0377 (10) C2 0.6198 (5) 0.3657 (4) 0.8086 (4) 0.0328 (9) C3 0.6258 (5) 0.2588 (4) 0.7431 (5) 0.0392 (11) H3 0.5515 0.2291 0.6783 0.047\* C4 0.7482 (6) 0.2053 (5) 0.7835 (5) 0.0486 (13) H4 0.7688 0.1359 0.7495 0.058\* C5 0.5029 (5) 0.4469 (4) 0.7705 (5) 0.0349 (10) C6 0.3643 (5) 0.3977 (4) 0.7066 (5) 0.0350 (10) C7 0.3112 (6) 0.2950 (4) 0.7492 (5) 0.0438 (12) H7 0.3628 0.2488 0.8166 0.053\* C8 0.1801 (6) 0.2717 (5) 0.6827 (6) 0.0499 (13) H8 0.1300 0.2093 0.6996 0.060\* C9 0.2680 (5) 0.4481 (4) 0.6055 (5) 0.0372 (10) I1 0.79608 (5) 0.51950 (4) 1.03536 (4) 0.05838 (16) I2 0.28839 (4) 0.58784 (3) 0.49276 (4) 0.05046 (14) O1 0.5191 (4) 0.5512 (3) 0.7870 (5) 0.0569 (10) S1 0.86152 (15) 0.28059 (13) 0.90534 (14) 0.0517 (4) S2 0.11662 (14) 0.37150 (14) 0.56270 (15) 0.0512 (3) ---- -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e857 .table-wrap} ---- ------------ ------------- ------------ --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.043 (3) 0.035 (3) 0.034 (2) 0.002 (2) 0.012 (2) 0.0020 (19) C2 0.036 (3) 0.033 (2) 0.030 (2) 0.0025 (19) 0.011 (2) 0.0009 (18) C3 0.043 (3) 0.037 (3) 0.034 (2) 0.004 (2) 0.006 (2) −0.003 (2) C4 0.059 (4) 0.044 (3) 0.042 (3) 0.010 (2) 0.012 (3) −0.006 (2) C5 0.034 (2) 0.030 (2) 0.043 (3) 0.0002 (18) 0.014 (2) 0.000 (2) C6 0.039 (3) 0.028 (2) 0.042 (2) 0.0007 (18) 0.018 (2) −0.0017 (19) C7 0.049 (3) 0.036 (3) 0.047 (3) −0.002 (2) 0.014 (2) 0.006 (2) C8 0.048 (3) 0.040 (3) 0.066 (4) −0.011 (2) 0.023 (3) 0.003 (3) C9 0.035 (3) 0.035 (2) 0.043 (3) −0.0045 (19) 0.014 (2) −0.002 (2) I1 0.0753 (3) 0.0496 (2) 0.0436 (2) −0.01260 (18) 0.0080 (2) −0.01168 (16) I2 0.0553 (3) 0.0435 (2) 0.0549 (2) 0.00141 (15) 0.02021 (19) 0.01160 (16) O1 0.041 (2) 0.0288 (18) 0.094 (3) 0.0001 (15) 0.011 (2) −0.005 (2) S1 0.0430 (8) 0.0537 (9) 0.0501 (8) 0.0140 (6) 0.0018 (6) 0.0014 (6) S2 0.0357 (7) 0.0542 (8) 0.0600 (8) −0.0072 (6) 0.0092 (6) 0.0008 (7) ---- ------------ ------------- ------------ --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1135 .table-wrap} ------------------- ------------ ------------------- ------------ C1---C2 1.376 (7) C5---C6 1.485 (7) C1---S1 1.712 (5) C6---C9 1.364 (7) C1---I1 2.063 (5) C6---C7 1.433 (6) C2---C3 1.431 (7) C7---C8 1.339 (8) C2---C5 1.471 (7) C7---H7 0.9300 C3---C4 1.339 (8) C8---S2 1.713 (6) C3---H3 0.9300 C8---H8 0.9300 C4---S1 1.709 (6) C9---S2 1.714 (5) C4---H4 0.9300 C9---I2 2.070 (5) C5---O1 1.215 (6) C2---C1---S1 111.7 (4) C9---C6---C7 111.2 (4) C2---C1---I1 129.8 (4) C9---C6---C5 124.6 (4) S1---C1---I1 118.5 (3) C7---C6---C5 124.1 (4) C1---C2---C3 110.8 (4) C8---C7---C6 113.7 (5) C1---C2---C5 125.1 (4) C8---C7---H7 123.2 C3---C2---C5 123.8 (4) C6---C7---H7 123.2 C4---C3---C2 113.9 (5) C7---C8---S2 111.4 (4) C4---C3---H3 123.1 C7---C8---H8 124.3 C2---C3---H3 123.1 S2---C8---H8 124.3 C3---C4---S1 111.6 (4) C6---C9---S2 111.8 (4) C3---C4---H4 124.2 C6---C9---I2 129.3 (4) S1---C4---H4 124.2 S2---C9---I2 118.7 (3) O1---C5---C2 121.4 (4) C4---S1---C1 92.1 (3) O1---C5---C6 120.8 (4) C8---S2---C9 92.0 (3) C2---C5---C6 117.8 (4) S1---C1---C2---C3 1.2 (5) C2---C5---C6---C7 44.7 (7) I1---C1---C2---C3 −175.7 (4) C9---C6---C7---C8 −0.8 (6) S1---C1---C2---C5 −172.4 (4) C5---C6---C7---C8 175.3 (5) I1---C1---C2---C5 10.6 (7) C6---C7---C8---S2 1.6 (6) C1---C2---C3---C4 −1.6 (6) C7---C6---C9---S2 −0.3 (5) C5---C2---C3---C4 172.2 (5) C5---C6---C9---S2 −176.4 (4) C2---C3---C4---S1 1.2 (6) C7---C6---C9---I2 −173.7 (4) C1---C2---C5---O1 24.2 (7) C5---C6---C9---I2 10.1 (7) C3---C2---C5---O1 −148.6 (5) C3---C4---S1---C1 −0.4 (5) C1---C2---C5---C6 −158.0 (5) C2---C1---S1---C4 −0.5 (4) C3---C2---C5---C6 29.2 (7) I1---C1---S1---C4 176.8 (3) O1---C5---C6---C9 38.0 (7) C7---C8---S2---C9 −1.5 (5) C2---C5---C6---C9 −139.7 (5) C6---C9---S2---C8 1.0 (4) O1---C5---C6---C7 −137.6 (5) I2---C9---S2---C8 175.2 (3) ------------------- ------------ ------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1539 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C4---H4···O1^i^ 0.93 2.51 3.233 (7) 135 C8---H8···O1^ii^ 0.93 2.40 3.324 (6) 172 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+3/2, *y*−1/2, −*z*+3/2; (ii) −*x*+1/2, *y*−1/2, −*z*+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- C4---H4⋯O1^i^ 0.93 2.51 3.233 (7) 135 C8---H8⋯O1^ii^ 0.93 2.40 3.324 (6) 172 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.852631

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052158/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o691", "authors": [ { "first": "Hua", "last": "Cheng" } ] }

PMC3052159

Related literature {#sec1} ================== For related structures, see: Subha Nandhini *et al.* (2003[@bb11]); Nithya *et al.* (2009[@bb8]); Aravindhan *et al.* (2009[@bb1]); Aridoss *et al.* (2009[@bb2], 2010[@bb3]). For ring conformational analysis, see: Cremer & Pople (1975[@bb5]); Nardelli (1983[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~27~H~25~NO~4~*M* *~r~* = 427.48Triclinic,*a* = 8.2784 (7) Å*b* = 10.6116 (9) Å*c* = 12.7572 (11) Åα = 85.681 (4)°β = 89.963 (4)°γ = 82.508 (5)°*V* = 1107.91 (16) Å^3^*Z* = 2Mo *K*α radiationμ = 0.09 mm^−1^*T* = 293 K0.25 × 0.23 × 0.20 mm ### Data collection {#sec2.1.2} Bruker SMART APEXII area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2008[@bb4]) *T* ~min~ = 0.979, *T* ~max~ = 0.98320295 measured reflections5526 independent reflections4179 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.024 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.043*wR*(*F* ^2^) = 0.120*S* = 1.045526 reflections290 parametersH-atom parameters constrainedΔρ~max~ = 0.20 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e414} Data collection: *APEX2* (Bruker, 2008[@bb4]); cell refinement: *SAINT* (Bruker, 2008[@bb4]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb9]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb9]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb6]); software used to prepare material for publication: *SHELXL97* and *PLATON* (Spek, 2009[@bb10]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003266/is2669sup1.cif](http://dx.doi.org/10.1107/S1600536811003266/is2669sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003266/is2669Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003266/is2669Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?is2669&file=is2669sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?is2669sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?is2669&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [IS2669](http://scripts.iucr.org/cgi-bin/sendsup?is2669)). This research was supported by the Industrial Technology Development Program, which was conducted by the Ministry of Knowledge Economy of the Korean Government. SS and DV thank the TBI X-ray Facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection and the University Grants Commission (UGC&SAP) for financial support. Comment ======= Owing to the relevance of piperidine-containing bioactive compounds, the development of new piperidine based derivatives continues to be a subject of considerable interest. The pharmacological effects of potential new drugs depend entirely on the stereochemistry and ring conformations of the compounds and hence the crystallographic study of the title compound has been carried out. The *ORTEP* diagram of the title compound is shown in Fig. 1. The tetrahydropyridine ring adopts a half-chair conformation. The puckering parameters (Cremer & Pople, 1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) for this ring are q~2~ = 0.344 (1) Å, q~3~ = -0.288 (1) Å; Q~T~ = 0.4485 Å and θ = 130.02 (2)°, φ~2~ = 205.6 (2)°, respectively. The three phenyl rings are twisted away from the best plane of the tetrahydropyridine ring by 66.33 (7), 87.36 (8) and 36.90 (7)°, respectively. The sum of the bond angles around the atom N1 \[360.09 (10)°\] of the tetrahydropyridine ring in the molecule is in accordance with *sp^2^* hybridization. The ethyl acetate group shows an extended conformation \[C18---O3---C19---C20 = 90.67 (2)°\]. The molecular structure is stabilized by a strong O---H···O hydrogen bond, wherein, atom O1 acts as a donor to O2, generating an *S*(6) motif. Experimental {#experimental} ============ To a mixture of 3-carboxyethyl-2,6-diphenylpiperidin-4-one (1 equiv.) and triethylamine (1.5 equiv.) in benzene, freshly distilled benzoyl chloride in benzene was added dropwise and stirred well at room temperature until completion. The crude mass obtained by the base work upon purification and recrystallization in distilled ethanol gave fine white crystals suitable for X-ray study. Refinement {#refinement} ========== The C bound H atoms positioned geometrically (C---H = 0.93--0.98 Å) and allowed to ride on their parent atoms, with 1.5*U*~eq~(C) for methyl H and 1.2*U*~eq~(C) for other H atoms. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Perspective view of the title compound, showing displacement ellipsoids drawn at the 30% probability level. ::: ![](e-67-0o540-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Crystal packing of the title compound, viewed down the a axis. For clarity, hydrogen atoms not involved in hydrogen bonding have been omitted. ::: ![](e-67-0o540-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e139 .table-wrap} ------------------------- --------------------------------------- C~27~H~25~NO~4~ *Z* = 2 *M~r~* = 427.48 *F*(000) = 452 Triclinic, *P*1 *D*~x~ = 1.281 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.2784 (7) Å Cell parameters from 1225 reflections *b* = 10.6116 (9) Å θ = 1.6--28.4° *c* = 12.7572 (11) Å µ = 0.09 mm^−1^ α = 85.681 (4)° *T* = 293 K β = 89.963 (4)° Block, white γ = 82.508 (5)° 0.25 × 0.23 × 0.20 mm *V* = 1107.91 (16) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e272 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART APEXII area-detector diffractometer 5526 independent reflections Radiation source: fine-focus sealed tube 4179 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.024 ω and φ scans θ~max~ = 28.4°, θ~min~ = 1.6° Absorption correction: multi-scan (*SADABS*; Bruker, 2008) *h* = −11→11 *T*~min~ = 0.979, *T*~max~ = 0.983 *k* = −14→14 20295 measured reflections *l* = −17→17 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e389 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.120 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0497*P*)^2^ + 0.2116*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5526 reflections (Δ/σ)~max~ \< 0.001 290 parameters Δρ~max~ = 0.20 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e546 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e645 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.35152 (15) 0.26735 (12) 0.41384 (9) 0.0431 (3) H1 0.3276 0.2416 0.4870 0.052\* C2 0.44264 (18) 0.38303 (14) 0.41541 (11) 0.0551 (3) H2A 0.4025 0.4326 0.4731 0.066\* H2B 0.5573 0.3539 0.4285 0.066\* C3 0.42551 (17) 0.46663 (12) 0.31645 (11) 0.0483 (3) C4 0.31584 (15) 0.45704 (11) 0.23982 (9) 0.0421 (3) C5 0.19897 (14) 0.35828 (11) 0.24886 (9) 0.0382 (2) H5 0.0906 0.4048 0.2328 0.046\* C6 0.22569 (15) 0.25498 (11) 0.17071 (9) 0.0410 (3) C7 0.34280 (18) 0.25430 (15) 0.09352 (12) 0.0585 (4) H7 0.4142 0.3152 0.0911 0.070\* C8 0.3555 (2) 0.16428 (18) 0.01975 (15) 0.0758 (5) H8 0.4340 0.1660 −0.0324 0.091\* C9 0.2530 (2) 0.07296 (16) 0.02343 (14) 0.0739 (5) H9 0.2626 0.0117 −0.0255 0.089\* C10 0.1359 (2) 0.07199 (15) 0.09956 (12) 0.0663 (4) H10 0.0657 0.0102 0.1020 0.080\* C11 0.12177 (19) 0.16256 (13) 0.17261 (11) 0.0528 (3) H11 0.0416 0.1614 0.2236 0.063\* C12 0.44595 (15) 0.15211 (13) 0.36780 (10) 0.0447 (3) C13 0.59156 (19) 0.15546 (17) 0.31517 (14) 0.0692 (4) H13 0.6367 0.2313 0.3062 0.083\* C14 0.6700 (2) 0.0462 (2) 0.27598 (19) 0.0929 (7) H14 0.7676 0.0494 0.2403 0.112\* C15 0.6072 (2) −0.0660 (2) 0.28857 (17) 0.0873 (6) H15 0.6602 −0.1385 0.2606 0.105\* C16 0.4653 (2) −0.07137 (17) 0.34282 (16) 0.0748 (5) H16 0.4226 −0.1482 0.3531 0.090\* C17 0.38547 (18) 0.03709 (14) 0.38216 (12) 0.0573 (4) H17 0.2892 0.0326 0.4190 0.069\* C18 0.29783 (17) 0.55330 (12) 0.15177 (10) 0.0477 (3) C19 0.1465 (2) 0.63209 (17) −0.00422 (12) 0.0685 (4) H19A 0.1880 0.7112 0.0078 0.082\* H19B 0.0311 0.6514 −0.0203 0.082\* C20 0.2327 (2) 0.5731 (2) −0.09393 (13) 0.0832 (6) H20A 0.3479 0.5599 −0.0799 0.125\* H20B 0.2108 0.6286 −0.1567 0.125\* H20C 0.1954 0.4927 −0.1033 0.125\* C21 0.04496 (15) 0.30444 (11) 0.40464 (10) 0.0416 (3) C22 0.03654 (15) 0.27946 (12) 0.52150 (10) 0.0433 (3) C23 −0.04315 (18) 0.18014 (14) 0.56215 (11) 0.0549 (3) H23 −0.0836 0.1265 0.5172 0.066\* C24 −0.0628 (2) 0.16050 (17) 0.66984 (12) 0.0655 (4) H24 −0.1142 0.0925 0.6971 0.079\* C25 −0.0065 (2) 0.24121 (17) 0.73612 (12) 0.0643 (4) H25 −0.0203 0.2280 0.8083 0.077\* C26 0.0700 (2) 0.34139 (15) 0.69651 (12) 0.0620 (4) H26 0.1068 0.3965 0.7417 0.074\* C27 0.09253 (18) 0.36049 (13) 0.58943 (11) 0.0531 (3) H27 0.1454 0.4280 0.5628 0.064\* N1 0.19330 (12) 0.30648 (9) 0.35920 (7) 0.0388 (2) O1 0.52511 (14) 0.55669 (10) 0.31367 (9) 0.0663 (3) H1A 0.5089 0.6028 0.2592 0.099\* O2 0.38767 (14) 0.63583 (10) 0.13602 (9) 0.0687 (3) O3 0.17091 (12) 0.54509 (9) 0.08975 (7) 0.0530 (2) O4 −0.08244 (11) 0.32515 (10) 0.35338 (8) 0.0563 (3) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1408 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0447 (6) 0.0496 (7) 0.0359 (6) −0.0114 (5) −0.0075 (5) −0.0002 (5) C2 0.0608 (8) 0.0598 (8) 0.0487 (7) −0.0218 (7) −0.0139 (6) −0.0056 (6) C3 0.0527 (7) 0.0446 (7) 0.0511 (7) −0.0167 (6) −0.0007 (6) −0.0096 (5) C4 0.0474 (7) 0.0384 (6) 0.0417 (6) −0.0098 (5) 0.0013 (5) −0.0042 (5) C5 0.0418 (6) 0.0381 (6) 0.0350 (6) −0.0079 (5) −0.0044 (5) −0.0006 (4) C6 0.0457 (6) 0.0398 (6) 0.0372 (6) −0.0047 (5) −0.0091 (5) −0.0016 (5) C7 0.0539 (8) 0.0606 (9) 0.0643 (9) −0.0121 (7) 0.0074 (7) −0.0191 (7) C8 0.0766 (11) 0.0824 (12) 0.0721 (11) −0.0086 (9) 0.0160 (9) −0.0333 (9) C9 0.0989 (13) 0.0620 (10) 0.0636 (10) −0.0070 (9) −0.0032 (9) −0.0282 (8) C10 0.0967 (12) 0.0514 (8) 0.0556 (9) −0.0254 (8) −0.0139 (8) −0.0085 (7) C11 0.0701 (9) 0.0494 (7) 0.0417 (7) −0.0193 (6) −0.0052 (6) −0.0026 (5) C12 0.0398 (6) 0.0529 (7) 0.0400 (6) −0.0036 (5) −0.0081 (5) 0.0025 (5) C13 0.0483 (8) 0.0712 (10) 0.0847 (12) −0.0031 (7) 0.0098 (8) 0.0087 (9) C14 0.0584 (10) 0.0983 (16) 0.1135 (17) 0.0163 (10) 0.0255 (10) 0.0017 (13) C15 0.0693 (12) 0.0831 (13) 0.1018 (15) 0.0267 (10) −0.0038 (10) −0.0202 (11) C16 0.0639 (10) 0.0571 (9) 0.1021 (14) 0.0026 (8) −0.0138 (9) −0.0147 (9) C17 0.0485 (8) 0.0558 (8) 0.0685 (9) −0.0080 (6) 0.0002 (7) −0.0080 (7) C18 0.0531 (7) 0.0427 (7) 0.0476 (7) −0.0077 (6) 0.0080 (6) −0.0022 (5) C19 0.0756 (10) 0.0728 (10) 0.0521 (8) −0.0055 (8) −0.0031 (7) 0.0214 (7) C20 0.0807 (12) 0.1220 (16) 0.0467 (9) −0.0197 (11) 0.0016 (8) 0.0062 (9) C21 0.0462 (7) 0.0372 (6) 0.0424 (6) −0.0089 (5) −0.0010 (5) −0.0027 (5) C22 0.0443 (6) 0.0419 (6) 0.0430 (6) −0.0025 (5) 0.0029 (5) −0.0030 (5) C23 0.0579 (8) 0.0568 (8) 0.0518 (8) −0.0168 (6) 0.0020 (6) −0.0002 (6) C24 0.0652 (9) 0.0736 (10) 0.0566 (9) −0.0149 (8) 0.0087 (7) 0.0130 (8) C25 0.0656 (9) 0.0780 (11) 0.0440 (8) 0.0082 (8) 0.0107 (7) −0.0014 (7) C26 0.0753 (10) 0.0596 (9) 0.0489 (8) 0.0073 (7) −0.0004 (7) −0.0188 (7) C27 0.0654 (9) 0.0428 (7) 0.0514 (8) −0.0055 (6) 0.0025 (6) −0.0085 (6) N1 0.0415 (5) 0.0405 (5) 0.0347 (5) −0.0073 (4) −0.0034 (4) −0.0013 (4) O1 0.0744 (7) 0.0620 (6) 0.0700 (7) −0.0369 (5) −0.0074 (5) −0.0056 (5) O2 0.0769 (7) 0.0583 (6) 0.0731 (7) −0.0273 (5) 0.0042 (6) 0.0116 (5) O3 0.0599 (6) 0.0546 (5) 0.0427 (5) −0.0073 (4) −0.0006 (4) 0.0081 (4) O4 0.0445 (5) 0.0718 (7) 0.0530 (6) −0.0128 (5) −0.0049 (4) 0.0030 (5) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2071 .table-wrap} ----------------------- -------------- ----------------------- -------------- C1---N1 1.4798 (15) C14---H14 0.9300 C1---C12 1.5197 (19) C15---C16 1.369 (3) C1---C2 1.5237 (18) C15---H15 0.9300 C1---H1 0.9800 C16---C17 1.379 (2) C2---C3 1.4831 (19) C16---H16 0.9300 C2---H2A 0.9700 C17---H17 0.9300 C2---H2B 0.9700 C18---O2 1.2263 (16) C3---O1 1.3397 (15) C18---O3 1.3315 (17) C3---C4 1.3531 (18) C19---O3 1.4545 (16) C4---C18 1.4543 (18) C19---C20 1.484 (2) C4---C5 1.5145 (16) C19---H19A 0.9700 C5---N1 1.4751 (14) C19---H19B 0.9700 C5---C6 1.5315 (16) C20---H20A 0.9600 C5---H5 0.9800 C20---H20B 0.9600 C6---C7 1.3812 (19) C20---H20C 0.9600 C6---C11 1.3852 (18) C21---O4 1.2276 (15) C7---C8 1.385 (2) C21---N1 1.3597 (16) C7---H7 0.9300 C21---C22 1.4976 (17) C8---C9 1.367 (3) C22---C23 1.3833 (19) C8---H8 0.9300 C22---C27 1.3863 (18) C9---C10 1.372 (3) C23---C24 1.387 (2) C9---H9 0.9300 C23---H23 0.9300 C10---C11 1.383 (2) C24---C25 1.371 (2) C10---H10 0.9300 C24---H24 0.9300 C11---H11 0.9300 C25---C26 1.372 (2) C12---C17 1.3782 (19) C25---H25 0.9300 C12---C13 1.383 (2) C26---C27 1.382 (2) C13---C14 1.381 (3) C26---H26 0.9300 C13---H13 0.9300 C27---H27 0.9300 C14---C15 1.359 (3) O1---H1A 0.8200 N1---C1---C12 111.53 (9) C14---C15---C16 119.40 (17) N1---C1---C2 108.76 (10) C14---C15---H15 120.3 C12---C1---C2 114.90 (11) C16---C15---H15 120.3 N1---C1---H1 107.1 C15---C16---C17 120.01 (18) C12---C1---H1 107.1 C15---C16---H16 120.0 C2---C1---H1 107.1 C17---C16---H16 120.0 C3---C2---C1 113.62 (10) C12---C17---C16 121.14 (15) C3---C2---H2A 108.8 C12---C17---H17 119.4 C1---C2---H2A 108.8 C16---C17---H17 119.4 C3---C2---H2B 108.8 O2---C18---O3 122.55 (12) C1---C2---H2B 108.8 O2---C18---C4 124.16 (13) H2A---C2---H2B 107.7 O3---C18---C4 113.28 (11) O1---C3---C4 123.70 (12) O3---C19---C20 109.75 (14) O1---C3---C2 112.47 (11) O3---C19---H19A 109.7 C4---C3---C2 123.74 (11) C20---C19---H19A 109.7 C3---C4---C18 118.69 (11) O3---C19---H19B 109.7 C3---C4---C5 122.01 (11) C20---C19---H19B 109.7 C18---C4---C5 118.95 (11) H19A---C19---H19B 108.2 N1---C5---C4 109.42 (9) C19---C20---H20A 109.5 N1---C5---C6 113.34 (9) C19---C20---H20B 109.5 C4---C5---C6 115.47 (10) H20A---C20---H20B 109.5 N1---C5---H5 105.9 C19---C20---H20C 109.5 C4---C5---H5 105.9 H20A---C20---H20C 109.5 C6---C5---H5 105.9 H20B---C20---H20C 109.5 C7---C6---C11 118.09 (12) O4---C21---N1 122.22 (11) C7---C6---C5 122.82 (11) O4---C21---C22 118.89 (11) C11---C6---C5 118.96 (11) N1---C21---C22 118.87 (11) C6---C7---C8 121.02 (14) C23---C22---C27 119.20 (13) C6---C7---H7 119.5 C23---C22---C21 118.91 (12) C8---C7---H7 119.5 C27---C22---C21 121.59 (12) C9---C8---C7 120.12 (16) C22---C23---C24 120.09 (14) C9---C8---H8 119.9 C22---C23---H23 120.0 C7---C8---H8 119.9 C24---C23---H23 120.0 C8---C9---C10 119.73 (14) C25---C24---C23 120.07 (15) C8---C9---H9 120.1 C25---C24---H24 120.0 C10---C9---H9 120.1 C23---C24---H24 120.0 C9---C10---C11 120.26 (15) C24---C25---C26 120.31 (14) C9---C10---H10 119.9 C24---C25---H25 119.8 C11---C10---H10 119.9 C26---C25---H25 119.8 C10---C11---C6 120.77 (14) C25---C26---C27 120.03 (14) C10---C11---H11 119.6 C25---C26---H26 120.0 C6---C11---H11 119.6 C27---C26---H26 120.0 C17---C12---C13 118.23 (14) C26---C27---C22 120.27 (14) C17---C12---C1 118.10 (12) C26---C27---H27 119.9 C13---C12---C1 123.64 (13) C22---C27---H27 119.9 C14---C13---C12 120.02 (17) C21---N1---C5 118.15 (10) C14---C13---H13 120.0 C21---N1---C1 124.93 (10) C12---C13---H13 120.0 C5---N1---C1 116.82 (9) C15---C14---C13 121.17 (18) C3---O1---H1A 109.5 C15---C14---H14 119.4 C18---O3---C19 118.01 (12) C13---C14---H14 119.4 N1---C1---C2---C3 −39.33 (16) C1---C12---C17---C16 −179.77 (14) C12---C1---C2---C3 86.47 (15) C15---C16---C17---C12 0.1 (3) C1---C2---C3---O1 −170.79 (12) C3---C4---C18---O2 8.2 (2) C1---C2---C3---C4 12.3 (2) C5---C4---C18---O2 −178.52 (12) O1---C3---C4---C18 −3.4 (2) C3---C4---C18---O3 −170.63 (12) C2---C3---C4---C18 173.15 (13) C5---C4---C18---O3 2.68 (17) O1---C3---C4---C5 −176.51 (12) O4---C21---C22---C23 57.04 (17) C2---C3---C4---C5 0.1 (2) N1---C21---C22---C23 −124.55 (13) C3---C4---C5---N1 15.95 (16) O4---C21---C22---C27 −116.66 (15) C18---C4---C5---N1 −157.13 (11) N1---C21---C22---C27 61.75 (17) C3---C4---C5---C6 −113.35 (13) C27---C22---C23---C24 −1.6 (2) C18---C4---C5---C6 73.57 (14) C21---C22---C23---C24 −175.44 (13) N1---C5---C6---C7 −130.38 (13) C22---C23---C24---C25 1.5 (2) C4---C5---C6---C7 −3.03 (17) C23---C24---C25---C26 −0.3 (2) N1---C5---C6---C11 53.88 (14) C24---C25---C26---C27 −0.8 (2) C4---C5---C6---C11 −178.77 (11) C25---C26---C27---C22 0.6 (2) C11---C6---C7---C8 0.4 (2) C23---C22---C27---C26 0.5 (2) C5---C6---C7---C8 −175.42 (14) C21---C22---C27---C26 174.22 (13) C6---C7---C8---C9 −1.0 (3) O4---C21---N1---C5 11.51 (17) C7---C8---C9---C10 1.0 (3) C22---C21---N1---C5 −166.85 (10) C8---C9---C10---C11 −0.3 (3) O4---C21---N1---C1 −172.21 (11) C9---C10---C11---C6 −0.4 (2) C22---C21---N1---C1 9.43 (17) C7---C6---C11---C10 0.3 (2) C4---C5---N1---C21 129.05 (11) C5---C6---C11---C10 176.29 (13) C6---C5---N1---C21 −100.50 (12) N1---C1---C12---C17 −68.07 (15) C4---C5---N1---C1 −47.53 (13) C2---C1---C12---C17 167.57 (11) C6---C5---N1---C1 82.92 (12) N1---C1---C12---C13 113.98 (14) C12---C1---N1---C21 116.28 (12) C2---C1---C12---C13 −10.38 (18) C2---C1---N1---C21 −115.98 (13) C17---C12---C13---C14 1.8 (2) C12---C1---N1---C5 −67.39 (13) C1---C12---C13---C14 179.77 (16) C2---C1---N1---C5 60.35 (13) C12---C13---C14---C15 −0.4 (3) O2---C18---O3---C19 4.6 (2) C13---C14---C15---C16 −1.3 (3) C4---C18---O3---C19 −176.56 (12) C14---C15---C16---C17 1.4 (3) C20---C19---O3---C18 90.67 (17) C13---C12---C17---C16 −1.7 (2) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3206 .table-wrap} --------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1A···O2 0.82 1.85 2.570 (2) 146 --------------- --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- --------- ------- ----------- ------------- O1---H1*A*⋯O2 0.82 1.85 2.570 (2) 146 :::

PubMed Central

2024-06-05T04:04:18.855678

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052159/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o540", "authors": [ { "first": "G.", "last": "Aridoss" }, { "first": "S.", "last": "Sundaramoorthy" }, { "first": "D.", "last": "Velmurugan" }, { "first": "Y. T.", "last": "Jeong" } ] }

PMC3052160

Related literature {#sec1} ================== For related structures, see: Li (2011[@bb2]); Liang (2008[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~3~H~10~N^+^·C~9~H~3~Cl~4~O~4~ ^−^*M* *~r~* = 377.03Monoclinic,*a* = 28.387 (3) Å*b* = 14.9600 (13) Å*c* = 7.8054 (6) Åβ = 93.216 (1)°*V* = 3309.5 (5) Å^3^*Z* = 8Mo *K*α radiationμ = 0.73 mm^−1^*T* = 298 K0.47 × 0.32 × 0.23 mm ### Data collection {#sec2.1.2} Bruker SMART diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 1997[@bb1]) *T* ~min~ = 0.726, *T* ~max~ = 0.8518267 measured reflections2920 independent reflections1405 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.069 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.054*wR*(*F* ^2^) = 0.135*S* = 1.022920 reflections193 parametersH-atom parameters constrainedΔρ~max~ = 0.37 e Å^−3^Δρ~min~ = −0.20 e Å^−3^ {#d5e464} Data collection: *SMART* (Bruker, 1997[@bb1]); cell refinement: *SAINT* (Bruker, 1997[@bb1]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb4]) and *PLATON* (Spek, 2009[@bb5]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004879/ng5113sup1.cif](http://dx.doi.org/10.1107/S1600536811004879/ng5113sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004879/ng5113Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004879/ng5113Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5113&file=ng5113sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5113sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5113&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5113](http://scripts.iucr.org/cgi-bin/sendsup?ng5113)). The author thanks Shandong Provincial Natural Science Foundation, China (ZR2009BL027) for support. Comment ======= We have been studying synthesis of 4,5,6,7-tetrachloro-2-propylisoindoline-1,3-dione. In the present work, the reaction of 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoic acid and propylamine in methanol is expected to yield 4,5,6,7-tetrachloro-2-propylisoindoline-1,3-dione. However, the product is propylaminium 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoate (Scheme I, Fig. 1), the reason may be shorter time and cooler temperature in the reaction. The asymmetric unit of the title compound (I) contains one propylaminium cation and one 2-(methoxycarbonyl)-3,4,5,6-tetrachlorobenzoate anion (Fig. 1). The cation adopts N---C---C---C torsion angle of -178.6 (3) °, the dihedral angles of benzene ring with the methoxycarbonyl and carboxylate groups are 57.8 (3) and 62.5 (3) °, respectively, in the antion. The bond lengths and angles are in agreement with those in ethylammonium 2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate methanol solvate (Li, 2011) and in ethane-1,2-diammonium bis(2-(methoxycarbonyl)-3,4,5,6-tetrabromobenzoate) methanol solvate (Liang, 2008). In the crystal structure the cations and anions are connected by intermolecular N---H···O hydrogen bonds into one-dimensional chains along \[001\](Fig. 2 and Table 1). Experimental {#experimental} ============ A mixture of 4,5,6,7-tetrachloroisobenzofuran-1,3-dione (2.86 g, 0.01 mol) and methanol (15 ml) was refluxed for 0.5 h. And then Propylamine (0.59 g, 0.01 mol) was added to the above solution, being mixed round for 10 min at room temperature. And then the solution was kept at room temperature for 5 d. Natural evaporation gave colourless single crystals of the title compound, suitable for X-ray analysis. Refinement {#refinement} ========== H atoms were initially located from difference maps and then refined in a riding model with C---H = 0.96--0.97 Å, N---H = 0.89 Å, O---H = 0.82Å and *U*~iso~(H) = 1.2*U*~eq~(C) or 1.5*U*~eq~(O, N, methyl C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of (I), drawn with 30% probability ellipsoids. ::: ![](e-67-0o630-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of (I), viewed along c axis. Hydrogen bonds are indicated by dashed lines. ::: ![](e-67-0o630-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e113 .table-wrap} ------------------------------------ --------------------------------------- C~3~H~10~N^+^·C~9~H~3~Cl~4~O~4~^−^ *F*(000) = 1536 *M~r~* = 377.03 *D*~x~ = 1.513 Mg m^−3^ Monoclinic, *C*2/*c* Mo *K*α radiation, λ = 0.71073 Å *a* = 28.387 (3) Å Cell parameters from 1429 reflections *b* = 14.9600 (13) Å θ = 2.9--23.7° *c* = 7.8054 (6) Å µ = 0.73 mm^−1^ β = 93.216 (1)° *T* = 298 K *V* = 3309.5 (5) Å^3^ Block, colorless *Z* = 8 0.47 × 0.32 × 0.23 mm ------------------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e249 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker SMART diffractometer 2920 independent reflections Radiation source: fine-focus sealed tube 1405 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.069 φ and ω scans θ~max~ = 25.0°, θ~min~ = 2.6° Absorption correction: multi-scan (*SADABS*; Bruker, 1997) *h* = −23→33 *T*~min~ = 0.726, *T*~max~ = 0.851 *k* = −17→17 8267 measured reflections *l* = −9→9 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e366 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.054 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.135 H-atom parameters constrained *S* = 1.02 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0475*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2920 reflections (Δ/σ)~max~ \< 0.001 193 parameters Δρ~max~ = 0.37 e Å^−3^ 0 restraints Δρ~min~ = −0.20 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e520 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e619 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cl1 0.50360 (3) 0.81553 (7) 0.52072 (18) 0.0958 (5) Cl2 0.55595 (5) 0.99424 (7) 0.6113 (3) 0.1375 (7) Cl3 0.66359 (4) 0.99436 (7) 0.6998 (2) 0.1342 (7) Cl4 0.72101 (4) 0.81799 (7) 0.68593 (18) 0.0961 (5) N1 0.44237 (10) 0.58365 (18) 0.4533 (4) 0.0630 (9) H1A 0.4637 0.6137 0.3968 0.095\* H1B 0.4443 0.5257 0.4286 0.095\* H1C 0.4480 0.5915 0.5657 0.095\* O1 0.68601 (9) 0.63305 (17) 0.7732 (4) 0.0749 (8) O2 0.66423 (10) 0.5995 (2) 0.5002 (4) 0.0908 (10) O3 0.56435 (9) 0.59345 (17) 0.6786 (4) 0.0749 (8) O4 0.54157 (9) 0.63029 (17) 0.4104 (4) 0.0710 (8) C1 0.66366 (13) 0.6473 (3) 0.6217 (7) 0.0604 (11) C2 0.56159 (12) 0.6450 (2) 0.5521 (6) 0.0530 (10) C3 0.63685 (11) 0.7345 (2) 0.6219 (5) 0.0527 (10) C4 0.58827 (12) 0.7341 (2) 0.5810 (5) 0.0522 (9) C5 0.56380 (12) 0.8150 (2) 0.5743 (5) 0.0665 (12) C6 0.58697 (14) 0.8952 (2) 0.6135 (6) 0.0797 (14) C7 0.63492 (14) 0.8952 (2) 0.6518 (6) 0.0779 (13) C8 0.66020 (12) 0.8156 (2) 0.6525 (5) 0.0619 (11) C9 0.71825 (15) 0.5576 (3) 0.7804 (7) 0.1017 (16) H9A 0.7007 0.5031 0.7637 0.153\* H9B 0.7352 0.5562 0.8904 0.153\* H9C 0.7402 0.5635 0.6919 0.153\* C10 0.39403 (12) 0.6172 (2) 0.4012 (5) 0.0634 (11) H10A 0.3714 0.5914 0.4756 0.076\* H10B 0.3856 0.5984 0.2846 0.076\* C11 0.39174 (14) 0.7179 (2) 0.4118 (5) 0.0731 (12) H11A 0.4139 0.7436 0.3354 0.088\* H11B 0.4010 0.7367 0.5278 0.088\* C12 0.34187 (16) 0.7531 (3) 0.3628 (6) 0.0944 (15) H12A 0.3335 0.7382 0.2454 0.142\* H12B 0.3413 0.8168 0.3767 0.142\* H12C 0.3197 0.7262 0.4357 0.142\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1066 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cl1 0.0429 (6) 0.0713 (7) 0.1698 (14) 0.0085 (5) −0.0226 (7) −0.0073 (7) Cl2 0.0788 (9) 0.0531 (7) 0.276 (2) 0.0161 (6) −0.0340 (11) −0.0109 (9) Cl3 0.0782 (9) 0.0619 (7) 0.259 (2) −0.0211 (6) −0.0221 (10) −0.0134 (9) Cl4 0.0379 (6) 0.0906 (8) 0.1587 (13) −0.0099 (5) −0.0041 (7) −0.0034 (8) N1 0.053 (2) 0.0559 (18) 0.080 (2) −0.0011 (15) 0.0030 (17) −0.0029 (17) O1 0.0562 (17) 0.0818 (19) 0.085 (2) 0.0207 (14) −0.0071 (16) 0.0062 (16) O2 0.087 (2) 0.090 (2) 0.094 (3) 0.0328 (17) −0.0111 (18) −0.0228 (19) O3 0.085 (2) 0.0574 (17) 0.083 (2) −0.0072 (14) 0.0046 (16) 0.0042 (16) O4 0.0572 (17) 0.0811 (19) 0.073 (2) −0.0115 (14) −0.0083 (15) −0.0113 (16) C1 0.041 (2) 0.059 (3) 0.081 (4) 0.0008 (19) −0.001 (2) 0.002 (2) C2 0.035 (2) 0.050 (2) 0.075 (3) −0.0007 (17) 0.005 (2) 0.000 (2) C3 0.039 (2) 0.048 (2) 0.071 (3) 0.0034 (18) −0.0019 (18) 0.0013 (19) C4 0.042 (2) 0.048 (2) 0.067 (3) −0.0035 (18) −0.0029 (18) 0.0037 (19) C5 0.038 (2) 0.054 (2) 0.106 (4) 0.0011 (18) −0.008 (2) −0.001 (2) C6 0.047 (3) 0.049 (2) 0.141 (4) 0.0082 (19) −0.010 (3) −0.002 (2) C7 0.053 (3) 0.049 (2) 0.130 (4) −0.009 (2) −0.009 (3) 0.002 (2) C8 0.033 (2) 0.062 (2) 0.090 (3) −0.0047 (18) −0.003 (2) 0.003 (2) C9 0.071 (3) 0.101 (3) 0.132 (4) 0.040 (3) −0.002 (3) 0.032 (3) C10 0.050 (2) 0.059 (2) 0.081 (3) −0.0034 (18) 0.000 (2) −0.002 (2) C11 0.076 (3) 0.062 (3) 0.081 (3) −0.005 (2) 0.000 (2) 0.002 (2) C12 0.080 (3) 0.087 (3) 0.115 (4) 0.022 (3) −0.005 (3) 0.005 (3) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1501 .table-wrap} -------------------- ------------ ---------------------- ------------ Cl1---C5 1.736 (3) C4---C5 1.396 (4) Cl2---C6 1.724 (4) C5---C6 1.393 (5) Cl3---C7 1.723 (4) C6---C7 1.377 (5) Cl4---C8 1.732 (3) C7---C8 1.391 (5) N1---C10 1.496 (4) C9---H9A 0.9600 N1---H1A 0.8900 C9---H9B 0.9600 N1---H1B 0.8900 C9---H9C 0.9600 N1---H1C 0.8900 C10---C11 1.510 (5) O1---C1 1.327 (5) C10---H10A 0.9700 O1---C9 1.453 (4) C10---H10B 0.9700 O2---C1 1.189 (4) C11---C12 1.538 (5) O3---C2 1.251 (4) C11---H11A 0.9700 O4---C2 1.234 (4) C11---H11B 0.9700 C1---C3 1.511 (5) C12---H12A 0.9600 C2---C4 1.544 (5) C12---H12B 0.9600 C3---C8 1.396 (4) C12---H12C 0.9600 C3---C4 1.398 (4) C10---N1---H1A 109.5 C7---C8---C3 120.2 (3) C10---N1---H1B 109.5 C7---C8---Cl4 119.5 (3) H1A---N1---H1B 109.5 C3---C8---Cl4 120.2 (3) C10---N1---H1C 109.5 O1---C9---H9A 109.5 H1A---N1---H1C 109.5 O1---C9---H9B 109.5 H1B---N1---H1C 109.5 H9A---C9---H9B 109.5 C1---O1---C9 115.3 (3) O1---C9---H9C 109.5 O2---C1---O1 126.0 (4) H9A---C9---H9C 109.5 O2---C1---C3 123.4 (4) H9B---C9---H9C 109.5 O1---C1---C3 110.7 (4) N1---C10---C11 111.2 (3) O4---C2---O3 127.1 (3) N1---C10---H10A 109.4 O4---C2---C4 118.8 (4) C11---C10---H10A 109.4 O3---C2---C4 114.1 (4) N1---C10---H10B 109.4 C8---C3---C4 119.7 (3) C11---C10---H10B 109.4 C8---C3---C1 121.1 (3) H10A---C10---H10B 108.0 C4---C3---C1 119.1 (3) C10---C11---C12 111.7 (3) C5---C4---C3 119.1 (3) C10---C11---H11A 109.3 C5---C4---C2 120.3 (3) C12---C11---H11A 109.3 C3---C4---C2 120.5 (3) C10---C11---H11B 109.3 C6---C5---C4 120.7 (3) C12---C11---H11B 109.3 C6---C5---Cl1 119.7 (3) H11A---C11---H11B 107.9 C4---C5---Cl1 119.6 (3) C11---C12---H12A 109.5 C7---C6---C5 119.8 (3) C11---C12---H12B 109.5 C7---C6---Cl2 120.0 (3) H12A---C12---H12B 109.5 C5---C6---Cl2 120.2 (3) C11---C12---H12C 109.5 C6---C7---C8 120.2 (3) H12A---C12---H12C 109.5 C6---C7---Cl3 119.8 (3) H12B---C12---H12C 109.5 C8---C7---Cl3 120.0 (3) C9---O1---C1---O2 7.9 (6) C4---C5---C6---C7 2.9 (7) C9---O1---C1---C3 −171.6 (3) Cl1---C5---C6---C7 −178.3 (4) O2---C1---C3---C8 −119.1 (4) C4---C5---C6---Cl2 −178.0 (3) O1---C1---C3---C8 60.5 (5) Cl1---C5---C6---Cl2 0.8 (6) O2---C1---C3---C4 57.3 (6) C5---C6---C7---C8 −0.4 (7) O1---C1---C3---C4 −123.1 (4) Cl2---C6---C7---C8 −179.5 (4) C8---C3---C4---C5 −1.0 (6) C5---C6---C7---Cl3 179.9 (4) C1---C3---C4---C5 −177.4 (4) Cl2---C6---C7---Cl3 0.7 (6) C8---C3---C4---C2 −178.1 (4) C6---C7---C8---C3 −2.8 (7) C1---C3---C4---C2 5.5 (6) Cl3---C7---C8---C3 176.9 (3) O4---C2---C4---C5 64.5 (5) C6---C7---C8---Cl4 175.4 (4) O3---C2---C4---C5 −117.7 (4) Cl3---C7---C8---Cl4 −4.9 (6) O4---C2---C4---C3 −118.5 (4) C4---C3---C8---C7 3.5 (6) O3---C2---C4---C3 59.3 (5) C1---C3---C8---C7 179.8 (4) C3---C4---C5---C6 −2.2 (6) C4---C3---C8---Cl4 −174.7 (3) C2---C4---C5---C6 174.9 (4) C1---C3---C8---Cl4 1.6 (5) C3---C4---C5---Cl1 179.1 (3) N1---C10---C11---C12 −178.6 (3) C2---C4---C5---Cl1 −3.8 (5) -------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2129 .table-wrap} -------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1A···O4 0.89 2.22 2.938 (4) 137 N1---H1A···O4^i^ 0.89 2.41 2.984 (4) 123 N1---H1B···O3^ii^ 0.89 1.98 2.845 (4) 164 N1---H1C···O3^iii^ 0.89 2.05 2.894 (4) 159 -------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, *y*, −*z*+1/2; (ii) −*x*+1, −*y*+1, −*z*+1; (iii) −*x*+1, *y*, −*z*+3/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------------- --------- ------- ----------- ------------- N1---H1*A*⋯O4 0.89 2.22 2.938 (4) 137 N1---H1*A*⋯O4^i^ 0.89 2.41 2.984 (4) 123 N1---H1*B*⋯O3^ii^ 0.89 1.98 2.845 (4) 164 N1---H1*C*⋯O3^iii^ 0.89 2.05 2.894 (4) 159 Symmetry codes: (i) ; (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.862848

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052160/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o630", "authors": [ { "first": "Jian", "last": "Li" } ] }

PMC3052161

Related literature {#sec1} ================== For the structure of dinuclear \[Pb(C~6~H~5~N~2~O~2~)~2~\]~2~, see: Najafi *et al.* (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Pb(C~6~H~5~N~2~O~2~)~2~(C~12~H~8~N~2~)\]*M* *~r~* = 661.63Monoclinic,*a* = 7.7033 (4) Å*b* = 15.9948 (8) Å*c* = 18.8929 (10) Åβ = 100.919 (1)°*V* = 2285.7 (2) Å^3^*Z* = 4Mo *K*α radiationμ = 7.43 mm^−1^*T* = 100 K0.20 × 0.10 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART APEX diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb4]) *T* ~min~ = 0.318, *T* ~max~ = 0.52421418 measured reflections5233 independent reflections4676 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.028 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.018*wR*(*F* ^2^) = 0.047*S* = 0.915233 reflections316 parametersH-atom parameters constrainedΔρ~max~ = 0.74 e Å^−3^Δρ~min~ = −0.53 e Å^−3^ {#d5e448} Data collection: *APEX2* (Bruker, 2009[@bb2]); cell refinement: *SAINT* (Bruker, 2009[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *X-SEED* (Barbour, 2001[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006787/bt5481sup1.cif](http://dx.doi.org/10.1107/S1600536811006787/bt5481sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006787/bt5481Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006787/bt5481Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5481&file=bt5481sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5481sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5481&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5481](http://scripts.iucr.org/cgi-bin/sendsup?bt5481)). We thank Shahid Beheshti University and the University of Malaya for supporting this study. Comment ======= The cupferronate ion is a common ion used for the complexation of metals; the lead(II) derivative exists as a dinuclear compound, the four cupferronate ions in dinuclear \[Pb(C~6~H~5~N~2~O~2~)~2~\]~2~*O*,*O*\'-chelate to the lead(II) atom, and two of the four nitroso O atoms are also involved in bridging. The geometry of both five-coordinate lead atoms is Ψ-octahedral; if another longer intermolecular Pb···O interactions (approx. 3.0 Å) are considered, the geometry is a Ψ-square-antiprism (Najafi *et al.*, 2011). The 1,10-phenanthroline adduct is monomeric (Scheme I, Fig. 1). The two cupferronate ions and the *N*-heterocycle in mononuclear Pb(C~12~H~8~N~2~)(C~6~H~5~N~2~O~2~)~2~ chelate to the lead(II) atom; the geometry of the lead atom is a Ψ-pentagonal bipyramid. Experimental {#experimental} ============ Lead(II) nitrate (0.33 g, 1 mmol) dissolved in ethanol (20 ml) was added to the cupferron ligand (0.31 g, 2 mmol) and 1,10-phenanthroline hydrate (0.40, 2 mmol) dissolved in ethanol (20 ml). The mixture was stirred and then set aside for the growth of brown colored crystals. Refinement {#refinement} ========== Hydrogen atoms were placed in calculated positions (C--H 0.95 Å) and were included in the refinement in the riding model approximation, with *U*(H) set to 1.2*U*~eq~(C). Omitted from the refinement were the following reflections owing to bad disagreement between the observed and calculated *F*^2^ values: (0 0 1), (0 1 2), (1 0 1), (0 0 2), (11 4 7), (-9 - 11 5), (11 3 8), (11 5 6), (-4 - 9 10), (-9 - 9 2) and (3 - 2 14). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of Pb(C12H8N2)(C6H5N2O2)2 at the 70% probability level. Hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0m378-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e193 .table-wrap} -------------------------------------------- --------------------------------------- \[Pb(C~6~H~5~N~2~O~2~)~2~(C~12~H~8~N~2~)\] *F*(000) = 1272 *M~r~* = 661.63 *D*~x~ = 1.923 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 9896 reflections *a* = 7.7033 (4) Å θ = 2.2--28.3° *b* = 15.9948 (8) Å µ = 7.43 mm^−1^ *c* = 18.8929 (10) Å *T* = 100 K β = 100.919 (1)° Prism, brown *V* = 2285.7 (2) Å^3^ 0.20 × 0.10 × 0.10 mm *Z* = 4 -------------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e337 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX diffractometer 5233 independent reflections Radiation source: fine-focus sealed tube 4676 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.028 ω scans θ~max~ = 27.5°, θ~min~ = 2.2° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −9→10 *T*~min~ = 0.318, *T*~max~ = 0.524 *k* = −20→18 21418 measured reflections *l* = −24→24 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e451 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.018 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.047 H-atom parameters constrained *S* = 0.91 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0315*P*)^2^ + 1.0382*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5233 reflections (Δ/σ)~max~ = 0.001 316 parameters Δρ~max~ = 0.74 e Å^−3^ 0 restraints Δρ~min~ = −0.53 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e610 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Pb1 0.545412 (12) 0.564925 (6) 0.707994 (5) 0.01407 (4) O1 0.6518 (3) 0.57008 (11) 0.83910 (10) 0.0215 (4) O2 0.6004 (3) 0.43217 (11) 0.77043 (10) 0.0221 (4) O3 0.3666 (2) 0.67625 (11) 0.74664 (10) 0.0171 (4) O4 0.2682 (2) 0.52341 (11) 0.72411 (10) 0.0168 (4) N1 0.6651 (3) 0.49786 (14) 0.87218 (11) 0.0167 (4) N2 0.6420 (3) 0.42654 (14) 0.84043 (12) 0.0207 (5) N3 0.2048 (3) 0.65180 (13) 0.74731 (10) 0.0123 (4) N4 0.1479 (3) 0.57674 (12) 0.73517 (11) 0.0139 (4) N5 0.4379 (3) 0.44824 (13) 0.60458 (12) 0.0156 (4) N6 0.3223 (3) 0.61102 (14) 0.58176 (11) 0.0160 (4) C1 0.7119 (4) 0.49851 (17) 0.94969 (14) 0.0189 (5) C2 0.6692 (4) 0.43069 (17) 0.98924 (15) 0.0228 (6) H2 0.6111 0.3831 0.9657 0.027\* C3 0.7135 (5) 0.43430 (18) 1.06373 (16) 0.0298 (7) H3 0.6877 0.3882 1.0917 0.036\* C4 0.7955 (5) 0.5050 (2) 1.09786 (15) 0.0355 (8) H4 0.8229 0.5075 1.1490 0.043\* C5 0.8371 (5) 0.57181 (19) 1.05735 (16) 0.0345 (8) H5 0.8947 0.6196 1.0808 0.041\* C6 0.7950 (4) 0.56902 (18) 0.98277 (15) 0.0254 (6) H6 0.8225 0.6147 0.9548 0.031\* C7 0.0758 (3) 0.71352 (15) 0.75744 (13) 0.0132 (5) C8 −0.0737 (3) 0.68857 (16) 0.78329 (13) 0.0159 (5) H8 −0.0865 0.6325 0.7980 0.019\* C9 −0.2042 (4) 0.74779 (17) 0.78711 (14) 0.0193 (5) H9 −0.3089 0.7319 0.8034 0.023\* C10 −0.1817 (4) 0.83009 (17) 0.76720 (14) 0.0211 (6) H10 −0.2722 0.8701 0.7686 0.025\* C11 −0.0270 (4) 0.85391 (16) 0.74523 (14) 0.0187 (5) H11 −0.0099 0.9108 0.7338 0.022\* C12 0.1030 (3) 0.79543 (15) 0.73976 (13) 0.0156 (5) H12 0.2084 0.8115 0.7242 0.019\* C13 0.4890 (4) 0.36929 (17) 0.61474 (14) 0.0195 (6) H13 0.5640 0.3550 0.6590 0.023\* C14 0.4390 (4) 0.30593 (17) 0.56419 (14) 0.0213 (6) H14 0.4786 0.2502 0.5743 0.026\* C15 0.3320 (4) 0.32538 (17) 0.49995 (14) 0.0202 (6) H15 0.2974 0.2832 0.4647 0.024\* C16 0.2737 (3) 0.40803 (17) 0.48634 (14) 0.0174 (5) C17 0.3300 (3) 0.46863 (17) 0.54094 (13) 0.0153 (5) C18 0.1582 (4) 0.43202 (17) 0.42116 (14) 0.0204 (6) H18 0.1205 0.3912 0.3850 0.024\* C19 0.1015 (4) 0.51195 (18) 0.41007 (14) 0.0198 (6) H19 0.0243 0.5263 0.3664 0.024\* C20 0.1563 (4) 0.57524 (16) 0.46329 (14) 0.0177 (5) C21 0.2698 (3) 0.55380 (16) 0.52921 (13) 0.0156 (5) C22 0.0991 (4) 0.65833 (18) 0.45407 (14) 0.0210 (6) H22 0.0237 0.6750 0.4106 0.025\* C23 0.1520 (4) 0.71536 (18) 0.50770 (14) 0.0217 (6) H23 0.1136 0.7718 0.5021 0.026\* C24 0.2643 (3) 0.68889 (17) 0.57130 (14) 0.0194 (5) H24 0.3002 0.7287 0.6085 0.023\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1302 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Pb1 0.01178 (6) 0.01599 (6) 0.01461 (5) −0.00027 (4) 0.00298 (4) −0.00125 (3) O1 0.0316 (12) 0.0155 (10) 0.0164 (9) −0.0056 (8) 0.0021 (8) 0.0018 (7) O2 0.0287 (12) 0.0188 (10) 0.0172 (9) 0.0091 (8) 0.0003 (8) −0.0034 (7) O3 0.0097 (8) 0.0152 (9) 0.0267 (9) −0.0040 (7) 0.0043 (7) −0.0032 (7) O4 0.0155 (9) 0.0112 (9) 0.0250 (9) 0.0015 (7) 0.0073 (7) −0.0010 (7) N1 0.0163 (11) 0.0166 (11) 0.0173 (10) 0.0003 (9) 0.0031 (8) 0.0008 (9) N2 0.0243 (13) 0.0184 (12) 0.0181 (11) 0.0058 (9) 0.0008 (9) −0.0022 (9) N3 0.0109 (10) 0.0117 (10) 0.0137 (9) 0.0006 (8) 0.0006 (8) 0.0003 (8) N4 0.0140 (11) 0.0102 (10) 0.0175 (10) −0.0011 (8) 0.0033 (8) 0.0001 (8) N5 0.0143 (11) 0.0172 (11) 0.0162 (10) 0.0009 (9) 0.0049 (9) 0.0002 (8) N6 0.0139 (11) 0.0187 (11) 0.0160 (10) 0.0012 (9) 0.0047 (8) 0.0001 (9) C1 0.0192 (14) 0.0211 (14) 0.0157 (12) 0.0002 (11) 0.0015 (10) 0.0006 (10) C2 0.0258 (16) 0.0186 (14) 0.0225 (14) −0.0020 (11) 0.0004 (11) 0.0013 (11) C3 0.043 (2) 0.0256 (16) 0.0197 (14) −0.0043 (14) 0.0019 (13) 0.0061 (11) C4 0.058 (2) 0.0329 (18) 0.0131 (13) −0.0125 (16) −0.0011 (13) 0.0020 (12) C5 0.053 (2) 0.0283 (17) 0.0179 (14) −0.0126 (15) −0.0028 (14) −0.0020 (12) C6 0.0319 (17) 0.0239 (16) 0.0197 (13) −0.0081 (12) 0.0031 (12) 0.0041 (11) C7 0.0126 (12) 0.0131 (12) 0.0128 (11) 0.0004 (9) −0.0002 (9) −0.0021 (9) C8 0.0152 (13) 0.0117 (12) 0.0204 (12) −0.0026 (10) 0.0025 (10) −0.0019 (10) C9 0.0158 (13) 0.0186 (14) 0.0237 (13) −0.0008 (11) 0.0041 (11) −0.0066 (10) C10 0.0202 (14) 0.0175 (13) 0.0249 (13) 0.0068 (11) 0.0023 (11) −0.0047 (11) C11 0.0245 (15) 0.0108 (12) 0.0193 (12) 0.0002 (11) 0.0007 (11) −0.0009 (10) C12 0.0167 (13) 0.0130 (12) 0.0163 (11) −0.0010 (10) 0.0010 (10) −0.0005 (10) C13 0.0178 (14) 0.0215 (14) 0.0202 (13) 0.0035 (11) 0.0059 (11) −0.0002 (11) C14 0.0225 (14) 0.0148 (13) 0.0288 (14) 0.0008 (11) 0.0100 (11) −0.0006 (11) C15 0.0197 (14) 0.0196 (14) 0.0230 (13) −0.0040 (11) 0.0082 (11) −0.0043 (11) C16 0.0140 (13) 0.0218 (13) 0.0186 (12) −0.0045 (11) 0.0085 (10) −0.0022 (10) C17 0.0101 (12) 0.0196 (13) 0.0175 (12) −0.0046 (10) 0.0059 (10) −0.0019 (10) C18 0.0192 (14) 0.0249 (15) 0.0180 (12) −0.0082 (11) 0.0060 (11) −0.0036 (11) C19 0.0163 (13) 0.0294 (15) 0.0135 (12) −0.0051 (11) 0.0020 (10) 0.0003 (10) C20 0.0145 (13) 0.0254 (15) 0.0146 (12) −0.0024 (11) 0.0062 (10) 0.0024 (10) C21 0.0127 (13) 0.0206 (14) 0.0152 (12) −0.0025 (10) 0.0068 (10) −0.0008 (10) C22 0.0143 (13) 0.0293 (15) 0.0188 (12) 0.0008 (11) 0.0018 (10) 0.0078 (11) C23 0.0207 (14) 0.0219 (15) 0.0238 (13) 0.0004 (11) 0.0073 (11) 0.0044 (11) C24 0.0198 (13) 0.0187 (13) 0.0212 (12) 0.0003 (11) 0.0080 (10) −0.0002 (10) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1958 .table-wrap} --------------------- -------------- ----------------------- -------------- Pb1---O4 2.3106 (18) C7---C8 1.392 (3) Pb1---O2 2.4270 (18) C8---C9 1.393 (4) Pb1---O3 2.4457 (17) C8---H8 0.9500 Pb1---O1 2.4586 (19) C9---C10 1.389 (4) Pb1---N5 2.715 (2) C9---H9 0.9500 Pb1---N6 2.763 (2) C10---C11 1.387 (4) O1---N1 1.308 (3) C10---H10 0.9500 O2---N2 1.304 (3) C11---C12 1.389 (4) O3---N3 1.309 (3) C11---H11 0.9500 O4---N4 1.305 (3) C12---H12 0.9500 N1---N2 1.285 (3) C13---C14 1.396 (4) N1---C1 1.440 (3) C13---H13 0.9500 N3---N4 1.284 (3) C14---C15 1.367 (4) N3---C7 1.439 (3) C14---H14 0.9500 N5---C13 1.326 (3) C15---C16 1.404 (4) N5---C17 1.365 (3) C15---H15 0.9500 N6---C24 1.325 (3) C16---C17 1.422 (4) N6---C21 1.354 (3) C16---C18 1.428 (4) C1---C6 1.386 (4) C17---C21 1.443 (4) C1---C2 1.392 (4) C18---C19 1.354 (4) C2---C3 1.385 (4) C18---H18 0.9500 C2---H2 0.9500 C19---C20 1.433 (4) C3---C4 1.392 (4) C19---H19 0.9500 C3---H3 0.9500 C20---C22 1.401 (4) C4---C5 1.387 (4) C20---C21 1.421 (4) C4---H4 0.9500 C22---C23 1.367 (4) C5---C6 1.385 (4) C22---H22 0.9500 C5---H5 0.9500 C23---C24 1.406 (4) C6---H6 0.9500 C23---H23 0.9500 C7---C12 1.378 (3) C24---H24 0.9500 O4---Pb1---O2 76.42 (7) C8---C7---N3 119.2 (2) O4---Pb1---O3 65.37 (6) C7---C8---C9 118.5 (2) O2---Pb1---O3 123.25 (6) C7---C8---H8 120.8 O4---Pb1---O1 90.97 (7) C9---C8---H8 120.8 O2---Pb1---O1 62.97 (6) C10---C9---C8 120.1 (2) O3---Pb1---O1 76.93 (6) C10---C9---H9 119.9 O4---Pb1---N5 74.56 (6) C8---C9---H9 119.9 O2---Pb1---N5 75.51 (6) C11---C10---C9 120.0 (2) O3---Pb1---N5 127.08 (6) C11---C10---H10 120.0 O1---Pb1---N5 138.25 (6) C9---C10---H10 120.0 O4---Pb1---N6 75.59 (6) C10---C11---C12 120.7 (2) O2---Pb1---N6 132.52 (7) C10---C11---H11 119.7 O3---Pb1---N6 76.70 (6) C12---C11---H11 119.7 O1---Pb1---N6 153.50 (7) C7---C12---C11 118.5 (2) N5---Pb1---N6 60.47 (6) C7---C12---H12 120.8 N1---O1---Pb1 115.64 (14) C11---C12---H12 120.8 N2---O2---Pb1 122.70 (14) N5---C13---C14 123.8 (3) N3---O3---Pb1 112.12 (13) N5---C13---H13 118.1 N4---O4---Pb1 122.37 (14) C14---C13---H13 118.1 N2---N1---O1 124.7 (2) C15---C14---C13 118.9 (3) N2---N1---C1 117.8 (2) C15---C14---H14 120.5 O1---N1---C1 117.5 (2) C13---C14---H14 120.5 N1---N2---O2 113.4 (2) C14---C15---C16 119.7 (2) N4---N3---O3 124.9 (2) C14---C15---H15 120.2 N4---N3---C7 116.4 (2) C16---C15---H15 120.2 O3---N3---C7 118.64 (19) C15---C16---C17 117.8 (2) N3---N4---O4 114.2 (2) C15---C16---C18 122.4 (2) C13---N5---C17 118.0 (2) C17---C16---C18 119.8 (3) C13---N5---Pb1 120.57 (17) N5---C17---C16 121.8 (2) C17---N5---Pb1 121.42 (16) N5---C17---C21 119.0 (2) C24---N6---C21 118.7 (2) C16---C17---C21 119.2 (2) C24---N6---Pb1 121.10 (17) C19---C18---C16 121.1 (2) C21---N6---Pb1 120.19 (16) C19---C18---H18 119.4 C6---C1---C2 121.9 (2) C16---C18---H18 119.4 C6---C1---N1 118.0 (2) C18---C19---C20 121.0 (2) C2---C1---N1 120.1 (2) C18---C19---H19 119.5 C3---C2---C1 118.4 (3) C20---C19---H19 119.5 C3---C2---H2 120.8 C22---C20---C21 117.7 (2) C1---C2---H2 120.8 C22---C20---C19 122.6 (2) C2---C3---C4 120.5 (3) C21---C20---C19 119.7 (2) C2---C3---H3 119.8 N6---C21---C20 121.9 (2) C4---C3---H3 119.8 N6---C21---C17 118.9 (2) C5---C4---C3 120.2 (3) C20---C21---C17 119.3 (2) C5---C4---H4 119.9 C23---C22---C20 119.9 (3) C3---C4---H4 119.9 C23---C22---H22 120.0 C6---C5---C4 120.1 (3) C20---C22---H22 120.0 C6---C5---H5 119.9 C22---C23---C24 118.8 (3) C4---C5---H5 119.9 C22---C23---H23 120.6 C1---C6---C5 119.0 (3) C24---C23---H23 120.6 C1---C6---H6 120.5 N6---C24---C23 123.1 (3) C5---C6---H6 120.5 N6---C24---H24 118.5 C12---C7---C8 122.1 (2) C23---C24---H24 118.5 C12---C7---N3 118.6 (2) O4---Pb1---O1---N1 68.29 (18) C1---C2---C3---C4 1.3 (5) O2---Pb1---O1---N1 −5.91 (16) C2---C3---C4---C5 −1.4 (6) O3---Pb1---O1---N1 132.71 (18) C3---C4---C5---C6 1.0 (6) N5---Pb1---O1---N1 0.7 (2) C2---C1---C6---C5 0.3 (5) N6---Pb1---O1---N1 126.70 (18) N1---C1---C6---C5 178.4 (3) O4---Pb1---O2---N2 −92.0 (2) C4---C5---C6---C1 −0.4 (5) O3---Pb1---O2---N2 −44.2 (2) N4---N3---C7---C12 −152.2 (2) O1---Pb1---O2---N2 6.17 (19) O3---N3---C7---C12 23.7 (3) N5---Pb1---O2---N2 −169.3 (2) N4---N3---C7---C8 26.5 (3) N6---Pb1---O2---N2 −147.37 (18) O3---N3---C7---C8 −157.6 (2) O4---Pb1---O3---N3 −7.02 (13) C12---C7---C8---C9 3.9 (4) O2---Pb1---O3---N3 −59.47 (16) N3---C7---C8---C9 −174.7 (2) O1---Pb1---O3---N3 −104.23 (15) C7---C8---C9---C10 −1.7 (4) N5---Pb1---O3---N3 37.44 (17) C8---C9---C10---C11 −1.7 (4) N6---Pb1---O3---N3 73.02 (14) C9---C10---C11---C12 2.9 (4) O2---Pb1---O4---N4 146.36 (18) C8---C7---C12---C11 −2.7 (4) O3---Pb1---O4---N4 9.37 (16) N3---C7---C12---C11 176.0 (2) O1---Pb1---O4---N4 84.50 (17) C10---C11---C12---C7 −0.8 (4) N5---Pb1---O4---N4 −135.20 (18) C17---N5---C13---C14 0.0 (4) N6---Pb1---O4---N4 −72.39 (17) Pb1---N5---C13---C14 179.90 (19) Pb1---O1---N1---N2 6.5 (3) N5---C13---C14---C15 0.5 (4) Pb1---O1---N1---C1 −174.66 (17) C13---C14---C15---C16 −0.5 (4) O1---N1---N2---O2 −1.0 (4) C14---C15---C16---C17 0.2 (4) C1---N1---N2---O2 −179.9 (2) C14---C15---C16---C18 −178.3 (2) Pb1---O2---N2---N1 −5.4 (3) C13---N5---C17---C16 −0.4 (4) Pb1---O3---N3---N4 5.5 (3) Pb1---N5---C17---C16 179.72 (17) Pb1---O3---N3---C7 −170.04 (15) C13---N5---C17---C21 178.8 (2) O3---N3---N4---O4 2.4 (3) Pb1---N5---C17---C21 −1.1 (3) C7---N3---N4---O4 177.98 (19) C15---C16---C17---N5 0.3 (4) Pb1---O4---N4---N3 −10.2 (3) C18---C16---C17---N5 178.9 (2) O4---Pb1---N5---C13 −96.9 (2) C15---C16---C17---C21 −178.9 (2) O2---Pb1---N5---C13 −17.25 (19) C18---C16---C17---C21 −0.3 (4) O3---Pb1---N5---C13 −138.21 (18) C15---C16---C18---C19 178.8 (3) O1---Pb1---N5---C13 −23.3 (2) C17---C16---C18---C19 0.3 (4) N6---Pb1---N5---C13 −178.8 (2) C16---C18---C19---C20 0.3 (4) O4---Pb1---N5---C17 83.03 (18) C18---C19---C20---C22 −179.3 (3) O2---Pb1---N5---C17 162.6 (2) C18---C19---C20---C21 −0.9 (4) O3---Pb1---N5---C17 41.7 (2) C24---N6---C21---C20 0.6 (4) O1---Pb1---N5---C17 156.59 (17) Pb1---N6---C21---C20 −179.48 (18) N6---Pb1---N5---C17 1.10 (17) C24---N6---C21---C17 −178.8 (2) O4---Pb1---N6---C24 98.62 (19) Pb1---N6---C21---C17 1.0 (3) O2---Pb1---N6---C24 154.25 (17) C22---C20---C21---N6 −0.1 (4) O3---Pb1---N6---C24 31.04 (18) C19---C20---C21---N6 −178.6 (2) O1---Pb1---N6---C24 37.1 (3) C22---C20---C21---C17 179.4 (2) N5---Pb1---N6---C24 178.8 (2) C19---C20---C21---C17 0.9 (4) O4---Pb1---N6---C21 −81.27 (18) N5---C17---C21---N6 0.0 (3) O2---Pb1---N6---C21 −25.6 (2) C16---C17---C21---N6 179.2 (2) O3---Pb1---N6---C21 −148.84 (19) N5---C17---C21---C20 −179.5 (2) O1---Pb1---N6---C21 −142.83 (17) C16---C17---C21---C20 −0.3 (4) N5---Pb1---N6---C21 −1.08 (17) C21---C20---C22---C23 −0.4 (4) N2---N1---C1---C6 158.2 (3) C19---C20---C22---C23 178.1 (2) O1---N1---C1---C6 −20.8 (4) C20---C22---C23---C24 0.3 (4) N2---N1---C1---C2 −23.7 (4) C21---N6---C24---C23 −0.7 (4) O1---N1---C1---C2 157.4 (3) Pb1---N6---C24---C23 179.37 (18) C6---C1---C2---C3 −0.7 (5) C22---C23---C24---N6 0.3 (4) N1---C1---C2---C3 −178.8 (3) --------------------- -------------- ----------------------- -------------- :::

PubMed Central

2024-06-05T04:04:18.867365

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052161/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):m378", "authors": [ { "first": "Ezzatollah", "last": "Najafi" }, { "first": "Mostafa M.", "last": "Amini" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052162

Related literature {#sec1} ================== For background to the synthesis: see: Yadigarov *et al.* (2010[@bb7]). For the structure of tolperisone hydrochloride, see: Tanaka & Hirayama (2007[@bb5]). For a related structure, see: Maharramov *et al.* (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~17~H~27~NO*M* *~r~* = 261.40Monoclinic,*a* = 11.7992 (12) Å*b* = 8.0940 (8) Å*c* = 17.0196 (17) Åβ = 107.489 (1)°*V* = 1550.3 (3) Å^3^*Z* = 4Mo *K*α radiationμ = 0.07 mm^−1^*T* = 100 K0.30 × 0.20 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometer6615 measured reflections3537 independent reflections2964 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.016 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.040*wR*(*F* ^2^) = 0.110*S* = 1.023537 reflections179 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.36 e Å^−3^Δρ~min~ = −0.19 e Å^−3^ {#d5e377} Data collection: *APEX2* (Bruker, 2005[@bb2]); cell refinement: *SAINT* (Bruker, 2005[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *X-SEED* (Barbour, 2001[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006568/bt5478sup1.cif](http://dx.doi.org/10.1107/S1600536811006568/bt5478sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006568/bt5478Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006568/bt5478Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5478&file=bt5478sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5478sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5478&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5478](http://scripts.iucr.org/cgi-bin/sendsup?bt5478)). We thank Baku State University and the University of Malaya for supporting this study. Comment ======= A recent study reported the reaction of 1-chloro-3-(2,4,6-trimethylphenyl)propan-2-one and primary amines. The chlorine atom in the α-chloro ketone is not replaced directly by the amino RNH-- group; the intermediate product undergoes a Favorskii rearrangement that furnishes a compound having two methylene groups between the aromatic system and the amido unit (Yadigarov *et al.*, 2010). A recent study used thiourea as the amino reactant (Maharramov *et al.*, 2011). The present study employs a cyclic secondary amine as the amino reactant in the synthesis of a compound having a formulation similar to that of tolperisone (a piperidine derivative that is commercially used as a muscle relaxant), which has been characterized as a hydrochloride (Tanaka & Hirayama, 2007). The title compound, C~17~H~27~NO, (Scheme I) is a bufferfly-shaped substituted 2-propanol having an aromatic ring on one carbon end and a piperidinyl ring on the other. The hydroxy group interacts with the N atom of an inversion-related molecule to generate a hydrogen-bonded dimer (Fig. 1). Experimental {#experimental} ============ 1-Chloro-3-(2,4,6-trimethylphenyl)propan-2-one (1 mol) and piperidine (1 mmol) were stirred in water for 18 h at 53 K. The water was decanted and the oil was distilled in vacuum. The distallate was a liquid; the liquid crystallized after 6 months; yield 70%. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C--H 0.95 to 0.99 Å; *U*(H) 1.2 to 1.5*U*(C)\] and were included in the refinement in the riding model approximation, with *U*(H) set to 1.2 to 1.5*U*(C). The hydroxy H-atom was located in a difference Fourier map, and was refined with a distance restraint of O--H 0.84±0.01 Å. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Anisotropic displacement ellipsoid plot (Barbour, 2001) of the hydrogen-bonded dimeric structure of C17H27NO at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o739-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e123 .table-wrap} ------------------------- --------------------------------------- C~17~H~27~NO *F*(000) = 576 *M~r~* = 261.40 *D*~x~ = 1.120 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 1896 reflections *a* = 11.7992 (12) Å θ = 2.8--29.2° *b* = 8.0940 (8) Å µ = 0.07 mm^−1^ *c* = 17.0196 (17) Å *T* = 100 K β = 107.489 (1)° Prism, colorless *V* = 1550.3 (3) Å^3^ 0.30 × 0.20 × 0.20 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e248 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII diffractometer 2964 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.016 graphite θ~max~ = 27.5°, θ~min~ = 2.5° φ and ω scans *h* = −13→15 6615 measured reflections *k* = −8→10 3537 independent reflections *l* = −15→22 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e346 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.040 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.110 H atoms treated by a mixture of independent and constrained refinement *S* = 1.02 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0565*P*)^2^ + 0.4799*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3537 reflections (Δ/σ)~max~ = 0.001 179 parameters Δρ~max~ = 0.36 e Å^−3^ 1 restraint Δρ~min~ = −0.19 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e505 .table-wrap} ------ --------------- -------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O1 0.42350 (7) 0.36548 (10) 0.53159 (5) 0.0213 (2) H1 0.4165 (15) 0.373 (2) 0.4804 (6) 0.042 (5)\* N1 0.54620 (8) 0.67399 (12) 0.62908 (6) 0.0164 (2) C1 0.64459 (10) 0.66941 (15) 0.70653 (7) 0.0196 (2) H1A 0.6716 0.5539 0.7190 0.023\* H1B 0.6161 0.7100 0.7522 0.023\* C2 0.74826 (10) 0.77528 (15) 0.70081 (7) 0.0219 (3) H2A 0.7807 0.7296 0.6580 0.026\* H2B 0.8121 0.7723 0.7541 0.026\* C3 0.70960 (11) 0.95379 (15) 0.67944 (7) 0.0229 (3) H3A 0.7759 1.0172 0.6697 0.027\* H3B 0.6890 1.0054 0.7261 0.027\* C4 0.60210 (11) 0.95923 (15) 0.60243 (7) 0.0225 (3) H4A 0.5717 1.0738 0.5930 0.027\* H4B 0.6263 0.9249 0.5540 0.027\* C5 0.50422 (10) 0.84561 (14) 0.61153 (7) 0.0196 (2) H5A 0.4751 0.8863 0.6568 0.024\* H5B 0.4369 0.8481 0.5601 0.024\* C6 0.44843 (10) 0.56903 (15) 0.63656 (7) 0.0194 (2) H6A 0.4001 0.6329 0.6644 0.023\* H6B 0.4825 0.4734 0.6721 0.023\* C7 0.36711 (10) 0.50483 (14) 0.55465 (7) 0.0173 (2) H7 0.3549 0.5928 0.5116 0.021\* C8 0.24722 (10) 0.45733 (15) 0.56663 (7) 0.0186 (2) H8A 0.2625 0.3806 0.6140 0.022\* H8B 0.2107 0.5583 0.5813 0.022\* C9 0.15852 (10) 0.37740 (14) 0.49344 (7) 0.0162 (2) C10 0.08491 (10) 0.47543 (14) 0.43015 (7) 0.0170 (2) C11 −0.00046 (10) 0.40041 (14) 0.36511 (7) 0.0177 (2) H11 −0.0496 0.4676 0.3226 0.021\* C12 −0.01591 (10) 0.22964 (14) 0.36054 (7) 0.0175 (2) C13 0.05775 (10) 0.13441 (14) 0.42312 (7) 0.0178 (2) H13 0.0488 0.0177 0.4209 0.021\* C14 0.14458 (10) 0.20477 (14) 0.48924 (7) 0.0172 (2) C15 0.21904 (11) 0.09380 (15) 0.55627 (7) 0.0229 (3) H15A 0.2038 −0.0219 0.5394 0.034\* H15B 0.1984 0.1125 0.6072 0.034\* H15C 0.3034 0.1187 0.5657 0.034\* C16 −0.11163 (11) 0.15251 (15) 0.29073 (7) 0.0245 (3) H16A −0.0934 0.0354 0.2861 0.037\* H16B −0.1153 0.2092 0.2391 0.037\* H16C −0.1884 0.1627 0.3015 0.037\* C17 0.09396 (11) 0.66162 (14) 0.43230 (8) 0.0213 (3) H17A 0.0326 0.7081 0.3851 0.032\* H17B 0.1726 0.6948 0.4297 0.032\* H17C 0.0825 0.7028 0.4835 0.032\* ------ --------------- -------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1113 .table-wrap} ----- ------------ ------------ ------------ ------------- ------------ ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O1 0.0219 (4) 0.0226 (4) 0.0206 (4) 0.0023 (3) 0.0080 (4) −0.0009 (3) N1 0.0141 (4) 0.0170 (5) 0.0163 (5) −0.0008 (4) 0.0017 (4) 0.0007 (4) C1 0.0176 (5) 0.0214 (6) 0.0169 (5) −0.0004 (4) 0.0010 (4) 0.0011 (4) C2 0.0172 (6) 0.0247 (6) 0.0214 (6) −0.0025 (5) 0.0022 (4) −0.0019 (5) C3 0.0249 (6) 0.0212 (6) 0.0227 (6) −0.0065 (5) 0.0074 (5) −0.0038 (5) C4 0.0275 (6) 0.0180 (5) 0.0216 (6) −0.0005 (5) 0.0066 (5) 0.0007 (5) C5 0.0189 (6) 0.0187 (5) 0.0194 (6) 0.0029 (4) 0.0028 (4) 0.0000 (4) C6 0.0185 (6) 0.0233 (6) 0.0164 (5) −0.0042 (4) 0.0050 (4) −0.0009 (4) C7 0.0161 (5) 0.0185 (5) 0.0169 (5) −0.0018 (4) 0.0045 (4) −0.0011 (4) C8 0.0175 (5) 0.0210 (5) 0.0179 (5) −0.0027 (4) 0.0064 (4) −0.0035 (4) C9 0.0142 (5) 0.0177 (5) 0.0180 (5) −0.0015 (4) 0.0067 (4) −0.0027 (4) C10 0.0167 (5) 0.0156 (5) 0.0205 (6) −0.0002 (4) 0.0083 (4) −0.0012 (4) C11 0.0157 (5) 0.0185 (5) 0.0186 (5) 0.0011 (4) 0.0048 (4) 0.0012 (4) C12 0.0158 (5) 0.0193 (5) 0.0181 (5) −0.0018 (4) 0.0059 (4) −0.0024 (4) C13 0.0192 (6) 0.0140 (5) 0.0214 (6) −0.0017 (4) 0.0079 (5) −0.0014 (4) C14 0.0164 (5) 0.0174 (5) 0.0187 (5) 0.0009 (4) 0.0068 (4) 0.0015 (4) C15 0.0227 (6) 0.0204 (6) 0.0236 (6) 0.0005 (5) 0.0040 (5) 0.0033 (5) C16 0.0256 (6) 0.0236 (6) 0.0209 (6) −0.0052 (5) 0.0017 (5) −0.0025 (5) C17 0.0226 (6) 0.0152 (5) 0.0261 (6) −0.0010 (4) 0.0072 (5) −0.0009 (4) ----- ------------ ------------ ------------ ------------- ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1495 .table-wrap} -------------------- -------------- ----------------------- -------------- O1---C7 1.4233 (14) C8---C9 1.5106 (15) O1---H1 0.852 (9) C8---H8A 0.9900 N1---C6 1.4687 (14) C8---H8B 0.9900 N1---C1 1.4720 (14) C9---C14 1.4062 (15) N1---C5 1.4749 (14) C9---C10 1.4079 (16) C1---C2 1.5205 (16) C10---C11 1.3923 (15) C1---H1A 0.9900 C10---C17 1.5104 (15) C1---H1B 0.9900 C11---C12 1.3933 (16) C2---C3 1.5258 (17) C11---H11 0.9500 C2---H2A 0.9900 C12---C13 1.3883 (16) C2---H2B 0.9900 C12---C16 1.5068 (15) C3---C4 1.5262 (17) C13---C14 1.3955 (16) C3---H3A 0.9900 C13---H13 0.9500 C3---H3B 0.9900 C14---C15 1.5092 (16) C4---C5 1.5203 (17) C15---H15A 0.9800 C4---H4A 0.9900 C15---H15B 0.9800 C4---H4B 0.9900 C15---H15C 0.9800 C5---H5A 0.9900 C16---H16A 0.9800 C5---H5B 0.9900 C16---H16B 0.9800 C6---C7 1.5265 (15) C16---H16C 0.9800 C6---H6A 0.9900 C17---H17A 0.9800 C6---H6B 0.9900 C17---H17B 0.9800 C7---C8 1.5375 (15) C17---H17C 0.9800 C7---H7 1.0000 C7---O1---H1 108.5 (12) C6---C7---H7 109.8 C6---N1---C1 109.65 (9) C8---C7---H7 109.8 C6---N1---C5 109.73 (9) C9---C8---C7 115.77 (9) C1---N1---C5 109.36 (9) C9---C8---H8A 108.3 N1---C1---C2 111.20 (9) C7---C8---H8A 108.3 N1---C1---H1A 109.4 C9---C8---H8B 108.3 C2---C1---H1A 109.4 C7---C8---H8B 108.3 N1---C1---H1B 109.4 H8A---C8---H8B 107.4 C2---C1---H1B 109.4 C14---C9---C10 119.03 (10) H1A---C1---H1B 108.0 C14---C9---C8 120.59 (10) C1---C2---C3 111.12 (10) C10---C9---C8 120.32 (10) C1---C2---H2A 109.4 C11---C10---C9 119.67 (10) C3---C2---H2A 109.4 C11---C10---C17 118.91 (10) C1---C2---H2B 109.4 C9---C10---C17 121.40 (10) C3---C2---H2B 109.4 C10---C11---C12 121.89 (11) H2A---C2---H2B 108.0 C10---C11---H11 119.1 C2---C3---C4 110.11 (10) C12---C11---H11 119.1 C2---C3---H3A 109.6 C13---C12---C11 117.82 (10) C4---C3---H3A 109.6 C13---C12---C16 121.53 (10) C2---C3---H3B 109.6 C11---C12---C16 120.64 (10) C4---C3---H3B 109.6 C12---C13---C14 122.05 (10) H3A---C3---H3B 108.2 C12---C13---H13 119.0 C5---C4---C3 110.84 (10) C14---C13---H13 119.0 C5---C4---H4A 109.5 C13---C14---C9 119.52 (10) C3---C4---H4A 109.5 C13---C14---C15 119.10 (10) C5---C4---H4B 109.5 C9---C14---C15 121.35 (10) C3---C4---H4B 109.5 C14---C15---H15A 109.5 H4A---C4---H4B 108.1 C14---C15---H15B 109.5 N1---C5---C4 111.78 (9) H15A---C15---H15B 109.5 N1---C5---H5A 109.3 C14---C15---H15C 109.5 C4---C5---H5A 109.3 H15A---C15---H15C 109.5 N1---C5---H5B 109.3 H15B---C15---H15C 109.5 C4---C5---H5B 109.3 C12---C16---H16A 109.5 H5A---C5---H5B 107.9 C12---C16---H16B 109.5 N1---C6---C7 114.35 (9) H16A---C16---H16B 109.5 N1---C6---H6A 108.7 C12---C16---H16C 109.5 C7---C6---H6A 108.7 H16A---C16---H16C 109.5 N1---C6---H6B 108.7 H16B---C16---H16C 109.5 C7---C6---H6B 108.7 C10---C17---H17A 109.5 H6A---C6---H6B 107.6 C10---C17---H17B 109.5 O1---C7---C6 107.70 (9) H17A---C17---H17B 109.5 O1---C7---C8 111.31 (9) C10---C17---H17C 109.5 C6---C7---C8 108.36 (9) H17A---C17---H17C 109.5 O1---C7---H7 109.8 H17B---C17---H17C 109.5 C6---N1---C1---C2 179.35 (9) C14---C9---C10---C11 0.41 (16) C5---N1---C1---C2 −60.29 (12) C8---C9---C10---C11 −176.83 (10) N1---C1---C2---C3 57.57 (13) C14---C9---C10---C17 178.63 (10) C1---C2---C3---C4 −52.80 (13) C8---C9---C10---C17 1.39 (16) C2---C3---C4---C5 52.23 (13) C9---C10---C11---C12 0.14 (17) C6---N1---C5---C4 −179.48 (9) C17---C10---C11---C12 −178.12 (11) C1---N1---C5---C4 60.20 (12) C10---C11---C12---C13 −0.52 (17) C3---C4---C5---N1 −56.81 (13) C10---C11---C12---C16 178.08 (10) C1---N1---C6---C7 −155.49 (10) C11---C12---C13---C14 0.34 (16) C5---N1---C6---C7 84.37 (12) C16---C12---C13---C14 −178.24 (11) N1---C6---C7---O1 81.03 (12) C12---C13---C14---C9 0.20 (17) N1---C6---C7---C8 −158.46 (9) C12---C13---C14---C15 178.26 (10) O1---C7---C8---C9 −56.80 (13) C10---C9---C14---C13 −0.57 (16) C6---C7---C8---C9 −175.04 (10) C8---C9---C14---C13 176.66 (10) C7---C8---C9---C14 98.81 (13) C10---C9---C14---C15 −178.59 (10) C7---C8---C9---C10 −84.00 (13) C8---C9---C14---C15 −1.36 (16) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2315 .table-wrap} ----------------- ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1···N1^i^ 0.85 (1) 2.07 (1) 2.880 (1) 158.(2) ----------------- ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------- ---------- ---------- ----------- ------------- O1---H1⋯N1^i^ 0.85 (1) 2.07 (1) 2.880 (1) 158 (2) Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.874164

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052162/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o739", "authors": [ { "first": "Abel M.", "last": "Maharramov" }, { "first": "Ali N.", "last": "Khalilov" }, { "first": "Atash V.", "last": "Gurbanov" }, { "first": "Mirze A.", "last": "Allahverdiyev" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052163

Related literature {#sec1} ================== For related structures, see: Bikas *et al.* (2010[@bb1]); Silva *et al.* (2006[@bb5]); Zimmer *et al.* (1959[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~16~N~2~O~3~S*M* *~r~* = 340.40Monoclinic,*a* = 15.740 (3) Å*b* = 10.573 (2) Å*c* = 10.322 (2) Åβ = 103.86 (3)°*V* = 1667.8 (6) Å^3^*Z* = 4Mo *K*α radiationμ = 0.21 mm^−1^*T* = 298 K0.35 × 0.25 × 0.2 mm ### Data collection {#sec2.1.2} Stoe IPDS 2T diffractometerAbsorption correction: numerical (*X-SHAPE*; Stoe & Cie, 2005[@bb6]) *T* ~min~ = 0.935, *T* ~max~ = 0.95713245 measured reflections4474 independent reflections2439 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.080 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.053*wR*(*F* ^2^) = 0.143*S* = 0.924474 reflections219 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.28 e Å^−3^ {#d5e514} Data collection: *X-AREA* (Stoe & Cie, 2005[@bb6]); cell refinement: *X-AREA*; data reduction: *X-AREA*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb2]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb3]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811006088/vm2077sup1.cif](http://dx.doi.org/10.1107/S1600536811006088/vm2077sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006088/vm2077Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006088/vm2077Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?vm2077&file=vm2077sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?vm2077sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?vm2077&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [VM2077](http://scripts.iucr.org/cgi-bin/sendsup?vm2077)). The authors are grateful to the Islamic Azad University, Tabriz Branch, and Shahid Beheshti University for financial support. Comment ======= Sulfonyl hydrazones are found to exhibit large medicinal applications. Similar to sulfonamides, sulfonyl hydrazones also have various biological activities. For example, imidosulfonylhydrazones have antibacterial and antineociceptive properties (Silva *et al.*, 2006). Acidic sulfonyl hydrazone derivatives have analgesic and anti-inflammatory activities. 4-Substituted benzenesulfonylhydrazone has been found to have antibacterial activity (Zimmer *et al.*, 1959). As part of our studies on the synthesis and characterization of hydrazone derivatives (Bikas *et al.*, 2010), we report here the crystal structure of (*E*)-*N*\'-((2-hydroxynaphthalen-1-yl)methylene)-4-methylbenzenesulfonohydrazide. The asymmetric unit of the title compound contains one molecule, which is shown in Fig. 1. The packing diagram of the title compound is shown in Fig. 2. The structure is stabilized by an intramolecular O---H···N hydrogen bond, with the nitrogen of the azomethine group (--C=N--) acting as hydrogen bond acceptor and intermolecular N---H···O hydrogen bonds with the S=O group as hydrogen bond acceptor (Table 1 and Fig. 2). The packing is characterized by a π-π interaction between the naphthyl rings (Fig. 3) with *Cg*2···*Cg*3^ii^ distance = 3.7556 (15) Å where *Cg*2 and *Cg*3 are the centroids of C9-C13/C18 and C13-C18, respectively (symmetry code ii: -*x*,1 - *y*,-*z*). Furthermore, C---H~naphthyl~···π~tolyl~ and C---H~naphthyl~···π~naphthyl~ interactions are observed with distances equal to 2.72 and 2.75 Å, respectively (Table 1 & Fig. 3). Experimental {#experimental} ============ All reagents were commercially available and used as received. A methanol (10 ml) solution of 2-hydroxy-1-naphtaldehyde (1.63 mmol) was dropwise added to a methanol solution (10 ml) of 4-methyl-benzenesulfonic acid hydrazide (1.63 mmol), and the mixture was refluxed for 3 hrs. Then the solution was evaporated on a steam bath to 5 ml and cooled to room temperature. A yellow precipitate of the title compound was separated and filtered off, washed with 5 ml of cooled methanol and then dried in air. X-ray quality crystals of the title compound were obtained from methanol by slow solvent evaporation. Yield: 81%, mp: 167.8--168.2 °C. Refinement {#refinement} ========== The hydrogen atom of N---H and O---H group were positioned geometrically and refined as riding atoms with, N---H = 0.86 Å and *U*iso(H) = 1.2 *U*eq(N) and O---H = 0.82 Å and *U*iso(H) = 1.5 *U*eq(O). The C---H protons were positioned geometrically and refined as riding atoms with C---H = 0.93 Å and *U*iso(H) = 1.2 *U*eq(C) for imine and aromatic C---H groups and C---H = 0.96 Å and *U*iso(H) = 1.5 *U*eq(C) for methyl group. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, with atom labels and anisotropic displacement ellipsoids (drawn at 30% probability level) for non-H atoms. ::: ![](e-67-0o713-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The packing diagram of the title compound. Hydrogen bonds are shown as blue dashed line. ::: ![](e-67-0o713-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The packing diagram of the title compound showing π-π and C---H···π interactions as blue and orange dashed lines, respectively. Cg1, Cg2 and Cg3 are the centroids of rings C1-C3/C5-C7, C9-C13/C18 and C13-C18, respectively; symmetry codes: (i) x, -y + 1/2, z - 1/2; (ii) -x, -y + 1, -z.). ::: ![](e-67-0o713-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e221 .table-wrap} ------------------------- --------------------------------------- C~18~H~16~N~2~O~3~S *F*(000) = 712 *M~r~* = 340.40 *D*~x~ = 1.356 Mg m^−3^ Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2ybc Cell parameters from 4474 reflections *a* = 15.740 (3) Å θ = 2.3--29.2° *b* = 10.573 (2) Å µ = 0.21 mm^−1^ *c* = 10.322 (2) Å *T* = 298 K β = 103.86 (3)° Plate, yellow *V* = 1667.8 (6) Å^3^ 0.35 × 0.25 × 0.2 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ---------------------------------------------------------------- -------------------------------------- Stoe IPDS 2T diffractometer 4474 independent reflections Radiation source: fine-focus sealed tube 2439 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.080 Detector resolution: 0.15 mm pixels mm^-1^ θ~max~ = 29.2°, θ~min~ = 2.3° rotation method scans *h* = −21→21 Absorption correction: numerical (*X-SHAPE*; Stoe & Cie, 2005) *k* = −14→13 *T*~min~ = 0.935, *T*~max~ = 0.957 *l* = −13→14 13245 measured reflections ---------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e470 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.053 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.143 H-atom parameters constrained *S* = 0.92 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0771*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4474 reflections (Δ/σ)~max~ \< 0.001 219 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.28 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e624 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e723 .table-wrap} ----- --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C6 0.41858 (14) 0.4904 (3) 0.3196 (2) 0.0705 (8) H6 0.4426 0.4414 0.2626 0.085\* S1 0.34568 (3) 0.27206 (7) 0.38051 (5) 0.0577 (2) O2 0.31790 (11) 0.23002 (19) 0.49498 (15) 0.0713 (5) N1 0.26101 (10) 0.25594 (19) 0.25177 (17) 0.0534 (5) H1A 0.2632 0.2147 0.1808 0.064\* O1 0.41463 (10) 0.2084 (2) 0.34045 (19) 0.0783 (6) N2 0.18558 (10) 0.31574 (17) 0.26935 (16) 0.0474 (4) C8 0.11925 (12) 0.3191 (2) 0.16968 (19) 0.0436 (5) H8 0.1228 0.2816 0.0896 0.052\* C9 0.03862 (12) 0.38038 (19) 0.17943 (18) 0.0414 (4) O3 0.10297 (10) 0.45363 (19) 0.40269 (14) 0.0656 (5) H3 0.1464 0.4217 0.3853 0.098\* C18 −0.03826 (12) 0.37537 (19) 0.07041 (19) 0.0429 (4) C7 0.36860 (12) 0.4348 (3) 0.39778 (19) 0.0553 (6) C17 −0.04179 (15) 0.3112 (2) −0.0504 (2) 0.0539 (6) H17 0.0077 0.2688 −0.0618 0.065\* C10 0.03447 (13) 0.4460 (2) 0.29415 (19) 0.0489 (5) C1 0.33366 (15) 0.5089 (3) 0.4823 (2) 0.0660 (7) H1 0.3007 0.4723 0.5361 0.079\* C11 −0.04155 (15) 0.5093 (2) 0.3048 (2) 0.0610 (6) H11 −0.0425 0.5538 0.3821 0.073\* C15 −0.19112 (16) 0.3721 (3) −0.1373 (3) 0.0675 (7) H15 −0.2415 0.3704 −0.2062 0.081\* C13 −0.11516 (13) 0.4395 (2) 0.0837 (2) 0.0500 (5) C14 −0.19068 (14) 0.4359 (3) −0.0229 (3) 0.0637 (7) H14 −0.2410 0.4779 −0.0145 0.076\* C12 −0.11397 (15) 0.5057 (2) 0.2025 (2) 0.0598 (6) H12 −0.1641 0.5481 0.2110 0.072\* C16 −0.11621 (17) 0.3097 (3) −0.1513 (2) 0.0653 (7) H16 −0.1166 0.2664 −0.2299 0.078\* C3 0.39614 (15) 0.6954 (3) 0.4084 (3) 0.0700 (8) C5 0.43222 (16) 0.6196 (3) 0.3274 (3) 0.0787 (9) H5 0.4668 0.6565 0.2762 0.094\* C2 0.34799 (17) 0.6369 (3) 0.4863 (3) 0.0738 (8) H2 0.3243 0.6860 0.5437 0.089\* C4 0.4090 (2) 0.8355 (4) 0.4087 (4) 0.0969 (10) H4A 0.3725 0.8711 0.3290 0.145\* H4B 0.4692 0.8539 0.4117 0.145\* H4C 0.3937 0.8715 0.4854 0.145\* ----- --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1284 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C6 0.0495 (12) 0.105 (3) 0.0628 (15) 0.0036 (13) 0.0256 (11) 0.0034 (14) S1 0.0488 (3) 0.0843 (5) 0.0418 (3) 0.0121 (3) 0.0145 (2) 0.0078 (3) O2 0.0796 (10) 0.0930 (15) 0.0447 (9) 0.0094 (9) 0.0215 (8) 0.0149 (8) N1 0.0489 (9) 0.0698 (14) 0.0440 (9) 0.0081 (8) 0.0159 (7) −0.0049 (9) O1 0.0576 (9) 0.1076 (16) 0.0717 (11) 0.0291 (9) 0.0196 (8) 0.0054 (10) N2 0.0468 (8) 0.0557 (12) 0.0426 (9) 0.0048 (7) 0.0168 (7) 0.0009 (8) C8 0.0503 (10) 0.0455 (13) 0.0370 (10) 0.0002 (9) 0.0145 (8) 0.0005 (8) C9 0.0483 (10) 0.0396 (12) 0.0377 (9) 0.0012 (8) 0.0133 (8) 0.0014 (8) O3 0.0641 (9) 0.0914 (14) 0.0413 (8) 0.0074 (9) 0.0124 (7) −0.0137 (8) C18 0.0508 (10) 0.0363 (12) 0.0429 (10) 0.0012 (8) 0.0138 (8) 0.0052 (8) C7 0.0388 (9) 0.0851 (19) 0.0410 (10) 0.0006 (10) 0.0075 (8) 0.0010 (11) C17 0.0605 (12) 0.0487 (14) 0.0489 (12) 0.0027 (10) 0.0059 (9) −0.0041 (10) C10 0.0554 (11) 0.0537 (14) 0.0398 (10) 0.0019 (9) 0.0157 (9) 0.0001 (9) C1 0.0621 (13) 0.092 (2) 0.0478 (12) −0.0105 (13) 0.0207 (10) −0.0082 (12) C11 0.0748 (15) 0.0609 (17) 0.0533 (13) 0.0125 (12) 0.0269 (11) −0.0063 (11) C15 0.0601 (13) 0.0675 (19) 0.0645 (15) −0.0075 (12) −0.0053 (11) 0.0088 (13) C13 0.0517 (11) 0.0447 (14) 0.0549 (12) 0.0014 (9) 0.0151 (9) 0.0091 (10) C14 0.0495 (11) 0.0630 (18) 0.0763 (16) 0.0046 (11) 0.0106 (11) 0.0169 (13) C12 0.0584 (12) 0.0594 (16) 0.0669 (15) 0.0153 (11) 0.0255 (11) 0.0050 (12) C16 0.0759 (15) 0.0604 (17) 0.0513 (13) −0.0027 (12) −0.0011 (11) −0.0032 (11) C3 0.0472 (12) 0.096 (2) 0.0622 (15) −0.0087 (12) 0.0032 (11) 0.0008 (14) C5 0.0523 (13) 0.105 (3) 0.0819 (19) −0.0119 (14) 0.0222 (13) 0.0181 (17) C2 0.0712 (15) 0.094 (2) 0.0565 (14) −0.0097 (15) 0.0160 (12) −0.0129 (14) C4 0.0861 (19) 0.099 (3) 0.098 (2) −0.0163 (18) 0.0068 (17) 0.0056 (19) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1723 .table-wrap} ----------------------- -------------- ----------------------- -------------- C6---C5 1.383 (4) C10---C11 1.398 (3) C6---C7 1.386 (3) C1---C2 1.370 (4) C6---H6 0.9300 C1---H1 0.9300 S1---O1 1.4204 (17) C11---C12 1.356 (3) S1---O2 1.4257 (17) C11---H11 0.9300 S1---N1 1.6499 (18) C15---C14 1.359 (4) S1---C7 1.758 (3) C15---C16 1.389 (4) N1---N2 1.395 (2) C15---H15 0.9300 N1---H1A 0.8600 C13---C12 1.408 (3) N2---C8 1.279 (2) C13---C14 1.413 (3) C8---C9 1.450 (3) C14---H14 0.9300 C8---H8 0.9300 C12---H12 0.9300 C9---C10 1.387 (3) C16---H16 0.9300 C9---C18 1.443 (3) C3---C5 1.375 (4) O3---C10 1.358 (2) C3---C2 1.376 (4) O3---H3 0.8200 C3---C4 1.496 (5) C18---C17 1.409 (3) C5---H5 0.9300 C18---C13 1.422 (3) C2---H2 0.9300 C7---C1 1.382 (3) C4---H4A 0.9600 C17---C16 1.368 (3) C4---H4B 0.9600 C17---H17 0.9300 C4---H4C 0.9600 C5---C6---C7 119.2 (3) C7---C1---H1 120.3 C5---C6---H6 120.4 C12---C11---C10 120.1 (2) C7---C6---H6 120.4 C12---C11---H11 120.0 O1---S1---O2 120.06 (12) C10---C11---H11 120.0 O1---S1---N1 104.04 (10) C14---C15---C16 119.9 (2) O2---S1---N1 106.64 (10) C14---C15---H15 120.1 O1---S1---C7 109.94 (12) C16---C15---H15 120.1 O2---S1---C7 108.50 (11) C12---C13---C14 121.6 (2) N1---S1---C7 106.82 (10) C12---C13---C18 119.13 (18) N2---N1---S1 113.38 (13) C14---C13---C18 119.3 (2) N2---N1---H1A 123.3 C15---C14---C13 121.2 (2) S1---N1---H1A 123.3 C15---C14---H14 119.4 C8---N2---N1 117.67 (17) C13---C14---H14 119.4 N2---C8---C9 121.08 (18) C11---C12---C13 121.7 (2) N2---C8---H8 119.5 C11---C12---H12 119.2 C9---C8---H8 119.5 C13---C12---H12 119.2 C10---C9---C18 118.81 (18) C17---C16---C15 120.6 (2) C10---C9---C8 120.25 (17) C17---C16---H16 119.7 C18---C9---C8 120.94 (17) C15---C16---H16 119.7 C10---O3---H3 109.5 C5---C3---C2 117.3 (3) C17---C18---C13 117.44 (18) C5---C3---C4 120.1 (3) C17---C18---C9 123.77 (18) C2---C3---C4 122.5 (3) C13---C18---C9 118.79 (18) C3---C5---C6 122.0 (3) C1---C7---C6 119.7 (3) C3---C5---H5 119.0 C1---C7---S1 121.08 (19) C6---C5---H5 119.0 C6---C7---S1 119.2 (2) C1---C2---C3 122.4 (3) C16---C17---C18 121.6 (2) C1---C2---H2 118.8 C16---C17---H17 119.2 C3---C2---H2 118.8 C18---C17---H17 119.2 C3---C4---H4A 109.5 O3---C10---C9 122.90 (18) C3---C4---H4B 109.5 O3---C10---C11 115.60 (19) H4A---C4---H4B 109.5 C9---C10---C11 121.50 (19) C3---C4---H4C 109.5 C2---C1---C7 119.4 (2) H4A---C4---H4C 109.5 C2---C1---H1 120.3 H4B---C4---H4C 109.5 O1---S1---N1---N2 −178.38 (16) C8---C9---C10---C11 178.0 (2) O2---S1---N1---N2 53.77 (18) C6---C7---C1---C2 0.9 (3) C7---S1---N1---N2 −62.10 (17) S1---C7---C1---C2 −175.48 (18) S1---N1---N2---C8 173.14 (15) O3---C10---C11---C12 −179.0 (2) N1---N2---C8---C9 −179.48 (18) C9---C10---C11---C12 1.1 (4) N2---C8---C9---C10 5.5 (3) C17---C18---C13---C12 −179.4 (2) N2---C8---C9---C18 −175.04 (19) C9---C18---C13---C12 0.0 (3) C10---C9---C18---C17 −179.7 (2) C17---C18---C13---C14 0.2 (3) C8---C9---C18---C17 0.8 (3) C9---C18---C13---C14 179.6 (2) C10---C9---C18---C13 0.9 (3) C16---C15---C14---C13 −0.4 (4) C8---C9---C18---C13 −178.56 (19) C12---C13---C14---C15 179.7 (2) C5---C6---C7---C1 −0.3 (3) C18---C13---C14---C15 0.1 (4) C5---C6---C7---S1 176.16 (18) C10---C11---C12---C13 −0.1 (4) O1---S1---C7---C1 −154.14 (17) C14---C13---C12---C11 180.0 (2) O2---S1---C7---C1 −21.0 (2) C18---C13---C12---C11 −0.4 (4) N1---S1---C7---C1 93.57 (18) C18---C17---C16---C15 0.1 (4) O1---S1---C7---C6 29.5 (2) C14---C15---C16---C17 0.3 (4) O2---S1---C7---C6 162.58 (17) C2---C3---C5---C6 2.3 (4) N1---S1---C7---C6 −82.81 (18) C4---C3---C5---C6 −177.0 (2) C13---C18---C17---C16 −0.3 (3) C7---C6---C5---C3 −1.4 (4) C9---C18---C17---C16 −179.7 (2) C7---C1---C2---C3 0.1 (4) C18---C9---C10---O3 178.6 (2) C5---C3---C2---C1 −1.7 (4) C8---C9---C10---O3 −1.9 (3) C4---C3---C2---C1 177.6 (2) C18---C9---C10---C11 −1.5 (3) ----------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2511 .table-wrap} ----------------------------------------------------------------------------------------- Cg1 and Cg2 are the centroids of the C1--C3/C5--C7 and C9--C13/C18 rings, respectively. ----------------------------------------------------------------------------------------- ::: ::: {#d1e2515 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O3---H3···N2 0.82 1.85 2.563 (2) 145. N1---H1A···O2^i^ 0.86 2.36 2.998 (2) 132. C15---H15···Cg1^ii^ 0.92 2.72 3.625 (3) 164 C16---H16···Cg2^i^ 0.92 2.75 3.501 (3) 139 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*, −*y*+1/2, *z*−1/2; (ii) −*x*, −*y*+1, −*z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 and *Cg*2 are the centroids of the C1--C3/C5--C7 and C9--C13/C18 rings, respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- O3---H3⋯N2 0.82 1.85 2.563 (2) 145 N1---H1*A*⋯O2^i^ 0.86 2.36 2.998 (2) 132 C15---H15⋯*Cg*1^ii^ 0.92 2.72 3.625 (3) 164 C16---H16⋯*Cg*2^i^ 0.92 2.75 3.501 (3) 139 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.879638

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052163/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o713", "authors": [ { "first": "Gholam Hossein", "last": "Shahverdizadeh" }, { "first": "Rahman", "last": "Bikas" }, { "first": "Maryam", "last": "Eivazi" }, { "first": "Parisa", "last": "Mahboubi Anarjan" }, { "first": "Behrouz", "last": "Notash" } ] }

PMC3052164

Related literature {#sec1} ================== For hydrogen bonds and crystal engineering, see: Aakeröy & Seddon (1993[@bb1]). For potential applications of transition metal complexes, see: Liu *et al.* (2007[@bb3]); Shibasaki & Yoshikawa (2002[@bb8]). For carboxylate compounds with six-coordinate metal atoms, see: Liu *et al.* (2010[@bb4]); Su *et al.* (2005[@bb9]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[Cu(C~8~H~7~O~3~)~2~(C~10~H~8~N~2~)\]·H~2~O*M* *~r~* = 540.01Monoclinic,*a* = 19.888 (4) Å*b* = 10.887 (2) Å*c* = 11.612 (2) Åβ = 103.62 (3)°*V* = 2443.5 (8) Å^3^*Z* = 4Mo *K*α radiationμ = 0.94 mm^−1^*T* = 293 K0.1 × 0.1 × 0.1 mm ### Data collection {#sec2.1.2} Rigaku R-AXIS RAPID diffractometerAbsorption correction: multi-scan (*ABSCOR*; Higashi, 1995[@bb2]) *T* ~min~ = 0.710, *T* ~max~ = 0.78012080 measured reflections2796 independent reflections2391 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.054 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.041*wR*(*F* ^2^) = 0.113*S* = 1.052796 reflections165 parametersH-atom parameters constrainedΔρ~max~ = 0.35 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e530} Data collection: *RAPID-AUTO* (Rigaku, 1998[@bb5]); cell refinement: *RAPID-AUTO*; data reduction: *CrystalStructure* (Rigaku/MSC, 2004[@bb6]); program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *ORTEPII* (Johnson, 1976)[@bb10]; software used to prepare material for publication: *SHELXL97*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005563/rn2078sup1.cif](http://dx.doi.org/10.1107/S1600536811005563/rn2078sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005563/rn2078Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005563/rn2078Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rn2078&file=rn2078sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rn2078sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rn2078&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RN2078](http://scripts.iucr.org/cgi-bin/sendsup?rn2078)). This project was supported by the Education Department of Zhejiang Province and the scientific research fund of Nibong University (grant No. XKL069). Thanks are also extended to the K. C. Wong Magna Fund, Ningbo University. Comment ======= In the past decade, a variety of supramolecular architectures based on hydrogen bonds, π···π interactions have been achieved by using transition metal centers and organic ligands (Aakeroy *et al.*, 1993), they have potential application in catalysis, gas storage, and in molecular--based magnetic materials (Liu *et al.*, 2007, Shibasaki *et al.*, 2002). Herein, we are interested in self-assemblies of Cu^2+^ ions and bipy with 3--methoxybenzoic acid, which led to the preparation of \[Cu(bipy)~2~(C~8~H~8~O~3~)~2~\].H~2~O. The title compound, \[Cu(bipy)~2~(C~8~H~8~O~3~)~2~\].H~2~O, is comprised of a Cu^II^ ion, two 3--methoxybenzoate ligands, a 2,2\'--bipyridine(bipy) ligand and one lattice H~2~O molecule. As illustrated in Fig.1, the Cu ion and water O atom lie on a two fold axis. The Cu^II^ ion has a six--coordinate distorted octahedral geometry with two N atoms from the bipy ligand \[Cu--N = 1.9996 (16) Å\] and four O atoms from two 3--methoxybenzoate ligands \[Cu--O = 1.9551 (15) and 2.6016 (16) Å\]. Owing to geometric constraints and the Jahn--Teller effect, the Cu--O bonds in the axial direction are longer than in the equatorial plane. Two O atoms and two N atoms occupy the equatorial plane position with the r.m.s. deviation from the ideal plane of 0.214 Å, while two O atoms lie in the apical positions with an axis angle of 140.53 (5)° showing a large deviation from the normal 180°,which is also seen in similar carboxylate complexes (Liu *et al.*, 2010; Su *et al.*, 2005). For 3--methoxybenzoate anions, the plane of benzene ring and carboxylate group are nearly co--planar where the dihedral angle between the benzene ring and carboxylate plane is 5.2 (3)°. The water molecules are not coordinated to Cu and the distance between copper and water oxygen atoms is 4.019 (2) Å. The molecules are linked *via* hydrogen bonds (O4--H41···O1, C12--H12A···O4, C11--H11A···O3) into one-dimensional supramolecular chains extending along the \[100\] direction, which are linked by hydrogen bonds (C5--H5A···O2) into two dimensional layers parallel to (100) (Fig. 2). The layers are arranged alternately in an ···ABAB···sequence and further assembled into there--dimensional network by hydrogen bonds (C10--H10A···O2). Experimental {#experimental} ============ CuCl~2~.2H~2~O (0.1705 g, 1.000 mmol) was successively added to 20 ml C~2~H~5~OH--H~2~O(1:1, *v*/*v*), 3--methoxybenzoate (0.1520 g, 1.000 mmol) and bipy (0.1569 g, 1.004 mmol) were subsequently added, then 1.4 ml (1 *M*) NaOH was added dropwise and stirred continuously for 1 h to give a blue suspension. After filtration, the blue filtrate (pH = 5.80) was allowed to stand at room temperature for several weeks to give blue block--shaped crystals Refinement {#refinement} ========== H atoms bonded to C atoms were placed in geometrically calculated positions and were refined using a riding model, with *U*~iso~(H) = 1.2 *U*~eq~(C). H atoms attached to O atoms were found in a difference Fourier synthesis and were refined using a riding model, with the O---H distances fixed as initially found and with *U*~iso~(H) values set at 1.2 *U*eq(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound,with atom labels and 45% probability displacement ellipsoids for non-H atoms. Symmetry code for the symbol \'A\': -x, y + 1, 0.5 - z. ::: ![](e-67-0m352-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The two-dimensional supramolecular layers of the title compound parallel to (100) showing O--H···O, C--H···O hydrogen bonds. ::: ![](e-67-0m352-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e226 .table-wrap} ---------------------------------------------- ---------------------------------------- \[Cu(C~8~H~7~O~3~)~2~(C~10~H~8~N~2~)\]·H~2~O *F*(000) = 1116 *M~r~* = 540.01 *D*~x~ = 1.468 Mg m^−3^ Monoclinic, *C*2/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -C 2yc Cell parameters from 12080 reflections *a* = 19.888 (4) Å θ = 3.6--27.5° *b* = 10.887 (2) Å µ = 0.94 mm^−1^ *c* = 11.612 (2) Å *T* = 293 K β = 103.62 (3)° Block, blue *V* = 2443.5 (8) Å^3^ 0.1 × 0.1 × 0.1 mm *Z* = 4 ---------------------------------------------- ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e367 .table-wrap} ------------------------------------------------------------- -------------------------------------- Rigaku R-AXIS RAPID diffractometer 2796 independent reflections Radiation source: fine-focus sealed tube 2391 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.054 Detector resolution: 0 pixels mm^-1^ θ~max~ = 27.5°, θ~min~ = 3.6° ω scans *h* = −25→25 Absorption correction: multi-scan (*ABSCOR*; Higashi, 1995) *k* = −14→14 *T*~min~ = 0.710, *T*~max~ = 0.78 *l* = −15→14 12080 measured reflections ------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.113 H-atom parameters constrained *S* = 1.05 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0638*P*)^2^ + 0.7842*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2796 reflections (Δ/σ)~max~ = 0.001 165 parameters Δρ~max~ = 0.35 e Å^−3^ 0 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ------ --------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Cu 0.0000 0.52776 (3) 0.7500 0.04304 (15) O1 −0.04555 (7) 0.40392 (14) 0.82712 (14) 0.0539 (4) O2 −0.12489 (8) 0.44707 (15) 0.66421 (15) 0.0598 (4) O3 −0.15000 (9) 0.11263 (17) 1.05759 (15) 0.0669 (5) N1 −0.03034 (8) 0.66715 (15) 0.83787 (14) 0.0426 (4) C1 −0.10582 (10) 0.39069 (18) 0.75900 (19) 0.0470 (5) C2 −0.15286 (10) 0.30133 (18) 0.79947 (19) 0.0475 (5) C3 −0.21724 (12) 0.2726 (2) 0.7265 (2) 0.0611 (6) H3A −0.2317 0.3089 0.6523 0.073\* C4 −0.25923 (13) 0.1895 (3) 0.7658 (3) 0.0724 (7) H4A −0.3021 0.1702 0.7170 0.087\* C5 −0.23949 (12) 0.1344 (2) 0.8754 (3) 0.0646 (6) H5A −0.2688 0.0790 0.9003 0.078\* C6 −0.17571 (11) 0.16247 (19) 0.9479 (2) 0.0534 (5) C7 −0.13269 (10) 0.24562 (19) 0.9099 (2) 0.0498 (5) H7A −0.0898 0.2643 0.9590 0.060\* C8 −0.19197 (18) 0.0270 (3) 1.1014 (3) 0.0818 (9) H8A −0.1674 −0.0022 1.1777 0.123\* H8B −0.2028 −0.0410 1.0476 0.123\* H8C −0.2340 0.0664 1.1085 0.123\* C9 −0.06227 (11) 0.6578 (2) 0.92759 (18) 0.0492 (5) H9A −0.0705 0.5802 0.9549 0.059\* C10 −0.08304 (12) 0.7594 (2) 0.97979 (19) 0.0557 (5) H10A −0.1055 0.7507 1.0411 0.067\* C11 −0.07033 (13) 0.8737 (2) 0.9407 (2) 0.0599 (6) H11A −0.0838 0.9434 0.9757 0.072\* C12 −0.03730 (12) 0.8849 (2) 0.8490 (2) 0.0552 (5) H12A −0.0282 0.9619 0.8215 0.066\* C13 −0.01811 (10) 0.77943 (18) 0.79901 (17) 0.0426 (4) O4 0.0000 0.1586 (2) 0.7500 0.0842 (8) H41 −0.0138 0.2109 0.7975 0.126\* ------ --------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1215 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Cu 0.0395 (2) 0.0333 (2) 0.0560 (2) 0.000 0.01071 (15) 0.000 O1 0.0423 (8) 0.0427 (8) 0.0740 (10) −0.0074 (6) 0.0083 (7) 0.0071 (7) O2 0.0532 (9) 0.0576 (9) 0.0692 (10) 0.0083 (7) 0.0159 (8) 0.0082 (8) O3 0.0646 (10) 0.0641 (11) 0.0774 (11) −0.0110 (8) 0.0277 (9) 0.0081 (8) N1 0.0407 (9) 0.0405 (9) 0.0468 (9) −0.0013 (7) 0.0108 (7) 0.0020 (6) C1 0.0435 (11) 0.0356 (10) 0.0642 (12) 0.0055 (8) 0.0174 (9) −0.0021 (9) C2 0.0367 (10) 0.0361 (10) 0.0696 (13) 0.0015 (8) 0.0125 (9) −0.0064 (9) C3 0.0457 (12) 0.0546 (13) 0.0777 (15) −0.0014 (10) 0.0040 (11) −0.0038 (11) C4 0.0400 (12) 0.0667 (16) 0.103 (2) −0.0126 (11) 0.0024 (12) −0.0111 (15) C5 0.0459 (13) 0.0512 (13) 0.1009 (19) −0.0111 (10) 0.0258 (12) −0.0081 (12) C6 0.0478 (12) 0.0425 (11) 0.0754 (14) −0.0041 (9) 0.0254 (10) −0.0069 (10) C7 0.0383 (10) 0.0447 (11) 0.0671 (13) −0.0052 (8) 0.0135 (9) −0.0048 (9) C8 0.093 (2) 0.0693 (19) 0.098 (2) −0.0154 (15) 0.0526 (19) 0.0040 (14) C9 0.0461 (11) 0.0513 (12) 0.0508 (11) −0.0028 (9) 0.0127 (9) 0.0042 (9) C10 0.0557 (13) 0.0657 (14) 0.0502 (11) 0.0017 (11) 0.0211 (10) −0.0018 (10) C11 0.0696 (15) 0.0536 (13) 0.0614 (13) 0.0079 (11) 0.0255 (11) −0.0082 (10) C12 0.0679 (14) 0.0386 (11) 0.0629 (13) 0.0042 (10) 0.0232 (11) −0.0006 (9) C13 0.0430 (10) 0.0384 (10) 0.0462 (10) 0.0013 (8) 0.0100 (8) −0.0011 (7) O4 0.124 (3) 0.0464 (14) 0.0887 (18) 0.000 0.0370 (17) 0.000 ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1588 .table-wrap} -------------------- ------------- -------------------- ------------- Cu---O1^i^ 1.9551 (15) C5---C6 1.381 (3) Cu---O1 1.9551 (15) C5---H5A 0.9300 Cu---N1^i^ 1.9996 (16) C6---C7 1.387 (3) Cu---N1 1.9996 (16) C7---H7A 0.9300 O1---C1 1.279 (3) C8---H8A 0.9600 O2---C1 1.239 (3) C8---H8B 0.9600 O3---C6 1.368 (3) C8---H8C 0.9600 O3---C8 1.423 (3) C9---C10 1.371 (3) N1---C13 1.345 (2) C9---H9A 0.9300 N1---C9 1.346 (3) C10---C11 1.369 (3) C1---C2 1.500 (3) C10---H10A 0.9300 C2---C7 1.390 (3) C11---C12 1.382 (3) C2---C3 1.395 (3) C11---H11A 0.9300 C3---C4 1.380 (4) C12---C13 1.380 (3) C3---H3A 0.9300 C12---H12A 0.9300 C4---C5 1.378 (4) C13---C13^i^ 1.483 (4) C4---H4A 0.9300 O4---H41 0.8800 O1^i^---Cu---O1 92.80 (10) O3---C6---C7 115.6 (2) O1^i^---Cu---N1^i^ 93.53 (7) C5---C6---C7 119.8 (2) O1---Cu---N1^i^ 170.12 (6) C6---C7---C2 120.8 (2) O1^i^---Cu---N1 170.12 (6) C6---C7---H7A 119.6 O1---Cu---N1 93.53 (7) C2---C7---H7A 119.6 N1^i^---Cu---N1 81.25 (9) O3---C8---H8A 109.5 C1---O1---Cu 105.20 (13) O3---C8---H8B 109.5 C6---O3---C8 118.1 (2) H8A---C8---H8B 109.5 C13---N1---C9 118.97 (17) O3---C8---H8C 109.5 C13---N1---Cu 114.74 (12) H8A---C8---H8C 109.5 C9---N1---Cu 126.27 (14) H8B---C8---H8C 109.5 O2---C1---O1 122.66 (19) N1---C9---C10 121.83 (19) O2---C1---C2 121.1 (2) N1---C9---H9A 119.1 O1---C1---C2 116.23 (18) C10---C9---H9A 119.1 C7---C2---C3 119.2 (2) C11---C10---C9 119.26 (19) C7---C2---C1 120.43 (19) C11---C10---H10A 120.4 C3---C2---C1 120.4 (2) C9---C10---H10A 120.4 C4---C3---C2 119.1 (2) C10---C11---C12 119.6 (2) C4---C3---H3A 120.4 C10---C11---H11A 120.2 C2---C3---H3A 120.4 C12---C11---H11A 120.2 C5---C4---C3 121.9 (2) C13---C12---C11 118.6 (2) C5---C4---H4A 119.1 C13---C12---H12A 120.7 C3---C4---H4A 119.1 C11---C12---H12A 120.7 C4---C5---C6 119.2 (2) N1---C13---C12 121.68 (17) C4---C5---H5A 120.4 N1---C13---C13^i^ 114.60 (10) C6---C5---H5A 120.4 C12---C13---C13^i^ 123.71 (12) O3---C6---C5 124.6 (2) -------------------- ------------- -------------------- ------------- ::: Symmetry codes: (i) −*x*, *y*, −*z*+3/2. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2046 .table-wrap} ---------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O4---H41···O1 0.88 2.24 3.023 (3) 147 C12---H12A···O4^ii^ 0.93 2.41 3.339 (3) 178 C11---H11A···O3^ii^ 0.93 2.57 3.483 (3) 166 C10---H10A···O2^iii^ 0.93 2.66 3.342 (3) 131 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) *x*, *y*+1, *z*; (iii) *x*, −*y*+1, *z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------------- --------- ------- ----------- ------------- O4---H41⋯O1 0.88 2.24 3.023 (3) 147 C12---H12*A*⋯O4^ii^ 0.93 2.41 3.339 (3) 178 C11---H11*A*⋯O3^ii^ 0.93 2.57 3.483 (3) 166 C10---H10*A*⋯O2^iii^ 0.93 2.66 3.342 (3) 131 Symmetry codes: (ii) ; (iii) . :::

PubMed Central

2024-06-05T04:04:18.885418

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052164/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m352", "authors": [ { "first": "Ming-Hao", "last": "Lin" }, { "first": "Jing-Fan", "last": "Zhou" }, { "first": "Bin-Bin", "last": "Liu" }, { "first": "Jian-Li", "last": "Lin" } ] }

PMC3052165

Related literature {#sec1} ================== For the structures of some Zn^II^--pyridine complexes, see: Le Querler *et al.* (1977[@bb5]); Pasaoglu *et al.* (2006[@bb7]); Fan & Wu (2006[@bb2]). For the structure of a mixed-ligand Pt^II^ complex with 4-(4-nitrobenzyl)pyridine, see: Chan *et al.* (1993[@bb1]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\]*M* *~r~* = 747.61Orthorhombic,*a* = 18.2091 (2) Å*b* = 15.8998 (3) Å*c* = 19.0327 (3) Å*V* = 5510.37 (15) Å^3^*Z* = 8Mo *K*α radiationμ = 3.17 mm^−1^*T* = 200 K0.40 × 0.22 × 0.15 mm ### Data collection {#sec2.1.2} Oxford Diffraction Gemini-S Ultra CCD detector diffractometerAbsorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010[@bb6]) *T* ~min~ = 0.865, *T* ~max~ = 0.98018536 measured reflections10102 independent reflections7499 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.024 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.032*wR*(*F* ^2^) = 0.056*S* = 0.8910102 reflections627 parameters25 restraintsH-atom parameters not refinedΔρ~max~ = 0.63 e Å^−3^Δρ~min~ = −0.47 e Å^−3^Absolute structure: Flack (1983[@bb4]), 4516 Friedel pairsFlack parameter: 0.430 (14) {#d5e387} Data collection: *CrysAlis PRO* (Oxford Diffraction, 2010[@bb6]); cell refinement: *CrysAlis PRO*; data reduction: *CrysAlis PRO*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb8]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb8]) within *WinGX* (Farrugia, 1999[@bb3]); molecular graphics: *PLATON* (Spek, 2009[@bb9]); software used to prepare material for publication: *PLATON*. Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005939/ng5114sup1.cif](http://dx.doi.org/10.1107/S1600536811005939/ng5114sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005939/ng5114Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005939/ng5114Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5114&file=ng5114sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5114sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5114&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5114](http://scripts.iucr.org/cgi-bin/sendsup?ng5114)). The authors acknowledge financial support from the Australian Research Committee, the Faculty of Science and Technology and the University Library, Queensland University of Technology, and the School of Biomolecular and Physical Sciences, Griffith University. Comment ======= The structures of complexes of ZnI~2~ with pyridine and substituted pyridine ligands, of the type \[ZnI~2~(py)~2~\] are common in the crystallographic literature *e.g.* with pyridine (Le Querler *et al.*, 1977), and with nicotinamide and isonicotinamide (Pasaoglu *et al.*, 2006). These complexes are usually discrete with distorted tetrahedral stereochemistry. Polymeric complexes having similar stereochemistry are also formed with bifunctional pyridines such as 4,4\'-bipyridine (Fan & Wu, 2006). We obtained the title compound \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\] (I) from the reaction of zinc(II) iodide with 4-(4-nitrobenzyl)pyridine (*L*) and the structure is reported here. This substituted pyridine has only occasionally been used as a ligand in metal complex formation *e.g.* in the mixed-ligand Pt^II^ complex with 2,9-diphenyl-1,10-phenanthroline (Chan *et al.*, 1993). In the structure of (I), the asymmetric unit contains two independent discrete distorted tetrahedral \[ZnI~2~*L*~2~\] complex units, involving Zn1 and Zn2 (Figs. 1, 2). The Zn---I range is 2.5472 (8)--2.5666 (7) Å, the Zn---N range is 2.044 (4)--2.052 (4) Å and the bond angle range about Zn is 98.99 (17)--119.96 (2)° (for I1---Zn1---I2 and N1*A*---Zn1---N1*B*, respectively). The two complex molecules are essentially identical conformationally and are related by pseudo-symmetry, being treated as a racemic twin in the structure refinement. In the crystal packing of (I) there are only weak intermolecular aromatic *C*---*H*···O~nitro~ interactions \[C5A---H···O41D, 3.211 (9) Å and C6B---H···O41B, 3.295 Å\] but there are some aromatic ring π--π associations involving the C11B--C61B rings: ring centroid separation, 3.591 (3) Å; inter-ring dihedral angle, 3.46 (1)°\] (Fig. 3). Experimental {#experimental} ============ The title compound was synthesized by heating together under reflux for 10 minutes, 1 mmol of zinc(II) iodide and 2 mmol of 4-(4-nitrobenzyl)pyridine in 50 ml of 50% ethanol--water. After concentration to *ca* 30 ml, partial room temperature evaporation of the hot-filtered solution gave pale yellow flattened prisms of (I) from which a suitable specimen was cleaved for the X-ray analysis. Refinement {#refinement} ========== Hydrogen atoms were included in the refinement in calculated positions with C--H = 0.93 Å (aromatic) or 0.97 Å (aliphatic) and allowed to ride, with *U*~iso~(H) = 1.2*U*~eq~(C). A racemic twin was identified and treated as such using the appropriate *SHELXL97* function \[BASF factor, 0.430 (14)\]. Oxygen atoms of the terminal nitro groups were significantly disordered, one in particular (O41*C*, *U*~iso~ = 0.142 Å^2^) subsequently being refined isotropically. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular configuration and atom-numbering scheme for the first of the two independent complex units (about Zn1) in the asymmetric unit of (I), with non-H atoms drawn as 30% probability ellipsoids. ::: ![](e-67-0m359-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The molecular configuration and atom-numbering scheme for the second complex unit (about Zn2) in (I) (30% probability). ::: ![](e-67-0m359-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### The packing of (I) in the unit cell, viewed down the a cell direction. Hydrogen atoms are omitted. ::: ![](e-67-0m359-fig3) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e215 .table-wrap} ----------------------------------- --------------------------------------- \[ZnI~2~(C~12~H~10~N~2~O~2~)~2~\] *D*~x~ = 1.802 Mg m^−3^ *M~r~* = 747.61 Melting point = 473--475 K Orthorhombic, *Pca*2~1~ Mo *K*α radiation, λ = 0.71073 Å Hall symbol: P 2c -2ac Cell parameters from 5528 reflections *a* = 18.2091 (2) Å θ = 3.3--28.7° *b* = 15.8998 (3) Å µ = 3.17 mm^−1^ *c* = 19.0327 (3) Å *T* = 200 K *V* = 5510.37 (15) Å^3^ Prism, pale yellow *Z* = 8 0.40 × 0.22 × 0.15 mm *F*(000) = 2880 ----------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e352 .table-wrap} ------------------------------------------------------------------------------ -------------------------------------- Oxford Diffraction Gemini-S Ultra CCD detector diffractometer 10102 independent reflections Radiation source: Enhance (Mo) X-ray source 7499 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.024 Detector resolution: 16.077 pixels mm^-1^ θ~max~ = 26.0°, θ~min~ = 3.4° ω scans *h* = −22→22 Absorption correction: multi-scan (*CrysAlis PRO*; Oxford Diffraction, 2010) *k* = −19→19 *T*~min~ = 0.865, *T*~max~ = 0.980 *l* = −23→22 18536 measured reflections ------------------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e472 .table-wrap} ---------------------------------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Secondary atom site location: difference Fourier map Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.032 H-atom parameters not refined *wR*(*F*^2^) = 0.056 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0262*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *S* = 0.89 (Δ/σ)~max~ = 0.024 10102 reflections Δρ~max~ = 0.63 e Å^−3^ 627 parameters Δρ~min~ = −0.47 e Å^−3^ 25 restraints Absolute structure: Flack (1983), 4516 Friedel pairs Primary atom site location: structure-invariant direct methods Flack parameter: 0.430 (14) ---------------------------------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e631 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. Bond distances, angles *etc*. have been calculated using the rounded fractional coordinates. All su\'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.\'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e733 .table-wrap} ------ ------------- ------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ I1 0.95618 (2) 0.12807 (3) 0.69072 (2) 0.0518 (1) I2 1.15212 (2) 0.14231 (3) 0.82772 (2) 0.0567 (1) Zn1 1.01354 (3) 0.12528 (4) 0.81338 (3) 0.0432 (2) O41A 0.6840 (4) 0.3754 (6) 1.2662 (4) 0.179 (5) O41B 0.6256 (3) −0.0954 (3) 1.1910 (3) 0.0767 (19) O42A 0.7998 (4) 0.3645 (5) 1.3010 (4) 0.123 (3) O42B 0.5740 (3) −0.1013 (4) 1.0908 (3) 0.100 (3) N1A 0.9587 (2) 0.2149 (3) 0.8705 (2) 0.0440 (17) N1B 0.9820 (2) 0.0205 (3) 0.8686 (2) 0.0393 (16) N41A 0.7532 (6) 0.3685 (6) 1.2560 (5) 0.146 (5) N41B 0.6283 (3) −0.1037 (3) 1.1280 (4) 0.060 (2) C2A 0.8847 (3) 0.2146 (4) 0.8703 (3) 0.064 (3) C2B 1.0121 (3) 0.0043 (3) 0.9320 (3) 0.0413 (19) C3A 0.8434 (3) 0.2746 (4) 0.9017 (3) 0.065 (3) C3B 0.9891 (3) −0.0596 (4) 0.9745 (3) 0.0447 (19) C4A 0.8780 (4) 0.3398 (4) 0.9357 (3) 0.053 (2) C4B 0.9333 (3) −0.1124 (3) 0.9535 (3) 0.038 (2) C5A 0.9519 (4) 0.3414 (4) 0.9358 (4) 0.066 (3) C5B 0.9039 (3) −0.0982 (4) 0.8879 (3) 0.045 (2) C6A 0.9918 (3) 0.2776 (4) 0.9036 (3) 0.058 (3) C6B 0.9289 (3) −0.0329 (3) 0.8476 (3) 0.0440 (19) C11A 0.8119 (4) 0.3939 (4) 1.0439 (4) 0.056 (3) C11B 0.8332 (3) −0.1589 (3) 1.0348 (3) 0.0343 (19) C21A 0.7428 (4) 0.3758 (6) 1.0609 (5) 0.098 (4) C21B 0.7678 (3) −0.1709 (3) 0.9985 (4) 0.049 (2) C31A 0.7239 (4) 0.3700 (6) 1.1283 (5) 0.107 (4) C31B 0.7012 (3) −0.1499 (4) 1.0273 (3) 0.052 (2) C41A 0.7739 (4) 0.3750 (5) 1.1802 (5) 0.078 (3) C41B 0.7001 (3) −0.1210 (3) 1.0951 (3) 0.040 (2) C42A 0.8329 (4) 0.4105 (4) 0.9687 (4) 0.080 (3) C42B 0.9056 (3) −0.1818 (3) 1.0005 (3) 0.0453 (19) C51A 0.8454 (4) 0.3902 (4) 1.1653 (5) 0.072 (3) C51B 0.7630 (3) −0.1092 (3) 1.1331 (3) 0.042 (2) C61A 0.8651 (4) 0.3999 (4) 1.0951 (4) 0.068 (3) C61B 0.8296 (3) −0.1277 (4) 1.1026 (4) 0.048 (2) I3 1.16361 (2) 0.37425 (3) 0.36527 (2) 0.0519 (2) I4 0.97184 (2) 0.40341 (3) 0.50705 (2) 0.0539 (1) Zn2 1.02497 (3) 0.39353 (4) 0.38352 (4) 0.0426 (2) O41C 0.6595 (4) 0.1413 (4) −0.0106 (4) 0.142 (3)\* O41D 0.6107 (3) 0.6158 (3) −0.0002 (4) 0.087 (3) O42C 0.7457 (4) 0.0960 (4) −0.0805 (4) 0.111 (3) O42D 0.5606 (3) 0.6355 (4) 0.0996 (3) 0.100 (3) N1C 0.9779 (2) 0.2952 (3) 0.3310 (2) 0.0397 (16) N1D 0.9879 (2) 0.4909 (3) 0.3227 (2) 0.0410 (16) N41C 0.7239 (3) 0.1135 (5) −0.0243 (4) 0.095 (3) N41D 0.6136 (3) 0.6286 (4) 0.0638 (4) 0.072 (3) C2C 0.9348 (3) 0.2378 (4) 0.3602 (3) 0.0467 (19) C2D 1.0279 (3) 0.5244 (4) 0.2716 (3) 0.060 (2) C3C 0.9099 (3) 0.1676 (4) 0.3250 (3) 0.050 (2) C3D 1.0007 (3) 0.5839 (4) 0.2253 (3) 0.056 (2) C4C 0.9291 (3) 0.1548 (4) 0.2565 (4) 0.048 (2) C4D 0.9294 (3) 0.6108 (3) 0.2306 (3) 0.0383 (19) C5C 0.9721 (3) 0.2143 (4) 0.2250 (3) 0.0510 (19) C5D 0.8890 (3) 0.5774 (4) 0.2850 (3) 0.055 (2) C6C 0.9953 (3) 0.2838 (4) 0.2631 (3) 0.054 (2) C6D 0.9198 (3) 0.5191 (3) 0.3297 (3) 0.053 (2) C11C 0.8593 (3) 0.0910 (3) 0.1544 (3) 0.0437 (19) C11D 0.8235 (3) 0.6580 (3) 0.1517 (3) 0.0400 (19) C21C 0.8846 (3) 0.0790 (4) 0.0877 (4) 0.056 (3) C21D 0.8159 (3) 0.6233 (3) 0.0871 (3) 0.040 (2) C31C 0.8426 (3) 0.0866 (4) 0.0299 (4) 0.060 (3) C31D 0.7475 (3) 0.6113 (3) 0.0565 (4) 0.049 (2) C41C 0.7692 (3) 0.1101 (4) 0.0397 (4) 0.058 (3) C41D 0.6878 (3) 0.6352 (4) 0.0956 (3) 0.044 (2) C42C 0.9073 (4) 0.0765 (4) 0.2176 (3) 0.061 (3) C42D 0.8996 (3) 0.6763 (4) 0.1819 (3) 0.049 (2) C51C 0.7415 (4) 0.1250 (5) 0.1052 (4) 0.085 (4) C51D 0.6927 (3) 0.6680 (4) 0.1617 (3) 0.050 (2) C61C 0.7878 (3) 0.1152 (4) 0.1627 (4) 0.069 (3) C61D 0.7615 (3) 0.6803 (3) 0.1900 (4) 0.051 (2) H2A 0.86070 0.17080 0.84750 0.0770\* H2B 1.05040 0.03830 0.94750 0.0500\* H3A 0.79250 0.27180 0.90020 0.0770\* H3B 1.01130 −0.06760 1.01810 0.0540\* H5A 0.97650 0.38550 0.95760 0.0800\* H5B 0.86700 −0.13300 0.87090 0.0540\* H6A 1.04280 0.27900 0.90520 0.0690\* H6B 0.90830 −0.02500 0.80340 0.0530\* H21A 0.70790 0.36740 1.02590 0.1180\* H21B 0.76920 −0.19370 0.95350 0.0590\* H31A 0.67470 0.36220 1.13990 0.1280\* H31B 0.65800 −0.15520 1.00160 0.0630\* H42A 0.86090 0.46230 0.96660 0.0960\* H42B 0.94180 −0.19310 1.03670 0.0540\* H43A 0.78850 0.41860 0.94130 0.0960\* H43B 0.89930 −0.23270 0.97310 0.0540\* H51A 0.88020 0.39410 1.20090 0.0860\* H51B 0.76080 −0.08890 1.17890 0.0500\* H61A 0.91370 0.41040 1.08290 0.0820\* H61B 0.87270 −0.11920 1.12790 0.0570\* H2C 0.92080 0.24520 0.40670 0.0560\* H2D 1.07640 0.50710 0.26670 0.0720\* H3C 0.87990 0.12900 0.34790 0.0600\* H3D 1.03090 0.60580 0.19040 0.0670\* H5C 0.98570 0.20820 0.17820 0.0610\* H5D 0.84060 0.59430 0.29160 0.0660\* H6 0.89140 0.49860 0.36650 0.0630\* H6C 1.02390 0.32410 0.24070 0.0650\* H21C 0.93370 0.06470 0.08190 0.0670\* H21D 0.85770 0.60700 0.06250 0.0480\* H31C 0.86160 0.07670 −0.01470 0.0720\* H31D 0.74240 0.58810 0.01190 0.0580\* H42C 0.88150 0.03960 0.24980 0.0730\* H42D 0.93370 0.68300 0.14310 0.0590\* H43C 0.95150 0.04760 0.20250 0.0730\* H43D 0.89760 0.72940 0.20680 0.0590\* H51C 0.69290 0.14130 0.11120 0.1020\* H51D 0.65060 0.68170 0.18700 0.0600\* H61C 0.76970 0.12520 0.20770 0.0830\* H61D 0.76650 0.70340 0.23460 0.0610\* ------ ------------- ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e2155 .table-wrap} ------ ------------ ------------ ------------ ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ I1 0.0442 (2) 0.0799 (3) 0.0313 (2) −0.0069 (2) −0.0057 (2) 0.0026 (2) I2 0.0398 (2) 0.0944 (3) 0.0359 (2) −0.0126 (2) −0.0025 (2) 0.0057 (2) Zn1 0.0402 (3) 0.0605 (4) 0.0289 (4) −0.0065 (3) −0.0014 (3) 0.0019 (3) O41A 0.108 (6) 0.285 (11) 0.143 (8) 0.053 (6) 0.055 (5) 0.074 (6) O41B 0.081 (3) 0.107 (4) 0.042 (3) 0.013 (3) 0.015 (3) −0.013 (3) O42A 0.097 (4) 0.186 (6) 0.085 (5) 0.013 (5) 0.010 (4) 0.029 (5) O42B 0.048 (3) 0.181 (6) 0.070 (4) 0.016 (3) 0.000 (3) −0.004 (4) N1A 0.046 (3) 0.055 (3) 0.031 (3) −0.008 (2) −0.001 (2) −0.005 (2) N1B 0.036 (2) 0.054 (3) 0.028 (3) −0.002 (2) −0.001 (2) 0.003 (2) N41A 0.100 (6) 0.260 (12) 0.079 (7) 0.001 (8) 0.027 (5) 0.046 (8) N41B 0.068 (4) 0.062 (4) 0.051 (4) 0.005 (3) 0.011 (3) 0.002 (3) C2A 0.061 (4) 0.063 (4) 0.068 (5) −0.004 (3) 0.005 (4) −0.009 (4) C2B 0.036 (3) 0.058 (4) 0.030 (3) −0.006 (3) −0.001 (3) 0.000 (3) C3A 0.057 (4) 0.070 (5) 0.067 (5) 0.009 (4) −0.003 (3) −0.007 (4) C3B 0.036 (3) 0.070 (4) 0.028 (3) 0.004 (3) −0.001 (3) 0.002 (3) C4A 0.062 (4) 0.056 (4) 0.041 (4) 0.013 (4) 0.010 (3) 0.005 (3) C4B 0.036 (3) 0.047 (4) 0.032 (4) 0.007 (3) 0.006 (3) −0.004 (3) C5A 0.084 (5) 0.066 (5) 0.049 (4) −0.013 (4) −0.002 (4) −0.006 (4) C5B 0.043 (3) 0.050 (4) 0.041 (4) −0.008 (3) −0.008 (3) −0.002 (3) C6A 0.057 (4) 0.072 (5) 0.045 (4) −0.001 (4) −0.003 (3) −0.003 (3) C6B 0.046 (3) 0.059 (4) 0.027 (3) −0.004 (3) −0.009 (2) 0.002 (3) C11A 0.063 (4) 0.055 (4) 0.049 (5) 0.023 (3) −0.007 (4) −0.008 (3) C11B 0.038 (3) 0.031 (3) 0.034 (4) 0.003 (3) 0.006 (2) 0.002 (3) C21A 0.048 (4) 0.168 (9) 0.079 (7) 0.006 (5) −0.014 (4) −0.020 (6) C21B 0.044 (3) 0.064 (4) 0.039 (4) 0.004 (3) 0.001 (3) −0.007 (3) C31A 0.056 (5) 0.196 (10) 0.068 (6) −0.019 (6) 0.003 (4) 0.014 (7) C31B 0.044 (3) 0.066 (4) 0.046 (4) 0.003 (3) −0.013 (3) −0.001 (3) C41A 0.063 (4) 0.108 (6) 0.064 (6) 0.008 (4) 0.005 (4) 0.004 (5) C41B 0.041 (3) 0.036 (4) 0.042 (4) 0.007 (3) 0.008 (3) 0.005 (3) C42A 0.090 (5) 0.062 (5) 0.089 (6) 0.034 (4) −0.017 (5) −0.002 (4) C42B 0.045 (3) 0.041 (3) 0.050 (4) 0.003 (3) −0.004 (3) 0.006 (3) C51A 0.050 (4) 0.096 (6) 0.069 (6) 0.012 (4) −0.003 (4) 0.000 (4) C51B 0.059 (4) 0.039 (4) 0.027 (4) 0.005 (3) 0.007 (3) 0.005 (3) C61A 0.049 (4) 0.080 (5) 0.076 (6) 0.004 (4) 0.000 (4) 0.000 (4) C61B 0.046 (3) 0.053 (4) 0.045 (4) −0.006 (3) −0.005 (3) 0.006 (3) I3 0.0382 (2) 0.0769 (3) 0.0405 (3) 0.0048 (2) −0.0001 (2) −0.0048 (2) I4 0.0483 (2) 0.0798 (3) 0.0335 (2) 0.0107 (2) 0.0042 (2) 0.0021 (2) Zn2 0.0391 (3) 0.0570 (5) 0.0317 (4) 0.0012 (3) −0.0014 (3) 0.0019 (3) O41D 0.075 (3) 0.112 (5) 0.075 (5) −0.010 (3) −0.030 (3) 0.002 (3) O42C 0.101 (4) 0.171 (6) 0.062 (5) −0.020 (4) −0.020 (4) 0.002 (4) O42D 0.045 (3) 0.154 (5) 0.100 (5) 0.004 (3) 0.000 (3) −0.028 (4) N1C 0.035 (2) 0.049 (3) 0.035 (3) −0.003 (2) 0.003 (2) −0.001 (2) N1D 0.038 (2) 0.056 (3) 0.029 (3) 0.001 (2) 0.001 (2) 0.003 (2) N41C 0.049 (4) 0.158 (7) 0.077 (6) −0.013 (4) −0.012 (4) 0.017 (5) N41D 0.057 (4) 0.086 (5) 0.073 (5) −0.001 (3) −0.016 (4) 0.001 (4) C2C 0.044 (3) 0.062 (4) 0.034 (3) 0.007 (3) 0.003 (3) −0.001 (3) C2D 0.035 (3) 0.086 (5) 0.060 (4) 0.013 (3) 0.006 (3) 0.019 (4) C3C 0.050 (3) 0.056 (4) 0.044 (4) −0.008 (3) 0.003 (3) 0.011 (3) C3D 0.037 (3) 0.081 (5) 0.050 (4) −0.002 (3) 0.011 (3) 0.031 (4) C4C 0.045 (3) 0.044 (4) 0.055 (5) 0.002 (3) −0.018 (3) 0.008 (3) C4D 0.047 (3) 0.040 (4) 0.028 (3) −0.007 (3) −0.004 (3) 0.002 (3) C5C 0.055 (3) 0.065 (4) 0.033 (3) −0.003 (3) 0.003 (3) −0.004 (3) C5D 0.043 (3) 0.074 (5) 0.047 (4) 0.011 (3) 0.010 (3) 0.020 (4) C6C 0.045 (3) 0.074 (5) 0.043 (4) −0.010 (3) −0.003 (3) 0.007 (3) C6D 0.046 (3) 0.069 (4) 0.043 (4) −0.003 (3) 0.003 (3) 0.012 (3) C11C 0.044 (3) 0.035 (3) 0.052 (4) −0.004 (3) −0.006 (3) −0.007 (3) C11D 0.043 (3) 0.038 (3) 0.039 (4) −0.010 (3) −0.002 (3) 0.017 (3) C21C 0.048 (3) 0.066 (5) 0.054 (5) 0.006 (3) 0.003 (3) −0.005 (4) C21D 0.051 (3) 0.039 (4) 0.030 (4) 0.002 (3) 0.006 (3) −0.001 (3) C31C 0.051 (4) 0.072 (5) 0.056 (5) −0.003 (3) 0.009 (3) −0.001 (4) C31D 0.054 (3) 0.054 (4) 0.038 (4) 0.006 (3) −0.007 (3) −0.003 (3) C41C 0.045 (3) 0.082 (5) 0.048 (5) −0.016 (3) −0.015 (3) 0.006 (4) C41D 0.043 (3) 0.046 (4) 0.042 (4) 0.005 (3) −0.009 (3) −0.002 (3) C42C 0.083 (5) 0.050 (4) 0.049 (4) 0.001 (3) −0.011 (4) −0.009 (3) C42D 0.047 (3) 0.062 (4) 0.038 (4) −0.002 (3) 0.002 (3) 0.002 (3) C51C 0.042 (4) 0.160 (8) 0.054 (6) 0.012 (4) 0.007 (4) −0.003 (5) C51D 0.040 (3) 0.060 (4) 0.050 (4) 0.004 (3) 0.006 (3) 0.002 (3) C61C 0.053 (4) 0.107 (6) 0.048 (5) 0.004 (4) 0.014 (3) −0.011 (4) C61D 0.057 (4) 0.064 (4) 0.031 (3) −0.004 (3) 0.006 (3) −0.004 (3) ------ ------------ ------------ ------------ ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e3427 .table-wrap} --------------------------- ------------- --------------------------- ------------ I1---Zn1 2.5578 (7) C6A---H6A 0.9300 I2---Zn1 2.5525 (7) C6B---H6B 0.9300 I3---Zn2 2.5666 (7) C21A---H21A 0.9300 I4---Zn2 2.5472 (8) C21B---H21B 0.9300 Zn1---N1A 2.052 (4) C31A---H31A 0.9300 Zn1---N1B 2.052 (4) C31B---H31B 0.9300 Zn2---N1C 2.044 (4) C42A---H42A 0.9700 Zn2---N1D 2.048 (4) C42A---H43A 0.9700 O41A---N41A 1.280 (13) C42B---H42B 0.9700 O41B---N41B 1.207 (9) C42B---H43B 0.9700 O42A---N41A 1.207 (13) C51A---H51A 0.9300 O42B---N41B 1.217 (8) C51B---H51B 0.9300 O41C---N41C 1.280 (9) C61A---H61A 0.9300 O41D---N41D 1.236 (11) C61B---H61B 0.9300 O42C---N41C 1.174 (11) C2C---C3C 1.379 (9) O42D---N41D 1.187 (8) C2D---C3D 1.385 (8) N1A---C2A 1.348 (7) C3C---C4C 1.365 (9) N1A---C6A 1.324 (7) C3D---C4D 1.371 (8) N1B---C2B 1.350 (7) C4C---C5C 1.367 (9) N1B---C6B 1.347 (7) C4C---C42C 1.502 (9) N41A---C41A 1.495 (13) C4D---C5D 1.377 (8) N41B---C41B 1.476 (8) C4D---C42D 1.496 (8) N1C---C6C 1.343 (7) C5C---C6C 1.388 (9) N1C---C2C 1.326 (7) C5D---C6D 1.378 (8) N1D---C6D 1.325 (7) C11C---C21C 1.364 (9) N1D---C2D 1.327 (7) C11C---C42C 1.505 (8) N41C---C41C 1.472 (10) C11C---C61C 1.367 (8) N41D---C41D 1.484 (8) C11D---C21D 1.355 (8) C2A---C3A 1.354 (8) C11D---C42D 1.528 (8) C2B---C3B 1.365 (8) C11D---C61D 1.390 (8) C3A---C4A 1.375 (9) C21C---C31C 1.345 (10) C3B---C4B 1.377 (8) C21D---C31D 1.388 (8) C4A---C5A 1.346 (10) C31C---C41C 1.400 (8) C4A---C42A 1.527 (9) C31D---C41D 1.371 (8) C4B---C42B 1.507 (7) C41C---C51C 1.366 (11) C4B---C5B 1.377 (8) C41D---C51D 1.365 (8) C5A---C6A 1.390 (9) C51C---C61C 1.390 (10) C5B---C6B 1.369 (8) C51D---C61D 1.378 (8) C11A---C61A 1.377 (11) C2C---H2C 0.9300 C11A---C21A 1.331 (10) C2D---H2D 0.9300 C11A---C42A 1.505 (11) C3C---H3C 0.9300 C11B---C42B 1.516 (8) C3D---H3D 0.9300 C11B---C61B 1.384 (9) C5C---H5C 0.9300 C11B---C21B 1.390 (8) C5D---H5D 0.9300 C21A---C31A 1.331 (13) C6C---H6C 0.9300 C21B---C31B 1.372 (8) C6D---H6 0.9300 C31A---C41A 1.346 (12) C21C---H21C 0.9300 C31B---C41B 1.370 (8) C21D---H21D 0.9300 C41A---C51A 1.354 (10) C31C---H31C 0.9300 C41B---C51B 1.368 (8) C31D---H31D 0.9300 C51A---C61A 1.392 (12) C42C---H42C 0.9700 C51B---C61B 1.376 (8) C42C---H43C 0.9700 C2A---H2A 0.9300 C42D---H42D 0.9700 C2B---H2B 0.9300 C42D---H43D 0.9700 C3A---H3A 0.9300 C51C---H51C 0.9300 C3B---H3B 0.9300 C51D---H51D 0.9300 C5A---H5A 0.9300 C61C---H61C 0.9300 C5B---H5B 0.9300 C61D---H61D 0.9300 I1---Zn1---I2 119.96 (2) C4A---C42A---H43A 109.00 I1---Zn1---N1A 105.83 (11) C4A---C42A---H42A 109.00 I1---Zn1---N1B 111.55 (11) H42A---C42A---H43A 108.00 I2---Zn1---N1A 110.54 (11) C11A---C42A---H43A 109.00 I2---Zn1---N1B 107.94 (11) C11A---C42A---H42A 109.00 N1A---Zn1---N1B 98.99 (17) C11B---C42B---H42B 109.00 I4---Zn2---N1D 110.49 (11) C4B---C42B---H43B 109.00 N1C---Zn2---N1D 99.42 (17) C4B---C42B---H42B 109.00 I3---Zn2---I4 120.39 (3) C11B---C42B---H43B 109.00 I3---Zn2---N1C 104.77 (11) H42B---C42B---H43B 108.00 I3---Zn2---N1D 109.76 (11) C41A---C51A---H51A 121.00 I4---Zn2---N1C 109.83 (11) C61A---C51A---H51A 121.00 Zn1---N1A---C6A 123.6 (3) C61B---C51B---H51B 120.00 C2A---N1A---C6A 117.3 (5) C41B---C51B---H51B 120.00 Zn1---N1A---C2A 118.9 (4) C11A---C61A---H61A 120.00 Zn1---N1B---C6B 124.1 (3) C51A---C61A---H61A 120.00 Zn1---N1B---C2B 119.9 (3) C11B---C61B---H61B 120.00 C2B---N1B---C6B 115.9 (4) C51B---C61B---H61B 120.00 O41A---N41A---C41A 112.9 (8) N1C---C2C---C3C 123.3 (5) O41A---N41A---O42A 126.1 (9) N1D---C2D---C3D 123.0 (5) O42A---N41A---C41A 120.7 (9) C2C---C3C---C4C 120.0 (6) O42B---N41B---C41B 118.6 (7) C2D---C3D---C4D 120.4 (5) O41B---N41B---O42B 122.8 (6) C3C---C4C---C5C 117.6 (6) O41B---N41B---C41B 118.6 (6) C3C---C4C---C42C 121.8 (6) Zn2---N1C---C2C 124.7 (4) C5C---C4C---C42C 120.6 (6) Zn2---N1C---C6C 118.4 (4) C3D---C4D---C5D 116.2 (5) C2C---N1C---C6C 116.8 (5) C3D---C4D---C42D 121.0 (5) Zn2---N1D---C2D 122.5 (4) C5D---C4D---C42D 122.7 (5) Zn2---N1D---C6D 120.5 (3) C4C---C5C---C6C 119.8 (6) C2D---N1D---C6D 116.8 (5) C4D---C5D---C6D 120.4 (5) O41C---N41C---O42C 125.2 (7) N1C---C6C---C5C 122.6 (5) O41C---N41C---C41C 110.9 (7) N1D---C6D---C5D 123.1 (5) O42C---N41C---C41C 123.8 (6) C21C---C11C---C42C 121.8 (5) O41D---N41D---C41D 116.9 (6) C21C---C11C---C61C 118.0 (6) O42D---N41D---C41D 120.0 (7) C42C---C11C---C61C 120.3 (6) O41D---N41D---O42D 123.1 (6) C21D---C11D---C42D 120.8 (5) N1A---C2A---C3A 123.5 (5) C21D---C11D---C61D 119.8 (5) N1B---C2B---C3B 123.2 (5) C42D---C11D---C61D 119.4 (5) C2A---C3A---C4A 119.0 (5) C11C---C21C---C31C 123.8 (5) C2B---C3B---C4B 120.6 (5) C11D---C21D---C31D 121.9 (5) C3A---C4A---C5A 118.2 (6) C21C---C31C---C41C 117.2 (7) C3A---C4A---C42A 120.1 (6) C21D---C31D---C41D 116.5 (6) C5A---C4A---C42A 121.5 (6) N41C---C41C---C31C 115.8 (6) C3B---C4B---C5B 116.7 (5) N41C---C41C---C51C 122.8 (6) C3B---C4B---C42B 121.4 (5) C31C---C41C---C51C 121.4 (7) C5B---C4B---C42B 121.9 (5) N41D---C41D---C31D 118.7 (6) C4A---C5A---C6A 120.5 (6) N41D---C41D---C51D 117.5 (5) C4B---C5B---C6B 120.2 (5) C31D---C41D---C51D 123.7 (5) N1A---C6A---C5A 121.4 (5) C4C---C42C---C11C 114.9 (5) N1B---C6B---C5B 123.4 (5) C4D---C42D---C11D 115.4 (5) C21A---C11A---C42A 120.6 (7) C41C---C51C---C61C 118.4 (6) C42A---C11A---C61A 118.8 (6) C41D---C51D---C61D 118.3 (5) C21A---C11A---C61A 120.5 (8) C11C---C61C---C51C 121.2 (7) C21B---C11B---C61B 118.2 (5) C11D---C61D---C51D 119.8 (6) C42B---C11B---C61B 121.9 (5) N1C---C2C---H2C 118.00 C21B---C11B---C42B 119.9 (5) C3C---C2C---H2C 118.00 C11A---C21A---C31A 119.6 (8) N1D---C2D---H2D 118.00 C11B---C21B---C31B 121.7 (6) C3D---C2D---H2D 119.00 C21A---C31A---C41A 121.9 (7) C2C---C3C---H3C 120.00 C21B---C31B---C41B 118.1 (5) C4C---C3C---H3C 120.00 N41A---C41A---C51A 117.2 (8) C2D---C3D---H3D 120.00 C31A---C41A---C51A 120.5 (9) C4D---C3D---H3D 120.00 N41A---C41A---C31A 122.3 (8) C4C---C5C---H5C 120.00 N41B---C41B---C51B 119.5 (5) C6C---C5C---H5C 120.00 C31B---C41B---C51B 122.1 (5) C4D---C5D---H5D 120.00 N41B---C41B---C31B 118.4 (5) C6D---C5D---H5D 120.00 C4A---C42A---C11A 113.5 (5) N1C---C6C---H6C 119.00 C4B---C42B---C11B 111.8 (4) C5C---C6C---H6C 119.00 C41A---C51A---C61A 117.9 (8) N1D---C6D---H6 119.00 C41B---C51B---C61B 119.1 (6) C5D---C6D---H6 118.00 C11A---C61A---C51A 119.4 (7) C11C---C21C---H21C 118.00 C11B---C61B---C51B 120.8 (5) C31C---C21C---H21C 118.00 N1A---C2A---H2A 118.00 C11D---C21D---H21D 119.00 C3A---C2A---H2A 118.00 C31D---C21D---H21D 119.00 N1B---C2B---H2B 118.00 C21C---C31C---H31C 121.00 C3B---C2B---H2B 118.00 C41C---C31C---H31C 121.00 C2A---C3A---H3A 120.00 C21D---C31D---H31D 122.00 C4A---C3A---H3A 121.00 C41D---C31D---H31D 122.00 C4B---C3B---H3B 120.00 C4C---C42C---H42C 109.00 C2B---C3B---H3B 120.00 C4C---C42C---H43C 109.00 C4A---C5A---H5A 120.00 C11C---C42C---H42C 108.00 C6A---C5A---H5A 120.00 C11C---C42C---H43C 109.00 C4B---C5B---H5B 120.00 H42C---C42C---H43C 108.00 C6B---C5B---H5B 120.00 C4D---C42D---H42D 108.00 N1A---C6A---H6A 119.00 C4D---C42D---H43D 108.00 C5A---C6A---H6A 119.00 C11D---C42D---H42D 108.00 C5B---C6B---H6B 118.00 C11D---C42D---H43D 108.00 N1B---C6B---H6B 118.00 H42D---C42D---H43D 107.00 C11A---C21A---H21A 120.00 C41C---C51C---H51C 121.00 C31A---C21A---H21A 120.00 C61C---C51C---H51C 121.00 C11B---C21B---H21B 119.00 C41D---C51D---H51D 121.00 C31B---C21B---H21B 119.00 C61D---C51D---H51D 121.00 C41A---C31A---H31A 119.00 C11C---C61C---H61C 119.00 C21A---C31A---H31A 119.00 C51C---C61C---H61C 119.00 C21B---C31B---H31B 121.00 C11D---C61D---H61D 120.00 C41B---C31B---H31B 121.00 C51D---C61D---H61D 120.00 I1---Zn1---N1A---C2A 49.9 (4) C5B---C4B---C42B---C11B −76.6 (7) I1---Zn1---N1A---C6A −124.7 (4) C3B---C4B---C42B---C11B 102.9 (6) I2---Zn1---N1A---C2A −178.7 (4) C4A---C5A---C6A---N1A 1.8 (10) I2---Zn1---N1A---C6A 6.7 (5) C4B---C5B---C6B---N1B −0.3 (9) N1B---Zn1---N1A---C2A −65.6 (4) C42A---C11A---C61A---C51A 175.8 (6) N1B---Zn1---N1A---C6A 119.8 (4) C61A---C11A---C21A---C31A 5.3 (13) I1---Zn1---N1B---C2B 173.9 (3) C21A---C11A---C42A---C4A −108.2 (8) I1---Zn1---N1B---C6B −9.9 (4) C42A---C11A---C21A---C31A −173.0 (8) I2---Zn1---N1B---C2B 40.1 (4) C21A---C11A---C61A---C51A −2.6 (10) I2---Zn1---N1B---C6B −143.7 (4) C61A---C11A---C42A---C4A 73.5 (8) N1A---Zn1---N1B---C2B −75.0 (4) C61B---C11B---C21B---C31B 2.3 (8) N1A---Zn1---N1B---C6B 101.1 (4) C42B---C11B---C21B---C31B −179.1 (5) I3---Zn2---N1D---C6D −171.8 (4) C21B---C11B---C42B---C4B 83.4 (6) I4---Zn2---N1D---C2D 148.3 (4) C61B---C11B---C42B---C4B −98.1 (6) I4---Zn2---N1D---C6D −36.8 (4) C21B---C11B---C61B---C51B 0.1 (8) N1C---Zn2---N1D---C2D −96.3 (4) C42B---C11B---C61B---C51B −178.5 (5) N1C---Zn2---N1D---C6D 78.6 (4) C11A---C21A---C31A---C41A −5.6 (14) I4---Zn2---N1C---C2C −9.4 (5) C11B---C21B---C31B---C41B −3.8 (9) I4---Zn2---N1C---C6C 175.3 (4) C21A---C31A---C41A---N41A −180.0 (9) N1D---Zn2---N1C---C2C −125.4 (4) C21A---C31A---C41A---C51A 3.1 (14) N1D---Zn2---N1C---C6C 59.4 (4) C21B---C31B---C41B---N41B −176.0 (5) I3---Zn2---N1D---C2D 13.3 (5) C21B---C31B---C41B---C51B 2.9 (8) I3---Zn2---N1C---C2C 121.2 (4) C31A---C41A---C51A---C61A −0.3 (11) I3---Zn2---N1C---C6C −54.1 (4) N41A---C41A---C51A---C61A −177.4 (7) C2A---N1A---C6A---C5A −1.1 (8) N41B---C41B---C51B---C61B 178.2 (5) Zn1---N1A---C6A---C5A 173.6 (5) C31B---C41B---C51B---C61B −0.7 (8) Zn1---N1A---C2A---C3A −174.7 (5) C41A---C51A---C61A---C11A 0.1 (10) C6A---N1A---C2A---C3A 0.2 (8) C41B---C51B---C61B---C11B −0.9 (9) Zn1---N1B---C6B---C5B −173.9 (4) N1C---C2C---C3C---C4C −0.4 (9) C2B---N1B---C6B---C5B 2.4 (8) N1D---C2D---C3D---C4D −0.3 (9) Zn1---N1B---C2B---C3B 173.8 (4) C2C---C3C---C4C---C5C −1.1 (9) C6B---N1B---C2B---C3B −2.7 (8) C2C---C3C---C4C---C42C 176.0 (6) O41A---N41A---C41A---C51A 163.4 (8) C2D---C3D---C4D---C5D 2.0 (8) O41A---N41A---C41A---C31A −13.6 (13) C2D---C3D---C4D---C42D 178.8 (5) O42A---N41A---C41A---C31A 172.3 (9) C3C---C4C---C5C---C6C 0.9 (9) O42A---N41A---C41A---C51A −10.7 (13) C42C---C4C---C5C---C6C −176.2 (6) O41B---N41B---C41B---C31B 164.8 (5) C3C---C4C---C42C---C11C 118.7 (6) O42B---N41B---C41B---C31B −12.7 (8) C5C---C4C---C42C---C11C −64.4 (8) O42B---N41B---C41B---C51B 168.3 (5) C3D---C4D---C5D---C6D −1.3 (8) O41B---N41B---C41B---C51B −14.2 (7) C42D---C4D---C5D---C6D −178.0 (5) Zn2---N1C---C6C---C5C 173.4 (4) C3D---C4D---C42D---C11D 135.3 (6) Zn2---N1C---C2C---C3C −173.3 (4) C5D---C4D---C42D---C11D −48.1 (8) C6C---N1C---C2C---C3C 2.1 (8) C4C---C5C---C6C---N1C 0.8 (9) C2C---N1C---C6C---C5C −2.2 (8) C4D---C5D---C6D---N1D −1.3 (9) Zn2---N1D---C2D---C3D 172.8 (4) C42C---C11C---C21C---C31C 176.1 (6) C6D---N1D---C2D---C3D −2.3 (8) C61C---C11C---C21C---C31C −2.5 (9) C2D---N1D---C6D---C5D 3.1 (8) C21C---C11C---C42C---C4C 110.0 (6) Zn2---N1D---C6D---C5D −172.2 (4) C61C---C11C---C42C---C4C −71.4 (7) O42C---N41C---C41C---C31C 1.9 (11) C21C---C11C---C61C---C51C 1.8 (9) O42C---N41C---C41C---C51C −175.3 (8) C42C---C11C---C61C---C51C −176.9 (6) O41C---N41C---C41C---C31C −175.3 (6) C42D---C11D---C21D---C31D −175.6 (5) O41C---N41C---C41C---C51C 7.5 (10) C61D---C11D---C21D---C31D 1.9 (8) O41D---N41D---C41D---C51D 165.3 (6) C21D---C11D---C42D---C4D −97.1 (6) O42D---N41D---C41D---C31D 167.7 (6) C61D---C11D---C42D---C4D 85.4 (6) O42D---N41D---C41D---C51D −14.8 (10) C21D---C11D---C61D---C51D −0.8 (8) O41D---N41D---C41D---C31D −12.3 (9) C42D---C11D---C61D---C51D 176.7 (5) N1A---C2A---C3A---C4A 0.1 (9) C11C---C21C---C31C---C41C 1.5 (10) N1B---C2B---C3B---C4B 0.9 (9) C11D---C21D---C31D---C41D −1.0 (8) C2A---C3A---C4A---C42A 177.2 (6) C21C---C31C---C41C---N41C −176.9 (6) C2A---C3A---C4A---C5A 0.5 (9) C21C---C31C---C41C---C51C 0.3 (10) C2B---C3B---C4B---C42B −178.2 (5) C21D---C31D---C41D---N41D 176.4 (5) C2B---C3B---C4B---C5B 1.3 (8) C21D---C31D---C41D---C51D −1.1 (9) C3A---C4A---C42A---C11A 89.9 (7) N41C---C41C---C51C---C61C 176.1 (7) C42A---C4A---C5A---C6A −178.1 (6) C31C---C41C---C51C---C61C −0.9 (11) C3A---C4A---C5A---C6A −1.4 (10) N41D---C41D---C51D---C61D −175.3 (6) C5A---C4A---C42A---C11A −93.5 (8) C31D---C41D---C51D---C61D 2.1 (10) C3B---C4B---C5B---C6B −1.6 (8) C41C---C51C---C61C---C11C −0.2 (10) C42B---C4B---C5B---C6B 177.9 (5) C41D---C51D---C61D---C11D −1.1 (9) --------------------------- ------------- --------------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e5613 .table-wrap} ---------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C5A---H5A···O41D^i^ 0.93 2.57 3.211 (9) 126 C6B---H6B···O41B^ii^ 0.93 2.49 3.295 (8) 145 ---------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) *x*+1/2, −*y*+1, *z*+1; (ii) −*x*+3/2, *y*, *z*−1/2.

PubMed Central

2024-06-05T04:04:18.889453

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052165/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):m359", "authors": [ { "first": "Graham", "last": "Smith" }, { "first": "Urs D.", "last": "Wermuth" }, { "first": "Michael L.", "last": "Williams" } ] }

PMC3052166

Related literature {#sec1} ================== For another ammonium tetrachlorido(pyridine-2-carboxylato)stannate, see: Najafi *et al.* (2011[@bb3]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} (C~6~H~16~N)\[SnCl~4~(C~6~H~4~NO~2~)\]*M* *~r~* = 484.79Monoclinic,*a* = 11.6310 (7) Å*b* = 10.4912 (6) Å*c* = 16.4452 (9) Åβ = 109.672 (1)°*V* = 1889.57 (19) Å^3^*Z* = 4Mo *K*α radiationμ = 1.92 mm^−1^*T* = 100 K0.30 × 0.25 × 0.05 mm ### Data collection {#sec2.1.2} Bruker SMART APEX diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1996[@bb4]) *T* ~min~ = 0.596, *T* ~max~ = 0.91017476 measured reflections4344 independent reflections3896 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.033 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.019*wR*(*F* ^2^) = 0.048*S* = 1.014344 reflections242 parameters25 restraintsH-atom parameters constrainedΔρ~max~ = 0.41 e Å^−3^Δρ~min~ = −0.39 e Å^−3^ {#d5e459} Data collection: *APEX2* (Bruker, 2009[@bb2]); cell refinement: *SAINT* (Bruker, 2009[@bb2]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb5]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb5]); molecular graphics: *X-SEED* (Barbour, 2001[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005460/si2335sup1.cif](http://dx.doi.org/10.1107/S1600536811005460/si2335sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005460/si2335Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005460/si2335Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?si2335&file=si2335sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?si2335sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?si2335&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [SI2335](http://scripts.iucr.org/cgi-bin/sendsup?si2335)). We thank the University of Malaya for supporting this study. Comment ======= In the reaction of pyridine-2-carboxylic acid and stannic chloride in methanol, one equivalent of the carboxylic acid is protonated at the amino site and is also esterified, the reaction yielding the salt, (C~7~H~8~NO~2~)^+^ \[SnCl~4~(C~6~H~4~NO~2~)\]^-^. The Sn^IV^ atom in the anion is *N*,*O*-chelated by the pyridine-2-carboxylate in a *cis*-SnNOCl~4~ octahedral geometry (Najafi *et al.*, 2011). In the present study, triethylamine was added to function as proton abstractor. The reaction affords a similar salt, (Et~3~NH)^+^ \[SnCl~4~(C~6~H~4~NO~2~)\]^-^ (Scheme I, Fig. 1). The tin atom in the stannate is chelated by the pyridine-2-carboxylate group and it exists in a *cis*-SnCl~4~NO octahedral geometry. Experimental {#experimental} ============ The reaction was carried out under a nitrogen atmosphere. Pyridine-2-carboxylic acid (1.0 mmol, 0.12 g) and the triethylamine (1.0 mmol, 0.10 g) were dissolved in dry methanol (20 ml). Stannic chloride ((1.0 mmol, 0.35 g) was added to the mixture and stirred for 12 h. Suitable crystals were obtained by slow evaporation of the solvent. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions (C---H 0.95 to 0.99, N--H 0.88 Å) and were included in the refinement in the riding model approximation, with *U*(H) set to 1.2 to 1.5*U*(C). The triethylammonium cation is disordered over two positions in a 56.4 (1): 43.6 (1) ratio. The N--C distances were restrained to within 0.01 Å of each other, as were the C--C distances. Because the C11\' atom is close to the C11 atom (the C12\' atom is also close to the C12 atom), the temperature factors of the C11\' atom were restrained to those of the C11 atom; those of the C12\' atom were set to those of the C12 atom. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of (Et3NH)+ \[SnCl4(C6H4NO2)\]- at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. The disorder in the cation is not shown. ::: ![](e-67-0m351-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e195 .table-wrap} ---------------------------------------- --------------------------------------- (C~6~H~16~N)\[SnCl~4~(C~6~H~4~NO~2~)\] *F*(000) = 960 *M~r~* = 484.79 *D*~x~ = 1.704 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 8286 reflections *a* = 11.6310 (7) Å θ = 2.3--28.3° *b* = 10.4912 (6) Å µ = 1.92 mm^−1^ *c* = 16.4452 (9) Å *T* = 100 K β = 109.672 (1)° Prism, colorless *V* = 1889.57 (19) Å^3^ 0.30 × 0.25 × 0.05 mm *Z* = 4 ---------------------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e333 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART APEX diffractometer 4344 independent reflections Radiation source: fine-focus sealed tube 3896 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.033 ω scans θ~max~ = 27.5°, θ~min~ = 2.3° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1996) *h* = −15→15 *T*~min~ = 0.596, *T*~max~ = 0.910 *k* = −13→13 17476 measured reflections *l* = −19→21 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e447 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.019 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.048 H-atom parameters constrained *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0213*P*)^2^ + 0.5451*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4344 reflections (Δ/σ)~max~ = 0.001 242 parameters Δρ~max~ = 0.41 e Å^−3^ 25 restraints Δρ~min~ = −0.39 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e606 .table-wrap} ------- --------------- --------------- -------------- -------------------- ------------ *x* *y* *z* *U*~iso~\*/*U*~eq~ Occ. (\<1) Sn1 0.563342 (11) 0.304590 (11) 0.743404 (8) 0.01440 (5) Cl1 0.37811 (4) 0.38342 (5) 0.64455 (3) 0.02443 (11) Cl2 0.47250 (5) 0.23860 (5) 0.84821 (3) 0.02561 (11) Cl3 0.56293 (4) 0.08950 (4) 0.69586 (3) 0.01948 (10) Cl4 0.67771 (4) 0.36886 (4) 0.65317 (3) 0.01872 (10) O1 0.59288 (12) 0.48336 (12) 0.80497 (8) 0.0200 (3) O2 0.69627 (13) 0.58704 (13) 0.92554 (9) 0.0263 (3) N1 0.74369 (14) 0.28596 (14) 0.84631 (10) 0.0150 (3) C1 0.68201 (17) 0.49487 (17) 0.87734 (12) 0.0187 (4) C2 0.77238 (17) 0.38638 (17) 0.90022 (11) 0.0151 (4) C3 0.87950 (17) 0.39107 (17) 0.96906 (12) 0.0183 (4) H3 0.8968 0.4612 1.0079 0.022\* C4 0.96192 (18) 0.29127 (18) 0.98084 (12) 0.0207 (4) H4 1.0377 0.2933 1.0269 0.025\* C5 0.93224 (19) 0.18882 (18) 0.92456 (12) 0.0208 (4) H5 0.9873 0.1195 0.9317 0.025\* C6 0.82192 (18) 0.18857 (17) 0.85810 (12) 0.0189 (4) H6 0.8009 0.1178 0.8199 0.023\* N2 0.5100 (3) 0.7717 (3) 0.8635 (2) 0.0168 (8) 0.564 (3) H2 0.5718 0.7181 0.8804 0.020\* 0.564 (3) C7 0.5607 (4) 0.9017 (4) 0.8956 (3) 0.0209 (9) 0.564 (3) H7A 0.6002 0.9376 0.8559 0.025\* 0.564 (3) H7B 0.4927 0.9589 0.8948 0.025\* 0.564 (3) C8 0.6523 (4) 0.8976 (4) 0.9858 (3) 0.0289 (9) 0.564 (3) H8A 0.6834 0.9837 1.0035 0.043\* 0.564 (3) H8B 0.7203 0.8416 0.9868 0.043\* 0.564 (3) H8C 0.6130 0.8648 1.0256 0.043\* 0.564 (3) C9 0.4203 (3) 0.7295 (3) 0.9059 (2) 0.0227 (8) 0.564 (3) H9A 0.3543 0.7936 0.8941 0.027\* 0.564 (3) H9B 0.4623 0.7263 0.9691 0.027\* 0.564 (3) C10 0.3642 (5) 0.6008 (5) 0.8754 (4) 0.0307 (12) 0.564 (3) H10A 0.3067 0.5791 0.9053 0.046\* 0.564 (3) H10B 0.4286 0.5361 0.8882 0.046\* 0.564 (3) H10C 0.3207 0.6036 0.8130 0.046\* 0.564 (3) C11 0.4630 (14) 0.7685 (17) 0.7665 (4) 0.0215 (11) 0.564 (3) H11A 0.4388 0.6801 0.7472 0.026\* 0.564 (3) H11B 0.5297 0.7934 0.7450 0.026\* 0.564 (3) C12 0.3551 (13) 0.8558 (13) 0.7272 (9) 0.0279 (18) 0.564 (3) H12A 0.3340 0.8565 0.6643 0.042\* 0.564 (3) H12B 0.3762 0.9423 0.7497 0.042\* 0.564 (3) H12C 0.2852 0.8250 0.7422 0.042\* 0.564 (3) N2\' 0.4707 (4) 0.7281 (4) 0.8540 (3) 0.0178 (10) 0.436 (3) H2\' 0.5376 0.6845 0.8801 0.021\* 0.436 (3) C7\' 0.4711 (4) 0.8380 (4) 0.9124 (3) 0.0232 (11) 0.436 (3) H7\'A 0.4561 0.8058 0.9645 0.028\* 0.436 (3) H7\'B 0.4036 0.8968 0.8822 0.028\* 0.436 (3) C8\' 0.5902 (5) 0.9107 (6) 0.9395 (5) 0.0281 (14) 0.436 (3) H8\'A 0.5857 0.9819 0.9770 0.042\* 0.436 (3) H8\'B 0.6050 0.9438 0.8882 0.042\* 0.436 (3) H8\'C 0.6570 0.8537 0.9711 0.042\* 0.436 (3) C9\' 0.3664 (5) 0.6386 (5) 0.8450 (4) 0.0206 (12) 0.436 (3) H9\'A 0.3600 0.5777 0.7977 0.025\* 0.436 (3) H9\'B 0.2895 0.6881 0.8289 0.025\* 0.436 (3) C10\' 0.3807 (5) 0.5650 (5) 0.9267 (4) 0.0288 (12) 0.436 (3) H10D 0.3119 0.5061 0.9166 0.043\* 0.436 (3) H10E 0.3822 0.6245 0.9730 0.043\* 0.436 (3) H10F 0.4572 0.5167 0.9435 0.043\* 0.436 (3) C11\' 0.4774 (19) 0.765 (2) 0.7673 (6) 0.0215 (11) 0.44 H11C 0.4877 0.6871 0.7366 0.026\* 0.436 (3) H11D 0.5502 0.8194 0.7762 0.026\* 0.436 (3) C12\' 0.3646 (18) 0.8367 (19) 0.7110 (11) 0.0279 (18) 0.44 H12D 0.3698 0.8490 0.6533 0.042\* 0.436 (3) H12E 0.3603 0.9198 0.7370 0.042\* 0.436 (3) H12F 0.2913 0.7872 0.7066 0.042\* 0.436 (3) ------- --------------- --------------- -------------- -------------------- ------------ ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1462 .table-wrap} ------- ------------- ------------- ------------- --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Sn1 0.01336 (7) 0.01342 (7) 0.01478 (7) 0.00074 (5) 0.00259 (5) −0.00027 (5) Cl1 0.0152 (2) 0.0307 (3) 0.0233 (2) 0.00400 (19) 0.00109 (19) 0.00435 (19) Cl2 0.0271 (3) 0.0307 (3) 0.0228 (2) 0.0027 (2) 0.0133 (2) 0.0037 (2) Cl3 0.0254 (2) 0.0132 (2) 0.0181 (2) −0.00356 (17) 0.00515 (18) −0.00112 (17) Cl4 0.0195 (2) 0.0163 (2) 0.0205 (2) −0.00436 (17) 0.00697 (18) −0.00023 (17) O1 0.0195 (7) 0.0164 (6) 0.0194 (7) 0.0054 (5) 0.0005 (6) −0.0035 (5) O2 0.0283 (8) 0.0197 (7) 0.0251 (7) 0.0066 (6) 0.0015 (6) −0.0080 (6) N1 0.0164 (8) 0.0141 (7) 0.0131 (7) 0.0015 (6) 0.0033 (6) −0.0008 (6) C1 0.0198 (10) 0.0157 (9) 0.0197 (9) 0.0019 (7) 0.0054 (8) −0.0004 (7) C2 0.0180 (9) 0.0149 (8) 0.0139 (9) 0.0008 (7) 0.0072 (7) 0.0005 (7) C3 0.0204 (10) 0.0179 (9) 0.0146 (9) 0.0006 (7) 0.0033 (7) −0.0012 (7) C4 0.0187 (10) 0.0236 (10) 0.0159 (9) 0.0029 (8) 0.0008 (8) 0.0029 (7) C5 0.0234 (10) 0.0183 (9) 0.0191 (10) 0.0073 (8) 0.0049 (8) 0.0024 (7) C6 0.0221 (10) 0.0152 (9) 0.0192 (9) 0.0031 (7) 0.0069 (8) −0.0005 (7) N2 0.0134 (19) 0.018 (2) 0.0199 (17) 0.0040 (13) 0.0071 (15) 0.0005 (15) C7 0.021 (2) 0.0159 (18) 0.028 (2) 0.0027 (15) 0.012 (2) −0.0004 (19) C8 0.036 (3) 0.028 (2) 0.026 (2) −0.0108 (19) 0.015 (2) −0.0077 (18) C9 0.0178 (17) 0.0273 (19) 0.0266 (19) −0.0008 (14) 0.0120 (15) −0.0011 (15) C10 0.030 (2) 0.027 (3) 0.038 (4) −0.012 (2) 0.015 (3) −0.003 (2) C11 0.021 (3) 0.0250 (13) 0.0191 (10) 0.0037 (17) 0.0075 (11) 0.0019 (8) C12 0.026 (2) 0.029 (4) 0.026 (5) 0.004 (2) 0.006 (2) 0.005 (3) N2\' 0.015 (3) 0.018 (3) 0.022 (2) 0.0004 (17) 0.009 (2) 0.0004 (19) C7\' 0.021 (2) 0.019 (2) 0.030 (3) −0.0010 (18) 0.010 (2) −0.0072 (19) C8\' 0.030 (4) 0.023 (3) 0.032 (4) −0.005 (3) 0.012 (3) −0.009 (3) C9\' 0.020 (3) 0.018 (3) 0.027 (3) −0.002 (2) 0.013 (2) −0.001 (2) C10\' 0.036 (3) 0.027 (3) 0.027 (3) −0.005 (2) 0.016 (3) 0.001 (2) C11\' 0.021 (3) 0.0250 (13) 0.0191 (10) 0.0037 (17) 0.0075 (11) 0.0019 (8) C12\' 0.026 (2) 0.029 (4) 0.026 (5) 0.004 (2) 0.006 (2) 0.005 (3) ------- ------------- ------------- ------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1978 .table-wrap} --------------------- -------------- ----------------------------- -------------- Sn1---O1 2.1039 (13) C10---H10A 0.9800 Sn1---N1 2.2163 (15) C10---H10B 0.9800 Sn1---Cl1 2.3686 (5) C10---H10C 0.9800 Sn1---Cl3 2.3876 (5) C11---C12 1.512 (8) Sn1---Cl4 2.3990 (5) C11---H11A 0.9900 Sn1---Cl2 2.4066 (5) C11---H11B 0.9900 O1---C1 1.294 (2) C12---H12A 0.9800 O2---C1 1.226 (2) C12---H12B 0.9800 N1---C6 1.338 (2) C12---H12C 0.9800 N1---C2 1.345 (2) N2\'---C7\' 1.499 (5) C1---C2 1.509 (2) N2\'---C9\' 1.501 (5) C2---C3 1.374 (3) N2\'---C11\' 1.504 (7) C3---C4 1.388 (3) N2\'---H2\' 0.8800 C3---H3 0.9500 C7\'---C8\' 1.511 (6) C4---C5 1.384 (3) C7\'---H7\'A 0.9900 C4---H4 0.9500 C7\'---H7\'B 0.9900 C5---C6 1.377 (3) C8\'---H8\'A 0.9800 C5---H5 0.9500 C8\'---H8\'B 0.9800 C6---H6 0.9500 C8\'---H8\'C 0.9800 N2---C11 1.503 (6) C9\'---C10\' 1.509 (6) N2---C9 1.503 (4) C9\'---H9\'A 0.9900 N2---C7 1.508 (5) C9\'---H9\'B 0.9900 N2---H2 0.8800 C10\'---H10D 0.9800 C7---C8 1.508 (5) C10\'---H10E 0.9800 C7---H7A 0.9900 C10\'---H10F 0.9800 C7---H7B 0.9900 C11\'---C12\' 1.524 (13) C8---H8A 0.9800 C11\'---H11C 0.9900 C8---H8B 0.9800 C11\'---H11D 0.9900 C8---H8C 0.9800 C12\'---H12D 0.9800 C9---C10 1.510 (5) C12\'---H12E 0.9800 C9---H9A 0.9900 C12\'---H12F 0.9800 C9---H9B 0.9900 O1---Sn1---N1 75.63 (5) C9---C10---H10A 109.5 O1---Sn1---Cl1 89.00 (4) C9---C10---H10B 109.5 N1---Sn1---Cl1 164.42 (4) H10A---C10---H10B 109.5 O1---Sn1---Cl3 169.14 (4) C9---C10---H10C 109.5 N1---Sn1---Cl3 93.66 (4) H10A---C10---H10C 109.5 Cl1---Sn1---Cl3 101.778 (17) H10B---C10---H10C 109.5 O1---Sn1---Cl4 90.71 (4) N2---C11---C12 113.1 (11) N1---Sn1---Cl4 85.28 (4) N2---C11---H11A 108.9 Cl1---Sn1---Cl4 92.462 (18) C12---C11---H11A 108.9 Cl3---Sn1---Cl4 90.200 (16) N2---C11---H11B 108.9 O1---Sn1---Cl2 87.23 (4) C12---C11---H11B 108.9 N1---Sn1---Cl2 87.63 (4) H11A---C11---H11B 107.8 Cl1---Sn1---Cl2 94.290 (18) C11---C12---H12A 109.5 Cl3---Sn1---Cl2 90.554 (18) C11---C12---H12B 109.5 Cl4---Sn1---Cl2 172.905 (17) H12A---C12---H12B 109.5 C1---O1---Sn1 118.44 (11) C11---C12---H12C 109.5 C6---N1---C2 119.80 (16) H12A---C12---H12C 109.5 C6---N1---Sn1 126.91 (12) H12B---C12---H12C 109.5 C2---N1---Sn1 113.29 (12) C7\'---N2\'---C9\' 111.9 (4) O2---C1---O1 124.09 (17) C7\'---N2\'---C11\' 114.7 (10) O2---C1---C2 120.18 (17) C9\'---N2\'---C11\' 111.5 (10) O1---C1---C2 115.73 (16) C7\'---N2\'---H2\' 106.0 N1---C2---C3 121.77 (16) C9\'---N2\'---H2\' 106.0 N1---C2---C1 115.42 (16) C11\'---N2\'---H2\' 106.0 C3---C2---C1 122.75 (16) N2\'---C7\'---C8\' 112.5 (4) C2---C3---C4 118.69 (17) N2\'---C7\'---H7\'A 109.1 C2---C3---H3 120.7 C8\'---C7\'---H7\'A 109.1 C4---C3---H3 120.7 N2\'---C7\'---H7\'B 109.1 C5---C4---C3 119.16 (18) C8\'---C7\'---H7\'B 109.1 C5---C4---H4 120.4 H7\'A---C7\'---H7\'B 107.8 C3---C4---H4 120.4 C7\'---C8\'---H8\'A 109.5 C6---C5---C4 119.22 (17) C7\'---C8\'---H8\'B 109.5 C6---C5---H5 120.4 H8\'A---C8\'---H8\'B 109.5 C4---C5---H5 120.4 C7\'---C8\'---H8\'C 109.5 N1---C6---C5 121.32 (17) H8\'A---C8\'---H8\'C 109.5 N1---C6---H6 119.3 H8\'B---C8\'---H8\'C 109.5 C5---C6---H6 119.3 N2\'---C9\'---C10\' 112.9 (5) C11---N2---C9 115.1 (7) N2\'---C9\'---H9\'A 109.0 C11---N2---C7 110.6 (8) C10\'---C9\'---H9\'A 109.0 C9---N2---C7 110.8 (3) N2\'---C9\'---H9\'B 109.0 C11---N2---H2 106.6 C10\'---C9\'---H9\'B 109.0 C9---N2---H2 106.6 H9\'A---C9\'---H9\'B 107.8 C7---N2---H2 106.6 C9\'---C10\'---H10D 109.5 C8---C7---N2 112.4 (4) C9\'---C10\'---H10E 109.5 C8---C7---H7A 109.1 H10D---C10\'---H10E 109.5 N2---C7---H7A 109.1 C9\'---C10\'---H10F 109.5 C8---C7---H7B 109.1 H10D---C10\'---H10F 109.5 N2---C7---H7B 109.1 H10E---C10\'---H10F 109.5 H7A---C7---H7B 107.8 N2\'---C11\'---C12\' 113.2 (14) C7---C8---H8A 109.5 N2\'---C11\'---H11C 108.9 C7---C8---H8B 109.5 C12\'---C11\'---H11C 108.9 H8A---C8---H8B 109.5 N2\'---C11\'---H11D 108.9 C7---C8---H8C 109.5 C12\'---C11\'---H11D 108.9 H8A---C8---H8C 109.5 H11C---C11\'---H11D 107.7 H8B---C8---H8C 109.5 C11\'---C12\'---H12D 109.5 N2---C9---C10 113.6 (3) C11\'---C12\'---H12E 109.5 N2---C9---H9A 108.8 H12D---C12\'---H12E 109.5 C10---C9---H9A 108.8 C11\'---C12\'---H12F 109.5 N2---C9---H9B 108.8 H12D---C12\'---H12F 109.5 C10---C9---H9B 108.8 H12E---C12\'---H12F 109.5 H9A---C9---H9B 107.7 N1---Sn1---O1---C1 −11.42 (13) O1---C1---C2---N1 −5.5 (2) Cl1---Sn1---O1---C1 171.18 (14) O2---C1---C2---C3 −7.3 (3) Cl3---Sn1---O1---C1 −1.6 (3) O1---C1---C2---C3 171.81 (17) Cl4---Sn1---O1---C1 −96.37 (14) N1---C2---C3---C4 2.5 (3) Cl2---Sn1---O1---C1 76.84 (14) C1---C2---C3---C4 −174.58 (18) O1---Sn1---N1---C6 −171.97 (17) C2---C3---C4---C5 −1.8 (3) Cl1---Sn1---N1---C6 −162.25 (12) C3---C4---C5---C6 0.2 (3) Cl3---Sn1---N1---C6 9.87 (16) C2---N1---C6---C5 −0.2 (3) Cl4---Sn1---N1---C6 −80.03 (15) Sn1---N1---C6---C5 179.52 (14) Cl2---Sn1---N1---C6 100.27 (16) C4---C5---C6---N1 0.8 (3) O1---Sn1---N1---C2 7.73 (12) C11---N2---C7---C8 −156.5 (7) Cl1---Sn1---N1---C2 17.5 (2) C9---N2---C7---C8 74.7 (4) Cl3---Sn1---N1---C2 −170.42 (12) C11---N2---C9---C10 52.6 (8) Cl4---Sn1---N1---C2 99.68 (12) C7---N2---C9---C10 179.0 (4) Cl2---Sn1---N1---C2 −80.02 (12) C9---N2---C11---C12 61.6 (14) Sn1---O1---C1---O2 −167.96 (16) C7---N2---C11---C12 −64.9 (13) Sn1---O1---C1---C2 12.9 (2) C9\'---N2\'---C7\'---C8\' 166.0 (5) C6---N1---C2---C3 −1.5 (3) C11\'---N2\'---C7\'---C8\' −65.8 (10) Sn1---N1---C2---C3 178.74 (14) C7\'---N2\'---C9\'---C10\' −69.7 (6) C6---N1---C2---C1 175.77 (17) C11\'---N2\'---C9\'---C10\' 160.4 (10) Sn1---N1---C2---C1 −4.0 (2) C7\'---N2\'---C11\'---C12\' −66.1 (18) O2---C1---C2---N1 175.38 (18) C9\'---N2\'---C11\'---C12\' 62.3 (19) --------------------- -------------- ----------------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3088 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N2---H2···O2 0.88 1.95 2.828 (4) 172 N2\'---H2\'···O2 0.88 2.02 2.895 (5) 173 ------------------ --------- --------- ----------- --------------- ::: ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* -------------- --------- ------- ----------- ------------- N2---H2⋯O2 0.88 1.95 2.828 (4) 172 N2′---H2′⋯O2 0.88 2.02 2.895 (5) 173 :::

PubMed Central

2024-06-05T04:04:18.898715

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052166/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):m351", "authors": [ { "first": "Ezzatollah", "last": "Najafi" }, { "first": "Mostafa M.", "last": "Amini" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052167

Related literature {#sec1} ================== For polymorphism and pseudopolymorphs, see: Bernstein (2002[@bb3]); Byrn *et al.* (1999[@bb4]); Aitipamula *et al.* (2010[@bb1]). For nitrofurantoin hydrate and anhydrate crystal structures, see: Otsuka *et al.* (1991[@bb9]); Pienaar *et al.* (1993*a* [@bb10],*b* [@bb11]); Bertolasi *et al.* (1993)[@bb17] and for nitrofurantoin pseudopolymorphs, see: Caira *et al.* (1996[@bb5]); Tutughamiarso *et al.* (2011[@bb15]). For a 1:1 co-crystal involving nitrofurantoin and 4-hydroxybenzoic acid, see: Vangala *et al.* (2011[@bb16]). For hydrogen bonding, see: Desiraju & Steiner (1999[@bb8]); Desiraju (2002[@bb6], 2007[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~8~H~6~N~4~O~5~·CH~4~O*M* *~r~* = 270.21Monoclinic,*a* = 6.4084 (13) Å*b* = 6.5941 (13) Å*c* = 26.705 (5) Åβ = 91.70 (3)°*V* = 1128.0 (4) Å^3^*Z* = 4Mo *K*α radiationμ = 0.14 mm^−1^*T* = 110 K0.13 × 0.11 × 0.11 mm ### Data collection {#sec2.1.2} Rigaku Saturn 70 CCD area-deterctor diffractometerAbsorption correction: multi-scan (*CrystalClear*; Rigaku, 2008[@bb12]) *T* ~min~ = 0.983, *T* ~max~ = 0.98517441 measured reflections3299 independent reflections2849 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.048 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.071*wR*(*F* ^2^) = 0.129*S* = 1.243299 reflections212 parametersAll H-atom parameters refinedΔρ~max~ = 0.24 e Å^−3^Δρ~min~ = −0.26 e Å^−3^ {#d5e532} Data collection: *CrystalClear* (Rigaku, 2008)[@bb12]; cell refinement: *CrystalClear* [@bb12]; data reduction: *CrystalClear* [@bb12]; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb13]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb13]); molecular graphics: *X-SEED* (Barbour, 2001[@bb2]); software used to prepare material for publication: *SHELXTL* (Sheldrick, 2008[@bb13]) and *PLATON* (Spek, 2009[@bb14]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811003679/ng5112sup1.cif](http://dx.doi.org/10.1107/S1600536811003679/ng5112sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811003679/ng5112Isup2.hkl](http://dx.doi.org/10.1107/S1600536811003679/ng5112Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?ng5112&file=ng5112sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?ng5112sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?ng5112&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [NG5112](http://scripts.iucr.org/cgi-bin/sendsup?ng5112)). This work was supported by the Science and Engineering Research Council of A\*STAR (Agency for Science, Technology and Research), Singapore. Comment ======= Polymorphism is an ability of a molecule to exist in two or more crystal structures. Incorporation of solvent molecules into the crystalline lattice are routinely referred to as solvates, inclusion complexes and/or pseudopolymorphs (Bernstein, 2002; Byrn *et al.*, 1999; Aitipamula *et al.*, 2010). A full characterization of various crystal forms of an active pharmaceutical ingredient (API) may reveal desired physical form. Thus, it is relevant to pharmaceutical industry. Nitrofurantoin {(*E*)-1-\[(5-nitro-2-furyl)methylideneamino\]imidazoldine-2,4-dione} is an antibacterial agent used in the treatment of genitourinary tract infections. It exists in both anhydrous (α- and β-) and hydrate forms (Forms I and II) (Pienaar *et al.*, 1993*a*, 1993*b*; Bertolasi *et al.*, 1993), and literature findings show that nitrofurantoin has poor physical properties (Otsuka *et al.*, 1991; Caira *et al.*, 1996). We have recently reported a 1:1 co-crystal involving nitrofurantoin and 4-hydroxybenzoic acid and shown that co-crystal displayed superior physicochemical and photo-stability to that of nitrofurantoin. However, co-crystallization attempt of nitrofurantoin with fumaric acid in methanol instead yielded the title pseudopolymorph, nitrofurantoin methanol monosolvate. It was reported that this API is known to form inclusion complexes with dimethylformamide, dimethyl sulfoxide and dimethylacetamide (Caira *et al.*, 1996; Tutughamiarso *et al.*, 2011). Herein we report the structural features of a 1:1 pseudopolymorph involving nitrofurantoin and methanol (Fig. 1). Thermogravimetric analysis (TGA traces) of the title compound is shown in Fig. 2. The measured weight loss (11.6% *w*/*w*) in the temperature range of 110--140 °C is in agreement with the stoichiometric weight content for a methanol monosolvate (11.8% *w*/*w*). Single crystal X-ray diffraction analysis reveals that the crystal structure contains one molecule each of nitrofurantoin and methanol in the asymmetric unit (Fig. 1). It has crystallized in the monoclinic crystal system with *P*2~1~/*c* space group. In the structure, nitrofurantoin and methanol molecules were essentially held together by a primary co-operative synthon of N---H···O---H···O \[*D*/Å, *θ*/°: 2.755 (2), 170 (3); 2.787 (2), 172 (3)\] between amide N4---H4, methanolic O6---H6 and imide O5 along the *a*-axis (Fig. 3). In addition, there are significant C---H···O hydrogen bonds (Desiraju & Steiner 1999; Desiraju 2002; Desiraju 2007) within nitrofurantoin molecules, which lead to ribbons running along *a*-axis and support the key hydrogen bonding synthon (Fig. 4). It has structural reminiscences with anhydrous nitrofurantoin (β-form), where the packing is stabilized by imide catemer of N---H···O interactions (Pienaar *et al.*, 1993*b*; Bertolasi *et al.*, 1993). Here, however, it is replaced with N---H···O---H···O catemer type of heterosynthon by retaining a two fold screw axis. Recently, we have noted an identical synthon in a 1:1 co-crystal involving nitrofurantoin and phenolic co-former (4-hydroxybenzoic acid) (Vangala *et al.*, 2011). Hence, supramolecularly methnolic O--H interacted similar to what phenolic O--H is able to do in the reported co-crystal. The overall crystal packing of the title pseudopolymorph is further assisted by weak C---H···O interactions to give a herringbone type of pattern (Fig. 5). Further analysis showed that this herringbone pattern was comparable to that of a crystal structure of nitrofurantoin dimethyl sulfoxide monosolvate (Tutughamiarso *et al.*, 2011). Experimental {#experimental} ============ The title psuedopolymorph was obtained by evaporative crystallization during attempts to co-crystallize a commercially available (purchased from Aldrich) nitrofurantoin (β-form, 119 mg, 0.5 mmol) with fumaric acid (58 mg, 0.5 mmol) in methanol (25 ml) at ambient conditions. The yellow needle shaped crystals suitable for single-crystal X-ray diffraction were obtained in three days. Refinement {#refinement} ========== All H atoms bonded to C, N, O atoms were located in a difference map and allowed to ride on their parent atoms in the refinement cycles. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### A perspective view showing the molecular structures of nitrofurantoin and methanol, with atom labels and 50% probability displacement ellipsoids for non-H atoms. The dashed line shows the N---H···O hydrogen bond. ::: ![](e-67-0o550-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### TGA traces showed that there was a weight loss of 11.6% (w/w), which can be attributed to a methanol solvate. ::: ![](e-67-0o550-fig2) ::: ::: {#Fap3 .fig} Fig. 3. ::: {.caption} ###### A partial packing diagram of the title pseudopolymorph is viewed down b-axis, showing formation of the N---H···O---H···O synthon along a-axis. Notice the strong C---H···O hydrogen bonds within nitrofurantoin molecules to support the solid-state structure. ::: ![](e-67-0o550-fig3) ::: ::: {#Fap4 .fig} Fig. 4. ::: {.caption} ###### A partial packing diagram of the title pseudopolymorph is viewed down b-axis, showing ribbons running along a-axis. Notice the methanol monosolvate showed in space filled style. ::: ![](e-67-0o550-fig4) ::: ::: {#Fap5 .fig} Fig. 5. ::: {.caption} ###### Crystal packing of the title pseudopolymorph is viewed down the a-axis, showing a herringbone pattern. Notice also the methanol monosolvate showed in space filled style. ::: ![](e-67-0o550-fig5) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e239 .table-wrap} ------------------------- --------------------------------------- C~8~H~6~N~4~O~5~·CH~4~O *D*~x~ = 1.591 Mg m^−3^ *M~r~* = 270.21 Melting point: 547 K Monoclinic, *P*2~1~/*c* Mo *K*α radiation, λ = 0.71073 Å *a* = 6.4084 (13) Å Cell parameters from 2901 reflections *b* = 6.5941 (13) Å θ = 1.5--31.2° *c* = 26.705 (5) Å µ = 0.14 mm^−1^ β = 91.70 (3)° *T* = 110 K *V* = 1128.0 (4) Å^3^ Block, yellow *Z* = 4 0.13 × 0.11 × 0.11 mm *F*(000) = 560 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e373 .table-wrap} ------------------------------------------------------------------ -------------------------------------- Rigaku Saturn 70 CCD area-deterctor diffractometer 3299 independent reflections Radiation source: fine-focus sealed tube 2849 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.048 ω scans θ~max~ = 31.2°, θ~min~ = 3.2° Absorption correction: multi-scan (*CrystalClear*; Rigaku, 2008) *h* = −6→9 *T*~min~ = 0.983, *T*~max~ = 0.985 *k* = −8→9 17441 measured reflections *l* = −37→37 ------------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e487 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.071 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.129 All H-atom parameters refined *S* = 1.24 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.033*P*)^2^ + 0.7077*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3299 reflections (Δ/σ)~max~ \< 0.001 212 parameters Δρ~max~ = 0.24 e Å^−3^ 0 restraints Δρ~min~ = −0.26 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e644 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e743 .table-wrap} ----- ------------ ------------- ------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ O6 0.9997 (2) −0.1389 (2) 0.22463 (5) 0.0263 (3) C9 0.9409 (4) −0.0216 (3) 0.18136 (8) 0.0278 (4) H9C 0.997 (4) 0.115 (4) 0.1824 (10) 0.042 (7)\* H9B 0.990 (4) −0.085 (4) 0.1496 (10) 0.039 (7)\* H9A 0.786 (4) −0.017 (4) 0.1807 (10) 0.047 (8)\* H6 1.134 (5) −0.139 (4) 0.2267 (10) 0.046 (8)\* O3 0.6808 (2) 0.3602 (2) 0.58168 (5) 0.0284 (3) N3 0.5389 (2) 0.0501 (2) 0.36110 (6) 0.0215 (3) O2 0.4103 (2) 0.4243 (2) 0.62695 (5) 0.0295 (3) C7 0.5011 (3) −0.0753 (3) 0.28106 (7) 0.0215 (4) N2 0.5159 (3) 0.1188 (2) 0.40903 (6) 0.0215 (3) N4 0.7053 (3) −0.0642 (3) 0.29543 (6) 0.0221 (3) C4 0.3538 (3) 0.3193 (3) 0.54700 (7) 0.0217 (4) C8 0.3751 (3) −0.0024 (3) 0.32458 (7) 0.0212 (4) C1 0.2822 (3) 0.2104 (3) 0.47230 (7) 0.0210 (4) C6 0.7351 (3) 0.0089 (3) 0.34419 (7) 0.0218 (4) C3 0.1432 (3) 0.3112 (3) 0.54369 (8) 0.0250 (4) C2 0.0962 (3) 0.2407 (3) 0.49475 (8) 0.0238 (4) C5 0.3262 (3) 0.1396 (3) 0.42254 (7) 0.0214 (4) H5 0.208 (3) 0.109 (3) 0.4017 (8) 0.016 (5)\* H2 −0.034 (4) 0.218 (3) 0.4794 (9) 0.027 (6)\* H8B 0.284 (4) −0.114 (4) 0.3365 (9) 0.028 (6)\* O1 0.4459 (2) 0.2587 (2) 0.50437 (5) 0.0212 (3) H4 0.807 (4) −0.098 (4) 0.2753 (10) 0.039 (7)\* H3 0.053 (4) 0.348 (4) 0.5693 (9) 0.034 (7)\* H8A 0.292 (4) 0.116 (4) 0.3134 (9) 0.038 (7)\* O5 0.4315 (2) −0.1331 (2) 0.24050 (5) 0.0259 (3) O4 0.9013 (2) 0.0278 (2) 0.36653 (5) 0.0281 (3) N1 0.4910 (3) 0.3720 (2) 0.58760 (6) 0.0226 (3) ----- ------------ ------------- ------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1153 .table-wrap} ---- ------------- ------------- ------------- ------------- ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ O6 0.0204 (7) 0.0356 (8) 0.0228 (7) 0.0026 (6) 0.0015 (6) 0.0021 (6) C9 0.0291 (11) 0.0273 (10) 0.0269 (10) −0.0001 (8) 0.0004 (8) 0.0039 (8) O3 0.0195 (7) 0.0364 (8) 0.0294 (7) −0.0017 (6) 0.0000 (6) −0.0018 (6) N3 0.0171 (8) 0.0272 (8) 0.0200 (7) −0.0002 (6) 0.0007 (6) −0.0018 (6) O2 0.0340 (8) 0.0333 (8) 0.0216 (7) −0.0004 (6) 0.0075 (6) −0.0031 (6) C7 0.0192 (9) 0.0216 (9) 0.0236 (9) 0.0011 (7) −0.0004 (7) 0.0016 (7) N2 0.0243 (8) 0.0214 (8) 0.0186 (7) −0.0018 (6) 0.0003 (6) 0.0005 (6) N4 0.0176 (8) 0.0279 (8) 0.0208 (8) 0.0013 (6) 0.0019 (6) 0.0001 (6) C4 0.0229 (9) 0.0212 (9) 0.0211 (8) 0.0006 (7) 0.0037 (7) −0.0008 (7) C8 0.0179 (9) 0.0240 (9) 0.0215 (9) 0.0005 (7) −0.0014 (7) −0.0014 (7) C1 0.0189 (9) 0.0205 (9) 0.0236 (9) −0.0006 (7) −0.0003 (7) 0.0020 (7) C6 0.0184 (9) 0.0242 (9) 0.0228 (9) −0.0016 (7) 0.0000 (7) 0.0027 (7) C3 0.0229 (10) 0.0254 (10) 0.0269 (10) 0.0021 (8) 0.0058 (8) 0.0014 (7) C2 0.0187 (9) 0.0250 (9) 0.0276 (10) 0.0004 (7) −0.0003 (8) 0.0025 (7) C5 0.0185 (9) 0.0214 (9) 0.0241 (9) −0.0001 (7) −0.0012 (7) 0.0003 (7) O1 0.0196 (7) 0.0246 (7) 0.0195 (6) 0.0005 (5) 0.0015 (5) −0.0007 (5) O5 0.0235 (7) 0.0324 (8) 0.0217 (7) 0.0007 (6) −0.0016 (5) −0.0036 (5) O4 0.0186 (7) 0.0390 (8) 0.0267 (7) −0.0029 (6) −0.0004 (5) 0.0026 (6) N1 0.0246 (9) 0.0215 (8) 0.0219 (8) −0.0017 (6) 0.0026 (6) 0.0013 (6) ---- ------------- ------------- ------------- ------------- ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1532 .table-wrap} ---------------- ------------- ---------------- ------------- O6---C9 1.432 (2) N4---H4 0.88 (3) O6---H6 0.86 (3) C4---C3 1.351 (3) C9---H9C 0.97 (3) C4---O1 1.358 (2) C9---H9B 1.00 (3) C4---N1 1.419 (3) C9---H9A 1.00 (3) C8---H8B 1.00 (2) O3---N1 1.234 (2) C8---H8A 0.99 (3) N3---N2 1.370 (2) C1---C2 1.365 (3) N3---C6 1.375 (2) C1---O1 1.372 (2) N3---C8 1.454 (2) C1---C5 1.444 (3) O2---N1 1.234 (2) C6---O4 1.212 (2) C7---O5 1.220 (2) C3---C2 1.411 (3) C7---N4 1.355 (2) C3---H3 0.94 (2) C7---C8 1.513 (3) C2---H2 0.93 (2) N2---C5 1.286 (3) C5---H5 0.95 (2) N4---C6 1.396 (2) C9---O6---H6 107.0 (19) N3---C8---H8A 112.7 (15) O6---C9---H9C 112.9 (16) C7---C8---H8A 108.3 (15) O6---C9---H9B 112.2 (15) H8B---C8---H8A 111.3 (19) H9C---C9---H9B 106 (2) C2---C1---O1 110.68 (17) O6---C9---H9A 105.6 (16) C2---C1---C5 130.44 (18) H9C---C9---H9A 110 (2) O1---C1---C5 118.88 (16) H9B---C9---H9A 109 (2) O4---C6---N3 128.06 (18) N2---N3---C6 119.80 (15) O4---C6---N4 126.05 (18) N2---N3---C8 127.60 (15) N3---C6---N4 105.89 (16) C6---N3---C8 112.43 (15) C4---C3---C2 104.99 (17) O5---C7---N4 126.39 (18) C4---C3---H3 125.3 (16) O5---C7---C8 126.25 (17) C2---C3---H3 129.7 (16) N4---C7---C8 107.36 (16) C1---C2---C3 106.88 (18) C5---N2---N3 115.25 (16) C1---C2---H2 124.4 (15) C7---N4---C6 112.76 (16) C3---C2---H2 128.8 (15) C7---N4---H4 122.4 (17) N2---C5---C1 120.33 (17) C6---N4---H4 124.8 (17) N2---C5---H5 124.0 (13) C3---C4---O1 113.05 (17) C1---C5---H5 115.7 (13) C3---C4---N1 130.92 (18) C4---O1---C1 104.40 (14) O1---C4---N1 115.98 (16) O2---N1---O3 124.47 (17) N3---C8---C7 101.52 (15) O2---N1---C4 116.97 (16) N3---C8---H8B 112.3 (14) O3---N1---C4 118.54 (16) C7---C8---H8B 110.1 (14) ---------------- ------------- ---------------- ------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1894 .table-wrap} ------------------ ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N4---H4···O6 0.88 (3) 1.88 (3) 2.755 (2) 170 (3) O6---H6···O5^i^ 0.86 (3) 1.93 (3) 2.787 (2) 172 (3) C5---H5···O4^ii^ 0.95 (2) 2.22 (2) 3.155 (2) 169.2 (18) C3---H3···O3^ii^ 0.94 (2) 2.42 (2) 3.176 (3) 138 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) *x*+1, *y*, *z*; (ii) *x*−1, *y*, *z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- ---------- ---------- ----------- ------------- N4---H4⋯O6 0.88 (3) 1.88 (3) 2.755 (2) 170 (3) O6---H6⋯O5^i^ 0.86 (3) 1.93 (3) 2.787 (2) 172 (3) C5---H5⋯O4^ii^ 0.95 (2) 2.22 (2) 3.155 (2) 169.2 (18) C3---H3⋯O3^ii^ 0.94 (2) 2.42 (2) 3.176 (3) 138 (2) Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.906845

2011-2-02

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052167/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 2; 67(Pt 3):o550-o551", "authors": [ { "first": "Venu R.", "last": "Vangala" }, { "first": "Pui Shan", "last": "Chow" }, { "first": "Reginald B. H.", "last": "Tan" } ] }

PMC3052168

Related literature {#sec1} ================== For the synthesis, see: Bossio *et al.* (1985[@bb2]); Shestakov *et al.* (2006[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~13~H~13~N~5~*M* *~r~* = 239.28Triclinic,*a* = 8.2836 (4) Å*b* = 9.6135 (5) Å*c* = 16.5694 (8) Åα = 92.121 (1)°β = 96.100 (1)°γ = 112.597 (1)°*V* = 1206.94 (10) Å^3^*Z* = 4Mo *K*α radiationμ = 0.09 mm^−1^*T* = 295 K0.30 × 0.20 × 0.20 mm ### Data collection {#sec2.1.2} Bruker APEXII diffractometer13373 measured reflections5550 independent reflections4124 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.019 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.044*wR*(*F* ^2^) = 0.136*S* = 1.015550 reflections345 parameters4 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.25 e Å^−3^Δρ~min~ = −0.18 e Å^−3^ {#d5e444} Data collection: *APEX2* (Bruker, 2005[@bb3]); cell refinement: *SAINT* (Bruker, 2005[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb4]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb4]); molecular graphics: *X-SEED* (Barbour, 2001[@bb1]); software used to prepare material for publication: *publCIF* (Westrip, 2010[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006507/hg5003sup1.cif](http://dx.doi.org/10.1107/S1600536811006507/hg5003sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006507/hg5003Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006507/hg5003Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?hg5003&file=hg5003sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?hg5003sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?hg5003&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [HG5003](http://scripts.iucr.org/cgi-bin/sendsup?hg5003)). We thank Manchester Metropolitan University, Baku State University and the University of Malaya for supporting this study. Comment ======= The reported synthesis involves the reaction of 4,6-dimethylpyrimidin-2-ylcyanamide with *o*-phenylenediamine, and it illustrates the type of heterocycles that are formed by the reaction of cyanamides with *N*,*N*-binucleophiles (Shestakov *et al.*, 2006). The unsubstituted compound was reported earlier (Bossio *et al.*, 1985). The present synthesis is a more convenient synthesis that uses acetylacetone as one of the reactants. An amino N atom in the approximately planar C~13~H~13~N~5~ molecule is connected to a benzimidazoyl fused-ring and a pyrimidyl ring; the amino N atom of the fused ring forms an intramolecular N--H···O hydrogen bond to a pyridmidyl N atom (Scheme I, Fig. 1). There are two independent molecules; each molecule is connected to an inversion-related molecule by an N--H···O hydrogen bond. Experimental {#experimental} ============ 1*H*-Benzo\[*d*\]imidazol-2-yliminomethanediamine (0.05 mol) and acetylacetone (0.10 mol, approx.10 ml) along with several drops of acetic acid were heated at 473 for 1 h. The solid that formed on cooling was collected and recrystallized from ethanol to give the title compound in 80% yield; m.p. 623 K. Refinement {#refinement} ========== Carbon-bound H-atoms were placed in calculated positions \[C--H 0.93 to 0.96 Å; *U*(H) 1.2 to 1.5*U*(C)\] and were included in the refinement in the riding model approximation. The amino H-atoms were located in a difference Fourier map, and were refined with a distance restraint of N--H 0.86±0.01 Å; their temperature factors were refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Thermal ellipsoid plot (Barbour, 2001) of the two independent molecules of C13H13N5 at the 50% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. ::: ![](e-67-0o719-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e136 .table-wrap} ------------------------- --------------------------------------- C~13~H~13~N~5~ *Z* = 4 *M~r~* = 239.28 *F*(000) = 504 Triclinic, *P*1 *D*~x~ = 1.317 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 8.2836 (4) Å Cell parameters from 4428 reflections *b* = 9.6135 (5) Å θ = 2.3--27.4° *c* = 16.5694 (8) Å µ = 0.09 mm^−1^ α = 92.121 (1)° *T* = 295 K β = 96.100 (1)° Prism, colorless γ = 112.597 (1)° 0.30 × 0.20 × 0.20 mm *V* = 1206.94 (10) Å^3^ ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e269 .table-wrap} ------------------------------------------ -------------------------------------- Bruker APEXII diffractometer 4124 reflections with *I* \> 2σ(*I*) Radiation source: fine-focus sealed tube *R*~int~ = 0.019 graphite θ~max~ = 27.5°, θ~min~ = 1.2° φ and ω scans *h* = −10→10 13373 measured reflections *k* = −12→12 5550 independent reflections *l* = −21→21 ------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e367 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.044 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.136 H atoms treated by a mixture of independent and constrained refinement *S* = 1.01 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0736*P*)^2^ + 0.1933*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 5550 reflections (Δ/σ)~max~ = 0.001 345 parameters Δρ~max~ = 0.25 e Å^−3^ 4 restraints Δρ~min~ = −0.18 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e526 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ N1 0.66435 (17) 0.61916 (15) 0.45010 (8) 0.0480 (3) N2 0.80016 (16) 0.45944 (14) 0.43969 (8) 0.0470 (3) N3 0.94151 (17) 0.67635 (15) 0.53228 (8) 0.0498 (3) N4 1.11489 (17) 0.88346 (14) 0.61816 (8) 0.0491 (3) N5 0.83527 (16) 0.86534 (14) 0.55242 (8) 0.0477 (3) N6 0.98905 (15) 1.11808 (14) 0.92502 (8) 0.0453 (3) N7 0.72463 (16) 1.09201 (14) 0.86230 (8) 0.0452 (3) N8 0.74067 (16) 0.92463 (15) 0.96388 (8) 0.0485 (3) N9 0.52809 (16) 0.73369 (14) 1.01630 (8) 0.0477 (3) N10 0.44770 (16) 0.87329 (14) 0.91397 (8) 0.0464 (3) C1 0.5574 (2) 0.50529 (17) 0.39234 (9) 0.0453 (3) C2 0.3985 (2) 0.48064 (19) 0.34608 (11) 0.0570 (4) H2 0.3415 0.5464 0.3516 0.068\* C3 0.3283 (2) 0.3542 (2) 0.29138 (11) 0.0648 (5) H3A 0.2219 0.3343 0.2590 0.078\* C4 0.4132 (2) 0.2562 (2) 0.28378 (11) 0.0646 (5) H4 0.3630 0.1726 0.2458 0.077\* C5 0.5706 (2) 0.27942 (19) 0.33104 (10) 0.0566 (4) H5 0.6258 0.2122 0.3261 0.068\* C6 0.64326 (19) 0.40638 (17) 0.38613 (9) 0.0446 (3) C7 0.80551 (19) 0.58625 (16) 0.47531 (9) 0.0433 (3) C8 0.96246 (19) 0.81387 (17) 0.56914 (9) 0.0444 (3) C9 1.1398 (2) 1.01836 (18) 0.65380 (10) 0.0502 (4) C10 1.0141 (2) 1.07950 (19) 0.64206 (10) 0.0541 (4) H10 1.0317 1.1723 0.6684 0.065\* C11 0.8619 (2) 0.99939 (18) 0.59025 (10) 0.0492 (4) C12 1.3142 (2) 1.1021 (2) 0.70528 (13) 0.0679 (5) H12A 1.3969 1.0598 0.6921 0.102\* H12B 1.2994 1.0930 0.7618 0.102\* H12C 1.3577 1.2069 0.6949 0.102\* C13 0.7188 (2) 1.0572 (2) 0.57189 (12) 0.0638 (5) H13A 0.6895 1.0528 0.5140 0.096\* H13B 0.7591 1.1600 0.5946 0.096\* H13C 0.6163 0.9959 0.5953 0.096\* C14 1.01079 (19) 1.22562 (16) 0.86868 (9) 0.0423 (3) C15 1.1636 (2) 1.33597 (18) 0.84877 (10) 0.0510 (4) H15 1.2738 1.3468 0.8743 0.061\* C16 1.1476 (2) 1.42941 (19) 0.78990 (10) 0.0563 (4) H16 1.2488 1.5041 0.7758 0.068\* C17 0.9839 (2) 1.41438 (19) 0.75126 (10) 0.0569 (4) H17 0.9777 1.4789 0.7117 0.068\* C18 0.8299 (2) 1.30521 (19) 0.77048 (10) 0.0525 (4) H18 0.7199 1.2954 0.7451 0.063\* C19 0.84684 (19) 1.21133 (16) 0.82922 (9) 0.0433 (3) C20 0.81693 (18) 1.04241 (16) 0.91841 (9) 0.0417 (3) C21 0.56341 (18) 0.84116 (16) 0.96416 (9) 0.0433 (3) C22 0.3584 (2) 0.64850 (18) 1.01769 (10) 0.0489 (4) C23 0.2285 (2) 0.67368 (19) 0.96860 (11) 0.0554 (4) H23 0.1101 0.6147 0.9705 0.066\* C24 0.27647 (19) 0.78683 (18) 0.91699 (10) 0.0494 (4) C25 0.3156 (2) 0.5228 (2) 1.07291 (12) 0.0647 (5) H25A 0.4053 0.5504 1.1191 0.097\* H25B 0.3105 0.4326 1.0439 0.097\* H25C 0.2036 0.5048 1.0911 0.097\* C26 0.1440 (2) 0.8194 (2) 0.86077 (12) 0.0683 (5) H26A 0.1696 0.9257 0.8660 0.102\* H26B 0.0280 0.7643 0.8746 0.102\* H26C 0.1495 0.7889 0.8056 0.102\* H1 0.653 (2) 0.6974 (15) 0.4721 (10) 0.062 (5)\* H3 1.0279 (19) 0.647 (2) 0.5423 (11) 0.067 (5)\* H7 0.6096 (12) 1.0539 (19) 0.8546 (11) 0.063 (5)\* H8 0.811 (2) 0.902 (2) 0.9979 (9) 0.059 (5)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1311 .table-wrap} ----- ------------- ------------- ------------- ------------ ------------- ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ N1 0.0468 (7) 0.0444 (7) 0.0547 (8) 0.0227 (6) −0.0035 (6) 0.0018 (6) N2 0.0440 (7) 0.0451 (7) 0.0521 (7) 0.0199 (6) −0.0010 (6) −0.0007 (6) N3 0.0447 (7) 0.0479 (7) 0.0585 (8) 0.0243 (6) −0.0064 (6) −0.0042 (6) N4 0.0465 (7) 0.0477 (7) 0.0525 (7) 0.0203 (6) −0.0013 (6) −0.0007 (6) N5 0.0470 (7) 0.0495 (7) 0.0504 (7) 0.0239 (6) 0.0032 (6) 0.0015 (6) N6 0.0374 (6) 0.0460 (7) 0.0527 (7) 0.0178 (5) −0.0004 (5) 0.0092 (5) N7 0.0379 (6) 0.0476 (7) 0.0497 (7) 0.0186 (6) −0.0035 (5) 0.0055 (5) N8 0.0357 (6) 0.0484 (7) 0.0606 (8) 0.0167 (5) −0.0021 (6) 0.0146 (6) N9 0.0400 (6) 0.0491 (7) 0.0567 (8) 0.0203 (6) 0.0054 (6) 0.0072 (6) N10 0.0383 (6) 0.0493 (7) 0.0498 (7) 0.0179 (5) −0.0032 (5) −0.0003 (6) C1 0.0457 (8) 0.0438 (8) 0.0443 (8) 0.0157 (6) 0.0015 (6) 0.0101 (6) C2 0.0526 (9) 0.0554 (9) 0.0616 (10) 0.0228 (8) −0.0072 (8) 0.0119 (8) C3 0.0567 (10) 0.0670 (11) 0.0595 (10) 0.0173 (9) −0.0133 (8) 0.0074 (9) C4 0.0641 (11) 0.0588 (10) 0.0566 (10) 0.0128 (9) −0.0057 (8) −0.0046 (8) C5 0.0571 (10) 0.0504 (9) 0.0582 (10) 0.0182 (8) 0.0030 (8) −0.0021 (7) C6 0.0438 (8) 0.0451 (8) 0.0438 (8) 0.0160 (6) 0.0047 (6) 0.0079 (6) C7 0.0415 (7) 0.0440 (8) 0.0456 (8) 0.0189 (6) 0.0020 (6) 0.0058 (6) C8 0.0442 (8) 0.0441 (8) 0.0458 (8) 0.0187 (6) 0.0041 (6) 0.0032 (6) C9 0.0507 (9) 0.0489 (8) 0.0486 (8) 0.0178 (7) 0.0029 (7) 0.0017 (7) C10 0.0586 (10) 0.0495 (9) 0.0560 (9) 0.0245 (8) 0.0055 (8) −0.0047 (7) C11 0.0523 (9) 0.0510 (8) 0.0501 (8) 0.0259 (7) 0.0095 (7) 0.0035 (7) C12 0.0601 (11) 0.0584 (10) 0.0767 (12) 0.0205 (9) −0.0115 (9) −0.0104 (9) C13 0.0617 (11) 0.0672 (11) 0.0729 (12) 0.0382 (9) 0.0051 (9) −0.0016 (9) C14 0.0429 (7) 0.0425 (7) 0.0427 (7) 0.0196 (6) 0.0004 (6) 0.0015 (6) C15 0.0464 (8) 0.0503 (9) 0.0527 (9) 0.0161 (7) 0.0018 (7) 0.0046 (7) C16 0.0619 (10) 0.0485 (9) 0.0538 (9) 0.0158 (8) 0.0094 (8) 0.0069 (7) C17 0.0740 (11) 0.0530 (9) 0.0490 (9) 0.0308 (9) 0.0052 (8) 0.0115 (7) C18 0.0580 (9) 0.0567 (9) 0.0482 (9) 0.0306 (8) −0.0026 (7) 0.0052 (7) C19 0.0472 (8) 0.0428 (8) 0.0418 (7) 0.0218 (6) −0.0007 (6) −0.0004 (6) C20 0.0381 (7) 0.0419 (7) 0.0466 (8) 0.0193 (6) −0.0016 (6) 0.0028 (6) C21 0.0370 (7) 0.0434 (8) 0.0503 (8) 0.0181 (6) 0.0009 (6) −0.0005 (6) C22 0.0431 (8) 0.0494 (8) 0.0560 (9) 0.0194 (7) 0.0101 (7) 0.0004 (7) C23 0.0370 (8) 0.0599 (10) 0.0646 (10) 0.0145 (7) 0.0051 (7) 0.0024 (8) C24 0.0372 (7) 0.0552 (9) 0.0527 (9) 0.0176 (7) −0.0023 (6) −0.0058 (7) C25 0.0547 (10) 0.0660 (11) 0.0781 (12) 0.0242 (9) 0.0201 (9) 0.0210 (9) C26 0.0422 (9) 0.0854 (13) 0.0718 (12) 0.0228 (9) −0.0082 (8) 0.0089 (10) ----- ------------- ------------- ------------- ------------ ------------- ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1956 .table-wrap} ---------------------- -------------- ----------------------- -------------- N1---C7 1.3535 (18) C5---H5 0.9300 N1---C1 1.377 (2) C9---C10 1.380 (2) N1---H1 0.86 (1) C9---C12 1.502 (2) N2---C7 1.3176 (19) C10---C11 1.376 (2) N2---C6 1.3960 (19) C10---H10 0.9300 N3---C7 1.3689 (19) C11---C13 1.499 (2) N3---C8 1.3756 (19) C12---H12A 0.9600 N3---H3 0.87 (1) C12---H12B 0.9600 N4---C9 1.336 (2) C12---H12C 0.9600 N4---C8 1.3396 (19) C13---H13A 0.9600 N5---C8 1.3343 (18) C13---H13B 0.9600 N5---C11 1.340 (2) C13---H13C 0.9600 N6---C20 1.3183 (18) C14---C15 1.385 (2) N6---C14 1.3917 (19) C14---C19 1.397 (2) N7---C20 1.3558 (18) C15---C16 1.380 (2) N7---C19 1.383 (2) C15---H15 0.9300 N7---H7 0.87 (1) C16---C17 1.388 (2) N8---C20 1.3650 (19) C16---H16 0.9300 N8---C21 1.3771 (19) C17---C18 1.383 (2) N8---H8 0.87 (1) C17---H17 0.9300 N9---C22 1.3310 (19) C18---C19 1.384 (2) N9---C21 1.3367 (19) C18---H18 0.9300 N10---C21 1.3352 (18) C22---C23 1.380 (2) N10---C24 1.3481 (19) C22---C25 1.498 (2) C1---C2 1.382 (2) C23---C24 1.372 (2) C1---C6 1.396 (2) C23---H23 0.9300 C2---C3 1.378 (3) C24---C26 1.496 (2) C2---H2 0.9300 C25---H25A 0.9600 C3---C4 1.384 (3) C25---H25B 0.9600 C3---H3A 0.9300 C25---H25C 0.9600 C4---C5 1.382 (2) C26---H26A 0.9600 C4---H4 0.9300 C26---H26B 0.9600 C5---C6 1.386 (2) C26---H26C 0.9600 C7---N1---C1 106.87 (13) C9---C12---H12C 109.5 C7---N1---H1 120.2 (12) H12A---C12---H12C 109.5 C1---N1---H1 132.8 (12) H12B---C12---H12C 109.5 C7---N2---C6 104.12 (12) C11---C13---H13A 109.5 C7---N3---C8 126.91 (13) C11---C13---H13B 109.5 C7---N3---H3 115.8 (13) H13A---C13---H13B 109.5 C8---N3---H3 117.0 (13) C11---C13---H13C 109.5 C9---N4---C8 115.66 (13) H13A---C13---H13C 109.5 C8---N5---C11 116.23 (13) H13B---C13---H13C 109.5 C20---N6---C14 104.20 (12) C15---C14---N6 129.94 (13) C20---N7---C19 106.69 (12) C15---C14---C19 119.88 (14) C20---N7---H7 121.9 (12) N6---C14---C19 110.18 (13) C19---N7---H7 131.3 (12) C16---C15---C14 118.09 (15) C20---N8---C21 127.59 (13) C16---C15---H15 121.0 C20---N8---H8 116.5 (13) C14---C15---H15 121.0 C21---N8---H8 115.9 (12) C15---C16---C17 121.51 (16) C22---N9---C21 116.15 (13) C15---C16---H16 119.2 C21---N10---C24 115.57 (14) C17---C16---H16 119.2 N1---C1---C2 132.25 (15) C18---C17---C16 121.25 (15) N1---C1---C6 105.39 (13) C18---C17---H17 119.4 C2---C1---C6 122.37 (15) C16---C17---H17 119.4 C3---C2---C1 116.96 (16) C17---C18---C19 116.95 (15) C3---C2---H2 121.5 C17---C18---H18 121.5 C1---C2---H2 121.5 C19---C18---H18 121.5 C2---C3---C4 121.27 (16) N7---C19---C18 132.51 (14) C2---C3---H3A 119.4 N7---C19---C14 105.17 (12) C4---C3---H3A 119.4 C18---C19---C14 122.32 (15) C5---C4---C3 121.77 (16) N6---C20---N7 113.75 (13) C5---C4---H4 119.1 N6---C20---N8 122.52 (13) C3---C4---H4 119.1 N7---C20---N8 123.73 (13) C4---C5---C6 117.67 (16) N10---C21---N9 127.34 (13) C4---C5---H5 121.2 N10---C21---N8 118.60 (14) C6---C5---H5 121.2 N9---C21---N8 114.06 (12) C5---C6---C1 119.94 (14) N9---C22---C23 120.91 (15) C5---C6---N2 130.14 (14) N9---C22---C25 117.17 (14) C1---C6---N2 109.91 (13) C23---C22---C25 121.90 (15) N2---C7---N1 113.70 (13) C24---C23---C22 119.11 (14) N2---C7---N3 123.06 (13) C24---C23---H23 120.4 N1---C7---N3 123.24 (14) C22---C23---H23 120.4 N5---C8---N4 126.91 (14) N10---C24---C23 120.91 (14) N5---C8---N3 118.65 (13) N10---C24---C26 116.69 (15) N4---C8---N3 114.42 (13) C23---C24---C26 122.39 (15) N4---C9---C10 121.78 (15) C22---C25---H25A 109.5 N4---C9---C12 116.46 (14) C22---C25---H25B 109.5 C10---C9---C12 121.74 (15) H25A---C25---H25B 109.5 C11---C10---C9 118.16 (15) C22---C25---H25C 109.5 C11---C10---H10 120.9 H25A---C25---H25C 109.5 C9---C10---H10 120.9 H25B---C25---H25C 109.5 N5---C11---C10 121.22 (14) C24---C26---H26A 109.5 N5---C11---C13 116.37 (15) C24---C26---H26B 109.5 C10---C11---C13 122.40 (15) H26A---C26---H26B 109.5 C9---C12---H12A 109.5 C24---C26---H26C 109.5 C9---C12---H12B 109.5 H26A---C26---H26C 109.5 H12A---C12---H12B 109.5 H26B---C26---H26C 109.5 C7---N1---C1---C2 −179.49 (17) C20---N6---C14---C15 −179.64 (15) C7---N1---C1---C6 0.26 (16) C20---N6---C14---C19 0.28 (16) N1---C1---C2---C3 178.38 (17) N6---C14---C15---C16 −179.89 (15) C6---C1---C2---C3 −1.3 (2) C19---C14---C15---C16 0.2 (2) C1---C2---C3---C4 0.4 (3) C14---C15---C16---C17 0.0 (2) C2---C3---C4---C5 0.7 (3) C15---C16---C17---C18 0.2 (3) C3---C4---C5---C6 −0.9 (3) C16---C17---C18---C19 −0.6 (2) C4---C5---C6---C1 0.0 (2) C20---N7---C19---C18 −179.50 (16) C4---C5---C6---N2 −178.51 (16) C20---N7---C19---C14 0.38 (16) N1---C1---C6---C5 −178.65 (14) C17---C18---C19---N7 −179.37 (15) C2---C1---C6---C5 1.1 (2) C17---C18---C19---C14 0.8 (2) N1---C1---C6---N2 0.17 (17) C15---C14---C19---N7 179.52 (13) C2---C1---C6---N2 179.95 (14) N6---C14---C19---N7 −0.42 (16) C7---N2---C6---C5 178.13 (16) C15---C14---C19---C18 −0.6 (2) C7---N2---C6---C1 −0.53 (16) N6---C14---C19---C18 179.48 (14) C6---N2---C7---N1 0.72 (17) C14---N6---C20---N7 −0.03 (17) C6---N2---C7---N3 −179.09 (14) C14---N6---C20---N8 179.56 (13) C1---N1---C7---N2 −0.64 (18) C19---N7---C20---N6 −0.23 (17) C1---N1---C7---N3 179.17 (14) C19---N7---C20---N8 −179.82 (14) C8---N3---C7---N2 176.24 (14) C21---N8---C20---N6 177.63 (14) C8---N3---C7---N1 −3.6 (3) C21---N8---C20---N7 −2.8 (3) C11---N5---C8---N4 −1.6 (2) C24---N10---C21---N9 0.1 (2) C11---N5---C8---N3 179.66 (14) C24---N10---C21---N8 179.65 (13) C9---N4---C8---N5 0.2 (2) C22---N9---C21---N10 0.6 (2) C9---N4---C8---N3 179.02 (13) C22---N9---C21---N8 −178.95 (13) C7---N3---C8---N5 3.8 (2) C20---N8---C21---N10 1.4 (2) C7---N3---C8---N4 −175.12 (15) C20---N8---C21---N9 −179.03 (14) C8---N4---C9---C10 1.5 (2) C21---N9---C22---C23 −1.1 (2) C8---N4---C9---C12 −176.69 (15) C21---N9---C22---C25 177.35 (14) N4---C9---C10---C11 −1.8 (3) N9---C22---C23---C24 1.0 (2) C12---C9---C10---C11 176.30 (16) C25---C22---C23---C24 −177.42 (16) C8---N5---C11---C10 1.2 (2) C21---N10---C24---C23 −0.3 (2) C8---N5---C11---C13 −179.73 (14) C21---N10---C24---C26 −179.39 (14) C9---C10---C11---N5 0.4 (3) C22---C23---C24---N10 −0.2 (2) C9---C10---C11---C13 −178.64 (16) C22---C23---C24---C26 178.81 (16) ---------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3158 .table-wrap} ------------------ ---------- ---------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1···N5 0.86 (1) 2.05 (2) 2.664 (2) 128 (2) N3---H3···N2^i^ 0.87 (1) 2.05 (1) 2.912 (2) 170 (2) N7---H7···N10 0.87 (1) 2.10 (2) 2.695 (2) 125 (2) N8---H8···N6^ii^ 0.87 (1) 2.05 (1) 2.908 (2) 170 (2) ------------------ ---------- ---------- ----------- --------------- ::: Symmetry codes: (i) −*x*+2, −*y*+1, −*z*+1; (ii) −*x*+2, −*y*+2, −*z*+2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- ---------- ---------- ----------- ------------- N1---H1⋯N5 0.86 (1) 2.05 (2) 2.664 (2) 128 (2) N3---H3⋯N2^i^ 0.87 (1) 2.05 (1) 2.912 (2) 170 (2) N7---H7⋯N10 0.87 (1) 2.10 (2) 2.695 (2) 125 (2) N8---H8⋯N6^ii^ 0.87 (1) 2.05 (1) 2.908 (2) 170 (2) Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.910416

2011-2-26

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052168/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 26; 67(Pt 3):o719", "authors": [ { "first": "Shaaban Kamel", "last": "Mohamed" }, { "first": "Mahmoud A. A.", "last": "El-Remaily" }, { "first": "Atash V.", "last": "Gurbanov" }, { "first": "Ali N.", "last": "Khalilov" }, { "first": "Seik Weng", "last": "Ng" } ] }

PMC3052169

Related literature {#sec1} ================== For the preparation of the title compound see: Lamani *et al.* (2009[@bb8]). For the biological activity of benzisoxazole derivatives, see: Priya *et al.* (2005[@bb11]). For the use of five-membered heterocyclic ring 1,3,4-thiadiazoles in the design of compounds, see: Katritzky (1984)[@bb7]; Diamond & Sevrain (2003*a* [@bb3],*b* [@bb4]); Nakao *et al.* (2002*a* [@bb9],*b* [@bb10]). For related structures, see: Sun & Zhang (2009[@bb13]). For hydrogen-bond motifs, see: Bernstein *et al.* 1995[@bb1]) Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~11~ClN~4~OS*M* *~r~* = 366.83Monoclinic,*a* = 38.419 (7) Å*b* = 5.7761 (10) Å*c* = 14.772 (3) Åβ = 108.004 (5)°*V* = 3117.5 (10) Å^3^*Z* = 8Mo *K*α radiationμ = 0.39 mm^−1^*T* = 123 K0.18 × 0.16 × 0.16 mm ### Data collection {#sec2.1.2} Bruker SMART APEX CCD detector diffractometerAbsorption correction: multi-scan Bruker Smart Apex *T* ~min~ = 0.933, *T* ~max~ = 0.9408822 measured reflections3379 independent reflections2587 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.051 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.053*wR*(*F* ^2^) = 0.185*S* = 1.313379 reflections226 parametersH-atom parameters constrainedΔρ~max~ = 0.74 e Å^−3^Δρ~min~ = −0.58 e Å^−3^ {#d5e523} Data collection: *SMART* (Bruker, 1998[@bb2]); cell refinement: *SAINT-Plus* (Bruker, 1998[@bb2]); data reduction: *SAINT-Plus*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb12]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb12]); molecular graphics: *ORTEP-3* (Farrugia, 1997[@bb5]) and *CAMERON* (Watkin *et al.*, 1996)[@bb14]; software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811004582/gw2098sup1.cif](http://dx.doi.org/10.1107/S1600536811004582/gw2098sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004582/gw2098Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004582/gw2098Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gw2098&file=gw2098sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gw2098sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gw2098&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GW2098](http://scripts.iucr.org/cgi-bin/sendsup?gw2098)). NSB is thankful to the University Grants Commission (UGC), India, for financial assistance and the Department of Science and Technology, (DST), India, for the data-collection facility under the IRHPA--DST program. Comment ======= Imidazo\[2,1-*b*\]\[1,3,4\]thiadiazole derivatives are reported to possess diverse pharmacological properties such as anticancer, antitubercular, antibacterial, antifungal, anticonvulsant, analgesic and antisecretory activities. Moreover, the are known to possess important biological activities (Priya *et al.*, 2005) and are useful in different therapies. Amongst them, five membered heterocyclic ring 1,3,4-thiadiazoles find wide application in designing compounds possessing useful properties (Katritzky *et al.*, 1984; Diamond & Sevrain, 2003*a*,*b*; Nakao *et al.*, 2002*a*,*b*). Due to the increasing importance of these heterocycles in biological and pharmaceutical fields, new chemical entities were synthesized by incorporating active pharmacophores in a single molecular frame work so as to enhance their biological activities.In the title compound, the benzisoxazole (O1/N4/C3/C13--18) and imidazothiadiazole (S1/N1---N3/C1/C4---C6) rings are individually planar similar to those reported earlier (Sun & Zhang, 2009) with maximum deviations of 0.038 (3)Å for C1 and 0.016 (3)Å for C3 respectively. The mean planes of the benzisoxazole and imidazothiadiazole are inclined at an angle 23.81 (7)° with each other. The imidazothiadiazole and chlorophenyl rings make a dihedral angle of 27.34 (3)°. The thiadiazole moiety displays differences in the bond lengths between S1---C1/S1---C4 \[1.756 (3)/1.736 (3)\]. This can be attributed to the resonance effects of the imidazole ring which is stronger than that due to thiadiazole group. The crystal structure is stabilized by intermolecular C---H···N, C---H···O and S···N interactions. The C---H···N interaction generates chain like pattern along c axis. The C---H···O interaction forms centrosymmetric head-to-head dimers about inversion centers corresponding to R22(26) graph set motif (Bernstein *et al.*, 1995). The C---H···N interaction along with S···N \[3.206 (4) Å\]interaction results in a ring motif with a graph set *R*(7). The molecular packing is further stabilized by π-π stacking interactions between thiadiazole rings (*Cg*3: centroid of S1/C1/N2/N3/C4) with the shortest centroid---centroid distance 3.497 (3) Å. In addition, π-ring interactions of the type C---H···Cg (*Cg* being the centroids of rings C7---C12 and C13---C18) are also observed in the crystal structure; details have been given in Table 1. Experimental {#experimental} ============ The title compound was synthesized by following the procedure reported earlier (Lamani *et al.*, 2009). Refinement {#refinement} ========== The H atoms were placed at calculated positions in the riding model approximation with aromatic C---H = 0.93Å and methylene C---H = 0.97 Å, and *U*~iso~(H) = 1.2*U*~eq~(N/C). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### ORTEP (Farrugia, 1997) view of the title compound, showing 50% probability ellipsoids and the atom numbering scheme. ::: ![](e-67-0o617-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A unit cell packing of the title compound depicting the C---H···N, C---H···O and S···N intermolecular interactions with dotted lines. H-atoms not involved in hydrogen bonding have been excluded. ::: ![](e-67-0o617-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e158 .table-wrap} ------------------------ --------------------------------------- C~18~H~11~ClN~4~OS *F*(000) = 1504 *M~r~* = 366.83 *D*~x~ = 1.563 Mg m^−3^ Monoclinic, *C*2/*c* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -C 2yc Cell parameters from 3379 reflections *a* = 38.419 (7) Å θ = 2.2--27.0° *b* = 5.7761 (10) Å µ = 0.39 mm^−1^ *c* = 14.772 (3) Å *T* = 123 K β = 108.004 (5)° Block, yellow *V* = 3117.5 (10) Å^3^ 0.18 × 0.16 × 0.16 mm *Z* = 8 ------------------------ --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e283 .table-wrap} ----------------------------------------------------- -------------------------------------- Bruker SMART APEX CCD detector diffractometer 3379 independent reflections Radiation source: fine-focus sealed tube 2587 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.051 ω scans θ~max~ = 27.0°, θ~min~ = 2.2° Absorption correction: multi-scan Bruker Smart Apex *h* = −46→48 *T*~min~ = 0.933, *T*~max~ = 0.940 *k* = −6→7 8822 measured reflections *l* = −18→14 ----------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e394 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.053 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.185 H-atom parameters constrained *S* = 1.31 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0894*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 3379 reflections (Δ/σ)~max~ \< 0.001 226 parameters Δρ~max~ = 0.74 e Å^−3^ 0 restraints Δρ~min~ = −0.58 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e548 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. The compound was synthesized by following the procedure given in Lamani *et al.*, (2009) Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e656 .table-wrap} ----- ------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.19871 (8) 0.2236 (5) 0.1424 (2) 0.0151 (6) C2 0.16451 (8) 0.1564 (5) 0.1657 (2) 0.0183 (7) H2A 0.1565 0.0071 0.1366 0.022\* H2B 0.1711 0.1355 0.2341 0.022\* C3 0.13263 (8) 0.3171 (5) 0.1363 (2) 0.0166 (7) C4 0.25323 (8) 0.4023 (5) 0.1246 (2) 0.0160 (7) C5 0.28417 (8) 0.0835 (6) 0.1177 (2) 0.0167 (6) H5 0.2910 −0.0704 0.1157 0.020\* C6 0.30436 (8) 0.2790 (5) 0.1142 (2) 0.0149 (6) C7 0.34193 (8) 0.2930 (5) 0.1098 (2) 0.0148 (7) C8 0.35464 (9) 0.4896 (5) 0.0746 (2) 0.0181 (7) H8 0.3389 0.6139 0.0527 0.022\* C9 0.39034 (9) 0.5024 (5) 0.0718 (2) 0.0192 (7) H9 0.3986 0.6340 0.0484 0.023\* C10 0.41322 (8) 0.3176 (6) 0.1039 (2) 0.0183 (7) C11 0.40183 (9) 0.1192 (6) 0.1396 (2) 0.0206 (7) H11 0.4178 −0.0038 0.1616 0.025\* C12 0.36610 (8) 0.1082 (6) 0.1418 (2) 0.0178 (7) H12 0.3580 −0.0244 0.1649 0.021\* C13 0.07777 (9) 0.4766 (5) 0.1117 (2) 0.0176 (7) C14 0.04157 (9) 0.5159 (6) 0.1076 (2) 0.0209 (7) H14 0.0292 0.6519 0.0834 0.025\* C15 0.02526 (9) 0.3370 (6) 0.1424 (2) 0.0219 (7) H15 0.0010 0.3519 0.1407 0.026\* C16 0.04440 (8) 0.1336 (6) 0.1800 (3) 0.0212 (7) H16 0.0326 0.0188 0.2036 0.025\* C17 0.08036 (8) 0.1001 (6) 0.1828 (2) 0.0178 (7) H17 0.0928 −0.0352 0.2074 0.021\* C18 0.09718 (8) 0.2764 (5) 0.1474 (2) 0.0166 (7) O1 0.09977 (6) 0.6281 (4) 0.08271 (17) 0.0222 (5) N1 0.28445 (7) 0.4813 (4) 0.11762 (19) 0.0161 (6) N2 0.22129 (7) 0.0628 (5) 0.13533 (19) 0.0171 (6) N3 0.25177 (7) 0.1673 (4) 0.12454 (19) 0.0158 (6) N4 0.13496 (7) 0.5207 (5) 0.1006 (2) 0.0208 (6) S1 0.21240 (2) 0.51078 (13) 0.13431 (6) 0.0182 (2) Cl1 0.45843 (2) 0.33439 (15) 0.10073 (6) 0.0267 (3) ----- ------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1135 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0141 (14) 0.0126 (15) 0.0175 (16) 0.0005 (12) 0.0032 (13) 0.0015 (12) C2 0.0170 (15) 0.0154 (16) 0.0248 (18) 0.0016 (12) 0.0095 (14) 0.0034 (13) C3 0.0197 (15) 0.0141 (15) 0.0155 (16) −0.0028 (12) 0.0049 (13) −0.0002 (12) C4 0.0202 (15) 0.0121 (15) 0.0152 (16) 0.0008 (12) 0.0047 (13) −0.0006 (12) C5 0.0152 (14) 0.0138 (15) 0.0214 (16) 0.0032 (12) 0.0062 (13) 0.0002 (13) C6 0.0131 (14) 0.0162 (16) 0.0153 (16) −0.0011 (12) 0.0042 (13) 0.0011 (12) C7 0.0137 (14) 0.0156 (16) 0.0159 (16) −0.0034 (12) 0.0054 (12) −0.0023 (12) C8 0.0206 (16) 0.0157 (16) 0.0191 (17) 0.0021 (12) 0.0078 (14) 0.0006 (12) C9 0.0252 (17) 0.0161 (17) 0.0176 (17) −0.0052 (13) 0.0086 (14) −0.0021 (12) C10 0.0142 (14) 0.0231 (17) 0.0179 (17) −0.0048 (12) 0.0051 (13) −0.0056 (13) C11 0.0231 (16) 0.0177 (17) 0.0220 (18) 0.0049 (13) 0.0084 (14) −0.0019 (13) C12 0.0193 (15) 0.0169 (16) 0.0178 (17) 0.0012 (13) 0.0067 (13) 0.0014 (13) C13 0.0190 (16) 0.0158 (16) 0.0204 (17) −0.0004 (12) 0.0096 (14) 0.0009 (13) C14 0.0194 (16) 0.0200 (17) 0.0220 (18) 0.0035 (13) 0.0042 (14) 0.0000 (13) C15 0.0177 (16) 0.0283 (19) 0.0209 (18) −0.0017 (13) 0.0077 (14) −0.0013 (14) C16 0.0149 (15) 0.0216 (17) 0.0276 (19) −0.0029 (13) 0.0075 (14) 0.0010 (14) C17 0.0172 (15) 0.0163 (16) 0.0202 (17) 0.0005 (12) 0.0060 (13) 0.0023 (13) C18 0.0136 (14) 0.0178 (16) 0.0183 (16) 0.0011 (12) 0.0049 (13) −0.0003 (13) O1 0.0200 (11) 0.0167 (12) 0.0325 (14) 0.0044 (9) 0.0120 (11) 0.0055 (10) N1 0.0114 (12) 0.0167 (14) 0.0206 (14) 0.0006 (10) 0.0054 (11) −0.0008 (11) N2 0.0127 (12) 0.0178 (14) 0.0211 (15) −0.0055 (10) 0.0059 (11) 0.0001 (11) N3 0.0174 (13) 0.0115 (13) 0.0189 (15) −0.0012 (10) 0.0059 (11) 0.0013 (10) N4 0.0147 (13) 0.0244 (16) 0.0251 (16) 0.0015 (11) 0.0087 (12) 0.0010 (12) S1 0.0184 (4) 0.0124 (4) 0.0257 (5) −0.0008 (3) 0.0096 (4) −0.0007 (3) Cl1 0.0177 (4) 0.0329 (5) 0.0318 (5) −0.0021 (3) 0.0110 (4) −0.0057 (4) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1603 .table-wrap} ----------------------- ------------ ---------------------- ------------ C1---N2 1.297 (4) C9---C10 1.371 (4) C1---C2 1.508 (4) C9---H9 0.9300 C1---S1 1.756 (3) C10---C11 1.387 (5) C2---C3 1.490 (4) C10---Cl1 1.755 (3) C2---H2A 0.9700 C11---C12 1.384 (4) C2---H2B 0.9700 C11---H11 0.9300 C3---N4 1.304 (4) C12---H12 0.9300 C3---C18 1.440 (4) C13---O1 1.374 (4) C4---N1 1.316 (4) C13---C14 1.392 (4) C4---N3 1.358 (4) C13---C18 1.389 (4) C4---S1 1.736 (3) C14---C15 1.387 (5) C5---C6 1.380 (4) C14---H14 0.9300 C5---N3 1.369 (4) C15---C16 1.406 (5) C5---H5 0.9300 C15---H15 0.9300 C6---N1 1.406 (4) C16---C17 1.383 (4) C6---C7 1.468 (4) C16---H16 0.9300 C7---C12 1.398 (4) C17---C18 1.392 (4) C7---C8 1.398 (4) C17---H17 0.9300 C8---C9 1.387 (4) O1---N4 1.436 (3) C8---H8 0.9300 N2---N3 1.370 (3) N2---C1---C2 119.1 (3) C12---C11---C10 118.5 (3) N2---C1---S1 116.7 (2) C12---C11---H11 120.7 C2---C1---S1 124.0 (2) C10---C11---H11 120.7 C3---C2---C1 117.9 (3) C11---C12---C7 121.1 (3) C3---C2---H2A 107.8 C11---C12---H12 119.4 C1---C2---H2A 107.8 C7---C12---H12 119.4 C3---C2---H2B 107.8 O1---C13---C14 125.8 (3) C1---C2---H2B 107.8 O1---C13---C18 109.8 (3) H2A---C2---H2B 107.2 C14---C13---C18 124.4 (3) N4---C3---C18 112.3 (3) C13---C14---C15 115.0 (3) N4---C3---C2 121.8 (3) C13---C14---H14 122.5 C18---C3---C2 125.9 (3) C15---C14---H14 122.5 N1---C4---N3 112.7 (3) C14---C15---C16 121.9 (3) N1---C4---S1 138.5 (3) C14---C15---H15 119.1 N3---C4---S1 108.8 (2) C16---C15---H15 119.1 C6---C5---N3 104.3 (3) C17---C16---C15 121.6 (3) C6---C5---H5 127.8 C17---C16---H16 119.2 N3---C5---H5 127.8 C15---C16---H16 119.2 C5---C6---N1 111.2 (3) C16---C17---C18 117.5 (3) C5---C6---C7 128.2 (3) C16---C17---H17 121.3 N1---C6---C7 120.6 (3) C18---C17---H17 121.3 C12---C7---C8 118.3 (3) C17---C18---C13 119.7 (3) C12---C7---C6 120.2 (3) C17---C18---C3 136.7 (3) C8---C7---C6 121.5 (3) C13---C18---C3 103.7 (3) C9---C8---C7 121.1 (3) C13---O1---N4 107.6 (2) C9---C8---H8 119.4 C4---N1---C6 103.5 (2) C7---C8---H8 119.4 C1---N2---N3 108.1 (3) C10---C9---C8 118.8 (3) C4---N3---N2 118.5 (3) C10---C9---H9 120.6 C4---N3---C5 108.4 (3) C8---C9---H9 120.6 N2---N3---C5 133.0 (3) C9---C10---C11 122.1 (3) C3---N4---O1 106.6 (2) C9---C10---Cl1 118.8 (2) C4---S1---C1 87.82 (14) C11---C10---Cl1 119.1 (2) N2---C1---C2---C3 −155.9 (3) O1---C13---C18---C3 −0.9 (3) S1---C1---C2---C3 30.1 (4) C14---C13---C18---C3 179.8 (3) C1---C2---C3---N4 −7.1 (5) N4---C3---C18---C17 −177.9 (4) C1---C2---C3---C18 176.2 (3) C2---C3---C18---C17 −0.9 (6) N3---C5---C6---N1 −0.8 (3) N4---C3---C18---C13 1.6 (4) N3---C5---C6---C7 177.9 (3) C2---C3---C18---C13 178.6 (3) C5---C6---C7---C12 −22.8 (5) C14---C13---O1---N4 179.2 (3) N1---C6---C7---C12 155.8 (3) C18---C13---O1---N4 0.0 (3) C5---C6---C7---C8 157.7 (3) N3---C4---N1---C6 −0.8 (3) N1---C6---C7---C8 −23.7 (4) S1---C4---N1---C6 178.9 (3) C12---C7---C8---C9 −0.3 (5) C5---C6---N1---C4 1.0 (3) C6---C7---C8---C9 179.2 (3) C7---C6---N1---C4 −177.8 (3) C7---C8---C9---C10 0.2 (5) C2---C1---N2---N3 −173.3 (3) C8---C9---C10---C11 −0.3 (5) S1---C1---N2---N3 1.1 (3) C8---C9---C10---Cl1 −179.8 (2) N1---C4---N3---N2 177.4 (3) C9---C10---C11---C12 0.5 (5) S1---C4---N3---N2 −2.5 (3) Cl1---C10---C11---C12 180.0 (2) N1---C4---N3---C5 0.3 (4) C10---C11---C12---C7 −0.7 (5) S1---C4---N3---C5 −179.5 (2) C8---C7---C12---C11 0.6 (5) C1---N2---N3---C4 0.9 (4) C6---C7---C12---C11 −179.0 (3) C1---N2---N3---C5 177.1 (3) O1---C13---C14---C15 −179.3 (3) C6---C5---N3---C4 0.3 (3) C18---C13---C14---C15 −0.1 (5) C6---C5---N3---N2 −176.1 (3) C13---C14---C15---C16 0.9 (5) C18---C3---N4---O1 −1.7 (4) C14---C15---C16---C17 −1.1 (5) C2---C3---N4---O1 −178.8 (3) C15---C16---C17---C18 0.4 (5) C13---O1---N4---C3 1.1 (3) C16---C17---C18---C13 0.4 (5) N1---C4---S1---C1 −177.4 (4) C16---C17---C18---C3 179.8 (4) N3---C4---S1---C1 2.4 (2) O1---C13---C18---C17 178.7 (3) N2---C1---S1---C4 −2.1 (3) C14---C13---C18---C17 −0.6 (5) C2---C1---S1---C4 172.1 (3) ----------------------- ------------ ---------------------- ------------ ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2426 .table-wrap} -------------------------------------------------------------------------------- Cg1 and Cg2 are the centroids of the C7--C12 and C13--C18 rings, respectively. -------------------------------------------------------------------------------- ::: ::: {#d1e2430 .table-wrap} --------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* C9---H9···O1^i^ 0.93 2.39 3.232 (4) 150 C2---H2B···N1^ii^ 0.97 2.49 3.352 (4) 148 C5---H5···N1^iii^ 0.93 2.60 3.478 (4) 157 C17---H17···Cg1^iv^ 0.93 2.78 3.470 (4) 131 C11---H11···Cg2^iv^ 0.93 2.93 3.548 (4) 126 --------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1/2, −*y*+3/2, −*z*; (ii) −*x*+1/2, *y*−1/2, −*z*+1/2; (iii) *x*, *y*−1, *z*; (iv) −*x*+1/2, *y*+1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 and *Cg*2 are the centroids of the C7--C12 and C13--C18 rings, respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- --------- ------- ----------- ------------- C9---H9⋯O1^i^ 0.93 2.39 3.232 (4) 150 C2---H2*B*⋯N1^ii^ 0.97 2.49 3.352 (4) 148 C5---H5⋯N1^iii^ 0.93 2.60 3.478 (4) 157 C17---H17⋯*Cg*1^iv^ 0.93 2.78 3.470 (4) 131 C11---H11⋯*Cg*2^iv^ 0.93 2.93 3.548 (4) 126 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . :::

PubMed Central

2024-06-05T04:04:18.917327

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052169/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):o617-o618", "authors": [ { "first": "Afshan", "last": "Banu" }, { "first": "Mohamed", "last": "Ziaulla" }, { "first": "Noor Shahina", "last": "Begum" }, { "first": "Ravi S.", "last": "Lamani" }, { "first": "I. M.", "last": "Khazi" } ] }

PMC3052170

Related literature {#sec1} ================== For metal complexes with phosphoryl donor ligands, see: Gholivand *et al.* (2010[@bb4]). For a polyoxometalate-based inorganic--organic compound containing a phosphoryl ligand, see: Niu *et al.* (1996[@bb6]). For phosphoric triamide compounds having a C(=O)NHP(=O) skeleton, see: Pourayoubi & Sabbaghi (2009[@bb7]) and references cited therein. For bond lengths in related structures, see: Sabbaghi *et al.* (2010[@bb8]). For hydrogen-bond motifs, see: Etter *et al.* (1990[@bb3]); Bernstein *et al.* (1995[@bb1]). For the synthesis of the starting material, CClF~2~C(O)NHP(O)Cl~2~, see: Iriarte *et al.* (2008[@bb5]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~21~ClF~2~N~3~O~2~P*M* *~r~* = 415.80Triclinic,*a* = 10.3059 (9) Å*b* = 10.5030 (9) Å*c* = 10.9473 (9) Åα = 71.743 (2)°β = 67.294 (2)°γ = 63.265 (2)°*V* = 962.15 (14) Å^3^*Z* = 2Mo *K*α radiationμ = 0.32 mm^−1^*T* = 120 K0.28 × 0.22 × 0.15 mm ### Data collection {#sec2.1.2} Bruker SMART 1000 CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 1998[@bb9]) *T* ~min~ = 0.916, *T* ~max~ = 0.9549258 measured reflections4148 independent reflections3359 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.025 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.049*wR*(*F* ^2^) = 0.111*S* = 1.004148 reflections247 parametersH-atom parameters constrainedΔρ~max~ = 0.39 e Å^−3^Δρ~min~ = −0.37 e Å^−3^ {#d5e534} Data collection: *SMART* (Bruker, 1998[@bb2]); cell refinement: *SAINT-Plus* (Bruker, 1998[@bb2]); data reduction: *SAINT-Plus*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb10]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811005423/lh5205sup1.cif](http://dx.doi.org/10.1107/S1600536811005423/lh5205sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005423/lh5205Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005423/lh5205Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?lh5205&file=lh5205sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?lh5205sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?lh5205&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [LH5205](http://scripts.iucr.org/cgi-bin/sendsup?lh5205)). Support of this investigation by Islamic Azad University--North Tehran Branch is gratefully acknowledged. Comment ======= Phosphoryl donor ligands have been used to prepare coordination complexes (Gholivand *et al.*, 2010) and polyoxometalate-based inorganic-organic hybrid compounds (Niu *et al.*, 1996). The structure determination of title compound was performed as a part of a project on the synthesis of new potential phosphoric triamide ligands having a C(═O)NHP(═O) skeleton (Pourayoubi & Sabbaghi, 2009). In the title compound, C~18~H~21~ClF~2~N~3~O~2~P, the phosphoryl group and NH unit are *syn* to each other and the phosphorus atom has a slightly distorted tetrahedral configuration (Fig. 1). The P atom adopts a slightly distorted tetrahedral environment and the N atoms of the tertiary amine groups are bonded in an essentially planar geometry (see Table 1). The P═O bond length is comparable to those in similar compounds e.g. in P(O)\[NHC(O)C~6~H~4~(4-NO~2~)\]\[NHC~6~H~11~\]~2~ (Sabbaghi *et al.*, 2010). In the (CClF~2~)C(O) unit, the O---C---C---F dihedral angles showing the orientation of flourine atoms relative to carbonyl group are 17.7 (3) and 137.1 (2)° and the O---C---C---Cl dihedral angle is -101.9 (2)°. The phosphoryl is a better H-acceptor relative to the carbonyl counterpart (Pourayoubi & Sabbaghi, 2009); so, the hydrogen atom of the C(═ O)NHP(═ O) group is involved in an intermolecular --P═O···H---N-- hydrogen bond (see Table 2) to form a centrosymmetric dimeric aggregate \[graph set: *R*~2~^2^(8) (Etter *et al.*, 1990; Bernstein *et al.*, 1995)\], Fig. 2. Experimental {#experimental} ============ Synthesis of CClF~2~C(O)NHP(O)Cl~2~: CClF~2~C(O)NHP(O)Cl~2~ was prepared according to procedure reported by Iriarte *et al.* (2008) from a reaction between phosphorus pentachloride (16.91 mmol) and CClF~2~C(O)NH~2~ (16.91 mmol) in dry CCl~4~ at 358 K (3 h) and then the treatment of formic acid (16.91 mmol) at ice bath temperature; then removing of solvent in vacuum to yield CClF~2~C(O)NHP(O)Cl~2~. Synthesis of title compound: To a solution of CClF~2~C(O)NHP(O)Cl~2~ (1.04 mmol) in dry CHCl~3~, a solution of *N*-methylbenzylamine (4.16 mmol) in dry CHCl~3~ was added dropwise and stirred at 273 K. After 4 h, the solvent was removed at room temperature. The solid was washed with H~2~O. The product was obtained after recrystallization from a methanol/n-heptane mixture (4:1) after a slow evaporation at room temperature. IR (KBr, cm^-1^): 3066, 2886, 1729 (C═O), 1592, 1481, 1359, 1286, 1218, 1150, 1009, 965, 863, 809, 698. ^19^F NMR (470.59 MHz, DMSO-d6, 300 K, CFCl~3~): -63.69 p.p.m. (*s*). ^31^P{^1^H} NMR (202.46 MHz, DMSO-d6, 300 K, 85% H~3~PO~4~): 12.80 p.p.m. (*s*). ^1^H NMR (500.13 MHz, DMSO-d6, 300 K, TMS): 2.48 (*s*, 3H, CH~3~), 2.50 (*s*, 3H, CH~3~), 4.16 (*m*, 4H, CH~2~), 7.25--7.38 (*m*, 10H, Ar--H), 10.60 p.p.m. (*s*, 1H, NH). ^13^C NMR (125.76 MHz, DMSO-d6, 300 K, TMS): 33.16 (*d*, ^2^J(P,*C*) = 4.6 Hz, 2 C, CH~3~), 51.78 (*d*, ^2^J(P,*C*) = 5.1 Hz, 2 C, CH~2~), 118.08 (*dt*, 1C, CClF~2~), 127.17 (*s*), 127.96 (*s*), 128.32 (*s*), 137.68 (*d*, ^3^J(P,*C*) = 3.9 Hz, 2 C, C*~ipso~*), 159.81 p.p.m. (*t*, ^2^J(F,*C*) = 35.0 Hz, 1 C, C═O). Refinement {#refinement} ========== H atoms were placed in calculated postions with C---H = 0.95 - 0.99Å and N---H = 0.87Å and were included in the refinement with U~iso~(H) = 1.2U~eq~(C) or 1.5U~eq~(C~methyl~). The U~iso~(H) value of the H atom bonded to N3 was refined. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound with displacement ellipsoids at the 50% probability level. ::: ![](e-67-0o663-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### A view of the H-bonded (dashed lines) centrosymmetric dimer (symmetry code: (A) 1-x, 1-y, -z). ::: ![](e-67-0o663-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e381 .table-wrap} --------------------------- --------------------------------------- C~18~H~21~ClF~2~N~3~O~2~P *Z* = 2 *M~r~* = 415.80 *F*(000) = 432 Triclinic, *P*1 *D*~x~ = 1.435 Mg m^−3^ Hall symbol: -P 1 Mo *K*α radiation, λ = 0.71073 Å *a* = 10.3059 (9) Å Cell parameters from 3946 reflections *b* = 10.5030 (9) Å θ = 2.3--29.1° *c* = 10.9473 (9) Å µ = 0.32 mm^−1^ α = 71.743 (2)° *T* = 120 K β = 67.294 (2)° Prism, colourless γ = 63.265 (2)° 0.28 × 0.22 × 0.15 mm *V* = 962.15 (14) Å^3^ --------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e521 .table-wrap} --------------------------------------------------------------- -------------------------------------- Bruker SMART 1000 CCD area-detector diffractometer 4148 independent reflections Radiation source: fine-focus sealed tube 3359 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.025 φ and ω scans θ~max~ = 27.0°, θ~min~ = 2.1° Absorption correction: multi-scan (*SADABS*; Sheldrick, 1998) *h* = −13→13 *T*~min~ = 0.916, *T*~max~ = 0.954 *k* = −13→13 9258 measured reflections *l* = −13→13 --------------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e638 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.049 Hydrogen site location: mixed *wR*(*F*^2^) = 0.111 H-atom parameters constrained *S* = 1.00 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0309*P*)^2^ + 1.6759*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 4148 reflections (Δ/σ)~max~ \< 0.001 247 parameters Δρ~max~ = 0.39 e Å^−3^ 0 restraints Δρ~min~ = −0.37 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e795 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e894 .table-wrap} ------ -------------- -------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ P1 0.24133 (6) 0.55399 (6) 0.07097 (5) 0.01766 (13) Cl1 0.40224 (7) 0.93801 (7) −0.06620 (6) 0.03255 (16) F1 0.45008 (15) 0.79512 (15) 0.15810 (14) 0.0304 (3) F2 0.25207 (16) 0.99322 (15) 0.16926 (15) 0.0346 (3) O1 0.37544 (16) 0.44767 (15) −0.00684 (15) 0.0207 (3) O2 0.09472 (17) 0.85802 (17) 0.16326 (17) 0.0290 (4) N1 0.11179 (19) 0.66717 (19) −0.00324 (17) 0.0194 (4) N2 0.1560 (2) 0.47741 (19) 0.21311 (17) 0.0205 (4) N3 0.3102 (2) 0.66075 (19) 0.09736 (18) 0.0197 (4) H3N 0.4088 0.6297 0.0731 0.039 (8)\* C1 −0.0432 (3) 0.6755 (3) 0.0358 (2) 0.0300 (5) H1A −0.0678 0.6791 −0.0435 0.045\* H1B −0.1129 0.7630 0.0751 0.045\* H1C −0.0534 0.5902 0.1021 0.045\* C2 0.1497 (3) 0.7723 (2) −0.1223 (2) 0.0232 (4) H2A 0.2436 0.7795 −0.1257 0.028\* H2B 0.0671 0.8685 −0.1125 0.028\* C3 0.1726 (2) 0.7347 (2) −0.2540 (2) 0.0215 (4) C4 0.1249 (2) 0.8454 (2) −0.3561 (2) 0.0241 (5) H4A 0.0693 0.9420 −0.3396 0.029\* C5 0.1583 (3) 0.8152 (3) −0.4825 (2) 0.0281 (5) H5A 0.1265 0.8912 −0.5521 0.034\* C6 0.2378 (3) 0.6744 (3) −0.5067 (2) 0.0299 (5) H6A 0.2612 0.6537 −0.5929 0.036\* C7 0.2835 (3) 0.5633 (3) −0.4041 (2) 0.0293 (5) H7A 0.3371 0.4666 −0.4204 0.035\* C8 0.2511 (3) 0.5929 (2) −0.2784 (2) 0.0254 (5) H8A 0.2825 0.5165 −0.2088 0.030\* C9 0.0398 (3) 0.5614 (2) 0.3182 (2) 0.0254 (5) H9A −0.0450 0.5282 0.3573 0.038\* H9B 0.0031 0.6641 0.2790 0.038\* H9C 0.0839 0.5478 0.3885 0.038\* C10 0.2044 (3) 0.3195 (2) 0.2526 (2) 0.0235 (4) H10A 0.2779 0.2738 0.1736 0.028\* H10B 0.1151 0.2927 0.2808 0.028\* C11 0.2766 (2) 0.2604 (2) 0.3657 (2) 0.0217 (4) C12 0.4040 (3) 0.2854 (2) 0.3528 (2) 0.0249 (5) H12A 0.4465 0.3391 0.2720 0.030\* C13 0.4683 (3) 0.2321 (2) 0.4577 (2) 0.0263 (5) H13A 0.5547 0.2497 0.4485 0.032\* C14 0.4077 (3) 0.1535 (2) 0.5757 (2) 0.0267 (5) H14A 0.4521 0.1177 0.6473 0.032\* C15 0.2827 (3) 0.1271 (2) 0.5896 (2) 0.0279 (5) H15A 0.2415 0.0723 0.6702 0.034\* C16 0.2175 (3) 0.1812 (2) 0.4847 (2) 0.0250 (5) H16A 0.1309 0.1635 0.4948 0.030\* C17 0.2317 (2) 0.7958 (2) 0.1275 (2) 0.0213 (4) C18 0.3323 (3) 0.8782 (2) 0.1073 (2) 0.0242 (5) ------ -------------- -------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1556 .table-wrap} ----- ------------- ------------- ------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ P1 0.0166 (3) 0.0174 (3) 0.0179 (3) −0.0063 (2) −0.0047 (2) −0.0021 (2) Cl1 0.0383 (3) 0.0335 (3) 0.0279 (3) −0.0217 (3) −0.0053 (2) −0.0007 (2) F1 0.0315 (7) 0.0306 (7) 0.0366 (8) −0.0135 (6) −0.0154 (6) −0.0052 (6) F2 0.0362 (8) 0.0289 (7) 0.0408 (8) −0.0132 (6) −0.0024 (6) −0.0182 (6) O1 0.0184 (7) 0.0203 (7) 0.0230 (8) −0.0061 (6) −0.0055 (6) −0.0059 (6) O2 0.0209 (8) 0.0242 (8) 0.0371 (9) −0.0052 (7) −0.0030 (7) −0.0108 (7) N1 0.0179 (8) 0.0201 (9) 0.0189 (9) −0.0076 (7) −0.0057 (7) −0.0004 (7) N2 0.0197 (9) 0.0193 (9) 0.0186 (8) −0.0077 (7) −0.0038 (7) 0.0002 (7) N3 0.0167 (8) 0.0188 (9) 0.0237 (9) −0.0056 (7) −0.0065 (7) −0.0044 (7) C1 0.0195 (11) 0.0406 (14) 0.0272 (12) −0.0104 (10) −0.0092 (9) −0.0002 (10) C2 0.0294 (11) 0.0194 (10) 0.0213 (11) −0.0098 (9) −0.0103 (9) 0.0008 (8) C3 0.0211 (10) 0.0259 (11) 0.0195 (10) −0.0124 (9) −0.0057 (8) −0.0013 (8) C4 0.0208 (10) 0.0270 (11) 0.0239 (11) −0.0105 (9) −0.0070 (9) −0.0005 (9) C5 0.0277 (12) 0.0373 (13) 0.0210 (11) −0.0146 (10) −0.0114 (9) 0.0023 (9) C6 0.0314 (12) 0.0449 (14) 0.0208 (11) −0.0212 (11) −0.0062 (9) −0.0060 (10) C7 0.0321 (12) 0.0300 (12) 0.0285 (12) −0.0155 (10) −0.0046 (10) −0.0079 (10) C8 0.0282 (11) 0.0242 (11) 0.0246 (11) −0.0125 (9) −0.0084 (9) 0.0001 (9) C9 0.0250 (11) 0.0295 (12) 0.0173 (10) −0.0114 (9) −0.0016 (9) −0.0023 (9) C10 0.0275 (11) 0.0203 (10) 0.0243 (11) −0.0116 (9) −0.0102 (9) 0.0016 (8) C11 0.0236 (10) 0.0171 (10) 0.0237 (11) −0.0063 (8) −0.0084 (9) −0.0025 (8) C12 0.0253 (11) 0.0253 (11) 0.0236 (11) −0.0119 (9) −0.0055 (9) −0.0020 (9) C13 0.0222 (11) 0.0258 (11) 0.0317 (12) −0.0078 (9) −0.0096 (9) −0.0054 (9) C14 0.0273 (11) 0.0249 (11) 0.0264 (11) −0.0042 (9) −0.0125 (9) −0.0051 (9) C15 0.0308 (12) 0.0236 (11) 0.0241 (11) −0.0102 (10) −0.0080 (9) 0.0026 (9) C16 0.0242 (11) 0.0245 (11) 0.0268 (11) −0.0116 (9) −0.0092 (9) 0.0013 (9) C17 0.0235 (11) 0.0205 (10) 0.0192 (10) −0.0088 (9) −0.0054 (8) −0.0025 (8) C18 0.0249 (11) 0.0205 (10) 0.0261 (11) −0.0072 (9) −0.0055 (9) −0.0068 (9) ----- ------------- ------------- ------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e2156 .table-wrap} -------------------- -------------- ----------------------- -------------- P1---O1 1.4769 (15) C5---H5A 0.9500 P1---N2 1.6241 (18) C6---C7 1.391 (3) P1---N1 1.6308 (18) C6---H6A 0.9500 P1---N3 1.7093 (18) C7---C8 1.387 (3) Cl1---C18 1.768 (2) C7---H7A 0.9500 F1---C18 1.345 (3) C8---H8A 0.9500 F2---C18 1.336 (2) C9---H9A 0.9800 O2---C17 1.215 (3) C9---H9B 0.9800 N1---C1 1.453 (3) C9---H9C 0.9800 N1---C2 1.471 (3) C10---C11 1.512 (3) N2---C9 1.469 (3) C10---H10A 0.9900 N2---C10 1.469 (3) C10---H10B 0.9900 N3---C17 1.353 (3) C11---C16 1.387 (3) N3---H3N 0.8700 C11---C12 1.399 (3) C1---H1A 0.9800 C12---C13 1.387 (3) C1---H1B 0.9800 C12---H12A 0.9500 C1---H1C 0.9800 C13---C14 1.383 (3) C2---C3 1.517 (3) C13---H13A 0.9500 C2---H2A 0.9900 C14---C15 1.379 (3) C2---H2B 0.9900 C14---H14A 0.9500 C3---C4 1.393 (3) C15---C16 1.391 (3) C3---C8 1.394 (3) C15---H15A 0.9500 C4---C5 1.394 (3) C16---H16A 0.9500 C4---H4A 0.9500 C17---C18 1.543 (3) C5---C6 1.384 (4) O1---P1---N2 112.34 (9) C7---C8---C3 120.0 (2) O1---P1---N1 117.13 (9) C7---C8---H8A 120.0 N2---P1---N1 107.02 (9) C3---C8---H8A 120.0 O1---P1---N3 105.06 (9) N2---C9---H9A 109.5 N2---P1---N3 110.57 (9) N2---C9---H9B 109.5 N1---P1---N3 104.38 (9) H9A---C9---H9B 109.5 C1---N1---C2 114.36 (17) N2---C9---H9C 109.5 C1---N1---P1 126.21 (15) H9A---C9---H9C 109.5 C2---N1---P1 119.42 (14) H9B---C9---H9C 109.5 C9---N2---C10 115.45 (17) N2---C10---C11 113.28 (18) C9---N2---P1 121.56 (14) N2---C10---H10A 108.9 C10---N2---P1 122.42 (15) C11---C10---H10A 108.9 C17---N3---P1 127.29 (15) N2---C10---H10B 108.9 C17---N3---H3N 117.5 C11---C10---H10B 108.9 P1---N3---H3N 114.0 H10A---C10---H10B 107.7 N1---C1---H1A 109.5 C16---C11---C12 118.6 (2) N1---C1---H1B 109.5 C16---C11---C10 120.9 (2) H1A---C1---H1B 109.5 C12---C11---C10 120.59 (19) N1---C1---H1C 109.5 C13---C12---C11 120.2 (2) H1A---C1---H1C 109.5 C13---C12---H12A 119.9 H1B---C1---H1C 109.5 C11---C12---H12A 119.9 N1---C2---C3 114.05 (17) C14---C13---C12 120.4 (2) N1---C2---H2A 108.7 C14---C13---H13A 119.8 C3---C2---H2A 108.7 C12---C13---H13A 119.8 N1---C2---H2B 108.7 C15---C14---C13 120.1 (2) C3---C2---H2B 108.7 C15---C14---H14A 120.0 H2A---C2---H2B 107.6 C13---C14---H14A 120.0 C4---C3---C8 119.4 (2) C14---C15---C16 119.6 (2) C4---C3---C2 119.3 (2) C14---C15---H15A 120.2 C8---C3---C2 121.15 (19) C16---C15---H15A 120.2 C3---C4---C5 120.3 (2) C11---C16---C15 121.2 (2) C3---C4---H4A 119.8 C11---C16---H16A 119.4 C5---C4---H4A 119.8 C15---C16---H16A 119.4 C6---C5---C4 120.1 (2) O2---C17---N3 127.4 (2) C6---C5---H5A 120.0 O2---C17---C18 118.39 (19) C4---C5---H5A 120.0 N3---C17---C18 114.16 (18) C5---C6---C7 119.7 (2) F2---C18---F1 107.18 (18) C5---C6---H6A 120.1 F2---C18---C17 110.49 (18) C7---C6---H6A 120.1 F1---C18---C17 111.98 (17) C8---C7---C6 120.5 (2) F2---C18---Cl1 108.70 (15) C8---C7---H7A 119.8 F1---C18---Cl1 109.06 (15) C6---C7---H7A 119.8 C17---C18---Cl1 109.35 (15) O1---P1---N1---C1 115.12 (19) C6---C7---C8---C3 −0.1 (3) N2---P1---N1---C1 −12.0 (2) C4---C3---C8---C7 1.2 (3) N3---P1---N1---C1 −129.24 (19) C2---C3---C8---C7 −173.7 (2) O1---P1---N1---C2 −64.27 (18) C9---N2---C10---C11 −61.8 (2) N2---P1---N1---C2 168.61 (15) P1---N2---C10---C11 109.64 (19) N3---P1---N1---C2 51.38 (17) N2---C10---C11---C16 122.1 (2) O1---P1---N2---C9 167.42 (16) N2---C10---C11---C12 −57.4 (3) N1---P1---N2---C9 −62.69 (18) C16---C11---C12---C13 −0.2 (3) N3---P1---N2---C9 50.40 (19) C10---C11---C12---C13 179.2 (2) O1---P1---N2---C10 −3.55 (19) C11---C12---C13---C14 0.2 (3) N1---P1---N2---C10 126.34 (17) C12---C13---C14---C15 0.3 (3) N3---P1---N2---C10 −120.57 (16) C13---C14---C15---C16 −0.6 (3) O1---P1---N3---C17 158.89 (18) C12---C11---C16---C15 −0.1 (3) N2---P1---N3---C17 −79.68 (19) C10---C11---C16---C15 −179.6 (2) N1---P1---N3---C17 35.1 (2) C14---C15---C16---C11 0.6 (4) C1---N1---C2---C3 −75.1 (2) P1---N3---C17---O2 13.3 (3) P1---N1---C2---C3 104.32 (19) P1---N3---C17---C18 −164.20 (15) N1---C2---C3---C4 143.87 (19) O2---C17---C18---F2 17.7 (3) N1---C2---C3---C8 −41.2 (3) N3---C17---C18---F2 −164.59 (18) C8---C3---C4---C5 −1.5 (3) O2---C17---C18---F1 137.1 (2) C2---C3---C4---C5 173.5 (2) N3---C17---C18---F1 −45.2 (2) C3---C4---C5---C6 0.7 (3) O2---C17---C18---Cl1 −101.9 (2) C4---C5---C6---C7 0.4 (3) N3---C17---C18---Cl1 75.8 (2) C5---C6---C7---C8 −0.6 (4) -------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e3051 .table-wrap} ------------------ --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N3---H3N···O1^i^ 0.87 1.91 2.772 (3) 174 ------------------ --------- --------- ----------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+1, −*z*. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Selected bond angles (°) ::: --------------- ------------- O1---P1---N2 112.34 (9) O1---P1---N1 117.13 (9) N2---P1---N1 107.02 (9) O1---P1---N3 105.06 (9) N2---P1---N3 110.57 (9) N1---P1---N3 104.38 (9) C1---N1---C2 114.36 (17) C1---N1---P1 126.21 (15) C2---N1---P1 119.42 (14) C9---N2---C10 115.45 (17) C9---N2---P1 121.56 (14) C10---N2---P1 122.42 (15) --------------- ------------- ::: ::: {#table2 .table-wrap} Table 2 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------ --------- ------- ----------- ------------- N3---H3*N*⋯O1^i^ 0.87 1.91 2.772 (3) 174 Symmetry code: (i) . :::

PubMed Central

2024-06-05T04:04:18.922846

2011-2-19

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052170/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 19; 67(Pt 3):o663-o664", "authors": [ { "first": "Akbar", "last": "Raissi Shabari" }, { "first": "Mehrdad", "last": "Pourayoubi" }, { "first": "Anahid", "last": "Saneei" } ] }

PMC3052171

Related literature {#sec1} ================== For similar complexes of the type \[RuCl~2~(DMSO)(arene)\], see: Ogata *et al.* (1970[@bb8]) (arene = benzene); Chandra *et al.* (2002[@bb5]) (arene = *p*-cymene); Beasley *et al.* (1993[@bb2]) (arene = 1,4,9,10-tetrahydroanthracene); Haquette *et al.* (2008[@bb7]) (arene = 9,10-dihydroanthracene); Sadler *et al.* (2005[@bb9]) (arene = 2-chloro-*N*-(2-phenylethyl)acetamide). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} \[RuCl~2~(C~9~H~12~)(C~2~H~6~OS)\]*M* *~r~* = 370.28Monoclinic,*a* = 8.1184 (4) Å*b* = 22.9372 (13) Å*c* = 8.3417 (4) Åβ = 116.443 (3)°*V* = 1390.82 (12) Å^3^*Z* = 4Mo *K*α radiationμ = 1.64 mm^−1^*T* = 100 K0.24 × 0.15 × 0.09 mm ### Data collection {#sec2.1.2} Stoe IPDS 2T diffractometerAbsorption correction: multi-scan (Blessing, 1995[@bb3]) *T* ~min~ = 0.630, *T* ~max~ = 0.9949737 measured reflections2935 independent reflections2753 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.051 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.017*wR*(*F* ^2^) = 0.044*S* = 1.042935 reflections150 parametersH-atom parameters constrainedΔρ~max~ = 0.42 e Å^−3^Δρ~min~ = −0.71 e Å^−3^ {#d5e448} Data collection: *X-AREA* (Stoe & Cie, 2001[@bb11]); cell refinement: *X-AREA*; data reduction: *X-RED* (Stoe & Cie, 2001[@bb11]); program(s) used to solve structure: *SIR92* (Altomare *et al.*, 1993[@bb1]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb10]); molecular graphics: *DIAMOND* (Brandenburg, 2007[@bb4]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb6]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S160053681100314X/kj2168sup1.cif](http://dx.doi.org/10.1107/S160053681100314X/kj2168sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S160053681100314X/kj2168Isup2.hkl](http://dx.doi.org/10.1107/S160053681100314X/kj2168Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?kj2168&file=kj2168sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?kj2168sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?kj2168&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [KJ2168](http://scripts.iucr.org/cgi-bin/sendsup?kj2168)). Routine data collection was performed by the XRD service department (Dr K. Harms, G. Geiseler, R. Riedel) of the Chemistry Department, Philipps University, and is gratefully acknowledged. Comment ======= Complexes of the type \[{RuCl~2~(arene)}~2~\] are valuable starting materials for the preparation of ruthenium(II) complexes because they allow facile ligand substitution. During our investigations concerning the arene substitution behaviour of such complexes, we found that \[{RuCl~2~(C~6~H~3~Me~3~)}~2~\] readily reacts with dimethylsulfoxide, yielding the monomeric title compound \[RuCl~2~(DMSO)(C~6~H~3~Me~3~)\]. Similar reactivity has been reported for the corresponding benzene and *p*-cymene complexes (Ogata *et al.*, 1970; Chandra *et al.*, 2002). The overall complex geometry of the title compound is best described as a piano-stool configuration. Another possible description is that of an octahedral d^6^ low-spin complex with the arene ligand occupying three *fac*-oriented coordination sites. The angles between the monodentate chloro and DMSO ligands are thus close to 90° (Table 1). The planar, η^6^-bound mesitylene ligand shows almost equal Ru--C distances of 2.1978 (15) to 2.2219 (16) Å. Dimethylsulfoxide is coordinated *via* sulfur as usual for complexes without sufficient steric bulk to force *O*-coordination. All numerical parameters concerning the molecular geometry are similar to those observed for the corresponding *p*-cymene complex (Chandra *et al.*, 2002). Experimental {#experimental} ============ \[{RuCl~2~(C~6~H~3~Me~3~)}~2~\] (175 mg, 0.30 mmol) was dissolved in DMSO (12 ml). The solution was heated to 100 °C for 45 min and a small amount of ruthenium black was removed by filtration. The dark red solution was concentrated *in vacuo* until the formation of crystals was observed. The product was isolated by filtration and dried *in vacuo*. A second crop of material was obtained from the mother liquor by layering with toluene. Yield: 150 mg (68%) of red crystals. Crystals suitable for X-ray diffraction were obtained by slow evaporation of a saturated DMSO solution. Refinement {#refinement} ========== Hydrogen atoms were placed on idealized positions and refined using a riding model with *U*~iso~(H) = 1.2 × *U*~eq~(C) (1.5 for methyl groups) and C--H bond lengths of 0.95 Å for aromatic protons and 0.98 Å for methyl groups. Reflexes 0 1 1 and -1 1 1 were omitted from the refinement because they were effected by the diffractometer\'s beamstop. Reflex -5 0 3 was also omitted because of its exceptionally large deviation from the calculated intensity. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### Molecular structure of the title compound. Displacement ellipsoids are shown for 50% probability. ::: ![](e-67-0m319-fig1) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e192 .table-wrap} ------------------------------------ ---------------------------------------- \[RuCl~2~(C~9~H~12~)(C~2~H~6~OS)\] *F*(000) = 744 *M~r~* = 370.28 *D*~x~ = 1.768 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 16004 reflections *a* = 8.1184 (4) Å θ = 1.9--27.2° *b* = 22.9372 (13) Å µ = 1.64 mm^−1^ *c* = 8.3417 (4) Å *T* = 100 K β = 116.443 (3)° Block, light red *V* = 1390.82 (12) Å^3^ 0.24 × 0.15 × 0.09 mm *Z* = 4 ------------------------------------ ---------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e326 .table-wrap} ---------------------------------------------------- -------------------------------------- Stoe IPDS 2T diffractometer 2935 independent reflections Radiation source: fine-focus sealed tube 2753 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.051 Detector resolution: 6.67 pixels mm^-1^ θ~max~ = 26.7°, θ~min~ = 2.9° rotation method scans *h* = −10→10 Absorption correction: multi-scan (Blessing, 1995) *k* = −28→29 *T*~min~ = 0.630, *T*~max~ = 0.994 *l* = −9→10 9737 measured reflections ---------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e441 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------ Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.017 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.044 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0208*P*)^2^ + 0.742*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 2935 reflections (Δ/σ)~max~ = 0.002 150 parameters Δρ~max~ = 0.42 e Å^−3^ 0 restraints Δρ~min~ = −0.71 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------ ::: Special details {#specialdetails} =============== ::: {#d1e598 .table-wrap} ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Experimental. Anal. calc. for C~11~H~18~Cl~2~ORuS (370.29 g/mol) C 35.68, H 4.90%; found C 35.42, H 4.98%. ^1^H NMR (250 MHz, DMSO-*d*~6~, 300 K) δ = 2.14 (s, 9H, CH~3~), 2.54 (s, 6H, DMSO), 5.46 (s, 3H, CH) p.p.m.; ^13^C NMR (75 MHz, DMSO-*d*~6~, 300 K) δ = 18.2 (CH~3~), 40.4 (DMSO), 82.0 (CH), 104.8 (*C*CH~3~) p.p.m.. IR (neat, ATR) ν = 3063 w, 3024 m, 2963 w, 2931 w, 1525 m, 1447 m, 1408 m, 1377 m, 1303 m, 1286 m, 1105 s, 1034 m, 1008 *versus*, 983 s, 971 m, 932 m, 905 m, 887 m, 721 m, 680 m, 641 m, 507 w, 415 s cm^-1^. Geometry. All s.u.\'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.\'s are taken into account individually in the estimation of s.u.\'s in distances, angles and torsion angles; correlations between s.u.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.\'s is used for estimating s.u.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> 2σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e758 .table-wrap} ------ --------------- --------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.1365 (2) 0.08700 (8) −0.1389 (2) 0.0176 (4) C2 0.2204 (2) 0.03526 (7) −0.0475 (2) 0.0172 (3) H2 0.2639 0.0074 −0.1039 0.021\* C3 0.2406 (2) 0.02437 (7) 0.1282 (2) 0.0168 (3) C4 0.1758 (2) 0.06592 (7) 0.2106 (2) 0.0162 (3) H4 0.1889 0.0588 0.3279 0.019\* C5 0.0910 (2) 0.11842 (7) 0.1211 (2) 0.0161 (3) C6 0.0741 (2) 0.12862 (7) −0.0535 (2) 0.0168 (3) H6 0.0201 0.1639 −0.1137 0.020\* C7 0.1190 (3) 0.09819 (10) −0.3227 (2) 0.0283 (4) H7A 0.2138 0.0762 −0.3392 0.042\* H7B 0.1348 0.1399 −0.3369 0.042\* H7C −0.0030 0.0858 −0.4122 0.042\* C8 0.3318 (3) −0.03050 (8) 0.2244 (3) 0.0257 (4) H8A 0.3877 −0.0238 0.3539 0.039\* H8B 0.4273 −0.0420 0.1891 0.039\* H8C 0.2400 −0.0616 0.1930 0.039\* C9 0.0139 (2) 0.16108 (8) 0.2056 (3) 0.0244 (4) H9A −0.1136 0.1506 0.1753 0.037\* H9B 0.0174 0.2004 0.1609 0.037\* H9C 0.0875 0.1602 0.3359 0.037\* C10 0.5260 (2) 0.16583 (7) 0.5447 (2) 0.0178 (3) H10A 0.5907 0.1970 0.6298 0.027\* H10B 0.6034 0.1309 0.5755 0.027\* H10C 0.4105 0.1570 0.5500 0.027\* C11 0.7007 (2) 0.21278 (7) 0.3628 (2) 0.0169 (3) H11A 0.6939 0.2315 0.2544 0.025\* H11B 0.7841 0.1793 0.3935 0.025\* H11C 0.7470 0.2408 0.4618 0.025\* O1 0.35990 (15) 0.24130 (5) 0.28238 (15) 0.0164 (2) S1 0.47771 (5) 0.188752 (16) 0.32416 (5) 0.01120 (8) Cl1 0.65955 (5) 0.066716 (17) 0.30769 (5) 0.01704 (9) Cl2 0.50102 (5) 0.159381 (18) −0.04032 (5) 0.01767 (9) Ru1 0.364774 (16) 0.110410 (5) 0.124893 (15) 0.01033 (5) ------ --------------- --------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1237 .table-wrap} ----- -------------- -------------- -------------- --------------- -------------- --------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0100 (8) 0.0246 (9) 0.0132 (8) −0.0059 (6) 0.0007 (6) −0.0026 (6) C2 0.0133 (8) 0.0158 (7) 0.0200 (8) −0.0048 (6) 0.0052 (6) −0.0089 (6) C3 0.0126 (7) 0.0115 (7) 0.0229 (8) −0.0046 (6) 0.0048 (6) −0.0011 (6) C4 0.0138 (8) 0.0175 (8) 0.0167 (8) −0.0050 (6) 0.0062 (6) 0.0005 (6) C5 0.0102 (8) 0.0152 (7) 0.0219 (8) −0.0033 (6) 0.0063 (7) −0.0044 (6) C6 0.0075 (7) 0.0165 (8) 0.0200 (8) −0.0007 (6) 0.0003 (6) 0.0032 (6) C7 0.0219 (10) 0.0449 (11) 0.0126 (8) −0.0066 (8) 0.0029 (7) −0.0010 (8) C8 0.0215 (9) 0.0144 (8) 0.0358 (10) −0.0009 (7) 0.0079 (8) 0.0028 (7) C9 0.0184 (9) 0.0226 (9) 0.0368 (10) −0.0024 (7) 0.0165 (8) −0.0075 (8) C10 0.0231 (9) 0.0162 (8) 0.0126 (7) −0.0017 (7) 0.0067 (7) −0.0004 (6) C11 0.0140 (8) 0.0169 (8) 0.0189 (8) −0.0046 (6) 0.0065 (6) −0.0047 (6) O1 0.0164 (6) 0.0114 (5) 0.0179 (5) 0.0031 (4) 0.0044 (5) −0.0005 (4) S1 0.01161 (18) 0.00975 (17) 0.01084 (17) −0.00026 (13) 0.00373 (14) −0.00063 (13) Cl1 0.01246 (19) 0.01451 (18) 0.01854 (19) 0.00243 (14) 0.00185 (15) −0.00313 (14) Cl2 0.01695 (19) 0.0227 (2) 0.01450 (18) −0.00450 (15) 0.00802 (15) −0.00160 (14) Ru1 0.00945 (8) 0.00984 (7) 0.01029 (8) −0.00034 (4) 0.00314 (5) −0.00124 (4) ----- -------------- -------------- -------------- --------------- -------------- --------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1577 .table-wrap} --------------------- -------------- ---------------------- -------------- C1---C2 1.411 (2) C7---H7C 0.9800 C1---C6 1.413 (3) C8---H8A 0.9800 C1---C7 1.498 (2) C8---H8B 0.9800 C1---Ru1 2.2209 (15) C8---H8C 0.9800 C2---C3 1.423 (2) C9---H9A 0.9800 C2---Ru1 2.2162 (15) C9---H9B 0.9800 C2---H2 0.9500 C9---H9C 0.9800 C3---C4 1.407 (2) C10---S1 1.7807 (16) C3---C8 1.499 (2) C10---H10A 0.9800 C3---Ru1 2.2219 (16) C10---H10B 0.9800 C4---C5 1.423 (2) C10---H10C 0.9800 C4---Ru1 2.2097 (16) C11---S1 1.7792 (17) C4---H4 0.9500 C11---H11A 0.9800 C5---C6 1.420 (2) C11---H11B 0.9800 C5---C9 1.496 (2) C11---H11C 0.9800 C5---Ru1 2.2160 (17) O1---S1 1.4806 (11) C6---Ru1 2.1978 (15) S1---Ru1 2.3399 (4) C6---H6 0.9500 Cl1---Ru1 2.4097 (4) C7---H7A 0.9800 Cl2---Ru1 2.3963 (4) C7---H7B 0.9800 C2---C1---C6 119.41 (15) S1---C10---H10A 109.5 C2---C1---C7 120.01 (17) S1---C10---H10B 109.5 C6---C1---C7 120.56 (17) H10A---C10---H10B 109.5 C2---C1---Ru1 71.28 (9) S1---C10---H10C 109.5 C6---C1---Ru1 70.47 (9) H10A---C10---H10C 109.5 C7---C1---Ru1 129.03 (12) H10B---C10---H10C 109.5 C1---C2---C3 120.71 (15) S1---C11---H11A 109.5 C1---C2---Ru1 71.64 (9) S1---C11---H11B 109.5 C3---C2---Ru1 71.52 (9) H11A---C11---H11B 109.5 C1---C2---H2 119.6 S1---C11---H11C 109.5 C3---C2---H2 119.6 H11A---C11---H11C 109.5 Ru1---C2---H2 129.7 H11B---C11---H11C 109.5 C4---C3---C2 119.20 (15) O1---S1---C11 106.80 (8) C4---C3---C8 120.71 (16) O1---S1---C10 107.79 (8) C2---C3---C8 120.09 (16) C11---S1---C10 99.56 (8) C4---C3---Ru1 71.02 (9) O1---S1---Ru1 116.76 (5) C2---C3---Ru1 71.09 (9) C11---S1---Ru1 114.32 (6) C8---C3---Ru1 129.33 (12) C10---S1---Ru1 110.09 (6) C3---C4---C5 121.05 (16) C6---Ru1---C4 67.42 (6) C3---C4---Ru1 71.97 (10) C6---Ru1---C5 37.53 (6) C5---C4---Ru1 71.49 (10) C4---Ru1---C5 37.50 (6) C3---C4---H4 119.5 C6---Ru1---C2 67.06 (6) C5---C4---H4 119.5 C4---Ru1---C2 66.92 (6) Ru1---C4---H4 129.6 C5---Ru1---C2 79.51 (6) C6---C5---C4 118.76 (15) C6---Ru1---C1 37.29 (7) C6---C5---C9 120.37 (16) C4---Ru1---C1 79.38 (6) C4---C5---C9 120.83 (16) C5---Ru1---C1 67.47 (6) C6---C5---Ru1 70.54 (9) C2---Ru1---C1 37.08 (6) C4---C5---Ru1 71.01 (9) C6---Ru1---C3 79.68 (6) C9---C5---Ru1 132.43 (12) C4---Ru1---C3 37.01 (6) C1---C6---C5 120.86 (15) C5---Ru1---C3 67.42 (6) C1---C6---Ru1 72.24 (9) C2---Ru1---C3 37.40 (6) C5---C6---Ru1 71.93 (9) C1---Ru1---C3 67.33 (6) C1---C6---H6 119.6 C6---Ru1---S1 107.34 (5) C5---C6---H6 119.6 C4---Ru1---S1 103.51 (4) Ru1---C6---H6 128.6 C5---Ru1---S1 91.13 (4) C1---C7---H7A 109.5 C2---Ru1---S1 170.04 (5) C1---C7---H7B 109.5 C1---Ru1---S1 141.22 (5) H7A---C7---H7B 109.5 C3---Ru1---S1 135.20 (5) C1---C7---H7C 109.5 C6---Ru1---Cl2 98.80 (5) H7A---C7---H7C 109.5 C4---Ru1---Cl2 165.32 (4) H7B---C7---H7C 109.5 C5---Ru1---Cl2 132.05 (5) C3---C8---H8A 109.5 C2---Ru1---Cl2 103.74 (5) C3---C8---H8B 109.5 C1---Ru1---Cl2 86.49 (5) H8A---C8---H8B 109.5 C3---Ru1---Cl2 138.75 (5) C3---C8---H8C 109.5 S1---Ru1---Cl2 85.030 (14) H8A---C8---H8C 109.5 C6---Ru1---Cl1 166.37 (4) H8B---C8---H8C 109.5 C4---Ru1---Cl1 103.89 (4) C5---C9---H9A 109.5 C5---Ru1---Cl1 138.64 (5) C5---C9---H9B 109.5 C2---Ru1---Cl1 100.16 (5) H9A---C9---H9B 109.5 C1---Ru1---Cl1 132.98 (5) C5---C9---H9C 109.5 C3---Ru1---Cl1 87.19 (4) H9A---C9---H9C 109.5 S1---Ru1---Cl1 84.567 (14) H9B---C9---H9C 109.5 Cl2---Ru1---Cl1 88.636 (15) C6---C1---C2---C3 0.8 (2) C9---C5---Ru1---Cl1 86.88 (18) C7---C1---C2---C3 179.05 (15) C1---C2---Ru1---C6 29.22 (10) Ru1---C1---C2---C3 54.15 (14) C3---C2---Ru1---C6 −103.49 (11) C6---C1---C2---Ru1 −53.39 (13) C1---C2---Ru1---C4 103.39 (11) C7---C1---C2---Ru1 124.90 (15) C3---C2---Ru1---C4 −29.32 (10) C1---C2---C3---C4 0.0 (2) C1---C2---Ru1---C5 66.34 (10) Ru1---C2---C3---C4 54.18 (13) C3---C2---Ru1---C5 −66.37 (10) C1---C2---C3---C8 −179.36 (15) C3---C2---Ru1---C1 −132.71 (15) Ru1---C2---C3---C8 −125.15 (15) C1---C2---Ru1---C3 132.71 (15) C1---C2---C3---Ru1 −54.21 (14) C1---C2---Ru1---Cl2 −64.65 (10) C2---C3---C4---C5 −0.1 (2) C3---C2---Ru1---Cl2 162.64 (9) C8---C3---C4---C5 179.26 (15) C1---C2---Ru1---Cl1 −155.73 (9) Ru1---C3---C4---C5 54.15 (14) C3---C2---Ru1---Cl1 71.55 (9) C2---C3---C4---Ru1 −54.21 (13) C2---C1---Ru1---C6 −132.10 (15) C8---C3---C4---Ru1 125.12 (15) C7---C1---Ru1---C6 114.0 (2) C3---C4---C5---C6 −0.6 (2) C2---C1---Ru1---C4 −65.58 (10) Ru1---C4---C5---C6 53.79 (13) C6---C1---Ru1---C4 66.52 (10) C3---C4---C5---C9 176.92 (15) C7---C1---Ru1---C4 −179.48 (19) Ru1---C4---C5---C9 −128.72 (15) C2---C1---Ru1---C5 −102.83 (11) C3---C4---C5---Ru1 −54.37 (14) C6---C1---Ru1---C5 29.27 (10) C2---C1---C6---C5 −1.4 (2) C7---C1---Ru1---C5 143.28 (19) C7---C1---C6---C5 −179.70 (15) C6---C1---Ru1---C2 132.10 (15) Ru1---C1---C6---C5 −55.19 (13) C7---C1---Ru1---C2 −113.9 (2) C2---C1---C6---Ru1 53.77 (13) C2---C1---Ru1---C3 −28.92 (10) C7---C1---C6---Ru1 −124.51 (15) C6---C1---Ru1---C3 103.18 (11) C4---C5---C6---C1 1.3 (2) C7---C1---Ru1---C3 −142.81 (19) C9---C5---C6---C1 −176.18 (15) C2---C1---Ru1---S1 −163.99 (8) Ru1---C5---C6---C1 55.34 (13) C6---C1---Ru1---S1 −31.89 (13) C4---C5---C6---Ru1 −54.01 (13) C7---C1---Ru1---S1 82.11 (19) C9---C5---C6---Ru1 128.48 (15) C2---C1---Ru1---Cl2 118.42 (10) C1---C6---Ru1---C4 −102.51 (11) C6---C1---Ru1---Cl2 −109.48 (9) C5---C6---Ru1---C4 29.64 (9) C7---C1---Ru1---Cl2 4.53 (17) C1---C6---Ru1---C5 −132.15 (14) C2---C1---Ru1---Cl1 33.57 (12) C1---C6---Ru1---C2 −29.07 (10) C6---C1---Ru1---Cl1 165.67 (8) C5---C6---Ru1---C2 103.08 (11) C7---C1---Ru1---Cl1 −80.32 (19) C5---C6---Ru1---C1 132.15 (14) C4---C3---Ru1---C6 −66.00 (10) C1---C6---Ru1---C3 −65.95 (10) C2---C3---Ru1---C6 65.54 (10) C5---C6---Ru1---C3 66.20 (10) C8---C3---Ru1---C6 179.40 (18) C1---C6---Ru1---S1 159.72 (9) C2---C3---Ru1---C4 131.54 (14) C5---C6---Ru1---S1 −68.13 (9) C8---C3---Ru1---C4 −114.6 (2) C1---C6---Ru1---Cl2 72.21 (10) C4---C3---Ru1---C5 −28.87 (9) C5---C6---Ru1---Cl2 −155.64 (9) C2---C3---Ru1---C5 102.67 (11) C1---C6---Ru1---Cl1 −50.2 (2) C8---C3---Ru1---C5 −143.47 (18) C5---C6---Ru1---Cl1 81.9 (2) C4---C3---Ru1---C2 −131.54 (14) C3---C4---Ru1---C6 103.26 (11) C8---C3---Ru1---C2 113.9 (2) C5---C4---Ru1---C6 −29.67 (9) C4---C3---Ru1---C1 −102.85 (11) C3---C4---Ru1---C5 132.92 (14) C2---C3---Ru1---C1 28.69 (10) C3---C4---Ru1---C2 29.61 (9) C8---C3---Ru1---C1 142.55 (18) C5---C4---Ru1---C2 −103.31 (11) C4---C3---Ru1---S1 38.27 (12) C3---C4---Ru1---C1 66.25 (10) C2---C3---Ru1---S1 169.81 (8) C5---C4---Ru1---C1 −66.67 (10) C8---C3---Ru1---S1 −76.33 (18) C5---C4---Ru1---C3 −132.92 (14) C4---C3---Ru1---Cl2 −157.62 (8) C3---C4---Ru1---S1 −153.33 (9) C2---C3---Ru1---Cl2 −26.08 (13) C5---C4---Ru1---S1 73.75 (9) C8---C3---Ru1---Cl2 87.78 (17) C3---C4---Ru1---Cl2 82.2 (2) C4---C3---Ru1---Cl1 117.67 (9) C5---C4---Ru1---Cl2 −50.7 (2) C2---C3---Ru1---Cl1 −110.79 (9) C3---C4---Ru1---Cl1 −65.67 (9) C8---C3---Ru1---Cl1 3.07 (16) C5---C4---Ru1---Cl1 161.41 (8) O1---S1---Ru1---C6 −11.73 (8) C4---C5---Ru1---C6 131.39 (14) C11---S1---Ru1---C6 −137.40 (8) C9---C5---Ru1---C6 −113.8 (2) C10---S1---Ru1---C6 111.55 (8) C6---C5---Ru1---C4 −131.39 (14) O1---S1---Ru1---C4 −81.94 (7) C9---C5---Ru1---C4 114.8 (2) C11---S1---Ru1---C4 152.39 (8) C6---C5---Ru1---C2 −65.82 (10) C10---S1---Ru1---C4 41.34 (8) C4---C5---Ru1---C2 65.57 (10) O1---S1---Ru1---C5 −46.16 (7) C9---C5---Ru1---C2 −179.61 (18) C11---S1---Ru1---C5 −171.83 (8) C6---C5---Ru1---C1 −29.10 (10) C10---S1---Ru1---C5 77.11 (8) C4---C5---Ru1---C1 102.29 (11) O1---S1---Ru1---C1 7.87 (9) C9---C5---Ru1---C1 −142.89 (19) C11---S1---Ru1---C1 −117.80 (9) C6---C5---Ru1---C3 −102.88 (10) C10---S1---Ru1---C1 131.14 (9) C4---C5---Ru1---C3 28.51 (10) O1---S1---Ru1---C3 −104.49 (8) C9---C5---Ru1---C3 143.33 (19) C11---S1---Ru1---C3 129.85 (9) C6---C5---Ru1---S1 117.62 (9) C10---S1---Ru1---C3 18.79 (9) C4---C5---Ru1---S1 −110.99 (9) O1---S1---Ru1---Cl2 85.96 (6) C9---C5---Ru1---S1 3.83 (17) C11---S1---Ru1---Cl2 −39.71 (6) C6---C5---Ru1---Cl2 33.29 (11) C10---S1---Ru1---Cl2 −150.77 (6) C4---C5---Ru1---Cl2 164.69 (7) O1---S1---Ru1---Cl1 175.05 (6) C9---C5---Ru1---Cl2 −80.50 (18) C11---S1---Ru1---Cl1 49.39 (6) C6---C5---Ru1---Cl1 −159.32 (8) C10---S1---Ru1---Cl1 −61.67 (6) C4---C5---Ru1---Cl1 −27.93 (12) --------------------- -------------- ---------------------- -------------- ::: Table 1 ::: {.caption} ###### Selected geometric parameters (Å, °) ::: ::: {#d32e520 .table-wrap} ----------- ------------- C1---Ru1 2.2209 (15) C2---Ru1 2.2162 (15) C3---Ru1 2.2219 (16) C4---Ru1 2.2097 (16) C5---Ru1 2.2160 (17) C6---Ru1 2.1978 (15) S1---Ru1 2.3399 (4) Cl1---Ru1 2.4097 (4) Cl2---Ru1 2.3963 (4) ----------- ------------- ::: ::: {#d32e568 .table-wrap} ----------------- ------------- S1---Ru1---Cl2 85.030 (14) S1---Ru1---Cl1 84.567 (14) Cl2---Ru1---Cl1 88.636 (15) ----------------- ------------- :::

PubMed Central

2024-06-05T04:04:18.929270

2011-2-12

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052171/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 12; 67(Pt 3):m319", "authors": [ { "first": "Benjamin", "last": "Oelkers" }, { "first": "Lars Hendrik", "last": "Finger" }, { "first": "Jörg", "last": "Sundermeyer" } ] }

PMC3052172

Related literature {#sec1} ================== For general background to *N*-acyl-*N′*,*N′*-disubstituted thiourea, see: Koch (2001[@bb10]); Sosa-Albertus & Piris (2001[@bb17]); Pérez *et al.* (2008*a* [@bb14]). For related structures, see: Arslan *et al.* (2003[@bb1]); Bolte & Fink (2003[@bb3]); Pérez *et al.* (2008*b* [@bb15]); Gomes *et al.* (2010[@bb9]). For details of the synthesis, see: Nagasawa & Mitsunobu (1981[@bb12]); Che *et al.* (1999[@bb4]). For graph-set notation, see: Bernstein *et al.* (1995[@bb2]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~10~H~12~N~2~OS*M* *~r~* = 208.28Monoclinic,*a* = 10.8602 (9) Å*b* = 5.5590 (6) Å*c* = 18.6864 (10) Åβ = 102.768 (5)°*V* = 1100.24 (16) Å^3^*Z* = 4Mo *K*α radiationμ = 0.26 mm^−1^*T* = 294 K0.26 × 0.13 × 0.13 mm ### Data collection {#sec2.1.2} Nonius KappaCCD diffractometerAbsorption correction: gaussian (Coppens et al., 1965[@bb5]) *T* ~min~ = 0.943, *T* ~max~ = 0.9697078 measured reflections2282 independent reflections1762 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.041 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.043*wR*(*F* ^2^) = 0.120*S* = 1.052282 reflections133 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.17 e Å^−3^Δρ~min~ = −0.27 e Å^−3^ {#d5e499} Data collection: *COLLECT* (Enraf--Nonius, 2000[@bb6]); cell refinement: *SCALEPACK* (Otwinowski & Minor 1997[@bb13]); data reduction: *DENZO* (Otwinowski & Minor 1997[@bb13]) and *SCALEPACK*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb16]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb16]); molecular graphics: *ORTEP-3 for Windows* (Farrugia, 1997[@bb7]) and *Mercury* (Macrae *et al.*, 2006[@bb11]); software used to prepare material for publication: *WinGX* (Farrugia, 1999[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811005137/gk2336sup1.cif](http://dx.doi.org/10.1107/S1600536811005137/gk2336sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811005137/gk2336Isup2.hkl](http://dx.doi.org/10.1107/S1600536811005137/gk2336Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?gk2336&file=gk2336sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?gk2336sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?gk2336&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GK2336](http://scripts.iucr.org/cgi-bin/sendsup?gk2336)). The authors thank the Grupo de Cristalografia, IFSC, USP, Brazil, for allowing the X-ray data collection. The authors acknowledge financial support from the PhD Cooperative Program - ICTP/CLAF. RSC thanks FAPESP for a fellowship. Comment ======= *N*-Acyl-*N\'*,*N\'*-disubstituted thiourea derivatives have been a subject of investigations due to their ability to form stable metal complexes (Koch *et al.*, 2001). The crystal structure analysis of the title compound was undertaken as a continuation of our interest in these *N\'*,*N\'*-disubstituted acylthiourea derivatives as intermediates towards novel heterocycles and for the systematic study of their bioactivity and complexation behavior (Pérez *et al.*, 2008*a*). On the other hand, the crystal structure determination of this compound helps to confirm its most stable molecular conformation, previously predicted by theoretical methods (Sosa-Albertus & Piris, 2001) in order to explain the behavior of polydentate systems in alkylation reactions. The main bond lengths of the title compound are within the ranges obtained for similar compounds (Pérez *et al.*, 2008*b*; Arslan *et al.*, 2003). The C--S and C--O bonds both show the expected double-bond character. However, the C--N bonds of acylthioureido fragment are intermediate between those expected for single and double C--N bonds (1.47 and 1.27 Å, respectively). These results can be explained by the existence of resonance in this part of the molecule. The conformation with respect to the thiocarbonyl and carbonyl groups is twisted, as reflected by the torsion angles O1/C1/N1/C2 and C1/N1/C2/N2 of -2.6 (3) and 57.9 (2)°. The dihedral angle between the O1/C1/N1 and S1/C2/N2 planes is 55.3 (2)°, while that between the O1/C1/N1 plane and the benzene ring is 35.8 (2)°. Compared to the diethyl analog (Bolte & Fink, 2003) and its monoclinic polymorph (Gomes, *et al.*, 2010), the molecular confomation of the title molecule is significantly less twisted, as reflected by the corresponding torsion angles O/C/N/C \[12.48 (4)°, in Bolte & Fink (2003); 7.58 (17)° in Gomes *et al.* (2010) and C/N/C/N (-80.79 (3)° in Bolte & Fink (2003); -71.44 (14)° in Gomes *et al. (*2010)\]. The dihedral angle between the O/C/N and S/C/N planes is also smaller than those of the diethyl analog \[(73.9 (2)° in Bolte & Fink (2003); 67.3 (1)° in Gomes *et al.* (2010)\]. In the crystal structure (Fig. 2), an N---H···S(-*x* + 1,-*y* + 2,-*z* + 1) hydrogen bond links the molecules into *R*^2^~2~(8) centrosymetric dimers (Bernstein *et al.*, 1995) across the crystallographic centre of symmetry at (1/2, 0, 1/2). The molecules are also linked by weak C---H···O hydrogen bonds (Table 1). Experimental {#experimental} ============ *N*-Benzoyl-*N\'*,*N\'*-dimethylthiourea was prepared using the standard procedure previously reported in the literature (Nagasawa & Mitsunobu, 1981) by the reaction of benzoyl chloride with KSCN in anhydrous acetone, and then condensation with dimethylamine. The synthesis of title compound was previously reported (Che *et al.*, 1999). Recrystallization from acetone/water solution (1:1, *v*/*v*) yielded colourless crystals (1.6 g, 7.5 mmol, 75%). m.p. 448 K. Analysis calculated for C~10~H~12~N~2~OS: C 57.67, H 5.80, N 13.45, S 15.40%. Found: C 57.88, H 5.92, N 13.60, S 15.19%. Refinement {#refinement} ========== H atoms bonded to C atoms were included in calculated positions and refined as riding, with C--H = 0.93 or 0.96 Å and with *U*~iso~(H) = 1.2Ueq(C) or 1.5Ueq(C). H atom bonded to N atom was located in difference Fourier synthesis and was refined isotropically. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. ::: ![](e-67-0o647-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The R22(8) centrosymmetric dimer lying across the centre of symmetry at (1/2,0, 1/2). Hydrogen bonds are shown as dashed lines \[symmetry code (i) -x + 1, -y + 2, -z + 1\]. ::: ![](e-67-0o647-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e211 .table-wrap} ------------------------- --------------------------------------- C~10~H~12~N~2~OS *F*(000) = 440 *M~r~* = 208.28 *D*~x~ = 1.257 Mg m^−3^ Monoclinic, *P*2~1~/*n* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yn Cell parameters from 1912 reflections *a* = 10.8602 (9) Å θ = 3.5--26.7° *b* = 5.5590 (6) Å µ = 0.26 mm^−1^ *c* = 18.6864 (10) Å *T* = 294 K β = 102.768 (5)° Prism, colourless *V* = 1100.24 (16) Å^3^ 0.26 × 0.13 × 0.13 mm *Z* = 4 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e339 .table-wrap} -------------------------------------------------------- -------------------------------------- Nonius KappaCCD diffractometer 1762 reflections with *I* \> 2σ(*I*) ω scan *R*~int~ = 0.041 Absorption correction: gaussian (Coppens et al., 1965) θ~max~ = 26.7°, θ~min~ = 3.5° *T*~min~ = 0.943, *T*~max~ = 0.969 *h* = −13→13 7078 measured reflections *k* = −6→7 2282 independent reflections *l* = −22→23 -------------------------------------------------------- -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e445 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ 0 restraints Least-squares matrix: full H atoms treated by a mixture of independent and constrained refinement *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.043 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0587*P*)^2^ + 0.1899*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 *wR*(*F*^2^) = 0.120 (Δ/σ)~max~ \< 0.001 *S* = 1.05 Δρ~max~ = 0.17 e Å^−3^ 2282 reflections Δρ~min~ = −0.27 e Å^−3^ 133 parameters ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e596 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e616 .table-wrap} ------ -------------- -------------- -------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.55382 (16) 0.7917 (3) 0.35288 (9) 0.0475 (4) C2 0.38501 (16) 0.6859 (3) 0.41573 (8) 0.0459 (4) C3 0.69073 (16) 0.8469 (3) 0.36576 (9) 0.0484 (4) C4 0.7314 (2) 1.0217 (4) 0.32357 (10) 0.0638 (5) H4 0.6731 1.103 0.2878 0.077\* C5 0.8583 (2) 1.0756 (5) 0.33449 (13) 0.0778 (6) H5 0.8853 1.1951 0.3067 0.093\* C6 0.9442 (2) 0.9537 (5) 0.38608 (14) 0.0822 (7) H6 1.0296 0.9899 0.393 0.099\* C7 0.90569 (19) 0.7787 (5) 0.42771 (14) 0.0785 (6) H7 0.965 0.6965 0.4627 0.094\* C8 0.77898 (18) 0.7235 (4) 0.41797 (11) 0.0608 (5) H8 0.7529 0.6042 0.4463 0.073\* C9 0.3971 (3) 0.3391 (4) 0.33595 (14) 0.0806 (7) H9A 0.4844 0.3341 0.3609 0.121\* H9B 0.3906 0.3891 0.2861 0.121\* H9C 0.3607 0.182 0.3366 0.121\* C10 0.19432 (19) 0.4648 (5) 0.36413 (12) 0.0753 (6) H10A 0.1503 0.6153 0.3619 0.113\* H10B 0.1803 0.373 0.4051 0.113\* H10C 0.1636 0.3765 0.3196 0.113\* N1 0.51125 (13) 0.7326 (3) 0.41555 (8) 0.0485 (4) N2 0.32963 (14) 0.5100 (3) 0.37299 (8) 0.0557 (4) O1 0.48381 (12) 0.7991 (3) 0.29255 (6) 0.0623 (4) S1 0.31430 (4) 0.84543 (10) 0.47135 (3) 0.0602 (2) H1 0.5514 (19) 0.802 (4) 0.4545 (11) 0.066 (6)\* ------ -------------- -------------- -------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e966 .table-wrap} ----- ------------- ------------- ------------- -------------- ------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0508 (9) 0.0491 (10) 0.0440 (8) 0.0049 (7) 0.0133 (7) −0.0020 (7) C2 0.0449 (9) 0.0501 (10) 0.0416 (8) −0.0028 (7) 0.0073 (6) 0.0012 (7) C3 0.0505 (9) 0.0528 (10) 0.0452 (8) 0.0041 (7) 0.0176 (7) −0.0013 (7) C4 0.0672 (12) 0.0686 (13) 0.0596 (11) 0.0016 (10) 0.0228 (9) 0.0091 (9) C5 0.0744 (14) 0.0826 (15) 0.0854 (14) −0.0127 (12) 0.0369 (12) 0.0106 (13) C6 0.0530 (12) 0.0933 (18) 0.1055 (17) −0.0082 (11) 0.0288 (12) 0.0052 (15) C7 0.0476 (11) 0.0905 (16) 0.0961 (16) 0.0084 (11) 0.0130 (11) 0.0168 (13) C8 0.0541 (11) 0.0630 (12) 0.0669 (11) 0.0047 (9) 0.0170 (9) 0.0115 (9) C9 0.0980 (17) 0.0543 (12) 0.0940 (16) −0.0025 (11) 0.0312 (14) −0.0231 (11) C10 0.0614 (12) 0.0833 (16) 0.0749 (13) −0.0227 (11) 0.0017 (10) −0.0145 (11) N1 0.0435 (8) 0.0610 (9) 0.0410 (7) −0.0033 (6) 0.0093 (6) −0.0038 (7) N2 0.0561 (9) 0.0519 (9) 0.0582 (8) −0.0062 (7) 0.0106 (7) −0.0106 (7) O1 0.0590 (8) 0.0824 (10) 0.0436 (7) 0.0056 (6) 0.0075 (6) 0.0021 (6) S1 0.0504 (3) 0.0722 (4) 0.0626 (3) −0.0118 (2) 0.0222 (2) −0.0184 (2) ----- ------------- ------------- ------------- -------------- ------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1252 .table-wrap} ------------------- -------------- -------------------- -------------- C1---O1 1.2133 (19) C6---H6 0.93 C1---N1 1.390 (2) C7---C8 1.382 (3) C1---C3 1.485 (2) C7---H7 0.93 C2---N2 1.321 (2) C8---H8 0.93 C2---N1 1.396 (2) C9---N2 1.464 (3) C2---S1 1.6759 (17) C9---H9A 0.96 C3---C4 1.384 (3) C9---H9B 0.96 C3---C8 1.388 (3) C9---H9C 0.96 C4---C5 1.381 (3) C10---N2 1.464 (2) C4---H4 0.93 C10---H10A 0.96 C5---C6 1.364 (3) C10---H10B 0.96 C5---H5 0.93 C10---H10C 0.96 C6---C7 1.368 (3) N1---H1 0.85 (2) O1---C1---N1 122.28 (16) C7---C8---C3 119.70 (19) O1---C1---C3 122.89 (15) C7---C8---H8 120.1 N1---C1---C3 114.83 (14) C3---C8---H8 120.1 N2---C2---N1 116.90 (15) N2---C9---H9A 109.5 N2---C2---S1 123.85 (14) N2---C9---H9B 109.5 N1---C2---S1 119.21 (12) H9A---C9---H9B 109.5 C4---C3---C8 119.31 (17) N2---C9---H9C 109.5 C4---C3---C1 119.15 (16) H9A---C9---H9C 109.5 C8---C3---C1 121.52 (16) H9B---C9---H9C 109.5 C5---C4---C3 120.14 (19) N2---C10---H10A 109.5 C5---C4---H4 119.9 N2---C10---H10B 109.5 C3---C4---H4 119.9 H10A---C10---H10B 109.5 C6---C5---C4 120.0 (2) N2---C10---H10C 109.5 C6---C5---H5 120 H10A---C10---H10C 109.5 C4---C5---H5 120 H10B---C10---H10C 109.5 C5---C6---C7 120.5 (2) C1---N1---C2 123.76 (14) C5---C6---H6 119.7 C1---N1---H1 114.1 (14) C7---C6---H6 119.7 C2---N1---H1 113.5 (14) C6---C7---C8 120.3 (2) C2---N2---C10 120.48 (16) C6---C7---H7 119.9 C2---N2---C9 123.91 (17) C8---C7---H7 119.9 C10---N2---C9 115.48 (17) O1---C1---C3---C4 34.5 (3) C4---C3---C8---C7 0.8 (3) N1---C1---C3---C4 −144.94 (17) C1---C3---C8---C7 179.32 (19) O1---C1---C3---C8 −144.04 (19) O1---C1---N1---C2 −2.6 (3) N1---C1---C3---C8 36.5 (2) C3---C1---N1---C2 176.89 (15) C8---C3---C4---C5 −1.3 (3) N2---C2---N1---C1 57.9 (2) C1---C3---C4---C5 −179.87 (19) S1---C2---N1---C1 −124.37 (16) C3---C4---C5---C6 1.1 (3) N1---C2---N2---C10 −173.79 (17) C4---C5---C6---C7 −0.4 (4) S1---C2---N2---C10 8.6 (2) C5---C6---C7---C8 −0.1 (4) N1---C2---N2---C9 10.6 (3) C6---C7---C8---C3 −0.1 (4) S1---C2---N2---C9 −167.03 (16) ------------------- -------------- -------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1700 .table-wrap} --------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N1---H1···S1^i^ 0.85 (2) 2.65 (2) 3.4335 (17) 154.2 (18) C9---H9A···N1 0.96 2.43 2.778 (3) 101 C9---H9B···O1 0.96 2.49 2.902 (3) 106 C10---H10C···O1^ii^ 0.96 2.38 3.265 (3) 153 --------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −*x*+1, −*y*+2, −*z*+1; (ii) −*x*+1/2, *y*−1/2, −*z*+1/2. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* --------------------- ---------- ---------- ------------- ------------- N1---H1⋯S1^i^ 0.85 (2) 2.65 (2) 3.4335 (17) 154.2 (18) C10---H10*C*⋯O1^ii^ 0.96 2.38 3.265 (3) 153 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.936147

2011-2-16

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052172/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 16; 67(Pt 3):o647", "authors": [ { "first": "Hiram", "last": "Pérez" }, { "first": "Rodrigo S.", "last": "Corrêa" }, { "first": "Ana María", "last": "Plutín" }, { "first": "Anislay", "last": "Álvarez" }, { "first": "Yvonne", "last": "Mascarenhas" } ] }

PMC3052173

Related literature {#sec1} ================== For isophthalic acid, see: Bhogala *et al.* (2005[@bb1]); Derissen (1974[@bb5]). For the use of the title compound in crystal engineering, see: Zhang *et al.* (2010[@bb8]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~8~H~5~FO~4~*M* *~r~* = 184.12Monoclinic,*a* = 3.7736 (8) Å*b* = 16.292 (4) Å*c* = 6.2753 (14) Åβ = 91.871 (5)°*V* = 385.60 (14) Å^3^*Z* = 2Mo *K*α radiationμ = 0.14 mm^−1^*T* = 297 K0.22 × 0.20 × 0.15 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD diffractometerAbsorption correction: multi-scan (*SADABS*; Sheldrick, 2003[@bb6]) *T* ~min~ = 0.969, *T* ~max~ = 0.9792201 measured reflections743 independent reflections603 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.018 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.041*wR*(*F* ^2^) = 0.161*S* = 1.04743 reflections64 parametersH-atom parameters constrainedΔρ~max~ = 0.16 e Å^−3^Δρ~min~ = −0.15 e Å^−3^ {#d5e398} Data collection: *APEX2* (Bruker, 2003[@bb4]); cell refinement: *SAINT* (Bruker, 2001[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXS97* (Sheldrick, 2008[@bb7]); program(s) used to refine structure: *SHELXL97* (Sheldrick, 2008[@bb7]); molecular graphics: *SHELXTL* (Sheldrick, 2008[@bb7]) and *DIAMOND* (Brandenburg, 2005[@bb2]); software used to prepare material for publication: *SHELXTL*. Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536811004004/go2002sup1.cif](http://dx.doi.org/10.1107/S1600536811004004/go2002sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811004004/go2002Isup2.hkl](http://dx.doi.org/10.1107/S1600536811004004/go2002Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?go2002&file=go2002sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?go2002sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?go2002&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [GO2002](http://scripts.iucr.org/cgi-bin/sendsup?go2002)). The authors gratefully acknowledge the Jiangsu Province Outstanding Science and Technology Innovation Team and Changzhou University for financial support. Comment ======= As an analogue of isophthalic acid (Bhogala *et al.* 2005; Derissen, 1974), 5-fluoroisophthalic acid has been seldom used in the crystal engineering of organic or inorganic-organic systems (Zhang *et al.* 2010). The fluorinated group may participate in hydrogen-bonding and may also induce luminescence properties. Herein we report the crystal structure of the title compound, C~8~H~5~FO~4~, to further investigate the supramolecular interactions involving the fluorine atom. The structure of the title compound, is shown below. The molecule presents *C*~2~symmetry with the fundamental unit lying on a *C*~2~-axis at \[*x*, 3/4, *z*\]. Intermolecular O---H···O interactions between adjoining centrosymmetry-related carboxylic groups form a hydrogen-bonded ribbon running along the \[010\] direction. C---H···F interactions connect the ribbons into a two-dimensional supramolecular array. Experimental {#experimental} ============ 5-Fluoroisophthalic acid and solvents for synthesis and analysis were commercially available and used as received. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of the methanol solution of the title compound. Refinement {#refinement} ========== Benzene H atoms were assigned to calculated positions with C---H = 0.93 Å, and refined using a riding model, with *U*iso(H) = 1.2*U*eq(C). H atoms bound to carboxylic O atoms were located in difference maps and refined as riding with *U*~iso~(H) = 1.5 *U*~eq~(O). Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound drawn with 30% probability ellipsoids. ::: ![](e-67-0o590-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### Two-dimensional hydrogen-bonded layer of the title compound. Hydrogen bonds are indicated as dashed lines. ::: ![](e-67-0o590-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e143 .table-wrap} ------------------------- --------------------------------------- C~8~H~5~FO~4~ *F*(000) = 188 *M~r~* = 184.12 *D*~x~ = 1.586 Mg m^−3^ Monoclinic, *P*2~1~/*m* Mo *K*α radiation, λ = 0.71073 Å Hall symbol: -P 2yb Cell parameters from 1020 reflections *a* = 3.7736 (8) Å θ = 2.5--28.0° *b* = 16.292 (4) Å µ = 0.14 mm^−1^ *c* = 6.2753 (14) Å *T* = 297 K β = 91.871 (5)° Block, colourless *V* = 385.60 (14) Å^3^ 0.22 × 0.20 × 0.15 mm *Z* = 2 ------------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e270 .table-wrap} --------------------------------------------------------------- ------------------------------------- Bruker APEXII CCD diffractometer 743 independent reflections Radiation source: fine-focus sealed tube 603 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.018 φ and ω scans θ~max~ = 25.5°, θ~min~ = 2.5° Absorption correction: multi-scan (*SADABS*; Sheldrick, 2003) *h* = −4→4 *T*~min~ = 0.969, *T*~max~ = 0.979 *k* = −17→19 2201 measured reflections *l* = −7→5 --------------------------------------------------------------- ------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e387 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.041 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.161 H-atom parameters constrained *S* = 1.04 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.1244*P*)^2^\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 743 reflections (Δ/σ)~max~ \< 0.001 64 parameters Δρ~max~ = 0.16 e Å^−3^ 0 restraints Δρ~min~ = −0.15 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e541 .table-wrap} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e586 .table-wrap} ---- ------------ -------------- ------------ -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ C1 0.6268 (4) 0.59855 (9) 0.8588 (3) 0.0524 (5) C2 0.7105 (4) 0.67633 (9) 0.7484 (2) 0.0487 (5) C3 0.8602 (4) 0.67563 (10) 0.5486 (3) 0.0529 (5) H3 0.9107 0.6265 0.4806 0.063\* C4 0.9312 (5) 0.7500 0.4549 (3) 0.0540 (6) C5 0.6370 (5) 0.7500 0.8476 (3) 0.0477 (6) H5 0.5379 0.7500 0.9813 0.057\* F1 1.0787 (4) 0.7500 0.2629 (2) 0.0744 (6) O1 0.7073 (4) 0.53205 (8) 0.7622 (2) 0.0775 (6) H1 0.6348 0.4905 0.8205 0.116\* O2 0.4837 (4) 0.60037 (7) 1.0328 (2) 0.0722 (6) ---- ------------ -------------- ------------ -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e755 .table-wrap} ---- ------------- ------------- ------------- ------------- ------------ ------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ C1 0.0490 (9) 0.0612 (10) 0.0474 (10) −0.0023 (6) 0.0088 (7) −0.0080 (7) C2 0.0385 (8) 0.0652 (11) 0.0424 (9) −0.0012 (6) 0.0022 (6) −0.0051 (6) C3 0.0420 (9) 0.0726 (12) 0.0441 (10) −0.0006 (6) 0.0027 (7) −0.0087 (7) C4 0.0426 (11) 0.0852 (16) 0.0346 (11) 0.000 0.0069 (9) 0.000 C5 0.0400 (10) 0.0642 (14) 0.0395 (11) 0.000 0.0072 (8) 0.000 F1 0.0745 (10) 0.1105 (12) 0.0393 (8) 0.000 0.0190 (7) 0.000 O1 0.1022 (11) 0.0610 (8) 0.0715 (10) −0.0050 (6) 0.0359 (8) −0.0121 (6) O2 0.0938 (10) 0.0622 (9) 0.0628 (9) −0.0038 (6) 0.0355 (7) −0.0032 (5) ---- ------------- ------------- ------------- ------------- ------------ ------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e940 .table-wrap} ------------------- -------------- ---------------------- -------------- C1---O2 1.235 (2) C3---H3 0.9300 C1---O1 1.2826 (19) C4---F1 1.343 (2) C1---C2 1.483 (2) C4---C3^i^ 1.377 (2) C2---C5 1.3841 (18) C5---C2^i^ 1.3841 (19) C2---C3 1.392 (2) C5---H5 0.9300 C3---C4 1.377 (2) O1---H1 0.8201 O2---C1---O1 123.73 (15) C2---C3---H3 121.1 O2---C1---C2 119.91 (13) F1---C4---C3 118.37 (11) O1---C1---C2 116.35 (15) F1---C4---C3^i^ 118.36 (11) C5---C2---C3 120.34 (15) C3---C4---C3^i^ 123.3 (2) C5---C2---C1 118.83 (15) C2---C5---C2^i^ 120.3 (2) C3---C2---C1 120.83 (14) C2---C5---H5 119.9 C4---C3---C2 117.89 (16) C2^i^---C5---H5 119.9 C4---C3---H3 121.1 C1---O1---H1 113.5 O2---C1---C2---C5 2.3 (3) C1---C2---C3---C4 179.97 (14) O1---C1---C2---C5 −178.51 (16) C2---C3---C4---F1 179.40 (14) O2---C1---C2---C3 −177.68 (14) C2---C3---C4---C3^i^ −0.3 (3) O1---C1---C2---C3 1.5 (3) C3---C2---C5---C2^i^ 0.3 (3) C5---C2---C3---C4 0.0 (3) C1---C2---C5---C2^i^ −179.72 (12) ------------------- -------------- ---------------------- -------------- ::: Symmetry codes: (i) *x*, −*y*+3/2, *z*. Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e1178 .table-wrap} ------------------- --------- --------- ----------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* O1---H1···O2^ii^ 0.82 1.81 2.625 (2) 174 C5---H5···F1^iii^ 0.93 2.52 3.404 (2) 160 ------------------- --------- --------- ----------- --------------- ::: Symmetry codes: (ii) −*x*+1, −*y*+1, −*z*+2; (iii) *x*−1, *y*, *z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ---------------- --------- ------- ----------- ------------- O1---H1⋯O2^i^ 0.82 1.81 2.625 (2) 174 C5---H5⋯F1^ii^ 0.93 2.52 3.404 (2) 160 Symmetry codes: (i) ; (ii) . :::

PubMed Central

2024-06-05T04:04:18.939912

2011-2-09

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052173/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 9; 67(Pt 3):o590", "authors": [ { "first": "Jin-Ling", "last": "Mi" }, { "first": "Le", "last": "Chen" }, { "first": "Ming-Yang", "last": "He" } ] }

PMC3052174

Related literature {#sec1} ================== For background to chalcone synthesis and the biological activity of pyrazole derivatives, see: Bekhit *et al.* (2008[@bb2]); Ono *et al.* (2007[@bb12]); Cottineau *et al.* (2002[@bb6]); Gadakh *et al.* (2010[@bb8]); Hall *et al.* (2008[@bb9]); Hoepping *et al.* (2007[@bb10]); Mikhaylichenko *et al.* (2009[@bb11]); Park *et al.* (2005[@bb13]) Souza *et al.* (2002[@bb15]); Xie *et al.* (2008[@bb18]). For related structures, see; Chantrapromma *et al.* (2009[@bb4]); Suwunwong *et al.* (2009[@bb17]). For the stability of the temperature controller used in the data collection, see Cosier & Glazer (1986[@bb5]). For bond-length data, see: Allen *et al.* (1987[@bb1]). For puckering parameters, see: Cremer & Pople (1975[@bb7]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~18~H~19~BrN~4~S*M* *~r~* = 403.34Triclinic,*a* = 6.9153 (1) Å*b* = 9.5122 (1) Å*c* = 15.1545 (2) Åα = 72.196 (1)°β = 80.941 (1)°γ = 69.845 (1)°*V* = 889.48 (2) Å^3^*Z* = 2Mo *K*α radiationμ = 2.44 mm^−1^*T* = 100 K0.55 × 0.32 × 0.31 mm ### Data collection {#sec2.1.2} Bruker APEXII CCD area-detector diffractometerAbsorption correction: multi-scan (*SADABS*; Bruker, 2005[@bb3]) *T* ~min~ = 0.349, *T* ~max~ = 0.52028456 measured reflections7823 independent reflections6784 reflections with *I* \> 2σ(*I*)*R* ~int~ = 0.023 ### Refinement {#sec2.1.3} *R*\[*F* ^2^ \> 2σ(*F* ^2^)\] = 0.028*wR*(*F* ^2^) = 0.073*S* = 1.057823 reflections227 parametersH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.96 e Å^−3^Δρ~min~ = −0.50 e Å^−3^ {#d5e545} Data collection: *APEX2* (Bruker, 2005[@bb3]); cell refinement: *SAINT* (Bruker, 2005[@bb3]); data reduction: *SAINT*; program(s) used to solve structure: *SHELXTL* (Sheldrick, 2008[@bb14]); program(s) used to refine structure: *SHELXTL*; molecular graphics: *SHELXTL*; software used to prepare material for publication: *SHELXTL* and *PLATON* (Spek, 2009[@bb16]). Supplementary Material ====================== Crystal structure: contains datablocks global, I. DOI: [10.1107/S1600536811006106/rz2558sup1.cif](http://dx.doi.org/10.1107/S1600536811006106/rz2558sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536811006106/rz2558Isup2.hkl](http://dx.doi.org/10.1107/S1600536811006106/rz2558Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?rz2558&file=rz2558sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?rz2558sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?rz2558&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [RZ2558](http://scripts.iucr.org/cgi-bin/sendsup?rz2558)). TS thanks the Graduate School, Prince of Songkla University for partial financial support. The authors thank the Prince of Songkla University for financial support through the Crystal Materials Research Unit and also thank Universiti Sains Malaysia for the Research University Grant No. 1001/PFIZIK/811160. Comment ======= The pyrazole moiety is one of the core structures in a number of natural products (Xie *et al.*, 2008). Numerous compounds which contain the pyrazole moiety are known to exhibit a wide range of biological properties such as antihypertensive (Mikhaylichenko *et al.*, 2009), analgesic (Hall *et al.*, 2008), anti-inflammatory (Bekhit *et al.*, 2008), antipyretic (Souza *et al.*, 2002), antimicrobial (Gadakh *et al.*, 2010), hypoglycemic (Cottineau *et al.*, 2002), sedative-hypnotic (Hoepping *et al.*, 2007) and antitumor activities (Park *et al.*, 2005). Our on going research on biological activities of pyrazole derivatives led us to synthesize the title compound by cyclization of the chalcone derivative (Ono *et al.*, 2007) with excess thiosemicarbazide. Herein we report the crystal structure of the title compound. The molecular structure of the title compound is twisted. The central pyrazole ring adopts a flattened envelope conformation with puckering parameter Q = 0.1775 (11) Å and φ = 75.9 (3)° (Cremer & Pople, 1975), with the slightly puckered C9 atom having the maximum deviation of 0.1120 (11) Å. The pyrazole ring is coplanar with the 4-bromophenyl whereas inclined to the 4-dimethylaminophenyl rings with dihedral angles of 1.68 (6) and 85.12 (6)°, respectively. The dihedral angle between the two phenyl rings being 86.56 (6)°. The dimethylamino group is slightly twisted from the attached benzene ring with the torsion angles C16--N3--C13--C14 = 8.9 (2)° and C17--N3--C13--C12 = 8.4 (2)°. The carbothioamide is slightly twisted from the pyrazole ring as indicated by the torsions angles N4--C18--N2--N1 = 5.51 (14)° and S1--C18--N2--N1 = -172.28 (7)°. The bond distances agree with the literature values (Allen *et al.*, 1987) and are comparable to those observed in related structures (Chantrapromma *et al.*, 2009; Suwunwong *et al.*, 2009). In the crystal structure (Fig. 2), the molecules are linked by intermolecular N---H···S hydrogen bonds (Table 1) into chains along the \[2 1 0\] direction. The crystal is further stabilized by C---H···π interactions (Table 1). Experimental {#experimental} ============ The title compound was synthesized by dissolving (*E*)-1-(4-bromophenyl)-3-(4-(dimethylamino)phenyl)prop-2-en-1-one (Ono *et al.*, 2007) (0.33 g, 1.0 mmol) in a solution of KOH (0.06 g, 1.0 mmol) in ethanol (20 ml). An excess thiosemicarbazide (0.14 g, 1.5 mmol) in ethanol (20 ml) was then added, and the reaction mixture was vigorously stirred and refluxed for 7 h. The yellow solid of the title compound obtained after cooling of the reaction mixture was filtered off under vacuum. Pale yellow block-shaped single crystals of the title compound suitable for *X*-ray structure determination were recrystalized from acetone/ethanol (1:1 *v*/*v*) by slow evaporation of the solvent at room temperature after several days. M.p. 481--482 K. Refinement {#refinement} ========== The amino H atoms were located in difference Fourier map and refined isotropically. The remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with d(C---H) = 0.93 Å for aromatic, 0.97 Å for CH~2~ and 0.96 Å for CH~3~ atoms. The *U*~iso~ values were constrained to be 1.5*U*~eq~ of the carrier atom for methyl H atoms and 1.2*U*~eq~ for the remaining H atoms. A rotating group model was used for the methyl groups. The highest residual electron density peak is located at 0.75 Å from Br1 and the deepest hole is located at 0.56 Å from Br1. Figures ======= ::: {#Fap1 .fig} Fig. 1. ::: {.caption} ###### The molecular structure of the title compound, showing 50% probability displacement ellipsoids. ::: ![](e-67-0o701-fig1) ::: ::: {#Fap2 .fig} Fig. 2. ::: {.caption} ###### The crystal packing of the title compound viewed along the a axis. Hydrogen bonds are drawn as dashed lines. ::: ![](e-67-0o701-fig2) ::: Crystal data {#tablewrapcrystaldatalong} ============ ::: {#d1e188 .table-wrap} ----------------------- --------------------------------------- C~18~H~19~BrN~4~S *Z* = 2 *M~r~* = 403.34 *F*(000) = 412 Triclinic, *P*1 *D*~x~ = 1.506 Mg m^−3^ Hall symbol: -P 1 Melting point = 481--482 K *a* = 6.9153 (1) Å Mo *K*α radiation, λ = 0.71073 Å *b* = 9.5122 (1) Å Cell parameters from 7823 reflections *c* = 15.1545 (2) Å θ = 2.4--35.1° α = 72.196 (1)° µ = 2.44 mm^−1^ β = 80.941 (1)° *T* = 100 K γ = 69.845 (1)° Block, pale yellow *V* = 889.48 (2) Å^3^ 0.55 × 0.32 × 0.31 mm ----------------------- --------------------------------------- ::: Data collection {#tablewrapdatacollectionlong} =============== ::: {#d1e323 .table-wrap} ------------------------------------------------------------ -------------------------------------- Bruker APEXII CCD area-detector diffractometer 7823 independent reflections Radiation source: sealed tube 6784 reflections with *I* \> 2σ(*I*) graphite *R*~int~ = 0.023 φ and ω scans θ~max~ = 35.1°, θ~min~ = 2.4° Absorption correction: multi-scan (*SADABS*; Bruker, 2005) *h* = −11→10 *T*~min~ = 0.349, *T*~max~ = 0.520 *k* = −15→15 28456 measured reflections *l* = −24→24 ------------------------------------------------------------ -------------------------------------- ::: Refinement {#tablewraprefinementdatalong} ========== ::: {#d1e440 .table-wrap} ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on *F*^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.028 Hydrogen site location: inferred from neighbouring sites *wR*(*F*^2^) = 0.073 H atoms treated by a mixture of independent and constrained refinement *S* = 1.05 *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0344*P*)^2^ + 0.3232*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3 7823 reflections (Δ/σ)~max~ = 0.003 227 parameters Δρ~max~ = 0.96 e Å^−3^ 0 restraints Δρ~min~ = −0.50 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- ::: Special details {#specialdetails} =============== ::: {#d1e597 .table-wrap} ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of *F*^2^ against ALL reflections. The weighted *R*-factor *wR* and goodness of fit *S* are based on *F*^2^, conventional *R*-factors *R* are based on *F*, with *F* set to zero for negative *F*^2^. The threshold expression of *F*^2^ \> σ(*F*^2^) is used only for calculating *R*-factors(gt) *etc*. and is not relevant to the choice of reflections for refinement. *R*-factors based on *F*^2^ are statistically about twice as large as those based on *F*, and *R*- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ::: Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ::: {#d1e702 .table-wrap} ------ --------------- ---------------- --------------- -------------------- -- *x* *y* *z* *U*~iso~\*/*U*~eq~ Br1 1.641401 (17) −0.173962 (13) 0.169443 (10) 0.02713 (4) S1 0.08981 (4) 0.61386 (3) 0.083129 (18) 0.01668 (5) N1 0.62104 (13) 0.27982 (10) 0.13070 (6) 0.01465 (14) N2 0.44511 (13) 0.40189 (10) 0.14121 (6) 0.01404 (14) N3 −0.0497 (2) 0.25372 (15) 0.52890 (9) 0.0346 (3) N4 0.31575 (15) 0.37031 (12) 0.02111 (7) 0.01857 (16) C1 1.02110 (17) 0.05782 (12) 0.12650 (8) 0.01819 (18) H1A 0.9213 0.0544 0.0933 0.022\* C2 1.21950 (17) −0.04510 (13) 0.12460 (9) 0.02047 (19) H2A 1.2534 −0.1179 0.0908 0.025\* C3 1.36736 (16) −0.03752 (12) 0.17431 (8) 0.01850 (18) C4 1.32036 (16) 0.06853 (12) 0.22612 (8) 0.01758 (18) H4A 1.4208 0.0711 0.2593 0.021\* C5 1.12052 (15) 0.17132 (12) 0.22782 (7) 0.01604 (17) H5A 1.0873 0.2432 0.2623 0.019\* C6 0.96924 (15) 0.16730 (11) 0.17801 (7) 0.01418 (16) C7 0.76209 (15) 0.27851 (11) 0.17797 (7) 0.01395 (15) C8 0.69425 (15) 0.40713 (12) 0.22566 (7) 0.01553 (16) H8A 0.7585 0.4870 0.1952 0.019\* H8B 0.7266 0.3671 0.2904 0.019\* C9 0.45956 (15) 0.47007 (11) 0.21552 (7) 0.01428 (16) H9A 0.4135 0.5839 0.1937 0.017\* C10 0.33157 (15) 0.41586 (12) 0.30181 (7) 0.01506 (16) C11 0.40552 (17) 0.27201 (13) 0.36660 (8) 0.01809 (18) H11A 0.5411 0.2104 0.3590 0.022\* C12 0.28225 (18) 0.21843 (14) 0.44205 (8) 0.0221 (2) H12A 0.3371 0.1226 0.4842 0.027\* C13 0.07487 (19) 0.30739 (14) 0.45555 (8) 0.0219 (2) C14 0.00187 (17) 0.45394 (14) 0.39134 (8) 0.01970 (19) H14A −0.1332 0.5167 0.3988 0.024\* C15 0.12813 (16) 0.50602 (13) 0.31725 (7) 0.01712 (17) H15A 0.0761 0.6039 0.2765 0.021\* C16 −0.2680 (2) 0.3366 (2) 0.53468 (10) 0.0324 (3) H16A −0.3276 0.3493 0.4785 0.049\* H16B −0.2880 0.4370 0.5428 0.049\* H16C −0.3334 0.2786 0.5866 0.049\* C17 0.0361 (3) 0.1144 (2) 0.60089 (12) 0.0443 (4) H17A 0.1564 0.1203 0.6219 0.067\* H17B 0.0737 0.0256 0.5768 0.067\* H17C −0.0645 0.1046 0.6519 0.067\* C18 0.29283 (15) 0.45225 (12) 0.08212 (7) 0.01415 (16) H1N4 0.211 (3) 0.386 (2) −0.0067 (13) 0.028 (4)\* H2N4 0.414 (3) 0.287 (2) 0.0245 (12) 0.027 (4)\* ------ --------------- ---------------- --------------- -------------------- -- ::: Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ::: {#d1e1281 .table-wrap} ----- -------------- -------------- -------------- -------------- -------------- -------------- *U*^11^ *U*^22^ *U*^33^ *U*^12^ *U*^13^ *U*^23^ Br1 0.01316 (5) 0.01906 (5) 0.05023 (9) −0.00079 (4) −0.00226 (5) −0.01560 (5) S1 0.01295 (10) 0.01764 (10) 0.01829 (11) −0.00210 (8) −0.00309 (8) −0.00530 (8) N1 0.0112 (3) 0.0157 (3) 0.0161 (4) −0.0029 (3) −0.0005 (3) −0.0046 (3) N2 0.0112 (3) 0.0159 (3) 0.0149 (3) −0.0024 (3) −0.0014 (3) −0.0059 (3) N3 0.0276 (6) 0.0347 (6) 0.0316 (6) −0.0095 (5) 0.0114 (5) −0.0020 (5) N4 0.0150 (4) 0.0224 (4) 0.0189 (4) −0.0026 (3) −0.0039 (3) −0.0088 (3) C1 0.0155 (4) 0.0180 (4) 0.0224 (5) −0.0042 (3) −0.0027 (3) −0.0078 (4) C2 0.0165 (4) 0.0178 (4) 0.0284 (5) −0.0035 (3) −0.0014 (4) −0.0102 (4) C3 0.0125 (4) 0.0140 (4) 0.0282 (5) −0.0032 (3) −0.0008 (3) −0.0060 (4) C4 0.0128 (4) 0.0158 (4) 0.0251 (5) −0.0044 (3) −0.0029 (3) −0.0061 (4) C5 0.0131 (4) 0.0150 (4) 0.0210 (4) −0.0046 (3) −0.0012 (3) −0.0060 (3) C6 0.0112 (4) 0.0140 (4) 0.0170 (4) −0.0044 (3) −0.0005 (3) −0.0034 (3) C7 0.0120 (4) 0.0142 (4) 0.0153 (4) −0.0043 (3) −0.0001 (3) −0.0035 (3) C8 0.0122 (4) 0.0167 (4) 0.0194 (4) −0.0043 (3) −0.0012 (3) −0.0073 (3) C9 0.0124 (4) 0.0153 (4) 0.0164 (4) −0.0046 (3) −0.0016 (3) −0.0055 (3) C10 0.0133 (4) 0.0168 (4) 0.0161 (4) −0.0038 (3) −0.0011 (3) −0.0068 (3) C11 0.0154 (4) 0.0189 (4) 0.0185 (4) −0.0033 (3) 0.0000 (3) −0.0059 (3) C12 0.0207 (5) 0.0216 (5) 0.0194 (5) −0.0046 (4) 0.0007 (4) −0.0023 (4) C13 0.0208 (5) 0.0256 (5) 0.0199 (5) −0.0086 (4) 0.0040 (4) −0.0078 (4) C14 0.0147 (4) 0.0244 (5) 0.0204 (5) −0.0041 (4) 0.0008 (3) −0.0100 (4) C15 0.0142 (4) 0.0195 (4) 0.0173 (4) −0.0027 (3) −0.0017 (3) −0.0072 (3) C16 0.0234 (6) 0.0522 (9) 0.0273 (6) −0.0184 (6) 0.0087 (5) −0.0162 (6) C17 0.0419 (9) 0.0417 (8) 0.0351 (8) −0.0142 (7) 0.0126 (7) 0.0035 (6) C18 0.0124 (4) 0.0167 (4) 0.0131 (4) −0.0051 (3) −0.0005 (3) −0.0032 (3) ----- -------------- -------------- -------------- -------------- -------------- -------------- ::: Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ::: {#d1e1816 .table-wrap} --------------------- -------------- ----------------------- -------------- Br1---C3 1.8976 (10) C7---C8 1.5091 (14) S1---C18 1.6896 (10) C8---C9 1.5391 (14) N1---C7 1.2927 (13) C8---H8A 0.9700 N1---N2 1.3901 (12) C8---H8B 0.9700 N2---C18 1.3518 (13) C9---C10 1.5155 (14) N2---C9 1.4917 (13) C9---H9A 0.9800 N3---C13 1.3759 (16) C10---C11 1.3972 (15) N3---C17 1.441 (2) C10---C15 1.3990 (14) N3---C16 1.4450 (19) C11---C12 1.3893 (16) N4---C18 1.3404 (14) C11---H11A 0.9300 N4---H1N4 0.842 (19) C12---C13 1.4113 (17) N4---H2N4 0.841 (19) C12---H12A 0.9300 C1---C2 1.3859 (15) C13---C14 1.4090 (17) C1---C6 1.4049 (15) C14---C15 1.3848 (16) C1---H1A 0.9300 C14---H14A 0.9300 C2---C3 1.3945 (16) C15---H15A 0.9300 C2---H2A 0.9300 C16---H16A 0.9600 C3---C4 1.3848 (15) C16---H16B 0.9600 C4---C5 1.3926 (14) C16---H16C 0.9600 C4---H4A 0.9300 C17---H17A 0.9600 C5---C6 1.3999 (14) C17---H17B 0.9600 C5---H5A 0.9300 C17---H17C 0.9600 C6---C7 1.4583 (14) C7---N1---N2 107.84 (8) N2---C9---C8 100.12 (8) C18---N2---N1 119.42 (8) C10---C9---C8 114.94 (8) C18---N2---C9 127.78 (8) N2---C9---H9A 110.4 N1---N2---C9 112.61 (8) C10---C9---H9A 110.4 C13---N3---C17 120.35 (12) C8---C9---H9A 110.4 C13---N3---C16 120.36 (12) C11---C10---C15 117.01 (10) C17---N3---C16 119.29 (12) C11---C10---C9 122.25 (9) C18---N4---H1N4 117.0 (13) C15---C10---C9 120.66 (9) C18---N4---H2N4 120.0 (12) C12---C11---C10 121.88 (10) H1N4---N4---H2N4 119.5 (17) C12---C11---H11A 119.1 C2---C1---C6 120.68 (10) C10---C11---H11A 119.1 C2---C1---H1A 119.7 C11---C12---C13 120.90 (10) C6---C1---H1A 119.7 C11---C12---H12A 119.6 C1---C2---C3 118.82 (10) C13---C12---H12A 119.6 C1---C2---H2A 120.6 N3---C13---C14 121.54 (11) C3---C2---H2A 120.6 N3---C13---C12 121.30 (11) C4---C3---C2 121.77 (10) C14---C13---C12 117.15 (10) C4---C3---Br1 119.03 (8) C15---C14---C13 121.01 (10) C2---C3---Br1 119.19 (8) C15---C14---H14A 119.5 C3---C4---C5 119.05 (10) C13---C14---H14A 119.5 C3---C4---H4A 120.5 C14---C15---C10 122.00 (10) C5---C4---H4A 120.5 C14---C15---H15A 119.0 C4---C5---C6 120.47 (10) C10---C15---H15A 119.0 C4---C5---H5A 119.8 N3---C16---H16A 109.5 C6---C5---H5A 119.8 N3---C16---H16B 109.5 C5---C6---C1 119.21 (9) H16A---C16---H16B 109.5 C5---C6---C7 120.05 (9) N3---C16---H16C 109.5 C1---C6---C7 120.72 (9) H16A---C16---H16C 109.5 N1---C7---C6 121.29 (9) H16B---C16---H16C 109.5 N1---C7---C8 113.61 (8) N3---C17---H17A 109.5 C6---C7---C8 124.98 (9) N3---C17---H17B 109.5 C7---C8---C9 102.52 (8) H17A---C17---H17B 109.5 C7---C8---H8A 111.3 N3---C17---H17C 109.5 C9---C8---H8A 111.3 H17A---C17---H17C 109.5 C7---C8---H8B 111.3 H17B---C17---H17C 109.5 C9---C8---H8B 111.3 N4---C18---N2 116.40 (9) H8A---C8---H8B 109.2 N4---C18---S1 122.21 (8) N2---C9---C10 110.17 (8) N2---C18---S1 121.35 (8) C7---N1---N2---C18 164.20 (9) C7---C8---C9---N2 −16.35 (9) C7---N1---N2---C9 −11.12 (11) C7---C8---C9---C10 101.64 (9) C6---C1---C2---C3 −0.38 (17) N2---C9---C10---C11 82.45 (11) C1---C2---C3---C4 0.78 (18) C8---C9---C10---C11 −29.71 (13) C1---C2---C3---Br1 −178.27 (9) N2---C9---C10---C15 −94.19 (11) C2---C3---C4---C5 −0.65 (17) C8---C9---C10---C15 153.64 (9) Br1---C3---C4---C5 178.40 (8) C15---C10---C11---C12 1.39 (16) C3---C4---C5---C6 0.12 (16) C9---C10---C11---C12 −175.37 (10) C4---C5---C6---C1 0.25 (16) C10---C11---C12---C13 0.81 (18) C4---C5---C6---C7 −178.15 (10) C17---N3---C13---C14 −170.94 (15) C2---C1---C6---C5 −0.12 (16) C16---N3---C13---C14 8.9 (2) C2---C1---C6---C7 178.27 (10) C17---N3---C13---C12 8.4 (2) N2---N1---C7---C6 −177.42 (9) C16---N3---C13---C12 −171.79 (13) N2---N1---C7---C8 −1.24 (11) C11---C12---C13---N3 178.51 (13) C5---C6---C7---N1 178.25 (10) C11---C12---C13---C14 −2.16 (18) C1---C6---C7---N1 −0.12 (15) N3---C13---C14---C15 −179.34 (12) C5---C6---C7---C8 2.53 (15) C12---C13---C14---C15 1.33 (17) C1---C6---C7---C8 −175.85 (10) C13---C14---C15---C10 0.88 (17) N1---C7---C8---C9 12.11 (11) C11---C10---C15---C14 −2.23 (16) C6---C7---C8---C9 −171.88 (9) C9---C10---C15---C14 174.59 (10) C18---N2---C9---C10 81.36 (12) N1---N2---C18---N4 5.51 (14) N1---N2---C9---C10 −103.80 (9) C9---N2---C18---N4 −179.96 (9) C18---N2---C9---C8 −157.18 (10) N1---N2---C18---S1 −172.28 (7) N1---N2---C9---C8 17.65 (10) C9---N2---C18---S1 2.25 (15) --------------------- -------------- ----------------------- -------------- ::: Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ::: {#d1e2660 .table-wrap} ----------------------------------------------------------------------------------- *Cg*1 and *Cg*2 are the centroids of the C1--C6 and C10--C15 rings, respectively. ----------------------------------------------------------------------------------- ::: ::: {#d1e2669 .table-wrap} ----------------------- ---------- ---------- ------------- --------------- *D*---H···*A* *D*---H H···*A* *D*···*A* *D*---H···*A* N4---H1N4···S1^i^ 0.84 (2) 2.54 (2) 3.3679 (11) 170.8 (17) C5---H5A···Cg2^ii^ 0.93 2.72 3.5462 (12) 149 C16---H16B···Cg2^iii^ 0.96 2.71 3.6676 (18) 154 C17---H17C···Cg1^iv^ 0.96 2.74 3.5990 (19) 149 ----------------------- ---------- ---------- ------------- --------------- ::: Symmetry codes: (i) −*x*, −*y*+1, −*z*; (ii) *x*+1, *y*, *z*; (iii) −*x*, −*y*+1, −*z*+1; (iv) −*x*+1, −*y*, −*z*+1. ::: {#table1 .table-wrap} Table 1 ::: {.caption} ###### Hydrogen-bond geometry (Å, °) *Cg*1 and *Cg*2 are the centroids of the C1--C6 and C10--C15 rings, respectively. ::: *D*---H⋯*A* *D*---H H⋯*A* *D*⋯*A* *D*---H⋯*A* ------------------------- ---------- ---------- ------------- ------------- N4---H1*N*4⋯S1^i^ 0.84 (2) 2.54 (2) 3.3679 (11) 170.8 (17) C5---H5*A*⋯*Cg*2^ii^ 0.93 2.72 3.5462 (12) 149 C16---H16*B*⋯*Cg*2^iii^ 0.96 2.71 3.6676 (18) 154 C17---H17*C*⋯*Cg*1^iv^ 0.96 2.74 3.5990 (19) 149 Symmetry codes: (i) ; (ii) ; (iii) ; (iv) . ::: [^1]: ‡ Thomson Reuters ResearcherID: A-3561-2009. [^2]: § Additional correspondence author, e-mail: suchada.c@psu.ac.th. Thomson Reuters ResearcherID: A-5085-2009.

PubMed Central

2024-06-05T04:04:18.941954

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052174/", "journal": "Acta Crystallogr Sect E Struct Rep Online. 2011 Feb 23; 67(Pt 3):o701-o702", "authors": [ { "first": "Hoong-Kun", "last": "Fun" }, { "first": "Thitipone", "last": "Suwunwong" }, { "first": "Suchada", "last": "Chantrapromma" } ] }

PMC3052175

Background ========== WHO defined palliative care as \'\'the active total care of patients whose disease is not responsive to curative treatment\' \[[@B1]\]. In Belgium, palliative care relies on this definition and is provided in different settings: home care, residential units or hospices. These 51 residential units have 379 palliative beds, i.e. an insufficient number of beds in view of the palliative care demand. Therefore, every acute hospital is subsidized for an intramural palliative support team. Recently, 6 day centres have been created in Belgium. All these services are specialized in the care of palliative patients with more complex needs. The patients not treated in these services are treated in classic structures providing palliative care but not specialized in palliative care (general hospital wards, home care nursing services, general practitioners, nursing homes\...) \[[@B2]\]. Beside the specialised palliative services, the country is divided into 25 areas, called palliative networks, each covering around 300.000 inhabitants. These networks coordinate the intervention of palliative care services and integrate them into the health care system. Each network has its own home care team. Even though more than 70% of Belgian population would prefer to be treated at home, a large number of deaths occur in hospital \[[@B3]\]. A considerable amount of information regarding palliative inpatients is available and the place of death and its determinants in this specific context have been extensively investigated \[[@B4]\]. Van den Block et al. reported on the institutionalised nature of the final phase of life and concluded that clinical condition, expression of preferences, and characteristics of healthcare organisation seem to be associated with the transfer of such patients to the hospital \[[@B5]\]. However, the wider use of the hospital setting in providing palliative care has been less frequently considered. Most of the previous studies have been limited to specific diagnoses (e.g., cancer), age groups (e.g., the elderly), or settings (e.g., specialist palliative care services). Although some surveys have included the number of palliative inpatients, they do not give a global overview as they were all conducted in one single or in a university hospital \[[@B6]-[@B10]\]. Furthermore, two of them have focused only on terminally ill patients and another study was specifically interested in the need for specialist inpatient palliative care \[[@B6],[@B7],[@B10]\]. The purpose of this study was to assess the overall population of hospital palliative inpatients who should benefit from palliative care and to describe their main demographic and medical characteristics. Methods ======= The study was prospective and data was collected by interviews conducted with medical and nursing staff. The literature shows that the proportion of cancer patients among palliative inpatients varies around 50% \[[@B6]\]. The sample size was computed to detect a 25% difference between the proportions of cancer and non cancer patients. With a hypothesis of type I error equal to 0.05 and a power equal to 0.80, the sample size should be 364 palliative patients. In order to estimate the number of beds to include, we chose a proportion of palliative patients of 10% as this proportion varies between 5% and 15% in the literature \[[@B6],[@B9]\]. This would lead to investigate 364/0.10 = 3640 inpatients. Taking an occupation rate of 0.75 entails that 4842 beds should be checked. Fourteen hospitals were randomly selected from all Belgian hospitals, taking into account the type (academic/non academic; acute/non acute), the size (\< 300 beds, 300-500 beds and \>500 beds), and the geographical location (Brussels, Flanders and Wallonia). Twelve categories were created based on these hospital\'s characteristics and each Belgian hospital was allocated to a single category. The hospital sample was built by a random selection of one hospital in each category. Finally, a university hospital from Flanders and another from Wallonia were added to the sample. Two non university hospitals refused to participate and were replaced by 2 other hospitals randomly selected in the corresponding categories. All hospital beds were included (4746 beds), except obstetrics and psychiatry as such wards are only rarely involved in palliative care. Intensive care units were also excluded although these units present a high death rate and in spite of innovative and specific palliative care programs \[[@B11]\]. Indeed the survey design was not adapted to this type of patients and treatments (prognostic uncertainties, specific life-sustaining treatment\...). Paediatric and neonatology units were also not eligible due to their specific care plans. As we intended to measure the frequency of patients who could be considered as palliative and therefore should benefit from a palliative care program, the palliative units were not included in this survey. All patients hospitalised in an eligible unit for at least 48 hours (i.e. enough time for the physicians and the nurses to know the patient) were included in the study. Patients undergoing in-hospital transfer during the same stay were included only once. The Ethics Committee of St Luc Hospital-UCL gave a positive opinion to the protocol which was registered in the National Federal Experimentation Data Bank of the National Ethics Committee under the number B40320084090. The study was performed according the different Belgian laws concerning confidentiality and private life (2002), patients\' rights (2002) and experimentation on human beings (2004). This study was a sub-project of a larger one which was asked by the promoter, the Belgian Health Care Knowledge (KCE). Three specifically appointed nurses conducted the survey in 2008, over a 3-month period. After hospital approval, the caregivers of each ward included in the survey were interviewed once on a certain day fixed in advance. In small hospitals with few wards, all interviews were conducted in a single day. Larger hospitals with a greater number of wards to be surveyed required more time. Only 3 physicians refused to participate, i.e. less than 1% of the physicians contacted. The study nurses interviewed the nurses and physicians who were in charge of the patients and had daily contact with them. Firstly, the nurses and physicians were separately asked to assess whether that patient met the definition of a palliative patient. In 2002, the World Health Organisation defined palliative care as \"*an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness through the prevention and relief of suffering by means of early identification, impeccable assessment and treatment of pain and other problems physical psychosocial and spiritual*\" \[[@B12]\]. This definition is broader than the one given by the World Health Organisation in (1990): *\"Palliative care is the active total care of patients whose disease is not responsive to curative treatment\"*\[[@B1]\]. In Belgium, even though the notion of palliative patient is not officially defined, preferential reimbursement rate are granted to the patient having a \'palliative\' status. As mentioned by Keirse et al. and by Pastrana et al., there is no current consensus about the definition of palliative patient \[[@B13],[@B14]\]. Therefore within the context of our survey we used the following definition: \"*a patient suffering from an incurable, progressive, life-threatening disease, with no possibility of obtaining remission, stabilization or improvement of this illness*\". The term \"*incurable*\" excluded illnesses for which there is a chance of complete cure; the term \"*progressive*\" eliminated chronic, incurable but stable disease; the terms \"*no possibility of obtaining remission, stabilization or improvement of the illness*\" highlighted the ineffectiveness of specific therapeutics to control the disease \[[@B15]\]; and the term \"l*ife-threatening disease*\" introduced a notion of survival prediction and fatal outcome. This last notion could not be defined in a more precise way due to the difficulty in giving an accurate prognosis except when the patient is very close to death \[[@B16]\]. This definition of \"palliative patient\" does not include any criterion based on patient needs because we considered this aspect too difficult to define precisely, as it would have required taking into account many other factors deemed by the caregivers to be related to palliative care \[[@B17]\]. The second part of the study was carried out in respect of those patients who met these four criteria. The study nurses made an interview of the same caregivers using a structured questionnaire. The questionnaire collected data relating to the patient\'s socio-demographic characteristics, diagnoses, prognosis, and care plan. The questionnaire can be found in annex (File [1](#S1){ref-type="supplementary-material"}: English version; File [2](#S2){ref-type="supplementary-material"}: French version). In order to avoid any (mis)interpretation of the palliative patient\'s definition, the term \'palliative\' was not used during the interview of the caregivers. The interviewer presented to the caregivers a paper mentioning the 4 abovementioned criteria of our definition. Then the caregivers reviewed if the patient met each of the four criteria presented. Before the beginning of the hospital survey, the questionnaire was first tested in 2 hospitals not included in the survey\'s sample. Then, the study nurses performed in one hospital under the supervision of the survey\'s designer. Finally, during the survey, regular meetings were organised between the study nurses and the survey\'s designer. Univariate and multivariate statistics were performed to analyse the data. Pearson\'s chi square test was used to detect statistical differences between groups as the data were primarily categorical. Comparisons of age between groups were made using the Wilcoxon\'s test. Multivariate logistic regression was also used to test the effects of various factors on the intention to prolong life. The covariates introduced in the model were age, sex, pathology, prognosis and type of bed. The analysis was made with SAS version 9.1 and a p-value equal or less than 0.05 was considered as significant. Results ======= Prevalence of palliative patients --------------------------------- Two-hundred and forty-nine in-patients were identified as \"palliative\" by the medical and nursing staff, comprising 9.4% of the total in-patient population. Table [1](#T1){ref-type="table"} shows that the prevalence of palliative patients was significantly less in surgical and rehabilitation beds than in medical and geriatric beds. The prevalence also varied significantly among regions. One Brussels\' hospital had a particularly high prevalence value. After exclusion of this \'outlier\', there were no significant differences in the prevalence of palliative patients between university and other hospitals, private or public institutions, and hospitals with or without a palliative care unit. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Prevalence of palliative inpatients ::: N Palliative Patients Non Palliative Patients p-value ---------------------- ---------------- ------ --------------------- ------------------------- ------------ Type of beds Surgery 727 16 (2.2%) 711(97.8%) p ≤ 0,001 Rehabilitation 488 22 (4.5%) 466 (95.5%) Medicine 1015 134 (13.2%) 881 (86.8%) Geriatric 409 77 (18.8%) 332 (81.2%) Region Flanders 624 49 (7.9%) 575 (92.1%) p ≤ 0,001 Wallonia 692 56 (8.1%) 636 (91.9%) Brussels 534 85 (15.9%) 449 (84.1%) Palliative care unit With 1614 166 (10.3%) 1448 (89.7%) p = 0.0610 Without 1025 83 (8.1%) 942 (91.9%) Social status Public 1111 96 (8.6%) 1005 (91.4%) p = 0.2338 Private 1528 153 (10.0%) 1375 (90.0%) ::: Patients\' characteristics -------------------------- Of the 249 palliative patients, 55% (136/249) were female and the mean age was 72 years with a range of 21 to 99. The majority of patients were older than 65 years (175/249) with a considerable number older than 80 (93/249). About half of the patients were married (112/239) and the others were widowed (79), divorced (14) or single (34). Seventy percent of patients (174/249) had been admitted from home and 30% from another residence, such as a nursing home. The primary diagnoses are shown in Table [2](#T2){ref-type="table"}. Approximately half of the patients had a primary diagnosis of cancer. The most common non-cancer diagnoses were dementia, stroke, and cardiac, respiratory or hepatic failure. Cancer patients were significantly younger than the non-cancer patients (68 ± 14 versus 77 ± 13 years, p \< 0.0001) and mainly hospitalised in medical beds (81/128). Patients suffering from dementia and stroke were significantly older than the other palliative patients (82 ± 9 years versus 70 ± 15 years, p \< 0.0001) and were largely hospitalised in geriatric beds (34/49) (Figure [1](#F1){ref-type="fig"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Distribution of primary diagnoses ::: Cancer diagnoses 128 (51.4%) ------------------------- ------------- Solid tumour 108 (43.4%) Haematological cancer 19 (7.6%) Non-cancer diagnoses 121 (48.6%) Dementia 32 (12.9%) Stroke 17 (6.8%) Organ system failure 50 (20.0%) Cardiac failure 16 (6.4%) Respiratory failure 16 (6.4%) Hepatic failure 13 (5.2%) Renal failure 5 (2.0%) Other diseases 40 (16.0%) Neurological diseases 8 (3.2%) Vascular diseases 6 (2.4%) Infectious diseases 2 (0.8%) Others 6 (2.4%) Total 249 (100%) ::: ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Age distributions of palliative patients by diagnostic group**. The first bar represents the distribution of age of all palliative patients whatever the disease. The others display the distribution of age for the most frequent underlying diseases. ::: ![](1472-684X-10-2-1) ::: For almost one third of patients (71/242), the diagnosis had been established 3 months before the current hospitalisation and for half of them (112/242), it had been established during the year prior to the study. As illustrated in Table [3](#T3){ref-type="table"} the estimated life expectancy varied from less than 7 days to more than 5 years. One third of patients had a life expectancy of three months or less and, from the primary diagnosis, one half of patients would be expected to still be alive after six months (Figure [2](#F2){ref-type="fig"}). The prognosis was less than 1 year for 88% of cancer patients and for 56% of non-cancer patients (p \< 0.0001). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Distribution of estimated life expectancy ::: \< 7 days 10 (4.1%) 79 (32.5%) ---------------------- ------------ ------------ \> 3 and ≤ 6 months 40 (16.5%) 97 (40.0%) \> 6 and ≤ 12 months 57 (23.5%) \> 1 and ≤ 5 years 62 (25.5%) 67 (27.5%) \> 5 years 5 (2.0%) Total 243 (100%) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Survival prognosis according to disease**. The first bar represents the distribution of life expectancy of all palliative patients whatever the disease. The others display the distribution of survival prognosis for the most frequent underlying diseases. ::: ![](1472-684X-10-2-2) ::: Patients\' treatment -------------------- The caregivers had already established a treatment plan for 220 of the 249 patients (88%) before the interview. The plan had been discussed by physicians and nurses in 191 cases (77%) and by physicians alone in 27 cases (11%). These percentages were independent of the pathology, survival prognosis, or expectations of the treatment plan. When analysing the expectations of the treatment plan, it appears that the goal of physicians and nurses was to improve patient comfort rather than prolonging life. Multivariate logistic regression analysis showed that treatment expectations depended mainly on the patient\'s prognosis (OR = 1.760, CL = 1.360 - 2.279). For the 79 patients with a survival prognosis less than 3 months, an expectation of prolonging life was reported in just 6.3% of cases (5/79), while for the 67 patients with a prognosis of at least 1 year, the expectation of prolonging life was reported in 41.8% of cases. No significant differences in expectations were observed comparing cancer to non-cancer patients (Table [4](#T4){ref-type="table"}); however, the caregivers more frequently reported an expectation to prolong life in patients with stroke (6/17) or organ system failure (20/50) than in patients with dementia (1/32). ::: {#T4 .table-wrap} Table 4 ::: {.caption} ###### Physicians\' expectations from the treatment plan ::: -------------------------------------------------------------------------------------- Life prolongation\ Improvement of comfort\ n = 65 (100%) n = 179 (100%) ----------- ------------- -------------------- ------------------------- ------------- Age \< 75 years 37 (56.9%) 72 (40.2%) p = 0.0204 ≥ 75 years 28 (43.1%) 107 (59.8%) Prognosis ≤ 3 months 5 (7.7%) 73 (40.8%) p \< 0.0001 \> 3 months 56 (86.2%) 104 (58.1%) ≤ 1 year 33 (50.8%) 141 (78.8%) p = 0.0019 \> 1 year 28 (43.1%) 36 (20.1%) -------------------------------------------------------------------------------------- ::: The type of treatment was generally clearly documented and defined by the professional caregivers. Cardiac resuscitation was excluded for 71% of patients (177/249). Antibiotics, transfusions, treatments specific to the causative pathology (e.g., chemotherapy for cancer patients), artificial nutrition, and transfer to the intensive care unit were being considered, had been planned, or were ongoing in 90% (224/249), 78% (195/249), 57% (142/249), 50% (124/249) and 33% (81/249) of patients, respectively. These interventions were administered in order to control symptoms in 66% (149/224), 74% (144/195), 56% (80/142), 45% (56/124) and 25% (20/81) of the cases, respectively. Table [5](#T5){ref-type="table"} shows the proportion of patients for which treatments were excluded depending on their prognosis. In case of very poor prognosis, cardiac resuscitation and transfer to intensive care unit were excluded for all patients. These 2 treatments were excluded for more than half of patients whatever their prognosis. ::: {#T5 .table-wrap} Table 5 ::: {.caption} ###### Prognosis and treatment excluded ::: Prognosis --------------------------------------------- ----------- ------- ------- ------- ------- ------- Cardiac resuscitation 100% 91.7% 81.8% 72.5% 63.2% 67.2% Transfer to intensive care unit 100% 95.5% 72.7% 57.9% 58.2% 56.5% Treatment specific to the causative disease 90.0% 52.2% 54.8% 30.8% 28.6% 33.3% Artificial nutrition 90.0% 73.9% 47.6% 54.1% 40.0% 36.1% Antibiotics 80.0% 30.4% 4.4% 0 1.8% 3.1% Transfusion 80.0% 54.2% 20.5% 13.5% 9.1% 5.0% ::: Discussion ========== Several limitations should be mentioned when interpreting these results. The first is a possible bias in the recruitment of patients. The initial sample size calculations gave an estimate of at least 3640 beds to recruit 364 palliative patients. The final sample size was smaller, i.e. 249 patients, for two reasons. The mean bed occupation rate was lower than expected; the study excluded patients with a length of stay less than 48 hours (25% of patients in some acute hospitals). The second limitation is related to the fact that only the health care providers were interviewed and therefore, the survey inaccurately reflects patient treatment preferences. The third limitation concerns the method of patient selection. We quantified the palliative in-patient population on just one day. Visiting the same hospitals more than once would have provided a more precise measure. Nevertheless, this is the first survey to explore the number and characteristics of palliative inpatients at a national level. Slightly less than one out of ten inpatients was identified as palliative. Similar percentages have been reported from other surveys but these were conducted in just one institution. Morize et al included all patients with advanced or terminal stage life-threatening illness who were hospitalised in a large French university hospital \[[@B6]\]. These authors reported that 13% of the inpatients were palliative patients. A similar percentage (12%) was observed by Edmonds et al. and by Billings et al in an English and an American academic hospital, respectively \[[@B7],[@B8]\]. In a study by Gott and colleagues, the prevalence of palliative patients was higher (22%), but the inclusion criteria in this study were based on need for supportive and palliative care \[[@B9]\]. Similarly, Skilbek et al. concentrated on specialist palliative care services and observed that 4% of in-patients were considered suitable for referral to a palliative care unit \[[@B10]\]. As expected, the largest numbers of palliative in-patients were admitted to geriatric beds. Metropolitan hospitals also had greater number of palliative patients, supporting the findings of Houtekkier et al. who concluded that palliative patients died in hospital more often in Brussels than in other parts of country \[[@B18]\]. As mentioned in the section \'method\', one hospital was considered as an \'outlier\'. This hospital holds 22% of Brussels\' palliative beds and was the pioneer of in-hospital palliative care in the country. The higher proportion of palliative patients observed in this hospital could be due to a different culture about palliative care. The second aim of the present study was to describe the demographic and clinical characteristics of the palliative inpatients. Our results show that the palliative inpatient population is complex. A large number of cancer and non-cancer pathologies are represented, contrary to what is usually described in specialist palliative care services \[[@B19],[@B20]\]. As in previous reports, cancer was the leading diagnosis in our study but nearly half the patients had a non-malignant disease \[[@B6],[@B9]\]. Despite their typically insidious onset, prolonged disease trajectory and difficulty in predicting life expectancy, chronic illnesses are major causes of death in developed countries today \[[@B21]-[@B23]\]. Moreover, persons dying from chronic illness tend to have frequent exacerbations requiring hospitalisation. There is evidence suggesting that these patients may require palliative care, just as those who suffer from malignant disease \[[@B24]\]. In view of these findings, palliative care in hospital cannot be confined to one patient group and professional caregivers need to acquire sufficient expertise to meet the common but also the specific needs of cancer and non-cancer patients \[[@B13]\]. Even if a correct estimation of the patient\'s prognosis remains quite difficult, our results show considerable variation in the life-expectancy of our palliative population \[[@B16]\]. One third of the palliative inpatients had a life expectancy of 3 months or less. These patients can be considered \"terminally ill patients\" as they are referred to in the current literature. For approximately another one third of patients, the physicians and nurses considered the survival prognosis to be more than one year. Nevertheless, in 70% of all the palliative patients, the treatment plan aimed at improving symptoms rather than at prolonging life. As other researchers, we noted that when caregivers considered using potentially life-prolonging interventions, their decision was significantly associated with a long-term survival prognosis \[[@B25]\]. However, we found no difference between patients with and those without cancer, as reported by Van den Block et al \[[@B26]\]. In summary, in contrast to Becker and colleagues who noted that comfort-focused care concerned less than one dying patient out of two, our results indicate that the Belgian physicians and nurses are willing to limit aggressive treatments and to plan comprehensive palliative care \[[@B27]\]. Our results also indicate that the caregivers seem to be in agreement with the World Health Organisation\'s recommendation and tend to integrate palliative care as soon as possible into the course of illness, as reported by the majority of European medical oncologists \[[@B1],[@B12],[@B28]\]. Another striking finding of our study was that antibiotics, blood transfusions, specific treatments for primary disease, artificial nutrition, and transfer to the intensive care unit were considered for, or given, to about 90%, 80%, 60%, 50% and 33% of the patients, respectively. Several authors have already noted that in an acute care hospital, such therapeutic interventions, considered as comfort care, were continued for the majority of dying patients \[[@B26],[@B29],[@B30]\]. However, as these studies were retrospective charts reviews, the detailed reasons for the therapeutic procedures could not be clearly determined. In our survey, the treatment objective was generally clearly noted by the health care providers: transfusions and antibiotics were used largely to alleviate symptoms; whereas admission to the intensive care unit, artificial nutrition, and specific disease-related treatments were used more to prolong life. Undoubtedly, interventions such as antibiotics may contribute to a better management of distressing symptoms \[[@B31]\]. Furthermore, the long-term prognosis of some patients and uncertainty about the short-term prognosis in others may encourage a mixed management strategy and an interaction between a curative and palliative approach. Nevertheless, in a setting where priority is given to life-supporting and life prolonging activities, some of these interventions may be considered invasive and futile \[[@B32]\]. Van Leeuwen et al, who observed oncology multidisciplinary meetings discussing potentially life prolonging treatments, came to the conclusions that before making a decision, healthcare professionals should gather extensive information about gains that may be expected from an intervention \[[@B33]\]. If case of doubt about whether or not to start or continue treatment, the patient\'s wish could be a decisive consideration. Unfortunately, the purpose of our study was not to assess whether the decisions of the interviewed healthcare professionals were medically and ethically appropriate. Conclusions =========== The ability of health care providers to recognise the patient as \"palliative\" and their readiness to limit aggressive treatment and plan palliative care is essential to improve palliative care for hospitalised patients. The main result of this article is that physicians and nurses identified 10% of inpatients as \"palliative\" patients and that they adopted a comfort care plan in 70% of cases. Our results highlight that the palliative inpatient population is multifaceted and that therapeutic procedures are varied and complex. These findings may help in planning the organisation of palliative care in health care systems. Models of care that embrace all end-of-life paths and meet the common but also the specific needs of every disease must be developed. Medical and nursing staff also need to be educated and supported in provision of care so that palliative patients can live with comfort and dignity whatever their primary diagnosis or their life expectancy. Another challenge is to determine how many and which of the 10% of palliative in-patients should have access to specialised palliative care services. These issues are important and require careful consideration if high quality of care is to be provided to all patients at the end of life. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MSD conceived of the study, participated in its design and coordination and helped to the draft of the manuscript. YLK participated to the data analysis. CMB participated in the acquisition of data, statistical analysis and drafted the manuscript. All authors read and approved the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1472-684X/10/2/prepub> Supplementary Material ====================== ::: {.caption} ###### Additional file 1 **Questionnaire (English version)**. This file contains the questionnaire used by the study nurses when interviewing the caregivers. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 **Questionnaire (French version)**. This file contains the questionnaire used by the study nurses when interviewing the caregivers. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ We would like to thank Sylvie Roels, Pierre Fontaine and Ann Cardinael for data collection. These individuals were compensated as study personnel. We are also indebted to Chantal Doyen and Annie Drowart who tested the questionnaire. We also thank the reviewers for their constructive remarks.

PubMed Central

2024-06-05T04:04:18.947450

2011-3-2

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052175/", "journal": "BMC Palliat Care. 2011 Mar 2; 10:2", "authors": [ { "first": "Marianne S", "last": "Desmedt" }, { "first": "Yolande L", "last": "de la Kethulle" }, { "first": "Myriam I", "last": "Deveugele" }, { "first": "Emmanuel A", "last": "Keirse" }, { "first": "Dominique J", "last": "Paulus" }, { "first": "Johan J", "last": "Menten" }, { "first": "Steven R", "last": "Simoens" }, { "first": "Paul J", "last": "vanden Berghe" }, { "first": "Claire M", "last": "Beguin" } ] }

PMC3052176

Background ========== Slowed muscle relaxation due to persistent electrical discharges is the hallmark of myotonia \[[@B1]-[@B4]\]. Myotonia occurs naturally in several species (humans, goats, mice) as a result of genetic deficiency of the skeletal muscle CLC-1 channel, a disease which in humans is termed myotonia congenita \[[@B1]-[@B13]\]. It can also be produced experimentally by blocking muscle Cl^-^channels of normal muscle, for example with 9-anthracene carboxylic acid (9-AC), p-chloro-phenoxy-propionic acid, or 2,4-dichlorphenoxyacetate \[[@B4],[@B14]-[@B16]\]. Muscle from humans and animals with myotonia congenita has physiological, structural and biochemical alterations which transcend the loss of CLC-1 channels, including hypertrophy (goats, most humans) or atrophy (mice), alterations in fiber type composition (in particular loss of type IIB fibers, seen in most species with myotonia congenita), and altered amounts of parvalbumin \[[@B1],[@B5],[@B7],[@B9],[@B11]-[@B13],[@B17],[@B18]\]. These downstream changes may contribute to the complex abnormalities in contractile performance found in CLC-1 deficient muscle, in particular changes that occur during the contractile phase of the contraction-relaxation cycle, such as impaired force production and alterations in rate of fatigue during isometric contractions \[[@B19]\]. Humans with myotonia experience limb muscle stiffness which interferes particularly with the initiation of movements \[[@B3],[@B20]-[@B22]\]. Involvement of respiratory muscles may lead to \"breathing difficulties\", dyspnea, sleep apnea, and daytime alveolar hypoventilation \[[@B23]-[@B26]\]. For many subjects the myotonia has an adverse effect on their ability to engage in sports \[[@B2],[@B21]-[@B23]\]. The extent of myotonia, however, dissipates with repetitive contractions, the so-called warm-up phenomenon \[[@B2]-[@B4],[@B16],[@B21]\]. This has been examined in the context of a short series of low intensity contractions reducing myotonia during subsequent low intensity contractions \[[@B7],[@B16],[@B20],[@B27]\] rather than in the context of repetitive contractions of sufficient severity to produce fatigue, such as might occur during athletic activities. The general purpose of the present study was therefore to examine myotonia during fatigue-inducing stimulation. Based on previous studies examining the decline of myotonia in response to non-fatiguing contractions, the specific hypotheses of the present study were that a) myotonia declines more rapidly than force during fatigue-inducing stimulation, and b) the rate of decline of the myotonia during fatigue-inducing stimulation is affected by the frequency of stimulation producing fatigue (specifically higher stimulation frequencies augment the rate of dissipation). In order to avoid the effects of downstream structural and biochemical changes (eg., alterations in fiber type composition and atrophy or hypertrophy \[[@B1],[@B5],[@B7],[@B9],[@B11]-[@B13],[@B17],[@B18]\]) resulting from genetic CLC-1 channel deficiency that can affect muscle fatigue properties in manners apart from the myotonia itself, the present study utilized Cl^-^channel blockade with 9-AC to produce myotonia in otherwise normal muscle rather than testing muscle that is genetically deficient in Cl^-^channels. Muscles pertinent to breathing (diaphragm), fast twitch movements (EDL), and slow twitch movements (soleus) were tested to determine whether 9-AC has varying effects on muscles with different fiber type compositions. Methods ======= Studies were performed using adult male Sprague-Dawley rats (n = 35, weight = 390 ± 15 grams). All protocols were approved by the Institutional Animal Care and Use Committee and conformed to animal care guidelines established by the National Institutes of Health. Rats were well-anesthetized using a rodent anesthetic cocktail (initial dose, ketamine 21-30 mg/kg, xylazine 4.3-6.0 mg/kg and acepromazine 0.7-1.0 mg/kg, with supplemental smaller doses given as needed to produce and maintain a deep level of anesthesia). The EDL and soleus muscles were removed from the legs with intact tendons, and the diaphragm muscles were removed with intact rib origins and central tendon insertions. Contractile studies were performed in physiological solution consisting of (in mM): 135 NaCl, 5 KCl, 2.5 CaCl2, 1 MgSO4, 1 NaH2PO4, 15 NaHCO3, and 11 glucose, with the pH adjusted to 7.35-7.45 at 37°C while being aerated with 95% O~2~-5%CO~2~. The diaphragm muscle was cut into small strips parallel to the fiber direction keeping origin and insertion intact (strip width \~5 mm), and mounted vertically in a double-jacketed chamber while the temperature was maintained at 37°C. The soleus and EDL muscles were similarly mounted in the same chamber by the attached tendons, except that they were left whole and not cut into strips like the diaphragm. A pair of platinum electrodes was placed parallel to the diaphragm muscle strips or limb muscles, and supramaximal voltages were delivered with a pulse width of 1 ms. The lengths of the muscle samples were adjusted until the twitch force was maximized (optimal length), and kept at this length for the duration of the contractile study. Ten minutes after the diaphragm muscle or limb muscle (at optimal length) had equilibrated to the Kreb\'s solution, three twitch contractions were recorded 10 seconds apart to determine the baseline force of the muscle. Three minutes thereafter, another three twitches were recorded 10 seconds apart to verify stability of the muscle sample (defined as \<5% variability in force between first and second set of twitches). Subsequently 1 ml Kreb\'s solution containing 9-AC was added to half of the muscle samples to obtain a bath concentration of 100 μM, and to the other half of the muscle samples 1 ml of the Kreb\'s solution without 9-AC was added. Twenty minutes later repetitive train stimulation was initiated. This consisted of intermittent 20-Hz or 50-Hz train stimulations, with a train length of 0.33 s and one train every three seconds. The relatively long inter-train interval was needed due to the markedly slowed rate of relaxation in the presence of 9-AC, as this allowed time for muscle force to return back to baseline prior to the subsequent train. Due to the slow isometric kinetics of the soleus muscle, contractions have a high degree of fusion during 50 Hz stimulation, impairing the ability to measure contraction and relaxation times. Therefore soleus was only studied during 20 Hz stimulation. Muscle contractile performance was assessed with respect to four parameters (Figure [1](#F1){ref-type="fig"}), and in all instances this was relative to baseline passive tension. Peak force was defined as the largest value that occurred during the portion of the contraction while the muscle was being electrically stimulated (and thus did not include mechanical myotonia even if mechanical myotonia exceeded force during active electrical stimulation). These force values were normalized relative to twitch force before drug addition to factor out the effects of variability among muscle samples in absolute force related to variability in animal size and muscle sample size, similar to previous studies of a similar nature \[[@B11],[@B15],[@B19],[@B22]\]. Contraction time was defined as the time from the onset of force production to the top of the first peak of the non-fused contraction; values for contraction time are not presented in those instances in which a distinct first peak was not discernable (which was the case for 50 Hz stimulation for the diaphragm). Half-relaxation time was the time required for force to decrease from the peak value at the end of electrical stimulation to 50% of this value. Late relaxation time was the time for force to decline from 50% of peak to 10% of peak. These four values were quantified for a total duration of six minutes. All data presented are means and SD. Statistical analysis of paired data was performed with a paired t-test. Statistical analysis of data obtained during repetitive stimulation was performed with analysis of variance for repeated measures followed by the Newman-Keuls post-hoc test in the event of significance by analysis of variance. The level for statistical significance was set at P \< 0.05 (two tailed). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Parameters measured for a diaphragm myotonic contraction at 20 Hz**. The baseline is passive force related to stretching the muscle to optimal length, and all other active force values were quantified relative to baseline. ::: ![](1472-6793-11-5-1) ::: Results ======= Diaphragm --------- The effects of 9-AC on diaphragm force, contraction time, half relaxation time and late relaxation time at the outset of repetitive stimulation are listed in Table [1](#T1){ref-type="table"}. 9-AC increased force and contraction time during 20 Hz but not 50 Hz stimulation. Half relaxation and late relaxation times increased during both 20 Hz and 50 Hz stimulation, reaching values in the hundreds of milliseconds. Furthermore, values were generally longer for late relaxation (\~1 to 1.5 seconds) than for the half-relaxation time (\~0.5 to 1 second). None of these parameters changed at the outset of repetitive stimulation in the control muscle samples which were not treated with 9-AC. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### The outset of repetitive stimulation during 20 Hz and 50 Hz stimulation. ::: Stimulation Measurement Frequency Stimulation Before Krebs After Krebs Before 9-AC After 9-AC ------------------------------- ----------------------- -------------- ------------- ------------- ------------------ **Peak force (% of initial)** **20 Hz** 138 ± 8 142 ± 10 155 ± 21 315 ± 53\* **50 Hz** 319 ± 65 345 ± 91 293 ± 47 356 ± 58 **Contraction time (ms)** **20 Hz** 23.7 ± 2.3 23.8 ± 1.2 23.2 ± 2.8 44.8 ± 6.7\* **50 Hz** 20.1 ± 0.9 20.6 ± 1.3 20.0 ± 0.7 20.7 ± 1.2 **Half relaxation time (ms)** **20 Hz** 26.0 ± 4.4 26.5 ± 1.7 29.2 ± 5.0 883.5 ± 296.0\* **50 Hz** 26.4 ± 1.6 27.9 ± 2.6 28.6 ± 3.2 421.7 ± 308.3\* **Late relaxation time (ms)** **20 Hz** 45.5 ± 11.8 51.4 ± 10.4 73.6 ± 50.8 1324.4 ± 339.2\* **50 Hz** 32.0 ± 6.0 34.5 ± 3.9 28.6 ± 8.0 1142.6 ± 504.9\* The effect of Kreb\'s solution and 9-AC on diaphragm muscle at the outset of repetitive stimulation on peak force, contraction time, half relaxation time, and late relaxation time during 20 Hz and 50 Hz stimulation. Values are means ± SD. Asterisks indicate significant differences between before and after 9-AC data. ::: Force values for diaphragm during repetitive 20 and 50 Hz stimulation are depicted in Figure [2A](#F2){ref-type="fig"}. During 20 Hz repetitive stimulation, force declined rapidly in muscles that were treated with 9-AC after the initial 9-AC-induced augmentation. At one minute into the fatigue-inducing stimulation and all points thereafter, force values were equivalent in 9-AC treated and untreated muscles. In contrast, force values did not differ for drug-treated and untreated diaphragm at any time during 50 Hz stimulation. Contraction time also was prolonged by 9-AC during 20 Hz stimulation (Figure [2B](#F2){ref-type="fig"}) and not measurable during 50 Hz stimulation because successive stimulation was 20 ms apart and contraction time was greater than 20 ms. This prolongation waned with repetitive fatigue-inducing stimulation, but did not fully dissipate over the course of six minutes. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in diaphragm muscle during repetitive 20 Hz and 50 Hz train stimulation**. Contraction time was not measurable at 50 Hz. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-2) ::: Both the half relaxation time (Figure [2C](#F2){ref-type="fig"}) and the late relaxation time (Figure [2D](#F2){ref-type="fig"}) were prolonged substantially by 9-AC, but eventually declined to normal or near-normal values during fatigue-inducing stimulation. The decline was more precipitous for the early compared to the late phase of relaxation as well as during 50 Hz compared with 20 Hz stimulation. The rate at which myotonia resolved was much faster than the rate at which force decreased, in that myotonia was almost completely resolved over the first 60 seconds of stimulation whereas force continued to decline for the full duration of stimulation (compare Figures [2C](#F2){ref-type="fig"} and [2D](#F2){ref-type="fig"} with Figure [2A](#F2){ref-type="fig"}). Furthermore, during 50 Hz stimulation the mechanical myotonia was substantially resolved before there was any appreciable force loss. Limb Muscles ------------ Soleus muscle did not demonstrate myotonia in response to 9-AC (data shown for 20 Hz stimulation in Figure [3](#F3){ref-type="fig"}). There was a mild increase in force (Figure [3A](#F3){ref-type="fig"}), but contraction time (Figure [3B](#F3){ref-type="fig"}), half relaxation time (Figure [3C](#F3){ref-type="fig"}) and late relaxation time (Figure [3D](#F3){ref-type="fig"}) were unaffected. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **The effect of 9-AC on peak force, contraction time, half relaxation time, and late relaxation time in the soleus muscle during repetitive 20 Hz train stimulation**. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-3) ::: In contrast, the response of EDL was similar in most respects to that of the diaphragm. Peak EDL force increased during 20 Hz but only minimally so during 50 Hz stimulation (Figure [4A](#F4){ref-type="fig"}), and for 20 Hz stimulation this waned over time with repetitive stimulation. However, contraction time was not altered by 9-AC at either stimulation frequency (Figure [4B](#F4){ref-type="fig"}). Both half-relaxation time (Figure [4C](#F4){ref-type="fig"}) and late relaxation time (Figure [4D](#F4){ref-type="fig"}) of the EDL were prolonged by 9-AC. All relaxation times prolonged by 9-AC normalized rapidly during repetitive stimulation, and this occurred faster than the rate at which force declined, in that myotonia was almost completely resolved over the first 30 seconds of stimulation whereas force continued to decline for the full duration of stimulation (compare Figures [4C](#F4){ref-type="fig"} and [4D](#F4){ref-type="fig"} with Figure [4A](#F4){ref-type="fig"}). As seen with the diaphragm, during 50 Hz stimulation the mechanical myotonia was substantially resolved before there was any appreciable force loss. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in the EDL (extensor digitorum longus) muscle during repetitive 20 Hz and 50 Hz train stimulation**. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance. ::: ![](1472-6793-11-5-4) ::: Discussion ========== The inability of muscles to relax normally after voluntary contractions is characteristic of the disease myotonia. The results of this study showed that mechanical myotonia decreases rapidly during fatigue-inducing stimulation. Furthermore, myotonia was found to decrease faster than force in both the diaphragm and EDL muscles. The normalization of relaxation times was slightly faster at a higher frequency (50 Hz) than a lower frequency (20 Hz) in the diaphragm muscle; however this may have been due to the effects of myotonia being less during 50 Hz than 20 Hz stimulation. Furthermore, the resolution of myotonia was also slightly faster in the EDL muscle than the diaphragm muscle, although again possibly because of differences in the magnitude of the myotonia. Both the diaphragm and EDL muscles had much larger degrees of myotonia than the soleus in response to 9-AC. In addition, force production increased at the lower stimulation frequency (20 Hz) in the diaphragm and EDL, and increased slightly in the soleus at this frequency, but did not increase at the higher frequency (50 Hz) in any of the three muscles with 9-AC. Contraction time increased only in the diaphragm during 20 Hz stimulation. Myotonia, whether genetically- or drug-induced, decreases during repeated contractions, this resolution being termed the \"warm up\" phenomenon. This has been described in clinical reports of humans with myotonia congenita and is also apparent when observing the behavior of genetically myotonic mice \[[@B2],[@B3],[@B21]\]. Physiological manifestations when tested experimentally include improved rate of muscle relaxation and diminution of the duration and intensity of persistent electromyographic activity following repetitive muscle activation. One of the early experimental studies of the warm up phenomenon was that performed by Senges and Rudel \[[@B16]\] in a model of myotonia induced by 2,4-dichlorphenoxyacetate. They examined the effects of a conditioning tetanus preceding a test contraction by 0.5, 1, 2 and 4 seconds. The shortest time interval virtually abolished myotonia, with the effect diminishing markedly as the time interval increased. The warm up phenomenon was described by Heller et al.\[[@B7]\] in the original report of genetically myotonic mice. This was demonstrated based on electromyographic recordings from affected muscle in response to direct peripheral nerve stimulation rather than on measurements of muscle force. Heller and colleagues \[[@B7]\] described the myotonia as declining with repeated trials at 10 second intervals, but recovering when the muscle has rested for one minute. The warm-up phenomenon was also studied by Heimann et al \[[@B27]\]. EDL muscles from myotonic ADR mutants and ADR-MDX double mutants were shown to have similar degrees of myotonia as quantified by the myotonia index \[[@B28]\] (myotonia index of 0.49 vs. 0.57, respectively). Furthermore, they had similar degrees to which the myotonia improved when contractions were preceded by a series of single twitches and incomplete tetanic stimulations. However, the study also found that myotonia symptoms were more pronounced in ADR than ADR-MDX muscle, but ADR-MDX mice had higher levels of weight reduction and premature death. In contrast, for the soleus the ADR mutant had a significantly higher myotonia index than the ADR-MDX mutant (myotonia index of 0.90 vs. 0.61). Data for the warm up phenomenon were not depicted for the soleus. Van Beekvelt et al. \[[@B21]\] studied three humans with myotonia and defined the warming-up phenomenon as the force recovery phase after initial paresis during a sustained voluntary contraction. This study hypothesized that warming-up was due to the enhanced activation of Na+-K+-ATPase during exercise, and used ouabain (a Na+-K+-ATPase inhibitor) to test this. However, it was found that ouabain infusion did not prevent recovery from transient paresis. Therefore, it was concluded that the warm-up phenomenon was not due to Na+-K+-ATPase. Taken together, the above studies provide a comprehensive picture of the manner in which myotonia improves following brief contractions, but these studies had not examined changes in myotonia during the course of repetitive fatigue-inducing contractions. The latter issue has been examined to a limited extent in a previous study from our lab in which we examined isotonic contractions of diaphragm muscle from genetically myotonic mice \[[@B19]\]. Diaphragm from these mice had lesser degrees of myotonia than seen in the diaphragm of the present study. Total relaxation time during a singe train contraction ranged from \~0.2 to 0.6 seconds in contrast to values exceeding 2 seconds with 9-AC in the present study. In the genetically myotonic mice, repetitive train stimulation at a frequency of 50 Hz resulted in a rapid reduction in relaxation time over the course of 30 seconds, with minimal changes thereafter during the subsequent 30 seconds. The present study expands on our previous findings \[[@B19]\] in several manners. We found that the reduction of myotonia during fatigue-inducing contractions occurs during isometric as well as isotonic contractions, and in the drug-induced myotonia model as well as genetic myotonia. Furthermore, the present study indicates that the resolution of myotonia varies as a function of the frequency of muscle stimulation. In addition the extent of drug-induced myotonia differed among the three muscles studied, with the slow fiber type predominance of the soleus appearing to have had a protective effect. Finally, the present data indicate that the time course of the warm-up phenomenon is much faster than that of force loss during fatigue-inducing contractions. One of the limitations of the present study is that the studies were done in vitro, under conditions in which there is no blood flow and thus no delivery of nutrients and/or impaired removal of potentially adverse metabolites. Thus the development of fatigue may have occurred faster in the drug-induced myotonia model than would occur in vivo in humans or animals with genetic CLC-1 chloride channel deficient myotonia. A second limitation is that the genetic muscle diseases that cause myotonia are a heterogeneous group which include not only two variants of CLC-1 deficient myotonia but also myotonic dystrophy. Several of these disorders have features in addition to the myotonia, which for some includes muscle weakness. Among these additional features, muscle weakness in particular may impact the rate at which fatigue develops, thereby changing the temporal relationship between the improvement of the myotonia and the reduction of force in response to repetitive vigorous contractions. Conclusions =========== Fatigue-inducing contractions were shown to dissipate the amount of mechanical myotonia induced by the chloride channel blocker 9-AC. However the rate at which this occurred was considerably faster than the drop in force over time, consistent with different mechanisms accounting for the warm up phenomenon and the production of fatigue. From a clinical perspective this suggests that subjects with myotonia need not warm up to a sufficiently large extent to produce muscle fatigue in order for the myotonia to dissipate, but nonetheless suggest a role for vigorous rather than more modest contractions as a means for resolving the muscle myotonia more quickly. Abbreviations ============= 9-AC: 9-anthracene carboxylic acid. Authors\' contributions ======================= EvL conceived of, and designed the study, participated in statistical analysis, and helped to draft the manuscript. SS participated in the design of the study, collection of data, statistical analysis, and helped to draft the manuscript. MM participated in the design of the study, collection of data, and statistical analysis. All authors read and approved the final manuscript. Acknowledgements ================ This study was supported in part by funding from the Department of Veterans Affairs Medical Research Service.

PubMed Central

2024-06-05T04:04:18.951290

2011-2-28

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052176/", "journal": "BMC Physiol. 2011 Feb 28; 11:5", "authors": [ { "first": "Erik", "last": "van Lunteren" }, { "first": "Sarah E", "last": "Spiegler" }, { "first": "Michelle", "last": "Moyer" } ] }

PMC3052177

Background ========== Cognition-focused interventions are becoming increasingly popular techniques for older adult populations. These interventions are typically grouped into one of three categories - cognitive training, cognitive rehabilitation and cognitive stimulation. Interventions may vary in terms of the degree to which the program is individualised, the content of the activity and the nature of the facilitation (e.g. one-to-one, group, computer based) (see \[[@B1]\] for a review). Cognitive stimulation therapy (CST) has been recommended as the treatment of choice for individuals in the early stages of dementia (Mini Mental State Examination - MMSE, score ≥ 20) \[[@B2]\]. This type of intervention emphasises the benefits of group activities which, dependent on the target population, can range from education, discussion and debate, and problem solving to reality orientation, reminiscence and validation therapy. In a multi-centred randomised controlled trial (RCT), Spector and colleagues \[[@B3]\] allocated 201 participants with dementia to either a CST group or a no treatment control. People in the intervention demonstrated improved cognitive and quality of life scores. A Cochrane review of reminiscence therapy concluded that whilst there was a need for more rigorous trials, there were promising indications that this form of intervention was of potential benefit to patients and their carers \[[@B4]\]. The cost effectiveness of CST has also been established \[[@B5]\] and manuals operationalised \[[@B6]\]. CST has traditionally been implemented in group settings such as day centres and residential facilities and co-ordinated by trained facilitators. Some interventions have also adopted multi-modal programs targeting cognition and well being in the patient with dementia and addressing the coping abilities and needs of the family member/care-giver with positive results (e.g. \[[@B7]\]). However there is a paucity of research that has utilised cognitive stimulation techniques in a manner easily adopted for the home environment and implemented by the carer/family member. Quayhagen and Quayhagen \[[@B8]\] had spousal caregivers apply cognitive stimulation techniques and found that improvements in memory, as well as additional aspects of cognition, could be achieved, with a home-based program. This study, however, was limited to spouses and a research team modelled the programme in the home of the dyad. For those patients who are widowed or single, access to a carer or companion may be limited to less contact hours. The feasibility of having instructors/team members provide one-to-one instruction may also restrict the availability of this type of facilitation. We have designed a single-blind, randomized trial of an intervention drawing on principles of cognitive stimulation. The activities and intervention were selected with regard to suitability for older adults with mild Alzheimer\'s disease (AD) and designed in a manner that could be readily adapted for use in the home environment and implemented by a companion. The study aims to determine if a program of cognitive activity (CA) that includes both people with AD living in the community and a companion has better cognitive outcomes over six months for participants with dementia than a CA program delivered to companions only. Secondary outcomes for this trial include the quality of life and well being of people with AD and their companions. Methods/Design ============== Background ---------- The Promoting Healthy Ageing with Cognitive Exercise for the treatment of mild Alzheimer\'s Disease (PACE-AD) study is a randomised clinical trial that commenced recruitment of participants in October 2009. In 2007, our group developed a cognitive activity intervention program which was well received by older adults with mild cognitive impairment \[[@B9]\]. In early 2009, this program was modified for its suitability for participants with mild AD. Nine relatives of individuals with mild AD were invited to attend a morning education and activity session regarding the proposed study. Feedback from the relatives regarding the nature of the study was overwhelmingly positive, though the length of the proposed sessions, coupled with the complexity of the program content, were areas identified as requiring further consideration. After collating the verbal and written feedback, additional minor modifications were made to the study protocol and recruitment began. Study Design and Setting ------------------------ PACE-AD is a six-month, single blind randomised trial of a CA intervention delivered to older adults with mild AD and companions compared with companions alone. Ethics ------ The Human Research Ethics Committees of Royal Perth Hospital (RPH), Mercy Hospital and Bentley Hospital have approved the study protocol and procedures, and the study is being conducted according to the Declaration of Helsinki. Recruitment and Selection of participants ----------------------------------------- Recruitment for this trial is currently ongoing. Participants are community dwelling volunteers, recruited mainly from local memory clinics. Potentially suitable participants are approached via mail and receive a follow up telephone call. Interested volunteers are screened with a semi-structured telephone interview and invited to visit the Mercy Hospital for a more detailed screening assessment (clinic screen) and to provide written informed consent. ### Inclusion and Exclusion Criteria The defining feature of participants included in the PACE-AD study is a diagnosis of Alzheimer\'s disease (probable or possible) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer\'s Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer\'s Criteria. Participants need to have a Mini Mental State Examination (MMSE) score between 18-26 inclusive (i.e., mild severity), at the time of screening and be fluent in written and spoken English. Mild AD participants with a prevalent psychiatric disorder (e.g. depressive episode), current history of hazardous or harmful alcohol consumption (Alcohol Use Disorders Identification Test - AUDIT - score ≥15 \[[@B10]\]), or who do not have an available companion are excluded. Those individuals with a current medical condition preventing participation in the study tasks (such as severe sensory impairment) or associated with reduced survival over a six-month period (e.g. advanced cancer) are also excluded. ### Telephone Interview Volunteers are initially screened via a telephone interview to ascertain suitability for the study. Those without a suitable companion (someone who spends at least ten hours per week with the person, including time at their home) are immediately excluded. All individuals are asked about their general health (past and current), education, English literacy skills and current alcohol and cigarette consumption. Telephone interviews range from 10 to 20 minutes in length and those meeting provisional inclusion criteria are invited to a face-to-face assessment (clinic screen). ### Clinic Screen After obtaining written consent from volunteers with mild AD and their companions each person\'s eligibility for the study is established according to the following criteria: #### Mild AD • Mini Mental State Examination score ranging between 18-26 inclusive \[[@B11]\] • Patient Health Questionnaire (PHQ-9) score \<15 \[[@B12]\] #### For the companion of the volunteer with mild AD • MMSE total score of 26 or above \[[@B11]\] • PHQ-9 score \<15 \[[@B12]\] [The MMSE]{.underline}\[[@B11]\] is a brief test of mental status and cognitive function commonly used to screen for dementia and to monitor cognitive decline. It produces a total score that can range from 0 to 30. Scores lower than 24 are reliably associated with the diagnosis of dementia or other organic mental disorders. The present study also used the MMSE to exclude companions with cognitive impairment. The [PHQ-9]{.underline}\[[@B12]\] is a widely used scale to establish the presence of clinically significant depression amongst community-dwelling adults. Scores range from 0 to 27, with scores of 15 or greater indicative of clinically significant depression. In addition to the cognitive and mood screen, a self-reported medical history questionnaire is completed by each individual, which includes details regarding their medication usage. This information is also collected at the final assessment. The screening assessment of both volunteers takes approximately 30 minutes to complete and any pertinent clinical information is reported to the relevant treating physician with the consent of the study participant. If both volunteers meet criteria for the study, they proceed to undertake the baseline assessment. Outcome Measures and Assessment Procedures ------------------------------------------ ### Baseline and Follow-up Assessments Baseline assessments are completed immediately after the clinic screen, 1-2 weeks prior to the first intervention session and randomisation. Post-intervention assessments are undertaken within two weeks of program completion and the final assessment is completed 26 weeks after the baseline assessment (see Figure [1](#F1){ref-type="fig"}). All assessments take between 90 to 120 minutes to complete (including the provision of short breaks) and consist of the following series of tests and questionnaires (see also Table [1](#T1){ref-type="table"}). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### Baseline assessment ::: ![](1745-6215-12-47-1) ::: ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Outline of the primary and secondary outcome measures used in the PACE-AD trial ::: *Assessment Tool* Participant with mild AD Companion -------------------- -------------------------- ----------- ADAS-COG X RBMT-3 X ToL X COWAT X MMSE X X PHQ-9 X X DEMQOL-version 4 X X Short-Form IQ CODE X X IADL X NPI-Q X AUDIT X SF-12 X The X indicates who completed the respective assessments (participant with mild AD or companion). All measures were given at baseline, 13 and 26 weeks. ADAS-COG = Alzheimer Disease Assessment Scale-Cognitive; RBMT-3 = Rivermead Behavioural Memory Test-Third Edition; ToL = Tower of London; COWAT = Controlled Oral Word Association Test; MMSE = Mini Mental State Examination; PHQ-9 = Patient Health Questionnaire - Nine Item; Short-Form IQ CODE = Modified Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly; IADL = The Lawton Instrumental Activities of Daily Living; NPI-Q = The Neuropsychiatric Inventory Questionnaire; AUDIT = World Health Organisation\'s Alcohol Use Disorders Identification Test; SF-12 = Short-Form 12-Item Health Survey. ::: ### Primary outcome measure Alzheimer Disease Assessment Scale-Cognitive (ADAS-COG)\[[@B13]\] is a frequently used measure of global cognitive functioning and assesses cognitive domains including orientation, memory, language, and praxis; common areas of impairment present in AD. It provides sub-scale scores as well as a global score out of 70, with higher scores indicating lower levels of cognitive functioning. A four-point change on the ADAS-COG over a six month period is considered a clinically relevant difference \[[@B14],[@B15]\]. ### Secondary Outcome Measures #### Measures completed by participants with mild AD The Rivermead Behavioural Memory Test-Third Edition (RBMT-3)\[[@B16]\] comprises a series of memory tasks analogous to those faced in everyday situations. Sensitive to changes in memory functioning over time and well validated with patient groups \[[@B16]\], a parallel version also reduces the confounds of practice effects. Three subtests from the RBMT-3 are performed with mild AD participants at all assessment time points, with the parallel version administered at the post intervention assessment. The Tower of London (ToL) \[[@B17]\] consists of ten problems of increasing difficulty designed to assess executive planning abilities. The participant is required to manipulate three coloured beads across three pegs on a wooden board to mirror the examiner\'s board. Participants are instructed to solve the problem in as few moves as possible while adhering to two specific rules, within a two minute time limit. In the current trial this test is administered with minor modifications, in order to minimise frustration for participants with mild AD. The Controlled Word Association Test (COWAT) \[[@B18]\] requires the participant to generate as many words as possible with a given letter of the alphabet, within a one-minute time period, excluding proper nouns and the same word with a different suffix. This test is used as an indicator of executive functioning for participants with mild AD. #### Measures completed by participants with mild AD and their companions We use the MMSE total score and the PHQ-9 total score, as previously described, to monitor changes in cognition and mood of all participants throughout the trial. DEMQOL-version 4\[[@B19]\] is a 28-item self-reported, interviewer administered questionnaire assessing participants\' perceptions of their health related quality of life in the past week. It assesses five domains: daily activities/self care, health and well-being, cognitive functioning, social relationships, and self-concept. The DEMQOL has been demonstrated to show high reliability (internal consistency and test-retest) and moderate validity in people with mild to moderate dementia. In this trial, participants with mild AD are given the questions verbally with the aid of visual response options. Companions\' quality of life is also assessed with this measure. Modified Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (Short-Form IQ Code) \[[@B20]\] is an informant based, brief cognitive screening questionnaire for individuals with dementia. It assesses an individual\'s cognitive abilities as they apply to everyday situations and consists of 16 items. The original version asks the informant to judge the extent to which the patient\'s level of functioning has changed in the past ten years. Subsequent versions have used different time frames to allow for informants who might not have known the patient for very long. In this trial only AD participants\' current level of functioning will be assessed, to allow direct comparison at follow-up testing. #### Measures completed by companions The Lawton Instrumental Activities of Daily Living (IADL) \[[@B21]\] scale is an informant based questionnaire which assesses the patient\'s current ability to perform eight independent activities of daily living. These include using the telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, taking medications and handling finances. The Neuropsychiatric Inventory Questionnaire (NPI-Q)\[[@B22]\] is a brief screening instrument assessing the frequency and severity of twelve neuropsychiatric behavioural disturbances common in dementia. The companion is asked to rate the presence, change and severity of symptoms in the AD patient in the past month along with associated caregiver distress. The NPI-Q is considered to be a reliable and valid tool for assessing psychopathology in dementia patients and is sensitive to treatment effects. The World Health Organisation\'s Alcohol Use Disorders Identification Test (AUDIT) \[[@B10]\] is used to screen for risky, hazardous or harmful drinking. There are 10 items and supplementary questions, with questions scored on a scale of 0 to 4. Scores of 16 or above suggest \"high-risk\" or \"harmful level\" of drinking behaviour. This questionnaire is monitoring the companion\'s alcohol usage throughout the trial. Short-Form 12-Item Health Survey (SF-12) \[[@B23]\] is a self-report questionnaire consisting of twelve questions from the SF-36 Health Survey \[[@B24]\] and assesses an individual\'s perception of their general physical/health functioning, bodily pain, vitality, social functioning, general mental health, psychological wellbeing, and role limitations due to physical or emotional issues. This questionnaire is used to monitor change in the companion\'s mental and physical components of quality of life throughout the trial. ### DNA Collection Participants with mild AD are asked to provide a saliva sample for the extraction of DNA to assess the influence of common genetic polymorphisms (e.g., apolipoprotein E4 genotype) on the outcomes of the study. The samples are collected and processed by the Department of Clinical Pathology and Biochemistry at the RPH and stored at -80°C. All material is batched and will only be processed at the end of the trial. Intervention ------------ Following the baseline assessment, dyads (person with mild AD and companion) are randomised to one of two intervention groups. The intervention consists of a twelve-week CA program. Sessions are run by facilitators experienced in conducting research with older adults. The two groups are exposed to the same length of intervention, social interaction and contact with the program facilitators. The program was developed by a qualified Neuropsychologist (MV) and a manual produced. All of the sessions are delivered in a structured way for consistency, and audio-taped for subsequent fidelity assessment. Research assistants (RAs) blinded to group allocation conduct all assessments. RAs are provided with strict instructions to avoid any potential opportunity for disclosure regarding intervention participation. Following completion of the trial, RAs undertaking data collection will be asked to identify the group membership of participants, to determine the effectiveness of the blinding procedures that were put in place for this project. A brief summary of each intervention group is provided below. Participants with mild AD and their companions (Group 1): Each group consists of a maximum of five dyads taking part in 90-minute sessions once a week for seven weeks. Session One introduces the nature of the program and develops familiarity within the group, with personal introductions and sharing of background information and experiences. Sessions Two to Six focus on defining attention, processing speed, memory, language and executive functions. These sessions outline how these cognitive abilities are affected in AD and provide participants with strategies and techniques for managing declining capacity in each of these domains. Regular opportunity for supervised practice of such techniques and examples of activities to strengthen abilities occurs in all sessions. Dyads are also provided with an hour of home activities, to reinforce material learnt in the sessions. Sessions Seven to Eleven are completed by the participant with mild AD and their companion together in their own environment. Participants are provided with a workbook containing instructions and examples, along with phone calls from the facilitator once per week to address any questions and to monitor task completion. The final session (Session 12) offers an overview and discusses strategies to maximise participation. Companions of participants with mild AD alone (Group 2): This group consists of a maximum of five companions presented with the same session information and materials as Group 1. The only difference is that the companions attend the sessions with other companions, and are instructed to convey what is learnt during the sessions to the participant with mild AD during their home activities. Randomisation ------------- Randomisation is performed according to a random list of numbers generated by computer and undertaken in random blocks of 8 or 10 with no more than five dyads allocated to each group. The allocation list is handled by an independent investigator (OPA) who has no contact with study participants and is not involved in the supervision of staff responsible for the collection of data. The allocation table is then passed on to the facilitator running the intervention, who invites eligible participants to join the relevant groups. RAs undertaking the follow-up assessments remain blinded to group allocation. Sample Size and Power Calculation --------------------------------- This trial aims to recruit 128 participants with mild AD and their carers, with 64 patients being allocated to each study group. A study of this size will have 80% power to detect between group differences on the ADAS-COG associated with moderate effect size (Cohen\'s d = 0.5) and alpha of 5%. Analysis of the Data -------------------- Changes in the ADAS-COG score from baseline are the primary outcome of interest in the study. We will model these changes at 2 time points: 13 (immediately after the intervention comes to an end) and 26 weeks. We will use mixed effects models to analyse the data. This approach will enable us to take into account the cognitive performance of participants at baseline, as well as the intra-person correlation generated from repeated measures. Intention-to-treat (ITT) analyses will be based on the use of imputation by chain equations (ICE), which will precede the use of the mixed-effects model. The ITT will be the primary analysis of the study. Discussion ========== Cognition-focussed interventions are increasingly being adopted for the treatment of cognitive decline in older adults, with CST recently recommended as the treatment of choice for individuals with mild dementia \[[@B2]\]. However, the efficacy, sustainability of effect, and cost-effectiveness of involving and training a carer/companion to deliver cognitive tasks, and the degree to which cognitive changes can be maintained over time using this form of delivery, is yet to be established. This trial has been designed according to CONSORT guidelines and has been structured to enable its reproduction in both research and clinical settings. We expect to complete recruitment by December 2011 and anticipate that the results of this study will have implications for health care policy and resourcing and facilitate improvements in the management of people with mild AD. The results of this study will enable us to determine, for the first time, if a CA intervention delivered to companions alone is as effective at promoting changes in cognitive function as an intervention involving both the person with dementia and his/her companion. These results will have important implications for the design of sustainable cost-effective health services for people with mild AD. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= All authors are members of the PACE-AD project group. MV acts as guarantor of the data; she has designed the intervention and supervises research staff. MV and OPA designed the study, which is funded by a grant from ANZ Trustees Limited to OPA. JS is responsible for data collection and contributed to drafting the paper together with MV. OPA and LF reviewed the manuscript critically. All authors have approved the submission of the present paper to Trials. Acknowledgements ================ We are most grateful to all volunteers taking part in the study and to our research staff (Joanna Eaton, Rachel Lowry, Kendall Sharpe and Natalie Di Renzo). The staff at the WACHA as well as Bentley, Mercy and Royal Perth Hospitals have been instrumental in their assistance with recruiting patients. This project is supported by an unrestricted grant from ANZ Trustees Limited.

PubMed Central

2024-06-05T04:04:18.953487

2011-2-17

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052177/", "journal": "Trials. 2011 Feb 17; 12:47", "authors": [ { "first": "Mandy R", "last": "Vidovich" }, { "first": "Josephine", "last": "Shaw" }, { "first": "Leon", "last": "Flicker" }, { "first": "Osvaldo P", "last": "Almeida" } ] }

PMC3052178

Background ========== The placebo-controlled trial is a widely accepted design for evaluating pharmacological and device interventions. There has, however, been considerable debate in the literature about the ethical acceptability of including a placebo in procedures such as surgery. Whilst the use of a placebo in surgical trials is not new \[[@B1]-[@B8]\] the concept remains highly controversial. Several commentators have argued that placebo procedures are ethical for certain trials of surgery \[[@B9]\], but others have argued strongly that the use of surgical placebos cannot be justified as any surgical procedure carries risks of harm that are greater than those associated with no surgery \[[@B10],[@B11]\]. The term \"placebo\" is commonly used to describe any substance or procedure a patient accepts as medicine or therapy, but which has no known mechanism other than a patient\'s belief in its value \[[@B12]\]. The aim of any placebo is to maximise the mimic of the active intervention (and its benefits) whilst minimising the risks associated with it \[[@B13],[@B14]\]. A range of interventions, from dummy pills to surgical techniques, have been used as placebos \[[@B14]\]. Within a surgical context, however, no surgical placebo can be completely without the possibility of harm. This leads to particularly complex issues when trying to design a surgical placebo-controlled trial. In this paper we report on a study (the KORAL study) conducted to assess the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage (washing out of the knee space under general anaesthetic) for the management of people with osteoarthritis of the knee in the UK. Whilst the primary focus was on arthroscopic lavage (and was written up in a separate monograph \[[@B15]\]), the study highlighted a range of wider issues relevant to the design and conduct of surgical placebo-controlled trials in general, and it is those that we focus on in this paper. The KORAL study --------------- Our group was commissioned by the UK National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme to design and conduct a placebo-controlled trial to assess the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. The purpose of the trial was to confirm or refute the findings of an earlier study conducted in the US by Moseley and colleagues \[[@B16]\]. In the Moseley trial, patients had been randomised to arthroscopic lavage, arthroscopic debridement or placebo procedure and had found that whilst all groups improved, no significant difference was observed at follow-up between the placebo group and either \'active\' surgery group; the conclusion being that observed benefit was due to the placebo effect. Whilst the Moseley trial had been conducted with methodological rigour, it had been conducted in a single US centre by a single surgeon and the generalisability of the results had been questioned by a number of authors \[[@B17]-[@B19]\]. Given that it was unclear whether an acceptable placebo could be designed and delivered in a feasible manner, the project first explored in an in-depth manner issues around the design, acceptability and feasibility of a surgical placebo for this trial (it is this in-depth study that is presented in this paper). This study, which was known as KORAL (Knee Osteoarthritis: Role of Arthroscopic Lavage) had the following research questions (RQs) that were addressed in a staged way in a series of sub-studies: RQ1. Is there a need for a further placebo-controlled trial of arthroscopic lavage for osteoarthritis of the knee? If yes, RQ2. Can an appropriate surgical and anaesthetic placebo be designed for such a trial? If yes, RQ3. Would key stakeholders find the proposed placebo-controlled trial design acceptable? If yes, RQ4. Would conducting such a multi-centre surgical placebo-controlled trial be feasible in the UK? Methods ======= The research was conducted in two main phases. Firstly, an in-depth qualitative and quantitative exploration of possible placebo designs and their acceptability to key stakeholder groups (addressing RQs1-3) was conducted. Secondly a formal pilot of the proposed trial design to test feasibility (RQ4) was undertaken. Multi-centre Research Ethics Committee (MREC) approval was received separately for the two phases. Full details of the methods used in this study were given in the clinical monograph \[[@B15]\], however, brief details are provided below. Exploration of possible placebo designs and the acceptability of a placebo-controlled trial to key stakeholder groups --------------------------------------------------------------------------------------------------------------------- In the first phase, we particularly addressed: a) the perceived scientific merit of further evaluation of arthroscopic lavage (including by placebo-controlled trial); b) the choice of the placebo procedure, both surgical and anaesthetic; and c) the likely acceptability of different placebo-controlled trial designs to key stakeholder groups including surgeons, anaesthetists, potential participants and chairs of ethics committees. We conducted focus groups with, and postal surveys of, surgeons and anaesthetists; focus groups and interviews with people with osteoarthritis (potential trial participants); and interviews with Chairs of MRECs (Table [1](#T1){ref-type="table"}). Focus group discussions were informed by a presentation from the project team on background rates of arthroscopic lavage, details of the Moseley trial (including the design, results and perceived criticisms) and the project brief. Focus group discussions and interviews were audio-tape recorded and transcribed. Transcripts were analysed thematically using a modified Framework approach \[[@B20]\]. Within the focus groups and interviews we used the term \"placebo surgery\" (rather than possible alternatives such as \"sham\" or \"dummy\" surgery) as early on in the research we found that the choice of word could lead to different perceptions, despite the rationale behind their use being the same \[[@B15]\]. The term \"placebo surgery\" was adopted in an attempt to describe as accurately as possible the intention behind the procedure ie, to maximise the mimic, whilst minimising the risk. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Details of those who contributed to the focus groups, interviews and surveys ::: Study component Number who participated ----------------------------------------------------------------------------------------------- ------------------------- *Focus groups with health professionals:* • two surgeon focus groups at the 2005 British Orthopaedic Association meeting 16 surgeons • one regional surgeon focus group 25 surgeons • plenary discussion at the 2005 British Society of Orthopaedic Anaesthetists meeting 130 anaesthetists • detailed focus group at the 2005 British Society of Orthopaedic Anaesthetists meeting 8 anaesthetists • two regional focus groups with anaesthetists 50 anaesthetists *Focus group and interviews with people with osteoarthritis:* • two focus groups with members of the patient organisation *Arthritis Care* 7 people • telephone interviews with patients on consultant waiting lists from two UK regional centres 15 people *Interviews with Chairs of UK MRECs:* • telephone interviews with MREC Chairs 6 MREC Chairs *Surveys of health professionals:* • postal survey of all members of the British Association of Surgeons of the Knee 382 surgeons • postal survey of all members of the British Society of Orthopaedic Anaesthetists 398 anaesthetists Note: 12 of the 13 UK MRECs which were in existence at the time of the research were invited to take part in the research. (To preserve their independence with regard to any future ethics decisions about KORAL, the MREC that approved this part of the study was excluded from this component) ::: All members of the British Association of Surgeons of the Knee and members of the British Association of Orthopaedic Anaesthetists were surveyed for their opinion. Permission was received from both Societies for only a single mailing to members. Responses to the surveys were summarised using simple descriptive statistics. The final output of this first phase was the template for a preferred trial design. Formal pilot of the proposed trial design to test feasibility ------------------------------------------------------------- The second phase was a formal pilot of the preferred trial design that had been developed in Phase One. The formal pilot was conducted in two centres. Analysis of the pilot data consisted primarily of descriptive statistics including proportion of eligible patients randomised, and reasons for refusing to take part in the trial. Results ======= Need for proposed further evaluation of arthroscopic lavage ----------------------------------------------------------- From the focus groups and interviews, there was broad acceptance across all stakeholder groups of the need to find out more about the effects of arthroscopic lavage. Surgeons expressed uncertainty about the overall effectiveness of lavage. On the one hand some indicated that there was some evidence to suggest that lavage might offer at least short-term pain relief: \"if \... you end up washing the knee out, sometimes the symptoms do improve and make it pseudo-working. We had a lady recently, and she had a defect, and she\'s a lot better since we washed the knee out, that\'s three weeks ago now.\" (Surgeon 1, Group C) However, others commented that they often observed their patients \"all coming back\" with continuing problems after the procedure, thus raising concerns about the longer term and overall effectiveness of the technique. People with osteoarthritis of the knee also expressed the need to find out definitively whether arthroscopic lavage was effective. For example, one mentioned the scientific uncertainty surrounding the effectiveness of arthroscopic lavage, and another highlighted the need for research into the long-term effectiveness of such surgical procedures: \"Well, we have got to find out, you know, it has been going on for years and years and no one has ever found a complete answer so things have got to be tried, you know\... If you want to advance that is what you have to do.\"(Participant 1) \"I certainly think it \[a trial of arthroscopic lavage\] is worthwhile because at the end of the day \...I don\'t think that people should undergo surgery unless it was having some long term benefit to them \... it should only be done when it is going to have a positive effect and a long lasting effect.\" (Participant 2) Although all the groups accepted there was a need to find out more about the effects of arthroscopic lavage, there was variation in opinion about *how*researchers should investigate this and about whether it would be acceptable to investigate the effectiveness of arthroscopic lavage using placebo surgery. This is discussed below. Design of a surgical placebo ---------------------------- Discussion within the surgeons\' focus groups concentrated mainly on the ways in which a placebo could mimic arthroscopic lavage (the active surgery), whilst ensuring that any risks of harm were minimised. The consensus emerged fairly readily that three superficial skin incisions were needed, that these should only pierce the epidermis, and that any penetration of the knee capsule should be avoided. \"No, you don\'t have to do the dermis \... just enough to make it bleed\" (Surgeon 8, Group B) Ensuring that penetration of the knee capsule did not occur was promoted for two primary reasons: a) that it would reduce the risk of any infection and b) it would ensure that no form of lavage was inadvertently performed: \"If you put the scope in you introduce fluid therefore technically it becomes a lavage even if it\'s a tiny amount, doesn\'t it?\" \[several yes\'s round the table\] (Surgeon 7, Group C) Within the anaesthetists\' focus groups, the question about the most appropriate form of anaesthesia to incorporate within a placebo procedure was more contentious. Some anaesthetists objected to the ethics of conducting any research that involved a placebo (see acceptability section below), and did not feel comfortable discussing the design of an anaesthetic for such a procedure. However, a consensus eventually emerged that the patients in both trial groups should receive the same anaesthetic, and that this should be the regimen the individual anaesthetists who participated in the trial would customarily use for a simple arthroscopic procedure (i.e. a general anaesthetic). They believed that this would not only maximise the mimic of the active surgery but would also minimise the risks to participants. As they had more experience with general anaesthesia in these cases, they believed it would be safer than a technique using a combination of sedatives and analgesics as used in the Moseley trial (on the premise that it was less risky for their patients), but was felt to be less familiar and therefore less safe by our respondents: \"Hasn\'t the starting point got to be, you should do the same \[as for the active surgery group\] unless there is a really good reason not to? And if the really good reason is all about risk then you have to show that their \[the sedation procedure used by the Moseley trial, on the grounds that it was of lower risk to patients\] intervention has less risk than the standard full anaesthetic. I am convinced that that is not the case. So therefore you should do the standard straightforward general anaesthetic\" (Anaesthetist 5, Group B) \"Statistically, \[the sedation procedure used by the Moseley trial\], is more dangerous than a general anaesthetic \[on the grounds that it was of lower risk to patients\]\" (Anaesthetist 6, Group A) Assuming that general anaesthesia was to be adopted, the anaesthetists within the focus groups agreed that inclusion should be restricted to low risk patients, as defined by those who were American Society of Anesthesiologists (ASA) grades 1 or 2 \[[@B21],[@B22]\] - that is \"normal healthy patients\" or \"patients with mild systemic disease\" who had no other contraindication to anaesthesia. Acceptability of a surgical placebo-controlled trial ---------------------------------------------------- ### Views expressed by health professionals Although none of the surgeons who took part in the focus groups disputed the need for further investigation of the effectiveness or otherwise of arthroscopic lavage, there was extensive debate within the groups about whether a placebo-controlled trial was necessary to generate new knowledge, and whether it was acceptable. For example: \"It would be more ethically correct to compare doing nothing to a lavage first and then look at the results and see\"\... You don\'t need to know the benefits of the placebo, it\'s irrelevant. When you make a clinical decision, you have to decide whether it\'s lavage or not. And so all you need to know is benefit from lavage and benefit from not doing anything and if the benefit from the lavage is marginal, then you don\'t do lavage and that\'s all that you need to do\...\"(Surgeon 3, Group C) \"What you need to do first is a decent study to actually look at conservative versus operative \[management\] and then once you\'ve done that decent study, can you consider putting people at risk of placebo operations\" (Surgeon 10, Group C) Other surgeons disagreed, however, arguing that there was a methodological need for a placebo surgical trial because: a) a placebo component is needed to detect a small difference between the groups; and b) that a placebo is needed to attempt to disentangle what (if any) aspect of the arthroscopic lavage procedure is having a positive effect. Overall, the health professionals tended to be split between: a) those who were strongly opposed to the inclusion of a placebo surgical arm on the grounds that it could lead to potential harm among individuals who could expect no personal benefit; and b) those who were in favour as that they believed the small risks that relatively few people in a placebo surgery trial arm would be exposed to were justified (because they were outweighed by the potential benefit to future patients and broader society of helping to ensure either that a demonstrably effective surgical procedure was used or that a demonstrably ineffective procedure was stopped). Those opposed to the inclusion of a placebo surgical arm expressed strong personal views on their perceived ethics of such an approach: \"As an anaesthetist I would not anaesthetise someone for sham surgery. I just couldn\'t! I just think it\'s immoral and unethical \... I mean it\'s as simple as that, you wouldn\'t do it\". (Anaesthetist 1, Group A) \"The number who will do this willingly will be very, very small, most of my colleagues would say - no you\'re joking\"\...(Anaesthetist 6, Group A) On the other hand, those in favour pointed to the benefit to future patients and the desire to let patients rather than clinicians decide what was best for them: \"If the patient is prepared to accept the risk in order to have the operation and they are prepared to enter the trial on the understanding that they might not have an operation, are we all being a bit precious \[ie, overly protective\]?\" (Anaesthetist 4, Group B) \"34,000 people \... per year are having a procedure which has no proof to it. So you\'re already doing the ladies with the \[weak\] hearts, putting the tourniquets up, giving them the drugs for absolutely no proven evidence\... at the moment if there are 34,000 of these procedures being done and we are exposing that number of patients to all the risks of anaesthesia then we need to know the answer\" (Anaesthetist 5, Group A) Some individuals who were personally in favour of using a placebo were concerned that professional regulators would not be (with consequent implications for their potential participation): \"Interesting though \... I accept \[it\] is completely logical that the needs of the many outweigh the needs of the few but the GMC \[General Medical Council\] doesn\'t see that do they? The GMC make it very specific in their guidance to us that it is the needs of the individual which is your primary concern\" (Anaesthetist 4, Group B) One hundred and seventy three (43%) members of the British Association of Surgeons of the Knee responded to the survey as did 136 (34%) members of the British Society of Orthopaedic Anaesthetists (Table [2](#T2){ref-type="table"}). Findings from the surveys supported the insights observed in the focus groups. The surveys showed that a sizeable percentage of health professionals (51% of surgeons and 40% of anaesthetists) were supportive of a trial with a placebo arm being mounted. The survey also showed that 43% of surgeons would personally consider taking part in such a trial as would 47% of anaesthetists. It was interesting to note that although some anaesthetists were personally not in favour of a placebo arm being involved they would, however, consider taking part if their surgeon colleagues wished to take part. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Attitudes of surgeons and anaesthetists to a placebo controlled trial ::: Surgeons Anaesthetists --------------------------------------------------------------------------------------------- --------------- --------------- Number of questionnaires despatched 382 398 Number (%) of questionnaire returned 173 (45%) 136 (34%) ***Potential trial of arthroscopic lavage vs placebo surgery vs conservative management:*** **n/N (%)** **n/N (%)** • Supportive of trial with placebo arm being mounted 85/168 (50.6) 54/135 (40.0) • Would consider taking part in a trial with a placebo arm 71/166 (42.8) 63/134 (47.0) • Would encourage a friend or family member to sign up for a trial with a placebo arm 67/168 (39.9) 48/135 (35.6) ::: As part of the survey we also asked surgeons and anaesthetists for their views on the appropriate randomisation ratio for any potential trial. The majority favoured an allocation ratio of 1:1:1 to arthroscopic lavage, placebo surgery or non-operative management (60% of surgeons, 46% anaesthetists) or had no preference (25% surgeons, 41% anaesthetists), rather than a 2:1:1 ratio (10% surgeons, 10% anaesthetists) or some other ratio (5% surgeons, 3% anaesthetists). ### Views expressed by people with osteoarthritis In their focus groups and interviews, people with osteoarthritis echoed the need to find out more about the effects of arthroscopic lavage, and many of our sample indicated that they would consider taking part in a placebo-controlled trial. Two participants also discussed how, from a research point of view, including a placebo surgical component could be very useful. They drew on the information presented by the interviewers and explained that a placebo arm would help check whether any perceived benefit from arthroscopic lavage was due to a placebo effect. For example: \"\... I would say it is important to have the placebo in it because if there is a sort of mind set that it does help to heal you, I mean it has been proven over the years that placebos do benefit in certain things.\" (Participant 1) \"\... I think the placebo group is a very good idea because it can almost fool somebody into thinking they have had a procedure when they haven\'t and basically prove to some people that you think you are better because you think you have had this procedure but in fact you didn\'t have any treatment done at all.\"(Participant 2) However, a few people in our sample thought involvement in a placebo-controlled trial would not be appropriate for them: \"if I was informed then that I had had the placebo and I realised that I had still got the pain I would be so furious\...so angry\" (Participant 14) Those who were willing to take part openly acknowledged the risks of general anaesthetic and endorsed the need for anaesthetists to select only those at low risk. For example: \"\... there is always, albeit I think it is quite small, risk of complications with anaesthesia \... there can be problems but they are very few and far between and if the right patients are selected then I don\'t think there would be any problems.\" (Participant 2) ### Views expressed by Chairs of Ethics Committees The Chairs of Ethics Committees highlighted a range of issues that should be addressed in any ethics application, eg, justifying the need for the placebo and the general anaesthetic, plans for minimising risks to patients, etc. Whilst they acknowledged that a surgical placebo-controlled trial would not simply be dismissed on principle, they predicted a \"rough journey\" through the ethics process for any such proposal: \"\... I would have to think extremely laterally to envisage that this would get through without a very rough journey on the way \... We have one committee in particular which anything placebo \... is evaluated with a fine tooth comb and there we\'re talking little white tablets\... The prospect of using a surgical approach I think raises the stakes enormously\" (MREC 3) \"\...*I would think that in conclusion it\'s probably the general anaesthesia that will cause ethics committees the most problems because then they will say now is this really too much of a risk to be giving somebody a general anaesthetic for nothing\... I can see everybody say, \'Oh oh no way, not general anaesthetics\'\" (MREC 1)* \" \... I\'d want a very robust justification for tackling the equipoise in this rather risky, in this potentially risky way. I think any self-respecting Committee that is the question they would ask. I would certainly be weighed by what risks our anaesthetic colleagues thought fair. I mean you\'ve got to, you can\'t negate the risk\... If the study is going ahead, there is a risk, you can\'t negate it. I think I\'d want evidence that the risks had been fully considered and minimised\... my experience is \[that\] anaesthetists are a very ethical lot indeed\... and they serve as a very useful counterbalance to the surgeons \...I can see the surgeons are faced with people in awful, intractable pain and they want to do something about it\" (MREC 4) Development of a preferred design to take to pilot study -------------------------------------------------------- The final output of the exploratory phase was to develop a preferred trial design to take forward to a formal pilot. The preferred design was developed from the insights gained from the exploratory work undertaken with surgeons anaesthetists and potential participants. The finalised design was agreed with the funder and was as follows - patients were to be eligible for inclusion if they were: adults aged 18 years or older with radiological evidence of osteoarthritis of the knee who might be considered for arthroscopic lavage; at low risk for general anaesthesia - ASA grades 1 and 2; and able to give informed consent. Following consent, patients would be randomly allocated to: arthroscopic lavage (with or without debridement as deemed clinically necessary); placebo surgery; or non-operative management (fuller details of the three intervention arms are presented in Figure [1](#F1){ref-type="fig"}). No change in treatment (other than in analgesia use) was to be allowed in any of the randomised groups for a period equivalent to three months after randomisation. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Schematic of pilot**. ::: ![](1745-6215-12-50-1) ::: For those randomised to some form of surgery, the type of surgery (whether arthroscopic lavage or placebo) was not to be revealed until the patient had been anaesthetised and was in the operating theatre. After surgery, discussions with patients would follow a pre-agreed approach: \"*you know that I cannot tell you whether you had the active surgery or the placebo, but I can tell you that the procedure went well and we will now need to see how well this helps your knee*\". This approach was to be maintained during follow-up clinic appointments. Feasibility of the proposed placebo-controlled design ----------------------------------------------------- ### Ethics approval Gaining ethics approval for the pilot study was difficult and took nine months. The initial application for the pilot phase was rejected. Two main concerns were raised: a) the potential inclusion of surgeons who would not routinely offer arthroscopic lavage; and b) the potential inclusion of centres where arthroscopic lavage was being phased out and was no longer a routine treatment choice. We appealed against this decision on the counter-arguments that: a) surgeons who would *never*consider arthroscopic lavage would not agree to take part in the trial, so one could assume that all patients recruited from surgeons who agreed to participate in the trial would have a possibility (albeit sometimes low) of having been offered lavage had the trial not been in place; and b) it could have been uncertainty of effectiveness of arthroscopic lavage rather than certainty about the lack of effectiveness that led centres to stop undertaking *routine*arthroscopic lavage. Thus including those centres where surgeons who still wished to find out whether lavage was truly effective was a further justification for the research, rather than an ethical objection to it. The second MREC which heard our appeal approved the pilot, subject to our considerably extending the patient information leaflet (which we duly did). ### Local authorisations Despite ethics committee approval, the pilot subsequently required major discussion and negotiation at each individual centre before local clinical approvals could be obtained. Some of the arguments discussed at the ethics committee were raised again at local level and the fact that ethics approval had been granted did not mean that clinicians would automatically accept that the process was ethical. There were also concerns about who would pay for any placebo procedure and about indemnity arrangements. Despite extensive negotiations full local approval was not achieved for one of the two pilot centres within the four-month timeframe of the pilot study (a number, but not all, of the authorisations were successfully in place). In the centre where the pilot did receive approval, the local authorisation process also led to caveats being placed on the delivery of the trial locally (eg, the restriction that only consultant anaesthetists take part). ### Delivery of the pilot design Eight clinics were held over the course of the pilot phase, drawing patients identified as potentially eligible for the trial by screening referral letters sent by the patients\' General Practitioners (GPs). Forty nine patients were invited to attend. Of the 40 patients who attended, 13 were eligible and nine consented to take part (Figure [2](#F2){ref-type="fig"}). Six were randomised to some form of surgery and three to non-operative management. Two of the six patients randomised to surgery subsequently withdrew from the pilot prior to surgery. Both cited anxieties about the possibility of receiving placebo rather than active surgery among their reasons for withdrawal. One also highlighted concerns about Methicillin-resistant *Staphylococcus Aureus*(MRSA). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Feasibility checklist for surgical placebo controlled trials**. ::: ![](1745-6215-12-50-2) ::: The three patients randomised to non-surgical management were reassessed by the treating clinician on the same day as the recruiting clinic, following randomisation. All three were advised on analgesic use. Two participants were given lifestyle modification advice and exercise information. The use of a walking stick was suggested to one participant but this was declined. Two participants were advised to use an elastic knee brace and one on the use of heat or ice. One surgical session took place which involved one active and one placebo procedure (the two remaining surgical patients were managed outwith the framework of the pilot - see below). The patient allocated to active procedure underwent arthroscopic lavage with three litres of saline (debridement was not required) and the procedure was completed as per protocol. The placebo surgery was also undertaken successfully as per protocol. The surgeon and anaesthetist reported that the practicalities of both active and placebo surgery presented no major problems. Operating theatre staff did, however, express some concern when it was revealed that a patient was to receive placebo surgery (despite the fact that they had previously been fully informed of the nature of the trial). Through the two month follow-up questionnaire, neither patient reported that they thought they had undergone placebo surgery. ### Decision whether to progress to a large-scale trial Towards the planned end of the pilot, the funders reviewed our study findings to decide whether to continue seamlessly into the conduct of a full-scale trial. They concluded that a surgical placebo for arthroscopic lavage could be successfully designed, was generally acceptable to the range of stakeholder groups (although a few held strong views against the use of a surgical placebo under any circumstances), but faced considerable feasibility barriers when trying to conduct the trial in practice. In the light of these findings, the funders decided that the anticipated time, energy and cost required to bring multiple centres on board to recruit sufficient numbers (approximately 800 would be required) to a definitive large-scale trial over a sustained period of time was not justified (especially against a background of a gradual, albeit slow, decline in arthroscopic lavage \[[@B23]\]). As two of the pilot patients were still awaiting their surgery at the time of this decision, and it was as yet unclear if this was to be active or placebo surgery, it was deemed inappropriate to continue their management under pilot conditions and their management was reviewed outside the pilot framework. Discussion ========== Our study illustrated that a surgical placebo for arthroscopic lavage could be designed that was acceptable to a sizeable proportion of people across the range of stakeholder groups (although a few held strong views against the use of a surgical placebo under any circumstances), but conducting such a trial in practice would face considerable feasibility issues. Our study also illustrated well the opposing and often strongly held opinions that are held about placebos in surgery, the ethical issues that underpins this controversy, and the challenges of mounting such a trial that exist even when ethics committee approval has been granted. Issues of ethical and scientific acceptability of a placebo design in surgery ----------------------------------------------------------------------------- There was widespread acceptance in our study that further investigation was required into the effectiveness of arthroscopic lavage. Whether that investigation should or should not include a placebo-controlled design generated much wider discussion. Commentators agree that the ethical principles appropriate to all clinical research must be satisfied as a minimum when considering a placebo-controlled design. These principles are that the study must: a) have scientific merit, b) be acceptable to participants in terms of the risk-to-benefit ratio of participation and c) respect the autonomy of participants by enabling them to determine whether they should participate \[[@B24]\]. In the qualitative components of our study participants raised and discussed these factors for the case of arthroscopic lavage. The scientific merit of the proposed study and the need for informed consent were readily accepted. Whether the proposed study design provided an acceptable balance of risks and potential benefits for participants generated much wider debate. The discussion of an acceptable risk-to-benefit ratio in a placebo-controlled study is not straightforward. As Horng and Miller \[[@B25]\] argue, the risks must be considered in the context of alternative study designs to answer the research question - could an evaluation of arthroscopic lavage be conducted without the use of a placebo control and without compromising scientific rigour? The subjective measurement of the primary outcome in our study (patient reported pain) was recognised to be prone to bias in an open trial design (ie, when people would know which intervention they had been randomised to) \[[@B26]\], and it was considered impossible to maintain an open trial sufficiently long for any placebo effect to have dissipated, and as such the inclusion of a placebo control was deemed to maximise scientific rigour. An additional consideration in the risk-to-benefit ratio for participants is the nature of the proposed placebo - how \"risky\" the proposed placebo is perceived to be. A placebo must be able to mimic the intervention under evaluation, but minimise the risks to those who might take part in the trial. Edwards *et al*suggest that perceptions of acceptability of placebo are likely to vary depending on the nature of the placebo in question \[[@B27]\]. In our study, agreement of the choice of placebo surgical procedure proved easier than the method of anaesthesia. The surgical approach chosen (three small skin incisions) was both a satisfactory mimic and had low intrusiveness and thus required little debate. However, the use of general anaesthesia, while an excellent mimic, was more intrusive and as such generated much greater discussion, and was the factor that caused most discussion with local decision-makers when seeking formal approval to conduct the pilot. It is interesting to note, however, that the content experts (ie, the anaesthetists) contended that the use of a general anaesthetic would be safer (because this is the technique which they used routinely and with which they have the greatest experience) than a supposedly less intrusive alternative, such as a form of analgeso-sedative regimen, with which they were less familiar. The wider literature supports this, suggesting that the success of a procedure is directly related to the number of procedures undertaken by that individual \[[@B28]\]. Further evidence of the controversial nature of the placebo design was the need to go to an appeal before the pilot trial received ethics committee approval, despite evidence of support from a range of surgeons, anaesthetists and potential participants. In response to the ethical debate raised by the Moseley trial \[[@B16]\], the American Medical Association produced a set of principles under which a placebo-controlled trial in surgery would be considered ethical \[[@B29]\]. These principles outlined: that surgical \"placebo\" controls should be used only when no other trial design will yield the requisite data; that particular attention must be paid to the informed consent process when enrolling participants in such trials; that the use of surgical \"placebo\" controls may be justified when an existing, accepted surgical procedure is being tested for efficacy (but that it was not justified when testing the effectiveness of an innovative surgical technique that represents only a minor modification of an existing, accepted surgical procedure); and that when a new surgical procedure is developed with the prospect of treating a condition for which no known surgical therapy exists, using surgical \"placebo\" controls may be justified, but must be evaluated in light of whether the current standard of care includes a non-surgical treatment and the benefits, risks and side-effects of that treatment. Our experience suggests that these principles remain relevant; but, for a placebo-controlled trial to be conducted successfully, it is clear that it must not only be an *ethically*and *scientifically*acceptable course of action but must also be a *feasible*course of action. Issues around feasibility of a placebo-controlled trial in surgery ------------------------------------------------------------------ Randomised controlled trials in surgery are well-known to be difficult to design and often suffer from recruitment problems \[[@B30],[@B31]\] and adding a placebo component to the design adds to this complexity. Our study also faced a number of practical hurdles before it commenced recruitment and it proved impossible to surmount all of these in one of the two pilot centres within the four-month timeframe of the pilot. We found that: a) stakeholders in each trial centre needed to be fully briefed and any ethical and practical concerns resolved prior to trial commencement; b) that arrangements needed to be put in place to cover the costs of the placebo before the trial could go ahead; and that c) appropriate indemnity arrangements needed to have been instituted. The crucial importance of local stakeholders and gatekeepers has been outlined by a number of authors and the need to develop explicit recruitment and communication strategies identified \[[@B32],[@B33]\]. Our study confirmed that recruitment to a surgical placebo-controlled trial is achievable - nine of 13 eligible patients approached agreed to join the trial - and the study also demonstrated that blinding of participants receiving surgery was successfully maintained. However, two of the six allocated to surgery subsequently withdrew before surgery citing concerns about the possibility of receiving placebo surgery and risks associated with hospitalisation as reasons. This raises questions about the potential influence of a placebo arm on retention rates in surgical trials. This range of feasibility issues is likely to be faced by anyone considering a placebo-controlled surgical trial, and a checklist of appropriate issues that trialists should consider is presented in Figure [2](#F2){ref-type="fig"}. Strengths and weaknesses of the study ------------------------------------- Surgical placebos are controversial and this is one of the few studies to have explored empirically the attitudes and perceptions of stakeholders on this important issue. In addition it sought to reflect the perspectives of a wide range of stakeholders including surgeons, anaesthetists, potential participants and ethics committee chairs. It also ensured UK-wide coverage of opinions through the professional surveys (although response rates were, like those for other surveys among health professionals, quite low), and this provides reassurance that the results are reflective of the current range of opinion on the issue of surgical placebos in general. Similarly the involvement of multiple centres in the research was a strength, as previous studies of placebos have often been conducted in a single centre setting. This was one of the key criticisms of the Moseley trial as it only involved a single surgeon in a single centre. We recognise, however, that our study concentrated on a relatively minor surgical procedure and that the results may have been different if we had been trying to design a placebo for a more invasive procedure which would have required a larger surgical incision or more complex anaesthetic or a higher risk of major complications. We anticipate that in those circumstances consensus on both the design and acceptability of the placebo would have been harder to achieve and that recruitment to the study may have been lower. In addition, the number of patients recruited to the pilot study was small; limiting the conclusions we can draw from their responses. However, we are confident that the range of issues which require to be considered when planning a placebo-controlled trial in surgery were encountered in this study. Conclusions =========== Our study showed in principle, a placebo-controlled trial of arthroscopic lavage could be conducted in the UK, albeit with difficulty. It highlighted well that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. In the light of our experience, the place of placebo-controlled surgical trials seems likely to be very limited. Our study suggests that the following conditions would need to be satisfied: a\) alternative designs would provide inferior (and potentially biased) results, particularly where the primary outcome is of a subjective nature and blinding cannot be sustained beyond the time of any placebo effect; b\) a placebo surgical procedure and type of anaesthesia can be devised which adequately mimic the active intervention with a level of intrusiveness and risk that is acceptable to the surgeons and anaesthetists who would take part in the trial, and to ethics committees, research governance assessors and potential participants; c\) appropriate practical arrangements can be instituted in local centres to ensure that the delivery of such a design would be feasible; d\) sufficient numbers of potential participants (after assessment of clear descriptions and careful explanations in patient information leaflets of the advantages and disadvantages of taking part) judge for *themselves*that the risk-to-benefit ratio of participation is acceptable to them; and e\) levels of compliance with the allocation are sufficiently high to sustain scientific rigour. Those who would rule out the use of surgical placebos in these circumstances come up against two difficult questions: 1) What about the apparent acceptability of the methodology to potential participants? and 2) What do we tell people with this painful, chronic and progressive condition why a procedure that is unproven is being offered or why a potentially effective intervention has been discarded? Abbreviations ============= ASA: American Society of Anesthesiologists; GMC: General Medical Council; GP: General Practitioner; HTA: Health Technology Assessment; KORAL: Knee Osteoarthritis: Role of Arthroscopic Lavage; MREC: Multi-centre Research Ethics Committee; MRSA: Methicillin-resistant *Staphylococcus Aureus*; NCCHTA: National Coordinating Centre for Health Technology Assessment; NIHR: National Institute for Health Research; RQ: Research Question; UK: United Kingdom; US: United States. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MC was the principal grant applicant, led on the development of the study protocol, led the writing of the manuscript, was responsible for the overall conduct of the study and is guarantor of the study. VE contributed to the development of the study design, led on the design of the qualitative component of the study, and contributed to the writing of the manuscript. BC contributed to the development of the study design, led on all anaesthetic and other clinical aspects of the study and contributed to the writing of the manuscript. ZS contributed to the development of the study design, was responsible for the day-to-day management of the qualitative component of the study, and contributed to the writing of the manuscript. AS and contributed to the development of the study design, led on all surgical aspects of the study and contributed to the writing of the manuscript. AMcD contributed to the design of the study materials, to the organisation of study authorisations and assisted in the preparation of the manuscript. JN contributed to the design and conduct of the study and assisted in the preparation of the manuscript. RC contributed to the design and conduct of the study, provided expert guidance on ethical arguments and the place of placebos within these frameworks and contributed to the writing of the manuscript. SB contributed to the design and conduct of the pilot at a local level and contributed to the preparation of the manuscript. The KORAL Study Group - Seonaidh Cotton, Angela Donaldson, Ray Fitzpatrick, Adrian Grant, Alastair Gray, James Hutchison, Marie Johnston, David Murray, Craig Ramsay, David Rowley, Luke Vale and Carlos Wigderowitz - were all members of the KORAL Project Management Group, advising on the design and conduct of the study, and commenting on drafts of the manuscript. All authors have seen and approved the final version of the manuscript. Acknowledgements ================ The authors wish to thank Nelda Wray and Carol Ashton for their invaluable insights into the design and co-ordination of the Moseley trial and for their guidance and contribution to the design of this study. The authors also wish to thank Paul Dieppe for his excellent insights into the feasibility of placebo-controlled studies and his advice in the field of osteoarthritis. The authors also wish to thank the following individuals for their assistance in the co-ordination and practical outworking of the study: Gladys McPherson for database and programming support; Alastair Chambers, Julie Downie, Nicola Maffulli, Ian Dos Remedios, Iain Smith, Lynne Swan and Gayle Walley for their contributions to the pilot phase of the study and Kathleen McIntosh for secretarial support. The authors would also like to thank all those who took part in the various aspects of this project - the focus groups, interviews, surveys and pilot study - for their time and detailed consideration of the issues. The authors would also like to thank the members of both MRECs who were involved in the assessment of this study and for their thoughtful consideration of the ethical issues raised by this project. The authors are also indebted to the staff of the National Coordinating Centre for Health Technology Assessment (NCCHTA) for their invaluable advice on the practical coordination of this study and especially Jon Nicholl for his expert guidance through the decision-making stages of the project. The study was funded by the NIHR HTA Programme (03/48/01). The funder had no role in the design, conduct or analysis of the study. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorates. The views expressed are those of the authors alone. \* The KORAL study group are: Seonaidh Cotton, Angela Donaldson, Ray Fitzpatrick, Adrian Grant, Alastair Gray, James Hutchison, Marie Johnston, David Murray, Craig Ramsay, David Rowley, Luke Vale and Carlos Wigderowitz.

PubMed Central

2024-06-05T04:04:18.955808

2011-2-21

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052178/", "journal": "Trials. 2011 Feb 21; 12:50", "authors": [ { "first": "MK", "last": "Campbell" }, { "first": "VA", "last": "Entwistle" }, { "first": "BH", "last": "Cuthbertson" }, { "first": "ZC", "last": "Skea" }, { "first": "AG", "last": "Sutherland" }, { "first": "AM", "last": "McDonald" }, { "first": "JD", "last": "Norrie" }, { "first": "RV", "last": "Carlson" }, { "first": "S", "last": "Bridgman" } ] }

PMC3052179

Background ========== Obesity is one of the main determinants of avoidable disease burden \[[@B1]-[@B3]\]. *In lieu*of affordable, non-invasive, effective obesity treatment over the long-term, and because the adverse effects of obesity on health status are not fully reversible, a stronger focus on the prevention of obesity has been advocated \[[@B4]\]. Since overweight status and obesity in adulthood are predicated on childhood and adolescent weight, obesity prevention should start early in life. One important target group is the child of school-age i.e. the age-group around adolescence \[[@B5]\]. Although genetic factors may influence the susceptibility of individuals to weight gain \[[@B6]\], there is a consensus that changes in lifestyle activities have driven the current obesity epidemic \[[@B7]\]. Therefore, obesity prevention among school children should target dietary habits as well as physical activity and sedentary behaviour \[[@B4]\]. The school environment is regarded as a good setting for the promotion of health interventions among children because no other institution has as much contact time with the target population \[[@B8]\]. Schools provide an environment where almost all children can be reached repeatedly and continuously, and where health education can be combined with health promoting environmental changes \[[@B5]\]. The development of personal skills and coping practices involves the promotion of healthier behaviour, particularly with respect to nutrition and physical activity, and this can be achieved by health education. Health education attempts to provide information regarding healthy diets and physical activity by means of active participation of the target population and, in soliciting a response, to promote health as the process of enabling people to increase control over, and to improve, their health \[[@B9]\]. Officially, teachers are preoccupied with academic activities and an option may be to involve young students from medical and health science departments of the local university who, as part of their new curriculum, receive health education oriented towards school-based interventions. Although some school-based interventions have had positive effects on overweight and/or obesity \[[@B10]-[@B12]\] most, particularly those involving large cohorts \[[@B13]-[@B15]\], have not. The effects of a long-term school-based intervention on improving diet and increasing physical activity and reducing obesity in the north-west Mediterranean area are, as-yet, unknown. Our hypothesis is that a regular systematic educational intervention in primary school improves lifestyle choices and reduces obesity. As such, the aims of the study are: 1) To evaluate the effects of a 3-year school-based program of lifestyle improvement, including diet and physical activity, on the prevalence of obesity; 2) To design a health promotion program for implementation by university students acting as \"health promoting agents\" (HPA) in primary schools. Methods/Design ============== University program ------------------ The training focuses on promoting a healthy lifestyle via activities designed to reduce obesity, and to prepare the HPA to implement these educational interventions in schools. The intervention approach combines constructs from education- and nutrition-based evidence. Two courses are proposed: Course \#1: Methodology for the promotion of health in schools Description of the course Bases of health education and health behaviour Theory and program planning: A study of determinants of health behaviour, factors influencing health behaviour, health behaviour theories and application of methodology are examined. Health education curriculum and instruction: Research methods in health education; principles of evidence-based nutrition. 12 lectures of 1 h duration each, delivered over 15 weeks per academic year. Eight topics in nutrition are chosen for scientific evidence to improve consumption of some foods. Increased physical activity and healthy habits such as teeth-brushing and hand-washing are highlighted. The objectives are: 1\. Healthy lifestyle. Taste (knowledge of previously-unknown food items) 2\. Healthy drinks 3\. Vegetables and legumes 4\. Candies and pastry *vs*. nuts 5\. Healthy habits: timetable (home meals preferably) and physical activity 6\. Fruits 7\. Dairy products 8\. Fish Course \#2. Interdisciplinary implementation of health education in schools This course provides a careful examination of strategies of design, implementation, and health program evaluations, including training and standardisation of each activity as well as the performance of these activities in schools. In the activity training, the primary school teachers are included in the jury to assess the performance of the HPA in the primary schools. 4 lectures of 1 h duration each; in 12 h for training and standardisation and 12 activities (1 h/activity/classroom) over 15 weeks per academic year Schools ------- The school-based lifestyle modification program is designed as an interdisciplinary health promotion program performed by HPA. All strategies are focused on children aged between 7 and 8 years. The program targets the whole school community including parents, pupils, staff and teachers within the school environment. The schools for the program needed to be representative of the child population. We offered the program to all schools whether public (funded by the government and termed \"charter\" schools) or private. To maintain independence between intervention and control schools, we selected schools from Reus (a town with about 100,000 citizens) to represent the intervention group, with Cambrils, Salou and Vilaseca (3 towns on the outskirts of Reus with about 70,000 citizens in total) to represent the control group. There are very good communications between schools within each town and, hence, to avoid cross influence between control schools that were masked with respect to intervention, the towns themselves were the units for randomisation. The coordinating Centre developed a randomization scheme in which the schools in Reus (designated as group A) and the schools in the three others towns of Cambrils, Salou and Vilaseca (designated as group B) had similar pupil populations. Randomisation defined A group as the intervention and B as the control group. In our area of Spain, each classroom contains approximately 25 children (at most 27 children and, occasionally, 20-22 children). When the numbers of children exceed the state-recommended level, a new classroom at the same education level is opened in the school. Thus, there could be 2 or more classrooms for any specific level; some schools may even have 3 classrooms per level with 25-27 children per classroom. All classes are co-educational Participating intervention institutions consist of 24 schools involving 36 classrooms (97% public or state funded \"charter\" schools and 3% private) involving at least 700 pupils in Reus. Participating control institutions consist of 14 schools involving 39 classrooms (96% public or state funded \"charter\" and 4% private) involving at least 700 pupils in the 3 surrounding towns of Cambrils, Salou and Vilaseca. The ethnic origin of control and intervention pupils are: 83.2% of Western European descent (mainly from Catalunya) and 16.8% are non- European; 7.8% from Latin America, 5% of North-African Arab descent, 3% recent immigrants from Eastern Europe (mainly Rumanian) and from other countries from the Asian Far East (such as China). For a school to be included in the study, at least 50% of the children in the classrooms needed to have volunteered to participate. In the intervention group, all children of the selected classroom are exposed to the intervention. For logistics reasons, the first scholastic group was enrolled in 2006 and followed-up for 3 years (2006-2009), and a second scholastic group was enrolled in 2007 and also followed-up for 3 years. Thus the final measures are performed in the year 2010. The data are collected on all the children, but only the data from individuals (and their parents) who provided informed consent are included in the final analyses. Name, gender, date and place of birth are recorded at the start of the program, while weight, height, body mass index (BMI) and waist circumference variables (identified set of anthropometric measures) are recorded in each of the 3 years of the study. The measurements were performed in May of the years 2006, 2007, 2008, 2009, and 2010. Body weight was measured to the nearest 0.05 kg using a standard beam balance (Tanita TBF-300 Body Composition Analyzer, Brooklyn NY, USA). The set of anthropometric measurements was performed three times each academic year. The mean values were used in all subsequent statistical analyses. To assess intra-observer variability, the anthropometric measurements were repeated in 20 children (10 boys and 10 girls). To assess inter-observer variability, all 5 observers conducted the 5 anthropometric measurements in 10 children. The standardisation of observers was performed in each year of the study \[[@B16]\]. If the child is lost to follow-up (the child is relocated to a different school, or the parents move to a different area) we are able to contact the child/parents via the name and date of birth; data that are held in the records of the local education authority. If the child moves to a school that is participating in the study, he/she is identified and followed-up within the new school. If, instead, the children move to another city outside the study area, they are lost to the study and are not replaced. We anticipate a loss of about 20% of pupils which, by chance, would be similar in intervention and control schools. The assumption would be that all losses are, also, by chance and the statistical methods used are robust enough to accommodate for randomly-produced missing values. Questionnaires regarding eating habits (Krece-Plus) developed by Serra-Majem et al \[[@B17]\] and physical activity as well as the level of parental education and their habits \[[@B18]\] are filled-in by the parents at the start and conclusion of the study. Intervention program -------------------- The intervention program consisted of three components: 1\. Classroom practice by HPA to highlight healthy lifestyle habits 2\. Teaching practice by HPA using books designed to include the nutritional objectives 3\. Parental activities included with their children In each of 12 activities (1 h/activity), the classroom practice consisted of three components: 1\. Experimental development of activities regarding each healthy lifestyle habit 2\. Assessment of activity performed in classroom 3\. An activity developed for use at home Approval -------- This study was approved by the Clinical Research Ethical Committee of the Hospital Universitari Sant Joan of Reus, Universitat Rovira i Virgili (Catalan ethical committee registry \#20; ref: 08-07-24/07aclproj1). The protocol conformed to the Helsinki Declaration and Good Clinical Practice guides of the International Conference of Harmonization (ICH GCP). This trial is registered with International Standard Randomised Controlled Trial Register, number ISRCTN29247645. Statistical Analyses -------------------- We estimated that with a sample of 700 pupils per group, the study would have 83.5% power to detect a difference of 5 percentage points between the intervention and control schools (9%-14%), with respect to the primary outcome (prevalence of obesity), setting the bilateral level of statistical significance at 5%. Descriptive data are presented as means ±SD (95%CI) or percentages. Generalised linear mixed models were used to analyse differences between the intervention and control pupils with respect to the primary outcome. Measurements were conducted at baseline when the pupils are 2^nd^-3^rd^graders (6 or 7 year olds) and at the end of the study when they are 4^th^-5^th^graders (9 or 10 year olds). Primary outcomes include obesity (BMI ≥95^th^percentile) and overweight (BMI ≥85^th^percentile) based on the 1988 BMI tables of Hernandez \[[@B19]\]. We analysed obesity and overweight and a measure of thinness according to the Cole criteria \[[@B20],[@B21]\] as well as other measures of adiposity such as BMI z score and waist circumference. The numbers of subjects having a particular dietary habit are expressed as percentages of the total number of individuals being evaluated. Discussion ========== Developing personal skills and coping practices involving the promotion of healthier behaviours or habits can be induced by health education, particularly with respect to nutrition and physical activity. Nutrition and health education programs attempt to inculcate nutritional values or healthy diets by means of active participation of the target population, often involving person-to-person interactions. Although genetic factors may influence the susceptibility of individuals to weight gain \[[@B6]\], there is growing awareness that recent changes in lifestyle habits underlie the current obesity epidemic \[[@B7]\]. We chose BMI as the measure of obesity and the changes in BMI as the effectiveness of the education program. Although waist circumference (WC) or skin-fold thickness, particularly tricipital, or BMI z score can be used as the measure of obesity, BMI values are acceptable. We proposed 3 evaluation methods based on the tables of Hernández et al and Cole et al \[[@B18],[@B19]\] and the EnKid study of 2003 \[[@B22]\] because each one has advantages and inconveniences. Hernandez is the oldest, and the values of BMI are the lowest corresponding to data before the increase in prevalence of overweight and obesity. The Enkid study contains BMI values from 1998-2000, which are ten years more recent than that of Hernández \[[@B18]\], and describe the increase in BMI in a youth population. Obesity is defined as BMI ≥95^th^percentile and overweight by BMI ≥85^th^percentile in order to compare the results of United States guidelines \[[@B23]\]. The tables from Cole et al \[[@B19],[@B20]\] enable comparisons to be made with European studies. We standardised intra- and inter-observer variation to assure quality in the anthropometric measurements. The results expected are the reduction of obesity prevalence based on improving lifestyle habits. Wang et al \[[@B24]\] had proposed that 1% increase/year in childhood obesity in Mediterranean Europe would induce an estimated 11.5% obesity and 30.2% overweight prevalence by the year 2010 and, as such, increase in prevalence of obesity and overweight will have an important health effect. The lifestyle interventions in the program implemented by the university students being trained as HPA include experimental activities using natural food in the habitual diet, and increasing physical activity in the schools. Multi-component foods, physical education, class curricula, behavioural knowledge and skills, communications and social marketing, and the acceptability of healthy behaviour have been proposed as means of reducing BMI. However, the efficacy observed has been inconsistent. Evidence for effectiveness on anthropometrical obesity-related measures is lacking \[[@B25]\]. The challenge is to identify and to develop a cohesive hypothesis which combines educational and health promotion, to examine the effects of the intervention with valid and reliable measurements of the outcomes. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= MG participated in the conception and design of the study and its final approval, drafting and revising the manuscript. RA participated in designing the study, drafting and revising the manuscript. DM participated in designing the biostatistical methods of the study, drafting and revising the manuscript. RS participated in designing the study, drafting and revising the manuscript. Acknowledgements ================ This research project has been supported by Reddis Private Foundation (Spain) \[*Fundació Privada Reddis\]*; the Municipality of Reus, Spain *\[Ajuntament de Reus\]*, the Ministry of Health of the Autonomous Government of Catalunya, Spain *\[Conselleria de Salut de Generalitat de Catalunya\]*, Central Market of Reus, Spain *\[Mercat Central de Reus\]*, Protected Designation of Origin Siurana, Spain *\[DOP Siurana\]*, La Morella Nuts, S.A. Spain; Nutrition and Health Technology Centre CT09-1-0019, Spain *\[Centre Tecnològic de Nutrició i Salut\]*. We express our appreciation to the university medical and health science students of the *Facultat de Medicina i Ciències de la Salut, Universitat Rovira I Virgili*(Reus, Spain) as well as the staff and parents of the pupils of the primary schools of Reus, Cambrils, Salou and Vilaseca for their enthusiastic support in this study

PubMed Central

2024-06-05T04:04:18.960547

2011-2-27

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052179/", "journal": "Trials. 2011 Feb 27; 12:54", "authors": [ { "first": "Montse", "last": "Giralt" }, { "first": "Rosa", "last": "Albaladejo" }, { "first": "Lucia", "last": "Tarro" }, { "first": "David", "last": "Moriña" }, { "first": "Victoria", "last": "Arija" }, { "first": "Rosa", "last": "Solà" } ] }

PMC3052180

1. Public Health and Economic Costs Associated with *Salmonella* ================================================================ *Salmonella*is an important foodborne pathogen world-wide. A recent study estimated that approx. 93.8 (95% Confidence Interval: 61.8-163.6) million human cases of gastroenteritis and 155 000 (95% Confidence Interval: 39 000 - 303 000) deaths occur due to *Salmonella*infection around the world each year \[[@B1]\]. In the USA alone, *Salmonella*causes an estimated 1.4 million human cases, 15 000 hospitalizations and more than 400 deaths annually \[[@B2],[@B3]\]. However, only a fraction of cases is reported, and in the USA, only an estimated 1-5% of cases are laboratory confirmed and reported to the Centers for Disease Control and Prevention (CDC) \[[@B4]\]. In 2006, the national case rate in the USA equaled 13.6 reported cases per 100 000 population per year \[[@B4]\]. Rates varied considerably by geographic region, with estimates particularly high in the Mid-Atlantic and New England States. This heterogeneity is likely in part due to differences in reporting. Differences in salmonellosis case rates between geographically and socio-economically similar USA states have been documented, with rates differing by as much as 200% between neighboring states \[[@B4]\]. Similarly, of the 168 929 human cases reported in the European Union (EU) during 2005, 31% stemmed from Germany even though less than 20% of the EU\'s population resides in Germany, again suggesting reporting differences \[[@B5],[@B6]\]. In 1999, non-typhoidal *Salmonella*infections in the USA were estimated to contribute 10% of foodborne human illnesses, 26% of hospitalizations, and 31% of deaths attributable to infections by known foodborne pathogens, thereby ranking first among all bacterial foodborne pathogens in hospitalizations and deaths and second after *Campylobacter*in the number of illnesses \[[@B3]\]. In 2009, *Salmonella*was the most commonly reported bacteriological agent of human foodborne disease in the USA, causing approx. 44% of confirmed foodborne bacterial infections \[[@B7]\]. More than 20% of human clinical *Salmonella*isolates in the USA are obtained from children under the age of 5 years, emphasizing the great importance of this age group \[[@B8],[@B9]\]. Approx. 1% of *Salmonella*cases are thought to require hospitalization \[[@B10]\]. However, due to the high prevalence of *Salmonella*infections, the Economic Research Service of the United States Department of Agriculture (USDA) \[[@B11]\] estimated the annual cost inflicted on the USA economy to equal approx. 2.5 billion US dollar, thereby clearly exceeding the annual economic cost attributable to human infections by *Escherichia coli*(\$460 million) or *Listeria monocytogenes*(\$2 billion) \[[@B12]\]. 2. *Salmonella*Epidemiology and Transmission Dynamics ===================================================== *Salmonella*serotypes can be divided into host restricted, host specific, and generalists serotypes, with important implications for epidemiology and public health \[[@B13]\]. Host specific serotypes, for instance serotypes Paratyphi A, Gallinarum biovars Gallinarum and Pullorum, or Typhi only cause disease in one host species \[[@B13],[@B14]\]. In contrast, host restricted serotypes are predominantly associated with one host species, but can cause disease in other species as well \[[@B13]\]. *Salmonella*Dublin, for example, is adapted to cattle but infections in small ruminants, pigs and humans have also been documented, and serotype Choleraesuis is adapted to swine but has also been isolated from a range of other host species \[[@B15],[@B16]\]. Generalist serotypes such as *Salmonella*Typhimurium commonly cause disease in a broad range of hosts, even though a narrow host range has been described for certain subtypes, for instance Typhimurium subtypes DT2 and DT99, which appear to be adapted to pigeons \[[@B17]\]. Serotypes with broad and narrow host range seem to differ in clinical manifestation even though other factors such as host species, age, and concomitant disease affect the clinical manifestation as well (see \[[@B17]\] for a comprehensive review). Infections with generalist serotypes are often characterized by high morbidity but low mortality, and gastro-intestinal symptoms are the predominant clinical manifestation \[[@B13],[@B17]\]. On the contrary, infections with host adapted or restricted serotypes, such as Choleraesuis, Abortusequi, Gallinarum biovar Gallinarum, or Gallinarum biovar Pullorum, are typically characterized by low morbidity and high mortality, and systemic disease is common \[[@B13],[@B17]\]. *Salmonella*serotypes clearly seem to differ in their pathogenic potential for humans and serotype distributions often vary vastly between human and animal populations as well as among different animal populations in the same geographic area (see Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). For instance, approximately 40% of all known *Salmonella*serotypes are predominantly associated with reptiles or amphibians, yet less than 1% of human salmonellosis cases are caused by these reptile-associated serotypes. The molecular determinants of serotype-specific host range differences have so far largely remained elusive. However, serotype-specific differences in virulence have been characterized in some cases. For instance, in competition experiments with *Salmonella*Typhimurium, reptile-associated *Salmonella*Arizonae and Diarizonae showed a significantly reduced ability to colonize and persist in the intestine of BALB/c mice, clearly suggesting virulence differences \[[@B18]\]. Majowicz et al. \[[@B1]\] recently estimated that approx. 80.3 of 93.8 million human *Salmonella*-related gastroenteritis cases that are estimated to occur globally each year are foodborne, thus representing approx. 86% of human salmonellosis cases. Another study based on formal elicitation of expert opinion estimated that approx. 55% (range 32-88%) of human *Salmonella*cases are foodborne, 14% (range 3-26%) are travel-related, 13% (range 0-29%) are acquired through environmental sources, 9% (range 0-19%) occur due to direct human-to-human transmission and 9% (range 0-19%) are attributable to direct animal contact \[[@B5],[@B19]\]. Yet another study, based on surveillance data, estimated that 95% of non-typhoidal human *Salmonella*cases in the USA are foodborne, emphasizing the complexity and controversy of the subject matter \[[@B3]\]. Food products derived from the animal species discussed in this review can also serve as sources of human infection, and such products have been implicated in numerous human outbreaks. However, as this review focuses on animal-acquired infection, foodborne infections will not be further discussed here. Several excellent reviews of foodborne salmonellosis have been published in recent years, and the reader is referred to these publications for further details regarding infections associated with the consumption of meat, eggs, dairy products, vegetables, reptile products, and other foods (see for instance \[[@B10],[@B20]-[@B29]\]). The comparison of *Salmonella*outbreak and surveillance data across geographic regions or from different time periods represents a considerable challenge. The advent of novel molecular subtyping methods has noticeably improved discriminatory power, with important impacts on sensitivity and specificity \[[@B30]\]. The impacts of differences in public health infrastructure, disease surveillance sampling plans, public health legislation etc. are difficult to measure, but differences in apparent prevalence between states or countries are clearly noticeable. Case and outbreak definitions are also variable. For clarity, we will henceforth define \"case\" to refer to any instance where strong epidemiological or molecular evidence suggests an animal source of human infection, while trying to point out instances where such conclusions are solely based on serotype data or circumstantial epidemiological links. Furthermore, we will define an outbreak as an event where two or more human cases are presumably linked to the same source. We acknowledge that the epidemiological definition of an outbreak differs from this definition, but due to the large amount of underreporting and the problem of attributing cases with broad host-range serotypes to animal sources we chose this definition. As some serotypes are strongly associated with specific animal species and some case definitions utilize serotype data to define for instance reptile-acquired cases (see for instance \[[@B31],[@B32]\]), serotype-dependent differences in case detection are likely. Similarly, unusual exposures, such as those attributable to newly acquired or exotic pets, visits to animal exhibits, or contacts with clinically sick animals, are more likely to be recalled than routine exposures (see for instance \[[@B33]-[@B36]\]). In addition, small outbreaks are probably less likely to be reported in the peer-reviewed literature. Animal acquired infections are therefore probably strongly underreported, and the data is potentially biased towards larger outbreaks, uncommon serotypes, certain animal species, and unusual exposures. 3. Mammals as Source of Human Infection ======================================= 3.1. Mammalian livestock species and *Salmonella* ------------------------------------------------- ### 3.1.1. The global distribution and economic importance of mammalian livestock The estimated number of mammals farmed for agricultural purposes around the world exceeds 4 billion animals \[[@B37]\]. In 2006, approx. 20% of the world\'s population, equaling approx. 1.3 of 6.55 billion people, were employed in the livestock sector, and livestock accounted for approx. 40% of global agricultural output \[[@B38]\]. An estimated 1 billion pigs and 2 billion small ruminants are farmed worldwide \[[@B39]\]. The global cattle population is believed to equal approx. 1.3 billion animals, and 181 million buffaloes as well as approx. 24.7 million camels are farmed for commercial purposes around the world \[[@B37]\]. The relative and absolute abundance of livestock differs considerably by country and geographic area. For instance, the USA is the world\'s largest producer of beef and the third-largest producer of pork, while large numbers of cattle and pigs are also farmed in the EU \[[@B37]\]. Australia is a leading producer of wool and sheep meat, and India is an important producer of goat, buffalo and cow milk and a leading producer of goat and buffalo meat. Africa as well as parts of Western Asia are major producers of camel and goat products \[[@B37]\]. ### 3.1.2. Cattle and *Salmonella* #### 3.1.2.1. The clinical and economic importance of *Salmonella*infections among cattle Abortions attributable to *Salmonella*infection are possible but rare in cattle, thus economic losses in cattle operations are primarily due to increased mortality, performance losses, and direct and indirect costs associated with treatment and infection control (see \[[@B40]\] for a review of the topic). Mortality rates attributable to *Salmonella*infection are particularly high in young animals, which also generally require the greatest amount of treatment. Significant weight losses in calves due to *Salmonella*infection have been reported in numerous studies, even though surviving calves seem to regain the weight after recovery (see \[[@B40]\]). In addition, *Salmonella*infection often leads to increased feed costs due to diminished feed conversion \[[@B40]\]. Clinically, *Salmonella*infection in cattle is typically manifested as watery or bloody diarrhea, and often associated with fever, depression, anorexia, dehydration and endotoxemia. Less common clinical manifestations include abortion and respiratory disease, and mortality rates can be high. Particularly in adult animals *Salmonella*frequently causes subclinical disease, and is known to persist on infected farms for months or years \[[@B41]-[@B44]\]. Individual animals shed *Salmonella*intermittently, over variable periods of time, and infections with host adapted serotypes such as *Salmonella*Dublin may potentially result more frequently in the development of asymptomatic shedders than infections with broad host-range serotypes \[[@B45]\]. One recent study estimated the median duration of shedding in dairy cattle to equal 50 days, with a maximum duration of 391 days, and the results appear comparable to previous reports \[[@B46],[@B47]\]. However, the duration of *Salmonella*persistence in herds exceeds maximum shedding durations observed for individual animals, and is believed to be largely attributable to endemic *Salmonella*infections within the herd \[[@B47]\]. Several studies report isolating *Salmonella*at high rates from farm environments, a likely important *Salmonella*reservoir \[[@B43],[@B47]-[@B50]\]. *Salmonella*within- and between-herd prevalence estimates vary considerably, with between-herd point prevalence estimates for cattle operations ranging from 2-42% and within-herd estimates for these operations ranging from 0-37% \[[@B47],[@B51]-[@B57]\]. In addition, herds with clinically sick animals are generally characterized by higher within-herd prevalence than herds where clinical salmonellosis is absent, and serotype distribution may differ between herds with and without clinical cases \[[@B58]-[@B63]\]. Large herd size represents an important risk factor for salmonellosis, and the risk of *Salmonella*shedding seems to vary by production system, housing type, general hygiene level, management type and animal age, although the results reported in the literature have been somewhat contradictory \[[@B64]\]. Calves, heifers, and periparturient cows generally appear to be at a particular risk of infection, and one study found heifers and periparturient cows to be the most likely cattle to become asymptomatic carriers \[[@B47],[@B65],[@B66]\]. The distribution of *Salmonella*serotypes among cattle varies greatly over time, and differs among geographic regions, age groups, clinical manifestation, and production systems. The United States National Veterinary Service Laboratory (NVSL), for instance, reported that serotypes Typhimurium, Newport, Orion, Montevideo, and Agona were the serotypes most frequently isolated from clinically sick cattle in 2005 and 2006, while serotypes Cerro, Kentucky, Anatum, Newport, Montevideo, and Orion were the serotypes most frequently isolated from clinically healthy cattle in the same time period \[[@B67]\]. In 2007, serotypes Cerro, Kentucky, Montevideo, Muenster, Meleagridis, Mbandaka and Newport were the serotypes most commonly isolated from healthy dairy cattle in the USA, while serotypes Montevideo, Meleagridis, Cerro, Mbandaka, Typhimurium, Anatum, Give, Kentucky, Muenchen and Senftenberg had been the serotypes most commonly isolated from healthy USA dairy cattle in 1996 \[[@B68]\]. In comparison, serotypes Montevideo, I 6,7:k:-, Braenderup, Meleagridis, Newport and I 3,10:-:1, were the serotypes most commonly isolated from USA beef cattle in 2007/2008, and serotypes Typhimurium, Anatum, Dublin, Montevideo, and Newport were the serotypes most commonly isolated from USA beef herds in 1999 \[[@B69],[@B70]\]. The implications of these differing serotype distributions for human health, however, are currently difficult to assess. #### 3.1.2.2 The public health importance of *Salmonella*infection among cattle Cattle play a paramount role as source of foodborne infection, and a considerable number of serotypes frequently isolated from humans have been isolated from sick or clinically healthy cattle (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Some human cases have also been linked to direct cattle exposure (Table [1](#T1){ref-type="table"}). For instance, in 2002 and 2004, human *Salmonella*Newport outbreaks in Michigan were linked to cattle contact in a public setting; in 2001, *Salmonella*Newport was transmitted to humans during a farm visit, even though the consumption of contaminated raw milk may have been a contributing factor; and in 2000, serotype Typhimurium was transmitted to children at a farm camp. In several instances, attribution of human cases to cattle exposure is further complicated by simultaneous consumption of raw milk or cheese from the same farm, as illustrated by recent outbreaks of *Salmonella*Newport and Dublin (Table [1](#T1){ref-type="table"}). Nail biting, contact with manure, thumb sucking, eating, or having soiled hands and shoes have been identified as risk factors for animal-acquired *E. coli*infections, and a similar role for *Salmonella*appears likely \[[@B71]\]. Much less is known about the *Salmonella*risk posed to humans by indirect animal contacts, especially through environmental contamination. Further studies, especially on spatial clustering of human cases around livestock premises, are needed to assess the indirect risks posed by livestock operations. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Documented reports of *Salmonella*transmissions from mammals to humans available in the peer-reviewed literature or otherwise published by public health agencies ::: Outbreak source Year *Salmonella*serotype Type of contact Human cases Country Reference --------------------------------------------- -------------- ---------------------- ------------------------------------------------------------------------- ------------- -------------- --------------------- **Livestock** Cattle 2005^a^ Stanley occupational (dead calf delivery); pustular dermatitis 1 UK \[[@B36]\] Cattle 2004 Newport public setting 6 USA \[[@B35]\] Cattle 2003 Newport public setting 3 USA \[[@B35]\] Cattle 2002 Newport public setting 6 USA \[[@B35]\] Cattle 2001 Newport farm visit; potentially raw milk consumption 4 USA \[[@B35]\] Cattle 2000 Typhimurium farm day camp 1 USA \[[@B35],[@B304]\] Cattle 1998 Typhimurium household or farm environment 1 USA \[[@B305]\] Cattle 1990 Virchow occupational (dead calf delivery); dermatitis 2 Netherlands \[[@B306]\] Cattle 1983 Newport farm environment, nocosomial, feed-borne 1 USA \[[@B307]\] Cattle 1979 Dublin farm environment, nocosomial, potentially raw milk n/a USA \[[@B307]\] Cattle 1976 Heidelberg farm environment, secondary perinatal &nocosomial n/a USA \[[@B307]\] Cattle 1975 Dublin occupational (dead calf delivery); pustular dermatitis; 3 cases 3 UK \[[@B308]\] Cattle 1973 Saintpaul occupational (dead calf delivery); folliculitis 3 Canada \[[@B309]\] Cattle 1973 Typhimurium farm environment, animal feed pot. source n/a USA \[[@B307]\] Cattle 1972 Typhimurium occupational, farm environment n/a USA \[[@B307]\] Cattle 1969 Dublin occupational (dead calf delivery); pustular dermatitis 1 UK \[[@B308]\] Cattle 1965 Typhimurium farm environment, cow and newborn calf 2 Canada \[[@B310]\] Cattle 1948 Typhimurium farm environment, household, well water 7 Canada \[[@B311]\] Cattle/Pigs 2001 Typhimurium farm or household (contaminated clothes) 1 Netherlands \[[@B37]\] Pigs 2005 Typhimurium public setting; potentially environmental 19 USA \[[@B35]\] Sheep 1998-2003^b^ Brandenburg occupational, household, prob. secondary dogs n/a New Zealand \[[@B97]\] Sheep/Cattle 1991-1993 Typhimurium occupational, household, farm environment 9 UK \[[@B73]\] Sheep 1975 Typhimurium occupational, farm environment, secondary dog infected 1 UK \[[@B72]\] Livestock 2000 Typhimurium petting zoo, animal source unclear 18 US \[[@B303]\] Livestock 1991 Typhimurium science fair, animal source unclear 5 US \[[@B303]\] **Equines** Horse 2001 Newport state fair, horse clinically sick 2 USA \[[@B35]\] Horse 1995/1996 Typhimurium occupational, veterinary hospital, secondary ruminants 2 USA \[[@B145],[@B312]\] Horse 1976 Typhimurium occupational, veterinary hospital, secondary dog 1 USA \[[@B313]\] Horse 1967/1968 Typhimurium occupational, veterinary hospital, complex epidemiology 2 - 14\* UK \[[@B314]\] Horse 1936 Abortusequi occupational, gynecological exam, developed abscess 1 Japan \[[@B315]\] **Canines & Felines** Cat 1999 Typhimurium occupational, veterinary clinic 10 USA \[[@B316]\] Cat 1999 Typhimurium household, secondary daycare contact, shelter cats 7 USA \[[@B316]\] Cat 1999 Typhimurium occupational, veterinary clinic, secondary environmental 3 USA \[[@B316]\] Cat/Dog 2003 Typhimurium occupational, veterinary clinic, household infections 7 USA \[[@B317]\] Cat/wild birds 1999 Typhimurium household, prob. complex transmissions n/a Sweden \[[@B318]\] Cat/Dog 1973 Typhimurium household, dog and cat breeder, common food source 4 Canada \[[@B319]\] Dog 1974 Enteritidis household 1 USA \[[@B148]\] Dog 1952 Paratyphi B household 1 UK \[[@B320]\] Dog 1938 Glostrup household, pot. common food source 6 Denmark \[[@B321],[@B322]\] Dog 1937 Paratyphi B^1^ household 6 Norway \[[@B322],[@B323]\] Dog 1938 Paratyphi B household, caused abortion in bitch 4 Sweden \[[@B322],[@B324]\] **Pet food & Treats** Dry pet food 2006-2008 Schwarzengrund household 70 USA \[[@B325]\] Pet treats 2004/2005 Thompson household 9 USA & Canada \[[@B326]\] Pet treats 2002 Newport household 5 Canada \[[@B327]\] Pet treats 1999 Infantis household, dogs potential shedders 12 Canada \[[@B328]\] **Rodents** Guinea pig 2000 Oranienburg household, guinea pig soft-tissue abscess and died 1 USA \[[@B329]\] Guinea pig 1967 Enteritidis breeding colony in household 3 Canada \[[@B330]\] Rodents 2005/2006 Typhimurium classroom or household, snakes fed frozen rodents 7 - 21\* USA \[[@B331]\] Rodents 2003/2004 Typhimurium household, sick pet rodents, secondary household 15 - 28\* USA \[[@B332]\] **Non-traditional mammalian pets/wildlife** Hedgehogs 2002 Typhimurium household, potentially eggs 6 Australia \[[@B333]\] Hedgehogs 2000/2001 Typhimurium unclear, wild animals, potentially contaminated produce 37 Norway \[[@B192]\] Hedgehogs 1996 Typhimurium unclear, wild animals, potentially contaminated produce, 2 outbreaks 28 - 65\* Norway \[[@B192]\] Hedgehogs 1995-1997 Tiliene household, pet hedgehogs, multiple outbreaks, interspecies transmission 9 Canada \[[@B334]\] Hedgehogs 1994/1995^c^ Typhimurium household, pet hedgehog 1 Canada \[[@B196]\] Hedgehogs 1994 Tiliene household, pet hedgehog, indirect contact, breeding herd in household 1 USA \[[@B335]\] Sugar glider 1995 Tiliene household 1 Canada \[[@B334]\] Wallaby 2003 Enteritidis farm environment, traveling petting zoo 17 USA \[[@B35]\] ^1^identical to serotype Abortuscanis ^a^estimated time of outbreak, exact time not specified; ^b^estimated time period for prolonged nationwide outbreak; ^c^exact time of outbreak not specified more precisely; \* exact number of cases unclear; n/a exact number of cases not specified ::: In conclusion, the studies summarized above show that direct cattle contacts represent a potential human health risk. Clinically sick animals probably pose the greatest risk to humans because they are more likely to shed *Salmonella*, and at higher concentration, than apparently healthy animals. However, even asymptomatic carriers can shed *Salmonella*for long periods of time, and increased stress, as often experienced during exhibitions, represents an important risk factor for shedding. In addition, herds with clinical signs of *Salmonella*have higher within-herd prevalence than those without clinical signs, *Salmonella*prevalence is correlated with animal age as well as management-related factors, and environmental contamination can play an important epidemiologic role. Clinically affected herds and certain management systems may therefore pose an increased risk to the public. Several additional management practices may mitigate the human health risk associated with cattle contacts, for instance strict enforcement of good hygiene practices, the prevention of contact with manure, or targeted education of vulnerable human subpopulations. Several *Salmonella*infections have been attributed to occupational livestock contact (see for instance \[[@B36],[@B72],[@B73]\]). Surprisingly, a considerable number of cutaneous infections among veterinarians have been reported as results of obstetric manipulations, reinforcing the need for good hygiene practices and adequate protective equipment (Table [1](#T1){ref-type="table"}). However, quantitative estimates of the occupational risks are scarce. One study reported *Salmonella*-specific antibodies in 60% of poultry workers and nearly 10% of workers in meat-packaging plants in Russia, with highest prevalence among those handling sick poultry or pathological material (or consuming raw meat sausages) \[[@B74]\]. Similarly, occupational transmission of *Salmonella*Typhimurium to a slaughterhouse employee has been reported by Molbak et al. \[[@B75]\]. Another study found nearly 9% of poultry workers and 6% of duck workers were *Salmonella*carriers, with intermittent clinical symptoms \[[@B76]\]. Conversely, another study of *Salmonella*Muenster reported no occupational transmission in an affected dairy herd, but the study relied exclusively on self-reporting of clinical disease in farm personnel, and sample size as well as observational period were limited \[[@B77]\]. Future studies are therefore clearly needed to understand the magnitude and specific nature of the risks associated with occupational exposure. ### 3.1.3. Small ruminants and *Salmonella* #### 3.1.3.1. The clinical and economic importance of *Salmonella*infections among small ruminants The severity and clinical manifestation of *Salmonella*infection in small ruminants differs by age group and serotype \[[@B78]\]. Acute enteric salmonellosis is common in adult sheep, leading to fever, anorexia, depression, and diarrhea, while septicemia is common in young animals \[[@B79],[@B80]\]. However, asymptomatic carriage, chronic gastro-enteritis, and abortion have also been described \[[@B80],[@B81]\]. Late term abortion, mortality in ewes, and high calf mortality can lead to extensive economic losses in sheep operations, making *Salmonella*abortion one of the economically most important diseases of small ruminants \[[@B40]\]. Abortion due to infection with serotypes such as Typhimurium or Dublin has been reported, but abortion is most frequently caused by *Salmonella*Abortusovis, an ovine-adapted serotype that also occasionally infects goats, and abortion generally occurs in the last weeks before parturition \[[@B78],[@B82]-[@B84]\]. Infections of ewes with serotype Abortusovis can also lead to stillbirth, metritis, placental retention, or peritonitis, and infected ewes may present with fever, anorexia, and depression prior to abortion \[[@B85]\]. Mortality rates in ewes are highly variable, and mortality is often associated with the occurrence of secondary diseases such as placental retention. Neonatal mortality in affected herds is usually high. Lambs carried to term frequently die of septicemia \[[@B78]\]. While neonates often die within hours of birth, lambs can in some cases survive for weeks, and in these instances disease is often manifested as polyarthritis, pneumonia, and severe diarrhea. *Salmonell*a Abortusovis infection in non-pregnant ewes and rams appears to be predominantly asymptomatic and venereal infection have been described in some instances \[[@B86]\]. The prevalence of *Salmonella*among small ruminants seems to vary considerably between serotypes, herds, and geographic regions. Large outbreaks of *Salmonella*Abortusovis among sheep have been reported repeatedly, for instance in Switzerland, where infections with serotype Abortusovis seem to have contributed up to 70% of lambing losses between 2003 and 2007 \[[@B87]\]. The prevalence of serotype Abortusovis within herds can be high, and within-herd prevalence estimates of between 20 and 50% have been reported \[[@B82],[@B87]\]. Animals that survive infection with *Salmonella*Abortusovis usually develop robust immunity, so that infections tend to be associated with primigravide animals \[[@B82]\]. *Salmonella*Diarizonae is the causative agent of winter dysentery, a disease of sheep that is also associated with abortion and stillbirth. Serotype Diarizonae represents another common, sheep-adapted serotype. The prevalence of serotype Diarizonae in Norwegian sheep herds, for instance, has been estimated at approx. 12%, with within-herd prevalence in the range of 0-45%, even though the samples were collected at the abattoir and increased stress may have contributed to the high observed prevalence \[[@B88]\]. Other studies have also reported a high prevalence of various *Salmonella*serotypes including for instance serotypes Typhimurium, Anatum, or Saintpaul, in goats and sheep at slaughterhouses in different countries, with prevalence estimates generally in the range of 17-60%, even though a considerably lower prevalence among slaughtered goats and sheep in India and Ethiopia has been reported in some studies \[[@B81],[@B89]-[@B93]\]. The prevalence of *Salmonella*among healthy goats and sheep on farms generally appears to be considerably lower, with reported prevalence estimates often in the range of 0-4% \[[@B94],[@B95]\]. However, environmental contamination on farms is potentially high, and Edrington et al. \[[@B96]\], for instance, reported isolating *Salmonella*from 50% of wool samples but only 7% of fecal samples collected from feedlot sheep in the USA, indicating a potentially important epidemiological role of environmental reservoirs. ### 3.3.2. The human public health importance of *Salmonella*infections among small ruminants A limited number of zoonotic transmissions from sheep to humans have been reported in the literature, mostly associated with occupational exposures (Table [1](#T1){ref-type="table"}). For instance, occupational sheep exposure was found to be significantly associated with human *Salmonella*Brandenburg infections in New Zealand \[[@B97]\]. In addition, human outbreaks have repeatedly been linked to occupational contacts on farms in the UK, reiterating the potential public health importance of sheep and goat contacts \[[@B73]\]. In conclusion, *Salmonella*infections represent an economic and potential public health risk on sheep and goat farms, but considerable differences between the serotypes exist. Infections with serotype Abortusovis are responsible for large economic losses, but carry little health hazards for humans. However, several other serotypes such as Typhimurium can cause similar clinical disease in ewes, with potentially important implications for human health. Good hygiene practices and personal protective clothing are crucial to prevent occupational infections, especially during lambing or obstetrical intervention. Secondary transmissions to family members after occupational exposure have also been documented, reinforcing the importance of good hygiene practices on farms to reduce the human health risk \[[@B73]\]. Animals with clinical signs of gastro-intestinal disease or septicemia may pose the highest risk for humans, but asymptomatic shedding at relatively high prevalence has been documented at slaughter, indicating that clinically healthy animals may also pose a considerable risk. *Salmonella*carriage among healthy animals on farms appears to be relatively rare, but environmental contamination likely contributes to the infection risk. In conclusion, contacts with small ruminants pose a potential health risk to occupationally exposed subpopulations as well as the general public, but the risk depends strongly on the serotype involved. 3.4. *Salmonella*and pigs ------------------------- ### 3.4.1. The clinical and economic importance of *Salmonella*infections among pigs A variety of clinical manifestations have been observed in *Salmonella*infected pigs, ranging from asymptomatic to peracute disease. Infections with generalist serotypes such as Typhimurium usually cause mild or no disease, and infected animals may shed *Salmonella*for considerable periods of time. For instance, piglets experimentally inoculated with *Salmonella*Typhimurium developed mild gastro-intestinal disease and were found to shed bacteria in their feces for several days \[[@B98]\]; however, systemic disease and mortality associated with broad host-range serotypes has also been reported \[[@B99]\]. In contrast, infection with host adapted serotype Choleraesuis generally causes severe systemic disease with high mortality (see \[[@B99]\] for a recent review). All age groups are susceptible to *Salmonella*infection, but disease is most commonly observed among weaned pigs more than eight weeks of age, and asymptomatic carriers are thought to represent the most important source of *Salmonella*introduction onto pig farms. A variety of clinical manifestations have been documented among *Salmonella*-infected pigs, including enteritis, septicemia, pneumonia, meningitis, and arthritis. Fever, diarrhea, inappetence, depression, respiratory distress, lameness, edema, and hypoxia in the extremities are common symptoms in clinically sick pigs, and mortality rates in such instances are high. Schofield \[[@B100]\], for instance, reported salmonellosis outbreaks among pigs manifested as ataxia, fever, depression, diarrhea, and necrotic enteritis, which resulted in approx. 17% mortality. *Salmonella*prevalence estimates for pig farms seem to differ considerably by production and management type, with average between-herd estimates in the USA equaling 53% in 2006 and exceeding 80% for some farrow-to-finish production systems, while within-herd estimates range from 3.5 to 28% \[[@B58]-[@B63]\]. High *Salmonella*prevalence on pig breeding farms and considerably lower prevalence on replacement gilt development farms have been described in one study \[[@B58]\]. However, another study reported high prevalence among replacement gilts and finishing gilts, suggesting variability between herds and studies \[[@B60]\]. Surprisingly, Davies et al. \[[@B101]\] reported a higher *Salmonella*prevalence in all-in-all-out than continuous flow management systems, and distinct *Salmonella*serotype populations in breeding herds, nursery and finishing herds from the same farrow-to-finish system have been reported \[[@B101]\]. Breeding herds or nurseries therefore seem to represent epidemiologically relatively unimportant sources of infection in finishing herds, and environmental contamination may play an important role in maintaining endemic infections. In fact, Dahl et al. \[[@B102]\] demonstrated that *Salmonella*free finishing herds can be produced from endemically infected herds if pigs are strategically moved to clean stalls as they move through the farrow-to-finish system. Reducing the prevalence of *Salmonella*is particularly important because *Salmonella*prevalence at slaughter tends to be considerably higher than on farm \[[@B64]\]. Indeed, one study reported 7-fold higher *Salmonella*prevalence in pigs sampled at the abattoir than in animals from the same herds sampled on farm, indicating an important effect of stress or other transportation-related factors \[[@B103]\]. In addition to host adapted serotype Choleraesuis, serotypes Typhimurium, Derby, Agona and Anatum are frequently isolated from sick and clinically healthy pigs, indicating a potential risk for human health (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Distribution of the 20 most common human *Salmonella*serotypes**\[[@B7]\]**among animals, based on US data from 2006**. *Salmonella*Typhi was excluded from this analysis as it represents a host-restricted serotype adapted to humans and non-human primates. ::: ![](1297-9716-42-34-1) ::: #### 3.1.4.2. The human public health importance of *Salmonella*infections among pigs On few occasions, likely zoonotic transmissions of *Salmonella*from pigs to humans have been described (Table [1](#T1){ref-type="table"}). For instance, in 2005, a Typhimurium outbreak among humans in Wisconsin was linked to indirect pig contact in a public setting \[[@B34]\]. Similarly, in 2001 occupational exposure to pigs likely led to human infection, even though in this case the possibility of a transmission from calves could not be conclusively eliminated \[[@B36]\]. In conclusion, *Salmonella*represents an occupational hazard for those working with pigs, especially since asymptomatic carriage of broad host-range serotypes appears to be relatively common. Environmental reservoirs appear to play an important role in maintaining endemic infections, and contaminated clothing has been implicated in the transmission of *Salmonella*from pigs or calves to the son of a farmer, indicating the paramount importance of good hygiene practices \[[@B36]\]. Stress probably represents a major reason for the increased *Salmonella*prevalence among pigs at slaughter relative to that observed on farms, and a similarly increased prevalence of shedding during exhibitions or at other public venues appears likely. Contact with pigs on farms, at the slaughterhouse, or in the scope of public exhibitions therefore likely represents a risk to occupationally exposed population subgroups and the general population. 3.2. Companion animals and *Salmonella* --------------------------------------- ### 3.2.1. The changing role of companion animals in the 20^th^century The keeping of animals as pets has a long tradition, but historically, companion animals were foremost held for labor \[[@B104],[@B105]\]. Dogs served as guard dogs, hunting companions, or were used for herding, while cats were kept to catch rodents. Dogs and cats were rarely kept in homes, even pet animals \[[@B104]\]. During the 19^th^century engine-powered machines replaced horses as sources of labor. Simultaneously, the public\'s attitude towards animals changed, manifested in the foundation of animal welfare organizations such as the British Royal Society for the Prevention of Cruelty to Animals (RSPCA) in 1824 \[[@B104],[@B105]\]. The number of pet animals held for companionship increased drastically after World War II \[[@B104]\]. Currently, an estimated 63% of households in the USA own at least one pet; approximately 83.2 million households own dogs or cats, and roughly 4.3 million households own horses \[[@B106]\]. Similarly, in the United Kingdom, an estimated 26% of households own cats and 31% of households own dogs, amounting to approximately 10.3 million cats and 10.5 million dogs \[[@B85]\]. Today, dogs and cats primarily live indoors, share living spaces with their owners, and assume integral roles as companions, family members, or service animals \[[@B104],[@B107]\]. In one recent survey 95% of USA dog owners reported petting their animals, 67% reported playing with them, and 30% reported sharing their beds with their dogs \[[@B108]\]. Companion animals are also increasingly used in therapeutic settings, for instance in psychotherapy, or to support AIDS patients, children with disabilities, orthopedic and cardiac patients, Alzheimer patients, or the elderly \[[@B109]-[@B114]\]. The potential risks associated with such contacts, particularly for young children or immune-compromised patients, are difficult to quantify. In some parts of the world, companion animals still fulfill functional roles as source of food or labor, and may be allowed to roam around freely \[[@B115]\]. ### 3.2.2. *Salmonella*infections in horses and humans #### 3.2.2.1. The clinical and economic importance of *Salmonella*infections among horses Salmonellosis is an important disease of horses. Equine mortality rates vary depending on host age, predisposing factors and potentially the *Salmonella*serotype involved \[[@B116]\]. Mortalities as high as 40 to 60% have been reported, but in general, mortality appears to be considerably lower \[[@B117],[@B118]\]. In most cases, animals present with profuse, watery and malodorous diarrhea, frequently associated with abdominal pain and endotoxemia. Fever, dehydration and depression are common, and in severe cases these symptoms are accompanied by colic, gastric reflux, cardiovascular shock or coagulopathies. However, the severity of disease can vary considerably and, in animals of the same age group, may range from severe to asymptomatic \[[@B119]\]. Both peracute and chronic forms of disease are common, and convalescent carriers may shed *Salmonella*for months, but a carrier state does not appear to develop in all instances \[[@B118],[@B120],[@B121]\]. Disease may also manifest without gastrointestinal signs. Some serotypes appear to result more frequently in systemic disease than others, but the underlying mechanisms are still incompletely understood \[[@B122]\]. Respiratory forms are comparably frequent, and systemic forms of infection are commonly associated with arthritis, osteomyelitis, or soft-tissue abscesses \[[@B123],[@B124]\]. Foals, pregnant mares, and immune compromised horses are at a heightened risk of infection and, among foals, *Salmonella*-associated meningoencephalitis has been described \[[@B125],[@B126]\]. Abortions due to *Salmonella*cause important economic losses on stud farms \[[@B127]-[@B129]\]. Numerous studies have focused on horses in equine hospitals, with apparent prevalence estimates ranging from 1.8 to 18%; Anderson and Lee, however, report isolating *Salmonella*from 26.6% of slaughter horses \[[@B125],[@B130]-[@B135]\]. The prevalence among healthy horses on farms or in riding schools appears to be considerably lower, in the range of 1 to 2% \[[@B117],[@B131],[@B135],[@B136]\]. Asymptomatic carriers shed *Salmonella*intermittently. Increased shedding has been associated with antibiotic treatment and stressful situations such as transportation, horse competitions, co-morbid disease, or surgery \[[@B125],[@B133],[@B137]-[@B140]\]. High population density is thought to be another predisposing factor. The epidemiological significance of environmental contamination remains difficult to assess, but good environmental hygiene practices have been efficient in controlling hospital outbreaks \[[@B132],[@B141]-[@B143]\]. Numerous serotypes have been isolated from clinically healthy or sick horses, and a considerable number of outbreaks involving a variety of medically important serotypes have occurred in large animal hospitals (Table [1](#T1){ref-type="table"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). #### 3.2.2.2. The public health importance of *Salmonella*infection among horses Zoonotic transmission in large animal veterinary hospitals and private veterinary clinics is thought to occur frequently, even though only a small number of human cases associated with such transmissions have been documented (Table [1](#T1){ref-type="table"}) \[[@B144],[@B145]\]. *Salmonella*transmission to humans at a state fair has also been reported (Table [1](#T1){ref-type="table"}) \[[@B34]\]. In conclusion, horse contacts clearly represent a risk to humans. However, clinically healthy horses in riding schools or on farms, especially if held under optimal conditions, seem to pose a comparably low risk. The risk at competitions, state fairs or other public venues might be considerably higher due to increased stress, whereas pregnant mares, foals and hospitalized horses clearly represent a high risk. *Salmonella*-infected horses often present with no or atypical clinical symptoms, emphasizing the need for strict quarantine, environmental contamination control, and good hygiene practices. Due to the high *Salmonella*prevalence, high risk population subgroups may choose to refrain from entering equine hospitals or stud farms, or take particular precautionary measures. ### 3.2.3. *Salmonella*infections in dogs, cats and humans #### 3.2.3.1. The veterinary importance of *Salmonella*infections among dogs and cats A considerable number of *Salmonella*serotypes have been isolated from domestic dogs and cats around the world (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). The majority of infections are asymptomatic \[[@B146]\]. However, gastrointestinal disease manifested as enterocolitis and endotoxemia can occur and is often associated with fever, vomiting, anorexia, dehydration and depression \[[@B147]-[@B149]\]. Abortion, stillbirth, meningoencephalitis, respiratory distress and conjunctivitis have also been described \[[@B150],[@B151]\]. *Salmonella*prevalence among dogs and cats appears variable and probably depends on a variety of factors. One study analyzed the apparent *Salmonella*prevalence among greyhounds on race tracks and found 43.5% of dogs were shedders, while another study described the apparent prevalence among racing Alaskan sled dogs at approx. 60%, and the prevalence among stray dogs is likely equally high \[[@B147],[@B152]-[@B154]\]. In general, however, the rate of shedding is thought to be much lower, and a number of studies on non-racing client-owned dogs and client-owned cats report shedding rates in the range of 1-5% \[[@B155]-[@B160]\]. Ingestion of contaminated food is thought to be the predominant risk factor. *Salmonella*has been isolated at high frequency from raw dog food on greyhound race tracks, and asymptomatic carriers developed after experimental oral inoculation, with shedding observed for periods of up to four weeks \[[@B161],[@B162]\]. Dogs fed raw food diets appear to be at particular risk. Finley et al. \[[@B163]\] report that, in the absence of clinical signs, 50% of dogs fed contaminated raw food diets shed *Salmonella*in their feces, while none of the control dogs fed *Salmonella*-free diets shed *Salmonella*. In another, longitudinal study, Joffe et al. \[[@B164]\] isolated *Salmonella*at least once from the feces of 80% of client-owned dogs fed a common bone and raw food (BARF) diet. Surprisingly, *Salmonella*was also isolated on one or more occasions from 30% of client-owned controls, which were fed commercial dog food. Some serotypes such as *Salmonella*Typhimurium, Heidelberg, and Kentucky appear to be predominantly isolated from dogs fed raw food diet, and one study estimated the odds of shedding *Salmonella*to be approx. 23 times greater for dogs fed raw food diets than commercial diets \[[@B165]\]. Asymptomatic carriers shed *Salmonella*intermittently, and longitudinal studies provide evidence for multiple coinfections during relatively short time periods \[[@B166]\]. #### 3.2.3.2. The public health risk associated with *Salmonella*infection among dogs and cats A number of medically important serotypes for humans have been isolated from domestic dogs and cats (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1), and several studies have reported the isolation of multidrug-resistant isolates (see \[[@B167]\] for a comprehensive review of the topic). Human *Salmonella*cases have been attributed to contact with infected dogs or cats at home or in veterinary clinics (Table [1](#T1){ref-type="table"}). For instance, in 1938 the family dog was implicated as source of a human *Salmonella*Glostrup outbreak and in 1952 a human case of Paratyphi B was linked to direct dog contacts at home. In 1999 human outbreaks of *Salmonella*Typhimurium in Idaho and Washington were linked to contact with clinically ill kittens in veterinary clinics, and a human outbreak in Minnesota was linked to contact with cats from a shelter. A 2003 outbreak of *Salmonella*Typhimurium among humans in New York was also linked to a small animal veterinary clinic, but the index animal was not clearly identified. A recent case-control study of childhood salmonellosis in Michigan identified cat exposure, as well as reptile contacts, as risk factor for *Salmonella*infection, emphasizing the potential risk \[[@B168]\]. The risk posed to humans by indirect contact, for instance with excrement, is currently not clear. Infected humans also represent a possible source of infection for their animals. In addition, animal-to-animal spread occurs readily and has been clearly documented during a *Salmonella*outbreak in a military dog kennel \[[@B169]\]. In this instance, the index case acquired *Salmonella*through feed. Together, these data indicate that contacts with dogs and cats in homes, veterinary clinics and shelters clearly represent potential threats to human health. Raw food diets are associated with a significantly higher prevalence of *Salmonella*than other pet food diets, and since asymptomatic shedding is common it appears that animals on such diets might be suspected of *Salmonella*shedding regardless of clinical symptoms. Especially if some household members are at a heightened risk of infection, or if animals are introduce into therapeutic settings, other feed types may be preferable. *Salmonella*represents a clear occupational hazard. Good hygiene practices, environmental infection control, strict quarantine procedures, personal protective equipment, and other biosecurity measures are therefore crucial to reduce the risk wherever dogs or cats are kept in large groups or subjected to high levels of stress. ### 3.2.4. Commercial pet food and treats as sources of infection *Salmonella*contamination in pet foods and treats varies considerably by food type. Commercial raw food diets, representing combinations of raw meat, vegetables, grain and eggs or fruit, are available fresh or frozen in a large number of pet stores and veterinary clinics, and a recent Canadian study estimated *Salmonella*prevalence in these feeds to equal approx. 21% \[[@B170]\]. Several *Salmonella-*related recalls of raw foods have been reported in recent years, for instance of frozen cat food in the USA in 2007. Contamination rates in dry or canned foods are thought to be considerably lower, and to our knowledge *Salmonella*has not been isolated from canned dog food, but the number of available studies is very limited \[[@B8],[@B9]\]. Dry dog food has recently been linked to a large human salmonellosis outbreak, and dog and cat vitamins have been recalled due to *Salmonella*contamination, but prevalence data is currently scarce \[[@B9],[@B171]\]. Dried pigs ears and a variety of other dried animal parts are commercially available as dog treats. Contamination rates in these commodities appear to be high. For instance, in 2001 a Canadian study reported isolating *Salmonella*from 50% of pig ears and other animal-derived pet treats, and a 2003 study found 41% of animal derived pet treats sold commercially in the USA contaminated with *Salmonella*\[[@B172],[@B173]\]. Isolates included *Salmonella*Typhimurium, Heidelberg, Anatum, Infantis, and Derby, and a considerable number of samples contained more than one serotype (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Voluntary preventive measures implemented by the pet treat industry appear to have led to a considerable reduction in contamination rates, but a disease risk remains \[[@B174]\]. For instance, in December 2009, pig ears and beef hoof products were recalled in the USA because of a potential *Salmonella*contamination. Exposure to commercial pet food and animal derived pet treats has also repeatedly led to human outbreaks (Table [1](#T1){ref-type="table"}). For instance, in 2007 the CDC identified a multi-state outbreak of *Salmonella*Schwarzengrund linked to commercial dry pet foods, which affected dogs and their owners in 18 states of the USA and led to a nation-wide product recall. In 1999, pig ear treats contaminated with *Salmonella*Infantis led to a human outbreak of salmonellosis in Canada, and in 2002, pet treats contaminated with *Salmonella*Newport were responsible for human *Salmonella*infections in Canada. *Salmonella*outbreaks among humans have also been linked to rodents commercially sold as pet food, but these are more appropriately described in the section regarding rodents. In conclusion, pet feeds represent a direct and indirect threat to human and animal health. The choice of pet food and treats can considerably influence the *Salmonella*risk for animals and humans, and might be of particular importance if high-risk human population subgroups are exposed at home or in therapy settings, or if animals are exposed to stressful situation such as in kennels, veterinary clinics or shelters. However, good hygiene practices such as hand washing before and after feeding, appropriate cleaning of bowls and contact surfaces, and adequate storage can probably decrease the direct risk for humans considerably. 3.3. Rodents, rabbits and *Salmonella* -------------------------------------- ### 3.3.1. The clinical and environmental importance of *Salmonella*infections among rodents and rabbits *Salmonella*has repeatedly been isolated from wild mice and rats, which represent important reservoir hosts on farms and in food production environments (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Prevalence estimates for wild or captive rodents are relatively scarce, variable among geographic regions, and the numbers of studies as well as the prevalence seem to have decreased over time. In general, *Salmonella*shedding rate estimates are in the range of 1 to 15% \[[@B175]-[@B179]\]. *Salmonella*prevalence among captive rodents is low, and environmental reservoirs may play a paramount epidemiologic role \[[@B180]\]. *Salmonella*has also been isolated from pet rabbits, indicating a potential risk associated with this animal species \[[@B181]\]. However, the available prevalence data, especially for pet rabbits, is currently very scarce. *Salmonella*might to be fairly common in intensive rabbit meat production systems, with one study reporting that as many as 30% of intensive rabbit farms in Italy were positive for *Salmonella*\[[@B182]\]. However, a low prevalence of *Salmonella*among rabbit carcasses in Spanish slaughterhouses has also been reported, indicating that *Salmonella*prevalence among commercially farmed rabbits is probably variable \[[@B183]\]. *Salmonella*infection can cause severe disease in rabbits, which is sometimes associated with high mortality \[[@B182]\]. Clinical symptoms include enteritis, metritis and abortion, but striking differences in pathogenic potential seem to exist among different *Salmonella*serotypes \[[@B182]\]. In contrast, the majority of infections in mice and rats are asymptomatic. However, clinical disease among rodents has also been described, for instance during large outbreaks among laboratory rodents, which were associated with high mortality rates (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Indeed, *Salmonella*Typhimurium and Enteritidis have been widely used as rodenticide in the first half of the 20^th^century and continue to be used in some countries despite the public health risk \[[@B184],[@B185]\]. Systemic disease appears to be the most common clinical manifestation in mice and rats, and mortality is predominantly attributable to septicemia \[[@B186]\]. Pathogenicity is age and host strain dependent, with the highest mortality rates observed in young animals under three weeks of age \[[@B187]\]. A number of serotypes with importance for humans have been isolated from wild, laboratory or pet rodents (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Clinical *Salmonella*outbreaks among guinea pigs and hamsters, associated with conjunctivitis and soft tissue abscesses, have also been described \[[@B188],[@B189]\]. ### 3.3.2. The public health importance of *Salmonella*infection among rodents and rabbits In recent years, human outbreaks have repeatedly been associated with captive rodents sold in the USA as snake feed or pets (Table [1](#T1){ref-type="table"}). For instance, in 2004 a large multi-state outbreak of *Salmonella*Typhimurium among humans was associated with hamsters, rats and mice sold in pet shops across the USA. Similarly, in 2005 and 2006, a multi-state outbreak of *Salmonella*Typhimurium among humans was linked to frozen rodents sold as commercial snake feed. Sporadic human cases have also been linked to rodent contact, for instance a human case of *Salmonella*Oranienburg attributable to contact with a clinically sick guinea pig. In conclusion, rodent contacts represent a direct and indirect threat to human health. Wild rodents can serve as source of human infection by contaminating feeds, food, water or the environment, and they can conceivably infect dogs, cats or other animals if ingested. Salmonellosis represents an occupational hazard for exterminators, rodent breeders, and others that professionally handle rodents. Rodents often show no or atypical signs of salmonellosis, thus clinical symptoms in animals are of limited diagnostic value. To our knowledge, data on zoonotic transmissions from rabbits is not available at the point of writing, likely at least in part due to underreporting of human salmonellosis cases. Contacts with sick or clinically healthy rodents or rabbits can potentially lead to human exposures, and the enforcement of good hygiene practices is important to minimize the risk for humans. 3.4. The role of non-traditional mammalian pets and wildlife ------------------------------------------------------------ Non-traditional pets are captive-bred or wild-caught, endogenous or exotic animals held as pets that have not reached wide-spread popularity among pet owners and are therefore not commonly bred for human companionship \[[@B190]\]. Apart from reptiles, amphibians, and fish, non-traditional pets include a variety of mammalian species such as non-human primates, African pygmy hedgehogs, ferrets, prairie dogs, and sugar gliders \[[@B190],[@B191]\]. Lack of husbandry expertise often results in stress, malnutrition or abandonment, and bites or scratches pose a considerable risk to pet owners \[[@B191]\]. ### 3.4.1. Exotic pets, wildlife and *Salmonella* Little is known about the prevalence, pathogenicity, and distribution of *Salmonella*among non-traditional mammalian pets or their wild relatives, but *Salmonella*has been isolated from a large number of wild mammals or their feces, including opossums, squirrels, woodchucks, raccoons, foxes, mink, cougars, tigers, wild boars, hippopotami, rhinoceroses, seals and whales (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Serotypes with particular importance for human health have also been isolated from white-tailed deer feces in Nebraska, even though *Salmonella*prevalence in this species is believed to be quite low (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). One Norwegian study of *Salmonella*in feral hedgehogs reported prevalence estimates between 0 and 41%, which varied considerably by geographic area \[[@B192]\]. High prevalence corresponded to human outbreaks in the same region, and isolates with identical PFGE patterns were isolated from wild hedgehogs and humans, potentially indicating an epidemiological link, which is also supported by an independent Danish study \[[@B193]\]. *Salmonella*prevalence among captive hedgehogs, sugar gliders and other non-traditional pets is currently unknown. Clinical disease associated with *Salmonella*infection has been described in sugar gliders and hedgehogs, but a large number of cases are believed to be asymptomatic \[[@B194],[@B195]\]. Several human cases and outbreaks of serotypes Typhimurium and Tielene have been linked to pet hedgehog contacts (Table [1](#T1){ref-type="table"}), and *Salmonella*Enteritidis and Sofia have also been isolated from hedgehogs kept as pets (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). *Salmonella*Tielene represents a very rare serotype. Human cases are strongly associated with hedgehog exposure, and children appear to be at heightened risk of infection \[[@B195]\]. *Salmonella*Tielene was first isolated in the USA in 1994 during a human outbreak associated with an African pygmy hedgehog breeding colony \[[@B195]\]. In Canada the geographic distribution of human Tielene cases starkly resembles that of pet hedgehogs, emphasizing the epidemiological role of this pet species \[[@B196]\]. Human Tielene outbreaks have also been linked to sugar glider exposure, indicating a role of this exotic pet in *Salmonella*Tielene epidemiology \[[@B196]\]. In conclusion, wildlife and exotic pets clearly represent potential sources of human infection, but relevant data is so far scarce. *Salmonella*can cause disease in these animals, but asymptomatic carriers appear to be common and likely also pose a considerable infection risk. Good hygiene practices and measures that reduce stress, such as adequate housing, nutrition and care, can likely reduce the risks associated with captive animals. 4. Avian Sources of Human Salmonellosis ======================================= 4.1. Overview of *Salmonella*infections in birds ------------------------------------------------ World-wide, birds are held for meat or egg production, companionship, sports, scientific or educational purposes. In 2007, an estimated 17.9 billion chickens, 1.1 billion ducks, 447 million turkeys and 343 million geese and guinea fowl were farmed world-wide \[[@B39]\]. Of these, approx. 9.4 billion chickens, 997 million ducks, 14 million turkeys and 307 million geese were farmed in Asia alone. In addition, a considerable number of animals are held as pets, with 6.4 million households in the USA alone owning pet birds \[[@B106]\]. 4.2. *Salmonella*infections among galliform birds ------------------------------------------------- Chickens, turkeys, quails, pheasants and other gamebirds are members of the order galliformes. *Salmonella*is common in galliform birds, and has been isolated at high rates from commercially reared chicken, turkeys, and other poultry (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Apart from the associated foodborne risk, farms may represent a direct risk to public health, even though relevant studies are so far missing and high biosecurity standards in most commercial poultry productions probably minimize the risk. The clinical symptoms associated with *Salmonella*infection vary considerably by age group and serotype \[[@B197]\]. Infections with generalist serotypes rarely cause clinical disease in galliform birds and most animals become asymptomatic carriers, even though severe clinical disease with high mortality has been observed in some instances, particularly during infections of young birds \[[@B198],[@B199]\]. Infections with the host adapted serotype Gallinarum biovars Gallinarum and Pullorum, however, cause severe disease with high mortality and immense economic losses on chicken and turkey farms (see \[[@B200]\] for a review of the topic). *Salmonella*Gallinarum biovar Pullorum causes \"Pullorum disease\" in young animals, which is associated with septicemia and high mortality that can exceed 85% in some instances \[[@B197]\]. *Salmonella*Gallinarum biovar Pullorum infections of adult birds are generally mild or asymptomatic, even though decreases in fertility and egg production as well as increased mortality have been observed in some instances. Adult animals can develop a carrier state, and transovarian transmission is thought to be the primary rout of transmission to young birds, even though rodents and other vectors are also thought to play an important epidemiologic role (see for instance \[[@B201]\]). Clinical symptoms include anorexia, diarrhea, dehydration, decreased hatching, and high mortality. *Salmonella*Gallinarum biovar Gallinarum causes \"fowl typhoid\" in young and particularly adult birds \[[@B200]\]. Clinical symptoms are very similar to those observed during infections with biovar Pullorum, and economic losses during outbreaks can be very high. Both Gallinarum biovars Gallinarum and Pullorum are host restricted and therefore pose a negligible risk to human health. In contrast, infections with *Salmonella*Enteritidis are typically asymptomatic in adult birds but can cause systemic disease in young birds, and transovarian transmission of serotype Enteritidis has also been described \[[@B202]\]. Infections with *Salmonella*Enteritidis pose a considerable human health risk, and have been estimated to inflict costs of approx. 1 billion US dollar per year on the USA economy \[[@B203]\]. *Salmonella*prevalence varies considerably by poultry type, differs between serotypes and biovars, and intestinal carriage often appears to be lower than isolation rates from egg shells, dead birds, and environmental samples \[[@B204],[@B205]\]. *Salmonella*prevalence in hatcheries is estimated between 0 and 17% for chickens, compared to approx. 25% for geese, and 20-60% for ducks \[[@B204],[@B205]\]. *Salmonella*Gallinarum biovars Pullorum and Gallinarum have been eradicated in commercial poultry productions in the developed world, but are still important in backyard flocks as well as the developing world \[[@B197]\]. It is conceivable that serotype Enteritidis filled the ecologic niche left by the eradication of serotype Gallinarum biovar Gallinarum, since a considerable increase in Enteritidis prevalence co-incided with the eradication of biovar Gallinarum in the 1960s (see \[[@B206]\] for a review of the subject). In fact, mathematical modeling results have suggested a potential role of competitive exclusion between serotypes Enteritidis and Gallinarum biovar Gallinarum in poultry \[[@B207]\]. *Salmonella*Enteritidis, as well as serotypes Typhimurium, Kentucky, and Heidelberg, are commonly detected among clinically healthy as well as sick chickens and turkeys, indicating a potentially important risk for human health (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). A number of people raise chickens and other poultry in their backyards for meat, egg production or as pets \[[@B208]\]. In addition to household exposure, human cases have been linked to poultry contact on farms, in agricultural feed stores, and at country fairs \[[@B209]\]. Young hatchlings pose a particularly high risk for humans, and remarkably often infect children (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). The number of human outbreaks increases strikingly around Easter, when chicken or duck hatchlings are especially popular pets. Such outbreaks have been documented every few years since the 1950s (see for example \[[@B209]-[@B211]\]). To reduce the risk associated with hobby farming, the sale of poultry for meat or egg production at feed stores is prohibited in all USA states \[[@B212]\]. In addition, the USA CDC and some state health departments work to increase public awareness and to promote customer education at the store level. Some USA states have passed additional regulations, such as legislations restricting the minimum age of animals at sale or the maximum number of animals purchased per person \[[@B212]\]. However, enforcement of these laws is difficult and legislation varies among states \[[@B213]\]. The USA CDC has published recommendations regarding pet poultry, including that no children under the age of 5 handle baby poultry \[[@B214]\]. In conclusion, the human health hazards posed by pet poultry, and young hatchlings in particular, are substantial, but fairly well understood. The laws and recommendations provided by the USA CDC and comparable institutions can successfully mitigate the risks. However, public awareness and collaboration between governmental agencies, related industries, special interest groups, and the veterinary community is crucial to assure sustainable results. The risks of direct transmission to humans that are associated with commercial poultry productions are less well understood. *Salmonella*certainly poses an occupational risk to farmers, veterinarians and slaughterhouse employees, but whether commercial poultry farming poses direct risks to the general population remains yet to be determined. 4.3. *Salmonella*infections among anseriform birds -------------------------------------------------- Ducks, geese and swans belong to the order Anseriformes. The majority of *Salmonella*infections in ducks appear to be asymptomatic, but severe clinical disease with high mortality has also been described \[[@B215]\]. Clinical disease is predominantly observed in young animals, and seems to generally be associated with environmental or management stressors. Common symptoms include anorexia, depression, diarrhea, dehydration, ataxia, opistothotonus, arthritis, and synoviatis, and decreases in fertility and hatching have also been reported \[[@B215]\]. The prevalence of *Salmonella*shedding appears to be species and age group dependent. *Salmonella*shedding is comparably common among commercially raised ducks and geese, yet highly variable across age groups. *Salmonella*Typhimurium, for instance, has been isolated from 40% of hatchlings and 1% of older ducklings in Taiwan, even though clear host species specific differences were also detected \[[@B216]\]. The prevalence of *Salmonella*shedding among wild birds appears to be quite variable (see for instance \[[@B217]\] for a review). Mitchell and Ridgwell, for instance, reported isolating *Salmonella*from approx. 4% of bird droppings in London \[[@B218]\]. Conversely, Cizec et al. reported isolating *Salmonella*from 19% of wild gulls sampled in the Czech Republic \[[@B219]\]. However, lower prevalence estimates among gulls have also been reported in the literature, in the range of 3-13%, and considerable differences between bird species and age groups seem to exist \[[@B219]-[@B221]\]. A number of human outbreaks have been linked to duckling exposure, and often both ducklings and chicken hatchlings are involved in the same outbreak, indicating great similarities in transmission and epidemiology (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). Analogous to chicken farms, it remains yet to be determined whether commercial duck and geese farms represent a substantial direct risk to human health. Similarly, the potential role of wild ducks and geese for human health is still subject to debate and conclusive evidence for or against an important role has yet to be presented (see \[[@B217]\] for a review of the subject). In conclusion, the risk associated with pet ducklings is high, but relatively well understood and bears great similarities to that observed for young chicken. Commercially reared or wild anseriform birds might conceivably pose a substantial risk to human health, but more data is needed before the subject can be evaluated conclusively. 4.4. *Salmonella*infections among columbiform birds --------------------------------------------------- Doves and pigeons belong to the order of columbiform birds. Upon *Salmonella*infection, most adult birds show no or mild signs of disease, but severe paratyphoid disease with high mortality has been reported among young birds \[[@B222]\]. Clinical manifestations are variable and include gastro-enteritis, growth retardation, anorexia, depression, fever, torticollis, opisthotonos, oophoritis or orchitis, arthrosynovitis, and abscesses. While a variety of serotypes have been isolated from pigeons and doves, *Salmonella*Typhimurium var. Copenhagen phage types 2 and 99 are the most commonly isolated subtypes \[[@B223]\]. Intriguingly, the Typhimurium isolates from pigeons differ biochemically and antigenically from other Typhimurium isolates, likely indicating host adaptation of these Typhimurium subtypes to pigeons \[[@B217],[@B222],[@B223]\]. *Salmonella*appears to be a relatively common pathogen among pigeons and doves, but the prevalence seems to differ by serotype and habitat (see \[[@B217]\] for a review of the subject). Petersen \[[@B224]\], for instance, compared *Salmonella*prevalence in wild pigeons from urban areas and dairy farms in Colorado, and detected *Salmonella*in approx. 8% of samples from dairy-exposed pigeons but not in samples from pigeons in urban areas. However, the isolation of various *Salmonella*serotypes from wild pigeons in urban areas in Japan has also been reported, indicating a potential risk for human health \[[@B225]\]. Endemic infections among domestic pigeons in lofts have been described, and prevalence estimates of 25-30% within individual lofts have been reported \[[@B217]\]. *Salmonella*Typhimurium var. Copenhagen phage types 2 and 99 seem to be the predominant serotypes among domestic pigeons, but other serotypes have also been isolated \[[@B217]\]. In conclusion, *Salmonella*appears to be relatively common among pigeons. However, most infections seem to be due to host adapted subtypes of Typhimurium, and therefore likely only pose a limited risk to humans. In fact, to our knowledge, no zoonotic transmission from pigeons to humans has been documented in the literature, even though underreporting of human cases likely contributed to this lack of observation. *Salmonella*can also be found in wild doves, probably mostly at low prevalence. Broad-spectrum serotypes have been isolated from wild pigeons and environmental contamination appears to represent an important risk factor for shedding in doves and pigeons, indicating that such birds may represent potentially important vectors on livestock premises and possibly carry some direct risk for humans. 4.5. *Salmonella*infections among passerine birds, psittacine birds, and other non-domesticated birds ----------------------------------------------------------------------------------------------------- Passerine birds are commonly referred to as songbirds, while psittacine birds include parrots, cockatoos and parakeets. Both passerine and psittacine species are not only important wild bird species, but also represent popular pets and are often kept in zoological exhibits. Numerous *Salmonella*serotypes have been isolated from a variety of captive birds held as pets (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Acute and chronic infections have been reported, which range from asymptomatic to clinically severe and can manifest as diarrhea, anorexia, dehydration, depression, crop stasis, septicemia or osteomyelitis \[[@B226]-[@B228]\]. For instance, *Salmonella*has been isolated from pet shop and household birds in Trinidad, imported finches, lories and parakeets in Japan, a variety of captive birds imported into Britain, numerous psittacine species held in Brazil, psittacine pet birds in Texas, Tennessee and Kansas, and captive as well as free-ranging parrots in Bolivia (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). *Salmonella*outbreaks with high bird mortalities have been described in zoologic exhibits, captive bird colonies and falcon collections \[[@B229]-[@B231]\]. Captive birds can also pose a *Salmonella*risk to humans, even though only a very limited number of cases have been documented (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). For instance, parakeets were involved in the transmission of *Salmonella*Typhimurium to a human infant and a cat, even though the exact transmission routes were not clearly determined \[[@B232]\]. Asymptomatic *Salmonella*carriage in wild birds is thought to be high, and wild birds have repeatedly been implicated as vehicles on farms and in feed mills \[[@B233]-[@B236]\]. Around the world, a variety of serotypes, including those frequently isolated from humans, have been isolated from free-ranging songbirds, parrots and parakees, with clinical manifestations ranging from asymptomatic to peracute death (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Stress increases the risk of shedding, and in songbirds salmonellosis commonly peaks in winter months, likely due to crowding and increased contact rates at bird feeders \[[@B237]\]. *Salmonella*prevalence among birds at feeders is commonly higher than in the general population, and epidemics have been reported repeatedly, for example during the winter of 1997/98, when an epidemic affected songbirds across the eastern parts of North America \[[@B237]-[@B239]\]. Wild songbirds have also been repeatedly implicated as source of human infection (Additional file [2](#S2){ref-type="supplementary-material"}: Table S2). For instance, during the winter of 2000, Typhimurium isolates with identical Pulsed Field Gel Electrophoresis (PFGE) patterns were associated with a *Salmonella*outbreak among wild birds as well as human cases in New Zealand, and an epidemiologic link, potentially due to contaminated water, appears plausible \[[@B239],[@B240]\]. Evidence also suggests that a large number of human Typhimurium cases in Norway were associated with wild bird contacts \[[@B241]\]. Other non-domesticated birds also potentially pose a risk to human health. In 2001 an elementary school Typhimurium outbreak involving at least 40 human cases was linked to dissecting owl pellets collected from captive owls, and more recently another outbreak in Massachusetts was also linked to owl pellets \[[@B242]\]. In conclusion, contacts with wild or captive birds pose a possible threat to human health, even though many epidemiological details remain to be understood. Birds, bird droppings, pellets, and feathers, as well as contaminated water and environments represent a potential risk. 5. Reptiles, Amphibians and Fish as Sources of Human Infection ============================================================== Contact with reptiles, amphibians or pet fish also represents an important source of *Salmonella*infection (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptiles, amphibians and fish have become popular pets in many countries. For example, approx. 3% of households in the USA own one or more reptiles as pets, resulting in a total of approx. 7.3 million reptiles \[[@B106]\]. The number of pet turtles has doubled in recent years, and in the USA approx. 2 million turtles are now kept in over 1 million households. More than 400 000 USA households keep snakes and in excess of 700 000 households own lizards \[[@B106]\]. Pet fish are present in an estimated 15 million USA households, with approx. 0.8 million households owning salt water fish tanks \[[@B191]\]. An estimated 1.3 million reptiles and 203 million fish were imported legally into the USA in 2005 alone, and a considerable number of pets are imported illegally each year \[[@B191]\]. Imports include captive-bred as well as wild-caught animals and the exotic pet trade poses a potential public health threat \[[@B191]\]. 5.1. Reptiles and *Salmonella* ------------------------------ ### 5.1.1. *Salmonella*prevalence and serotype diversity among reptiles *Salmonella*occurs naturally in the gastrointestinal tract of many reptiles, is commonly shed by these animals, and around the world a large number of serotypes have been isolated from feral and captive reptiles as well as their eggs (Figure [1](#F1){ref-type="fig"}, Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Clinical disease, including septicemia, osteomyelitis, salpingitis, nephritis, dermatitis and abscesses, seems to be occasionally associated with *Salmonella*infection in snakes, turtles, and lizards, but the overwhelming majority of infections in reptiles are undoubtedly asymptomatic; clinical salmonellosis in reptiles is rare, appears to be associated with underlying disease or other stressors, and a causal relationship between *Salmonella*infection and disease is generally difficult to establish conclusively \[[@B243]-[@B245]\]. Whether *Salmonella*infection causes diarrhea in reptiles is still subject to debate, and might depend on a variety of factors including host species and ambient temperature during infection \[[@B246],[@B247]\]. For instance, links between a case of necrotizing gastritis in a snake and *Salmonella*infection or between atrophic gastritis in a tortoise and *Salmonella*has been suggested, but so far reports are predominantly anecdotal (see for instance \[[@B248]\] for a review). Prevalence estimates in free-ranging reptiles vary widely, and a few studies report the absence of *Salmonella*in their study populations \[[@B249],[@B250]\]. Prevalence estimates in other studies range from 6 to 100% in turtles, from 30 to 76% in lizards and from 54 to 100% in snakes \[[@B251]-[@B257]\]. It has been estimated that as many as 90% of all captive reptiles carry *Salmonella*, including a large number of \'reptile-associated\' as well as \"broad host-range\" serotypes \[[@B196],[@B246]\]. Some studies have investigated the efficacy of antimicrobial treatments, sometimes combined with physical treatments, in reducing reptile *Salmonella*carriage, and initial laboratory experiments proved promising \[[@B258]-[@B260]\]. However, the routine treatment of reptiles, eggs, or pond water on commercial farms is complicated by farming conditions, intermittent *Salmonella*shedding, transovarian infections, coprophagy, and environmental reservoirs, and these treatments appear to be associated with a heightened risk of antibiotic resistance \[[@B261]-[@B264]\]. *Salmonella*has been isolated from commercially raised turtles, crocodiles, alligators, and iguanas, their meat, or the farm environment, and contamination levels appear to be substantial, with prevalence estimates for farmed turtles as high as 40% (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). The stress of transportation and the close physical contact during transport may further contribute to *Salmonella*shedding, especially among baby turtles and lizards. ### 5.1.2. The risk associated with contacts to reptiles Human salmonellosis attributable to reptile exposure was first documented in the 1940s, and a large number of case reports have since described zoonotic transmissions of *Salmonella*from reptiles to humans (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). The exact number of reptile-associated salmonellosis cases among humans is difficult to determine, but one study estimated that in the USA, reptile exposure contributes approx. 70 000 human cases each year \[[@B265]\]. This represents 6% of all sporadic human cases, and reptile-associated cases are estimated to contribute 11% of sporadic human cases in the population \< 21 years of age \[[@B265]\]. In the European Union, apparent prevalence estimates vary considerably among member states and over time \[[@B266]\]. In Sweden, for instance, 339 human reptile associated cases have been reported between 1990 and 2000, equaling approx. 5% of reported human cases \[[@B266],[@B267]\]. This number increased markedly in subsequent years until a public education campaign was launched in 1997 \[[@B267]\]. A large number of human salmonellosis cases have been linked to contact with turtles, terrapins, snakes, and lizards such as iguanas, bearded dragons, geckos, and chameleons (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptile-associated *Salmonella*infections in humans tend to be more likely associated with systemic disease than foodborne infections. Especially among children, the elderly or pregnant women, septicemia, meningitis, arthritis, soft-tissue abscesses, osteomyelitis, pericarditis, myocarditis, peritonitis and urinary tract infections have been repeatedly described, leading to severe disease and comparably high mortality rates (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). However, frequently only a single person or household is affect, and many reported cases involve children and infants. The reasons for the high prevalence among infants and children are not clear and might include biological, immunological and behavioral determinants \[[@B268],[@B269]\]. Few reptile owners are aware of the disease risk. In the USA, the CDC recently reported that only approx. 20% of interviewed human cases were aware of the link between reptiles and *Salmonella*\[[@B269]\]. Good hand hygiene, which has been shown to be a very effective measure to prevent infection, may therefore not be strictly enforced \[[@B270]\]. *Salmonella*survives over long time periods in the environment, and a number of human outbreaks have been attributed to indirect reptile contact (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). Reptile-associated salmonellosis occurs frequently in small children, which are rarely allowed direct contact with snakes or lizards, strongly suggesting indirect exposure routes (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). In fact, a case-control study found presence of reptiles in the home to be a highly significant risk factor for salmonellosis in infants \< 1 year of age, strongly suggesting a predominant role of indirect transmission \[[@B271],[@B272]\]. In other cases, the evidence is even more compelling. For instance, in 1996 a human *Salmonella*outbreak with at least 65 cases was linked to contact with a wooded barrier around a Komodo dragon habitat in the Colorado zoo \[[@B270]\]. In 1994, hospitalized infants were infected with *Salmonella*Kintambo \[[@B271]\]. One infant\'s family owned a lizard which shed Kintambo and the infant\'s mother reported diarrheal illness shortly before giving birth, potentially indicating prior infection. In 2001, *Salmonella*Nima was isolated from a sick infant and a boa at the school where the infant\'s father worked \[[@B273]\]. The father reported carefully washing his hands after handling the snake or its container, but frequently draped the snake around his arm and did not change his clothes before handling the infant. In 2004, *Salmonella*Typhimurium was isolated from an 80 year old woman and the bowl in which her daughter\'s turtle was kept \[[@B274]\]. The women had no direct contact with the turtle or its bowl, but the bowl was cleaned in the kitchen sink. Given the large number of indirect transmissions, the USA CDC recommends that households with young children (i.e. \< 5 years of age) do not own reptiles and that reptiles are not introduced into school settings. Several organizations have published information materials and recommendations concerning pet reptiles. In the USA, these include for instance governmental organizations such as the CDC and FDA, as well as professional organizations such as the American Veterinary Medical Association, the Association of Reptile and Amphibian Veterinarians, and the National Association of State Public Health Veterinarians (NASPHV). However, despite intense efforts awareness has remained limited. Given the high prevalence of *Salmonella*among feral alligators, crocodiles, turtles, and lizards, contamination of surface water, ponds and other natural surfaces also represents a potential public health concern, but quantitative risk estimates are currently not available \[[@B275]-[@B279]\]. At least two human cases have been linked to reptile-contaminated surface water. In this instance, pet turtles were allowed to swim in a non-chlorinated in-ground pool frequented by the two human case patients \[[@B269]\]. In conclusion, direct or indirect exposures to reptiles clearly represent a substantial risk to human health. Infants and young children are at a particularly high risk, and severe clinical manifestations seem common. A considerable fraction of cases occur due to indirect contacts. Moreover, the prevalence of *Salmonella*shedding among captive reptiles is high, and clinical symptoms are rare. Large parts of the general population may therefore be affected. Legislative efforts have achieved substantial successes in reducing the risk of reptile-acquired infection. However, regulations have to be integrated with public education to achieve maximum compliance. Governmental agencies and several stakeholder groups work to increase consciousness. However, despite long-standing efforts, awareness of the *Salmonella*risk has remained comparably low. A number of alternative exposure routes can also lead to reptile-associated infections, and should be taken into consideration as appropriate. ### 5.1.3. *Salmonella -*related regulations of pet turtle commerce Up to the 1970s, pet turtles represented a major source of salmonellosis in the USA, annually contributing an estimated 14 to 23% of salmonellosis cases among children \[[@B280],[@B281]\]. This prompted numerous state governments to mandate certification of *Salmonella*free status for all locally sold pet turtles, and since 1972 the USA FDA required similar certifications for all pet turtles sold in interstate commerce \[[@B281]\]. When these measures proved ineffective, the FDA posed a nation-wide ban on the sale and distribution of turtle eggs and small turtles with shells less than 4 inches (10.2 cm) in diameter in 1975 \[[@B281]\]. This legislation markedly decreased the number of reptile-associated cases, and has been estimated to prevent approx. 100 000 cases of salmonellosis, predominantly among young children, each year \[[@B281]\]. However, the ban did not prevent the sale of young turtles in all cases. Turtles less than 4 inches were still allowed to be sold for scientific, educational and exhibitional purposes, for export, or for purposes other than business, and the ban did not include marine turtles. In addition, small turtles were still illegally sold in pet stores and at unregulated vendors such as flea markets, and small turtles with shell diameters below 4 inches were still implicated in a considerable number of reptile-associated salmonellosis cases after the sale ban was enacted in 1975 (see for example \[[@B269],[@B282]\]). In 2007, Louisiana Congressmen proposed the \"Domestic Pet Turtle Market Access Act of 2007\" to the US Senate, which aimed to overrule the sales ban if the seller met certain regulations regarding licensing, sanitization and consumer information. The specified reasons included the fact that the sale of lizards, snakes, frogs and other amphibians and reptiles as pets is not regulated by the FDA, even though they are known to carry *Salmonella*, and that *Salmonella*treatment technologies have advanced since the ban was initiated in 1975. The bill was referred to the Senate committee on agriculture, nutrition and forestry, but had no action taken and never passed. 5.2. Amphibians and *Salmonella* -------------------------------- The prevalence of *Salmonella*among amphibians seems to vary considerably by host species, even though the number of studies that analyze *Salmonella*shedding by amphibians is quite limited. *Salmonella*has frequently been isolated from frogs and toads, in which *Salmonella*infection seems to be predominantly asymptomatic (see for instance \[[@B253],[@B283],[@B284]\]). The prevalence of *Salmonella*among salamanders and newts appears to be lower than among frogs and toads, but the available data is currently relatively limited \[[@B283]\]. Contacts with toads or frogs clearly pose a potential risk to humans. In 2009, for instance, an outbreak of *Salmonella*Typhimurium, which affected people in more than 30 USA states, was associated with African dwarf frogs (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3) \[[@B285]\]. Implicated frogs were traced back to a breeder in California, and Typhimurium isolates with PFGE patterns matching the outbreak strain were isolated from several environmental samples taken in the implicated breeding facility. In 2001 an outbreak of *Salmonella*Javiana in Mississippi was epidemiologically linked to contact with frogs and toads, even though the *Salmonella*serotype was not isolated from amphibians sampled during the outbreak investigation \[[@B286]\]. In 2000, frogs were epidemiologically implicated as the source of water contamination at a construction site in Australia, but no microbiological investigations of the frogs were performed \[[@B287]\]. Moreover, a case-control study estimated that the odds of *Salmonella*serogroup B or D infection among people \< 21 years of age were 2.9 (95% Confidence Interval: 1.5-5.8) times higher if amphibians were present in the household, again indicating a potential risk posed by these animal exposures \[[@B265]\]. 5.3. Fish and *Salmonella* -------------------------- Some studies have investigated the prevalence of *Salmonella*among wild, pet or farmed fish in different ecological niches, sometimes with somewhat conflicting results. Gaetner et al. \[[@B288]\], for instance, reported isolating *Salmonella*from 17-33% of fish sampled in the San Marcos river in Texas and Miruka et al. \[[@B289]\] isolated *Salmonella*from approx. 31% of fish samples collected in Lake Victoria, Kenya. Broughton and Walker \[[@B290]\], however, estimated the *Salmonella*prevalence among farmed fresh-water fish in China at approx. 5%, and estimates for fish in retail markets in India have ranged from 10-28% \[[@B291]\]. Clinical disease associated with *Salmonella*infected fish have been described, mainly manifested as septicemia \[[@B292]\]. Yet, fish can also shed *Salmonella*in the absence of clinical signs, and after experimental inoculation of silver carp, shedding has been observed for periods of up to 14 days \[[@B293]\]. Fish feed appears to represent a considerable source of *Salmonella*infection in commercial aquacultures, and frequent bacterial carriage in raw materials paired with insufficient heat treatment appears to be the major driver \[[@B294]\]. ### 5.3.1. The risk associated with contacts to fish A variety of *Salmonella*serotypes have been isolated from free-ranging or captive fish (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1), and *Salmonella*is common in wild and, probably to a lesser extent farmed, fish. Occupational infections have been linked to contacts with contaminated fish, and ornamental fish tanks have also been linked to human *Salmonella*outbreaks (Additional file [2](#S2){ref-type="supplementary-material"}: Table S3). An Australian study, for instance, reported that 82% of human cases during a *Salmonella*Java outbreak had been directly or indirectly exposed to exotic fish tanks, and the outbreak strain was detected in implicated tanks \[[@B295]\]. Surprisingly, clinical disease in fish was observed in a large number of tanks, indicating a high pathogenic potential in the fish \[[@B295]\]. In conclusion, exposure to pet, wild or farmed fish represents a potential risk to humans, but the data available regarding infections acquired through contact with fish is currently scarce. 6. Invertebrates and *Salmonella* ================================= *Salmonella*has been isolated from a large number of insects and worms including ants, flies, cockroaches, mealworms and mosquitoes (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). However, almost nothing is known about the pathogenic potential of *Salmonella*in invertebrates. *Salmonella*-induced mortality in butterflies and *Caenorhabditis elegans*has been described, and it appears likely that *Salmonella*can induce disease in other invertebrates \[[@B296],[@B297]\]. Whether *Salmonella*can survive metamorphosis is equally unclear and results might be partially serotype, environment, and host dependent (see \[[@B298]\] for a review of the topic). In general, *Salmonella*intestinal carriage decreases sharply during pupation, likely due to major changes in the gut environment, and competition with other gut microorganisms such as *Proteus*has been shown to effectively suppress *Salmonella*growth in flies \[[@B298]\]. The public health relevance of insects might therefore depend on the life stage, the breeding environment and the insect species, and some insects apparently represent more competent hosts than others \[[@B298]\]. Insects and worms have been proposed as disease vectors for *Salmonella*on farms, agricultural fields and in households; invertebrates have been associated with *Salmonella*transmissions between animal feeds; biting mites have been shown to efficiently transmit *Salmonella*to chickens, and house flies have been implicated as Typhoid fever vectors in military camps (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). Moreover, insects can represent reservoir hosts, and therefore may play pivotal roles in *Salmonella*persistence. 7. Animal Contact in Public Settings as Source of Human Infection ================================================================= 7.1. Human outbreaks linked to animal contacts in public settings ----------------------------------------------------------------- *Salmonella*has repeatedly been isolated from captive and domestic animals held in public settings. For instance, a Korean study sampling clinically health zoo animals reported isolating *Salmonella*from approx. 6% of animals, including 30% of reptiles, 7% of birds and 1% of mammals \[[@B299]\]. Other studies report the isolation of *Salmonella*Dublin from a clinically healthy tiger at a zoo in the UK, from large cats and rodents in a zoo in India, from rhinoceroses in an animal park in the USA, from a newborn moose and an iguana in a zoo in Canada, from approx. 6.5% of animals in a zoo in Trinidad and from two animals in Swiss petting zoos (Additional file [1](#S1){ref-type="supplementary-material"}: Table S1). *Salmonella*has also been isolated from environmental surfaces in zoological gardens \[[@B300]\]. The health threat is aggravated by risky behaviors. For instance, one recent study found that 87% of visitors in Tennessee petting zoos had contact with potentially contaminated surfaces, and 74% had direct animal contact, but only 38% used hand sanitizer, while 49% had hand-to-face contacts with 22% eating or drinking in animal contact areas \[[@B301]\]. Animal contact in public settings therefore represents another source of human infection, and direct or indirect animal contacts in petting zoos, zoological parks, country fairs, or other settings represent threats to public health \[[@B190]\]. As mentioned above, in 1996, for instance, 65 children became sick after visiting the Denver zoo, due to indirect contact with a Komodo dragon \[[@B270]\]. In 1991, a visit to a science center in Washington was associated with 5 human salmonellosis cases, in 2000, at least 18 people were affected by a *Salmonella*outbreak linked to a petting zoo in Ohio, in 2001, at least 19 salmonellosis cases were linked to animal contact at an agricultural exhibit in Alberta, Canada, in 2003, at least 17 human *Salmonella*cases were linked to contact with a wallaby in a public setting in Michigan, and in 2005, 19 human cases were linked to direct or indirect contact with pigs in a public setting in Wisconsin \[[@B34],[@B302],[@B303]\]. In conclusion, animal contacts in public settings represent a *Salmonella*risk to occupationally exposed subpopulations as well as the general public, but management practices can effectively reduce the risk. To minimize risks, several governmental agencies have passed legislations governing animal exhibitions, and governmental as well as professional organizations have published related recommendations. 7.2. Current legislation and recommendations: case study USA ------------------------------------------------------------ Minimizing the risk of disease transmission in public settings is a major concern for governments and professional organizations around the world. As one example, recommendations and legislation in the USA will be described in the following passage. The USA National Association of State Public Health Veterinarians (NASPHV), in conjunction with the CDC, published recommendations to prevent disease outbreaks in public settings, which are regularly updated. The recommendations are addressed to governmental agencies, educational settings, exhibit managers, veterinarians, caregivers, and visitors at particular risk of infection. The main focuses are on disseminating information, enhancing oversight and outbreak investigations, encouraging good hygiene practices, improving facility design, implementing disease monitoring and prevention systems, and prohibiting high risk contacts. To further address the threat, the CDC, the Association for Professionals in Infection Control and Epidemiology, the Animal-assisted Interventions Working Group and the NASPHV published a number of additional recommendations and the Association for Zoos and Aquariums has developed a certification program. Depending on the animal species, animal exhibits may also be subject to USDA inspections under the Animal Welfare act, but human disease risks are not explicitly addressed in these inspections. In addition, some states have passed additional legislations. For instance, North Carolina requires all animal exhibits with public access to obtain a license, Pennsylvania mandates minimum standards for exhibit sanitation, and Virginia requires a permit for the exhibition of wild animals. The relative effectiveness of these diverse mitigation strategies largely remains to be determined. 8. Conclusions ============== In conclusion, contact with animals is responsible for a number of human salmonellosis cases each year. A number of transmissions occur in the home, but others are occupational or related to public exposures in zoological gardens, schools, or state fairs. Infected animals can present with a great variety of clinical symptoms, and risk factors for transmission to humans clearly differ by animal species, age groups, animal purpose, and geographic region. However, some commonalities are clearly evident. Stress, concomitant disease, and contaminated feed represent universal risk factors for animal infection. Conversely, public awareness and proper hygiene practices are efficient measures to mitigate risks. In fact, frequent hand washing alone could likely prevent a substantial number of human infections each year. However, awareness of the risks is low and the collaboration between governmental agencies, professional organizations and special interest groups is necessary to resolve the problem. In some instances, new legislations or public awareness campaigns have led to dramatic decreases in *Salmonella*incidence. Yet, much remains to be done to safeguard public health and many aspects of *Salmonella*epidemiology remain to be discovered. *Salmonella*serotypes differ in host range and distribution among host species, but our understanding of the molecular and evolutionary determinants of these host range differences is still limited and the public health implications are currently difficult to assess. In summary, the risks associated with animal contacts are diverse and much remains to be uncovered, but we already posses important clues to manage the risks. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= KH, MW and AIMS conceived and outlined the study. KH and AIMS reviewed the pertinent scientific literature and collated references and tables. KH drafted the manuscript. All authors have read and approved the final manuscript. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 **Table S1**. Overview of *Salmonella*serotypes isolated from animals in different geographic regions. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 **Table S2**. Documented reports of Salmonella transmission from birds to humans available in the peer-reviewed literature or otherwise published by public health agencies. **Table S3**. Documented reports of *Salmonella*transmission from reptiles, amphibians fish to humans available in the peer-reviewed literature or otherwise published by public health agencies. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ We thank Dr Kevin Cummings, Cornell University, for helpful comments and suggestions. Support for this project was provided by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract N01-AI-30054-ZC-006-07. K Hoelzer was supported by Morris Animal Foundation Fellowship Training Grant D08FE-403.

PubMed Central

2024-06-05T04:04:18.962435

2011-2-14

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052180/", "journal": "Vet Res. 2011 Feb 14; 42(1):34", "authors": [ { "first": "Karin", "last": "Hoelzer" }, { "first": "Andrea Isabel", "last": "Moreno Switt" }, { "first": "Martin", "last": "Wiedmann" } ] }

PMC3052181

Introduction ============ Mastitis is the first cause of economical loss in milk production worldwide \[[@B1]\] and is a major concern in milk transformation \[[@B2]\]. The problem is however currently hard to tackle for mastitis in dairy cows, sheep and goats. Especially, *S. aureus*mastitis is typically refractory to antibiotic treatment. Prophylactic measures, including the development of an effective vaccine, have so far proven unsuccessful for the control of the disease. *S. aureus*is well-known to produce a large variety of virulence factors (including numerous proteins like toxins or adhesins). Consequently, it induces a large panel of infections, and the clinical acuteness of each infection type may also be variable. For example, *S. aureus*mastitis in dairy sheep ranges from subclinical mastitis to lethal gangrenous mastitis. Such variability relies on staphylococcal virulence factors as well as host factors. Until now, no study has been performed to identify the transcripts and proteins commonly or specifically produced in vivo by *S. aureus*strains during mastitis. To obtain such information using direct transcriptomic or proteomic approaches upon *S. aureus*samples collected within the infection site stumbles on technical bottlenecks such as the low amounts of *S. aureus*cells and the difficulty to localize the infection site within the udder. Serological proteome analysis (SERPA) is a promising technique that can be used to shed light on the host\'s immune response to staphylococcal infection. This technique was used to mine new antigen candidates for vaccine development in human infections \[[@B3]\]. SERPA has also been used to identify proteins produced in vivo, during infection \[[@B4]\]. In combination with whole genome shotgun sequencing, SERPA is a powerful tool to identify immunoreactive proteins produced by *S. aureus*during the infection \[[@B5]\]. Genotyping studies indicated that *S. aureus*strains isolated from dairy sheep farms in the south east of France were clonally related and are predominantly represented by a single pulse-field gel electrophoresis (PFGE) type OV/OV\' \[[@B6],[@B7]\]. Such close phylogenetic relationship was recently confirmed at the global scale using Multi Locus Sequence Typing and comparative genome hybridization \[[@B8],[@B9]\]. Among strains in this OV/OV\' PFGE profile, one was isolated from subclinical mastitis (O46) and another one from gangrenous mastitis (O11). Few genetic differences were identified \[[@B10]\] and their role in the development of mastitis with such different severity has not yet been determined. Moreover identification of the proteins produced by *S. aureus*in mastitis with different severity is an important step to better understand the host-pathogen interactions and to provide targets for the development of efficient prevention or treatment strategies against mastitis. Therefore, we applied SERPA to identify proteins that are produced by both *S. aureus*strains O11 and O46 (core seroproteome) and the ones specifically produced by each strain (\"accessory\" seroproteome). Materials and methods ===================== Bacterial strains, growth conditions and preparation of protein samples ----------------------------------------------------------------------- *S. aureus*strains used in this study are presented in Table [1](#T1){ref-type="table"}. *S. aureus*O46 was isolated from a case of ovine subclinical mastitis and O11 from a gangrenous lethal mastitis \[[@B10]\]. Genetic and genotypic background of *S. aureus*O46 and O11 are well-documented. They share the same pulsotype (OV/OV\') and are representative of the major lineage found associated to ewe mastitis in south east of France \[[@B6],[@B7]\]. Growth conditions and preparation of protein extracts were as described in Le Maréchal et al. 2009 \[[@B11]\]. Briefly, overnight cultures in BHI were diluted 1:1000 in fresh RPMI 1640 medium (Sigma, Saint Quentin Fallavier, France). RPMI was extemporaneously depleted of iron (and hereafter referred to as iron-depleted RPMI) by adding deferoxamine (0.15 mM) (Sigma). Growth conditions in which there is restriction in the bioavailability of iron can indeed lead to an increase of the expression of virulence factors which are normally expressed in vivo \[[@B12]\]. *S. aureus*strains were grown in 500 mL flasks under agitation (150 rpm) at 37 °C (a flask-to-broth volumetric ratio of 5), for aerobic conditions, or in falcon tubes (50 mL) completely filled with medium and incubated at 37 °C without agitation for anaerobic conditions. Protein samples for supernatant, cell wall or total fraction were prepared exactly as previously described \[[@B11]\]. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### *Staphylococcus aureus*strains used in this study ::: Strain Type of mastitis Origin **Isolated in**: ----------- ------------------ ------------------- ------------------ **O11\*** gangrenous south east France 2002 **1628** gangrenous south east France 2010 **1624** clinical south east France 2003 **1625** clinical south east France 2008 **1626** clinical south east France 2008 **1536** clinical south west France 1998 **O46\*** subclinical south east France 2002 **1627** subclinical south east France 2008 **O55** subclinical south east France 2003 **O117** subclinical Corsica. France 2001 **1535** subclinical south west France 1998 **O82** subclinical south east France 2003 \*: O11 and O46 were used for experimental infections and their genome was fully sequenced (see Materials and Methods). ::: Genome sequencing of O11 and O46 strains ---------------------------------------- To facilitate the analysis of SERPA results, the genome of the two strains used in experimental infection was fully sequenced using the Solexa technology (P Mayer, L Farinelli, and E Kawashima, 1997. Patent application WO98/44151) according to the manufacturer\'s protocol (Illumina, San Diego, CA, USA). Briefly, genomic DNA was physically fragmented by nebulization into 50- to 500-bp fragments. After end repair and ligation of the bar-coded paired-end adaptors, the products were purified on agarose gel to recover products with inserts of \~200 bp. Quality control was performed by cloning an aliquot of the library into a TOPO plasmid and capillary sequencing eight clones per library. The samples were then used to generate DNA colonies using one channel of a paired-end flow cell at dilutions of 4 pM. The flow cell was then submitted to 2 × 74 cycles of sequencing on the genome analyzer. Base calling was performed using the GAPipeline 1.4.0 software; a total of 27.6 million reads (pass filter) were obtained. After bar code selection, 13.9 and 11.8 million reads of 71 bases in length were obtained for the strains O11 and O46 respectively. The pool of sequences obtained was analyzed and assembled using the Edena assembler \[[@B13]\], which resulted in a set of 87 and 96 contigs for O11 and O46, respectively. The gene content of each strain (2787 and 2822 Coding Sequences -CDSs- for O11 and O46, respectively) was thus established and used in protein identification after SERPA. Detailed genome analysis of these strains is described elsewhere (Le Maréchal et al., submitted). 2-Dimensional Electrophoresis (2-DE) ------------------------------------ Samples (200 μg of proteins for Coomassie blue staining and 50 μg for Western blotting) were precipitated with 2D clean up kit (GE Healthcare, Orsay, France) according to the manufacturer\'s instructions. Pellets were solubilised in sample solution containing 7 M urea, 2 M thio-urea, 25 mM dithiothreitol (DTT), 4% (w/v) 3-\[(3-Cholamidopropyl)dimethylammonio\]-1-propane-sulfonate (CHAPS) and 2% (w/v) ampholyte containing buffer (IPG-Buffer 4-7 or 3-10 NL, GE Healthcare). Isoelectric focusing was carried out using pH 4 to 7 (Cell wall and total proteins) or 3 to 10 NL (exoproteins) 13 cm Immobiline Dry Strips on a Multiphor II electrophoresis system (Amersham Biosciences; GE Healthcare, Orsay, France) for a total of 60 kVh using a standard procedure described previously \[[@B14]\]. The second dimensional separation was performed on the Ettan™ DALTtwelve electrophoresis system (GE Healthcare) using 14% acrylamide separating gels without a stacking gel at a voltage of 50 V for 1 h and 180 V for about 7 h. Kaleidoscope Prestained Standards (Biorad) were used as standard. Gels were transferred onto membrane or stained with R250 Coomassie blue (Serva, Heildelberg, Germany) or MS-compatible silver nitrate (Sigma) \[[@B15]\]. Intramammary challenge with *S. aureus*in ewes ---------------------------------------------- Experimental mastitis was performed according to the Regional Committee for Animal Use and Care (Côte d\'Azur, France) and is recorded under reference NCA/2008-14/12-09. Healthy lactating primiparous ewes of Lacaune breeds were selected based on the absence of intramammary infections and milk somatic cell counts below 100 000 cells/mL. Repeated full bacteriological analysis of milk from the two quarters that were going to be infected showed that the ewes were negative for *Staphylococcus*sp. and *Mycoplasma*sp. Absence of nasal carriage for staphylococci was also checked after enrichment and culturing of swab samples of the nares of ewes on selective media, as described previously \[[@B6]\]. At D0, 12 ewes were divided into 2 groups and urethral catheters (Portex^®^Jackson Cat Catheter, Coveto, France) were inserted into the teat canal after a thorough disinfection of the teat orifice with 70% ethanol. 1 mL PBS containing 20 CFU of *S. aureus*(O11 or O46) was injected through the catheter, which was removed afterwards. Six ewes were thus infected by strain O11 (group O11) and six by strain O46 (group O46). Severity of the mastitis induced in ewes was estimated according to criteria presented in Additional file [1](#S1){ref-type="supplementary-material"}, Table S1. Mastitis was classified as subclinical, clinical, pyogenic and gangrenous. Classification was based on clinical symptoms, presence of *S. aureus*cells and Somatic Cell Count (SCC) in milk. Sample processing ----------------- Sera from ewes were prepared from blood samples collected aseptically from the jugular vein of the animals at D0, D7, D14, D21 and D28 post inoculation (pi). Briefly, blood samples were kept for 2 h at room temperature before centrifugation. Sera were then stored at -20°C. Milk samples were taken 24 and 36 h pi for bacteriological examination and determination of SCC. Milk was 1/10 diluted and 100 μL of this dilution was plated on selective Rabbit Plasma Fibrinogen Baird-Parker medium to confirm *S. aureus*presence in the mammary gland. SCC was measured with the Fossomatic method \[[@B16]\] to follow the onset of the infection. Western blot analysis --------------------- Total cell lysates were prepared as previously described \[[@B11]\]. Total protein extracts of *S. aureus*strains O11 and O46 were separated by SDS-PAGE on 12% acrylamide separating slab gels (70 × 100 × 0.5 mm), with a 4% acrylamide stacking gel on a mini-protean III gel system (BioRad, Ivry sur Seine, France) according to Laemmli \[[@B17]\]. Protein migration was performed for 2 h at room temperature at constant 80 V voltage. Samples were diluted in sample buffer and denatured at 100 °C for 3 min. Gels were transferred onto a PVDF membrane (GE Healthcare) at constant 250 mA amperage in Towbin transfer buffer \[[@B18]\] using a Trans-Blot cell (Biorad) for 1.25 h. Membranes were washed three times with Tris Buffered Saline (TBS) at pH 7.5 and saturated in blocking solution (3% non-fat dry milk in TBS with 0.3% Tween 20 (TBS-T)) at 4 °C overnight. After saturation in blocking solution, membranes were washed 3 × 10 min with TBS-T and exposed to the different ewe sera used as primary antibody for 4 h at room temperature. After washing, membranes were incubated with alkaline phosphatase conjugated anti-sheep IgG (Sigma) diluted 1:15,000 in 25 mL blocking solution for 1 h and finally BCIP/NBT (Sigma) was used to visualize immunoreactive proteins, according to the manufacturer\'s instructions. Selection of the hyper-immune sera ---------------------------------- Sera samples were analysed by western blotting as described above. Sera sampled on D0, D7, D14, D21 and D28 pi were compared using the mini-protean II Multiscreen apparatus (Biorad) (600 μL of serum diluted 1:10,000 in blocking solution). Immunostained Western blots were scanned using an Image Scanner II (Amersham biosciences) and further analyzed using Image- Quant 1D software. The number, volume and area of bands were taken into account for the analysis. Optimal dilution for the selected sera was determined as described above. Sera and dilutions yielding the best ratio signal/background were selected. Identification of immunoreactive proteins ----------------------------------------- Bacterial proteins separated by 2-DE were transferred onto a PVDF membrane (GE Healthcare) as described above. Series of four gels were migrated and treated in parallel. Three gels were used for immunoblotting, and the fourth one was Coomassie blue-stained for spot matching and further identification. After saturation in blocking solution the membranes were treated with selected sera in blocking solution during 4 h. Then, the membranes were washed with TBS-T and incubated with alkaline phosphatase conjugated anti-sheep IgG (Sigma) diluted 1:15 000 in 25 mL blocking solution for 1 h. Finally BCIP/NBT (Sigma) was used to visualize immunoreactive proteins, according to the manufacturer\'s instructions. Membranes were scanned using an Image Scanner II (Amersham biosciences) and further analyzed using Image- Master 2D software. Immunoblot profiles for 2-DE-separated proteins were reproducible in at least two individual experiments. Images of the 2D electrophoresis gels and the BCIP-NBT treated membranes were compared to detect immunoreactive proteins. Spots that were absent or had a significantly different intensity in one strain were considered as proteins that differed between O11 and O46. Spots corresponding to proteins of interest were excised and identified using Nano-Liquid Chromatography (Nano-LC) MS/MS analysis. Nano-LC MS/MS analysis ---------------------- Proteins were identified by tandem mass spectrometry (MS/MS) after an in-gel trypsin digestion adapted from Shevchenko \[[@B19]\]. Briefly, gel pieces were excised from the gel, washed with acetonitrile and ammonium bicarbonate solution, and then dried under vacuum in a SpeedVac concentrator (SVC100H-200; Savant, Thermo Fisher Scientific, Waltham, MA, USA). In-gel trypsin digestion was performed overnight at 37 °C and stopped with spectrophotometric-grade trifluoroacetic acid (TFA) (Sigma-Aldrich). The supernatants containing peptides were then vacuum dried in a Speed-Vac concentrator and stored at -20 °C until mass spectrometry analysis. Nano-LC experiments were performed using an on-line liquid chromatography tandem mass spectrometry (MS/MS) setup using a Dionex U3000-RSLC nano-LC system fitted to a QSTAR XL (MDS SCIEX, Ontario, Canada) equipped with a nano-electrospray ion source (ESI) (Proxeon Biosystems A/S, Odense, Denmark). Samples were first concentrated on a PepMap 100 reverse-phase column (C18, 5 μm, 300-μm inner diameter (i.d.) by 5 mm length) (Dionex, Amsterdam, The Netherlands). Peptides were separated on a reverse-phase PepMap column (C18, 3 μm, 75 μm i.d. by 150 mm length) (Dionex) at 35 °C, using solvent A (2% (vol/vol) acetonitrile, 0.08% (vol/vol) formic acid, and 0.01% (vol/vol) TFA in deionized water) and solvent B (95% (vol/vol) acetonitrile, 0.08% (vol/vol) formic acid, and 0.01% (vol/vol) TFA in deionized water). A linear gradient from 10 to 50% of solvent B in 40 min was applied for the elution at a flow rate of 0.3 μL/min. Eluted peptides were directly electrosprayed into the mass spectrometer operated in positive mode. A full continuous MS scan was carried out followed by three data-dependent MS/MS scans. Spectra were collected in the selected mass range 400 to 2 000 *m/z*for MS and 60 to 2 000 *m/z*for MS/MS spectra. The three most intense ions from the MS scan were selected individually for collision-induced dissociation (1+ to 4+ charged ions were considered for the MS/MS analysis). The mass spectrometer was operated in data-dependent mode automatically switching between MS and MS/MS acquisition using Analyst QS 1.1 software. The instrument was calibrated by multipoint calibration using fragment ions that resulted from the collision-induced decomposition of a peptide from β-casein, β-CN (193-209). The proteins present in the samples were identified from MS and MS/MS data by using MASCOT v.2.2 software for search into two concatenated databases: (i) a homemade database containing all the predicted proteins of the *S. aureus*strains O11 and O46 used in this study and (ii) a portion of the UniProtKB database corresponding to the *S. aureus*taxonomic group \[[@B20]\]. Search parameters were set as follows. A trypsin enzyme cleavage was used, the peptide mass tolerance was set to 0.2 Da for both MS and MS/MS spectra, and two variable modifications (oxidation of methionine and deamidation of asparagine and glutamine residues) were selected. For each protein identified in NanoLC-ESI-MS/MS, a minimum of four peptides with MASCOT score corresponding to a *P*value below 0.05 or an Exponentially Modified Protein Abundance Index \[[@B21]\] greater than 0.4 were necessary for validation with a high degree of confidence. For automatic validation of the peptides from MASCOT search results, the 1.19.2 version of the IRMa software was used \[[@B22]\]. Intramammary infection with *S. aureus*in mice ---------------------------------------------- The animal study was conducted according to current Good Scientific Practice-principles (2000) and approved by the Ethical Committee of the Faculty of Veterinary Medicine, Ghent University (Belgium). Sixteen CD-1 lactating female mice (Harlan Laboratories Inc., Horst, The Netherlands) were used 12-14 days after birth of the offspring. The pups were removed 1 to 2 h before bacterial inoculation of mammary glands and a mixture of ketamine/xylazine was used for anesthesia of the lactating mice. The orifice of both L4 (on the left) and R4 (on the right) abdominal mammary glands was exposed by a small cut at the near end of the teat. 100 μL PBS without (*n*= 2) or with 150 CFU of *S. aureus*strain O11 (*n*= 7) or O46 (*n*= 7) was injected slowly with a 32-gauge blunt needle through the teat canal. Rectal body temperature of the mice was measured at 0 h and 18 h pi. At 18 h pi mice were anesthetized with ketamine/xylazine to collect blood by cardiac puncture and serum was obtained after clotting at 37 °C and cold centrifugation. After cardiac puncture, mice were euthanized by cervical dislocation and mammary glands were isolated. Glands of six mice of each group were homogenated and bacterial CFU was quantified by plating serial logarithmic dilutions in PBS. Lysates from the homogenates were prepared in 1% NP40-based buffer. Serum and mammary gland lysates were quantified for IL-1β, IL-6, TNF, KC and MCP-1 using BD^™^Cytometric Bead Array technology. Mammary glands (inoculated and PBS control glands) of 4 mice (2 from each group) were embedded and used for further histopathological analysis (Vetopath, Antibes, France). Statistical analyses -------------------- A Fisher test was used with a risk α = 10% to determine the difference between the ewes infected with *S. aureus*O11 and the ewes infected with strain O46. Differences in rectal body temperature and cytokine levels in the mouse mastitis model were analyzed with the unpaired *T*-test. *P*\< 0.05 was considered statistically significant. Results ======= Ewes infected with O11 or O46 *S. aureus*strains developed mastitis with different severities --------------------------------------------------------------------------------------------- Although O11 and O46 strains share the same genotype and are highly genetically similar \[[@B10]\], they were isolated from dramatically different ewe mastitis episodes. One can thus wonder whether the clinical signs associated with O11 and O46 infection were or not related to strains characteristics or a fortuitous matter of sampling time (mastitis can indeed evolve from subclinical to severe clinical or even gangrenous within a few days). To check this, two groups of ewes were infected either with O11 or O46 *S. aureus*strains, as described in the previous section. Onset of the symptoms was followed up during the course of the experiment. All animals became infected and signs of mastitis were evident in most ewes as soon as 24 h pi. The animals shed the *S. aureus*strains over the sampling period and remained infected for the duration of the experiment. Shedding from the infected glands varied and *S. aureus*load in milk ranged from 10 CFU/mL to 3.16 × 10^8^CFU/mL, depending on the individual ewe, and on the day pi (not shown). Symptoms evoked by intramammary inoculation varied among ewes. In group O11, five out of six ewes developed a gangrenous mastitis, the last one developed a pyogenic mastitis according the criteria defined in Additional file [1](#S1){ref-type="supplementary-material"}, Table S1. In group O46, symptoms were more heterogeneous and mastitis cases were classified in subclinical mastitis (*n*= 1), pyogenic mastitis (*n*= 2), mild clinical mastitis (*n*= 2) and gangrenous mastitis (*n*= 1). Subclinical mastitis was determined with the presence of bacteria (250 CFU/mL of milk 36 h pi), a raise in SCC (\> 200 000 cells/mL in each milk sample after 24 h) and absence of fever or symptoms. Except for the ewe with subclinical mastitis, bacteria were detected in all milk samples and reached more than 10^6^CFU/mL 36 h pi. All animals had fever (above 40 °C 36 h pi) and SCC increased quickly and was above 10^6^cells/mL at 36 h pi. The proportion of the gangrenous mastitis was significantly higher in the group of ewes infected with O11 strain compared to the group infected with O46 (*p*= 0.08) (Additional file [2](#S2){ref-type="supplementary-material"}, Figure S1). *S. aureus*O11 and O46 induce dramatically different clinical features in infected mice. To confirm our observation that *S. aureus*strains O11 or O46 induce different types of mastitis, the mouse mastitis model was employed in the current study. Strains O11 and O46 grew equally well in the infected mouse mammary glands and induced mastitis, as determined by temperature measurement (hypothermia in O11 group and hyperthermia in O46 group, 24 h pi; Additional file [3](#S3){ref-type="supplementary-material"}, Figure S2) and histopathological analysis: polymorphonuclear neutrophils (PMN) infiltration was observed only in infected (either with O11 or O46 strains) mammary gland tissue (not shown). To analyse the role of each strain in the development of mastitis, cytokine profile of the serum and mammary gland tissue lysates of mice infected with O11 strain was compared to those infected with O46 strain. The results of cytokine quantification showed that mice infected with *S. aureus*O46 had significantly higher IL-1β and TNF levels in the mammary gland lysates and significantly higher systemic (serum) levels of IL-1β and MCP-1 (Additional files [4](#S4){ref-type="supplementary-material"} and [5](#S5){ref-type="supplementary-material"}, Figures S3 and S4). Altogether, these results demonstrate that despite their close genetic relationships, *S. aureus*O11 and O46 reproducibly induced mastitis with significantly different clinical signs. Antibody production in response to infection of ewes with *S. aureus*strains O11 or O46 --------------------------------------------------------------------------------------- To compare the relative level of antibodies developed in response to *S. aureus*presence in the mammary gland, serum sampled on D0, D7, D14, D21 and D28 pi were analysed by Western blotting using either O46 or O11 total bacterial extracts as described in the previous section. The number of bacterial proteins recognised by sera and signal intensity increased from D0 to D28 for both O11 and O46 samples (Figure [1](#F1){ref-type="fig"}). The intensity of the signal revealed with sera collected on D0 was low and much weaker compared to those obtained with sera collected on D21 or D28. Western blots membranes were analysed as described in the previous section. Sera collected either on D21 or D28 were selected for further analysis. Sera yielding the best signals in each group (one sample for each of the six ewes) were pooled to be used in SERPA experiments. Two pools were thus obtained: sera from ewes infected with O11 and sera from ewes infected by O46, hereafter referred to as group O11 sera and group O46 sera, respectively. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Western blot analysis of total lysates of *S. aureus*O11 (left panel) or *S. aureus*O46 (right panel) using D0, D7, D14, D21, D28 diluted 1:10,000 sera of ewes infected by O11 and O46**. Bacteria were grown in iron-depleted RPMI without aeration to late exponential phase. Protein samples were prepared from total cell, submitted to 1-DE, western blotted on PVDF membrane and revealed using each of the 6 serum samples collected on ewes infected in each group. One representative example is given for each group of infected ewes (with O11 or O46). ::: ![](1297-9716-42-35-1) ::: Detection and identification of immunogenic staphylococcal proteins by SERPA ---------------------------------------------------------------------------- Protein samples were prepared from O11 and O46 strains grown in conditions that best mimic the mastitis context \[[@B11]\]. Each fraction (total, cell wall and supernatant) of O11 and O46 culture was immunoblotted using either group O11 or group O46 sera. Altogether, 89 proteins were identified as immunoreactive (Table [2](#T2){ref-type="table"}). Comparison of SERPA results (see Figure [2](#F2){ref-type="fig"}, and Additional files [6](#S6){ref-type="supplementary-material"} and [7](#S7){ref-type="supplementary-material"}, Figures S5 and S6) on the three fractions analyzed showed that immunoreactive proteins were mainly identified in supernatant samples prepared from aerobic and anaerobic cultures (Figure [2](#F2){ref-type="fig"} and Additional file [7](#S7){ref-type="supplementary-material"}, Figure S6) and cell wall samples (Additional file [6](#S6){ref-type="supplementary-material"}, Figure S5, upper panels) whereas total protein samples were poorly recognized (Additional file [6](#S6){ref-type="supplementary-material"}, Figure S5, lower panels). A vast majority of the immunoreactive proteins are thus found in supernatant and cell wall fractions (88.7%), and only 11.3% are found in the total fractions (Figure [3A](#F3){ref-type="fig"}). Of note, secreted and surface proteins are expected to be exposed to the host immune system. The predicted location of the proteins (according to the SurfG+ analysis of O11 and O46 genome sequences) \[[@B23]\], showed that the immunoreactive proteins were mainly predicted cytoplasmic (52.8%) (Figure [3A](#F3){ref-type="fig"}). Proteins were classified into categories based on functional annotation (Figure [3B](#F3){ref-type="fig"}). Most immunogenic proteins identified here are found in various functional categories involved in cellular machinery and metabolism; while 20% were virulence factors and virulence associated proteins. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Proteins identified in this study. ::: Description^1^ Spots^2^ O11 CDS^3^ O46 CDS^3^ ED133 CDS^3^ pI^4^ Mass (Da)^5^ Score^6^ Cov.^7^ \#pep.^8^ EmPAI^9^ Comp.^10^ Loc.^11^ Immun.^12^ ------------------------------------------------------------------------- --------------------------------------------------------------- --------------- --------------- ----------------- ---------- -------------- ------------- ----------- ----------- ----------- ----------- ---------- ------------------------------------------------------------ **Metabolism** ***Energy production and conversion*** formate acetyltransferase 81, 83, 82 011\_0041 046\_0511 SAOV\_0163 5,31 84808 1301,60 34,31 22 1,57 CW C ldh L-lactate dehydrogenase 82, 99, 81, 83, 95 011\_0136 046\_0198 SAOV\_2646c 4,80 34389 1749,37 63,64 26 21,75 CW C \[[@B82]\] **L-LACTATE DEHYDROGENASE (O11)** **64** **011\_0021** **046\_0531** **SAOV\_0178** **5,00** **34548** **745,83** **50,79** **14** **2,59** **S** **C** \[[@B82]\] bifunctional acetaldehyde-CoA/alcohol dehydrogenase 79 011\_0796 046\_0709 SAOV\_0095 5,68 94945 2090,64 45,45 33 2,26 CW C D-3-phosphoglycerate dehydrogenase 100 011\_0585 046\_1131 SAOV\_2344 5,32 34652 717,85 43,53 11 1,72 CW C atpD F0F1 ATP synthase subunit beta 62, 90 011\_2064 046\_0898 SAOV\_2144c 4,68 51368 631,03 30,21 10 0,98 S,CW C \[[@B83]\] ***Nucleotide transport and metabolism*** adk adenylate kinase 9 011\_0510 046\_1206 SAOV\_2266c 4,80 23375 531,72 42,38 9 2,80 S C \[[@B84]\] deoD purine nucleoside phosphorylase 9 011\_1051 046\_0577 SAOV\_2178 4,85 25892 470,94 53,39 8 1,97 S C \[[@B4]\] guaB inositol-monophosphate dehydrogenase 102, 129 011\_0077 046\_0960 SAOV\_0412 5,61 52818 1237,95 54,30 20 3,52 CW,T C \[[@B4]\] ***Carbohydrate transport and metabolism*** gpmA 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 131 011\_1952 046\_0264 SAOV\_2463c 5,23 26663 271.65 30.26 5 0.80 S,T C eno enolase 2-phosphoglycerate dehydratase 62, 88, 90, 96, 137 011\_2336 046\_2241 SAOV\_0818 4,55 47088 1868,52 63,59 25 7,09 S,CW,T C \[[@B4],[@B52],[@B85]-[@B87]\] fda fructose-1,6-bisphosphate aldolase 107, 94, 72, 91, 95 011\_0131 046\_0202 SAOV\_2650 5,06 32878 852,09 46,62 13 2,48 CW,S C \[[@B85]-[@B88]\] gap glyceraldehyde-3-phosphate dehydrogenase 99, 57, 81, 82, 83 011\_2340 046\_2237 SAOV\_0814 4,89 36258 940,06 46,13 13 3,04 CW,S C \[[@B82],[@B86],[@B87],[@B89],[@B90]\] putative translaldolase 9 011\_1872 046\_2451 SAOV\_1765 4,72 25689 554,11 46,84 10 3,32 S C tpiA triosephosphate isomerase 9 011\_2338 046\_2239 SAOV\_0816 4,81 27271 1396,16 76,28 21 16,78 S C \[[@B4],[@B91],[@B92]\] atl autolysin 23, 31 011\_1991 046\_0320 SAOV\_0999c 9,59 136983 2567,68 42,14 42 1,87 S S \[[@B52],[@B76],[@B93]\] pyk pyruvate kinase 105 011\_1282 046\_0580 SAOV\_1685 5,23 63067 271,45 11,62 5 0,29 CW C \[[@B94]\] ***Lipid metabolism*** fabZ 3R-hydroxymyristoyl ACP dehydratase 126 011\_2356 046\_1839 SAOV\_2140c 5,71 16071 86,65 13,70 2 0,47 T C acetoin reductase 106 011\_1332 046\_1393 SAOV\_0074 5,04 27199 566,84 40,31 7 1,82 CW C ***Amino acid transport and metabolism*** dipeptidase PepV 62 011\_1904 046\_1329 SAOV\_1737 4,56 52762 235.33 10.66 4 0,27 S C **CYSTEINE SYNTHASE (O11)** **64** **011\_1382** **046\_2402** **SAOV\_0535** **5,38** **32955** **266.80** **28.71** **5** **0,61** **S** **C** **Information storage and processing** ***Translation, ribosomal structure and biogenesis*** fus elongation factor G 95 011\_0401 046\_1769 SAOV\_0582 4,80 76564 2173,77 68,11 30 4,11 CW C \[[@B3],[@B90]\] prs 50S ribosomal protein L25/general stress protein Ctc 94 011\_1370 046\_2414 SAOV\_0523 4,39 23773 384,17 34,56 6 2,26 CW,S C \[[@B95]\] rplC 50S ribosomal protein L3 131 011\_0531 046\_1185 SAOV\_2287c 9,72 22648 482,78 42,11 9 2,95 T C \[[@B95]\] rpsA 30S ribosomal protein S1 137, 62, 121, 171 011\_2142 046\_1743 SAOV\_1482 4,51 43252 1555,46 71,36 23 6,25 S,CW,T C \[[@B39],[@B95]\] rpsD 30S ribosomal protein S4 139 011\_1260 046\_1365 SAOV\_1706 10,02 22999 428,22 40,50 8 1,96 T C \[[@B95]\] rplB 50S ribosomal protein L2 91 011\_0528 046\_1188 SAOV\_2284c 10,77 30136 239,93 25,27 5 0,69 CW C \[[@B95]\] tsf elongation factor Ts 100, 64 011\_0909 046\_0755 SAOV\_1259 5,05 32474 436,02 31,06 7 0,97 CW,S C \[[@B4],[@B86],[@B93],[@B96]\] tuf elongation factor Tu 90, 88, 96, 10, 122, 137, 149, 81, 82, 83, 95 011\_0402 046\_1768 SAOV\_0583 4,74 43077 2665,48 84,26 38 52,14 S,CW,T C \[[@B3],[@B52],[@B82],[@B85],[@B86],[@B90],[@B93],[@B96]\] yfiA ribosomal subunit interface protein 106 011\_2483 046\_1255 SAOV\_0789 5,25 21511 376,75 35,33 6 1,76 CW C aspS aspartyl-tRNA synthetase 63 011\_2454 046\_2303 SAOV\_1627 4,99 66584 233,90 7,65 4 0,21 S C alaS alanyl-tRNA synthetase 82 011\_2466 046\_2291 SAOV\_1616 5,00 98604 442,31 11,74 8 0,30 O C \[[@B97]\] ***Transcription*** nusA transcription elongation factor NusA 62 011\_0919 046\_0765 SAOV\_1268 4,60 43701 247,74 11,00 4 0,34 S C ***DNA replication, recombination and repair*** dnaN DNA polymerase III subunit beta 90 011\_1166 046\_1471 SAOV\_0002 4,66 41888 706,28 45,62 11 1,30 CW C nuc staphylococcal thermonuclease precursor 151, 108, 5, 153, 206, 207, 217 011\_2070 046\_2528 SAOV\_0832 9,20 25089 967,00 50,00 20 14,46 S,CW PSE \[[@B98]\] ruvA Holliday junction DNA helicase 66 011\_2442 046\_2315 SAOV\_1639 5,77 22249 137,72 17,00 3 0,52 S C ***Posttranslational modification, protein turnover, chaperones*** ahpC alkyl hydroperoxide reductase subunit C 67, 82, 83, 99, 95 011\_0085 046\_0968 SAOV\_0404c 4,88 20963 667,36 56,08 11 4,95 S,CW C \[[@B93]\] **AhpF ALKYL HYDROPEROXIDE REDUCTASE SUBUNIT F (O11)** **97, 86** **011\_0086** **046\_0969** **SAOV\_0403c** **4,68** **54655** **2242,14** **67,06** **34** **9,91** **CW** **C** dnaK chaperone protein 96, 173, 137 011\_2230 046\_2216 SAOV\_1580 4,63 46021 2907,83 80,29 43 24,66 S,CW,T C \[[@B90],[@B96],[@B99]\] peptidyl-prolyl cis-isomerase 212, 1, 68, 91 011\_2089 046\_2477 SAOV\_1837 9,01 35602 574,32 31,56 11 1,66 S,CW PSE tig trigger factor 105 011\_1304 046\_0602 SAOV\_1664 4,34 48565 1061,87 61,43 17 2,25 CW C \[[@B94]\] **TrxB THIOREDOXIN REDUCTASE (O11)** **64** **011\_2580** **046\_2228** **SAOV\_0801** **5,21** **33595** **681,95** **33,76** **11** **1,81** **S** **C** \[[@B93]\] **Cellular processes** ***Cell envelope biogenesis, outer membrane*** **IsaA IMMUNODOMINANT ANTIGEN A (O46)** **185, 8, 161, 186, 9, 164, 189** **011\_0168** **046\_0166** **SAOV\_2614c** **5,91** **24219** **1516,56** **59,23** **22** **40,99** **S** **S** \[[@B3],[@B75]\] isdA iron-regulated cell wall-anchored protein 31, 27, 73, 74, 75, 83, 118, 79, 81, 82, 95 011\_1476 046\_1296 SAOV\_1125c 8,69 70445 2288,12 57,87 38 6,04 S,CW PSE \[[@B100]-[@B102]\] isdB cell surface transferrin-binding protein 212, 211, 210, 208, 193, 156, 138, 110, 70, 86, 131, 156, 193 011\_1477 046\_1295 SAOV\_1126c 9,54 39197 886,30 45,48 15 4,45 S,CW,T PSE \[[@B54],[@B100],[@B103]\] **IRON-REGULATED SURFACE DETERMINANT PROTEIN H (O11)** **55, 31** **011\_1248** **046\_1353** **SAOV\_1717** **5,05** **100650** **2209,72** **42,11** **37** **2,58** **S** **PSE** \[[@B75]\] IsdD iron-regulated protein 15, 16 011\_1480 046\_1292 SAOV\_1128 8,51 41357 278,05 15,36 5 0,47 S PSE ***Cell motility and secretion*** N-acetylmuramoyl-L-alanine amidase 52, 51, 187 011\_1090 046\_1546 SAOV\_2693 5,87 69226 3097,93 71,57 43 16,52 S S \[[@B57],[@B75],[@B76]\] ***Inorganic ion transport and metabolism*** nasE assimilatory nitrite reductase 10 011\_1932 046\_0245 SAOV\_2445c 4,95 11430 126,05 23,08 2 0,70 S C mntC Manganese/iron transport system substrate-binding protein 94 011\_2274 046\_0062 SAOV\_0666c 8,68 34719 1183,08 51,46 20 10,68 S,CW PSE sirA iron-regulated lipoprotein 135, 64 011\_1345 046\_1405 SAOV\_0062 9,20 36735 609,79 35,45 11 1,58 S,T PSE \[[@B104]\] fhuD2 ferrichrome-binding protein 91 011\_0566 046\_1150 SAOV\_2323c 9,16 33990 406,75 30,13 8 1,10 CW PSE \[[@B105]\] ferrichrome ABC transporter lipoprotein 91 011\_1857 046\_1674 SAOV\_2224c 9,44 36751 600,45 38,41 11 1,57 CW PSE ***Signal transduction mechanisms*** SA1540 GAF domain-containing protein 10 011\_1261 046\_1366 SAOV\_1705 5,09 17042 139,34 22,73 3 0,72 S C Universal stress response protein 7, 123 011\_1269 046\_1374 SAOV\_1697 5,60 18463 973,68 78,31 12 19,34 S,CW C \[[@B106]\] **Toxins and haemolysins** beta-hemolysin 15, 19, 205 011\_1750 046\_2394 SAOV\_2040 8,75 37386 1308,79 61,03 20 4,92 S S \[[@B57],[@B107]\] hla alpha-hemolysin precursor 13, 1, 15, 19, 21, 68, 72, 107, 146, 153 011\_1514 046\_1259 SAOV\_1161c 8,87 36329 2238,72 76,71 34 44,90 S,CW,T S \[[@B93],[@B107]\] hlgC gamma-hemolysin component C 68, 1 011\_1956 046\_0268 SAOV\_2469 9,29 35562 765,07 31,43 12 1,90 S,CW S \[[@B57]\] **Virulence/defence mechanisms** **Sbi IGG-BINDING PROTEIN SBI (O11)** **216, 217, 212** **011\_1954** **046\_0266** **SAOV\_2466** **9,38** **49998** **984,16** **41,74** **18** **2,80** **S** **S** \[[@B76]\] **SspB CYSTEINE PROTEASE PRECURSOR (O11)** **58, 57, 64, 182, 215** **011\_2154** **046\_0327** **SAOV\_0993c** **5,45** **42714** **2027,86** **65,52** **30** **11,52** **S** **S** \[[@B4]\] SplF serine proteinase 4 011\_0672 046\_2496 SAOV\_1795 9,36 25638 255,88 23,01 5 0,84 S S \[[@B108]\] lukD leukotoxin D subunit 1 011\_0685 046\_2484 SAOV\_1812 9,14 36936 365,37 22,02 7 0,98 S S \[[@B109]\] lukE leukotoxin E subunit 1, 68 011\_0686 046\_2483 SAOV\_1813c 9,38 34126 451,11 17,65 7 1,77 S,CW S \[[@B109]\] leukocidin chain lukM precursor 68, 1, 120, 145, 177, 194, 201, 202, 94 011\_1215 046\_2777 SAOV\_1909 9,41 35054 2504,69 71,43 35 29,80 S,CW,T S \[[@B58],[@B110]\] leukocidin F subunit 16, 70 011\_1752 046\_1972 SAOV\_2041 8,29 38639 1154,65 45,27 19 11,64 S,CW S \[[@B58],[@B110]\] leukocidin S subunit 199, 5, 70, 108, 109, 197, 200, 211 011\_1753 046\_1973 SAOV\_2042 9,38 40379 1399,91 55,56 23 6,70 S,CW S \[[@B58],[@B110]\] Panton-Valentine leukocidin LukF-PV chain precursor 1, 68, 70, 15, 31, 119, 195, 203, 204, 10, 91 011\_1216 046\_2776 SAOV\_1908 9,16 36496 965,38 50,31 15 3,37 S,CW S \[[@B58],[@B110]\] plc 1-phosphatidylinositol phosphodiesterase 11, 12, 19 011\_1424 046\_1419 SAOV\_0049 7,12 37030 2759,20 71,95 44 84,00 S S \[[@B4]\] **Aur ZINC METALLOPROTEINASE AUREOLYSIN (O11)** **220, 63** **011\_1083** **046\_1553** **SAOV\_2686c** **4,98** **54947** **921,93** **47,39** **17** **1,68** **S** **C** \[[@B76],[@B111]\] **Opp1A OLIGOPEPTIDE TRANSPORTER SUBSTRATE BINDING PROTEIN (O11)** **86** **011\_2424** **046\_2102** **SAOV\_2517c** **8,33** **59224** **1398,01** **47,53** **24** **3,28** **CW** **PSE** **SspA GLUTAMYL ENDOPEPTIDASE SERINE PROTEASE (O11)** **56, 184, 214** **011\_2155** **046\_0325** **SAOV\_0994c** **4,68** **32250** **1575,55** **69,26** **24** **24,18** **S** **C** \[[@B57]\] **SECRETED VON WILLEBRAND FACTOR-BINDING PROTEIN (O11)** **22** **011\_2679** **046\_0987** **SAOV\_2051c** **8,39** **57935** **1122,89** **36,67** **17** **1,70** **S** **S** epidermal cell differentiation inhibitor B 208, 209, 193, 156, 4 011\_0489 046\_2741 9,51 27969 1385,18 69,32 22 22,31 S S **Miscellaneous** adhA alcohol dehydrogenase 100 011\_1554 046\_0086 SAOV\_0640 5,34 36025 1167,82 66,37 16 4,30 CW C \[[@B87],[@B93]\] exported secretory antigen precursor 67 011\_0584 046\_1132 SAOV\_2343 5,77 17388 397,17 33,13 5 1,43 S S lip triacylglycerol lipase precursor 31, 27 011\_1119 046\_1518 SAOV\_2721c 8,13 76637 1723,17 50,95 29 2,36 S S \[[@B93]\] mqo malate:quinone oxidoreductase 128 011\_0130 046\_0203 SAOV\_2651c 6,12 55964 1047,99 46,79 17 2,50 T C putative staphylococcal enterotoxin 151 011\_0097 046\_0981 SAOV\_0394 9,54 23311 173,20 18,72 4 0,71 S S **Unknown** **HYPOTHETICAL PROTEIN (O11)** **220** **011\_0736** **046\_1969** **SAOV\_0454** **4,89** **56229** **823,11** **39,40** **14** **1,21** **S** **S** hypothetical protein (Similar to truncated map-w protein (91%)) 88, 10, 62 011\_1749 046\_2393 9,91 53686 899,64 34,52 18 2,09 S,CW S \[[@B112]\] hypothetical protein (Similar to beta-lactamase (84%)) 10 011\_0679 046\_2490 6,84 20800 726,52 47,15 10 7,09 S S **HYPOTHETICAL PROTEIN (O46)** **157, 160, 175, 189, 193** **011\_0490** **046\_2740** **8,88** **30854** **2343,27** **74,29** **41** **65,07** **S** **S** hypothetical protein (Similar to probable glutamyl-endopeptidase (76%)) 66 011\_0488 046\_2742 5,44 20552 741,93 47,62 12 5,11 S C **SA0570 HYPOTHETICAL PROTEIN (O46)** **219,154, 127** **011\_2290** **046\_0078** **SAOV\_0649** **9,17** **18554** **815,59** **69,05** **13** **15,93** **S,CW** **S** SA0663 hypothetical protein 10, 164, 94 011\_2561 046\_2636 SAOV\_0742c 9,15 16047 457,11 35,62 8 3,63 S PSE SA0914 hypothetical protein 6 011\_2000 046\_0311 SAOV\_1008c 6,55 11338 522,48 57,14 8 13,10 S S pathogenicity island protein 55 011\_2741 046\_0985 SAOV\_0429 9,55 12071 204,61 19,64 3 1,12 S S SA1607 hypothetical protein 91 011\_1867 046\_2456 SAOV\_1770 6,04 34973 232,41 16,56 4 0,43 CW S SA1402 hypothetical protein 91 011\_2223 046\_2209 SAOV\_1573 5,60 35160 448,93 28,27 6 0,72 CW S Gene products of the accessory seroproteome are indicated in bold capital letters, (O11) indicates O11-specific proteins, (O46) indicates O46-specific proteins. All the other proteins belong to the core seroproteome ^1^: Proteins are classified in Gene Ontology functional classes. Names are given according to annotation of available *S. aureus*sequence genomes. ^2^: Spot number (see figures) ^3^: Coding sequence numbers corresponding to the identified proteins in *S. aureus*O11, *S. aureus*O46, and ED133, respectively. ^4^: Theoretical isoelectric point as determined from the predicted protein sequence ^5^: Theoretical Mass as determined from the predicted protein sequence ^6^: Mascot standard score ^7^: % of the protein sequence covered by the peptides identified ^8^: number of peptides identified ^9^: exponentially modified protein abundance index ^10^: Subproteome compartment where the spot was identified. CW, cell wall; S, supernatant; T, total fraction ^11^: predicted protein localization. C, cytoplasmic; S, secreted; PSE, predicted surface exposed ^12^: reported as immunogen elsewhere ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Representative 2-DE gels and SERPA on supernatant fractions of *S. aureus*O11 (A) and *S. aureus*O46 (B)**. Supernatant samples were prepared from stationary phase cultures of *S. aureus*strains grown anaerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 3-10; 14% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ![](1297-9716-42-35-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **(**A**) Distribution of the immunoreactive proteins based on their experimentally observed (upper panel) or predicted (lower panel) subcellular localization**. (**B**) Distribution of the immunoreactive proteins based on their GO functional classes. (**C**) Venn diagram of immunoreactive proteins defining the core and the accessory seroproteomes. ::: ![](1297-9716-42-35-3) ::: Composition of the core and accessory seroproteomes --------------------------------------------------- SERPA revealed 74 proteins as being recognised by both group O11 and group O46 sera (Table [2](#T2){ref-type="table"}). These proteins defined the core seroproteome, i.e. a pool of staphylococcal proteins that are recognized by the host immune system in both *S. aureus*strains (Figure [3C](#F3){ref-type="fig"}). Moreover, 15 proteins were differentially recognized by group O11 sera or by group O46 sera. These proteins defined the accessory seroproteome, i.e. a pool of strain-specific proteins that are recognized by the host immune system. Among these 15 proteins, 12 appeared to be immunogenic only in infections with O11 (Table [2](#T2){ref-type="table"}). These proteins include 7 virulence-associated proteins (Sbi, SspB, SspA, Aur, IsdH, Opp1A, and VWbp), 2 stress response proteins (AhpF, TrxB), 1 hypothetical protein (product of CDS O11\_0736 or O46\_1969 in O11 or O46), Ldh and a cysteine synthase. Of note, when considering the corresponding genes, all of these 12 genes are present and highly similar in O11 and O46 strains. Only *ahpF*and *vwbp*present 2 and 1 non-synonymous single nucleotide polymorphisms (NS-SNPs), respectively. These results suggest that O11 produce these 12 proteins in vivo in a mastitis context whereas O46 does not, or to a much lesser extent. Three proteins appeared to be immunoreactive with group O46 sera only. Two of them are hypothetical proteins corresponding to SAOV0649 (CDS 011\_2290 and 046\_0078, in O11 and O46, respectively) encoding a probable esterase or lipase, and a gene 011\_0490/046\_2740 with no homology in ED133 genome sequence. The third protein is IsaA, a virulence-associated immunodominant antigen A. The genes encoding IsaA and the probable esterase or lipase are highly homologous in O11 and O46 with only 1 synonymous SNP found when comparing O11\_2290 and O46\_0078. Interestingly, the CDS O11-0490 in O11 genome shares homology with O46\_2740 in O46. However, sequence analysis reveals that O11-0490 corresponds to a truncated form of O46\_2740. This gene encodes a predicted protein that presents 59% identity and 76% homology with exfoliative toxin D \[[@B24]\]. Selected *S. aureus*immunoreactive proteins are widely distributed among a panel of strains isolated from clinical vs. subclinical ewe mastitis ----------------------------------------------------------------------------------------------------------------------------------------------- In order to test the hypothesis that the seroproteomic variations identified by SERPA on the two *S. aureus*isolates were more widely distributed among isolates of a specific host- and clinical-association, we screened an additional 10 strains isolated from subclinical (*n*= 5) and severe (i.e. clinical or gangrenous mastitis; *n*= 5) cases of ewe mastitis for the presence of 2 selected proteins by proteome analysis of supernatant samples (i.e. 2-DE and Coomassie blue staining). The O11 (severe mastitis) protein selected was SspB, which belongs to a proteolytic cascade where a metalloprotease aureolysin (Aur) activates a serine protease zymogen proSspA, which in turn activates the SspB cysteine protease \[[@B25]\]. SspB and the two other proteins, SspA and Aur of the cascade, were recognized in O11 and yielded a very faint signal in O46 (Figure [4A](#F4){ref-type="fig"}). SspB, one element of this proteolytic cascade, was detected in the culture supernatant of strains isolated from clinical mastitis cases whereas it was not found in the strains isolated from subclinical mastitis (Figure [5A](#F5){ref-type="fig"}). The other protein tested was O46\_2740 gene product (with similarity to exfoliative toxin family), which was specifically recognized in O46 infections and did not yield any significant signal in O11 infections (Figure [4B](#F4){ref-type="fig"}). When considering its presence in the culture supernatant of other *S. aureus*strains isolated from clinical or subclinical mastitis in ewes, we observed that it was only detected in the subclinical strains (100%) whereas it was undetectable in any of the strains isolated from clinical mastitis (Figure [5B](#F5){ref-type="fig"}). These results show that at least these tested proteins are differentially produced by *S. aureus*strains isolated from clinical or subclinical mastitis cases. Whether these differences are involved or not in the onset and the acuteness of the subclinical vs. clinical mastitis remains to be demonstrated. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **SERPA of O11-specific (**A**) and O46-specific (**B**) immunoreactive proteins**. Protein specific signals were zoomed in on Coomassie blue stained gels (CB) and membranes revealed using sera obtained from animals infected with O11 (Group1) or O46 (Group 2). Aur, aureolysin; SspA, glutamyl endopeptidase serine protease; SspB, staphopain B; O46-2740, gene product similar to exfoliative toxin family. ::: ![](1297-9716-42-35-4) ::: ::: {#F5 .fig} Figure 5 ::: {.caption} ###### **Distribution of SspB (**A**) and O46-2740 product (**B**) in a panel of *S. aureus*strains isolated from clinical (a) and subclinical (b) mastitis**. Supernatant samples were prepared on stationary phase cultures of strains grown on iron-depleted RPMI. 2-DE gels were Coomassie blue stained. ::: ![](1297-9716-42-35-5) ::: Discussion ========== Two closely related *S. aureus*ovine strains reproducibly induce distinct mastitis types in ewe and mouse models. Contrarily to *Escherichia coli*mastitis, which severity is mainly determined by host factors and not by the strains features \[[@B26]\], it seems that in *S. aureus*, inter-strain variations exist in terms of virulence potential. Such variations have been experimentally observed but the involved staphylococcal factors have not been clearly identified yet \[[@B27]-[@B29]\]. *S. aureus*content in virulence factors reportedly varies from strain to strain and this may account for the large panel of symptoms encountered in ruminant mastitis \[[@B30]\]. It was also shown that some elements of the core genome could account for host adaptation in *S. aureus*ruminant isolates \[[@B8]\]. Here, we show that two closely related *S. aureus*strains are able to induce dramatically different mastitis outcomes in animal model. The experimental mastitis induced in ewes confirmed that strain O11, originally isolated from a gangrenous mastitis, induced more severe infections than strain O46 in ewes. To corroborate the finding of the diversity of the clinical signs caused by O11 and O46, the mouse model of mastitis was employed for further investigation \[[@B31]\]. Despite variable susceptibility to viral, fungal or bacterial infections among the different mouse lines \[[@B32]\], the mouse model was validated as an experimental approach to the study of bovine mastitis \[[@B33]\]. In this study, CD-1 mice infected with O11 or O46 revealed diverse clinical signs and showed different cytokine profiles: O46 induced higher IL-1β and TNF-α levels in the mammary gland lysates and higher serum levels of IL-1β and MCP-1. It has been shown that the cytokines play a pivotal role in the development of the mastitis \[[@B34]-[@B36]\]. Recent investigation revealed that the proinflammatory cytokines, TNF-α and IL-1β, increased the capacity of bovine endothelial cells to eliminate intracellular *S. aureus*\[[@B37]\]. Endothelial cells may so represent a functional and active defence barrier against bacteria invasion of infected quarters. Higher synthesis of proinflammatory cytokines in O46-infected mice might thus reflect a higher anti-staphylococcal response and may allow more effective elimination of strain O46. Further investigation has to be conducted to confirm this hypothesis. Altogether, our findings demonstrated that these two well-characterized strains reproducibly induce drastically different mastitis in terms of severity, and will prove useful tools to gain further insights into host-pathogen interactions. Inventory of mastitis-associated core and accessory seroproteomes in *S. aureus*reveals new mastitis-related antigens --------------------------------------------------------------------------------------------------------------------- This study reports the application of SERPA to determine the core and accessory seroproteomes resulting from experimental ewe mastitis induced by two different *S. aureus*strains, isolated from a subclinical mastitis (O46) and a gangrenous mastitis (O11). To determine which proteins are recognized by the ewe immune system during mastitis with different severity, experimental infections were carried out on primiparous ewes using these two *S. aureus*strains. By comparison of the SERPA profiles, this study allowed, for the first time, the determination of core and accessory seroproteomes for *S. aureus*in a mastitis context. Eighty nine proteins were immunogenic in ewe mastitis implying they were produced during the infection. Seventy four were found in both seroproteome profiles and composed a core seroproteome. Fifteen of them were found strain-specific and composed the accessory seroproteome. Among the 74 proteins belonging to the core seroproteome, only 44 (59.5%) had already been reported to be immunogenic in infections caused by *S. aureus*or other pathogens (e.g. *Bacillus anthracis, Staphylococcus epidermidis, Clostridium perfringens*, *Schistosoma japonicum*) (Table [2](#T2){ref-type="table"}). Among these previously described antigens, only 30S ribosomal S1 and LukM/LukF\'-PV were previously reported to be immunogenic in *S. aureus*bovine mastitis \[[@B38],[@B39]\]. These 44 proteins include most of the immunoreactive proteins categorized in Toxins-Haemolysins and Virulence/Defence mechanisms. The remaining 30 proteins (40.5%) are described for the first time as potential staphylococcal antigens in a mastitis context and, to our knowledge, were not described as immunogenic elsewhere. In the accessory seroproteome, 8 out the 15 proteins identified were already described as immunogenic elsewhere whereas 7 of them (AhpF, Opp1A, VVbp, Mqo, cysteine synthase and two hypothetical proteins) are described as such for the first time (Table [2](#T2){ref-type="table"}). A majority of the proteins identified here are thus reported as immunogenic for the first time in a mastitis context. Furthermore, 37 out of 89 proteins of the total seroproteome (\~42%) correspond to proteins described as staphylococcal antigens for the first time whatever the infection considered. Only four of these new antigens are categorized in Toxins-Haemolysins and Virulence/defense mechanisms. The other ones are mostly found in Metabolism (*n*= 9), Information storage (*n*= 7), and Unknown function (*n*= 13). Only a few studies previously analyzed *S. aureus*proteome and all of them were carried out on human isolates, which reportedly differ from ruminant isolates \[[@B8],[@B9],[@B40]\] and the strains were grown in laboratory culture conditions \[[@B4],[@B41]-[@B46]\]. Here we used two ovine isolates grown in culture conditions mimicking the mastitis context \[[@B11]\]. These two criteria might account for the abundance of new staphylococcal antigens identified in this study. Importance of secreted and exported proteins in seroproteomic patterns ---------------------------------------------------------------------- It is commonly assumed that surface exposed proteins play a role in host-pathogen interactions and that, because of their cellular localization, they are preferentially recognized by the host immune system. In this study, immunoreactive proteins were mainly identified in protein samples prepared from supernatant and cell wall fractions revealing, somehow, discrepancies between experimental (gels of total, cell wall and supernatant protein fractions) and theoretical localization (as determined in silico). Indeed, among the 47 immunoreactive proteins that were predicted cytoplasmic, only 10 were experimentally found in the total fraction and 37 were found in supernatant or cell wall fractions (Table [2](#T2){ref-type="table"}). Such discrepancies were observed in other studies as well \[[@B4],[@B47],[@B48]\]. Some proteins are multifunctional and found both intra- and extracellularly. For example, glyceraldehyde-3-phosphate dehydrogenase \[[@B49]\] and enolase \[[@B50]\] were shown to be both cytoplasmic and surface exposed. In addition to their metabolic role in the cytoplasm, they play a role as adhesins when exposed on the bacterial surface. Furthermore, a new mechanism of protein exportation in Gram positive bacteria was recently described and not included yet in prediction tools for protein localization. It has actually been demonstrated that *S. aureus*, like some Gram negative bacteria, secretes membrane vesicles, which contained at least 90 different proteins \[[@B51]\]. Twelve of the proteins identified here were found in the vesicle-secreted proteins identified by Lee et al. \[[@B51]\]. Whether the other immunoreactive proteins identified here are secreted through a membrane vesicle mechanism remains undetermined. The core seroproteome --------------------- Proteins belonging to the core seroproteome are immunogenic regardless the severity of the induced mastitis. These proteins are therefore good targets for the development of new strategies against *S. aureus*mastitis. Some of them have been tested as vaccine target to prevent staphylococcal infections e.g., Enolase (Eno) \[[@B52]\], IsdA (an iron-regulated cell wall-anchored protein) and IsdB (a cell surface transferrin-binding protein) \[[@B53],[@B54]\], GapC/B protein (glyceraldehyde-3-phosphate dehydrogenase) \[[@B55]\], Hla (alpha-hemolysin) \[[@B56]\]. These vaccines seem at least to limit infection damage (by notably decreasing mortality) but not to provide total effective protection. Well-known virulence factors, such as Hla, Hlb (beta-hemolysin), SspA (V8 serine protease), ScpA (Staphopain A), and Plc (phosphatidylinositol phosphodiesterase), were identified here in a mastitis context and were previously identified as immunogenic in human infections \[[@B4],[@B57]\]. Hla and leukotoxins were reportedly produced in vivo during mastitis \[[@B58]\] but to our knowledge this is the first time that the other proteins listed in Table [2](#T2){ref-type="table"} are shown to be produced in vivo during mastitis. These proteins deserve more attention to test their role in the mastitis onset and to check their potential use as target for vaccine development. Of note, we found 5 iron-related proteins (IsdA, IsdB, IsdH, MntC and SirA, 4 of which belonged to the core seroproteome) consistent with the culture conditions (iron depletion) and with a role in the physiologically important and difficult iron uptake in the mastitis conditions. The accessory seroproteome -------------------------- Some proteins were shown to be specifically produced by strain O11 or by strain O46 in infected ewes. None of 12 proteins specifically produced by O11 in vivo had previously been reported as produced during mastitis. Their role in mastitis is thus unknown. Nevertheless most of them have been described as immunogenic in *S. aureus*infections in humans. Their function is mainly linked to resistance to host immune response like for IsdH \[[@B59]\], AhpF and TrxB, implied in oxidative stress responses \[[@B60]\] that may confer O11 resistance to neutrophils and so be an advantage compared to O46, Sbi that forms complexes with immunoglobulins Fc regions \[[@B61]\], Aur and SspB. Aureolysin is essential for activation of SspA \[[@B25]\], which in turn activates the SspB zymogen \[[@B62]\]. Aur, SspA and SspB seemed to be more produced in O11 than in O46. They can degrade conjunctive tissue \[[@B63]\]. Aureolysin has been shown to be involved in resistance to macrophage phagocytosis \[[@B64]\] and to significantly contribute to the activation of the fibrinolytic system \[[@B65]\]. It might thus reinforce the degradation of extracellular matrix in the mammary gland and promote bacterial spread and invasion. SspB can activate the chemoattractant chemerin, which results in a local inflammation of the tissue \[[@B66]\]. Moreover it induces the depletion of functional phagocytes at the site of infection by blocking phagocytosis by neutrophils and inhibiting their chemotactic activity \[[@B67]\]. SspB may so take part in the observed swelling of the mammary gland observed during gangrenous mastitis. Moreover, it has been shown that SspA and SspB play an important role in virulence in a mouse abscess model \[[@B68]\]. Opp1A was found to be produced by strain O11 in vivo. Opp proteins seem to take part in virulence in several infection models \[[@B69]\]. Although the role of Opp has not been clearly demonstrated until now, Opp proteins have also been reported to be involved in virulence in other Gram positive pathogens such as group A streptococci \[[@B70]\], *Streptococcus agalactiae*\[[@B71]\] or *Listeria monocytogenes*\[[@B72]\]. A variant of von Willebrand factor-binding protein gene has recently been located on the pathogenicity island SaPIov2, characteristic of small ruminant isolates \[[@B9]\]. Interestingly, besides being a coagulase, it is also an activator of pro-thrombin \[[@B73]\] that is present in cow milk \[[@B74]\]. Pro-thrombin activation in thrombin may have a pro-inflammatory effect during mastitis and thus take part in the symptoms observed in animals infected by O11. Whether and how these proteins are involved in the acuteness of the disease induced by O11 remains unknown. O46 specifically produced 3 immunoreactive proteins when compared to O11. IsaA has been reported to be immunogenic in many *S. aureus*infections \[[@B3],[@B52],[@B57],[@B75]-[@B77]\]. It presents autolytic activity and is necessary for complete virulence \[[@B78]\] but its role in mastitis is not known. Interestingly, a protein (encoded by O46-2740) which shows similarity to exfoliative toxin D (ETD) was found produced by O46 and not by O11. Three amino-acids were shown to constitute the active site common to all the exfoliative toxins \[[@B79]\]. These amino-acids are present in O46\_2740 gene (O46 strain) product but one is missing in O11-0490 gene product. The corresponding gene is not found in the recently released sequence of ovine strain ED133 \[[@B9]\] although we found its product in the exoproteome of 5 additional *S. aureus*strains isolated from subclinical mastitis. ETD is associated with cutaneous abscesses and furuncles \[[@B80]\]. Interestingly this toxin is also produced by Coagulase Negative Staphylococci species like *Staphylococcus hyicus*, *Staphylococcus pseudintermedius*and *Staphylococcus chromogenes*. CNS are highly prevalent in ovine subclinical mastitis \[[@B81]\]. Whether this particular toxin is specifically produced and plays a role during subclinical mastitis remains to be tested. Altogether, proteins differentially produced by O11 and O46 may be considered as potential marker of gangrenous or subclinical mastitis but this has still to be further demonstrated. Conclusion ========== To the best of our knowledge, this study provides the first comparative and comprehensive serological proteome analysis in a mastitis context. The proteins identified are immunogenic in ewes implying that they are also produced in the udder during infection. Many of them are found immunogenic for the first time and a great proportion was found in the supernatant and cell wall fractions even though they were predicted as cytoplasmic proteins. Whether or how these proteins are really involved in the mastitis infection and or the severity of the mastitis remains to be elucidated. This study provides a handful of interesting candidates for further investigations on their potential use as new targets for prophylactic or curative strategies such as vaccine or drug target as some appear to be involved in important virulence-associated functions (toxins, immune evasion, iron uptake). Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= CLM participated in the experimental mastitis in ewes, carried out the 2-DE analyses, participated in the identification of the immunoreactive proteins and drafted the manuscript. JJ and GJ participated in the identification of the immunoreactive proteins by mass spectrometry, SE, NB and RT participated in the design of the study and in the results analyses, CP, JMG and EV carried out the experimental mastitis in ewes, DD and EM carried out the experimental mastitis in mice, DH, PF and JS carried out the genome sequencing and genome sequence analyses, EV and YLL conceived the study, and participated in its design and coordination. All authors read and approved the final manuscript. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 **Table S1**: Criteria used to define the acuteness of mastitis symptoms ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 **Figure S1**: Dynamics of gangrenous mastitis onset in ewes infected by *S. aureus*O11 (argyles) and O46 (squares). ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 3 **Figure S2**: (**A**) Intramammary growth of *S. aureus*strain O11 and O46 in CD-1 mice. Populations are the mean values of *S. aureus*counts in homogenates of 12 mice mammary gland. (**B**) Temperature of infected mice 24h post-infusion. The mean value of the groups of mice infected with *S. aureus*O11 or O46 is given. The dashed line indicates the temperature of the animals at T0, before infection. Asterisks indicate statistically significant values. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 4 **Figure S3**: Quantification of IL1β, IL6, TNF, KC and MCP-1 in mammary gland lysates with BD^™^Cytometric Bead Array. Cytokines were quantified on homogenates of mammary glands infected by *S. aureus*O11 or O46. Quantities are the mean values of 6 homogenates for each group (O11 and O46) and are expressed in pg/20 μg of total protein. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 5 **Figure S4**: Quantification of IL1β, IL6, TNF, KC and MCP-1 in serum with BD^™^Cytometric Bead Array. Cytokines were quantified in sera collected on 12 mice infected by *S. aureus*O11 (6 sera) or O46 (6 sera). Quantities are the mean values of 6 sera for each group (O11 and O46) and are expressed in pg/mL. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 6 **Figure S5**: Representative 2-DE gels and SERPA on cell wall fraction (upper panels) and total proteins (lower panels) of *S. aureus*O11. Supernatant samples were prepared from late exponential phase cultures of *S. aureus*strains grown anaerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 4-7; 12% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 7 **Figure S6**: Representative 2-DE gels and SERPA on supernatant fractions of *S. aureus*O46 (upper panels) and *S. aureus*O11 (lower panels). Supernatant samples were prepared from late exponential phase cultures of *S. aureus*strains grown aerobically on iron-depleted RPMI. Preparative 2-DE gels were Coomassie blue stained (left panel). Gels run in parallel were immunoblotted using the pools of sera obtained from group 1 (infected with O11) animals (middle panels) or from group 2 (infected with O46) animals (right panels). Samples were run in parallel on 13 cm gels (pI 3-10; 12% SDS-PAGE). Spots identified by MS/MS are labeled. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ Caroline Le Maréchal is the recipient of a PhD grant from the French National Institute for Agricultural Research (INRA) and the Agence Nationale de Sécurité Sanitaire (ANSES), IMISa Project. CLM received a 3-month grant from Université Européenne de Bretagne (UEB).

PubMed Central

2024-06-05T04:04:18.971325

2011-2-15

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052181/", "journal": "Vet Res. 2011 Feb 15; 42(1):35", "authors": [ { "first": "Caroline", "last": "Le Maréchal" }, { "first": "Julien", "last": "Jardin" }, { "first": "Gwenaël", "last": "Jan" }, { "first": "Sergine", "last": "Even" }, { "first": "Coralie", "last": "Pulido" }, { "first": "Jean-Michel", "last": "Guibert" }, { "first": "David", "last": "Hernandez" }, { "first": "Patrice", "last": "François" }, { "first": "Jacques", "last": "Schrenzel" }, { "first": "Dieter", "last": "Demon" }, { "first": "Evelyne", "last": "Meyer" }, { "first": "Nadia", "last": "Berkova" }, { "first": "Richard", "last": "Thiéry" }, { "first": "Eric", "last": "Vautor" }, { "first": "Yves", "last": "Le Loir" } ] }

PMC3052182

Introduction ============ *Paramyxoviridae*is a large and diverse family whose members have been isolated from many species of avian, terrestrial, and aquatic animal species around the world \[[@B1]\]. Paramyxoviruses are pleomorphic, enveloped, cytoplasmic viruses that have a non-segmented, negative-sense RNA genome. The family is divided into two subfamilies, *Paramyxovirinae*and *Pneumovirinae*, based on their structure, genome organization, and sequence relatedness \[[@B2]\]. The subfamily *Paramyxovirinae*contains five genera: *Respirovirus, Rubulavirus, Morbillivirus, Henipavirus*, and *Avulavirus*, while the subfamily *Pneumovirinae*contains two genera, *Pneumovirus*and *Metapneumovirus*\[[@B3]\]. All paramyxoviruses that have been isolated to date from avian species can be segregated into two genera based on the taxonomic criteria mentioned above: genus *Avulavirus*, whose members are called the avian paramyxoviruses (APMV), and genus *Metapneumovirus*, whose members are called avian metapneumoviruses. The APMV of genus *Avulavirus*are separated into nine serotypes (APMV-1 through -9) based on Hemagglutination Inhibition (HI) and Neuraminidase Inhibition (NI) assays \[[@B4]\]. Various strains of APMV-1, which is also called Newcastle disease virus (NDV), have been analyzed in detail by biochemical analysis, genome sequencing, and pathogenesis studies, and important molecular determinants of virulence have been identified \[[@B5]-[@B9]\]. As a first step in characterizing the other APMV serotypes, complete genome sequences of one or more representative strains of APMV serotypes 2 to 9 were recently determined, expanding our knowledge about these viruses \[[@B10]-[@B18]\]. APMV-1 comprises all strains of NDV and is the best characterized serotype because of the severity of disease caused by virulent NDV strains in chickens. NDV strains vary greatly in their pathogenicity to chickens and are grouped into three pathotypes: highly virulent (velogenic) strains, which cause severe respiratory and neurological disease in chickens; moderately virulent (mesogenic) strains, which cause mild disease; and non-pathogenic (lentogenic) strains, which cause inapparent infections. In contrast, very little is known about the comparative disease potential of APMV-2 to APMV-9 in domestic and wild birds. APMV-2 strains have been isolated from chickens, turkeys and wild birds across the globe \[[@B4],[@B19]-[@B22]\]. APMV-2 infections in turkeys have been found to cause mild respiratory disease, decreases in egg production, and infertility \[[@B23],[@B24]\]. APMV-3 strains have been isolated from wild and domestic birds \[[@B25]\]. APMV-3 infections have been associated with encephalitis and high mortality in caged birds \[[@B26]-[@B28]\]. APMV-4 strains have been isolated from chickens, ducks and geese \[[@B29]\]. Experimental infection of chickens with APMV-4 resulted in mild interstitial pneumonia and catarrhal tracheitis \[[@B30]\]. APMV-5 strains have only been isolated from budgerigars (*Melopsittacus undulatus*) and cause depression, dyspnoea, diarrhea, torticollis, and acute fatal enteritis in immature budgerigars, leading to very high mortality \[[@B31]\]. APMV-6 was first isolated from a domestic duck and was found to cause mild respiratory disease and drop in egg production in turkeys, but was avirulent in chickens \[[@B10],[@B30],[@B32]\]. APMV-7 was first isolated from a hunter-killed dove and has also been isolated from a natural outbreak of respiratory disease in turkeys. APMV-7 infection in turkeys caused respiratory disease, mild multifocal nodular lymphocytic airsacculitis, and decreased egg production \[[@B33]\]. APMV-8 was isolated from a goose and a feral pintail duck \[[@B34],[@B35]\]. APMV-9 strains have been isolated from ducks around the world \[[@B36],[@B37]\]. APMV types -2, -3, and -7 have been associated with mild respiratory disease and egg production problems in domestic chickens \[[@B33]\]. There are no reports of isolation of APMV-5, -8 and -9 from poultry \[[@B32]\]. But recent serosurveillance of commercial poultry farms in USA indicated the possible prevalence of all APMV serotypes excluding APMV-5 in chickens \[[@B38]\]. APMV-1 (NDV) is known to replicate in non-avian species including humans \[[@B39]-[@B44]\], although its only natural hosts are birds. APMV-1 infections in non-avian species are usually asymptomatic or mild. Clinical signs in human infections commonly involve conjunctivitis, which usually is transient and self-limiting. Presently, APMV-1 is being evaluated as a vaccine vector against human pathogens \[[@B45]\]. When administered to the respiratory tract of non-human primates, NDV is highly restricted in replication, but foreign antigens expressed by recombinant NDV vectors are moderately to highly immunogenic. One of the major advantages of this approach is that most humans do not have pre-existing immunity to APMV-1. Pre-existing immunity is a potential drawback to using vectors derived from common human pathogens, and also can be a concern for any vector if two or more doses are necessary to elicit protective immunity. Therefore, we are investigating APMV types 2 to 9, which are antigenically distinct from APMV-1, as alternative human vaccine vectors. Also, some of these additional APMV types likely will have differences in replication, attenuation, and immunogenicity compared to APMV-1 that may be advantageous. However, the replication and pathogenicity of APMV-2 to -9 in non-avian species has not been studied. As a first step, we have evaluated the replication and pathogenicity of APMV-2 to -9 in hamsters. In this study, groups of hamsters were infected with a prototype strain of each APMV serotype by the intranasal route and monitored for virus replication, clinical symptoms, histopathology, and seroconversion. Our results showed that each of the APMV serotypes replicated in hamsters without causing adverse clinical signs of illness, although histopathologic evidence of disease was observed in some cases, and also induced high neutralizing antibody titers. Materials and methods ===================== Viruses and cells ----------------- The following nine prototype strains of APMV serotypes 1 to 9 were used, APMV-1, NDV lentogenic strain LaSota/46; APMV-2, APMV-2/Chicken/California/Yucaipa/56; APMV-3, APMV-3/PKT/Netherland/449/75; APMV-4, APMV-4/duck/HongKong/D3/75; APMV-5, APMV-5/budgerigar/Kunitachi/74; APMV-6, APMV-6/duck/HongKong/18/199/77; APMV-7, APMV-7/dove/Tennessee/4/75; APMV-8, APMV-8/goose/Delaware/1053/76; APMV-9, APMV-9/duck/New York/22/1978. All of the viruses were grown in 9-day-old embryonated specific-pathogen-free (SPF) chicken eggs inoculated by the allantoic route, except for APMV-5, which was grown in African green monkey kidney (Vero) cells (ATCC, Manassas, VA, USA) \[[@B17]\]. The allantoic fluids from infected eggs were collected 96 h post-inoculation and virus titers were determined by hemagglutination (HA) assay with 0.5% chicken RBC except in the case of APMV-5, which was titrated by plaque assay on Vero cells. The APMV-5 samples were inoculated in triplicate onto 24-well plates of Vero cells at 80% confluency, incubated for 1 h, washed with PBS, overlaid with 0.8% methylcellulose, and observed for plaque production till 7 days post infection (dpi). The cells were fixed with methanol and stained with 1% crystal violet. Values for each tissue sample were based on average plaque count from three wells. Vero cells were grown in Earle\'s minimum essential medium (EMEM) with 10% fetal bovine serum (FBS). Chicken embryo fibroblast (DF-1) cells were grown in Dulbecco\'s minimal essential medium (DMEM) containing 10% FBS at 37°C with 5% CO~2~. Preparation of hyperimmune antisera against viral nucleocapsid (N) proteins in rabbits -------------------------------------------------------------------------------------- For each of the prototype strains, virions were purified on discontinuous sucrose gradients \[[@B12]\]. The viral proteins were denatured and reduced and were separated on 10% SDS-Polyacrylamide gels and negatively stained using E-Zinc ™reversible stain kit (Pierce, Rockford, IL, USA). Each serotype was analyzed on a separate gel to avoid cross contamination. The N protein bands were excised from the gels and destained with Tris-glycine buffer, pH 8. The excised gel bands were minced in a clean pestle and mixed with elution buffer (50 mM Tris-HCl buffer pH 8, 150 mM NaCl, 0.5 mM EDTA, 5 mM DTT and 0.1% SDS) and transferred to the upper chambers of Nanosep centrifugal device (Pall Life Sciences, Ann Arbor, MI, USA). The proteins were eluted by centrifugation at 13000 × *g*for 5 minutes, and the eluted proteins were quantified and 200 μg of each protein was mixed in complete Freund\'s adjuvant and injected subcutaneously into a rabbit. After two weeks, a booster immunization was given with 200 μg of protein in incomplete Freund\'s adjuvant and two weeks later the hyperimmune sera were collected. The sera were tested by western blot and were found to recognize specifically the homologous N protein (data not shown). The sera were stored at -80°C until further use. Experimental infection of hamsters ---------------------------------- To study viral replication and pathogenicity, fifty seven 4-week-old Syrian golden hamsters (Charles River Laboratories Inc, Wilmington, MA, USA) were housed in negative-pressure isolators under Bio Safety Level (BSL)-2 conditions and provided feed and water ad libitum. The animals were cared for in accordance with the Animal Welfare Act and the Guide for Care and Use of Laboratory Animals and the protocols were approved by the institution\'s IACUC. Hamsters in groups of six were inoculated intranasally with 100 μL of infectious allantoic fluid containing 2^8^HAU of each individual APMV, except for APMV-5, which contained 3 × 10^3^PFU/mL, under isoflurane anesthesia. A group of three hamsters served as uninfected controls and were mock infected with normal allantoic fluid. The hamsters were observed three times daily for physical activity and for any clinical signs of illness, and were weighed on day 0, 5 and 14 dpi. Three hamsters from each group were euthanized at 3 dpi and the other three (as well as the three animals in the control group) at 14 dpi by rapid asphyxiation in a CO~2~chamber. Necropsies were performed immediately postmortem and the following tissue samples were collected for immunohistochemistry (IHC), histopathology, and virus isolation: brain, nasal turbinates, lung, spleen, kidney and small intestine. In addition serum samples were collected on 14 dpi immediately prior to euthanasia, and seroconversion was evaluated by HI assay \[[@B46]\]. Virus detection and quantification from tissue samples ------------------------------------------------------ Half of each tissue sample was used for virus titration. These samples were collected aseptically in 1 mL of DMEM in 10X antibiotic solution containing 2000 units/mL penicillin, 200 ug/mL gentamicin sulfate, and 4 ug/mL amphotericin B (Sigma chemical co., St. Louis, MO, USA). They were processed immediately to avoid any reduction in virus titers. Briefly, a 10% homogenate of the tissue samples were prepared by using a homogenizer and clarified by centrifugation at 420 × *g*for 10 min. For all of the serotypes except APMV-5, the virus titers in the clarified supernatants were determined by end-point dilution on DF-1 cells. Tenfold dilutions of tissue supernatant were inoculated onto DF-1 cells in 96-well plates and incubated for three days. The plates were fixed in 10% formalin for 30 min and the cells were permeabilized using 2% Triton X-100 for 2 min. The plates were washed five times with PBS to remove any residual formalin in the wells. The cells were blocked using 2% normal goat serum for 60 min and the plates were washed twice with PBS- Tween-20 (PBS-T). The cells were incubated with primary rabbit antiserum raised against the N protein of the homologous APMV serotype at room temperature for 1 h. The plates were washed with PBS twice, 5 min each. The cells were incubated with anti rabbit FITC antibody as secondary antibody for 45 min and washed finally with PBS twice, 5 min each. The slides were visualized and the virus titers were determined by end point titration method using the Reed and Muench formula, and were photomicrographed using a fluorescent microscope (Zeiss Axioshop 2000, Zeiss, Göttingen, Germany) \[[@B47]\]. The virus titers in the supernatants of tissue homogenates from APMV-5 infected hamsters were determined by plaque assay in Vero cells as described above using 10-fold dilution series. Values for each tissue sample were based on average plaque count from three wells. Immunohistochemistry (IHC) and histopathology --------------------------------------------- The other half of each tissue sample was used for IHC and histopathology. The tissues were fixed in 10% neutral buffered formalin, held for approximately seven days, and processed for IHC and histopathology. Paraffin embedded 5-micron sections of all the tissue samples were prepared at Histoserve, Inc. (Maryland, MD, USA). The sections were stained with hematoxylin and eosin for histopathology. Sections were also immunostained to detect viral N protein using the following protocol. Briefly, the tissue sections were deparaffinized in two changes of xylene for 5 min each, hydrated in two changes of 100% ethanol for 3 min each, changes of 95% and 80% ethanol for 1 min each, and finally washed in distilled water. The sections were processed for antigen retrieval in a water bath containing sodium citrate buffer (10 mM citric acid, 0.05% Tween 20, pH 6.0), at 95-100°C for 40 min and then allowed to cool to room temperature for another 60 min. The sections were rinsed in PBS-Tween 20, twice for 2 min each. The sections were blocked with 2% BSA in PBS for 1 h at room temperature. The sections were then incubated with a 1:500 dilution of the homologous primary N-specific rabbit antiserum in PBS for 1 h in a humidified chamber. After three washes in PBS, the sections were incubated with the secondary antibody (FITC conjugated goat anti-rabbit antibody) for 30 min. After a further wash cycle, the sections were mounted with glycerol and viewed under an immunofluorescence microscope. Serological analysis -------------------- Sera were collected from all the hamsters on 14 dpi and evaluated for seroconversion by HI assay \[[@B46]\], except in the case of APMV-5. In addition, cross-HI tests were performed to investigate cross reactivity with other APMV serotypes. Since APMV-5 does not cause hemagglutination of chicken RBC, the antibody titer was determined by plaque reduction neutralization assay. Briefly, the sera were heat inactivated at 56°C for 30 min. Ten-fold dilutions of sera were made and mixed with a constant amount of APMV-5 (3 × 10^3^PFU), and incubated at room temperature for 1 h in a shaker. The antigen antibody mixtures were analyzed by plaque assay as described above. The serum titer that reduced plaque numbers by 70% was the end point titer. Results ======= Clinical disease and gross pathology ------------------------------------ Four-week-old hamsters in groups of six were inoculated by the intranasal route with 2^8^HA units of each of the APMV serotypes except APMV-5, which was administered at a dose of 3 × 10^3^PFU/mL. Three animals were sacrificed at day 3 and the remaining three animals were sacrificed on day 14; following sacrifice, the animals were processed for gross pathology, histopathology, IHC, quantitative virology, and seroconversion. Three uninfected animals served as controls and were sacrificed and processed on day 14. All of the animals were observed three times daily and weighed daily. None of the hamsters infected with any of the APMV serotypes showed any visible clinical signs of disease except those infected with APMV-9. All the six hamsters infected with APMV-9 serotype were dull and had rough skin coat at 3 dpi. They appeared weak and lost weight (Table [1](#T1){ref-type="table"}) till 5 dpi, but later gained body weight and appeared normal by 10 dpi. None of the hamsters died of disease. The uninfected control hamsters appeared healthy and normal. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Body weights (in grams) of hamsters infected with APMV serotypes 1 to 9, measured on 0, 5 and 14 days post inoculation (dpi). ::: APMV 0 dpi 5 dpi 14 dpi Body weight difference at 5 dpi --------- ------------- -------------- -------------- --------------------------------- Control 79 ± 0.58 83 ± 0.58 89 ± 0.58 +4.82 APMV-1 75.8 ± 0.17 71 ± 0.58 74.3 ± 1.20 -6.33 APMV-2 77 ± 1.15 75.3 ± 0.3 79.3 ± 0.67 -2.22 APMV-3 78.3 ± 1.2 77.3 ± 2.69 80 ± 2.89 -1.33 APMV-4 77.6 ± 0.88 80.6 ± 0.67 84.67 ± 0.33 +3.72 APMV-5 82.3 ± 1.45 83.33 ± 1.67 90 ± 1.15 +1.2 APMV-6 77 ± 0.56 72.33 ± 1.45 80.33 ± 0.33 -6.45 APMV-7 77 ± 0.58 72.67 ± 1.78 74 ± 1 -5.96 APMV-8 78.3 ± 1.20 72.33 ± 1.45 75.3 ± 1.45 -8.26 APMV-9 78 ± 1.15 66.33 ± 0.67 80 ± 2.89 -17.59 Mean values with standard error are shown. The values of the difference in body weight at 5 dpi are calculated relative to day 0 for the same group and are expressed in percentage gain (+) or loss (-). ::: Following sacrifice on days 3 and 14, the followings organs were removed and examined for gross pathology, histopathology, immunohistochemical analysis, and quantitative virology: brain, lungs, nasal turbinates, small intestine, kidney and spleen. Gross pathologic findings were limited to the lungs of hamsters inoculated with APMV-2 (Figure [1a](#F1){ref-type="fig"}) and APMV-3 (Figure [1b](#F1){ref-type="fig"}), and were observed only at 3 dpi. In APMV-2-infected hamsters, the entire pulmonary parenchyma was wet, glistening and edematous, with some areas of reddening due to congestion and hemorrhages. There were several diffuse small round shaped red foci on the lungs. Similar gross pathology was also seen in the lungs of APMV-3 infected hamsters, but with foci that were five times larger than those seen in APMV-2 infected hamsters. No such gross lesions were observed in the hamsters of the other infected groups at 3 dpi. There were no gross visceral pathologic lesions in any of the infected hamsters at 14 dpi. No lesions were detected in the uninfected control hamsters. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Gross pathology in lungs from hamsters 3 dpi with APMV-2 (a) and -3 (b)**. (a) Lungs from a hamster infected with APMV-2, showing multifocal mottling with petechial hemorrhages (black arrow). (b) Lungs from a hamster infected with APMV-3, showing multifocal areas of consolidation (white arrow) and ecchymotic hemorrhage (black arrow). (c) Lungs from a mock infected hamster (control). ::: ![](1297-9716-42-38-1) ::: Histopathology -------------- Histopathological lesions at 3 dpi were observed in the nasal turbinates and lungs in all of the infected groups (Figure [2](#F2){ref-type="fig"}, and data not shown). Figure [2e](#F2){ref-type="fig"} and [2f](#F2){ref-type="fig"} show representative examples of the nasal turbinates for APMV-9 and -3, respectively. The most predominant histopathological lesions observed in the nasal turbinates were multifocal necrotic/apoptotic epithelial cells and nuclear pyknosis. Along the nasal septum were areas of epithelial necrosis, accumulation of nuclear debris in the mucosal epithelium, vacuolation of epithelial cells, and blunting or loss of cilia. Small numbers of mononuclear cells and neutrophils multifocally infiltrated the nasal mucosa, with transcytosis and exocytosis into the nasal cavity. There were small accumulations of inflammatory cells and necrotic cellular debris in the nasal cavity. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Representative histopathologic lesions in sections of lung (a-d) and nasal turbinates (e, f) from hamsters 3 dpi with APMV-1 (a, b), APMV-2 (c), APMV-7 (d) and APMV-9 (e, f)**. Lungs (g) and nasal turbinates (h) from uninfected hamster. (hematoxylin and eosin staining, magnification, ×400). (a) Section of lung infected with APMV-1. The bronchiolar and bronchial epithelia are multifocally hyperplastic (yellow arrow) and contain sloughed cellular debris and inflammatory cells (black arrow). There are moderate numbers of necrotic cells in the bronchiolar epithelium and in areas of inflammation in alveoli. (b) Section of lung infected with APMV-1. There is multifocal infiltration and consolidation of the pulmonary interstitium by moderate numbers of lymphocytes, monocytes, and neutrophils (black arrow), with an accumulation of inflammatory cells in alveoli (yellow arrow). Multifocally, alveoli are lined by rows of hyperplastic epithelial cells (white arrows) that sometimes exhibit cellular atypia, including anisocytosis, anisokaryosis, and cytomegaly (atypical type II pneumocyte hyperplasia). (c) Section of lung infected with APMV-2. The pulmonary interstitium is multifocally infiltrated by moderate numbers of lymphocytes, monocytes, and neutrophils (white arrows). (d) Section of lung infected with APMV-7. The pulmonary interstitium is multifocally infiltrated and consolidated by moderate numbers of lymphocytes, monocytes, and neutrophils (black arrow), with accumulations of inflammatory cells in alveoli. Multifocally, alveoli are lined by rows of hyperplastic epithelial cells (white arrow), with some areas exhibiting cellular atypia, including anisocytosis, anisokaryosis, and cytomegaly (atypical type II pneumocyte hyperplasia). The bronchiolar and bronchial epithelia are multifocally hyperplastic (yellow arrow). There are moderate numbers of necrotic cells in bronchiolar epithelium and in areas of inflammation in alveoli. (e) Section of nasal turbinate infected with APMV-9. There is massive cell death and necrosis of the epithelial tissue lining the turbinate bone (white arrow). There is no appreciable level of inflammatory cells in the surrounding tissues. (f) Section of nasal turbinate infected with APMV-3, showing necrotic tissue, loss of ciliary tissue, and blunting of cilia (white arrow). (g) Section of lung from a mock infected hamster (control). (h) Section of nasal turbinate from a mock infected hamster (control). ::: ![](1297-9716-42-38-2) ::: Examples of lung tissue are shown for APMV-1 (Figure [2a](#F2){ref-type="fig"} and [2b](#F2){ref-type="fig"}), -2 (Figure [2c](#F2){ref-type="fig"}), and -7 (Figure [2d](#F2){ref-type="fig"}). All the lung samples from the infected groups exhibited interstitial bronchopneumonia of varying severity at 3 dpi. The inflammatory cell infiltrates were mixed populations of lymphocytes, macrophages, and neutrophils. Additionally, bronchiolar and type II pneumocyte hyperplasia in areas of inflammation with variable degrees of cellular atypia were noticed and the degree of cellular atypia was quite prominent. There were no histopathologic findings for any other organs (brain, small intestine, kidney, and spleen) from any infected hamsters on day 3, or for any of the hamsters at 14 dpi. Immunohistochemistry -------------------- Deparaffinized sections of the virus-infected and uninfected control tissue (brain, lungs, nasal turbinates, small intestine, kidney, and spleen) were immunostained using polyclonal antisera against the N protein of the homologous APMV serotypes. Remarkably, animals infected with APMV-5 did not show any positive immunofluorescence in any of the tissues examined at 3 or 14 dpi. In animals infected with any of the other APMV serotypes, virus-specific antigens were detected on 3 dpi in the lungs and nasal turbinates (Figure [3](#F3){ref-type="fig"}). In the nasal turbinates, virus-positive immunofluorescence was noticed throughout the nasal epithelium lining the turbinate bone, and the harderian gland located near the eye showed complete diffuse fluorescence throughout the organ. In the lungs, the viral antigens were mostly localized in the epithelium surrounding the medium and small bronchi. Viral N antigens were not detected in any additional organs of infected hamsters at 3 dpi, and were not detected in any of the organs of infected hamsters at 14 dpi. The organs of uninfected control hamsters were also negative by immunohistochemistry assay. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Immunofluorescence localization of viral N antigen in sections of nasal turbinates (a, b), harderian glands (c, d) and lungs (e, f) from hamsters 3 dpi with APMV-9 (a), APMV-1 (b), APMV-9 (c), APMV-8 (d), APMV-3 (e), and APMV-2 (f)**. Nasal turbinates (g) and lung (h) from a representative uninfected control hamster (magnification, ×400). (a) Section of nasal turbinate infected with APMV-9. Immunofluorescence was evident in the ciliated epithelium lining the turbinate bone (white arrows). (b) Section of nasal turbinate infected with APMV-1. Immunofluorescence was evident primarily at the apical surface of the ciliated epithelial cells and in the cytoplasm (white arrows). (c) Section of harderian gland infected with APMV-9. Immunofluorescence was evident primarily in the collecting ducts of the gland and also in the cytoplasm of the infected cells (white arrows). (d) Section of harderian gland and nasal turbinate infected with APMV-8. Immunofluorescence was evident primarily the cytoplasm of the infected cells in the harderian gland (white arrows) and in the epithelial cells lining the turbinates (yellow arrows). (e) Section of the lung infected with APMV-3. Immunofluorescence was evident around the bronchial epithelium (white arrows). (f) Section of lung infected with APMV-2. Immunofluorescence was mainly evident around the bronchiolar epithelium (white arrows). (g) Section of nasal turbinate from a mock infected hamster (control). (h) Section of lung from a mock infected hamster (control). ::: ![](1297-9716-42-38-3) ::: Virus isolation and titration in tissue samples ----------------------------------------------- To analyze sites of virus replication, several organs (brain, lungs, nasal turbinate, small intestine, kidney and spleen) were collected on 3 and 14 dpi, for virus isolation and titration. For all of the APMV serotypes except APMV-5, titration was performed in DF-1 cells and the titers were expressed in TCID~50~/g tissue; for APMV-5, titration was by plaque assay in Vero cells (Table [2](#T2){ref-type="table"}). Virus was detected for a number of APMV serotypes on 3 dpi; no virus was detected in any sample for any serotype on 14 dpi. APMV-1 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 1.7 × 10^3^and 1 × 10^3^, respectively. APMV-2 was isolated from lungs (3/3 animals) and nasal turbinates (2/3 animals), with mean titers of 4.1 × 10^3^and 5.3 × 10^3^, respectively. APMV-3 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 5.3 × 10^2^and 3.6 × 10^4^, respectively. APMV-4 was isolated from lungs and nasal turbinates of all three animals, with mean titers of 1.7 × 10^2^and 4.2 × 10^3^, respectively, and from the kidneys of one animal (1 × 10^1^). APMV-6 was isolated from the lungs and nasal turbinates of all three animals, with mean titers of 2.6 × 10^3^and 7 × 10^1^, respectively, and from the spleen (1 animal, 3 × 10^1^) and small intestine (1 animal, 3 × 10^1^). APMV-9 was isolated from the nasal turbinates only from all three animals, with a mean titer of 2.5 × 10^5^. No virus was isolated from any tissues of the hamsters infected with APMV-5, -7 and -8. Also, no virus was isolated from the brain of any hamsters infected with APMV-1 to -9. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Virus titers in the indicated tissues from hamsters 3 dpi with APMV serotypes 1 to 9. ::: -------------------------------------------------------------------------------------------- Virus Hamster\ Nasal\ Lung Brain Spleen Kidney Small\ **No**. Turbinates Intestine -------- ---------- -------------- ------------- ------- ----------- ----------- ----------- APMV-1 1 3 × 10^3^ 2 × 10^3^ \-- \-- \-- \-- 2 2.4 × 10^3^ 3 × 10^3^ \-- \-- \-- \-- 3 4 × 10^3^ 1 × 10^2^ \-- \-- \-- \-- APMV-2 1 9.29 × 10^3^ 1.7 × 10^3^ \-- \-- \-- \-- 2 3.4 × 10^3^ 6.6 × 10^2^ \-- \-- \-- \-- 3 3.5 × 10^3^ ^-^ \-- \-- \-- \-- APMV-3 1 3 × 10^4^ 4 × 10^2^ \-- \-- \-- \-- 2 4.06 × 10^4^ 5.5 × 10^2^ \-- \-- \-- \-- 3 3.75 × 10^4^ 6.6 × 10^2^ \-- \-- \-- \-- APMV-4 1 2 × 10^3^ 3 × 10^2^ \-- \-- \-- \-- 2 2 × 10^3^ 1 × 10^1^ \-- \-- 1 × 10^1^ \-- 3 2 × 10^2^ 2 × 10^2^ \-- \-- \-- \-- APMV-5 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-6 1 1 × 10^2^ 3 × 10^3^ \-- \-- \-- 3 × 10^1^ 2 1 × 10^1^ 4 × 10^3^ \-- \-- \-- \-- 3 1 × 10^2^ 1 × 10^3^ \-- 3 × 10^1^ \-- \-- APMV-7 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-8 1 \-- \-- \-- \-- \-- \-- 2 \-- \-- \-- \-- \-- \-- 3 \-- \-- \-- \-- \-- \-- APMV-9 1 3 × 10^5^ \-- \-- \-- \-- \-- 2 1.5 × 10^5^ \-- \-- \-- \-- \-- 3 3.8 × 10^5^ \-- \-- \-- \-- \-- -------------------------------------------------------------------------------------------- The virus titer values are expressed in TCID~50~per gram of the indicated tissue sample ::: Serology -------- The virus replication in the hamsters infected with APMVs was further investigated by measuring seroconversion 14 dpi. Sera were analyzed by HI assay using chicken erythrocytes (Table [3](#T3){ref-type="table"}) in the case of all of the serotypes except APMV-5, which was analyzed by plaque reduction assay. The HI titers of the pre-infection hamsters were 2 or less. All HI titers greater than 8 were considered positive. Our results showed that all of the infected hamsters seroconverted at 14 dpi, indicating replication by all APMV serotypes. The mean HI titers in hamsters for APMV-1, -2, -3, -4, -6, -7, -8, -9 were 1:256, 1:512, 1:512, 1:32, 1:64, 1:64, 1:1024, 1:256, respectively. The mean serum antibody titer of APMV-5 as determined by virus plaque neutralization test was found to be 1:256. The antigenic relationship among APMV serotypes was evaluated by reciprocal HI tests using these sera, which represent convalescent sera obtained by a single infection of hamsters via the intranasal route. Each of the antisera exhibited very high HI titer against the homologous serotype and either no or very low HI titer against heterologous serotypes, with the exception of APMV -1 and APMV-9 (Table [3](#T3){ref-type="table"}). The antiserum specific for APMV-1 and APMV-9 exhibited substantial cross-reactivity, although the APMV-1-specific antiserum had a four-fold higher titer against APMV-1 than against APMV-9, and the APMV-9 specific antiserum had a two-fold higher titer against APMV-9 than against APMV-1. These reactions indicated the existence of antigenic relatedness between APMV-1 and APMV-9. ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Cross-reactivity of sera from hamsters infected with the indicated APMV serotype (top) against the indicated APMV serotype (left column)\*. ::: ----------- -------- ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ **SERUM** **APMV-1** **APMV-2** **APMV-3** **APMV-4** **APMV-5** **APMV-6** **APMV-7** **APMV-8** **APMV-9** **VIRUS** APMV-1 1:256 0 0 0 0 0 0 0 1:128 APMV-2 0 1:512 0 0 0 0 0 0 0 APMV-3 0 0 1:512 0 0 0 0 1:8 1:4 APMV-4 1:8 0 0 1:32 0 0 0 0 1:4 APMV-5 0 0 0 0 1:256 0 0 0 0 APMV-6 0 0 0 0 0 1:64 0 0 0 APMV-7 0 0 0 0 0 0 1:64 0 0 APMV-8 0 0 0 0 0 0 0 1:1024 0 APMV-9 1:64 0 0 0 0 0 0 0 1:256 ----------- -------- ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ ------------ \* Sera were harvested 14 dpi. Cross-reactivity was measured by HI assay except when tested against APMV-5, in which case a plaque neutralization assay was used. HI titers represent the highest dilution that displayed HI activity, and are expressed in mean HI units. For APMV-5, the 70% plaque reduction titer is shown as the mean. ::: Discussion ========== APMVs are frequently isolated from a wide variety of avian species and are grouped into nine serotypes based on antigenic reactions \[[@B48]\]. APMV-1 (NDV) is the most extensively characterized member of the APMV serotypes. APMV-2 to -9 have been isolated from both wild and domestic birds, but their disease potential in wild or domestic birds is largely unknown. APMV-1 has also been shown to infect a number of non avian species \[[@B41]\] and presently is being evaluated as a potential human vaccine vector for human pathogens \[[@B45]\]. Therefore, there is a possibility that APMV -2 to -9 could also be used as human vaccine vectors for human pathogens. However, the ability of APMV-2 to -9 to replicate in mammalian hosts was unknown. Hence, we have investigated the replication and pathogenicity of APMV-1 to -9 in hamsters inoculated intranasally. The intranasal route was intended to resemble the natural route of APMV infection as well as a likely route for vaccine vector administration. In this study, hamsters were chosen as the mammalian animal model because they are widely used to study replication and pathogenesis of a variety of viruses such as adenovirus \[[@B49]\], herpes virus \[[@B50]\], Nipah virus \[[@B51]\], human RSV \[[@B52]\], human parainfluenza viruses, SARS virus \[[@B53]\], and Eastern equine encephalitis \[[@B54]\]. Clinical disease was not evident with most of the APMV serotypes, and was observed only in the case of APMV-9. All of the animals infected with APMV-9 exhibited clinical disease including weakness and substantial weight loss. Only APMV-2 and -3 produced gross pathological lesions in the lungs, whereas in hamsters infected with the other APMV serotypes the appearance of the lungs was unremarkable. No gross pathology was evident for any other organs with any of the serotypes. Virus was recovered from animals infected with APMV-1, -2, -3, -4, -6, and -9. In all cases, virus was isolated 3 dpi: no virus was detected in any samples for any serotype 14 dpi. The viral titers were moderate and were mostly restricted to the lungs and nasal turbinates; there were isolated incidences of isolation from the spleen (APMV-6), small intestine (APMV-6), or kidneys (APMV-4). No virus was recovered from any tissue from animals infected with APMV-5, -7 and -8. However, the lungs and nasal turbinate tissues from animals infected with APMV-7 and -8 were positive by IHC, indicating that these viruses infected and replicated at a level that was below detection by our assays for quantitative virology. Although APMV-5 was not detected by virus isolation or by IHC in any of the tissues, all of the animals that were inoculated with APMV-5 developed titers of APMV-5 specific antibodies detected by virus plaque reduction neutralization assay, indicating a low level of replication. By 14 dpi, no virus could be detected in any of the tissues in any the infected hamsters for any serotype, whether by histopathology, histochemistry, or virus isolation. This suggests that the virus was cleared from all tissues and disease was resolved, indicating the self-limited nature of the infections. Similar results have been obtained from chickens infected with APMV-2, -3 and -4, where no virus could be isolated at 14 dpi \[[@B30]\]. Using IHC, viral N antigen was detected in the same tissues that were positive by virus isolation. An interesting finding was the presence of large amounts of viral antigens at the epithelial cell linings, suggesting that these cells are highly permissive to APMV replication. In addition, the detection of viral antigens, and in most cases infectious virus, in nasal turbinates and lungs of the hamsters indicate that APMV replication is mostly restricted to the respiratory tract. These results show that all APMV serotypes are capable of infecting hamsters using a nasal route of infection and the extensive amount of virus replication in the respiratory tract was not accompanied by severe disease in hamsters. Serologic assays demonstrated a humoral response in all the hamsters inoculated with APMV serotypes -1 to -9, a further indication of successful virus replication. Our results show that all APMVs (except APMV-5, which does not hemagglutinate) produced HI antibody titers that varied between 1:32 to 1:1024. Based on the HI titers, APMV-8 (1:1024) produced maximum antibody titer and APMV-4 (1:32) produced the least. Paradoxically, while APMV-8 induced the highest titer of HI antibodies, the virus could not be isolated from any of the infected hamsters. Conversely, APMV-4 replicated efficiently in hamsters as observed by virus isolation in nasal turbinates, lungs and kidneys, but produced low levels of virus-specific HI antibodies. Whether these examples of incongruity between levels of replication and serum antibody responses are indicative of differences in the antigenicity of the respective HN proteins or to some other factor remains to be determined. Warke et al. \[[@B30]\] have also provided evidence of low HI titers in the case of APMV-4, in chickens, which was taken as evidence of a low level of replication of this virus in chickens. The HI test is the most commonly used method to diagnose APMV infections and also is used to measure the antibody response. But chicken antiserum against NDV cross-reacts in HI tests with several of the other APMV serotypes, thus questioning the specificity of HI test in field cases \[[@B55]\]. Warke et al. \[[@B38]\] indicated that the HI test lacks sensitivity for detecting infection with these APMV serotypes. They also observed that even in the case of a high infectious dose and observed microscopic changes in the infected organs, high HI titers were not observed in the infected birds. On the contrary in our study, most of the APMV serotypes replicated well in hamsters, producing mild respiratory pathology and high neutralizing antibody titers. Our results indicated that the antibody developed in hamsters against these serotypes were very specific and no cross reaction was observed between serotypes except between APMV-1 and -9. Cross-reactivity between these two serotypes is not completely unanticipated, since they share the highest level of genome nucleotide sequence identity (58%) among the APMV serotypes \[[@B12]\]. Hence, we conclude that the HI test with hamster serum is highly specific and can be used to diagnose different APMV serotypes in field cases. The replication of APMVs in hamsters produced mild rhinitis and mild pathology that was mainly restricted to the respiratory tract. There was a concern that APMVs may also replicate in the intestine and shed in feces, which might act as a source of infection for the other animals. But our results indicated that none of the APMVs replicate in the intestinal epithelial cells of hamsters. Importantly, our results also suggest that these viruses do not cross the blood-brain barrier and do not induce neurological symptoms. Also, our previous experimental studies of all the APMVs in chickens showed that they were avirulent. Taken together, these results show that the APMVs replicate moderately in hamsters and produce either mild or no clinical signs, and elicit substantial antibody responses. Therefore, it is possible that APMVs might replicate in other mammalian species including humans. In conclusion, this study is the first comparative report on the replication and pathogenicity of prototype strains of all 9 APMV serotypes in hamsters. Our results lay the foundation for a good laboratory animal model for testing the replication and pathogenicity of APMV strains. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= AS carried out the pathogenesis studies, carried out the immunoassays, performed the analysis, and drafted the manuscript. MS carried out the pathogenesis studies. HS participated in the analysis, interpretation of histopathological slides. PC and SKS, conceived the study, participated in its design and coordination. All authors read and approved the final manuscript. Acknowledgements ================ We thank Daniel Rockemann, Flavia Dias and all our laboratory members for their excellent technical assistance and help. \"This research was supported by NIAID contract no. N01A060009 (85% support) and NIAID, NIH Intramural Research Program (15% support). The views expressed herein do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.\"

PubMed Central

2024-06-05T04:04:18.983039

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052182/", "journal": "Vet Res. 2011 Feb 23; 42(1):38", "authors": [ { "first": "Arthur S", "last": "Samuel" }, { "first": "Madhuri", "last": "Subbiah" }, { "first": "Heather", "last": "Shive" }, { "first": "Peter L", "last": "Collins" }, { "first": "Siba K", "last": "Samal" } ] }

PMC3052183

1. Introduction =============== The parasitic protozoa of the genus *Leishmania*cause a spectrum of diseases in humans, ranging from subclinical cutaneous infections to more serious disseminating diffuse cutaneous, mucocutaneous and visceral forms of the disease. Leishmaniosis is one of the most prevalent neglected tropical diseases affecting public health worldwide \[[@B1],[@B2]\]. It is transmitted by the bite of female sandflies. In developing countries it is associated with extreme poverty. It is estimated that at least 20 million people are infected with *Leishmania*. The visceral form is the most severe form of the disease. Annually, there are approximately 500 000 new cases of visceral leishmaniosis (VL) \[[@B3]\]. *Leishmania donovani*is the primary cause of VL in the Indian subcontinent and East Africa, *L. infantum*in the areas surrounding the Mediterranean Sea where it is a zoonosis, and *L. chagasi*in the New World. The last two species are identical. Human beings are the only known reservoir of *L. donovani*, while canines provide the reservoir for *L. infantum*and *L. chagasi*\[[@B4]\]. However, since asymptomatic parasitemic injecting drug users who share injecting devices seem to be a suitable reservoir for *L infantum*, an artificial anthro-ponotic cycle would be completed. Needles and syringes would be the vectors and uninfected injecting drug users the receptors \[[@B5]\]. Also, *L. infantum*is known to cause opportunistic infections in patients with HIV/AIDS \[[@B6]\]. *Canis familiaris*is the major host for these parasites, and the main reservoir for human visceral infection \[[@B7]\]. The risk for reintroduction of VL and other vector-borne diseases in Europe as a consequence of global warming has recently been highlighted \[[@B8]\]. Indeed, VL appears not to be limited to the Mediterranean region and has now spread northwards \[[@B9]\]. Manifestations of VL can vary from asymptomatic infection to progressive fatal visceral disease. Disease progression is dependent on both the species of *Leishmania*involved and the genetics and immune status of the host. Active VL is characterized by fever, weight loss, hypergammaglobulinemia, hepatosplenomegaly, anemia, thrombocytopenia, leukopenia and immunodepression \[[@B10],[@B11]\]. Also, the presence of parasite-specific antibodies forming immune complexes in the kidneys may lead to the development of glomerulonephritis \[[@B12],[@B13]\]. Leishmaniosis diagnosis and treatment are expensive. Despite considerable advances, there are still no efficient vaccines available against human leishmaniosis \[[@B14],[@B15]\]. Recently, a vaccine containing the fucose-mannose ligand has been industrialized and licensed for commercialization in Brazilian endemic areas under the name of Leishmune^®^(Fort Dodge Ltda, São Paulo, Brazil) to prevent canine VL. Unfortunately, the immune response induced by vaccination has not yet been fully investigated. Also, this vaccine is solely recommended for asymptomatic and seronegative dogs \[[@B16]-[@B19]\]. *L. infantum*has a digenetic life-cycle (Figure [1](#F1){ref-type="fig"}), alternating between free-living, flagellated, promastigotes in phlebotomine sand flies and obligate, intracellular, aflagellated amastigotes, which preferentially multiply within macrophages or dendritic cells (DCs) of the vertebrate host \[[@B20],[@B21]\]. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### ***L. infantum*life cycle**. (1) During the bloodmeal from an infected vertebrate host, the female sandfly ingests free amastigotes, as well as intracellular amastigotes. In the midgut of the sandfly the amastigotes transform into procyclic promastigotes. (2) The procyclic promastigotes multiply and transform into metacyclic promastigotes, the infective stage, that migrate towards the buccal cavity of the sandfly. (3) A bite from the sandfly transmits *Leishmania*promastigotes to susceptible mammalian hosts (i.e., humans and dogs). (4) Promastigotes invade macrophages and DCs. Within these host cells, promastigotes transform into intracellular amastigotes and replicate to produce a large number of parasites. (5) Consequently, the infected cell ruptures and releases amastigotes into the circulation. (6) Free amastigotes can infect other mononuclear phagocytic cells of the blood, spleen, liver, lymph nodes and bone marrow, and the life cycle is repeated. ::: ![](1297-9716-42-39-1) ::: Several experimental models of VL have been developed, but none of these entirely reproduce the disease in humans \[[@B22]\]. Much of the literature from these models documents the immune parameters contributing to resistance against the visceralizing *Leishmania*species used in vaccine studies \[[@B23]\]. This contrasts with a limited number of studies which have been prompted to study pathological aspects related to VL. In this context, close attention should be given to the histopathological alterations. Humans, dogs and hamsters often exhibit severe clinical signs and symptoms during visceral infection \[[@B23]-[@B25]\], whereas mice generally show a few minor signs or no clinical signs at all, depending mainly on the size of the parasite inoculum \[[@B26]\]. Under experimental conditions, progression of visceral disease also depends on the route of infection together with the strain of *Leishmania*parasites used \[[@B22]\]. These factors make the choice of a suitable laboratory model difficult. Studies using experimental murine models of VL do not allow exact extrapolations to be made concerning susceptibility in dogs and humans, but increase the ease of identifying genes and predicting their functional roles, as well as investigating the immune mechanisms involved in human and canine leishmaniosis. This review will aim to provide a better understanding of a variety of pathological-immune responses that have been described to date in the most widely used experimental models of VL (Syrian hamsters and BALB/c mice). Combining research approaches at the immunological, pathological and genetic levels helps to advance our understanding of the mechanisms involved in visceral infection at different stages of the disease. 2. Syrian hamster model of VL: suitability of this experimental model ===================================================================== The usual routes of infection in the hamster model of VL are intracardiac and intraperitoneal. However, the administration of parasites by the saphenous vein in order to minimize stress on the hamsters has also been reported \[[@B27]\]. Experimental studies in *L. infantum*and *L. donovani*-infected Syrian hamsters (*Mesocricetus auratus*) often reveal several clinical signs of progressive VL (hypergammaglobulinemia, hepatosplenomegaly, anemia, cachexia and immunodepression) that closely mimic active canine and human disease \[[@B22],[@B23],[@B25],[@B28],[@B29]\]. Surprisingly, there are significant amounts of Th1 cytokines (IFN-γ, IL-2 and TNF-α) in the spleen, but there is little or no IL-4. However, to allow the parasites to multiply, deactivating Th2 cytokines (TGF-β and IL-10) may act on infected macrophages as well as anti-*Leishmania*antibodies (which have no protective role in leishmaniosis) that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver \[[@B30]\]. Interestingly, Syrian hamsters exhibit reduced expression of the gene encoding inducible nitric oxide synthase (iNOS) in response to IFN-γ, and this is thought to lead to a low nitric oxide (NO) generation, subsequently defaulting in parasite killing \[[@B10],[@B28],[@B31]\]. Furthermore, there is a lack of reagents for immunological analysis in the hamster model of VL. Taking these factors into account, we consider the Syrian hamster to be a suitable experimental model for the study of the pathological features of active VL (as described below), but it is not a suitable model for the evaluation of immunization strategies, as a result of the animal\'s high innate susceptibility. In Syrian hamsters, manifestations of VL can range from asymptomatic and oligosymptomatic infections to progressive fatal visceral disease \[[@B28]\]. The pathological features reported during VL include hypoplasia of the white pulp in the spleen, hepatic granulomas and the deposition of a secondary amyloid substance both in the spleen and the liver \[[@B32],[@B33]\]. Also, other studies of active VL have reported that infected hamsters develop glomerulonephritis associated with deposition of immunoglobulins and parasite antigens (immune complexes) in the kidneys. Finally, the disseminated amyloidosis and glomerulonephritis produce renal failure and nephrotic syndrome in infected hamsters \[[@B12],[@B34]\]. The visceral infection in hamsters also induces pathological alterations in hepatocytes, mainly in the endomembrane system and the peroxisomal compartment, leading to a disturbance of liver metabolism \[[@B35]\]. In a recent study \[[@B36]\], hamsters infected with *L. infantum*were shown to develop analogous inflammatory myopathies to those observed in naturally infected dogs \[[@B37]\]. Taken together, all these factors probably contributed to the immune response disorders that resulted in the death of the animals \[[@B22],[@B33]\]. Pathological studies from our laboratory showed that after *L. infantum*intracardiac infection, hamsters exhibited severe histopathological alterations in both the spleen and liver at the peak of parasite burden. Among these alterations, we detected the apparition of granulomas in different maturation stages and giant cell granulomas with amastigotes in the liver (Figure [2A-D](#F2){ref-type="fig"}), as well as disruption of the splenic architecture accompanied by lymphoid depletion (Figure [2E-F](#F2){ref-type="fig"}). Interestingly, several months after intracardiac infection with 10^7^promastigotes of *L. infantum*, we found external mucocutaneous lesions localized in the snout, accompanied by ulcers on the back of the animals (Figure [3](#F3){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Liver and spleen histological sections from Syrian hamsters stained with H&E**. (A) Uninfected hamsters show normal liver histological sections (×40). (B) Hamsters infected with 10^5^*L. infantum*parasites show granuloma reactions after three months pi (×40). Compare (A) with (B). (C) Granuloma formation. Initial parasitization of KCs (arrows) surrounded by a few inflammatory cells (lymphocytes and monocytes), showing the lack of organization after three months pi (×400). (D) Developing granuloma and giant cells containing few residual amastigotes after three months pi (×400). (E) Normal splenic architecture in control hamsters (×40). (F) Disruption of the splenic architecture accompanied with lymphoid depletion in hamsters infected with 10^7^*L. infantum*promastigotes after three months pi (×40). Compare (E) with (F). Hamsters and BALB/c mice were purchased from Harlan Interfauna Ibérica S.A. (Barcelona, Spain). The animals were maintained under conventional conditions approved by the Ethical Committee for the Animal Experimentation of the Complutense University of Madrid. ::: ![](1297-9716-42-39-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **External lesions observed in Syrian hamsters infected with 10^7^*L. infantum*promastigotes at seven months pi**. (A-B) Mucocutaneous lesions localized in the snout. (C) Ulcers on the back of the hamsters. The isolate M/CAN/ES/96/BCN150 (zymodeme MON-1) of *L. infantum*was used for infection experiments. This strain was maintained in our laboratory by passage in Syrian hamsters. ::: ![](1297-9716-42-39-3) ::: 3. Mouse model of VL: genetic control of susceptibility to *L. infantum*infection ================================================================================= Genetic control studies of various host defense mechanisms in the mouse (*Mus musculus*) model during the course of progressive infection with visceralizing *Leishmania spp*. are summarized in Table [1](#T1){ref-type="table"}. These experiments made an important contribution in identifying genes involved in VL innate and acquired immunity. Identification of the *Slc11a1*gene aided our understanding of the susceptibility at early stages of infection in BALB/c mice, which reflects the strength of the innate immune response in controlling early parasite growth independently of acquired immune mechanisms. The *Slc11a*gene also controls susceptibility to bacteria. Indeed, mutations in *Slc11a1*cause susceptibility to infection with *Salmonella spp*. \[[@B38]\] and *Mycobacteria spp*. \[[@B39]\]. Interestingly, iron is required for replication of pathogens such as *Leishmania*parasites in phagosomes. The *Slc11a1*gene encodes a protein expressed on the membrane of infected phagosomes that removes Fe^2+^and Mn^2+^ions from the intra-phagosomal compartment restricting intracellular *Leishmania*multiplication in iron-limited intracellular environments \[[@B40],[@B41]\]. Genetically resistant mouse strains (e.g., CBA) possess a functional *Slc11a1*gene which confers innate resistance to early *Leishmania*parasite growth. In contrast, susceptible mice strains (e.g., C57BL/6 and BALB/c) possess a non-functional *Slc11a1*gene and early parasite growth in the liver cannot be controlled \[[@B42]\]. However, most susceptible mouse strains, including BALB/c, develop acquired immune mechanisms to control hepatic parasite growth at later stages of infection (as previously reviewed \[[@B43],[@B44]\]). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Genes that control the immune response to *L. donovani/L. infantum*infection. ::: Host defense mechanism(s) Locus or gene Chromosome Reference(s) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------- ------------ ------------------- Innate intraphagosomal control of infection in the spleen and the liver *Slc11a1* 1 \[[@B40]-[@B44]\] Influences antigen presentation during the acquired immune response in the splen, the liver and the bone marrow *H2* 17 \[[@B43],[@B45]\] Formation of hepatic granulomas. Acquired immune response *Ir2* 2 \[[@B43]\] Influences resistance to parasites in the spleen. C57BL/6J bg/bg mice expressed deficient natural killer cell activity and failed to eliminate *L. donovani*amastigotes *Lyst/Beige* 13 \[[@B46]\] ::: The parasite load in the liver at later stages of infection, which probably reflects the strength of the acquired immune response, was found to be controlled by the *H2*and *Ir2*loci. The haplotype at the *H2*genomic region on chromosome 17 is involved in antigen presentation through the major histocompatibility complex (MHC). Genetic polymorphism in the MHC influences the response to numerous antigens. Several MHC haplotypes have not only been associated with resistance to leishmaniosis, but also with resistance to many other infections \[[@B45]\]. Differences between the *H-2^b^*and *H-2^d^*haplotypes were observed in the BALB/c background, where *H-2^b^*resulted in lower parasite numbers in the liver than *H-2^d^*. In addition to the liver, the *H2*region influences parasite numbers in the spleen and bone marrow \[[@B43]\]. Histopathological analysis revealed that the *Ir2*locus in mice promoted fewer granulomas that were smaller in size, due to an efficient anti-parasite response. The parasite burden in the spleen was also found to be controlled by the *Lyst/Beige*gene on chromosome 13. Indeed, homozygous C57BL/6J bg/bg (beige) mice expressed deficient natural killer (NK) cell activity and failed to eliminate *L. donovani*amastigotes \[[@B46]\]. 4. BALB/c mouse model of VL: organ-specific immune responses ============================================================ The variations in the susceptibility to VL in different strains of mice were first described nearly 40 years ago \[[@B47]\]. In BALB/c mice, the immune response to *L. infantum*and *L. donovani*infection can vary markedly between different organs (liver and spleen) within the same animal. In the liver, the infection can resolve with subsequent immunity to re-infection, whereas in the spleen, *Leishmania*parasites can persist \[[@B48]\]. A schematic view of the organ-specific immune responses after experimental infection with *L. infantum*in susceptible BALB/c mice is shown in Figures [4](#F4){ref-type="fig"} and [6](#F6){ref-type="fig"}. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **A schematic view of the immune responses in BALB/c mice livers after experimental infection with *L. infantum***. After intravenous inoculation, the parasites enter the liver and invade macrophages and DCs. (A) During the hepatic acute phase (up to two weeks pi), *Leishmania*amastigotes multiply in the absence of both IL-12 production and activated T-cells. Consequently, the number of parasites in the liver reaches a peak. (B) Two weeks pi, *Leishmania*-specific T lymphocytes migrate to the liver from the spleen and the acquired hepatic immune response is initiated. The interaction of *Leishmania*-specific T cells with infected KCs and DCs provides the proinflammatory (Th1) environment required for efficient granuloma formation, resulting in the resolution of hepatic infection. (C) The kinetics of parasite burden and different stages of granuloma maturation in the liver after *L. infantum*infection. Infected KCs with no granulomatous reaction and immature granulomas were observed in high numbers at 14 days pi but these initial stages of granuloma formation decreased in number during the course of infection, developing mature and sterile granulomas. Significantly, by 56 days pi, the number of sterile granulomas, in which the amastigotes were killed, increased and consequently, the *Leishmania*parasite burden decreased. Finally, the infection in the liver of BALB/c mice was resolved. ::: ![](1297-9716-42-39-4) ::: ::: {#F5 .fig} Figure 5 ::: {.caption} ###### **The liver granuloma reaction after *L. infantum*infection**. (A) The histology of the liver and cellular infiltrates in infected mice at 28 days pi (×40). Compare (A) with the detail in the lower right corner of the image (non-infected mice showing normal histological appearance, ×40). Liver granuloma evolution: (B) immature granulomas. Early parasitization of KCs (arrows) with initial cell recruitment (×400), at 14 days pi. (C) Mature granuloma assembly at infected KCs, resulting in the attraction of lymphocytes and monocytes, at 28 days pi (×400). (D) Mature-sterile granuloma, free of amastigotes, at 56 days pi (×200). ::: ![](1297-9716-42-39-5) ::: ::: {#F6 .fig} Figure 6 ::: {.caption} ###### **A schematic view of the immune responses in the BALB/c mice spleens after experimental infection with *L. infantum***. (A) In the initial stage of infection, parasites from the blood invade macrophages and DCs into the splenic MZ. Also, DCs acquire parasite antigens in the MZ and subsequently migrate to the PALS. (B) DCs produce IL-12 and present parasite antigens to T cells in the PALS. (C) *Leishmania*-specific T-cells are activated in the PALS but a failure in the specific effector response prevents them from interacting with parasitized host cells in the MZ. Finally, chronicity of infection occurs in the spleen. (D) The kinetics of parasite burden and loss of germinal centers in the spleen after *L. infantum*infection. The progressive loss of splenic germinal centers increased with time. Thus, in the spleen, a site of chronic infection, the high levels of depletion in the white pulp at 56 days pi correlated with the high *Leishmania*parasite burden. ::: ![](1297-9716-42-39-6) ::: 4.1. Liver: control of hepatic infection ---------------------------------------- ### 4.1.1. Development of an immune response to the early stage of infection After being inoculated into the lateral vein of the tail, the parasites enter the liver via the portal vein and invade macrophages and DCs. In both these types of host cell, promastigotes transform into amastigotes. At this point, the innate immune system constitutes its first line of defence against *Leishmania*parasites. The parasitized resident macrophages (Kupffer cells, KCs) secrete chemokines (CCL3, CCL2 and CXCL10) that stimulate the recruitment of monocytes and granulocytes \[[@B44]\]. Despite the activation of these mechanisms in mice, amastigotes survive during the hepatic acute phase (up to two weeks post-infection (pi)) in an environment with small quantities of inflammatory cytokines, in the absence of activated T cells. Consequently, the number of parasites in the liver reaches a peak (Figure [4A](#F4){ref-type="fig"}). Nevertheless, the parasite burden may decrease dramatically with the acquisition of the granulomatous response during the next stage of infection, as described below. ### 4.1.2. Development of an immune response to the later stage of infection: granuloma formation Recent research favours a model in which *Leishmania*-specific T lymphocytes are pre-activated in the spleen and then migrate to the liver \[[@B48]\]. Once there, activated T cells interact with parasitized DCs, serving as a critical source of IL-12 production, that then triggers the subsequent *Leishmania*-specific CD4^+^Th1 effector response during the later stage of infection \[[@B21]\]. Interestingly, activated DCs can also trigger NK cell cytotoxicity and the production of IFN-γ \[[@B49]\]. In contrast to DCs, the production of IL-12 is blocked in infected macrophages. Consequently, the parasite-carrying macrophages are incompetent at priming CD4^+^T cells or stimulating antigen-specific CD4^+^T cells \[[@B50]\]. Therefore, the interaction of *Leishmania*-specific CD4^+^T cells with infected DCs in the liver provides the proinflammatory (Th1) environment required for efficient granuloma formation (Figure [4B](#F4){ref-type="fig"}), which includes IL-12, IFN-γ, TNF-α and IL-2 production \[[@B10],[@B48],[@B51]-[@B53]\]. It is at this stage of infection (weeks 2-4 pi) that the acquired hepatic immune response is initiated. Simultaneously, the fusion of infected KCs to form multinucleated cells also contributes to inflammatory cytokine production during granuloma formation \[[@B54],[@B55]\]. In BALB/c mice, acquired hepatic resistance to *L. infantum*clearly depends upon granuloma development. Thus, the structure of a mature tissue granuloma consists of a core of fused, parasitized KCs with an encircling mononuclear cell mantle containing blood monocytes and both CD4^+^and CD8^+^T cells. In some instances, B cells, plasma cells and granulocytes are also attracted. In immunologically active granulomas, antigen-presenting DCs and cytokine-secreting T cells are required for antimicrobial activity \[[@B54]\]. The formation of a granuloma is not always associated with parasite control, and the effectiveness of hepatic granulomas to kill parasites depends on their degree of maturation \[[@B52],[@B54]\]. It appears that the TNF family of cytokines are not involved in the formation of granulomas but instead are involved in their maturation, as well as the maintenance of splenic architecture \[[@B42]\]. Granulomas become fully evolved by 2-4 weeks pi. The overall antimicrobial efficacy of the granulomatous response appears to be variable, and only mature granulomas develop efficient leishmanicidal mechanisms to kill parasites. In contrast, developing granulomas have been reported to be less efficient at killing *Leishmania*parasites. Among other factors, granuloma development has been found to vary depending on the initial inoculum size. Indeed, higher numbers of mature and sterile granulomas are observed in mice infected with a low-inoculum size than in those infected with a high-inoculum size \[[@B26]\]. In structurally mature hepatic granulomas, the elaboration of leishmanicidal reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates (RNIs) is essential for parasite killing within infected KCs and DCs \[[@B44],[@B54]\]. There are various classification schemes for granulomatous inflammation in VL. Murray et al. \[[@B54]\] reported a summary of liver granuloma structure-function relationships in experimental VL. To score the progression of the granulomatous response, Stager et al. \[[@B56]\] also classified the infected focus as follows: (1) an infected KC with no associated cellular infiltrate, (2) an early granuloma comprising an infected KC surrounded by a few inflammatory cells, with no organization, (3) a mature granuloma with an organized structure, or (4) a sterile granuloma, in which amastigotes had been killed as a result of effective antileishmanial immunity. Following the above criteria our laboratory data also revealed that the resolution of disease in the livers of mice infected with *L. infantum*correlates with granuloma development (Figure [4C](#F4){ref-type="fig"} and Figure [5A](#F5){ref-type="fig"}). Early in the course of infection, granulomas at various stages of maturation are apparent \[[@B44]\]. Thus, relatively mature granulomas can be readily detected alongside infected KCs that have no associated cellular infiltrate at around four weeks pi (Figure [4C](#F4){ref-type="fig"}). Infected KCs exhibiting no granulomatous reaction and immature granulomas (Figure [5B](#F5){ref-type="fig"}) were observed in high numbers at two weeks pi, but their numbers decreased during the course of infection as mature (Figure [5C](#F5){ref-type="fig"}), sterile (Figure [5D](#F5){ref-type="fig"}) granulomas developed, in which the amastigotes were killed. After eight weeks pi, sterile granulomas gradually dissembled in an involution process \[[@B54]\]. Although sterile cure is never achieved in the liver, parasite growth is controlled without inducing pathology and it is resistant to secondary infections with *L. infantum*\[[@B44]\]. It is possible that parasite persistence might mediate long-term immunity in the liver in a similar manner to that seen in the cutaneous leishmaniosis model caused by low-dose infection with *L. major*\[[@B57]\]. Studying the granulomatous response is important because granuloma development has been associated with *Leishmania*infection in the liver, as demonstrated in rodent models. Moreover, enhanced granuloma maturation represents a good marker of successful vaccination against VL \[[@B58]\]. 4.2. Spleen: visceralizing *Leishmania*parasites persist and destroy the splenic architecture --------------------------------------------------------------------------------------------- In contrast to the liver, the spleen and bone marrow become chronically infected in mice \[[@B44]\]. The immune response to *L. infantum*in the spleen (Figure [6A-C](#F6){ref-type="fig"}) can be separated into two phases: acute and chronic. ### 4.2.1. The acute phase of infection Following intravenous experimental infection in mice, *L. infantum*promastigotes enter the spleen via the splenic artery and are rapidly removed from the circulation in the spleen by marginal zone (MZ) macrophages and rarely by DCs. It is likely that the majority of DCs acquire *Leishmania*antigens by phagocytosis of infected macrophages or their remnants in the MZ \[[@B44],[@B59]\]. Within these cells, promastigotes replicate intracellularly as amastigotes. In the spleen, MZ macrophages phagocytose \> 95% of intravenously administered *L. infantum*parasites, where \> 50% of the initial parasite inoculum is killed within 24 h of infection \[[@B48]\]. It appears that DCs acquire parasite antigens within the MZ (Figure [6A](#F6){ref-type="fig"}) and subsequently migrate to the periarteriolar lymphoid sheath (PALS). Once in the PALS, DCs secrete IL-12 \[[@B60]\] and present parasite antigens to T and NK cells, resulting in the activation of these effector cells (Figure [6B](#F6){ref-type="fig"}). Interestingly, *L. infantum*infection stimulates IL-12 production by splenic DCs within the PALS, but not infected macrophages within the MZ \[[@B61]\]. As described above, evidence suggests that *Leishmania*-specific T lymphocytes are primed in the spleen during the acute stage of infection (\< 4 weeks) and then migrate to the liver to initiate a granulomatous response \[[@B42],[@B44],[@B48],[@B62]\]. ### 4.2.2. The chronic phase of infection During the chronic stage of infection (\> 4 weeks) in the spleen, failure to resolve *L. infantum*infection occurs (Figure [6C](#F6){ref-type="fig"}) and the splenic architecture breaks down. There are at least three possible explanations for the failure of the specific effector response \[[@B48]\]: (1) assuming that the priming of T and NK cells by DCs occurs at the PALS, a site that is anatomically segregated from the MZ, infected macrophages fail to produce chemoattractants to bring effector cells into their vicinity. (2) Infected macrophages are unable to activate intrinsic leishmanicidal mechanisms following exposure to cytokines and ligands from T and NK cells. It has been reported that *L. infantum*-infected macrophages fail to produce IL-12 and also have a reduced capacity to generate both ROIs and NO, which are important microbicidal molecules for killing intracellular pathogens \[[@B44],[@B54],[@B61]\]. (3) Failure in the development of the efficient granulomatous immune effector response occurs in the spleen. Together, the low expression levels of MHC class II on *L. infantum*macrophages and their intrinsic defects in the generation of an antileishmanial response (see above), contribute to failure to form inflammatory foci around infected MZ macrophages \[[@B48]\]. Any of these three possibilities may contribute to the failure of the spleen to resolve murine VL. Paradoxically, the spleen is an initial site for the generation of cell-mediated immune responses, but ultimately becomes a site of parasite persistence, with associated immunopathological changes \[[@B44]\]. ### 4.2.3. Pathological changes in the spleen In the spleen, *L. infantum*parasite persistence is accompanied by a failure of granuloma formation, splenomegaly and other pathological changes, such as the disruption of splenic microarchitecture, including the disintegration of the white pulp accompanied by the destruction of follicular DCs, and the absence of germinal centres \[[@B10],[@B22],[@B24],[@B42],[@B48],[@B61],[@B63]\]. Interestingly, there is evidence that high levels of TNF mediate the destruction of MZ macrophages, while IL-10 promotes impaired DC migration into T-cell areas with subsequent ineffective T-cell priming \[[@B44]\]. Data from our laboratory showed that during the acute stage of infection (\< 4 weeks), parasite burden and the level of splenic disruption increases with time (Figure [6D](#F6){ref-type="fig"}). Previously, we have reported that the intensity of lymphoid depletion can vary depending on the initial inoculum size. Indeed, higher numbers of lymphoid-depleted BALB/c mice were observed when a high-inoculum size was used compared with a low-inoculum size \[[@B26]\]. In agreement with previous studies \[[@B44]\], our findings revealed the progressive development of splenic pathology in mice infected with *L. infantum*, including disruption of tissue anatomy accompanied by the loss of germinal centers (Figure [7](#F7){ref-type="fig"}). ::: {#F7 .fig} Figure 7 ::: {.caption} ###### **Changes in splenic anatomy after *L. infantum*infection**. (A) Non-infected mice showed normal histological appearance (×40). (B) After 56 days pi, the splenic architecture showed a significant loss of germinal centers (arrow) in the white pulp (×40). Compare (A) with (B). ::: ![](1297-9716-42-39-7) ::: 5. Remarks and discussion ========================= The experimental murine model of *L. infantum*infection mimics many of the features of canine and human infections. Syrian hamsters also exhibit severe clinical signs and symptoms that are similar to those observed in naturally infected dogs and humans \[[@B23],[@B24],[@B36]\]. However, the absence of iNOS expression \[[@B10],[@B28],[@B31]\] and the suppression of lymphoproliferative responses \[[@B64],[@B65]\] observed, lead us to argue that the hamster is a more suitable model for pathological studies of VL than for the evaluation of vaccine candidates. However, to date, most researchers have elected to use the BALB/c mouse model for investigating disease pathogenesis of VL, as well as for vaccine studies \[[@B26],[@B44],[@B54],[@B66]-[@B68]\]. In mice, the susceptibility to visceralizing *Leishmania*species is mainly determined by the *Slc11a1*gene that encodes a phagosomal component that confers the ability to control the early infection (as described above). Even so, BALB/c mice, lacking this gene, are able to control the infection at a later stage \[[@B42],[@B69]\]. In this context, BALB/c mice provide a better model of self-healing or subclinical infection than of disseminated visceral disease \[[@B10]\]. Paciello et al. \[[@B36]\] reported that susceptible mouse strains do not reproduce progressive disease as observed in human active VL. Furthermore, the intensity of pathological changes in the visceral organs of BALB/c mice can vary depending on the initial inoculum size, as described above. Indeed, we proposed that infecting mice with a large inoculum constitutes a suitable model for the study of the pathological changes of VL \[[@B26]\]. Infection with *L. infantum*, either intravenously or intradermally, leads to organ-specific immune responses that are important determinants of disease outcome in BALB/c mice \[[@B10],[@B48]\]. Apparently, the intravenous route of inoculation does not mimic natural infection by the sandfly \[[@B22]\]. However, during natural infection, the blood-sucking action of the vector on the skin of the host may result in both intravenous and intradermal administration of the parasite \[[@B26]\]. Subsequently, parasites multiply rapidly for the first few weeks in the liver. Curiously, the spleen is the initial site of generation of specific T effector cells with the ability to move to the liver. Once in the liver, the development of cell-mediated immune responses is essential for the clearance of *L. infantum*parasites. In contrast, the spleen ultimately becomes the site of parasite persistence \[[@B26],[@B44],[@B66],[@B70]\], suggesting that the spleen is more susceptible to *L. infantum*infection than the liver \[[@B71]\]. Interestingly, the leishmanicidal efficacy of hepatic granulomas is dependent on their degree of maturation \[[@B26],[@B51],[@B56]\]. Therefore, determining the degree of maturation of hepatic granulomas constitutes an effective tool for selecting VL vaccine candidates and for monitoring disease progression. In summary, it is reasonable to suppose that understanding the development of acquired parasite-specific immunity in the liver and the reasons for effector splenic response failure in VL, may lead to the development of effective strategies for parasite clearance in host target organs during VL and new treatments for canine and human leishmaniosis. 6. Competing interests ====================== The authors declare that they have no competing interests. 7. Authors\' contributions ========================== AN performed the histopathological analyses and participated in the design of the study. GDB, JAO, RDF and NME participated in the design and the discussion section of this paper. JC conceived of the study, carried out the experiments and wrote the paper. All authors read and approved the final manuscript. 8. Acknowledgements =================== This research was support in part by a grant from the Spanish Ministry of Education and Science (MEC) (AGL2007-62207). Francisco Javier Carrión Herrero is an investigator of the \"Juan de la Cierva\" program (JCI-2009-04069) from the Spanish Ministry of Science and Innovation (MICINN).

PubMed Central

2024-06-05T04:04:18.986467

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052183/", "journal": "Vet Res. 2011 Feb 23; 42(1):39", "authors": [ { "first": "Ana", "last": "Nieto" }, { "first": "Gustavo", "last": "Domínguez-Bernal" }, { "first": "José A", "last": "Orden" }, { "first": "Ricardo", "last": "De La Fuente" }, { "first": "Nadia", "last": "Madrid-Elena" }, { "first": "Javier", "last": "Carrión" } ] }

PMC3052184

Introduction ============ *Neospora caninum*is an obligate intracellular parasite that is phylogenetically related to *Toxoplasma gondii*and causes neuromuscular disease in dogs and abortion in cattle, although it can infect other host species \[[@B1],[@B2]\]. Neosporosis is currently recognised as one of the main causes of infectious bovine abortion worldwide \[[@B1]\]. Previous studies have demonstrated that differences occur in the genetic and biological characteristics of *N. caninum*isolates. Thus, genetic diversity among *N. caninum*isolates has been detected using different polymorphic markers \[[@B3]\], including those that are based on microsatellite sequences, which were demonstrated to be the most suitable for typing *N. caninum*isolates \[[@B4]-[@B8]\]. Importantly, *N. caninum*isolates exhibit differences in their capacity to produce pathology in cerebral mouse models \[[@B9]-[@B12]\], and in their efficacy to be transmitted from dams to offspring \[[@B13]-[@B16]\]. Genetic and biological intra-specific diversity of *N. caninum*isolates may influence their capacity to produce disease in the natural host, and the clinical presentation and epidemiology of neosporosis. Very little information is known about the inherent factors of this parasite that contribute to its intra-specific pathogenicity, but the capacity to produce pathology has been associated with the behaviour of different *N. caninum*isolates in the host. The dissemination capacity, the parasite burdens that are reached in target tissues, the ability to avoid the immune response produced against the infection by the host and the rate of tachyzoite-bradyzoite conversion in the host may all contribute to the different levels of pathogenicity that are caused by different isolates \[[@B11]-[@B13],[@B16],[@B17]\]. Previous in vitro studies have reported that the growth \[[@B18],[@B19]\] and bradyzoite conversion rates \[[@B14],[@B20],[@B21]\] are variable among different *N. caninum*isolates. Additionally, the low pathogenicity levels of the Nc-Spain 1 H isolate in mice and cattle have been attributed to the low viability rate and tachyzoite yield of this isolate in cell cultures \[[@B14],[@B15]\]. Therefore, similar to *T. gondii*, the inherent pathogenicity of different *N. caninum*isolates may be directly related to specific virulence traits, which include the migration capacity, the ability to cross barriers and the cell invasion and intracellular proliferation efficiencies \[[@B22]-[@B25]\]. In this work, we investigated the association between the in vitro phenotypes that were displayed by *N. caninum*isolates and their pathogenicity. Specifically, we examined the invasion efficiencies and the intracellular proliferation kinetics of eleven *N. caninum*isolates, including the naturally attenuated NcSpain-1 H isolate and the highly pathogenic Nc-Liverpool isolate, which showed profound differences in their vertical transmission characteristics and their capacities to induce pathology in pregnant cattle \[[@B14],[@B26]\]. Materials and methods ===================== Cell cultures, parasites and preparation of *N. caninum*isolates for in vitro assays ------------------------------------------------------------------------------------ The *N. caninum*isolates that were used in this study are shown in Table [1](#T1){ref-type="table"}. The Spanish *N. caninum*isolates and the Nc-Liverpool (Nc-Liv) isolate were routinely maintained in a monolayer culture of the MARC-145 monkey kidney cell line after reactivation from cryovials, as described previously \[[@B5]\]. The Nc-Liv isolate was previously passaged in a mouse and re-isolated in MARC-145 cell cultures as described previously \[[@B16]\], to minimise the occurrence of potential alterations in its biological characteristics due to prolonged cell culture maintenance, as has been previously reported \[[@B27]\]. The *N. caninum*isolates that were used in these in vitro assays were subjected to a limited number of culture passages (Table [1](#T1){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### *Neospora caninum*isolates included in the in vitro assays. ::: ---------------------------------------------------------------------------------------------------------------------------------------------------------- Isolate\* Host origin\*\* Geographical origin^&^ Passages number^§^ Neonatal morbidity\ Neonatal mortality\ Vertical\ (%)^\#^ (%)^\#^ transmission rate\ (%)^\#^ ---------------- -------------------------- ------------------------ -------------------- --------------------- --------------------- -------------------- Nc-Spain 1H^a^ 2-day-old healthy calf Madrid 12-18 0^L^ 5^L^ 5^L^ Nc-Spain 2H 2-day-old healthy calf Zaragoza 7-13 46.1^L^ 20.4^L^ 61.3^L^ Nc-Spain 3H^b^ 52-day-old healthy calf Navarra^1^ 19-25 10.6^L^ 7.7^L^ 89^H^ Nc-Spain 4H^b^ 22-day-old healthy calf Navarra^1^ 12-18 100^H^ 100^H^ 97.3^H^ Nc-Spain 5H 14-day-old healthy calf León 12-18 98.6^H^ 96^H^ 100^H^ Nc-Spain 6 30-day-old healthy calf País Vasco 20-26 34.5^L^ 29.8^L^ 57.6^L^ Nc-Spain 7 57-day-old healthy calf Navarra^2^ 17-23 98.3^H^ 95^H^ 79.1^L^ Nc-Spain 8 2-day-old healthy calf Navarra^1^ 8-14 4.7^L^ 1.1^L^ 56.4^L^ Nc-Spain 9 7-day-old healthy calf Navarra^2^ 9-15 39^L^ 32.5^L^ 52.6^L^ Nc-Spain 10^a^ 2-day-old affected calf? Madrid 21-27 25.5^L^ 17.9^L^ 65.5^L^ Nc-Liverpool 4-week-old affected dog UK 12R-19R^@^ 100^H^ 100^H^ 95.6^H^ ---------------------------------------------------------------------------------------------------------------------------------------------------------- Summary of name, genetic characterisation, host and geographical origin, passage number in cell culture, and their pathogenicity in a BALB/c pregnant mouse model determined in previous studies \[[@B14],[@B16]\]. \* Nc-Liv and Spanish isolates were genetically characterised by microsatellite analysis. Letters in superscript (^a^) and (^b^) indicate isolates with identical microsatellite profiles \[[@B4],[@B5],[@B14]\]. \*\*All Spanish isolates were obtained from asymptomatic calves from different cattle. Nc-Spain 10 was isolated from an affected calf, but its clinical signs could not be attributed to *Neospora*infection \[[@B5],[@B14]\]. Nc-Liv was isolated from a clinically affected dog \[[@B50]\]. **^&^**The geographical origin of Spanish isolates is indicated by province. Calves from Navarra originated from two dairy herds. Numbers in superscript (^1^) and (^2^) identify the dairy herd. Nc-Liverpool was isolated in the United Kingdom. ^§^The total number of cell culture passages of the *N. caninum*isolates included in these in vitro assays. (^@^) marks the total passages after re-isolation of Nc-Liv in cell culture from BALB/c *nu/nu*mice. **^\#^**The percentages of neonatal morbidity and neonatal mortality and vertical transmission rates were determined in previous studies using a pregnant BALB/c mouse model \[[@B14],[@B16]\]. ^L,\ H^Isolates were categorised into lowly/moderately pathogenic (^L^) or highly pathogenic (^H^) groups according to the significant differences found in neonatal morbidity and mortality. Identical superscript letters denote highly (^H^) and lowly/moderately transmissible (^L^) isolates. ::: The tachyzoites that were used in the in vitro assays were recovered from 3.5-day growth cultures, when the majority of the parasites were still intracellular (at least 80% of the parasite vacuoles were undisrupted in the cell monolayer), and purified using PD-10 (Sephadex G-25) columns (GE-Healthcare, Buckinghamshire, UK) prior to cell monolayer inoculations \[[@B28]\]. The tachyzoite inoculation dose was previously optimised for the maintenance of each isolate to estimate the recovery of tachyzoites from infected cultures under optimal conditions (actively replicating) at 3.5 days post-inoculation (pi). Infected cell cultures were scraped with a plastic cell scraper, harvested by centrifugation at 1 350 *g*for 10 min and suspended in Dulbecco Minimum Essential Medium (DMEM) supplemented with a 2% antibiotic-antimycotic solution (Gibco BRL, Paisley, UK), 10 mM HEPES and 2% heat-inactivated foetal bovine serum (FBS). The FBS employed in all in vitro assays was from the same production batch. Disrupted cell cultures were passed through 25 gauge needles, and tachyzoites were purified with PD-10 columns that had been previously equilibrated with the medium mentioned above. Tachyzoites were eluted from the columns with 5 mL of medium, and the number of tachyzoites was determined by trypan blue exclusion followed by counting in a Neubauer chamber. Tachyzoites were then resuspended at the required doses (2 × 10^5^tachyzoites/mL). Tachyzoite purification was performed at 4°C, and MARC-145 monolayers were inoculated within one hour of tachyzoite collection from flasks. In vitro invasion assays ------------------------ Host cell invasion was measured using a double (red/green) immunostaining probe that was described previously \[[@B28]\] and a laser scanning-cytometer-based assay that was previously described for *T. gondii*\[[@B29]\], with several modifications. All of the isolates were assayed in triplicate, and all of the assays were performed in three independent experiments. The Nc-Liv isolate was included as a control in each batch of experiments. Additionally, MARC-145 monolayers that were not inoculated were immunostained and included as negative controls in each assay. ### Double immunofluorescence staining Purified parasites (2 × 10^5^tachyzoites) were added onto MARC-145 monolayers that had grown to confluence on circular (13 mm diameter) glass coverslips and incubated at 37°C in a 5% CO~2~humidified incubator. At specific time periods (2 h, 4 h and 6 h pi), the coverslips were washed three times with 1 mL of phosphate buffered saline (PBS), fixed for 15 min in a 3% formaldehyde/0.05% glutaraldehyde solution and blocked with 3% bovine serum albumin (BSA) (Sigma-Aldrich, St. Louis, MO, USA) in PBS for 30 min. After blocking, the samples were labelled for 1 h with a 1:4000 dilution of a hyperimmune rabbit antiserum that was directed against *N. caninum*tachyzoites in PBS/0.3% BSA, washed three times with PBS and then labelled for 1 h with a 1:100 dilution of a secondary goat anti-rabbit IgG that was conjugated to PE-Cy5.5 (*red*, Invitrogen, Carlsbad, CA, USA). After washing, the samples were permeabilised with 0.25% Triton X-100 and blocked with PBS/3% BSA for 30 min. Parasites were then labelled with the rabbit anti-tachyzoite serum as described above, washed, and labelled with a 1:1000 dilution of a secondary goat anti-rabbit IgG conjugated to Alexa Fluor 488 (*green*, Molecular Probes, Eugene, OR, USA). Finally, the coverslips were washed, mounted on slides embedded with a 40% glycerol/2.5% 1,4-diazabicyclo\[2.2.2\]octane (Sigma-Aldrich) solution in PBS and analysed using a laser scanning cytometer. Polyclonal rabbit anti-*N. caninum*antiserum was raised in female New Zealand White rabbits (Harland Interfauna S.A., Barcelona, Spain) as described \[[@B30]\]. ### Laser scanning cytometry The coverslips were analysed on a CompuCyte laser scanning cytometer LSC (CompuCyte, Cambridge, MA, USA) equipped with a BX50 upright fluorescence microscope (Olympus America, Melville, NY, USA). A 60.8 mm^2^(4.4 mm radius) circular area was scanned with a 20× objective, an argon ion excitation laser (488 nm), and two detection filters (530/30 (green) and 650 LP (red)). Data were acquired and analysed using Wincyte 3.4 software (CompuCyte). ### Invasion rate determination The invasion rate (IR) was determined to be the number of green events (extracellular and intracellular parasites) minus the number of red events (extracellular parasites) per scanned field at specific times (2 h, 4 h and 6 h pi). Negative controls (the MARC-145 monolayer that was not inoculated) were included to eliminate potential fluorescent artefacts. No events were observed in the negative control samples. In vitro intracellular proliferation assays ------------------------------------------- Proliferation kinetics were determined by quantifying the number of tachyzoites at specific times (4 h, 8 h, 20 h, 32 h, 44 h, 56 h, and 68 h pi) by real-time PCR (qPCR). All of the isolates were assayed in triplicate, and all of the assays were performed in three independent experiments. The Nc-Liv isolate was included in each batch of experiments as mentioned above, and MARC-145 monolayers that were not inoculated were used as negative controls for PCR analyses. ### Culture conditions MARC-145 cells were grown to confluency in 24-well tissue culture plates. Purified *N. caninum*parasites (2 × 10^5^tachyzoites) were added to the monolayers at time 0 and incubated for 4 h at 37°C in 5% CO~2~. Next, the non-invading parasites were removed by washing the monolayer three times with DMEM/2% heat-inactivated FBS/2% antibiotic solution. The cultures were subsequently maintained at 37°C in 5% CO~2~for the time periods mentioned above. The samples were visualised by light microscopy to monitor parasite proliferation prior to their collection. Then, the media were removed and the cell cultures were recovered in 200 μL of PBS, 180 μL of lysis buffer and 20 μL of proteinase K (Qiagen, Hilden, Germany). The samples were transferred to Eppendorf tubes and were frozen at -80°C prior to DNA extraction. ### DNA extraction and real-time PCR Genomic DNA was extracted from cellular samples using the BioSprint 96 workstation and the BioSprint 96 DNA blood kit (Qiagen) according to the manufacturer\'s instructions. Genomic DNA was eluted in a final volume of 100 μL. Quantification of *N. caninum*DNA was performed by real-time PCR targeting the Nc-5 region as described previously \[[@B31]\]. A total of 5 μL (100 ng) DNA was used for the PCR amplifications. The number of *N. caninum*parasites was calculated by interpolating the corresponding Ct values (cycle threshold value, which represents the fractional cycle number reflecting a positive PCR result) on a standard curve that was generated in each real-time PCR run by assaying 10-fold serial dilutions of parasite DNA, which was equivalent to 10^-1^-10^5^tachyzoites. All of the tachyzoite quantifications were assessed from average values obtained from duplicate determinations. DNA extracted from the uninfected MARC-145 monolayer was also included as a negative PCR control in each batch of reactions. ### Proliferation rate, doubling time and tachyzoite yield determinations The proliferation rate (μ) and doubling time (Td) were assessed for each assay during the exponential multiplication period by applying non-linear regression analysis and an exponential growth equation using GraphPad Prism 5 Demo, v. 5.00 software (GraphPad, San Diego, CA, USA). The μ and Td for each isolate were defined as the average value obtained from all of the determinations that revealed a linear regression, *R^2^*≥ 0.95. The tachyzoite yield (TY~56h~) was defined as the average value of the number of tachyzoites quantified by qPCR at 56 h pi. Data statistics and correlation analysis ---------------------------------------- Differences between IRs determined over successive time points for each isolate were compared using the U Mann-Whitney test (2 h versus 4 h, 2 h versus 6 h, 4 h versus 6 h). The Kruskal-Wallis test was employed for comparisons among the IRs shown for the different isolates within each time point (2 h, 4 h, and 6 h pi). When statistically significant differences were found with the Kruskal-Wallis test, a Dunn\'s multiple-comparison test was applied to examine all of the possible pair-wise comparisons. A one-way ANOVA test, followed by the Tukey\'s multiple range tests, was employed to compare the Tds and TY~56h~s assessed for each isolate. Statistical analyses were carried out using a dataset composed of the values determined for each replicate obtained from the three independent experiments. The significance for these analyses was established at *P*\< 0.05. The Spearman\'s rank correlation coefficient (ρ) was applied to investigate the potential association between the in vitro parameters evaluated in this study (IR~2h~, IR~4h~, IR~6h~, Td, TY~56h~) and the neonatal morbidity, mortality and vertical transmission rates induced by these isolates in a well-established pregnant mouse model (Table [1](#T1){ref-type="table"}) \[[@B14],[@B16]\]. Statistical and correlation analyses were performed, and graphics were generated using GraphPad Prism 5 Demo, v. 5.00 software (GraphPad). Results ======= Invasion rate comparisons ------------------------- The IRs (the median number of intracellular events) of almost all isolates significantly increased from 2 h to 4 h pi or from 2 h to 6 h pi (*P*\< 0.05, *U*Mann-Whitney test), with the exception of the Nc-Spain 9 isolate. However, no significant differences were found between the IRs of most of the isolates at 4 and 6 h pi. The IRs were only observed to significantly increase from 4 h to 6 h pi for the Nc-Spain 1 H and Nc-Spain 10 isolates. Significant differences were also found among the IRs of different isolates at 2 and 4 h pi (*P*\< 0.0001, Kruskal-Wallis test) (Figure [1A](#F1){ref-type="fig"} and B). At 2 h pi, the Nc-Spain 4 H, Nc-Spain 8 and Nc-Liv isolates exhibited the highest IRs (IR~2h~) in comparison to the IR~2h~s of the Nc-Spain 3 H, Nc-Spain 6 and Nc-Spain 10 isolates, which displayed the lowest values (by Dunn\'s test). At 4 h pi, the Nc-Spain 4 H and Nc-Liv isolates exhibited significantly higher IRs (IR~4h~) than the Nc-Spain 3 H and Nc-Spain 1 H isolates when they were analysed by the Dunn\'s test. Significant variations among the IRs of the isolates were also detected at 6 h pi (*P*= 0.046, Kruskal-Wallis test), although no differences were found in pair-wise analyses between the IRs of the different isolates (Figure [1C](#F1){ref-type="fig"}). ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Box-plot graphs representing the maximum and minimum values, lower and upper quartiles and medians of invasion rate (IR) replicates from experiments performed in triplicate determined in vitro for each *N. caninum*isolate**. IRs at 2 h pi (A). IRs at 4 h pi (B). IRs at 6 h pi (C). Error bars indicate the SD. (\*\*) marks the significantly higher IRs compared with all of those IRs that were significantly lower (\*) according to the Kruskal-Wallis test and the Dunn\'s multiple-comparison test. ::: ![](1297-9716-42-41-1) ::: Proliferation kinetics, proliferation rate determination and doubling time comparisons -------------------------------------------------------------------------------------- The parasite proliferation kinetics of each *N. caninum*isolate was studied by plotting the numbers of tachyzoites, which were determined by qPCR, against the specific collection time periods (Figure [2A](#F2){ref-type="fig"}). After being inoculated onto MARC-145 cell monolayers, tachyzoites did not multiply for a specific period of time, which is known as the lag phase. The lag phase of the different isolates varied between the time periods of 8 h (Nc-Spain 10), 20 h (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 7, Nc-Spain 6 and Nc-Liv), 32 h (Nc-Spain 1 H, Nc-Spain 3 H and Nc-Spain 9) and 44 h (Nc-Spain 2 H, Nc-Spain 8) (Figure [2A](#F2){ref-type="fig"}). After the lag phase, an exponential proliferation phase was observed that persisted until 56 h pi for 3 of the 11 isolates (Nc-Spain 4 H, Nc-Spain 5 H and Nc-Spain 7 isolates) and until 68 h pi for the other 8 isolates (Figure [2B](#F2){ref-type="fig"}). Microscopic visualisation of the inoculated cultures prior to collection verified that some parasitophorous vacuoles with tachyzoite pairs were first observed for most of the isolates at 20 h pi. After 32 h, the number of tachyzoites from the *N. caninum*isolates that were undergoing endodyogeny inside of parasite vacuoles increased with increasing time. Between 56 and 68 h pi, non-synchronous rupture of the host cells and egression of the tachyzoites were observed in the cell monolayers infected with 7 of the 11 isolates (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 6, Nc-Spain 7, Nc-Spain 9, Nc-Spain 10, and Nc-Liv). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Plot graphs representing the proliferation kinetics over time, as assessed by real-time PCR (A), and the linear regression of the average numbers of tachyzoites (ln-transformed) determined by real-time PCR against the time of the exponential phase (B) for each isolate included in this study (see graph legend)**. The average number of tachyzoites for each time in plot graphs A and B is representative of all of the individual experiments with an *R^2^*\> 0.95, and the error bars indicate the SD. Line slopes in plot graph B define the proliferation rate (μ) and doubling time (Td, Ln 2/μ). For all isolates, *R^2^*\> 0.98. ::: ![](1297-9716-42-41-2) ::: The μ and the Td were determined for the exponential phase, excluding the lag and egression periods, for each replicate performed for each isolate with an *R*^2^\> 0.95. The average Td values for different isolates ranged from a minimum of 9.84 ± 1.516 h (Nc-Spain 6) to a maximum of 14.15 ± 2.364 h (Nc-Spain 4H) (Figure [3](#F3){ref-type="fig"}). When the Td values assessed for different isolates were compared, significant differences were detected (Figure [3](#F3){ref-type="fig"}). The Td value of the Nc-Spain 4 H isolate was significantly higher than the Td values of the Nc-Spain 5 H, Nc-Spain 6 and Nc-Liv isolates (*P*= 0.0016 by 1-way ANOVA, followed by Tukey\'s test). ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **A column graph representing the average doubling time (Td) values of replicates from experiments performed in triplicate determined in vitro for each *N. caninum*isolate**. Error bars indicate the SD. (\*\*) marks the significantly higher Tds compared with all of those Tds that were significantly lower (\*) according to the ANOVA test followed by the Tukey\'s test. ::: ![](1297-9716-42-41-3) ::: Evaluation of tachyzoite yield ------------------------------ The TY~56\ h~was assessed to determine the number of tachyzoites produced during the same intracellular period after invasion, but prior to complete tachyzoite egression from cell monolayers. The TY~56\ h~values were significantly different between isolates (*P*\< 0.0001 by 1-way ANOVA, followed by Tukey\'s test) and varied from 1 731 (Nc-Spain 8) to 36 170 tachyzoites (Nc-Spain 7) (Figure [4](#F4){ref-type="fig"}). At 56 h pi, the isolates that were already undergoing exponential proliferation from 20 h pi (Nc-Spain 4 H, Nc-Spain 5 H, Nc-Spain 6, Nc-Spain 7, Nc-Spain 10 and Nc-Liv) had significantly higher TY~56\ h~values than the other four isolates (Nc-Spain 1 H, Nc-Spain 2 H, Nc-Spain 3 H, and Nc-Spain 8), which began to exponentially proliferate after 20 h pi (Figure [4](#F4){ref-type="fig"}). ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **A column graph representing the average tachyzoite yield (TY~56h~) values of replicates from experiments performed in triplicate determined in vitro for each *N. caninum*isolate**. Error bars indicate the SD. (\*\*) marks the significantly higher TY~56\ h~values compared with all those TY~56\ h~values that were significantly lower (\*) according to the ANOVA test followed by the Tukey\'s test. ::: ![](1297-9716-42-41-4) ::: Correlation analysis -------------------- Previous studies using a well-established pregnant BALB/c mouse model demonstrated that extensive variability exists in the pathogenicity and transmissibility of the *N. caninum*isolates included in this study \[[@B14],[@B16]\]. Wide ranges in the morbidity, mortality and vertical transmission rates were observed (Table [1](#T1){ref-type="table"}), suggesting a relevant role of the implicated isolate in the outcome of infection in pregnant mice. Because the in vitro IRs, Td and TY~56\ h~values also varied significantly within this population of isolates, Spearman correlation analyses were applied to determine whether a potential association existed between the in vitro characteristics of isolates and their ability to be vertically transmitted and produce disease in mice. No correlations could be discerned between the Td or IR~2\ h~values and vertical transmission, neonatal morbidity or neonatal mortality rates. Additionally, no correlation could be established between the vertical transmission rates and the IR~4\ h,~IR~6\ h~or TY~56\ h~values. However, a significant correlation was found between the IR~4\ h,~IR~6\ h~and TY~56\ h~values and neonatal morbidity and mortality rates based on the Spearman\'s rho coefficient (Table [2](#T2){ref-type="table"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Spearman correlation analyses of the invasion rate at 2 h pi (IR~2h~), 4 h pi (IR~4h~), 6 h pi (IR~6h~), doubling time (Td), and the tachyzoite yield at 56 h pi (TY~56h~) that were determined in vitro for each isolate in this study. ::: IR~2h~ IR~4h~ IR~6h~ Td TY~56h~ -------------------------------- -------- -------- -------- ------- --------- ------- ------ ---- -------- -------- **Neonatal morbidity** N.C. \- 0.7107 0.018 0.7016 0.020 N.C. \- 0.7614 0.0065 **Neonatal mortality** N.C. \- 0.6287 0.044 0.7198 0.016 N.C. \- 0.7198 0.016 **Vertical transmission rate** N.C. \- N.C. \- N.C. \- N.C. \- N.C. \- \* Spearman rho coefficient. **^\#^***P*value (two-tailed). N.C. No correlation. ::: Discussion ========== The apicomplexan parasite *N. caninum*is an obligate intracellular parasite. The processes of parasite invasion, adaptation to new intra-cytoplasmatic conditions, intracellular proliferation, and egress from host cells constitute successive steps involved in the lytic cycle of *N. caninum*and other apicomplexa \[[@B32]-[@B34]\]. These processes are required for the maintenance and multiplication of the parasite in vitro and for parasite survival and propagation in the course of animal infection in vivo. As a result of a primo-infection or the reactivation of a *Neospora*infection in a chronically infected animal, tachyzoites rapidly disseminate throughout the body of the host, invade cells of different organs and cause cell death. Cell death results in the release of parasites, which develop new lytic replication cycles, thus allowing the infection to spread and cause disease \[[@B1]\]. Therefore, the processes involved in parasite invasion and intracellular proliferation are crucially important for understanding the pathogenesis of disease and for the development of protective vaccines and effective drug therapies. Recently, different studies have been performed to understand the precise mechanisms involved in the processes of the *N. caninum*lytic cycle, which includes parasite invasion \[[@B28],[@B35],[@B36]\] and egress \[[@B37]\]. However, intraspecific differences related to the efficiency of the lytic cycle processes, such as invasion and proliferation, and their association with isolate pathogenicity in vivo have been poorly investigated. The most detailed study in this regard was performed by Schock et al. \[[@B19]\], which revealed that differences occurred in the growth rates of six *N. caninum*isolates, although their potential correlation with virulence was not examined. Moreover, the isolates in this previous study were maintained by an undetermined number of culture passages, which could modify the original growth rate and pathogenicity of the isolates \[[@B27]\]. Attenuation of virulence, accompanied by faster multiplication in vitro has been previously demonstrated in *N. caninum*and *T. gondii*parasites maintained for extended periods in cell cultures, which may have been due to adaptation of the isolates to cell cultivation \[[@B27],[@B38]\]. In this study, we comparatively examined the in vitro invasion efficiencies and proliferation kinetics of the active tachyzoite stage of eleven different *N. caninum*isolates, which were maintained with limited passages in cell cultures from their original isolation \[[@B5],[@B14]\]. The IRs determined in this study demonstrated that the tachyzoites from most of the *N. caninum*isolates penetrated cell monolayers 2 to 4 h pi. In previous studies, tachyzoites from the Nc-1 *N. caninum*isolate penetrated bovine aorta endothelial cell cultures 45-60 min after inoculation \[[@B28]\]. After the initial penetrations, an insignificant increase in the number of invading tachyzoites was detected from 4 to 6 h pi. This slight increase was likely due to the loose invasion capacity of the remaining tachyzoites that had not invaded that monolayer at 4 h pi \[[@B28],[@B35]\]. These results were similar to the results reported by Hemphill et al. \[[@B28]\], who observed that maintaining Nc-1 tachyzoites extracellularly at 37°C for time periods longer than 4-6 h resulted in decreased infectivity of the parasite. The observed differences in the invasion time periods of *N. caninum*tachyzoites may also have been influenced by the experimental conditions and the host cell types used in each experiment. *N. caninum*can be maintained in vitro in a wide variety of well-established cell cultures, and thus, this parasite can invade a wide range of cell cultures, although *N. caninum*tachyzoites from different isolates may have different affinities for specific cell types. Based on this theory, the failure to isolate parasites in CV-1 and M617 cells from a clinically affected KO mouse can be attributed to the limited invasion and growth characteristics of the specific isolate in these cell lines \[[@B39]\]. This theory may also explain the natural host range and the tissue tropism displayed by *N. caninum*during infection. Moreover, in previous studies, substantial differences were observed in the cell invasion processes of the closely related *N. caninum*and *T. gondii*parasites, which could explain their dissimilar host preferences \[[@B35]\]. However, different *N. caninum*isolates, including those that were assayed in this study, could all be adapted to the MARC-145 cell line through a limited number of cell passages \[[@B5],[@B14],[@B18]\]. Therefore, the significant differences in the invasion efficiencies observed in this study could be attributed to the biological diversity of these *N. caninum*isolates. Throughout the experiments, the IRs determined for the Nc-Spain 4 H and Nc-Liv isolates were significantly higher than the IR of the Nc-Spain 3 H isolate. Furthermore, the IRs determined for the Nc-Spain 4 H and Nc-Liv isolates were significantly higher than the IR of the Nc-Spain 1 H isolate at 4 h pi (Figure [1](#F1){ref-type="fig"}). The intracellular proliferation kinetics also varied between the isolates that were analysed. Significant differences in the lag period, which ranged from 8 to 44 h pi, were observed between the isolates. Additionally, after the exponential proliferation period, the egress period, which occurred 56 to 68 h pi, was only detected in some of the isolates. Furthermore, we did not microscopically visualise parasitophorous vacuoles containing two or more tachyzoites until 20 h pi, and the cellular rupture releasing the tachyzoites was observed for some of the isolates from 56 h pi. The exponential proliferation period is delimited by the lag phase and the tachyzoite egress phase for each isolate. The Td values, which signify the μ, also varied from approximately 10 to 14 h, and significant differences in the values were detected between the isolates. Our results were similar to the results previously obtained for the Nc-1 isolate, which displayed a lag period of 10-12 h and a Td of 14-15 h using human foreskin fibroblasts \[[@B40]\]. However, we must consider, as we did for the IRs, that the proliferation kinetics may have been influenced by the host cell lines used in these assays \[[@B39]\]. In fact, previous studies on *T. gondii*have demonstrated that differences in tachyzoite multiplication occur based on the cell lines used as hosts \[[@B41]\]. Variations in the IR, Td (proliferation rate) and the exponential proliferation period will determine the number of tachyzoite division cycles reached and the tachyzoite yield attained in vitro and in vivo. Significant differences in the TY~56\ h~values were apparent between the isolates based on comparative analysis, and the isolates clearly grouped into two populations: \"highly prolific\" and \"less prolific\" (Figure [4](#F4){ref-type="fig"}). Interestingly, the severity of histopathological lesions and clinical signs have been directly related to the parasite burdens in the brains of experimentally infected mice \[[@B11],[@B12],[@B42]-[@B45]\] and to the spread of the parasite in foetal and placental tissues from infected pregnant cattle \[[@B1],[@B15],[@B26],[@B32],[@B46]\]. Furthermore, an association between the severity of histological lesions and parasite burdens was established in studies performed in bovine foetuses that were naturally aborted during different periods of pregnancy \[[@B47]\]. Therefore, the high dissemination rate, the ability to cross biological barriers (blood-brain barrier and placenta) and the enhanced invasion and proliferation rates of different *N. caninum*isolates may contribute to host tissue damage and to the severity of clinical signs in vivo. In support of this hypothesis, we observed that the isolates with the highest IRs (Nc-Spain 4 H and Nc-Liv) caused the highest morbidity in dams and the highest morbidity and mortality in neonates (100% succumbed to infection), while the isolates with the lowest IRs (Nc-Spain 1 H and Nc-Spain 3H) induced lower neonatal mortality in a pregnant mouse model \[[@B14],[@B16]\]. Furthermore~,~the \"highly prolific\" and \"less prolific\" isolate populations contained isolates that displayed the highest (Nc-Spain 5 H and Nc-Spain 7) and lowest (Nc-Spain 2 H and Nc-Spain 3H) parasite burdens and the levels of histopathological lesions in the brain during the chronic phase of infection in a cerebral mouse model, respectively \[[@B12]\]. Interestingly, this system of ordering grouped the isolates that had the highest and lowest capacities to produce disease in the pregnant mouse model together (Table [1](#T1){ref-type="table"}) \[[@B14],[@B16]\]. Based on these observations, the association between the in vitro IRs and TY~56\ h~values for these isolates and the neonatal morbidity, mortality and vertical transmission rates produced by these isolates in mice was investigated through a correlation analysis. A direct correlation between the IR~4\ h~and IR~6\ h~values when invasion was completed, as well as the TY~56\ h~value and their pathogenicity in mice was established, suggesting that the in vitro invasion and proliferation rate traits are related to the in vivo virulence of the *N. caninum*isolates, at least in the pregnant BALB/c mouse model. Moreover, the Nc-Spain 1 H isolate (a \"less prolific\" and less invasive isolate in this study) had a limited ability to induce foetal death in a pregnant bovine model \[[@B15]\]. High growth rates due to a higher reinvasion capacity, but not due to significant variations between isolate-specific Tds, have also been recognised as a virulence trait in *T. gondii*\[[@B25]\], though pathogenesis in toxoplasmosis has mainly been found to be related to the inflammatory immune response against infection by specific *T. gondii*types \[[@B22],[@B48]\]. However, virulence factors, such as the ROP18 and ROP16 rhoptry proteins, have recently been identified in *T. gondii*, and the ability of ROP18 to increase the intracellular proliferation of this parasite has been specifically suggested to cause enhanced virulence of the parasite \[[@B23],[@B25],[@B49]\]. Because the outcome of *N. caninum*infection is affected by a combination of host, parasite, and external factors, these factors need to be considered collectively when establishing direct associations between the in vitro and in vivo behaviour of *N. caninum*isolates. Various parasite factors, which include the efficacy of disseminating and crossing host barriers, may also be different between *N. caninum*isolates, as described for *T. gondii*isolate types I, II and III \[[@B22],[@B23]\]. Therefore, differences may also exist between *N. caninum*isolates in the number of parasites that are able to spread throughout the host and colonise target organs (brain and placenta) and, consequently, the tachyzoite yield reached in the target tissues, the outcome of an infection and the transmission of the parasite to foetuses in pregnant animals. These differences may explain the lack of a correlation found between the IRs and TY~56\ h~values with vertical transmission rates. Interestingly, the genetically identical Nc-Spain 1 - Nc-Spain 10 and Nc-Spain 3 H - Nc-Spain 4 H isolates displayed significant differences in their in vitro behaviour, as well as in their pathogenicity in mice \[[@B14],[@B16]\]. Both pairs of isolates were obtained from the same dairy herd, but from different calves, and therefore, they could be considered as different isolates that may include genetic variations in other *loci*that were not examined. In summary, this study showed that there is intraspecific diversity in the invasion rate and proliferation kinetics of different *N. caninum*isolates. More interestingly, the correlation found between the in vitro characteristics of the isolates with their in vivo pathogenicity in pregnant mice and their offspring confirms that invasion and proliferation rates are virulence traits in *N. caninum*. Within apicomplexan parasites, host cell invasion and intracellular proliferation are tightly regulated processes that involve the sequential secretion of components from specialised organelles (micronemes, rhoptries and dense granules). A large number of these secreted elements and their interactions have already been identified in *T. gondii*\[[@B24]\]. Some of these elements, such as the ROP18 and ROP16 proteins, are virulence factors in *T. gondii*\[[@B23],[@B25],[@B49]\]. In contrast to *T. gondii*, the role of orthologous microneme, roptry and dense granule proteins in *N. caninum*is still unclear. In addition, cell culture-based approaches have demonstrated significant differences between *T. gondii*and *N. caninum*species \[[@B32],[@B35]\]. Further studies are necessary to identify the molecular mechanisms within *N. caninum*that are directly involved in mediating the differences observed between various isolates. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= JRC carried out in vitro assays, conceived the study, participated in its design, and drafted the manuscript. MGB participated in invasion assays, in its design and helped to draft the manuscript. IS performed invasion and proliferation assays. GA participated in the design of the study and coordination. GAG participated in proliferation assays and performed the statistical analysis. IP carried out real-time PCR determinations. LMO also conceived the study, participated in the design of the study and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript. Acknowledgements ================ This work was supported by the INIA project RTA04-047-C2. We thank Diana Williams (Liverpool School of Tropical Medicine, Liverpool, UK), who kindly provided us with the Nc-Liv isolate. We also thank the Flow Cytometry and Confocal Microscopy Unit of the Complutense University of Madrid for their technical support and Ricardo García de la Mata from the Complutense University of Madrid for statistical analyses.

PubMed Central

2024-06-05T04:04:18.989889

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052184/", "journal": "Vet Res. 2011 Feb 23; 42(1):41", "authors": [ { "first": "Javier", "last": "Regidor-Cerrillo" }, { "first": "Mercedes", "last": "Gómez-Bautista" }, { "first": "Itsaso", "last": "Sodupe" }, { "first": "Gorka", "last": "Aduriz" }, { "first": "Gema", "last": "Álvarez-García" }, { "first": "Itziar", "last": "Del Pozo" }, { "first": "Luis Miguel", "last": "Ortega-Mora" } ] }

PMC3052185

Introduction ============ Neuropathic pain is a chronic condition that affects millions of people worldwide. It is characterized by pain hypersensitivity, including spontaneous ongoing or intermittent burning pain, an exaggerated response to painful stimuli, and pain in response to normally innocuous stimuli. Because the mechanisms of neuropathic pain induction and maintenance are far more complicated than previously assumed, current treatments can be ineffective or produce potentially severe adverse effects. Understanding molecular mechanisms of this disorder may allow improvement of its treatment. It is generally believed that neuropathic pain is caused by changes in expression and function of receptors, enzymes, and voltage-dependent ion channels in peripheral nerves and dorsal root ganglion (DRG) neurons, as well as at synapses in the nociceptive pathway in the central nervous system \[[@B1],[@B2]\]. DRG neurons express many kinds of ion channels/receptors. These channels and receptors have at least three functions (Figure [1](#F1){ref-type="fig"}): 1) Transduction (e.g., transient receptor potential channels, sodium channels, acid-sensing ion channels, and ATP-sensitive receptors that are expressed in the peripheral terminals of DRG neurons transduce noxious stimuli into electric impulses), 2) Conduction (e.g., sodium and potassium channels are involved in the propagation of action potentials), and 3) Modulation of synaptic transmission (e.g., voltage-gated calcium channels and glutamate receptors that are expressed on presynaptic terminals of the primary afferents in dorsal horn regulate the release of neurotransmitters). After nerve injury, injured and uninjured DRG neurons become more excitable and exhibit ectopic firing \[[@B3],[@B4]\]. It is reasonable to conclude that this abnormal spontaneous activity might be related to nerve injury-induced changes in the density, distribution, and functional activities of voltage-gated sodium channels in the DRG neurons. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Involvement of dorsal root ganglion (DRG) channels and receptors in the induction and modulation of pain**. A variety of DRG channels and receptors are involved in the transduction of noxious stimuli into electric impulses at the peripheral terminals of DRG neurons \[e.g., transient receptor potential (TRP) channels, voltage-sensitive sodium (Na^+^) channels, ATP-sensitive receptors, acid sensing ion channels\], in the conduction of action potentials along the axons \[e.g., voltage-sensitive Na^+^channels and potassium (K^+^) channels\], and in the modulation of neurotransmitter release at presynaptic terminals of primary afferents in the dorsal horn \[e.g., voltage-gated calcium (Ca^2+^) channels, GABA receptors, and glutamate receptors\]. ::: ![](1744-8069-7-16-1) ::: To date, at least nine subtypes of sodium channel have been cloned and identified on mammalian cells. All sodium channels consist of a central α-subunit and two auxiliary β-subunits. Nine α-subunits (Nav1.1-Nav1.9, also referred to as channels) and four β-subunits have been identified in mammals. The pore-forming α-subunit determines the primary function of sodium channels, but the kinetics and voltage-dependence of channel gating are in part modified by the β-subunits. The α-subunits form four homologous domains (I-IV), each of which contains six transmembrane α helices (S1-S6) and an additional pore loop located between the S5 and S6 segments. Voltage sensors of sodium channels are located in the highly conserved S4 transmembrane segments. Membrane depolarization produces changes in the transmembrane electric field and causes the S4 segment to spiral outward. This conformational change opens the pore. Following activation, sodium channels quickly inactivate to prevent further ion flow through the pore and to allow repetitive action potential firing of cells. Most voltage-gated sodium channels can be blocked by nanomolar concentrations of tetrodotoxin (TTX) and thereby are termed TTX-sensitive channels. These TTX-sensitive channels show rapidly activating and inactivating sodium currents. In contrast, Nav1.5, Nav1.8, and Nav1.9 are relatively resistant to this toxin and show sodium currents that are TTX-resistant \[[@B5]\]. Voltage-gated sodium channels can be modulated by receptors coupled to intracellular signaling molecules (Figure [2](#F2){ref-type="fig"}). The modulation can occur through phosphorylation of specific residues on the α-subunit after the activation of cytoplasmic protein kinases. Two protein kinases, protein kinase A and protein kinase C, have been shown to target voltage-gated sodium channels. Both are activated by G-protein-coupled second messenger systems. The specific amino acid residues that are phosphorylated by these two kinases are located primarily on the linker between domains 1 and 2. The phosphorylation of voltage-gated sodium channels alters their function \[[@B6]\]. Moreover, the expression of voltage-gated sodium channels can be up-regulated by neurotrophins, including nerve growth factor, brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) (Figure [3](#F3){ref-type="fig"}) \[[@B7]-[@B9]\]. Interestingly, intrathecal injection of neurotrophin-3 causes significant decreases in the levels of Nav1.8 and Nav1.9 in L5 DRGs ipsilateral and contralateral to chronic constriction injury (CCI) of sciatic nerve \[[@B10]\]. In addition, inflammatory cytokines such as tumor necrosis factor α (TNFα) up-regulate the expression of Nav1.3, Nav1.8, and Nav1.9 and increase both TTX-sensitive and -resistant currents in the DRG neurons \[[@B11],[@B12]\]. These effects of neurotrophins and pronociceptive cytokines on sodium channel expression might be mediated through regulation of intracellular downstream signaling pathways of their receptors, including p38 and ERK1/2 mitogen-activated protein kinase (Figure [3](#F3){ref-type="fig"}) \[[@B11],[@B13]\]. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Schematic representation of signaling pathways that modulate Na**^**+**^**channels (Nav)**. The activation of G-protein-coupled receptors (GPCR) by their ligands activates adenylyl cyclase (AC) and phospholipase C (PLC), which produce cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), respectively. cAMP then activates cAMP-dependent protein kinase (PKA), whereas DAG activates protein kinase C (PKC). Both PKA and PKC phosphorylate (P) the Na^+^channel to regulate its function. ::: ![](1744-8069-7-16-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Potential mechanisms by which sodium channel (Nav) expression is regulated**. Neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) bind to their respective receptors: tyrosine kinase receptor (Trk) A, TrkB, and Ret; receptor stimulation then activates the Ras/MEK/MAPK pathway. Activated MAPK promotes expression of sodium channels at the levels of mRNA and protein through unknown mechanisms (indicated by the red dashed arrows). An inflammatory cytokine, tumor necrosis factor α (TNFα), also up-regulates expression of sodium channels through activation of the TRAF2/MEK/MAPK pathway. In contrast, neurotrophin-3 (NT-3) down-regulates the expression of sodium channels through TrkA-mediated inhibition of the Ras/MEK/MAPK pathway (indicated by the blue dashed arrows). MAPK: mitogen-activated protein kinases; MEK: MAPK kinase; TNFR1: tumor necrosis factor receptor 1; TRAF2: TNF receptor-associated factor 2. ::: ![](1744-8069-7-16-3) ::: Most sodium channels (except for Nav1.4, which is predominantly expressed in adult skeletal muscle \[[@B14]\] and Nav1.5, which is expressed in cardiac tissue) have been identified in adult DRGs \[[@B15]\]. Their expression level and the cell types to which they are localized in the DRG are distinct under normal conditions. Unexpectedly, preclinical studies indicate that peripheral nerve injury down-regulates most pain-associated voltage-gated channels in the injured DRG. Whether and how voltage-gated channels participate in nerve injury-evoked ectopic firing in the DRG neurons is still not unclear. In this review, we describe the expression and distribution of each sodium channel subtype in the DRG. We also review evidence regarding changes that occur in channel expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. Finally, we discuss their potential involvement in this disorder. Nav1.1 ------ Nav1.1 is a TTX-sensitive sodium channel \[[@B16],[@B17]\], but the current properties of Nav1.1 have not been characterized in DRG neurons. In situ hybridization histochemistry has shown that Nav1.1 mRNA expression in DRGs is high in large-diameter neurons, moderate in medium-diameter neurons, and low in small-diameter neurons \[[@B18],[@B19]\]. Approximately 25-33% of DRG neurons in naïve rats are positive for Nav1.1 mRNA \[[@B20]\]. Double immunostaining has shown that most Nav1.1-labeled cells are positive for NF200 (a marker for myelinated A-fibers), and that 79.2% of NF200-positive neurons express Nav1.1 mRNA. Research also has shown that 65.0% of Nav1.1-positive cells co-express neurotrophin-3 receptor tyrosine kinase C (TrkC; a marker for non-nociceptive mechanosensors) and that 51.6% of TrkC-labeled DRG cells are positive for Nav1.1 \[[@B21]\]. These findings indicate that Nav1.1 is expressed predominantly in the large-diameter A-fiber DRG neurons and that it might participate mainly in proprioceptive transmission (Table [1](#T1){ref-type="table"}). It should be noted that approximately 11% of Nav1.1 mRNA-positive DRG neurons are positive for IB4 (a marker for small non-peptidergic nociceptive neurons), suggesting that Nav1.1 in these small-diameter DRG neurons may participate in nociceptive transmission and modulation \[[@B20]\]. Indeed, mutations in SCN1A (the gene for Nav1.1) have been associated with inherited epileptic syndromes \[[@B22]\] and familial hemiplegic migraine in humans \[[@B23]\]. Interestingly, preclinical studies showed that the level of Nav1.1 mRNA was decreased in the injured DRG after peripheral spinal nerve ligation (SNL) or spared nerve injury (SNI) \[[@B24],[@B25]\]. Thus, whether and how DRG Nav1.1 is involved in neuropathic pain development is still elusive and remains to be further studied. ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Summary of sodium channel distribution and potential involvement in pain conditions ::: Channel Distribution in normal DRG Inflammatory pain Neuropathic pain Effect of manipulation on behavioral consequences Human disorders --------- ----------------------------------------- ------------------------------------------ ------------------------------ --------------------------------------------------- -------------------------------------------------------------------------- ------------------------------------------------ ------------------------------------------------------------------------- --------------------------------------------------------------------------------------- 1.1 High in large cells, low in small cells Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A Migraine, epilepsy 1.2 Very low in most conditions Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A Epilepsy 1.3 Extremely low in adult DRG Increased (carrageenan) Increased (carrageenan) Increased (SNI, SNL) Increased (SNI, SNL) Effective on SCI and CCI, but no effect on SNI No effect on acute, inflammatory, or neuropathic pain Accumulates in neuromas of human painful neuropathy 1.6 High in large cells, low in small cells Unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNI, SNL) N/A N/A N/A N/A 1.7 Predominantly in small cells Increased (carrageenan, CFA) Increased (carrageenan, CFA) Decreased (SNI, SNL) Decreased (SNA, SNI, and SNL) Effective on CFA Effective on acute and inflammatory pain; no effect on neuropathic pain Decreased in human injured DRG; accumulates in neuromas; mutations: PE, PEPD, and CIP 1.8 Exclusively in small cells Increased (carrageenan) Increased (carrageenan) Decreased (SNI, SNL) Decreased in L5 DRG (SNL, SNI) but increased in L4 DRG and sciatic nerve Effective on CFA, SNL, and CCI Effective on inflammatory pain; no effect on neuropathic pain Accumulates in neuromas of human painful neuropathy 1.9 Selectively expressed in small cells Increased (CFA), unchanged (carrageenan) Unchanged (carrageenan) Decreased (SNA, SNI, and SNL) Decreased (SNA, SNI, and SNL) No effect on SNL Effective on inflammatory pain; no effect on neuropathic pain N/A Abbreviations: CCI, chronic constrictive injury; CFA, complete Freund\'s adjuvant; CIP, channelopathy-associated insensitivity to pain; DRG, dorsal root ganglion; N/A, not applicable; PE, primary erythermalgia; PEPD, paroxysmal extreme pain disorder; SCI, spinal cord injury; SNA, sciatic nerve axotomy; SNI, spared nerve injury; SNL, spinal nerve ligation. ::: Nav1.2 ------ Nav1.2 is one of the predominant sodium channels in the central nervous system; it is localized on dendrites, unmyelinated axons, and premyelinated axons \[[@B26]\]. The level of Nav1.2 mRNA expression in the adult DRG is very low \[[@B18]\], although its expression is moderate in early developmental stages. Peripheral nerve injury and inflammation do not alter the levels of Nav1.2 mRNA or protein in the DRG \[[@B19],[@B24],[@B25]\]. The evidence suggests that DRG Nav1.2 is unlikely to be involved in the development of neuropathic pain (Table [1](#T1){ref-type="table"}). Nav1.3 ------ Although Nav1.3 is expressed abundantly in DRG neurons during fetal and neonatal periods, it is normally undetectable in adult naïve DRG neurons \[[@B27]\]. However, it can be up-regulated in the injured DRG and ipsilateral dorsal horn after peripheral nerve injury. Approximately 37.5% of DRG neurons are Nav1.3-positive in the L5 DRG after sciatic nerve lesion and 15.8% after sural axotomy \[[@B28]\]. In situ hybridization histochemistry showed that, after L5 SNL, 40.7-47.2% of DRG neurons were Nav1.3 mRNA-positive cells, most of which were medium or large in size \[[@B20]\]. A recent study indicated that L5 ventral root transection produces a TNFα-dependent increase in Nav1.3 at both the mRNA and protein levels in the L4 and L5 DRGs \[[@B12]\]. Nav1.3 protein was also found to accumulate in neuromas of patients with painful neuropathy \[[@B29]\] and to up-regulate in second-order dorsal horn neurons after CCI \[[@B30]\]. These findings suggest that an increase in Nav1.3 in DRG and dorsal horn might be involved in nerve injury-induced pain hypersensitivities. Despite the accrued evidence, the role of Nav1.3 in neuropathic pain behavior is still controversial. Hains et al. \[[@B31]\] reported that knockdown of DRG Nav1.3 via intrathecal administration of Nav1.3 antisense oligodeoxynucleotides (ASO) attenuated pain hypersensitivities induced by spinal cord injury and sciatic nerve CCI. In contrast, Lindia et al. \[[@B28]\] found that intrathecal administration of Nav1.3 ASO did not attenuate SNI-induced mechanical or cold allodynia, although it did significantly block the SNI-induced increase in DRG Nav1.3. In addition, neuropathic pain development remained intact in both conventional and conditional Nav1.3 knockout mice \[[@B32]\]. Furthermore, ectopic discharges from the injured nerves were unaffected in the absence of Nav1.3 in conventional knockout mice \[[@B32]\]. These results suggest that Nav1.3 is unlikely to be a key player in the induction of abnormal spontaneous activity in injured neurons (Table [1](#T1){ref-type="table"}). Nav1.6 ------ Nav1.6 is predominantly located in the Nodes of Ranvier of both motor and sensory axons in the peripheral and central nervous systems \[[@B33]\]. In adult DRG, the cellular distribution pattern of Nav1.6 is similar to that of Nav1.1. That is, it is highly colocalized with NF200 \[[@B20]\], indicating that Nav1.6 is an A-fiber-specific channel (Table [1](#T1){ref-type="table"}). Nerve injury alters expression of DRG Nav1.6. Its mRNA is down-regulated in the injured L5 DRG following SNL and SNI \[[@B25]\]. However, in a rat model of infraorbital nerve injury, the level of Nav1.6 protein was found to be significantly increased proximal to the lesion site \[[@B34]\], suggesting that it might be transported quickly to the peripheral terminals under neuropathic pain conditions. Whether this increase participates in the generation of abnormal spontaneous activity in the injured DRG neurons remains to be further studied. Nav1.7 ------ Nav1.7 is widely expressed in sensory, sympathetic, and myenteric neurons \[[@B18],[@B35],[@B36]\]. In the DRG, Nav1.7 is distributed predominantly in small-diameter neurons \[[@B18],[@B19]\]. Double-labeling studies have shown that most NF200-negative neurons (\>99%) express Nav1.7 mRNA \[[@B20]\] (Table [1](#T1){ref-type="table"}). Nav1.7, as well as Nav1.6, Nav1.8, and Nav1.9, is present in most intra-epidermal free nerve endings \[[@B37]\], suggesting that these sodium channels are poised to participate in amplification of generator potentials, and sets the gain on nociceptors. Nav1.7 displays slow closed-state inactivation \[[@B38]\]. As a result of this characteristic, Nav1.7 is unable to respond during high-frequency stimulation, but it responds to small depolarizing stimuli close to the resting membrane potential \[[@B38]\]. Nav1.7 may be physiologically coupled to Nav1.8 within DRG neurons. It serves to boost subthreshold stimuli, resulting in the activation of Nav1.8, which recovers rapidly from inactivation and produces high-frequency action potentials \[[@B39]\]. The evidence indicates that Nav1.7 is expressed mainly on C- and Aδ-nociceptive fibers, contributes to amplification of generator potentials, and sets the gain on nociceptors \[[@B40],[@B41]\]. Indeed, data from animal studies have indicated that Nav1.7 plays a crucial role in nociception. Nav1.7 mRNA and protein are up-regulated in DRG after peripheral inflammation induced by carrageenan or complete Freund\'s adjuvant (CFA) \[[@B19],[@B42]\]. In addition, knockdown of DRG Nav1.7 significantly prevents the development of hyperalgesia in response to CFA \[[@B43]\]. Nav1.7 knockout mice also fail to develop hyperalgesia in several inflammatory pain models (Table [1](#T1){ref-type="table"}) \[[@B44]\]. In humans, mutations in the SCN9A gene (which encodes Nav1.7) are associated with three known pain disorders: channelopathy-associated insensitivity to pain (CIP), paroxysmal extreme pain disorder (PEPD), and primary erythermalgia (PE) \[[@B45],[@B46]\]. Patients with CIP lose normal response to painful insults such as puncture wounds, bone fracture, biting, or contact with hot surfaces, although other sensory responses are normal \[[@B47]\]. PEPD is characterized by severe burning pain in the rectal, ocular, and submandibular regions, and PE by burning pain and redness of the extremities \[[@B48]\]. The evidence indicates that DRG Nav1.7 plays a key role in acute and inflammatory pain. In contrast to its role in acute and inflammatory pain, whether Nav1.7 is involved in nerve injury-induced neuropathic pain is still unclear. Nav1.7 protein and current are both increased in the DRG in a rat model of painful diabetic neuropathy \[[@B49],[@B50]\], whereas the amount of Nav1.7 protein is reduced in the injured DRG after SNL, SNI, and sciatic nerve axotomy in animals \[[@B25],[@B51]\]. The level of Nav1.7 protein is also decreased in the injured DRG of humans after peripheral axotomy or traumatic central axotomy \[[@B52]\], but Nav1.7 protein has been observed to accumulate in painful neuromas of amputees with phantom limb pain \[[@B29],[@B53]\]. Interestingly, a mouse behavioral study showed that conditional knockout of DRG Nav1.7 did not affect SNL-induced development of mechanical allodynia \[[@B54]\]. Thus, it remains questionable whether DRG Nav1.7 has a role in the development of neuropathic pain. Nav1.8 ------ Nav1.8 is a sensory neuron-specific voltage-gated sodium channel that is expressed exclusively in small-diameter nociceptive DRG neurons \[[@B55]\]. Double-labeling studies have shown that 60.0% of Nav1.8-positive DRG neurons are IB4-positive \[[@B20]\]. Nav1.8 mRNA and protein are increased in DRG neurons of rodents following injection of carrageenan into a hind paw \[[@B19],[@B56],[@B57]\]. Knockdown of DRG Nav1.8 reduces the mechanical allodynia caused by intraplantar injection of CFA \[[@B58]\]. Furthermore, Nav1.8 knockout mice display impaired thermal and mechanical pain hypersensitivity in response to carrageenan-induced inflammation \[[@B59]\]. These results indicate that Nav1.8 in DRG plays a key role in inflammatory pain (Table [1](#T1){ref-type="table"}). In contrast to inflammatory insult, peripheral nerve injury down-regulates Nav1.8 mRNA and protein expression in the small-diameter neurons of the injured DRG \[[@B25],[@B60]-[@B62]\]. This down-regulation might be related to epigenetic gene silencing. Peripheral nerve injury up-regulates neuron-restrictive silence factor (NRSF) expression in the DRG and promotes NRSF binding to the neuron-restrictive silencer element within the Nav1.8 gene, thereby silencing its expression \[[@B63]\]. Interestingly, an increase in Nav1.8 protein was observed in the large-diameter neurons of the uninjured L4 DRG after L5 SNL \[[@B25],[@B64]\]. After L5 SNL, Nav1.8 immunoreactivity was also strikingly increased in the uninjured C-fibers of sciatic nerves \[[@B62]\]. Moreover, intrathecal administration of Nav1.8 ASO prevented the nerve injury-induced increase in Nav1.8 in the sciatic nerve \[[@B62]\]. TNFα might participate in this increase because inhibition of TNFα synthesis and knockout of TNFα strongly inhibited nerve injury-induced up-regulation of DRG Nav1.8 \[[@B12]\]. In patients with chronic neuropathic pain, Nav1.8 channel expression was reported to be increased in the nerves proximal to injury sites \[[@B29]\]. These results suggest that peripheral nerve injury might trigger TNFα-dependent translation of Nav1.8 in uninjured DRG neurons and promote the transportation of Nav1.8 from the uninjured DRG cell bodies to their axons. The elevated Nav1.8 in uninjured DRG neurons and their axons might account, at least in part, for the abnormal spontaneous activity and behavioral tactile allodynia observed after nerve injury. Behavioral studies appear to support this conclusion. Intrathecal administration of Nav1.8 ASO attenuated nerve injury-induced mechanical and thermal hyperalgesia \[[@B62]\], although it failed to reduce mechanical allodynia in vincristine-induced neuropathic pain \[[@B58]\]. Small interfering RNAs that specifically target Nav1.8 were able to reverse mechanical allodynia in a rat CCI model when administered intrathecally \[[@B65]\]. Additionally, a Nav1.8 blocker, A-803467, dose-dependently attenuated mechanical allodynia in rat neuropathic pain models of SNL and sciatic nerve injury \[[@B66]\]. Interestingly, neuropathic pain develops normally in the Nav1.8 knockout mouse \[[@B59],[@B67]\]. Moreover, the use of diphtheria toxin to selectively delete most nociceptors (\> 85%) that predominantly express Nav1.8 (as well as Nav1.7 and Nav1.9) in mouse DRG did not affect nerve injury-induced mechanical or thermal pain hypersensitivities \[[@B68]\]. These conflicting results indicate that the role of DRG Nav1.8 in neuropathic pain development is still uncertain and needs to be investigated further. Nav1.9 ------ Nav1.9 is selectively expressed in small-diameter (\<30 μm) DRG neurons. Sixty-two percent of Nav1.9-positive DRG neurons are IB4-positive \[[@B20]\]. DRG Nav1.9 is also highly co-localized with TRPV1, purinergic P2X3 receptor, and B2 bradykinin receptor \[[@B69]\]. Although carrageenan injection does not alter the expression of Nav1.9 mRNA or protein in DRG \[[@B19]\], the level of Nav1.9 mRNA in DRG neurons is significantly increased in the CFA model \[[@B70]\]. Nav1.9 knockout mice exhibit blunted pain behaviors in response to formalin, carrageenan, CFA, and prostaglandin E2 \[[@B71]\]. Similar to Nav1.7 and Nav1.8, DRG Nav1.9 may be required for the development of inflammatory pain (Table [1](#T1){ref-type="table"}). In contrast to its involvement in inflammatory pain, DRG Nav1.9 might not contribute to the development of neuropathic pain. The levels of Nav1.9 mRNA and protein, as well as its current density, are reduced in the DRG after sciatic nerve axotomy \[[@B60],[@B72]\], SNL, and SNI \[[@B25],[@B61]\]. In addition, intrathecal administration of Nav1.9 ASO has no effect on SNL-induced neuropathic pain \[[@B64]\]. Intact mechanical and thermal pain hypersensitivities were observed in Nav1.9 knockout mice after SNI and partial ligation of the sciatic nerve \[[@B69],[@B71]\]. Current preclinical evidence does not support a role for DRG Nav1.9 in the development of neuropathic pain. Conclusion ========== Voltage-gated sodium channels conduct sodium ion influx and control action potential generation. It has been assumed that DRG voltage-gated sodium channels participate in induction of neuropathic pain. However, as summarized in Table [1](#T1){ref-type="table"}, most voltage-gated sodium channels in DRG (with the exception of Nav1.3) are down-regulated after peripheral nerve injury. This down regulation is in contrast to the increased expression that is observed under persistent inflammatory pain conditions. The mechanisms that underlie the expression changes in neuropathic pain are still unclear. As discussed above, neurotrophins (e.g., BDNF and GDNF) and cytokines modulate voltage-gated sodium channel expression (Figure [3](#F3){ref-type="fig"}). Up-regulation of the neurotrophic factors and the release of cytokines cannot explain the down-regulation of voltage-gated sodium channels in the DRG under neuropathic pain conditions \[[@B73],[@B74]\]. More importantly, most behavioral findings from animal models do not support a role for DRG voltage-gated sodium channels in neuropathic pain (Table [1](#T1){ref-type="table"}). Interestingly, the use of sodium channel blockers (such as lidocaine) in patients can effectively inhibit a variety of neuropathic pain syndromes \[[@B75]\], although they also produce significant side effects. Inconsistent results between clinical and laboratory observations necessitate careful consideration of the differences between human and animal models and the methods for pain assessment. Therefore, a possible role for DRG voltage-gated sodium channel function in neuropathic pain cannot be excluded and remains to be further investigated. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= WW and YXT participated in the drafted manuscript. JG, YQL, and YXT contributed to critical review of the manuscript. All authors have read and approved the final manuscript. Acknowledgements ================ This work was supported by the Blaustein Pain Research Fund, Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund, and the Brain Science Institute at the Johns Hopkins University; NIH Grant NS 058886; the National Natural Science Foundation of China (30771133, 30971123, 31010103909); the National Program of Basic Research of China (G2006CB500808); and the Innovation Research Team Program of Ministry of Education of China (31010103909). The authors thank Claire F. Levine, MS, for her editorial assistance.

PubMed Central

2024-06-05T04:04:18.993470

2011-2-23

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052185/", "journal": "Mol Pain. 2011 Feb 23; 7:16", "authors": [ { "first": "Wei", "last": "Wang" }, { "first": "Jianguo", "last": "Gu" }, { "first": "Yun-Qing", "last": "Li" }, { "first": "Yuan-Xiang", "last": "Tao" } ] }

PMC3052186

Background ========== Ventricular assist devices (VAD) are mechanical pumps that replace or augment left and/or right ventricular function in cases of refractory cardiogenic shock. A number of approaches are currently taken related to the indications of these devices: VAD can be used as a bridge to heart transplantation, as a bridge to myocardial recovery leading in some cases to their prolonged use with meaningful survival and improved quality of life \[[@B1]\]. Recently VAD have also begun to be used as a \"bridge to destination\" that is, they are the final plan for the patient, being used for many years, until the patient succumbs. Fundamental differences regarding cardiac output and systemic circulation distinguish two main types of VAD: pulsatile and continuous-flow VAD. The main advantages of continuous-flow VAD being the self-contained nature, not requiring a pneumatic driver, longevity, lack of bearing contacting with blood and absence of artificial valves with theoretically smaller thrombogenic surface \[[@B2]\]. However, the effects of non-pulsatile perfusion on end-organ function remain controversial \[[@B3]-[@B5]\]. Pulsatile circulation and its effects on systemic vascular resistances have been related to the improvement of microcirculation and endothelial integrity \[[@B6],[@B7]\]; reduction in splanchnic perfusion and reduction of intestinal edema \[[@B8]\]; improvement of the cerebral haemodynamics and cerebrospinal fluid drainage \[[@B2]\] and the maintenance of neuro-endocrine cascades, specifically within the renin-angiotensine system and catecholamine release \[[@B5]\]. Despite the use of pulsatile VADs, non-homogeneous output is often generated as pulsatile VADs eject once the pre-established filling volume (stroke volume) has been reached. Therefore, the VAD ejection rate varies depending on preload and systemic resistance. Frequently there is a variable degree of persistent native cardiac contractibility, leading to asynchrony, and irregularities in arterial blood pressure waveform (Figure [1](#F1){ref-type="fig"}). In such situations of circulatory irregularity, end-organ perfusion such as cerebral blood flow may require an intact autoregulation to ensure stable microcirculation. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Real time, beat-to-beat traces of arterial blood pressure (BP) and cerebral blood flow velocity (CBFV) with a ventricular assist device (VAD)**. Upper channel: arterial BP waveform in a patient supported with a VAD, showing irregular fluctuations; middle channel: CBFV (insonated at the level of middle cerebral artery) with fluctuations transmitted from arterial BP; lower channel: electrocardiogram (ECG). ::: ![](1471-2253-11-4-1) ::: Cerebral autoregulation is the mechanism by which cerebral blood flow (CBF) is maintained despite changes in cerebral perfusion pressure (CPP). Cerebral autoregulation mediates states of hyperemia and ischemia to avoid vasogenic edema or infarction respectively \[[@B9]\]. Impaired autoregulation has been regarded as a risk factor associated with adverse neurological outcome after cardiac surgery \[[@B10],[@B11]\]. As a dynamic phenomenon, cerebral autoregulation may respond to spontaneous and induced changes in arterial blood pressure (BP) such as those occurring with pulsatile VADs \[[@B12],[@B13]\]. Cerebral autoregulation has been extensively studied using transcranial Doppler (TCD) which measures cerebral blood flow velocities (CBFV) as a surrogate of CBF \[[@B14],[@B15]\] using a variety of methods \[[@B16]\]. From all described methods, transfer function analysis (TFA) enables the analysis of phase shift, gain and coherence between two signals (arterial BP as input and CBFV as output) at a range of frequencies, and has the advantage of being applicable for continuous and non-invasive testing of cerebral autoregulation at the bedside. Rider and coworkers assessed cerebral autoregulation in patients supported with non-pulsatile VADs, by exposing them to dynamic maneuvers such as head-up tilting and measuring the change in CBFV. They found that cerebral autoregulation was impaired, suggesting that circulatory pulsatility is crucial for the maintenance of cerebral autoregulation \[[@B17]\]. However, their study occurred during the acute phase of the disease, after the insertion of a non-pulsatile VAD and prior to any myocardial \"modeling\" \[[@B18]\] could have occurred. Some authors have demonstrated that even with the use of non-pulsatile VAD, if a recovery time is allowed, CBF shows recovery of its pulsatility \[[@B2]\], attributing this finding to overall myocardial recovery and specifically right ventricular recovery. Whilst previous study examined the effects of non-pulsatile VAD on the regulation of steady state CBF, this study is the first to investigate the effects of pulsatile VAD, which generates irregular pressure waveform patterns, on the dynamic cerebral pressure-flow relationship by applying the cross-spectral TFA technique. Methods ======= Institutional Ethics Committee approval for the performance of the study was granted. All patients or their next of kin gave informed consent prior to enrolment in the study. A convenience sample of five patients supported with a pulsatile Thoratec VAD (Thoratec corporation, Pleasenton, CA, US) was compared with five control patients, matched for age, comorbidities, current diagnosis and cardiac output state (Table [1](#T1){ref-type="table"}). All cases were supported with a left ventricular pulsatile VAD and inotropic drugs for an average of 7 days. All patients were in their acute phase of their disease. Control subjects were in a low output state requiring inotropic or vasopressor support but without the support of VAD. Although their mean arterial blood pressure (MAP) was similar to the VAD cases, their native left ventricular ejection fraction (LV EF) was better. All patients in the control group survived, whereas 2 of the VAD cases died (Table [2](#T2){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Demographics and patients\' characteristics ::: VAD Age (years) Pathology comorbidities day of admission --------- ------------- ----------- --------------- ------------------ VAD1 52 MI none day 2 VAD2 43 MI hypertension day 29 VAD3 25 OHCA + MI none day 25 VAD4 35 OHCA hypertension day 7 VAD5 63 OHCA hypertension day 25 Control C1 64 MI none day 5 C2 65 MI hypertension day 4 C3 69 OHCA + MI hypertension day 3 C4 55 OHCA hypertension day 3 C5 50 OHCA hypertension day 2 MI: Myocardial infarct; OHCA: Out of hospital cardiac arrest; ::: ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Therapy and clinical variables ::: VAD Support therapy MAP (mmHg) CBFV (cm/s) PCO~2~(mmHg) LV EF (%) Outcome ----------- ----------------- ------------ ------------- -------------- ----------- --------------------- VAD1 VAD 82 38 36 35 Survived VAD2 VAD 96 47 40 30 Survived VAD3 VAD + DPM + NA 60 101 42 20 Intrahospital death VAD4 VAD 74 45 40 20 Survived VAD5 VAD + DPM 70 39 32 15 Intrahospital death Mean ± SD 76 ± 14 54 ± 26 38 ± 4 24 ± 8 Control C1 DPM 79 36 42 40 Survived C2 DPM 90 43 35 25 Survived C3 DPM + DBT 70 53 48 30 Survived C4 DPM + NA 75 39 41 30 Survived C5 DPM 80 42 37 40 Survived Mean ± SD 79 ± 7 43 ± 6 41 ± 5 33 ± 7 *P* 0.74 0.36 0.39 0.09 VAD: Ventricular Assist Device; MAP: Mean Arterial Pressure; CBFV: cerebral blood flow velocity (mean values are given); LV EF: Left Ventricular Ejection Fraction; NA: Noradrenaline; DPM: Dopamine; DBT: Dobutamine. ::: We recorded at least 5 minutes of data under resting conditions in all subjects. Simultaneous beat-to-beat recordings of BP and cerebral blood flow velocity (CBFV) waveforms were sampled using a data acquisition unit (ADInstruments, Australia). The BP waveform was acquired from an intra-arterial catheter; CBFV of middle cerebral artery (MCA) was measured using a transcranial Doppler device with a 2 MHz probe and a power of 100 mW/cm^2^(DWL, Germany). CBFV of middle cerebral arteries (MCAs) were measured using TCD following referenced criteria at the temporal acoustic window \[[@B15]\]. Both MCAs were insonated and the side with best acoustic characteristics chosen for study. Intra-patient variability was minimized by using only one investigator formally trained in TCD \[[@B16]\]. Stability of the insonated vessel diameter was assumed by maintaining a stable partial pressure of arterial carbon dioxide (pCO~2~) during measurements. Therapeutic and clinical variables were recorded at the moment of data acquisition. This study was merely observational and did not interfere with the treating physician\'s management plan. Spectral Analysis ----------------- For the assessment of cerebral autoregulation, this study used TFA based on frequency domain cross-spectral analysis. TFA assesses the relationship between two signals in the frequency domain and yields three interpretable parameters (i.e. gain, phase, and coherence). Gain is the indicator of the magnitude with which the change of output signal (i.e. CBFV) is caused by the change of input signal (i.e. BP). In the context of cerebral autoregulation analysis, a small gain indicates that cerebral blood flow does not change significantly when blood pressure changes, indicating that the cerebral autoregulatory mechanisms are intact. Phase shift relates to the temporal lag between BP and CBFV at each frequency. Zero phase lag signifies synchronous fluctuations, whilst positive phase suggests CBFV leading BP, and negative phase suggests BP leading CBFV. The gain and phase metrics, however, need to be interpreted in the context of the cross-spectral coherence, which is an estimation of the linear correlation between the input and output signals at particular frequencies. Coherence varies between 0 and 1; where 0 indicates no linear relationship and 1 indicates perfect linear relationship. It has been suggested that an increase in coherence may be indicative of a blunted cerebral autoregulation \[[@B21]\]. A low coherence, however, can be interpreted as presence of external noise/input, or nonlinear/lack of relationship between input and output. In this study, spectral analysis was performed on 5 min artifact-free segments of continuous CBFV and BP signals. Signals were downsampled to 1 Hz after appropriate anti-aliasing lowpass filtering, with any slow trend removed by cubic spline detrending. The frequency spectra and transfer function were obtained using the Welch method \[[@B21]\]. This involved subdividing the signal into 120s segments with 75% overlap (resulting in 7 segments), multiplying each segment with a Hanning window, then performing a Fast Fourier Transform (FFT), and finally averaging to give the spectra. Defining the autospectra of BP and CBFV as *S*~xx~(*f*) and *S*~yy~(*f*) (with *f*denoting frequency), the cross-spectrum of BP and CBFV, *S*~xy~(*f*), was computed as the product of *S*~xx~\*(*f*) and *S*~yy~(*f*) (*asterisk denotes the complex conjugate*). The transfer function from BP to CBFV was computed as *H*(*f*) = *S*~xy~(*f*)/*S*~xx~(*f*), and the gain magnitude and phase angle of the transfer function was obtained accordingly. The magnitude-squared coherence function was computed as γ^2^(*f*) = \|*S*~xy~(*f*)\|^2^/*S*~xx~(*f*)*S*~yy~(*f*), for detecting linear correlation between the spectral components in the two signals. Coherence ranged from 0 (*lack of linear correlation*) to 1 (*perfect linear relationship*). The spectral powers of BP and CBFV and the mean values of the transfer function gain, phase and coherence were calculated in the very low frequency (VLF, 0.02-0.07 Hz), low frequency (LF, 0.07-0.20 Hz) and high frequency (HF, 0.20-0.35 Hz) ranges as previously defined \[[@B22]\]. Unpaired Student\'s t-test was performed to compare the variables between the VAD and the control groups. *P*\< 0.05 was considered statistically significant. Results ======= The patient characteristics are presented in table [1](#T1){ref-type="table"} and [2](#T2){ref-type="table"}. No significant difference in MAP, pCO~2~and LVEF was found between the VAD and the control groups. The levels of pCO~2~were maintained within normal ranges and stable throughout the study, thus the effect of CO~2~on cerebral vessel was minimised. LVEF was generally lower for the VAD cases, whichwas expected as these were patients with baseline refractory cardiogenic shock who required a VAD for life support. However the difference did not reached statistical significance. The results from spectral and cross-spectral transfer function analysis of MAP and CBFV were presented in table [3](#T3){ref-type="table"} and [4](#T4){ref-type="table"}. Display of gain, phase and coherence for a representative case and control are shown in figures [2](#F2){ref-type="fig"} and [3](#F3){ref-type="fig"} respectively. No significant difference was found between the VAD and the control groups, apart from a significantly higher LF coherence between MAP and CBFV in the VAD cases (*P*= 0.04). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Power spectrum analysis of mean arterial pressure (MAP) and mean cerebral blood flow velocity (CBFV) in ventricular assist device (VAD) cases and controls ::: VAD VLF LF HF ------------- ------------- ------------- ------------- ------------- ------------- ------------- VAD1 0.80 2.77 0.28 0.48 0.94 0.47 VAD2 2.34 7.94 2.41 3.77 0.32 1.46 VAD3 1.06 3.22 0.20 0.94 8.88 3.72 VAD4 3.26 6.55 4.42 3.67 2.15 1.79 VAD5 2.97 2.61 0.49 1.14 5.44 2.24 Mean ± SD 2.09 ± 1.11 4.62 ± 2.46 1.56 ± 1.84 2.00 ± 1.59 3.55 ± 3.58 1.94 ± 1.19 **Control** **VLF** **LF** **HF** **pMAP** **pCBFV** **pMAP** **pCBFV** **pMAP** **pCBFV** C1 0.47 1.12 1.55 0.80 3.80 0.56 C2 1.52 4.92 0.08 0.61 2.44 1.42 C3 2.43 6.93 0.10 0.43 2.55 1.69 C4 0.95 2.72 0.23 0.65 0.17 0.25 C5 0.24 1.20 0.70 1.42 1.98 3.23 Mean ± SD 1.12 ± 0.88 3.38 ± 2.51 0.53 ± 0.62 0.78 ± 0.38 2.19 ± 1.31 1.43 ± 1.17 *P* 0.17 0.45 0.27 0.13 0.45 0.52 VLF, very low frequency (0.02-0.07 Hz); LF, low frequency (0.07-0.2 Hz); HF, high frequency (0.2-0.35 Hz). pMAP (in mmHg^2^) and pCBFV (in (cm/s)^2^) are spectral powers of MAP and mean CBFV respectively. \**P*\< 0.05 from t-test between VAD and Control. ::: ::: {#T4 .table-wrap} Table 4 ::: {.caption} ###### Transfer function analysis (TFA) of mean arterial pressure (MAP) and mean cerebral blood flow velocity (CBFV) in ventricular assist device (VAD) cases and controls ::: VAD VLF LF HF ------------- ------------- ------------- -------------- ------------- ------------- ------------- ------------- ------------- ------------- VAD1 0.67 1.35 1.00 0.65 1.20 -0.38 0.67 0.75 0.51 VAD2 0.76 1.82 0.98 0.79 1.25 -0.08 0.68 1.96 0.30 VAD3 0.20 0.95 0.32 0.45 1.52 0.27 0.54 1.13 0.21 VAD4 0.44 0.89 0.90 0.82 0.83 0.51 0.74 0.79 0.16 VAD5 0.45 0.63 1.04 0.56 1.18 0.72 0.77 0.72 0.00 Mean ± SD 0.50 ± 0.22 1.13 ± 0.47 0.85 ± 0.30 0.65 ± 0.16 1.20 ± 0.25 0.21 ± 0.44 0.68 ± 0.09 1.07 ± 0.52 0.24 ± 0.19 **Control** **VLF** **LF** **HF** **Coh** **Gain** **Phase** **Coh** **Gain** **Phase** **Coh** **Gain** **Phase** C1 0.13 0.55 0.73 0.65 0.65 0.62 0.74 0.36 -0.09 C2 0.61 1.43 0.63 0.21 1.71 -0.24 0.32 2.29 0.27 C3 0.72 1.33 0.33 0.30 1.89 0.07 0.34 2.24 -0.15 C4 0.46 1.12 -0.27 0.25 1.07 -0.40 0.28 1.02 -0.18 C5 0.25 1.15 -1.71 0.51 1.18 0.76 0.91 1.28 0.21 Mean ± SD 0.43 ± 0.25 1.12 ± 0.34 -0.06 ± 1.00 0.38 ± 0.19 1.30 ± 0.50 0.16 ± 0.51 0.52 ± 0.29 1.44 ± 0.83 0.01 ± 0.21 *P* 0.65 0.96 0.089 0.039\* 0.69 0.88 0.26 0.42 0.11 VLF, very low frequency (0.02-0.07 Hz); LF, low frequency (0.07-0.2 Hz); HF, high frequency (0.2-0.35 Hz). Coh, gain (in cm/s/mmHg) and phase (in rad) are the transfer function coherence, gain and phase from MAP to mean CBFV. \**P*\< 0.05 from t-test between VAD and Control. ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Transfer function analysis (TFA) of mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) in a patient with ventricular assist device (VAD)**. The gain, phase and coherence spectra of a representative case with VAD were shown. ::: ![](1471-2253-11-4-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Transfer function analysis (TFA) of mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) in a control patient**. The gain, phase and coherence spectra of a representative control were shown. ::: ![](1471-2253-11-4-3) ::: Discussion ========== In this study, the cross-spectral transfer function analysis technique was applied to study the dynamic relationship between systemic BP and CBFV in patients using pulsatile VAD. The rationale was to describe any potential alteration of cerebral autoregulation function associated with the use of VAD, as the long term use of VAD may lead to impaired cerebral autoregulation and worse neurological outcomes. The key finding of the study was the higher coherence between MAP and CBFV in the VAD patients compared with the controls, at the LF range. A low coherence between MAP and CBFV (\<0.5)indicates a lack of linear relationship between pressure and flow at the particular frequency range, and can be attributed to the presence of an intact cerebral autoregulation that introduces nonlinearity relationship \[[@B21],[@B22]\]. It has been suggested that the complex nonlinear behavior of the cerebral vasculature might be responsible for the low coherences at the VLF and LF ranges \[[@B24]-[@B26]\]. The augmented LF coherence in the VAD patients, on the other hand, might suggest a lower degree of cerebral autoregulation, possibly due to disruption of autoregulatory mechanisms by the use of VAD. However, one potential limitation to this interpretation was that, although no significant difference in the MAP power was observed between the two groups, the two VAD patients with the highest coherence (\~0.8) also had much higher spectral power in MAP than the rest of the group. It has been suggested that an increased input pressure change might lead to an increase in coherence, via an improved \"signal-to-noise\" ratio \[[@B27]\]. This effect might contribute in part to the higher coherence in the VAD group. The lack of differences in TFA gain and phase between the VAD and the control group also raised questions whether there was significant disruption of cerebral autoregulation by the use of pulsatile VAD. Alterations in cerebral autoregulation function by pathological conditions (such as stroke and autonomic failure \[[@B28],[@B29]\]) are typically associated with changes in gain and/or phase, which were not observed in the current study. Neverthelss, it appeared that the highpass filtering property of the cerebral circulation, characterised by smaller gain at the lower frequencies (VLF) and an increase in gain towards the higher frequencies (HF) \[[@B21],[@B27]\], was more apparent in the control group compared with the VAD group. It would therefore still be possible that gain properties of cerebral autoregulation might have changed in the VAD patients, although the interpretation of the gain parameter would have been limited somewhat by the low coherences in the control patients. Methodological considerations and limitations --------------------------------------------- In this study, direct assessment of CBF was not feasible as the use of non-imaging TCD does not facilitate the measurement of the cerebral vessel cross-sectional area. Instead, there is a global consensus supporting the use of CBFV as a surrogate for CBF, provided the vessel diameter remains stable during the study \[[@B30]\]. Among all factors intervening in changes of vessel diameter and therefore determining CBF \[[@B23]\], pCO~2~is directly related with vessel diameter and was maintained stable and within normal values, during patient recruitment. For TCD recordings, only the MCA with better acoustic properties was recorded and analyzed. Although spatial heterogeneity of cerebral perfusion as well as interhemispheric differences has been described \[[@B30]\]; the endpoint in this study was to ensure the best transcranial Doppler recordings in order to minimize the signal-to-noise ratio and increase data reliability \[[@B30]\]. No significant change in gain and phase was found between the two groups in this study, but the small population recruited could have contributed to the lack of statistical significance, thus further studies with larger sample size would be desirable. Conclusion ========== The use of pulsatile VAD affected the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range, thus whether there was any significant disruption of cerebral autoregulation mechanism was not clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed. Given the absence of all conditions that define autoregulation, these results should be regarded as preliminary data, and further studies, employing bigger samples, are warranted. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= JB and JFF conceived and designed the study; JB undertook patient screen and data acquisition; JB drafted the manuscript which was reviewed and amended by all other authors. GC and Y-C T undertook data analysis and contributed to its interpretation. AGB undertook statistical analysis. KRD conceived and designed the technical components of the study, also reviewed revised the manuscript. RB and PA reviewed and amended the manuscript. All authors read and approved the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1471-2253/11/4/prepub> Acknowledgements ================ We acknowledge Dr Daniel Mullany for ensuring patients\' availability during study recruitment. This research was supported by a research grant from the Royal Brisbane Hospital Research Foundation (Protocol 2007/076). Additional funding was provided by the Prince Charles Hospital Research Foundation.

PubMed Central

2024-06-05T04:04:18.995985

2011-2-22

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052186/", "journal": "BMC Anesthesiol. 2011 Feb 22; 11:4", "authors": [ { "first": "Judith", "last": "Bellapart" }, { "first": "Gregory S", "last": "Chan" }, { "first": "Yu-Chieh", "last": "Tzeng" }, { "first": "Philip", "last": "Ainslie" }, { "first": "Adrian G", "last": "Barnett" }, { "first": "Kimble R", "last": "Dunster" }, { "first": "Rob", "last": "Boots" }, { "first": "John F", "last": "Fraser" } ] }

PMC3052187

Background ========== Reverse transcription quantitative PCR (RT-qPCR) is rapidly becoming a valuable tool for mRNA biomarker quantification in clinical diagnostics. There has been a proliferation of RT-qPCR assay formats and platforms in recent years due to wider applications of this technology, coupled with improvements in sensitivity, specificity and accuracy of measurements of gene expression. However, there is one intrinsic limitation to the current qPCR platforms, namely lack of controls for cross-platform comparison. Although the manufacturers have developed platform-specific quality controls, they are often not adequate for cross-platform comparisons, particularly for the evaluation and standardization of transcriptomic data due to differences in protocols, data processing and analysis methods. Thus, development of universal RNA standards offers great potential in the validation of data obtained from different RT-qPCR methods. In the present investigation, we have compared the performance of Fluidigm^®^BioMark™ Integrated microfluidic (henceforth referred to as BioMark) dynamic arrays with the widely used ABI 7900HT real-time PCR platform (henceforth called ABI 7900HT system) using generic RNA standards. Pre-amplification of RNA or cDNA facilitates the investigation of a large number of genes when the starting material is limiting, such as with tissue biopsies and archival formalin-fixed paraffin-embedded (FFPE) samples \[[@B1],[@B2]\]. Pre-amplification methods used generally include either linear amplification of RNA or exponential (PCR-based) amplification of cDNA \[[@B3]-[@B5]\]. However, concerns have been raised as to whether pre-amplification of samples by exponential amplification introduces bias in expression levels between genes \[[@B6]\]. For the BioMark microfluidic PCR system, each sample in the 48 × 48 dynamic array is distributed amongst 48 different reaction chambers, therefore pre-amplification is recommended for certain applications. However the limit of detection (LOD) of using pre-amplified *vs*. non-amplified cDNA samples, and its impact on the technical performance of the PCR array have not been fully characterized. Exogenous RNA controls produced by *in vitro*transcription are ideal materials for investigating different RT-qPCR kits and methodologies \[[@B7]\]. Recently a panel of RNA controls have been developed for use in gene expression applications by the External RNA Controls Consortium (ERCC), an *ad hoc*group of 70 members from private, public and academic organizations led by the National Institute of Standards (NIST) \[[@B8],[@B9]\]. It is hoped that standards developed from these sequences will aid in comparisons of gene expression data generated from various platforms such as microarray, RT-qPCR and next generation sequencing, and also provide quality control of gene expression measurements in the clinical laboratory \[[@B10]\]. Multigene biomarker measurements are at the forefront of a new class of medical devices using *in vitro*diagnostic multivariate assays, such as MammaPrint and Oncotype Dx in the area of breast cancer prognosis \[[@B11]\]. Since gene expression biomarkers typically encompass a range of transcript abundances and differential expression ratios, it is more appropriate to use multiple RNA standards as quality controls for standardizing such measurements, as opposed to a single transcript at a fixed concentration. In the current study, we used a sub-set of the 96 ERCC RNA standards (Additional File [1](#S1){ref-type="supplementary-material"}) in order to characterize their performance on a nanofluidic PCR system, the BioMark 48 × 48 dynamic arrays, against a conventional qPCR platform, the ABI 7900HT system. We also investigated the impact of pre-amplification of cDNA samples on the linear range and precision of measurements by nanofluidic qPCR. Two prototype panels were constructed with selected RNA standards containing varying copy number within each panel, and varying ratios between them for mimicking non-differentially and differentially expressed mRNA biomarkers as represented in normal and disease states. The expression profile of the RNA standards was measured using both platforms and the accuracy and precision of their detection were compared. Results ======= Linear range of dynamic arrays ------------------------------ One advantage of the BioMark arrays is the capability to analyse a large number of genes in a single sample. In order to facilitate this, up to \~ 2 μL of sample is loaded into each sample inlet of the chip and further distributed in the channels of the microfluidic chip as 48 separate 9 nL reactions using the integrated fluidic circuit (IFC). Thus the original sample is diluted more than 200-fold prior to the PCR reaction. In order to ensure that there are sufficient copies of target molecules in each reaction, Fluidigm^®^recommends using either RNA samples that do not have a concentration lower than 250 ng total RNA/μL or that a pre-amplification stage is included, whereby the cDNA sample undergoes 14-18 cycles of amplification with a mix of up to 100 different primer pairs (Fluidigm Advanced Development Protocols 3, 5 and 8). In order to further investigate the requirement for pre-amplification, RNA standards were spiked into human total RNA at different concentrations (for sample composition, see Additional File [2](#S2){ref-type="supplementary-material"}) with the aim of mimicking a range of physiological abundances, from highly abundant mRNA transcripts (10^6^copies/ng total RNA; equivalent to 10^4^copies per cell) to transcripts only expressed in a sub-population of cells (1 copy/ng total RNA; equivalent to 0.01 copies per cell), based on the RNA content of a cell estimated as 26 pg \[[@B12]\]. A single RT reaction was performed for each RNA sample followed by 3 independent qPCR runs, with replicate assay measurements for each ERCC standard. Figure [1](#F1){ref-type="fig"} compares the results of real-time PCR with cDNA samples (equivalent to 1 ng total RNA) or pre-amplified cDNA on the BioMark arrays with non-amplified cDNA using the ABI 7900HT system. The linear range in terms of transcript copy numbers for the pre-amplified cDNA samples on the BioMark arrays was similar to the non-amplified cDNA samples on the ABI 7900HT system, covering five orders of magnitude between 10 and 10^6^copies/ng total RNA. Although the linear range of both platforms was similar, the Ct values from BioMark were over 10 units lower than those observed for ABI 7900HT system. This could be due to the higher concentration of the template in the 9 nL nanofluidic reaction chambers of BioMark arrays compared to the standard 20 μL volume used on the ABI 7900HT system, such that the fluorescence output of the PCR reaction exceeds the threshold level at an earlier cycle (personal communication: A. Meliss, Fluidigm, September 2009). For the RT-PCRs performed with non-amplified cDNA samples on BioMark arrays, the linear detection range covered only two orders of magnitude between the transcript numbers of 10^4^and 10^6^copies/ng. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Linear range of RT-qPCR platforms**. Example plot showing detection of an ERCC RNA standard (ERCC-42) across a range of transcript copy numbers from 1 to 10^6^copies per ng total RNA with cDNA (triangles) or pre-amplified cDNA (diamonds) as the template on (A) BioMark (B) ABI 7900HT system. Data-points are displayed as individual qPCR replicates. Dotted line indicates linear detection range. ::: ![](1471-2164-12-118-1) ::: LOD of dynamic arrays --------------------- Unlike hybridization-based technologies such as microarrays, the LOD cannot be ascribed for RT-qPCR using a baseline for sample blanks, as a Ct value is not obtained for zero control samples. Therefore, the incidence of failed PCR reactions (undetermined Ct value) across the range of transcript abundances was also compared for conventional and nanofluidic PCR platforms with pre- or non-amplified cDNA as the template (Figure [2](#F2){ref-type="fig"}). As in Figure [1](#F1){ref-type="fig"}, a high percentage of PCR failures was observed at 1 copy/ng total RNA for both pre-amplified cDNA on the BioMark arrays and cDNA using the ABI 7900HT system. The rate of failures was slightly lower on the BioMark arrays as the projected template concentration per 9 nL reaction was 6 copies (assuming 100% efficiency of RT and pre-amplification), whilst it was only 1 RNA copy per ABI 7900HT reaction. For non-amplified cDNA, high reaction failure rates with BioMark arrays were observed below 10^3^copies/ng, which equates to 2 copies per 9 nL reaction. ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Limit of detection of ERCC RNA standards**. Incidence of failed PCR reactions on ABI 7900HT system or BioMark using cDNA or pre-amplified cDNA as the template. Mean percentage of failed PCR reactions ± SD are displayed based on data from 8 different RNA standards from 3 independent qPCR experiments across a range from 1 to 10^6^copies ERCC standard per ng total RNA. ::: ![](1471-2164-12-118-2) ::: qPCR accuracy and precision --------------------------- The accuracy and precision of qPCR detection across the above noted linear range was assessed by linear regression, comparing the slope and R^2^of the data from three independent dynamic arrays (Table [1](#T1){ref-type="table"}). Pre-amplification of cDNA samples resulted in a significant improvement in the slope of the linear regression of copy number against Ct value (*p*\< 0.05), with the mean slope within 6% of the ideal slope of 1. The pre-amplified cDNA samples demonstrated greater precision of the instrument over the linear detection range (Figure [1](#F1){ref-type="fig"}) than cDNA (*p*\< 0.05) (Table [1](#T1){ref-type="table"}). The accuracy and precision of pre-amplified cDNA detection on the BioMark arrays were comparable to those of the ABI 7900HT where non-amplified cDNA was used as the template (Table [1](#T1){ref-type="table"}). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Accuracy and precision of linear detection range of PCR platforms ::: -------------------------------------------------------------------------------------------------------------------- Slope **R**^**2**^ -------------- -------------------- ---------------- -------------------- -------------------- ---------- ---------- **Platform** **Dynamic arrays** **ABI 7900HT** **Dynamic arrays** **ABI 7900HT** **Template** **Pre-amplified**\ **cDNA** **cDNA** **Pre-amplified**\ **cDNA** **cDNA** **cDNA** **cDNA** **ERCC-** 13 -1.06 -1.08 -1.06 0.999 0.993 0.997 42 -1.07 -1.11 -1.06 0.998 0.970 0.995 81 -1.02 -1.07 -1.04 0.998 0.976 0.998 84 -1.03 -1.07 -1.01 0.998 0.973 0.996 95 -1.07 -1.12 -1.08 0.997 0.975 0.998 99 -1.06 -1.06 -1.05 0.998 0.985 0.997 113 -1.06 -1.15 -1.04 0.998 0.971 0.997 171 -1.12 -1.13 -1.08 0.998 0.982 0.996 All -1.06 -1.10 -1.05 0.999 0.978 0.997 -------------------------------------------------------------------------------------------------------------------- Linear regression was performed with Ct values vs. log~2~(ERCC RNA copy number) for each PCR platform across the linear range marked in Figure 1. The mean slope and R^2^values from three independent qPCR experiments reflect the accuracy and precision of the detection of the 10-fold differences in copy numbers between samples. ::: Precision of qPCR detection as a function of transcript copy number for the two platforms is shown in Figure [3](#F3){ref-type="fig"}. For concentrations of RNA standards above 10^4^copies/ng (using cDNA with the ABI 7900HT system or pre-amplified cDNA for the BioMark arrays), and above 10^6^copies/ng (with non-amplified cDNA for the BioMark arrays), Ct standard deviation values are below 0.1 units, corresponding to less than 7% variation \[[@B13]\]. As RNA copy numbers decrease, variation between replicate qPCR measurements increases, with maximum average standard deviation values corresponding to 46% and 66% variation at 10 copies/ng for the BioMark arrays (pre-amplified cDNA) and ABI 7900HT system respectively (Figure [3](#F3){ref-type="fig"}). ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Precision of real-time PCR platforms**. Within-run qPCR precision across a range of transcript abundance levels (copies per ng total RNA) are displayed for cDNA or pre-amplified cDNA quantified using ABI 7900HT system or BioMark. Mean variation (SD) of Ct values ± SD is displayed based on data from eight different RNA standards from three independent qPCR experiments. ::: ![](1471-2164-12-118-3) ::: RNA biomarker panels -------------------- The accuracy of nanofluidic dynamic PCR for detection of multiple genetic biomarkers was further tested using two panels of RNA standards. With the aim of mimicking \'normal\' and \'disease\' states where some biomarkers are differentially expressed whilst others remain unchanged in their expression, standards were spiked at different ratios (1.0, 1.5, 2.0, 5.0, 10.0 and 20-fold differences) over a range of transcript copy numbers (Table [2](#T2){ref-type="table"}). Three independent RT experiments, each containing two replicate RT reactions, were performed in order to investigate how technical noise associated with the whole RT-qPCR process impacts on the detection of differential or non-differential transcript expression levels. The resulting cDNA was quantified on the ABI 7900HT system or pre-amplified and measured on the BioMark. Fold change values were calculated using ΔCt values and the results of pair-wise comparison of the expression levels of each ERCC standard in the two panels displayed in Figure [4](#F4){ref-type="fig"}. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Concentrations and ratios of ERCC RNA standards in simulated \'normal\' and \'disease\' panels ::: ERCC standard Copies/ng total RNA Ratio B/A --------------- --------------------- ------------- ------ 13 1 × 10^5^ 1 × 10^5^ 1.0 25 1 × 10^2^ 1.5 × 10^2^ 1.5 42 1 × 10^4^ 5 × 10^3^ 0.5 51 5 × 10^0^ 1 × 10^2^ 20.0 81 1 × 10^2^ 1 × 10^2^ 1.0 84 1 × 10^2^ 5 × 10^2^ 5.0 95 1 × 10^3^ 1 × 10^3^ 1.0 99 8 × 10^3^ 1.2 × 10^4^ 1.5 113 1 × 10^1^ 1 × 10^1^ 1.0 171 1 × 10^1^ 1 × 10^2^ 10.0 10 ERCC RNA standards were spiked in a background of Universal Human Reference RNA at different concentrations and ratios in order to create simulated \'normal\' and \'disease\' panels, A and B. ::: ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **Accuracy of fold change detection**. Two panels (A and B) containing different ratios of RNA standards across a range of copy numbers were quantified using (A) cDNA with the ABI 7900HT system or (B) pre-amplified cDNA with BioMark 48 × 48 dynamic arrays. Expected fold change values (see the tables below the Figures) are compared to the mean of measured fold changes from RT-qPCR reactions performed on six pairs of samples. The error bars represent standard error. ::: ![](1471-2164-12-118-4) ::: Overall, fold change estimation was found to be accurate for both ABI 7900HT system and BioMark arrays (Figures [4A](#F4){ref-type="fig"} and [4B](#F4){ref-type="fig"}), with the observed fold change values overlapping with the expected fold change measurements for all standards. For ERCC standards mimicking low abundance transcripts, the technical noise associated with the resulting fold change measurement was considerably greater than higher abundance RNA species. For example, a 20-fold increase in expression level at 5 copies/ng (ERCC-51) is associated with 16-fold and 10-fold difference in the minimum and maximum fold changes detected by the BioMark arrays and ABI 7900HT system respectively. For non-differential expression at low copy numbers (fold change = 1.0; ERCC-113), fold change measurements spanned a range of over 50% and 150% of the expected value on the BioMark and ABI 7900HT system respectively. At levels of abundance exceeding 100 copies/ng, mean fold change measurements were accurate to within 10% of expected values. Discussion ========== In this study we sought to demonstrate the utility of RNA standards for characterisation of a new platform, the BioMark, where PCR reactions are performed in volumes over a 1000-fold lower than on a conventional RT-qPCR instrument (ABI 7900HT system). The requirement for sample pre-amplification for this technology contrasts with standard two-step RT-qPCR approach, therefore the impact of this methodology was also evaluated. Dilutions of RNA standards across a wide physiological range demonstrated that the linear detection range of the BioMark arrays is similar to the ABI 7900HT real-time PCR system, when pre-amplified cDNA is used as the template (Figure [1](#F1){ref-type="fig"}). The precision of replicate measurements within the array also compared favourably to the intra-run standard deviation of Ct values for the ABI 7900HT system (Figure [3](#F3){ref-type="fig"}). At copy numbers mimicking medium to high abundance transcripts, the precision of the BioMark arrays is in a similar range to the minimum variation of \~ 0.1 units observed for another nanofluidic PCR array, the OpenArray format \[[@B14]\]. However, when non-amplified cDNA is quantified using the nanofluidic BioMark arrays, the linear range is severely limited, to only two orders of magnitude (Figure [1](#F1){ref-type="fig"}). At the lower detection limit of 10^4^RNA copies per reaction (Ct \~ 27), the variation between measurements increases significantly (Figure [3](#F3){ref-type="fig"}), whilst below this level of abundance, the rate of PCR failures increases rapidly (Figure [2](#F2){ref-type="fig"}). Pre-amplification of template cDNA using a preliminary PCR step of 14 cycles improves both the accuracy and precision of the transcript quantification using the dynamic arrays (Table [1](#T1){ref-type="table"}). The improved detection of the 10-fold differences in RNA copy numbers between sample series (resulting in an average slope within 6% of expected value) also indicates that the pre-amplification process does not introduce bias into the detection of transcripts which cover a wide dynamic range. Relative expression measurements are central to gene expression analysis by RT-qPCR and for determining whether a panel of biomarkers has predictive power for disease diagnosis and prognosis \[[@B15]\]. Therefore, we developed two panels of RNA standards in order to further investigate the accuracy of detecting gene expression ratios using the new type of PCR array compared to an established system. The standards were spiked at varying ratios between panels in order to obtain information on how well the methodologies can discriminate between differentially and non-differentially expressed candidate genes at different transcript abundance levels (Figure [4](#F4){ref-type="fig"}). Our results show good accuracy of observed *vs*. expected values for both platforms, which is in agreement with previous studies demonstrating good concordance of fold change measurements between the BioMark arrays and the ABI 7900HT system \[[@B16]\]. The precision of the fold change estimation varied according to the abundance of the transcripts, demonstrating increased variation in the observed values for lower concentrations of standards for both nanofluidic and standard real-time PCR approaches. This suggests that the sensitivity of the technique to correctly detect the expected fold change is reduced at low copy numbers (10 RNA copies or less per reaction on the ABI 7900HT system). Dixon et al. \[[@B14]\] also found that the sensitivity of the OpenArray platform was lower for Ct values corresponding to lower copy numbers, resulting in an increased number of false negative results. The increased variation in fold change detection at low copy numbers is likely to arise due to decreased efficiency at RT stage and increased stochastic variation in the PCR reaction for low target numbers \[[@B17]\]. We also found that both qPCR platforms were able to accurately detect a 1.5-fold change in mRNA expression, below the 2-fold cut-off which has been cited as a limit to the resolving power of conventional PCR, as it constitutes a difference of less than a single cycle \[[@B18]\]. The BioMark dynamic arrays were recently shown to be able to detect a 1.25-fold difference in DNA copy number by qPCR, with greater levels of precision achievable with the larger number of technical replicates possible with this high-throughput approach \[[@B19]\]. Since assay and sample loadings are in separate inlets on 48 × 48 dynamic arrays, it is possible to increase technical replication by using multiple assay inlets and/or multiple sample inlets. However, it should be noted that replication only at the assay level does not substitute for true sampling variation by the process of taking a sample from a population of molecules. The use of gene-specific oligonucleotide standards for inter-run and cross-platform calibration has been demonstrated to improve the accuracy of class prediction based on panels of biomarkers \[[@B15]\]. Although ERCC RNA standards do not directly provide information on the performance of biomarker-specific assays, a panel of multiple standards, such as that used here provides a robust means of evaluating platform performance by minimizing confounding effects resulting from differences in assay performance due to individual primer and probe specificity. RNA standards could also serve as calibrator samples between experiments where different sets of potential biomarkers genes are investigated, as well as in the context of a diagnostic assay where the expression of the same panel of genes is quantified. In addition to target gene normalization using a reference gene or panel of reference genes \[[@B20]\], normalization to an ERCC RNA standard or multiple RNA standards may be a useful control for elucidating technical variation due to RT and qPCR steps \[[@B21]\]. Conclusions =========== We conclude that universal RNA standards can provide robust information on the performance characteristics of different RT-qPCR platforms and methodologies. The results obtained using panels of multiple RNA standards indicate that the linear detection range, precision and accuracy of nanofluidic BioMark dynamic arrays are similar to those of an established real-time PCR instrument, the ABI 7900HT system, when pre-amplified cDNA is used as the template. The standards also provide reference values for the range of transcript abundance over which it would be possible to measure non-amplified cDNA on the nanofluidic BioMark high-throughput arrays. Carefully constructed panels of ERCC RNA standards have the potential to act as benchmarks for the calibration and interpretation of biomarker measurements in drug discovery and clinical diagnostics. Further evaluation of these standards is required for potential incorporation into a \'quality metrics\' toolkit for assessing their suitability for cross-platform comparisons. Methods ======= Preparation of *in vitro*transcribed RNA and samples ---------------------------------------------------- *In vitro*transcribed ERCC RNA standards were produced from ERCC plasmid DNA (courtesy of Dr. Marc Salit, NIST, USA). Plasmid DNA from standards ERCC-13, 25, 42, 51, 81, 84, 95, 99, 113 and 171 was cleaved into a single linear molecule using *Bam*HI restriction endonuclease (New England Biolabs, UK). 500 ng of plasmid DNA was used for each sample and digested by adding 40 U of *Bam*HI enzyme in NEB3 buffer provided by the manufacturer. The digestion mixture was incubated at 37°C for 2 hours followed by purification using QiaQuick PCR purification kit with an elution volume of 32 μl. *In vitro*transcription was carried out with 8 μl digested plasmid DNA using MEGAscript^®^T7 Kit (Applied Biosystems/Ambion, UK) followed by DN*ase*treatment and clean-up using RNeasy columns (Qiagen, UK). RNA concentration and insert sizes were estimated using the Nanodrop 1000 spectrophotometer (Thermo Scientific, UK) and 2100 Bioanalyzer (Agilent Technologies, USA) respectively. RNA standards were diluted in nuclease free-water and spiked into Universal Human Reference RNA (Stratagene, UK) (final concentration 100 ng/μl). For experiments investigating the linear range of platform detection, standards were spiked at 10-fold intervals between 1 and 10^6^copies/ng total RNA (Additional File [2](#S2){ref-type="supplementary-material"}). For the simulated \'normal\' and \'disease\' panels, standards were spiked at various copy numbers and ratios (Table [2](#T2){ref-type="table"}). Reverse transcription and pre-amplification of cDNA --------------------------------------------------- RNA samples were reverse-transcribed using the TaqMan^®^Reverse Transcription Reagents kit (Applied Biosystems, UK) in 40 μL reactions containing 400 ng total RNA and oligo(dT) primers according to manufacturer\'s instructions. cDNA samples were diluted to a concentration of 0.5 ng/μL (total RNA equivalent) with nuclease-free water. For experiments investigating the linear range of platform detection (Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}), a single RT reaction was performed for each RNA sample whilst for the simulated \'normal\' and \'disease\' panels (Figure [4](#F4){ref-type="fig"}), 6 replicate RT reactions were performed. A single aliquot of each cDNA sample, equivalent to 12.5 ng RNA, was pre-amplified with assays corresponding to all 10 standards in a 25 μL volume reaction using TaqMan^®^PreAmp Mastermix (Applied Biosystems, UK) according to manufacturer\'s protocol. Following pre-amplification, the samples were diluted 1:5 (v/v) in TE buffer, pH 8.0. Real-time PCR ------------- Further information on sample preparation and real-time PCR validation complying with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines \[[@B22]\] is available in Additional Files [2](#S2){ref-type="supplementary-material"} and [3](#S3){ref-type="supplementary-material"} (MIQE Additional Information and Checklist). Custom-designed primers and TaqMan^®^FAM-TAMRA probes for each ERCC standard (Additional File [1](#S1){ref-type="supplementary-material"}) were supplied by Applied Biosystems and a 20 × assay mix was prepared containing 18 μM primer and 5 μM probe (final concentration 900 nM primer and 250 nM probe). qPCR assays were tested initially using a serial dilution of ERCC cDNA and PCR efficiencies calculated (see Additional Data Table 2: MIQE Additional information). All 10 assays were found to have PCR efficiencies of greater than 86%. BioMark arrays were prepared according to the manufacturer\'s instructions. TaqMan^®^assays were diluted 1:1 (v/v) with DA Assay Loading Reagent (Fluidigm^®^) and 5 μL was added to each assay inlet of the array. Also, 5 μL reaction mix was prepared by mixing 2 × TaqMan^®^Universal Mastermix (Applied Biosystems), DA Sample Loading Reagent and nuclease-free water containing 2 μL of cDNA or pre-amplified cDNA. The samples were loaded into each sample inlet as per manufacturer\'s recommendations. Following loading of the assays and samples into the chip by the IFC controller, PCR was performed with the following reactions conditions: 50°C for 2 minutes, 95°C for 10 minutes, followed by 45 cycles of 95°C for 15 seconds and 60°C for 60 seconds. Data was processed by automatic global threshold setting with the same threshold value for all assays and linear baseline correction using BioMark Real-time PCR Analysis software (version 2.1.1). The quality threshold was set at the default setting of 0.65. For experiments investigating the linear range of platform detection (Figures [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}), 8 qPCR reactions consisting of 4 assay inlet and 2 sample inlet replicates were performed for each cDNA or pre-amplified cDNA sample. For the simulated \'normal\' and \'disease\' panels (Figure [4](#F4){ref-type="fig"}), 12 qPCR reactions consisting of 4 assay inlet and 3 sample inlet replicates were performed for each cDNA sample. Conventional real-time PCR was performed using ABI 7900HT system in 20 μL reaction volumes containing TaqMan^®^Universal PCR Master Mix and 2 μL of respective cDNA in optical 96-well plates (Applied Biosystems). Cycling conditions were as those used for the BioMark arrays. Triplicate qPCR reactions were performed for each cDNA sample for all experiments. The threshold fluorescence level was set manually for each plate using SDS software version 2.3 (Applied Biosystems). Following export of Cycle threshold (Ct) data, further data analysis for both platforms was performed in Microsoft^®^Excel 2003. Comparison of slope and R^2^values between pre-amplified and non-amplified cDNA, as a template on the BioMark arrays, was performed as paired *t*-test in Microsoft^®^Excel 2003. List of abbreviations ===================== ERCC: External RNA Controls Consortium; RT-qPCR: Reverse Transcription Quantitative PCR; LOD: limit of detection; FFPE: formalin-fixed paraffin-embedded; IFC: integrated fluidic circuit; RT: Reverse Transcription; PCR: polymerase chain reaction. Authors\' contributions ======================= AD performed RT-qPCR experiments, participated in the design of the study, performed data analysis and drafted the manuscript. RE participated in the design of the study and helped to draft the manuscript. CF conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Additional files ================ The following additional are available with the online version of this paper. Additional data file [1](#S1){ref-type="supplementary-material"} is a table detailing the primer and probe sequences used for qPCR assays. Additional files [2](#S2){ref-type="supplementary-material"} and [3](#S3){ref-type="supplementary-material"} are additional data and a checklist in compliance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines. Supplementary Material ====================== ::: {.caption} ###### Additional file 1 **Taqman assays for ERCC RNA standards**. Microsoft Word file detailing the sequences of primers and probes used for qPCR assays. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 2 **MIQE Additional Information**. Microsoft Excel file containing further information on RNA preparation, purity, PCR efficiency and negative control data complying with the MIQE guidelines. ::: ::: {.caption} ###### Click here for file ::: ::: {.caption} ###### Additional file 3 **MIQE Checklist**. Checklist in Microsoft Word format detailing information complying with MIQE guidelines. ::: ::: {.caption} ###### Click here for file ::: Acknowledgements ================ The work described in this paper was funded by the UK National Measurement System. We are grateful to Dr. Marc Salit (NIST, USA) for the provision of ERCC plasmid DNA. We would also like to thank Jesus Minguez (LGC) for statistical analysis and Dr. Bridget Fox (LGC) for assistance with the production of *in vitro*transcribed RNA standards.

PubMed Central

2024-06-05T04:04:19.000675

2011-2-18

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052187/", "journal": "BMC Genomics. 2011 Feb 18; 12:118", "authors": [ { "first": "Alison S", "last": "Devonshire" }, { "first": "Ramnath", "last": "Elaswarapu" }, { "first": "Carole A", "last": "Foy" } ] }

PMC3052188

Background ========== In the last few years it has became increasingly evident that, among the multiple gene expression regulation mechanisms, eukaryotic genes expression level is also dependent on their location within the genome \[[@B1]\]. For example, a more or less strong tendency for colocalization in the same chromosomal regions has been described for genes expressed at very high levels \[[@B2]\], genes constitutively expressed in most tissues (housekeeping genes) \[[@B3]\], genes encoding proteins assigned to the same functional pathway \[[@B4]\] or genes simultaneously expressed (coexpressed) in a particular tissue or organ \[[@B5]\]. The coexpression of colocalized genes could be determined by the conformation of chromatin domains to which they belong, or by local sharing of regulatory (e.g., enhancer) elements, thus raising questions about the functional significance of clustering of coexpressed genes \[[@B1]\]. Alternatively, clustering of genes could be explained by coinheritance, a selective pressure to maintain a genetic linkage among genes that encode for functionally related products and that will tend to be inherited together or, finally, it could merely reflect the origin of functionally related genes via tandem duplication of genes \[[@B6],[@B7]\]. Further studies about the relationships between the expression of eukaryotic genes and their relative position in the genome are needed to clarify this biological issue. Such studies will take great advantage of the ever increasing amount of genomic-scale expression data obtained by serial analysis of gene expression (SAGE), gene expression microarrays or high-throughput RNA sequencing that are now made available in public databases. In fact, the transcriptome maps studies mentioned above showed the biological relevance of a global view of gene expression distribution by exploiting the availability of gene expression profile data obtained by the method of SAGE \[[@B2],[@B3],[@B5]\]. These studies contributed to challenge the traditional view that genes are randomly distributed along each chromosome in eukaryotic genomes. However, no computational biology tool for the generation and analysis of transcriptome maps was released to perform the algorithms described in these papers, with the exception of the web-based application \"Transcriptome Map\" \[[@B2],[@B8]\]. Nevertheless, this only supports a limited number of input data types (derived from a few species, and, for human, only derived from SAGE experiments or from three Affymetrix microchip platforms), normalization methods and visualization options. The application \"Caryoscope\" \[[@B9]\] is a Java-based program, able to generate a graphical representation of microarray data in a genomic context. However, it is not intended to process input data (that must come from one single source, already containing all localization information for each element), or to perform any test of statistical significance on the resulting plot. The lack of software dedicated to constructing and analyzing transcriptome maps was already pointed out in 2006 \[[@B10]\], emphasizing that up until then, only algorithms or scripts had been presented and these were often tailored to specific uses (e.g., the study of a particular organism or the analysis of data derived from a single type of experimental platform). In addition, the tools that are available typically accept only gene lists as input and are not able to represent and analyze the continuous change, along the chromosome, of expression intensity assigned to overlapping regions of desired size, on the basis of the mean expression value calculated across all genes located in that region. This representation better reflects the biological reality of the quantitative changes of regional gene activity, rather than a simple count of the enrichment in differentially expressed genes, which is however also a desirable additional parameter of analysis. These considerations underline the need for a general tool able to generate and analyze quantitative transcriptome maps from any source, provided that gene expression values for a certain gene set are available. Such a tool should also be capable of accepting and integrating data from multiple sources and be easily configurable for the investigation of any organism. Here we describe TRAM (Transcriptome Mapper), a user-friendly graphical interface software that may be run locally on personal computers (based on both Macintosh and Windows operating systems) and that meets and exceeds these specifications, by integrating original methods for parsing, normalizing, mapping and statistically analyzing expression data (Figure [1](#F1){ref-type="fig"}); in addition, it has the ability to easily generate maps showing differential expression between two sample groups, relative to two different biological conditions. The results of a test, using the hematopoietic progenitors CD34+ cells differentiation toward megakaryocytic cells (the large bone marrow cells whose fragments form platelets that are released into the blood) as a biological model, are also presented and discussed. This shows the ability of TRAM to identify chromosomal segments and gene clusters which are biologically relevant for the cell differentiation toward the megakaryocyte phenotype. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **General architecture of TRAM software**. The user is guided step-by-step through import and analysis of any gene expression profile dataset in text format. The gene identifiers of any type are converted in official gene symbols/gene names, followed by intra-sample as well as inter-sample normalization of gene expression values. The expression is mapped along each chromosome and graphically displayed on the basis of mean value for all genes included in each segment of arbitrary length. Over- and under-expressed regions are determined following statistical analysis. ::: ![](1471-2164-12-121-1) ::: Results ======= Expression data import, parsing and normalization ------------------------------------------------- The software is composed of a set of 37 related database tables, with 118 relationships among them. Some tables are designed to convert gene identifiers associated with expression data, e.g. GenBank accession numbers and/or UniGene cluster identifiers, into official gene symbols. Gene identifier conversion tables may be loaded or updated by the user, or are provided pre-loaded for human, mouse and zebrafish organisms. In addition, the user may download genomic data from Entrez Gene (e.g. chromosome number, chromosome lengths and genomic coordinates for known mRNAs) relating to the organism investigated. These data files are then easily imported and processed by the software during the set up process. Three species-specific pre-loaded (pre-setup) versions are also distributed. In addition, TRAM makes fully original specific data management and analysis tools available, including a parser able to find the best and updated gene/RNA cluster name available to be assigned to a probe identifier. This is based on a converter of any RNA sequence accession number to the relative gene symbol, by searching an embedded parsed full UniGene updatable database table. For the human version, the parser locally resolves all 6,956,798 RNA sequence accession numbers, which are related to both known transcripts and to expression sequence tags (ESTs) included in *H. sapiens*UniGene build \#228, December 2010. This allows a better conversion of those sequence accession numbers listed in a platform that may have been registered in the past few years without the availability of the presently corresponding gene symbols. For example, in the commonly used GPL96 GEO platform (Affymetrix HG-U133A microarray), 597 probe identifiers, with unavailable gene symbols in the Affymetrix platform scheme, were successfully assigned to mapped gene symbols or UniGene clusters. A sample is defined as a homogeneous series of gene identifiers and their corresponding expression values, i.e. a list of values obtained in a single channel following a microarray hybridization experiment. To allow the comparison of expression data obtained from different samples, the absolute values of a sample may be converted into percentages of the mean (or median, or maximum) of all expression values within that sample. The software is also designed for the comparison between a sample (or a pool of samples) named \'A\' and another sample (or a pool of samples) named \'B\', each collected into specific tables. In this case, the ratio of \'A\' and \'B\' (named \'A/B\') expression for each locus will be analyzed. Although TRAM is a map-centred transcriptome analysis tool it can also summarize and allow the analysis of gene expression data of unmapped genes, exploiting its capability of parsing and normalization in order to highlight differential expression of single genes between two biological conditions even in the absence of data about genomic location of the gene. Scaled quantile normalization ----------------------------- We compared the correlation between sample datasets of the same pool but derived from different platforms, using the intra-sample normalization \'Mean\' method (by which each value is expressed as percentage of the mean gene expression value for that sample). Inter-sample scaled quantile normalization always gave analogous or better results compared to standard quantile normalization. For example, the correlation coefficient between two series of locus-matched values obtained by distinct Authors, using different microarray platforms (samples A1 and A3, respectively; see Table [1](#T1){ref-type="table"}), was 0.23 in absence of any inter-sample normalization, 0.34 following standard quantile normalization for all values and 0.41 following scaled quantile method. In the case of B10 and B12 samples, the quantile method worsened the correlation coefficient from 0.85 to 0.73, while this remained stable using scaled quantile normalization (0.83). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Samples selected for the biological model used to test TRAM software ::: TRAM ID GEO ID Sample GEO Platform Microarray Spots **Ref**. ---------------- ----------- ---------------------------- -------------- --------------------- -------- ------------ **Pool \'A\'** A1 GSM321577 Mk (BM) (n = pool) GPL96 Affymetrix U133A 22,283 \[[@B19]\] A2 GSM321578 Mk (BM) (n = pool) \" \" \" \" A3 GSM112277 Mk (PB) (n = 1, rep. 1) GPL887 Agilent 1A 22,575 \[[@B20]\] A4 GSM112278 Mk (PB) (n = 1, rep. 2) \" \" \" \" A5 GSM15648 Mk (BM) (n = 6) GPL96 Affymetrix U133A 22,283 \[[@B21]\] A6 GSM8649 Mk (BM) (n = 6) \" \" \" \" A7 GSM88022 Mk (PB) (n = 1) GPL887 Agilent 1A 22,575 \[[@B22]\] A8 GSM88014 Mk (PB) (n = 1) \" \" \" \" A9 GSM88034 Mk (PB) (n = 1) \" \" \" \" **Pool \'B\'** B1 GSM321567 CD34+ (BM) (n = pool) GPL96 Affymetrix U133A 22,283 \[[@B19]\] B2 GSM321568 CD34+ (BM) (n = pool) \" \" \" \" B3 GSM321569 CD34+ (CB) (n = pool) \" \" \" \" B4 GSM321570 CD34+ (CB) (n = pool) \" \" \" \" B5 GSM321571 CD34+ (PB) (n = pool) \" \" \" \" B6 GSM321572 CD34+ (PB) (n = pool) \" \" \" \" B7 GSM76923 CD34+ (BM) (n = 5) GPL96 Affymetrix U133A 22,283 \[[@B23]\] B8 GSM76924 CD34+ (BM) (n = 5) \" \" \" \" B9 GSM76925 CD34+ (BM) (n = 5) \" \" \" \" B10 GSM307288 CD34+ (BM) (n = 6, rep. 1) GPL7091 Agilent 22 k A 16,391 \- B11 GSM307289 CD34+ (BM) (n = 6, rep. 2) \" \" \" \- B12 GSM88023 CD34+ (PB) (n = 1) GPL887 Agilent 1A 22,575 \[[@B22]\] B13 GSM88003 CD34+ (PB) (n = 1) \" \" \" \" B14 GSM23407 CD34+ (BM) (n = 1) GPL201 Affymetrix HG-Focus 8,793 \[[@B24]\] B15 GSM23410 CD34+ (BM) (n = 1) \" \" \" \" B16 GSM23411 CD34+ (BM) (n = 1) \" \" \" \" B17 GSM23408 CD34+ (BM) (n = 1) \" \" \" \" B18 GSM23409 CD34+ (BM) (n = 1) \" \" \" \" B19 GSM23406 CD34+ (BM) (n = 1) \" \" \" \" **Sample**: Mk, megakaryocytic/megakaryoblast cells, obtained by in vitro differentiation of CD34+ cells; CD34+, undifferentiated CD34+ cells; (BM), (CB) or (PB): CD34+ cells derived from bone marrow, cord blood or peripheral blood, respectively. n = number of subjects from which the sample was derived (in some cases, where n = pool, the exact number of subjects included in a pool was not available). rep. = biological replicate. **Microarray**: U133A: Affymetrix Human Genome U133A Array; 1A: Agilent-012097 Human 1A Microarray (V2) G4110B; 22 k A: Agilent Human oligo 22 k A; HG-Focus: Affymetrix Human HG-Focus Target Array. When not directly provided, expression value was calculated as the median intensity value of a microarray feature minus the median background value. ::: In addition, we determined the standard deviation (SD, expressed as percentage of the mean) of measurements from different samples for housekeeping loci such as beta actin (*ACTB*) and a set of ribosomal proteins, using the intra-sample normalization \'Mean\' method. In the absence of any inter-sample normalization, the SD for *ACTB*was 84.95 for pool \'A\' (26 data points) and 148.80 for pool \'B\' (60 data points). After applying quantile normalization to all available data, the SD became 35.36 and 78.91, and following the use of the scaled quantile method it changed into 51.44 and 54.75, for pool \'A\' and \'B\' respectively. Therefore, the scaled quantile method allowed both a decrease in the variability among the samples within a sample pool, and an increase in comparability between the \'A\' and \'B\' sample pools compared to a reference gene expected to be stably expressed in both pools. In the absence of any inter-sample normalization the SD for genes encoding small ribosomal proteins was 85.80 for pool \'A\' and 138.75 for pool \'B\' (mean of SD for 34 loci with \"RPS\" prefix, total data points were 402 for pool \'A\' and 830 for pool \'B\'). Following quantile normalization of all available data the SD changed to 66.01 and 78.25, and after using the scaled quantile method the SD decreased to 56.21 and 49.06, for pool \'A\' and \'B\' respectively, thus improving homogeneity within each sample pool as well as between the two sample pools. Generation and analysis of transcriptome maps --------------------------------------------- Two main types of analysis are available within TRAM: \'Transcriptome map - search for over/under-expressed segments\' (\'Map\') mode and \'Search for clusters of neighbouring over/under-expressed genes\' (\'Cluster\') mode. In \'Map\' mode, the software generates a graphical map of the transcriptome showing a vertical line representing each chromosome. An expression value for a selected area of a chromosome is calculated as the mean for all available expression data relating to the genes included in that segment. The mean expression level of the segment is represented by an horizontal bar next to the corresponding segment of the chromosome, the bar size being proportional to the segment expression level (Figure [2](#F2){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Screenshot of the \'Map\' graphical display of TRAM software (detail)**. The length of each horizontal bar is proportional to the mean gene expression within a chromosomal segment of 0.5 Mb. Consecutive bars are shifted by 250 kb. The vertical line represents human chromosome 4, from position 64,750,001 (start of the top segment) to position 76,750,000 (end of the bottom segment). The expression value on the left of each bar is derived from the analysis of the test set used (Table 1). Bars are colour-coded in proportion to their expression values. Segments, whose expression value is greater (or lower) than the chosen percentile threshold, are highlighted in the \"Over/Under\" field, which is only filled when they also include the user-defined minimum number of over/under-expressed genes that must be present in the segment. Statistical significance p- and q-values are calculated for these regions. ::: ![](1471-2164-12-121-2) ::: Bars representing expression values included within the highest/lowest (n) user-defined percent of all segment expression values are pinpointed, thus highlighting genomic regions globally over/under-expressed with respect to the desired threshold. To avoid artefacts due to very high or very low expression of single genes in the region, the minimum number of over/under-expressed genes that must be present in the segment can be defined. The threshold for a gene to be considered as over- or under-expressed is the inclusion of the gene expression value within the highest/lowest (n) user-defined percent of all gene expression values. The user may also set the \'Shift\' parameter that causes the window to slide along the chromosome at pre-arranged intervals. In this way the user obtains a set of partially overlapping segments thereby attaining better sensitivity because a rigid division in chromosome segments, always starting from the fixed position 1, may let neighbouring over- or under-expressed genes be assigned to different segments. The user maintains full control of the numerical data associated with each segment and may easily navigate among the map of the genes and gene expression values data tables. Segments may be explored and searched according to any desired criteria and sorted and processed like ordinary database records. Differential transcriptome maps, based on the ratio between corresponding gene expression values from two \'A\' and \'B\' samples or sample pools, relative to two different biological conditions, may be easily generated. The statistical significance of the over/under-expression of each segment fulfilling the criteria to be tagged as over/under-expressed is displayed, and it is calculated as described in the \"Statistical analysis\" Methods section. The user may choose to refer the statistical calculations to data sets within each chromosome rather than to the whole genome dataset, in order to retrieve domains regionally over- or under-expressed within each DNA molecule. Differences between the genome- and chromosome-centred types of analysis are graphically highlighted when both have been performed. Search for clusters of neighbouring over/under-expressed genes -------------------------------------------------------------- In \'Cluster\' mode, the software searches for a set of at least two successive genes, arranged according to the position indicated by their known transcription start site, and over/under-expressed in terms of inclusion of the gene expression value within the highest/lowest (n) user-defined percent of gene expression values. In this type of analysis, each horizontal bar represents the expression level of an individual gene (Figure [3](#F3){ref-type="fig"}). Gene clusters are then built starting from over/under-expressed individual loci, if other contiguous genes fulfil the criteria defined for inclusion in the cluster. This analysis is complementary to that performed in \'Map\' mode, which requires an arbitrary segment window. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Screenshot of the \'Cluster\' graphical display of TRAM software (detail)**. Two example clusters, identified by default analysis of the biological model (Table 1) described in the text, are shown. The length of each horizontal bar is proportional to the mean \'A\'/\'B\' ratio gene expression across all samples. Bar red colour indicates gene over-expression according to set criteria. Genes without associated expression values in the samples are shown but are not considered in the cluster construction. \'Gap\' parameter was set equal to 1, so a maximum of one not over-expressed gene (hot pink colour bar) may separate two consecutive over-expressed genes. The cluster mean expression value, derived from all genes included in each cluster, is shown. The number of data points from which each value was derived, p-, q-value and length for each over/under-expressed cluster are also calculated (not shown here). ::: ![](1471-2164-12-121-3) ::: The results of the analysis are displayed in the \'Cluster\' layouts, as clusters of genes over/under-expressed. Each gene is actually a record (row) of the database. The user can find and sort genes and gene clusters using any desired criteria. Specific buttons help to retrieve entries from online databases for the desired genes. Clusters of differentially expressed genes between two different biological conditions may be easily generated, based on the ratio between corresponding gene expression values from two defined \'A\' and \'B\' pools. Statistical significance of the over/under-expression of each gene cluster fulfilling the criteria to be tagged as over/under-expressed is displayed, and it is calculated as described in the \"Statistical analysis\" Methods section. In \'Cluster\' mode the user may choose if statistical calculations are to be performed separately for each chromosome as it is possible in \'Map\' mode. Moreover, the user may choose how many genes can be tolerated in the cluster between each gene pair counted in the cluster, even if they do not fulfil the user-set criteria. Biological model - Chromosomal segments --------------------------------------- We compared several options of the software in the analysis of differential expression of pool \'A\' (9 megakaryocyte cells (Mk) samples, including RNA from at least 21 different subjects) versus pool \'B\' (19 CD34+ cells samples, including RNA from at least 41 different subjects) (Table [1](#T1){ref-type="table"}). A total of 180,365 data points (gene expression values) from the pool \'A\' and 294,987 data points from the pool \'B\', relative to 17,676 distinct loci, for which an \'A\'/\'B\' ratio value was determinable, were included in the analysis. Results obtained by default analysis (according to the parameters described in the \"Methods\" section) included 18 significantly over- or under-expressed segments (\'Map\' mode, Table [2](#T2){ref-type="table"}) and 73 clusters (\'Cluster\' mode, Table [3](#T3){ref-type="table"}). The use of inter-sample normalization (scaled quantile method) improved the identification of significantly over/under-expressed genome segments versus absence of any inter-sample normalization (18 vs. 12). In addition, segments enriched in relevant genes known to be over- or under-expressed in megakaryocytes/platelets were not identified in the absence of inter-sample normalization. For example an over-expressed segment on chromosome 17 was found to contain, among others genes, *ICAM2*and *PECAM1*, as well as an under-expressed segment on 6p21.3 containing several HLA (human leukocyte antigen) system class II members. The differential expression of these genes is expected in the differentiation process studied in our model: *ICAM2*is a functional integrin ligand present on platelets surface \[[@B11]\] and *PECAM1*encodes platelet/endothelial cell adhesion molecule, while the down-regulated genes *HLA-DRA*, *HLA-DRB1*and *HLA-DQA1*are typically expressed in antigen presenting cells. ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### Genomic segments significantly over/under-expressed in Mk cells (pool \'A\') vs. CD34+ cells (pool \'B\') ::: Chr and Location Segment Start Segment End \'A\'/\'B\' Ratio q-value Genes in the segment ------------------ --------------- ------------- ------------------- --------- --------------------------------------------------------------------------------------------------------------------------------------------------------- chr2 2q23-q24 160,250,001 160,750,000 0.398 0.00024 ***BAZ2B-****MARCH7-****CD302- LY75-*** chr4 4q11-q12 57,500,001 58,000,000 0.421 0.00039 ***HOPX- SPINK2-****REST- C4orf14- POLR2B+****IGFBP7-*** chr4 4p15.32 15,500,001 16,000,000 0.427 0.00039 *FBXL5-****BST1- CD38-****FGFBP1- FGFBP2-****PROM1-*** chr6 6p21.3 32,250,001 32,750,000 0.434 0.00079 *C6orf10+ BTNL2-****HLADRA- HLADRB1- HLADQA1-****HLADQB1- HLADQA2- HLADQB2-* chrX Xp11.23 47,000,001 47,500,000 1.806 0.00505 *NDUFB11+ RBM10+ UBA1+****INE1+****USP11- ZNF157+ ZNF41+ ARAF+****SYN1+ TIMP1+****CFP+ ELK1+* chr11 11q12.2 61,250,001 61,750,000 1.859 0.00573 *C11orf66+ SYT7- DAGLA- C11orf9+ C11orf10+ FEN1+****FADS1+ FADS2+****FADS3- RAB3IL1+ BEST1-****FTH1+*** chr16 16p12.1 28,500,001 29,000,000 1.877 0.00248 *CLN3+ APOB48R+ IL27+****NUPR1+****CCDC101- SULT1A2+****SULT1A1+****EIF3C- ATXN2L+ TUFM+ SH2B1-****ATP2A1+****RABEP2- CD19- NFATC2IP+ SPNS1+****LAT+*** chr17 17q23 62,000,001 62,500,000 1.957 0.00381 ***CD79B-****SCN4A-****C17orf72+ ICAM2+****ERN1+ TEX2+****PECAM1+****C17orf60- POLG2+ DDX5+* chr6 6p21-1 43,500,001 44,000,000 2.196 0.00235 *XPO5-****POLH+ GTPBP2+ MAD2L1BP+****MRPS18A+ VEGFA+ C6orf223+* chr5 5qter 178,750,001 179,250,000 2.367 0.00222 *ADAMTS2-****RUFY1+****HNRNPH1+ CANX+ MAML1+****LTC4S+ MGAT4B+****SQSTM1+* chr11 11p15 5,000,001 5,500,000 2.384 0.00796 *MMP26- OR51L1+ OR52J3+ OR52A1+ HBB+****HBD+ Hs.20205+ HBG1+****HBG2+ HBE1+ OR51B4+ OR51B2- OR51B6+ OR51M1- OR51I1+ OR51I2+* chr17 17p13.2 4,750,001 5,250,000 2.620 0.00796 *MINK1+ CHRNE+****GP1BA+****SLC25A11+ RNF167+****PFN1+****ENO3+ SPAG7+ CAMTA2+****KIF1C+****GPR172B+ ZFP3- ZNF232- USP6+ ZNF594- RABEP1-* chr4 4q13-q21 74,500,001 75,000,000 9.226 0.00000 *IL8+ CXCL6+****PF4V1+ CXCL1+ PF4+ PPBP+****CXCL5+****CXCL3+****PPBPL2+****CXCL2+*** Chr: chromosome; Segment Start/End: chromosomal coordinates for each segment. Bold and \'+\': over-expressed gene; bold and \'-\': under-expressed gene; \'+\' or \'-\': gene expression value higher or lower than the median value, respectively. Analysis was performed using default parameters (see \"Methods\" section). Segments are sorted by increasing \'A\'/\'B\' ratio. In the \'Map\' mode, TRAM displays UniGene EST clusters (with the prefix \"Hs.\" in the case of *H. sapiens*) only if they have an expression value. Five out of a total of 18 segments are not shown for simplicity, because their over-expressed genes are overlapping with those highlighted in the listed regions. The complete results for this model are available along with TRAM software. ::: ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Clusters of genes significantly over/under-expressed in Mk cells (pool \'A\') vs. CD34+ cells (pool \'B\') ::: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Chr and Location Cluster Start Cluster End\ \'A\'/\'B\' Ratio *q*-value Genes in the cluster (Cluster size) --------------------- --------------- ---------------------- ------------------- ----------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------- chr19 19p13.3 827,831 856,246 (28,416) 0.103 0.00011 ***AZU1- PRTN3- ELANE-*** chr4 4q11-q12 57,514,154 57,687,893 (173,740) 0.140 0.00084 ***HOPX-****Hs.630172 Hs.121443 Hs.673386 Hs.613041 Hs.677243 Hs.601479 Hs.44210 Hs.566128****SPINK2-*** chr10 10q23-q24 97,951,455 98,098,321 (146,867) 0.172 0.00084 ***BLNK-****Hs.716018 Hs.673979 Hs.444049 Hs.688648 Hs.679276****DNTT-*** chr1 1p36 26,644,411 26,647,014 (2,604) 0.192 0.00084 ***CD52- Hs.597423-*** chr1 1q21 153,330,330 153,363,549 (33,220) 0.212 0.00011 ***S100A9- S100A12-****LOC645900****S100A8-*** Chr6 6p21.3 32,407,647 32,611,429 (203,783) 0.217 0.00011 ***HLADRA-****LOC10028939 Hs.601001 Hs.544645 Hs.693189 Hs.654238 HLADRB5 Hs.664382 Hs.611927 Hs.606311****HLADRB1-****Hs.706474 Hs.625753 Hs.691818****HLADQA-*** chr8 8p23.1 6,835,171 6,875,816 (40,646) 0.233 0.00084 ***DEFA1-****DEFA1B****DEFA3-*** chr2 2p22.3 32,853,129 33,624,576 (771,448) 6.738 0.00084 ***TTC27+****Hs.616001 Hs.664352 Hs.639709 Hs.683829 Hs.678473 Hs.623026 LOC285045 LOC100271832****LTBP1+*** chr11 11q12.2-q13.1 61,567,097 61,634,825 (67,729) 7.059 0.00084 ***FADS1+****Hs.651782 Hs.621796 LOC100131326 Hs.667454****FADS2+*** chr17 17q21.32 42,422,491 42,466,873 (44,383) 7.976 0.00084 ***GRN+****Hs.602870 FAM171A2 LOC390800****ITGA2B+*** chr12 12p13.31 7,966,397 8,088,892 (158,906) 8.033 0.00084 ***SLC2A14+****Hs.664258 Hs.539507 Hs.668117 LOC100130582 Hs.662096****SLC2A3+*** chr11 11p15.5 5,254,059 5,271,087 (21,857) 8.722 0.00010 ***HBD+ Hs.20205+****Hs.295459 Hs.702082 Hs.702189****HBG1+*** chr12 12p13.3 6,058,040 6,347,427 (289,388) 10.492 0.00084 ***VWF+****Hs.605384 Hs.539512 Hs.712104****CD9+*** chr4 4q12-q21 74,719,013 74,964,997 (245,985) 11.289 0.00000 ***PF4V1+ CXCL1+****Hs.708652 LOC642958****PF4+****Hs.552264****PPBP+****CXCL5+ Hs.598417 Hs.603888 Hs.617230****CXCL3+****PPBPL2+ LOC643014 Hs.719458****CXCL2+*** ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Chr: chromosome; Cluster Start/End: chromosomal coordinates for each gene cluster. Bold and \'+\': over-expressed gene; bold and \'-\': under-expressed gene; \'+\' or \'-\': gene expression value higher or lower than the median value, respectively; gene name without \'+\' or \'-\' symbols: no expression value available in the investigated dataset. Analysis was performed using default parameters (see \"Methods\" section), choosing to list all colocalized known genes and mapped EST clusters, regardless of the availability of expression values for them in the investigated samples. Clusters are sorted by increasing \'A\'/\'B\' ratio. Only the 7 cluster with the highest and the 7 cluster with the lowest cluster mean gene expression are shown (out of a total of 31 significantly over- and 42 significantly under-expressed identified clusters). The complete results for this model are available along with TRAM software. ::: The higher expression ratio between Mk and CD34+ cells (9.23) was observed in the segment at coordinates 74,500,001-75,000,000 on chromosome 4 (4q13-q21). All 10 genes in this location showed expression values greater than the median, and 6 out of 10 showed values within the higher 2.5th percentile. While it was known that several genes in this region are sequence-related and form a structural cluster of members of the CXC chemokine gene family (*CXCL1*, *CXCL5*, *CXCL3*, *CXCL2*), this finding highlights the simultaneous very high activity of genes such as *PF4V1*(platelet factor 4 variant 1), *PF4*(platelet factor 4) and *PPBP*\[official name: pro-platelet basic protein (chemokine (C-X-C motif) ligand 7)\], previously known as beta-thromboglobulin \[[@B12]\], following differentiation of CD34+ cells in megakaryocytes. The second segment with highest expression was located on chromosome 6 and contained over-expressed genes such as *GP1BA*\[glycoprotein Ib (platelet), alpha polypeptide\], encoding the alpha chain of megakaryocyte- and platelet-specific surface membrane Glycoprotein Ib, and *KIF1C*(kinesin family member 1C). Over-expression of kinesin 1C, which is recruited in neural cells APP (amyloid precursor protein) transport vesicles, was not to date described in Mk cells. However, it is known that during the complex and poorly understood process by which Mks generate platelets, kinesin motors carry platelet-specific granules and organelles over microtubules into the pro-platelets \[[@B13]\]. The third over-expressed segment spans the cluster of haemoglobins on chromosome 11, highlighting the known common early origin of erythroid and Mk cells \[[@B14]\]. Under-expressed segments included genes encoding surface antigens whose expression is known to be restricted to leukocytes or leukocyte subpopulations (e.g., CD302, LY75/CD205, CD38 and HLA-DR; Table [2](#T2){ref-type="table"}), highlighting their down-regulation during differentiation of common CD34+ progenitors to megakaryocyte. Switching from \'Mean\' to \'Median\' intra-sample normalization (values expressed as a percentage of the median value for each array) globally decreased sensitivity from 18 significantly over- or under-expressed genome segments to 10. However, one segment was identified only with the \'Median\' mode. This segment includes *MYOM1*(myomesin 1/skelemin), *MYL12A*(myosin, light chain 12A, regulatory, non-sarcomeric) and *MYL12B*(myosin, light chain 12B, regulatory) and it went undetected with the \'Mean\' mode. Interestingly, myomesin 1 \[[@B15]\] and myosins \[[@B16]\] pathways have been involved in pro-platelet formation and platelet function. Some differences in the results while using different intra-sample normalization parameters are expected on the basis of the different distribution of the values for each sample. For example the sample mean value is greater than the sample median value if there is a tail of high values. Normalizing by median could uncover additional significantly over-expressed regions that were masked by the mean-based normalization. Concerning inter-sample normalization, the scaled quantile adjustment appeared to increase sensitivity in the identification of significantly over/under-expressed segments with respect to the standard quantile method (18 vs. 13). In particular, the quantile method was not able to detect any under-expressed segment, such as that containing the HLA class II genes typical of leukocytes that were identified by scaled quantile adjustment. Lowering or raising the threshold to define a gene and/or a segment as over/under-expressed makes the analysis more stringent or less stringent, respectively. We found that a good starting point is to use lower and upper 2.5th percentile, so that 5% of the data are included as positive results, which in a Gaussian distribution would roughly correspond to the percentage of values exceeding the mean by two standard deviations. The statistical test will compensate for the high number of segments or cluster marked as over/under-expressed obtained relaxing the threshold, by identifying which results are to be considered significant (Q \< 0.05). Biological model - Gene clusters -------------------------------- In the \'Cluster\' mode, the identified clusters included genes well known for being upregulated during megakaryocytopoiesis, as well as genes encoding leukocyte proteins expected to be down-regulated in the same context. For example, a cluster is composed by *DNTT*, encoding deoxynucleotidyl transferase, expressed in a restricted population of pre-B and pre-T lymphocytes, and *BLNK*, encoding B-cell linker, an adaptor protein that plays a critical role in B cell development (Table [3](#T3){ref-type="table"}). In this mode of use, the physical contiguity of at least two over/under-expressed genes is considered as the bond for cluster definition rather than an enrichment of such genes in a genomic region independently of their order. Results are in part similar and in part complementary to those obtained in the \'Map\' mode. In particular, the cluster with lowest \'A\'/\'B\' ratio mean value turned out to be the series of genes *AZU1*(azurocidin 1), *PRTN3*(proteinase 3) and *ELANE*(elastase, neutrophil expressed), located on chromosome 19 and known to be coordinately expressed in a granulocyte-specific fashion \[[@B17]\], which resulted to be significantly under-expressed only in this mode of analysis. On the other hand, an over-expressed cluster composed only by the two contiguous genes, encoding platelet-specific proteins VWF (Von Willebrand Factor, present in the alpha-granules of platelets) and CD9 (a specific platelet marker), was identified on chromosome 12 (Table [3](#T3){ref-type="table"}). This would have been undetected in the \'Map\' mode because the minimal number of over/under-expressed genes required to be present in a chromosomal segment was by default set equal to 3. Another over-expressed cluster included *GATA1*, encoding a major transcription factor for megakaryocytopoiesis. The modification of parameters used for \'Cluster\' mode analysis, such as those above listed for the \'Map\' mode, had analogous effects on the results. Some additional significant results were obtained by setting chromosome-specific thresholds for the analysis, rather than using the whole genome gene set as a reference. For example, the cluster of the two genes *HIPK2*(a nuclear kinase that interacts with homeodomain transcription factors, previously associated with megakaryocyte lineage) \[[@B18]\] and *TBXAS1*\[official name: thromboxane A synthase 1 (platelet), catalyzing the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation\] scored as significantly over-expressed on a local basis when the gene expression of chromosome 7 but not whole genome dataset was considered. In both \'Map\' and \'Cluster\' modes, TRAM displays EST clusters, in addition to known genes, mapped in the region of interest. In the case of \'Cluster\' mode this occurs independently of the availability of expression values for the loci within the cluster extension (Table [3](#T3){ref-type="table"}). The results for each mode of analysis of the presented test model, using default parameters, are available in the folder \'Biological\_Model\_Test\' of the TRAM distribution, allowing the user to explore the model following variation of analysis parameters. Individual gene expression values, summarized for each of the two pools \'A\' and \'B\', can be visualized and sorted in the \'Cluster\' results layout. Amongst the first 12 genes with the highest \'A\'/\'B\' ratio (*PF4V1*, *PF4*, *GP1BA*, *PPBP*, *RGS18*, *CMTM5*, *SLC44A1*, *VWF*, *SH3BP5*, *HSPC159*, *ITGA2B*and *HBG1*, ranging from 34.22 to 11.92 expression ratio, in this order, between CD34+ and Mk cells), 7 were placed in one significantly over-expressed segment or gene cluster by the transcriptome mapping analysis. The *CD34*gene was under-expressed in Mk cells compared to CD34+ cells, as expected (mean ratio across all samples was 0.29, within the lowest 2.5th percentile of \'A\'/\'B\' ratios). Discussion ========== Here, we have described an original software named TRAM, designed to create and analyze transcriptome maps for any organism, based on gene expression data in a general form and able to generate a relational, fully-indexed map database, usable on Macintosh and Windows operating systems-based computers. The \'Map\' mode allows the identification of chromosomal regions of defined size (with the possibility of using a sliding window) whose expression is defined as the gene expression average of the genes contained in the segment. This segment, also, must contain a specified number of loci transcribed beyond a desired threshold. The wide flexibility of the parameters required for the building of the Map (e.g., the independence of the threshold value chosen to consider each gene as over/under-expressed from the threshold value set to define a genomic segment as over/under-expressed) makes an open exploration of the expression data feasible at different levels; in addition, an estimate of statistical significance for the definition of a segment as over/under-expressed can then be obtained. This type of analysis considers the global expression of all genes in the region, regardless of their exact reciprocal position: in fact, it has been shown, for example for genes belonging to the same functional pathway, that clustering is loose and individual genes may be spread, despite remaining closer to each other than expected by chance \[[@B4]\]. In addition, we added a complementary mode of data visualization and analysis, the \'Cluster\' mode, where the window width is defined by a number of clustered genes rather than nucleotide range. This method can consider the gene-by-gene order in the region and can provide results about clusters of over/under-expressed genes that are adjacent or separated by a small user-defined number of not over/under-expressed genes within the cluster. All TRAM data and results tables are widely interconnected by simple navigation buttons, as well as linked to the relevant entries available on line (via automatic opening of the default web browser). The novelty of the tool is supported by several arguments. Firstly, the uniqueness of TRAM general basic architecture, which dynamically integrates an advanced and flexible relational database with parsing and meta-analysis capability, a map graphic displayer and a two-modes (\'Map\' and \'Cluster\') analyzer searching for significantly over/under-expressed genomic regions, starting from any source of global gene expression profiles data (Figure [1](#F1){ref-type="fig"}). The TRAM data model is also unique in two other aspects: users are given direct access to expression numerical values, which are always visualized near the horizontal expression bar used to visualize the expression intensity of chromosomal segments or clustered genes localized on the map; moreover, the users do not need to provide genomic coordinates for the investigated genes, whose location is resolved by the pre-setup gene database table. A series of buttons allows an easy, transparent tracking of gene expression measurements from raw input data to normalized values, up to expression intensity display on the map. In addition, TRAM makes original specific data management and analysis tools available such as: a parser which is able to find the best and updated gene/RNA cluster name suitable to be assigned to a probe identifier (e.g., the parser locally resolves all \~7 millions human RNA sequence accession numbers included in the latest available *H. sapiens*UniGene version); a novel effective method for the normalization of data derived from platforms with highly different number of probes (scaled quantile) which allows more samples to be included in a biologically homogeneous sample pool and maximizes gene expression information that may be extracted from each sample; the statistical analysis, based on individual chromosome data summary in addition to genome data summary, emphasizing local effects expected on the basis of the behaviour of single chromosomes with respect to chromatin organization and gene expression regulation. Finally, a powerful feature of TRAM is its ability to compare, within the same analysis, the transcriptome maps derived from two datasets (or two pools of datasets) related to different biological conditions (indicated as \'A\' and \'B\'), such as two tissues or cell types, two developmental stages, normal vs pathological cells or cells maintained in absence or in presence of a substance. The generation of a transcriptome map of the relative \'A\'/\'B\' ratio expression, allows the easy investigation of regional differential expression without the need to generate the results separately for the two datasets or pool of datasets and to devise additional calculations to compare them. TRAM was able to generate original results of relevant biological interest in the *ab initio*modelling of differentiation from CD34+ stem cells to megakaryocyte (Mk) cells in a meta-analysis of a total of 28 publicly available microarray datasets obtained from different sources. Many genes with a fundamental role in Mk/platelet biology, known since early classical studies (see \"Results\" section), were shown to significantly colocalize in genome segments or in clusters of adjacent genes. Moreover, additional regions significantly over/under-expressed during megakaryocytopoiesis were identified (Table [2](#T2){ref-type="table"} and Table [3](#T3){ref-type="table"}). These results are original compared to the data analysis presented in the relative primary works from which expression data were derived \[[@B19]-[@B24]\]. This may be ascribed to the lack of data integration in the original studies (analysis was typically applied only to the datasets produced in the context of the work itself) \[[@B19]-[@B24]\], to the lack of a search for local enrichment of over/under-expressed genes \[[@B20]-[@B24]\], to the use of a different analysis pipeline when a localization study was performed (in particular, use of gene lists as a starting point rather than the actual mean expression value of the genes in a region) \[[@B19]\], or to the different biological model considered (when the study was not intended to investigate differential expression during differentiation of CD34+ cells toward Mk cells) \[[@B21],[@B23],[@B24]\]. EST clusters can be mapped to the region of interest in addition to known genes by exploiting an original integration between NCBI UniGene and UCSC Genome Browser data (Table [2](#T2){ref-type="table"} and Table [3](#T3){ref-type="table"}). This feature offers useful hints for the functional investigation of uncharacterized transcripts, on the basis of their presence, and in case of their over/under-expression, within genomic regions differentially expressed in a certain biological context. While feasibility of integration of gene expression profile data, obtained from different experimental platforms or investigators, is highly desirable to build transcriptome maps representing all information available for a certain biological condition, the occurrence of systematic errors associated with each experimental situation requires advanced methods of inter-sample data normalization, such as the widely accepted quantile normalization \[[@B25]\]. However, this method may cause loss of data due to the removal of all genes whose expression values are missing for any dataset in order to obtain a fully filled data matrix, representing each sample as a column and the values for each gene as a row (for an example of this filtering see \[[@B26]\]). Alternatively, some Authors retain all data values in quantile normalization by placing missing values at the end of each sorted column \[[@B27]\]. In such cases, all available data are analyzed but with an artefact due to the misalignment of values included in similar classes of expression level, compared to their sample of origin (Figure [4](#F4){ref-type="fig"}). The original method of scaled quantile we propose here in order to properly manage data derived from platforms with different number of analyzed genes, has proven to be effective, allowing maximization of information that can be extracted from all pertinent available data. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **Scaled quantile normalization: concept**. If two data columns with different numbers of values, derived from two A1 and A2 samples, respectively, are individually sorted by magnitude of expression to obtain the mean value for all values with the same rank, i.e. in the same row (quantile normalization), the highest values in the sample A2 will be aggregate to the intermediate values in the sample A1. Proportional scaling of A2 ranks aligns them to A1 values located in analogous ordered positions with respect to each sample whole distribution (scaled quantile inter-sample normalization), allowing low, intermediate and high values to be aggregated with suited corresponding values from the other sample(s). ::: ![](1471-2164-12-121-4) ::: Interestingly, after selecting for the analysis only samples homogeneous with respect to the used experimental platform, a decrease in sensitivity was observed, thus showing the effectiveness and usefulness of analysis starting from multiple sources. For example, by performing the analysis only on the datasets obtained with commonly used Affymetrix U133A microarray (GPL96 GEO platform) among those listed in Table [1](#T1){ref-type="table"}, only 5 vs. 18 significantly over/under-expressed chromosomal segments, and 68 vs. 73 gene clusters were found, compared to the analysis integrating data from the whole available pool of samples. A variation of analysis parameters allows the exploration of data from different points of view. The final statistical significance test will provide the actual reliability of the corresponding results independently of the parameters selected to define the thresholds for considering segments and genes as over/under-expressed (selection performed at the start of the data analysis by descriptive statistics). For example, lowering the threshold to consider segments and genes as over/under-expressed will retrieve a larger number of differentially expressed regions but this will be taken into account during the calculation of the statistical significance of each result where only a minor fraction of these regions will have a q-value (p-value corrected for FDR) \< 0.05. It is noteworthy that, among the first 12 individual genes with the absolute highest \'A\'/\'B\' ratio between CD34+ and Mk cells, 7 were placed in one significantly over-expressed segment or gene cluster by the transcriptome mapping analysis. In addition, valuable information may also be extracted by using the capability of TRAM to numerically describe the normalized and summarized intensity of transcription along each chromosome. In this way a user could readily search, find and sort regions with no positive expression values despite containing known genes (\"expression deserts\"). Taken together, the described features of TRAM make it difficult to compare in details this tool with all other tools that, to our knowledge, are described in the literature as being capable of transcriptome mapping and analysis. This is because TRAM is actually a suite of different and strictly integrated data parsing and displaying as well as analysis tools. In particular, the existing software reviewed in the \"Background\" section, accept gene lists as an input (lists are to be obtained through different dedicated tools), so they cannot represent and analyze the gene expression level changing along the chromosome. Neither will they generate differential expression maps comparing two different biological conditions such as the one we have discussed in our biological model showing progression from CD34+ cells to megakaryocytes. The local differential gene expression between two conditions is a function offered by the \"R\" library MACAT \[[@B28]\], whose Authors used a set of publicly available microarray data \[[@B29]\] related to human T- (n = 43) and B-cell (n = 205) paediatric acute lymphoblastic leukaemias as biological test example. Only one chromosomal region in chromosome 6 was found to be differentially expressed between T- and B-leukaemia cells. This was a biologically meaningful finding since HLA genes are localized in this region and they are known to be under-expressed in T-cells vs. B-cells \[[@B28]\]. TRAM was able to replicate this result by using default analysis parameters. In addition, TRAM was able to individually list the loci under-expressed in T-cells present in this region (6p21.3, coordinates 32,2500,000-33,000,000, q-value \< 0.000002, under-expressed genes: *HLA-DRA*, *HLA-DRB1*, *HLA-DQA1*, *HLA-DQB1*, *TAP2*- involved in antigen presentation -, *HLA-DMB*, *HLA-DMA*). Moreover, TRAM has been able to identify three additional differentially expressed chromosomal regions, each of which contained several genes over-expressed in T-cells, one on chromosome 1 (1q22-q23, q-value = 0.000007, genes: *CD1D*, *CD1A*, *CD1B*, *CD1E*) and two on chromosome 11 (11q12.2, q-value \< 0.0007, genes: *CCDC86*, *GPR44*, a chemoattractant receptor homologous molecule expressed on T-helper type 2 cells, and *CD5*; 11q23, q-value \< 0.0007, genes: *CD3E*, *CD3D*and *CD3G*). These regions are of remarkable biological and clinical interest because they contain clusters of genes related to CD1, CD5 and CD3, respectively; these are well known as main and universally used specific surface markers of T-cells. In the \"Cluster\" mode, TRAM identifies 35 gene clusters significantly over- (n = 16) or under-expressed (n = 19) in leukaemic T-cells compared to B-cells, including several other genes known to be T- or B-cell specific (data not shown). Finally, MACAT is limited to the analysis of Affymetrix microarray, further underlining the need for a tool open to all platforms as well as to cross-platform analysis. The batch effects are the systematic differences between batches (groups) of samples in microarray experiments due to technical reasons, such as variability in materials, protocols or operators, possibly introducing a bias able to confound true biological differences (recently reviewed by Luo and coll. \[[@B30]\]). The TRAM data model described appears to be intrinsically resistant to the influence of batch effects, for the following reasons: the TRAM locus-centred data model does not attempt to separate subgroups within a sample pool, because it is assumed that the samples come from the same biological condition (e.g. cell type, disease) for which only one aggregate value per locus is obtained and considered; the TRAM algorithm is non-parametric at different levels of normalization and analysis and this is expected to reduce the noise due to different value scales; the biological model discussed above deliberately used data from different platforms, protocols and operators, showing results coherent with the current biological knowledge and even better with respect to the results obtained analyzing data deriving from a single platform. However, if the user suspects that batch effects could confound the results, in particular if two single and distinct batches of samples are loaded as pool \'A\' and \'B\', respectively, it could be useful to attempt removing batch effects from the raw data using one of the existing tools \[[@B30]\] prior to importing data in TRAM. While this manuscript was being revised, two novel software were described in addition to those reviewed in the \"Background\" section, able to analyze local enrichment of over/under-expressed genes. CROC \[[@B31]\] also uses the hypergeometric distribution to find genomic regions or gene clusters enriched in over/under-expressed genes, and supports calculations based on both whole genome data and individual chromosome values. However, like the previously published REEF tool \[[@B10]\], it accepts gene name lists as an input and it is not designed to parse, normalize and map original expression data and to display the corresponding quantitative transcriptome maps. The Integrated Genome Browser \[[@B32]\] can load expression data and visualize them along an *x*axis representing the chromosome sequence. However, it lacks any function of data integration, normalization and analysis (Figure [1](#F1){ref-type="fig"}), being essentially a graphical display tool for expression data, like the previously published program ChromoViz \[[@B33]\]. The large agreement of TRAM results, obtained without any *a priori*specific assumptions, with classical biological knowledge about megakaryocytopoiesis, shows that TRAM can perform integrated analysis of expression data from multiple platforms producing high confidence lists of over/under-expressed chromosomal segments and clustered genes. In conjunction with our previous implementation of a GenBank format full parsing system \[[@B34]\] (currently undergoing complete redesigning within FileMaker Pro 7 architecture) and UniGene Tabulator \[[@B35]\], TRAM may also contribute to the building of a novel, relational, multi-purpose, user-friendly and modular platform for the large-scale integrated analysis of genomic and post-genomic data. Conclusions =========== We have here described a unique package able to create and analyze transcriptome maps by integrating gene expression profile data from multiple sources and generating a relational, fully-indexed database-structured map, usable on Macintosh as well as on Windows operating systems-based computers, features that are non commonly available in other applications. TRAM provides a simple and intuitive system for the display and analysis of gene expression data within a single solution, including built-in multiple gene identifier conversion modules, intra-sample and inter-sample data normalization, map comparison between two biological conditions, graphical display and highly flexible data analysis (by both descriptive and inferential statistics) that has proven to generate results of biological interest. The current release of TRAM software is freely available at TRAM home page \[[@B36]\]. We also distribute preconfigured implementations ready for analysis of *Homo sapiens*(human), *Mus musculus*(mouse) and *Danio rerio*(zebrafish) gene expression profiles. Methods ======= Database development -------------------- TRAM was developed within the FileMaker Pro environment. This is a database management system with a user-friendly graphical interface usable on Macintosh and Windows operating systems-based computers. All data import, expression analysis and results of graphical output functions are obtained combining FileMaker Pro scripts and calculated fields (i.e. fields automatically calculating their result processing value from other fields by a pre-defined formula). No additional plug-in or software are required. A specific advantage of this platform as a transcriptome map generator and analyzer is the relational database environment at its core. As a consequence, each dataset in any table (e.g. gene expression values, gene names, expression value of chromosomal segments or gene clusters) is structured as a series of records that may be easily sought according to the desired criteria and then sorted, exported, and possibly related to other database tables. In this way, the graphical display of the map allows the user to maintain full control over the original expression data values at the basis of the map. The freely distributed licensed runtime application allows full data import and export in several formats, as well as full record management and analysis script execution. Only for the creation of new fields, further calculation or additional relationship definition an original copy of FileMaker Pro version 10 (or higher) package is required. TRAM set up ----------- In order to link gene identifiers to the corresponding gene symbols/gene names, it is possible to import in TRAM any text data file containing essential description (e.g., probe identifiers list and matching gene symbols or GenBank sequence accession numbers) for each experimental platform used to assess gene expression level in the examined samples (Figure [1](#F1){ref-type="fig"}). A typical use is loading a GEO \[[@B37]\] Platform file, in order to parse expression datasets obtained using that platform. Pre set-up human, mouse and zebrafish versions are distributed following loading of the most used GEO Platforms for those organisms. In order to uniform the assignment of gene identifiers to standard gene symbols, in absence of an available official gene symbol or an Entrez Gene \[[@B38]\] name, the UniGene \[[@B39]\] Cluster identifier (UniGene ID) is used as the gene name, if available, while the GenBank accession number is used, if provided, in absence of any match to an Entrez Gene or UniGene entry (Figure [1](#F1){ref-type="fig"}). TRAM 1.0 distribution was set up using data available at January 2011, downloading from Entrez Gene the gene localization data and parsing from UniGene tables, allowing the conversion of any RNA or expression sequence tag (EST) GenBank accession number into the corresponding gene symbol \[[@B35]\]. In the case of human UniGene latest available version (build \#228), about 7 millions RNA and EST code data were imported in TRAM. In addition, localization of EST clusters, which are sequences not characterized as official genes but represented in the transcriptome, was derived from UCSC \"ESTs\" track in the UCSC Genome Browser \[[@B40]\], which is also imported and processed during the TRAM set-up. A relationship between UniGene and UCSC ESTs data allows to determine the minimal available start genomic coordinate and maximum available end genomic coordinate for each set of ESTs belonging to the same UniGene cluster. These coordinates are operatively considered the limits of the locus while constructing the transcriptome map. Clusters containing ESTs mapped on different chromosomes are not further considered in the building of the map, as well as those with ESTs mapping on very distant positions on the same chromosome. To this aim, we set a rather conservative limit of 250,000 bp for TRAM, considering that the Entrez Gene set of 27,018 human genes, that is the largest known, has a mean size of 46,210 bp and a standard deviation of 107,161 bp, therefore our limit is equivalent to considering a size range within mean plus or minus 2 SD (approximately 95% of values in a Gaussian distribution). This correction effectively removes approximately 3,000 transcripts, erroneously mapped to regions of several Mb or tens of Mb. The user retains the possibility to inspect the list of EST clusters with a genomic extension greater than 250 kb present in a given chromosome segment, even if they are not considered in the creation of the transcriptome map. Expression data import, parsing and normalization ------------------------------------------------- Each series of data related to a TRAM \'Sample\' is defined as a \'distinct biological sample\'. For example, a sample should be a single channel in the case of two channels experiment, each channel data being imported as a distinct data file. The expression data file may be any tabulated (tab-delimited) text file containing two columns separated by a \'TAB\' character (tabulator key, ASCII9): a gene identifier and a numerical expression value, respectively. Gene symbol, Entrez gene name, custom identifier, GEO Platform probe ID or GenBank accession number are accepted as gene identifiers: the first two by default, the others provided that the software has been appropriately set up. The expression value is usually the pre-processed intensity value (i.e., the value assigned to the spot as it has been processed by the software of the specific experimental platform used, for example, following background subtraction for a microarray spot). An internal utility interactively assists the user in the preparation of text files in the required format, starting from raw expression data. Batch import of a large number of data files is possible. Each sample or set composed of any number of samples may be imported in one of two pools, \'A\' or \'B\', relative to two different biological conditions that may be then easily compared. TRAM is able to perform some useful data normalization methods (Figure [1](#F1){ref-type="fig"}) to allow comparison of gene expression data obtained by different biological samples and/or by different experimental platforms. Intra-sample (e.g., intra-array) normalization works within each distinct sample data, while inter-sample (e.g., inter-array) normalization is simultaneously applied to the desired sample set. The user may select different combinations between these types of normalization. Intra-sample normalization methods are \'Mean\' or \'Median\' (each value is expressed as the percentage of the corresponding sample mean or median value, respectively; this is equivalent to the classic \"global normalization\" in the microarray data analysis \[[@B41]\]) and \'Max\' (each value is expressed as the percentage of the corresponding sample maximum value, equivalent to the classic \"scale normalization\"). These methods rescale values within each data set using a standard internal reference for each sample. Inter-sample normalization method is the commonly used \"quantile\" algorithm \[[@B25]\]. Implementation of this algorithm in the database structure at the core of TRAM is realized as follows: each intra-sample normalized value is given a rank following sample data sorting in ascendant order, then the mean value for all the values with the same rank across all samples is calculated. This mean value is assigned as the expression value to each gene with the same rank in each sample. An original variant of this method implemented in TRAM is described below. The inter-sample normalization methods rescale values across a whole sample set, allowing inter-sample comparison. The summary of gene expression values, under the current mode of normalization, may be viewed as an indexed database table summarizing all data points available in the sample pool for each locus. The mean value of the data points available for each locus is considered the expression value for the respective gene and it is used in the subsequent analysis. Scaled quantile normalization ----------------------------- The quantile method assumes that each sample has the same number of values. However, datasets obtained from different platforms used to assess the gene expression profile, may have highly different numbers of values. In this case, applying the quantile method to the matrix resulting after aligning and sorting values from each sample (represented as a column) gives raise to artefacts, in that the highest values of a sample are summarized with intermediate values of samples with a greater number of values (Figure [4](#F4){ref-type="fig"}). To correct for this artefact, we applied the following formula in TRAM: Scaled Rank = Rank \* Max Rank/Max Sample Rank, were \'Rank\' is the rank (position in the ranking) of the value in the sample data column sorted in ascendant order, \'Max Rank\' is the highest rank present in the whole sample dataset, and \'Max Sample Rank\' is the highest rank assigned within each considered sample. The result of the calculation is rounded to the nearest integer number. The adjusted rank is then used to calculate the mean value across all genes which had the same rank assigned (Figure [4](#F4){ref-type="fig"}). In the case that the experimental platforms have the same number of features, the scaled quantile is identical to quantile. Comparability of values is best attained if previous intra-sample normalization has been performed too. Generation and analysis of transcriptome maps --------------------------------------------- In the \'Map\' mode of analysis, TRAM will generate a graphical map of the transcriptome showing a vertical line representing each chromosome (Figure [2](#F2){ref-type="fig"}). An expression value is associated to each segment of the line, whose size is determined by a window (in bp) set by the user. A differentially coloured horizontal bar is displayed for each chromosomal segment, with a length proportional to the expression value assigned to the relative segment. This value is the mean for all available expression data related to genes included in each segment. The available settings for this analysis are: Window, which defines the length for a segment; Sliding window shift, which defines the overlapping region between a segment and the next one; Percent (segment), which defines the threshold required to consider a segment as over/under-expressed, in terms of inclusion of the segment expression value within the highest/lowest (n) percent of segment expression values; Percent (gene), which defines the threshold expression value to consider a gene as over/under-expressed, in terms of inclusion of the gene expression value within the highest/lowest (n) percent of gene expression values; Number of genes in the window, which defines the minimum number of over/under-expressed genes required to mark the segment with the tag of over/under-expressed, respectively. The calculation of statistical significance of the over/under-expression of the segment is performed as described in the \"Statistical analysis\" Methods section below. Search for clusters of neighbouring over/under-expressed genes -------------------------------------------------------------- In the \'Cluster\' mode of analysis, TRAM will search for sets of at least two contiguous/neighbouring genes, all expressed beyond a defined \'n\' threshold, i.e. with expression values higher than the (100 - \'n\') percentile or lower than the \'n\' percentile. In this mode, results are centred on individual differentially expressed loci without any bond about the length of the over/under-expressed region. The available settings for this analysis are: Percent (gene), which defines the thresholds required to consider a gene as over/under-expressed, in terms of inclusion of the gene expression value within the highest/lowest (n) percent of gene expression values; Gap, which defines the maximum number of non over/under-expressed genes allowed to be localized between two over/under-expressed genes in a cluster (if Gap = 0, only strictly contiguous genes will be considered to be in cluster); Gene Type, which defines if TRAM, while constructing the linear map of genes, will use only genes with an official gene symbol assigned, or will use also genes with at least an Entrez Gene identifier available, or will use any locus with at least a UniGene cluster identifier, even in absence of an official or Entrez Gene symbol. The statistical significance of the results is calculated as described in the \"Statistical analysis\" Methods section below. Statistical analysis -------------------- To assess the statistical significance of the results, TRAM uses the hypergeometric distribution to test the probability \'P\' that colocalization of over/under-expressed genes within the same chromosomal segment (\'Map\' analysis mode) or in the same cluster of contiguous genes (\'Cluster\' analysis mode) may be due to chance. To this aim, calculations are performed as previously described \[[@B10]\]. The \'P\' value needs to be corrected to account for False Discovery Rate (FDR) due to the high number of segments or genes in a genome. The \'Q\' field in TRAM displays the p-value corrected for FDR. Q (q-value) for each chromosomal segment or cluster of contiguous genes is defined as Q = (p\*N)/i, where \'p\' is the p-value of the segment or of the cluster, \'N\' is the total number of segments or cluster considered (i.e., all those tagged as over/under-expressed under the criteria defined by the user selected analysis settings) and \'i\' is the number of windows with a p-value not higher than \'p\' \[[@B10]\]. Results are considered statistically significant for Q \< 0.05. Depending on the type of analysis selected by the user, TRAM may perform statistical significance computation taking into account all genes in the genome or, in order to emphasize local chromosomal effects, taking into account only the genes located in the same chromosome the chromosomal segment or gene cluster belongs to. The results discussed above, regarding the outcome of the normalization methods implemented in TRAM, were obtained using descriptive statistical analysis functions of the software JMP 5 for Mac OS X (SAS Institute, Cary, NC). Biological model test --------------------- To test the software, we performed a meta-analysis of a dataset obtained by gene expression profiling of human hematopoietic progenitor cells, searching for up- or down-regulated chromosomal segments and gene clusters in human megakaryocyte (Mk) cells, the precursors of platelets, compared to CD34+ hematopoietic undifferentiated stem cells. After searching in the GEO database, we selected 9 human Mk samples and 19 human CD34+ cell samples, using the following criteria: homogeneity of cell type, derivation from different Authors works and representation of microarray platforms with different technology and number of spots (Table [1](#T1){ref-type="table"}) \[[@B19]-[@B24]\]. The default analysis parameters were: expression values normalized both intra-sample (by percentage of sample mean) and inter-sample (by scaled quantile method); 2.5th percentile upper and lower threshold to define over- or under-expression, for both segments and genes, with respect to whole genome gene set; requirement of at least 3 over/under-expressed genes to define a segment accordingly; window (segment) of 500,000 bp (with shift of 250,000 bp). The wideness of the window and the minimum number of over/under-expressed genes required to lie in the window (\'n\') should be reciprocally adjusted so that the mean number of all genes included in a segment (shown at the end of the Segment Map) would exceed \'n\'. In our human genes data set, setting a window to 500,000 bp led to segments containing a mean of 4.3 genes, while lowering the window to 250,000 bp led to a mean of 2.7 genes (segments with no gene value are ignored in the calculation of mean). In the \'Cluster\' mode, all available genes including UniGene clusters of transcripts were selected to construct the map, and the Gap was set equal to 1. The test was run on March 2010, using Entrez Gene and UniGene data available at the time (UniGene build \#222). Authors\' contributions ======================= SF, PS and LL conceived the software. PS and LL developed and tested the basic version of the software and wrote the software guide. PS conceived, built and analyzed the biological model used to test the software. FP and MG systematically tested the software, debugged the Windows version and revised and expanded the software guide. FFa, MCP, FFr and RC tested and improved the Macintosh version of the software and developed the organism-specific versions. LV tested the software and collaborated to the biological model test. SC tested the software and developed its graphical interface. SB and AC critically revised the software and the manuscript. GAD, GP and SF supervised the work and revised the whole manuscript. All authors drafted, critically discussed and approved the final manuscript as well as the software guide. Acknowledgements ================ This work was funded by a grant from the Italian Ministry of University and Research (PRIN2005050779). The biological model test was performed on the Apple Mac Pro \"Multiprocessor Server\" available at the Center for Research in Molecular Genetics \"Fondazione CARISBO\", Bologna, and funded by \"Fondazione CARISBO\". We are grateful to Dr. Francesco Ferrari for his useful discussion about the project; to Dr. Mariangela Casadei (SAS Institute Australia, Sidney, Australia) for her helpful advices about statistical analysis and for manuscript revision; to Dr. Francesco Noferini for his helpful discussion of statistical analysis; to Dr. John Kenny for his expert revision of the manuscript; to Prof. Pier Paolo Gatta for his valuable advices about the manuscript. PS wishes to dedicate this work to his father Giuseppe, who died in December 2009, that lovingly followed and strongly supported his scientific endeavours.

PubMed Central

2024-06-05T04:04:19.004482

2011-2-18

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052188/", "journal": "BMC Genomics. 2011 Feb 18; 12:121", "authors": [ { "first": "Luca", "last": "Lenzi" }, { "first": "Federica", "last": "Facchin" }, { "first": "Francesco", "last": "Piva" }, { "first": "Matteo", "last": "Giulietti" }, { "first": "Maria Chiara", "last": "Pelleri" }, { "first": "Flavia", "last": "Frabetti" }, { "first": "Lorenza", "last": "Vitale" }, { "first": "Raffaella", "last": "Casadei" }, { "first": "Silvia", "last": "Canaider" }, { "first": "Stefania", "last": "Bortoluzzi" }, { "first": "Alessandro", "last": "Coppe" }, { "first": "Gian Antonio", "last": "Danieli" }, { "first": "Giovanni", "last": "Principato" }, { "first": "Sergio", "last": "Ferrari" }, { "first": "Pierluigi", "last": "Strippoli" } ] }

PMC3052189

Background ========== Bovine viral diarrhea virus, a single-stranded RNA is found in cattle and other ruminants worldwide \[[@B1]-[@B4]\]. The presence of BVDV in other domestic species such as sheep or wild species such as whitetail deer might be relevant to the epidemiology other disease in cattle \[[@B5]\]. The BVDV infections range from clinically in apparent infections to severe disease involving one or more organ systems. Historically, BVDV was associated with digestive tract disease including high mortality. Currently, BVDV is associated more frequently with respiratory disease and fetal infections \[[@B2]\]. Raise skia deer already had hundreds years at present artificially in china and farmed populations had reached hundreds of thousands in recent year. However, bovine viral diarrhea (BVD) caused significantly losses in the deer population. It was reported that infections rates of BVDV for young deer reached 60%\~86.7% in some areas of china in recently years \[[@B6]\], which caused economic losses to sika deer industry due to the high morbidity and fetal infections associated with the disease. Thus, the isolation and identification of BVDV from sika deer, which is fundamental to prevent and control of BVDV in sika deer, becomes an urgent task to many researchers. The Bovine viral diarrhea virus (BVDV) belongs to the genus *pestivirus*within the family *Flaviviridae*. BVDV is closely related to the classical swine fever virus (CSFV) and the ovine border disease virus (BDV) \[[@B7]\]. The pestiviral genome consists of a single stranded positive sense RNA with a length of about 12.3 kb. It contains one larger open reading frame (ORF), which is flanked by nontranslated regions (NTR) on both genome termini. The single ORF is translated into one polyprotein, which is co-and post- translationally processed into the mature proteins N^pro^, C, E0 (gp48, also named E^rns^), E1, E2, NS2/3, NS4a, NS4b, NS5a and NS5b by viral and cellular proteases \[[@B8]-[@B10]\]. E0 protein, the main structural protein of BVDV, plays a very important role in inducing protective immunoreaction against BVDV and diagnosing virus \[[@B2]\]. Although BVDV from the skia deer has been seriously concerned, there are only a few articles with respect to the prevalence of BVDV investigations and BVDV clinical sign \[[@B6]\], Particular, lacking in articles with regard to the molecular virology, gene sequences and genetically engineering vaccine of local BVDV isolates in China due to BVDV from skia deer without isolation and identification. The purpose of our study was isolation and identification BVDV from skia deer by a series of methods, which contributes this disease control. Results ======= Isolation and identification ---------------------------- The significant cytopathic effects (CPE) were observed in MDBK cell infected with virus 24h-48h. The MDBK cells generate obvious cell lesion and net between cells in comparison to the control cells, which is consistent with CPE of BVDV on MDBK cell (Figure [1](#F1){ref-type="fig"}). The IPX assay showed that the well of positive serum appeared red-brown cytoplasmic staining, which suggested that new isolation virus might be BVDV. The negatively stained virus particles extracted from liver were approximately 40 nm-60 nm in diameter when examined by electron microscope (Figure [2](#F2){ref-type="fig"}), and displayed a typical BVDV morphology. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **The CPE of BVDV**. A: The MDBK cell as negative control; B: The CPE of C~24~V strain as positive control. C: The CPE of CCSYD strain. ::: ![](1743-422X-8-83-1) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Negatively stained BVDV**. ::: ![](1743-422X-8-83-2) ::: Amplification, sequencing and analysis of E0 gene ------------------------------------------------- The MDBK cell infected with CCSYD were positive by the RT-PCR assays, and the expected sizes of the PCR products, 706 bp for E0 of CCSYD, were observed as clear electrophoretic band (Figure [3](#F3){ref-type="fig"}). The obtained E0 genes segment by sequencing has been deposited in GeneBank under accession No. FJ55520. Alignment with other 9 strains of BVDV, 7 strains of CSFV and 3 strains of BDV in the world, showed that the homology were 98.6%-84.8%, 76.0%-74.7%, 76.6%-77.0% for nucleotide sequence, respectively (Table [1](#T1){ref-type="table"}), which shows that there is no significant deviation of CCSYD E0 with conventional BVDV. ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **The amplified products by RT-PCR**. Lan1 and Lan2: E0 gene from infected MDBK cell; Lan3: MDBK cell as negative control. ::: ![](1743-422X-8-83-3) ::: ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Homology of E0 gene sequence of different RHDV isolates ::: C~24~V R1935 naqdl SD-1 Bega Y546 CCSYD VEDEVAC ILLC OSLOSS ALD GPE Brescia SM C LN9912 JL BD31 BDVX818 C413 --------- -------- ------- ------- ------ ------ ------ ------- --------- ------ -------- ------ ------ --------- ------ ------ -------- ------ ------ --------- ------ C~24~V 99.5 91.5 92.7 88.4 88.6 84.9 84.6 85.6 85.2 75.5 75.4 74.5 75.5 76.0 75.8 75.2 77.1 77.0 76.6 R1935 0.6 91.5 92.7 88.6 88.9 85.2 84.8 85.8 85.2 75.5 75.4 74.6 75.5 76.0 75.8 75.3 77.1 77.0 76.5 naqdl 11.8 11.8 91.5 87.7 87.8 86.2 85.5 87.0 85.6 75.6 75.8 75.2 75.3 75.1 74.8 75.1 77.8 77.5 76.9 SD-1 10.0 10.0 11.8 88.1 88.6 84.8 84.7 85.7 85.7 75.1 74.9 74.0 74.9 75.4 75.2 74.7 78.9 78.0 76.7 Bega 16.9 16.5 18.0 17.4 95.1 85.8 85.8 87.4 86.4 74.8 74.9 74.9 74.9 74.5 74.5 76.3 77.7 77.6 76.9 Y546 16.6 16.2 17.9 16.5 6.5 85.5 85.4 86.7 86.5 74.5 74.6 74.7 74.4 73.9 73.9 76.2 79.1 78.2 76.3 CCSYD 22.8 22.4 20.5 23.2 21.2 21.8 98.6 92.7 95.1 76.0 76.1 75.1 75.8 74.7 74.9 75.5 76.6 76.7 77.0 VEDEVAC 23.5 23.1 21.8 23.4 21.2 22.1 1.8 93.4 95.8 76.2 76.3 75.1 76.0 74.9 74.9 75.8 76.9 76.7 77.4 ILLC 21.7 21.3 19.2 21.5 18.6 19.9 10.0 9.0 92.6 76.0 76.2 75.3 76.0 75.5 75.5 76.7 77.4 77.1 77.8 OSLOSS 22.6 22.6 21.6 21.5 20.2 20.0 6.5 5.5 10.3 76.1 76.2 75.2 76.0 75.2 75.2 76.1 77.3 76.6 77.1 ALD 40.9 40.9 40.8 42.3 42.7 43.6 40.1 39.4 39.9 39.6 99.3 94.7 98.6 96.6 96.6 88.2 79.2 79.1 77.6 GPE 41.2 41.2 40.4 42.6 42.4 43.2 39.8 39.1 39.3 39.3 0.9 94.1 97.9 96.1 96.1 88.5 79.4 79.4 77.7 Brescia 43.2 42.9 41.6 44.6 42.1 42.6 42.0 41.9 41.3 41.5 7.1 8.0 94.4 92.8 93.3 87.4 78.3 78.0 76.8 SM 40.9 40.9 41.6 42.6 42.3 43.7 40.5 39.8 39.8 39.7 1.8 2.7 7.5 96.4 96.6 88.3 79.2 79.1 77.3 C 39.8 39.8 42.2 41.4 43.7 45.1 43.3 42.5 41.0 41.8 4.4 5.2 9.8 4.7 99.5 86.8 78.9 78.7 77.8 LN9912 40.3 40.3 42.7 41.9 43.6 45.1 42.6 42.5 40.9 41.7 4.4 5.2 9.2 4.4 0.6 86.8 78.9 78.7 77.6 JL 41.6 41.3 42.0 43.0 38.8 39.1 41.0 40.3 38.1 39.4 17.3 16.7 18.5 17.0 19.7 19.7 78.5 79.0 76.7 BD31 37.2 37.2 35.8 33.5 36.0 33.0 38.3 37.6 36.6 36.8 33.7 33.5 35.6 33.8 34.5 34.5 34.8 92.3 77.4 BDVX818 37.4 37.4 36.5 35.4 36.3 35.0 38.1 38.2 37.2 38.5 33.9 33.4 36.4 33.9 34.9 35.0 33.9 10.6 76.7 C413 38.4 38.7 37.8 38.2 37.8 39.1 37.2 36.5 35.5 36.9 36.2 35.9 37.9 37.0 35.7 36.2 37.9 36.7 38.3 ::: Phylogenetic analysis --------------------- To better understand the relationship of CCSYD to other 9 strain of BVDV, 7 strains of CSFV and 3 strains of BDV variants co-circulating in the word, genetic sequences of *Pestivirus*from cattle, swine and ovine in GenBank were used to construct phylogenetic trees. Figure [4](#F4){ref-type="fig"} clearly showed that E0 genes of the CCSYD belonged to BVDV1b. ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **Phylogenetic analysis of E0 protein sequence of different BVDV isolates**. ::: ![](1743-422X-8-83-4) ::: Discussion ========== In the present study, CCSYD strain was isolated from skia deer in Changchun city. By employing a series of biochemical and biophysical methods, we have firstly identified that CCSYD might be BVDV. The BVDV can be classified into biotypes and genotypes \[[@B2]\]. Biotypes are based on the presence or absence of visible CPE in infected cell cultures, cytopathic (CP) or noncytopathic (NCP) \[[@B2]\]. Genotype classification is based on divergence in the viral genome sequences revealed by phylogenetic analysis \[[@B11]-[@B15]\]. Based on phylogenetic comparison, the virus can be classified into two genotypes: BVDV1 and BVDV2. Whereas BVDV1 has a world-wide distribution, BVDV2 appears to be highly prevalent only in North America \[[@B13],[@B16]\] and relatively rare in other continents \[[@B15],[@B17]\]. Moreover, recently the BVDV1 and BVDV2 genotypes have been further divided into subgenotypes BVDV1a, BVDV1b, BVDV2a, and BVDV2b in North American \[[@B18],[@B19]\]. Genetic and phylogenetic analysis showed that the virus belonged to BVDV1b. Similar strains contain the VEDEVAC strain isolated Hungary, with 98.7% homology for amino acid. Moreover, we have also successfully cloned NS2/3 genes of CCSYD strain, with 100% homology for amino acid and NS2/3 genes of VEDEVAC strain, which further showed that CCSYD strain and VEDEVAC strain belonged to BVDV1b. The protection conferred by conventional inactivated BVDV vaccines is strongly correlated with genetically and antigenically of specific BVDV strain. In addition to, an increasing frequency of skia deer with elevated antibody titers to BVDV suggests that exposure to field strains has not been diminished despite the use of both management and vaccine \[[@B6]\]. This suggests that current vaccine may be inadequate in conferring skia deer protection against the acute disease in skia deer. Design of efficacious vaccines must be based on specific BVDV strain about the immune responses critical to development of protection. Hence, it is appropriate to guide the selection of the vaccine strain according to the specific BVDV strain from local area and similar strain, which depend on further studies of BVDV from skia deer distribution and identification. There is currently no commercial skia deer BVDV vaccine used in China, and therefore, it is important to select the vaccine candidate strain from control BVD from skia deer. Inactivated CCSYD strain by a certain method might be employed in preventing and counterchecking the skia deer BVD in Jilin province. Moreover, selected E~0~protein of CCSYD construction a DNA vaccine might induce cellular immune response and antibody responses specific for BVD from skia deer. Therefore, isolation and identifcation of a skia deer bovine viral diarrhea virus (CCSYD) contributes development new BVDV vaccine to prevent and control of BVDV in sika deer. Conclusions =========== The present study described the isolation and identifcation of a skia deer bovine viral diarrhea virus (CCSYD) isolated from sick skia deer for the first time in China. This study provided a detailed analysis of the genetic and evolution of CCSYD which is likely to be helpful to guide efficient diagnostic, preventive and control strategies against BVD from skia deer in China. Materials and methods ===================== Virus isolation --------------- Field samples came from skia deer at field of Changchun (China), which might infected with BVDV according to clinical sign such as diarrhea and miscarriage and stillbirth. Skia deer liver was collected from an aborted fetus deer. A total of 1 g of fresh liver tissue was homogenized in 4 ml of phosphate-buffered saline (PBS, PH 7.2) and then repeated freeze thawed 3 times, and centrifuged at 5000 rpm for 30 min. A certain liver extract was then inoculated onto MDBK monolayer cultures, 25 cm flasks with a 1 ml inoculum (1:10 dilution of original samples) and the total volume was 5 ml. The MDBK cultures were observed for 6 days with presence or absences of CPE recorded. The cultures were frozen at 70°C, thawed and supernatants collected after centrifugation with subsequent storage at 70°C. Uninoculated cultures were included as negative controls and inoculated C~24~V as positive control. Identification of virus ----------------------- BVDV was detected by indirect immunoperoxidase test (IPX) and electron microscopy technique (EM). For IPX, the test was carried out on 96-well plates using low-passage MDBK cells. Serum (20 μl) was added to each of four wells before the addition of 100 μl of cell suspension. Positive and negative control sera were run on each plate. The test plates were incubated for 4 days in 5% CO~2~, 37°C. Plates were fixed and dried, then stained with immunoperoxidase as described by Meyling \[[@B20]\], using a polyclonal bovine anti-BVDV serum (BVD virus positive control serum, China) to detect the virus. The presence of red-brown cytoplasmic staining in any of the wells exposed to the specific anti-BVDV antibody denoted a positive result. For electron microscopy technique (EM), chloroform (1/10 of the volume of the liver extract) was added into the liver extract, and then the liver extract) was added into the liver extract, and then the mixture was incubated for 30 min at 4°C and then centrifuged at 12000 rpm for 30 min. The precipitate was resuspended in 0.005 M moderate phosphate buffered saline (PBS; PH 7.2), and negatively stained with 2% phosphotungstic acid. The specimens were examined with a transmission electron microscope (Hitachi-8100, Japan) at 80 kV. PCR amplification and sequencing -------------------------------- Total RNA was isolated from infected MDBK cell using TRIzol reagent (Invitrogen China) according to the manufacturer\'s protocol and as described in the online supplement. In short, 200 μl infected MDBK cell was incubated with 1 ml TRIzol for 5 min at room temperature (RT). Cell debris was removed by centrifugation (12,000 × g at 4°C for 10 min) and 0.4 ml chloroform was added. After vortexing the mix was incubated for 5 min at RT. The phases were separated by centrifugation (12,000 × g at 4°C for 15 min) and the aqueous phase was transferred to a new tube. 0.6 × volume of isopropyl alcohol and a 0.1 × volume of 3 M sodium acetate were added to this aqueous phase and incubated for 10 min at 4°C. The precipitated RNA was pelleted by centrifugation (12,000 × g at 4°C for 15 min) and after the removal of the supernatant the RNA pellet was washed twice with 70% ethanol. After drying, the RNA was resuspended in 30 μl DEPC-treated water. Using mRNA as template, single-stranded cDNAs were generated by Superscript II reverse transcriptase (Invitrogen) according to the manufacturer\'s directions. The E0 primer sequences were as follows: sense prime: 5\'-CCGGATCCACCATGGAAAACATAACACAGTGG-3\'; anti-sense prime: 5\'- GCCTCGAGTTAAGCGTATGCTCCAAACCACGT -3\'. The PCR conditions were 94°C for 3 min, followed by 30 cycles of DNA amplification (45s at 94°C, 1 min at 61°C, and 1 min 30s at 72°C) and 8 min incubation at 72°C. PCR products were separated by electrophoresis at a constant voltage (2 V/cm) in a 1.2% (w/v) agarose gel. The full-length E0 gene subjected to DNA sequencing. Analysis of sequence -------------------- The sequence data were analyzed with computer programs such as DNAMAN and DNASTAR. Phylogenetic analysis was done by the distance-based Neighbor-joining method using software EGA 4.1. (DNAStar Inc.). Abbreviations ============= BDV: Border Disease Virus; BVD: Bovine viral diarrhea; BVDV: Bovine Viral Diarrhea Virus;CPE: Cytopathic Effects; CSFV: Classical Swine Fever Virus; DNA: Deoxyribonucleic Acid; EM: Electron Microscopy; IPX: Indirect Immunoperoxidase; MDBK: Bovine Kidney; PCR: Polymerase Chain Reaction; RNA: Ribonucleic Acid. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= YG and PZ participated in the design and conducted the majority of the experiments in the study and drafted the manuscript. RD and SW contributed to the interpretation of the findings and revised the manuscript. QW and NW edited the manuscript. CS performed analyses of data. All authors read and approved the final manuscript. Acknowledgements ================ The authors gratefully acknowledge the financial support provided by China Postdoctoral Science Foundation (20090461042), Supported by Ministry of Science and Technology of China(2009GJB10031) and Supported by National Natural Science Foundation of China (30570185).

PubMed Central

2024-06-05T04:04:19.012872

2011-2-25

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052189/", "journal": "Virol J. 2011 Feb 25; 8:83", "authors": [ { "first": "Yugang", "last": "Gao" }, { "first": "Shijie", "last": "Wang" }, { "first": "Rui", "last": "Du" }, { "first": "Quankai", "last": "Wang" }, { "first": "Changjiang", "last": "Sun" }, { "first": "Nan", "last": "Wang" }, { "first": "Pengju", "last": "Zhang" }, { "first": "Lianxue", "last": "Zhang" } ] }

PMC3052190

Introduction ============ Almost 170-200 million of the world population is infected with HBV, leading to world\'s most common cancer \"Hepatocellular carcinoma (HCC)\", causing nearly one million deaths per year. Approximately, 20% of chronic HBV patients have eventually progressed to liver cirrhosis, and some infections have evolved into HCC in a substantial number of patients \[[@B1],[@B2]\]. The most common contradiction in diagnosis of HBV patients is the differentiation of chronic active cases from the inactive carriers, as they share same serological profile. Diagnosis of disease outcome in these patients with PCR and HBV DNA levels assay, and defining the state of infection with these tools is emerging during last decade \[[@B3]-[@B5]\]. However, in many countries and regions like United States, Western Europe and other high or middle income countries, ELISA is still used and majority of the positive tests are not confirmed by PCR. It is interesting to note that many HBeAg (-) patients showed presence of chronic active HBV in further screening by PCR and vice versa \[[@B6]\]. To differentiate active chronic HBV from inactive carrier state, an arbitrary serum HBV DNA level of 100000 copies/mL has been proposed by the United States national Institute of health (NIH) \[[@B7]\]. During HBV disease progression, after seroconversion (HBeAg (+) to HBeAg (-), HBeAg consists of two clinical forms; one known as chronic inactive with low persistant aminotransferase levels and HBV DNA levels (≤ 100,000 copies/ml) and second with no HBeAg, high ALT and HBV DNA levels (≥ 100,000 copies/ml). In low-income countries like Pakistan, many patients refused to do PCR and liver biopsy procedure due to poverty and cost of these tests. Beside these challenges, the growing concern is the early detection of viral hepatic disease and liver damage. For this purpose, in routine laboratory tests, elevated alanine aminotransferase (ALT) levels are used as indicators of liver cell injury and as non-invasive diagnostic tests \[[@B8]\]. Elevated AST levels are usually predominant in liver cirrhosis with increased ALT levels \[[@B9],[@B10]\]. During assessment of liver disease due to hepatitis, serum AST and ALT levels are most commonly used serum markers to detect acute and chronic hepatocytes cytotoxicity \[[@B11]-[@B13]\]. Now a days, the main emphasis of workers is early detection of liver damage due to chronic HBV, however, there is always questions about the effectiveness of these test because of their low sensitivity \[[@B14],[@B15]\]. Several studies in Italy, China, Korea and Hong Kong showed that ALT levels higher than the normal limits are strongly associated with an increased risk of liver cirrhosis in HBV infected patients \[[@B16]-[@B19]\]. Recent studies revealed that in patients with HBeAg (-), high ALT levels greater than 0.5x to the upper limit of normal (ULN) relate to advance fibrosis and ALT \> 30 IU/L and 19 IU/L in male and female respectively, with base line HBV DNA levels \> 100000 copies/ml; can better differentiate between active chronic HBV patients from inactive chronic carriers \[[@B11],[@B12],[@B20]-[@B22]\]. While, Degertekin *et al.*proposed HBV DNA cutoff values of 5000 copies/mL to differentiate between active chronic HBV patients from inactive chronic carriers \[[@B23]\]. These studies indicates ALT level as a reliable serum marker leading to fact that HBV natural history can vary from one population to another \[[@B24]\]. Therefore, we should determine more reliable cutoff value for serum ALT and AST levels to predict active HBV patients according to our population. The aim of our study was to assess the relationship between HBV DNA load, AST and ALT levels in HBeAg (-) patients, review the performance of serum ALT and HBV DNA levels as the screening tool for liver disease and to find whether new cutoff values of ALT and HBV DNA are able to predict HBV infection in Pakistani population. The need of PCR and invasive procedure liver biopsy may be eradicated if the serum biochemical marker ALT with high positive or negative predictive values of HBeAg (-) patients can be obtained and thus minimize the cost of PCR and therapy time. Material and methods ==================== Patients -------- Patients of this study were the native Pakistani people referred to Pathology department, Jinnah Hospital, Lahore, Pakistan, for biochemical and serological tests. This retrospective cross-sectional study was carried out from March 2008 to September 2009 with collaboration of National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. Blood samples (10 mL) collected from each patient tested for HBsAg and HBeAg by ELISA. All patients did not have any history about HBV vaccination or disease infection, and/or other type of hepatitis. The routine liver function tests (LFTs) were estimated for each patient in hospital laboratory. Patients with positive serology and/or positive test for HBV alone and no evidence of liver failure were included in this study. Informed consents were obtained from patients containing their bio data and lab results. This study was approved by the Institutional ethics committee. Laboratory assays ----------------- Test for HBsAg and HBeAg were done by using ELISA kits (Abbot Diagnostics). Serum ALT and AST levels were measured by using commercially available Hitachi-7600 series automatic analyzer. The normal limits considered for ALT was 40 IU/L and for AST 35 IU/L. Serum HBV DNA was evaluated by using commercially available polymerase chain reaction assay (Amplicor HBV Moniter test; Roche Diagnostic System, Inc., Branchburg, New Jersey) with lower limit of detection 80 copies/mL and accurate range 500-200,000 copies/mL according to manufacturer protocol. Selected patients were HBeAg (-) with base line ALT determined at first visit. Patients ALT levels were determined four times every three months. Patients were divided into two groups as inactive (A) and active (B) chronic carriers based on HBeAg absence, liver diagnosis by ultrsonography, persistent ALT levels and HBV DNA load. Patients with ≥ 100000 HBV DNA copies/mL and continual elevated ALT levels were considered as active chronic carriers. Statistical analysis -------------------- Statistical analysis was performed using the statistical package for social studies (SPSS) version 16 for windows. Student t-test and chi-square tests were applied to evaluate differences in proportions. *P*value \<0.05 was considered significant. Univariate analysis includes the variables age, HBV DNA levels, ALT and AST. Gender and PCR results were taken as independent categorical factors. Spearman correlation was used to assess the association between two quantitative variables. The diagnostic validity of serum ALT, AST and HBV DNA load and their combination were tested for classification of HBeAg (-) patients into active and inactive chronic patients. ROC curves were drawn for predicting values of ALT, AST and ALT at specific cut off values. Cutoff values for AST and ALT were 40 and 35 IU/L for each respectively, while for HBV DNA cut off values were 2000, 5000, 20,000, 50,000 and 100,000 copies/mL, respectively. New cut off values with high sensitivity, specificity, PPV and NPV were also predicted. Results ======= Patient\'s clinical characteristics ----------------------------------- A total of 567 HBeAg (-) patients were selected for this study. Patient\'s data is given in Table [1](#T1){ref-type="table"}. The mean age of the patients was 32.20 ± 11.9. Of 567 patients, 228 were classified into HBeAg (-) chronic inactive, while remaining 339 were active. The age difference between both groups was not significant (*P*= 0.181). Male were dominant in both groups. Out of 228 inactive and 339 active patients, 58 and 114 were female respectively (*P*= 0.038). Among 170 chronic inactive male, 168 have ALT \< 30IU/L; while 51 chronic inactive female out of 58, have ALT \< 19 IU/L. Regarding AST levels, 225 inactive and 74 active carriers have their AST levels \< 35 IU/L. Baseline ALT and AST values were significantly higher in HBeAg (-) chronic active patients (*P \< 0.05*). ::: {#T1 .table-wrap} Table 1 ::: {.caption} ###### Clinical characteristics of HBsAg positive patients ::: Patients characteristics Inactive carriers n = 228 Active carriers n = 339 *P*-value -------------------------- --------------------------- ------------------------- ----------- M/F 170/58 225/114 0.038 Age 31.3 ± 12.1 32.75 ± 11.7 0.181 ALT (IU/L) 17.3 ± 4.3 70.3 ± 15.1 0.000 AST (IU/L) 15.9 ± 7.1 48.4 ± 22.6 0.000 HBV DNA (copies/mL) 4.9 × 10^3^ 6.5 × 10^8^ 0.000 ::: HBV DNA levels were five times elevated in active carriers (HBV DNA levels = 4.38 × 10^8^(± 1.04 × 10^9^) copies/mL *vs*6.9 × 10^4^(± 4.9 × 10^5^) copies/mL). More than 99% (n = 227) inactive carriers patients have HBV DNA levels less than 50, 000 copies/mL, and below undetected limits (\< 200 copies/mL) in 21 patients. Application of revised cutoff values ------------------------------------ Receiver operating characteristics (ROC) curves were drawn for ALT, AST and HBV DNA levels. All of them showed high area under the curve (AUC) to discriminate HBeAg (-) active carriers from inactive as mentioned in Table [2](#T2){ref-type="table"} (see also Figure [1](#F1){ref-type="fig"}). ::: {#T2 .table-wrap} Table 2 ::: {.caption} ###### ROC curve analysis of serum AST, ALT and HBV DNA levels ::: Test Result Variable(s) Area SE *P*-value 95% C I ------------------------- ------- ------- ----------- --------- ------- **AST** 0.969 0.006 0.000 0.957 0.982 **ALT** 0.997 0.002 0.000 0.994 1.001 **HBV DNA level** 1.000 0.000 0.000 1.000 1.000 ::: ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **ROC curve of serum ALT, AST and HBV DNA levels for HBeAg (-) patients showed serum ALT, AST and HBV levels could better predict HBV chronic active carriers at given cutoff value**. ::: ![](1743-422X-8-86-1) ::: We observed approximately same sensitivity and specificity for the HBV DNA level ≥ 50,000 and NIH described limits ≥100,000 copies/mL. This value was much better than HBV DNA value of 2000, 5000 and 20,000 copies/mL. In general cohort, ALT and AST ≤ 20 IU/L were observed in 200 and 191 patients, respectively. ALT ≤ 30 IU/L showed high sensitivity (99.1%) and specificity (97.4%), while normal AST value (≤ 35 IU/L) showed high sensitivity (98.6%) but low specificity (77.8%) to discriminate active and inactive chronic HBeAg (-) carriers, respectively. In combination, ALT and HBV DNA levels; if ALT value were ≥30 IU/L for male and ≥19 IU/L for female, and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers (Table [3](#T3){ref-type="table"}). ::: {#T3 .table-wrap} Table 3 ::: {.caption} ###### Validity of serum ALT, AST and HBV DNA levels for the differentiation of patients with HBeAg (-) inactive chronic hepatitisB from active chronic HBeAg (-) carriers ::: Lab tests Spe% Sen% PPV% NPV% Inactive carriers (n = 228) Chronic carriers (n = 339) ---------------------------------------------- ------ ------ ------ ------ ----------------------------- ---------------------------- **ALT (IU/L)** ≤ 20 99.1 87.7 99 92 200/28 2/337 ≤ 30 97.4 99.1 96 99.3 226/2 8/331 ≤ 35 96.6 99.6 96 99.6 227/1 9/330 ≤ 40 93.4 100 93 100 228/0 16/323 **AST (IU/L)** ≤ 20 93.5 83.7 82 89.5 191/37 40/317 ≤ 30 79.1 95.6 75.4 96.4 218/10 71/268 ≤ 35 77.8 98.6 75.2 98.8 225/3 74/264 ≤ 40 63.1 99.1 64.4 99.5 227/1 124/214 **HBV DNA (Copies/mL)** ≤ 2000 100 48.2 100 75 110/118 0/339 ≤ 5000 100 75.4 100 84 172/56 0/339 ≤ 20,000 100 95.1 100 95 217/21 0/339 ≤ 50,000 100 99.1 100 99 227/1 0/339 ≤ 100,000 100 100 100 100 228/0 0/339 **ALT + HBV DNA (Our findings)** ALT (30 M/19F) HBV DNA (≤ 100,000 copies/mL) 92 98 97 94 210/18 5/334 **ALT + HBV DNA (Assy *et al.***\[[@B22]\]) ALT (30 M/19F) HBV DNA (≤ 100,000 copies/mL) 100 92 100 86 \- \- ::: A statistical significant correlation was found between HBV DNA levels and ALT in HBeAg (-) chronic active patients (*r*= 0.911, *P \< 0.05*). However, no such association was observed in case of ALT in chronic inactive patients and AST in both groups (Figure [2](#F2){ref-type="fig"}). ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Correlation of ALT and AST with HBV DNA levels in HBeAg chronic inactive and active patients**. A and C: association between ALT and AST with HBV DNA levels in chronic inactive carriers; B and D: association between ALT and AST with HBV DNA levels in chronic active carriers. ::: ![](1743-422X-8-86-2) ::: Discussion ========== In this study, we assess the performance of new cut off values for serum ALT levels in male and female to predict active HBV in HBeAg (-) patients. As high ALT levels are thought to be associated with chronic HBV, and are commonly used during evaluation of HBV \[[@B10],[@B25]-[@B28]\]. It is interesting to know that HBV evaluation depend on geographical association of the host and viral factors. Prati *et al.*proposed new cutoff value of ALT ≥ 30 IU/L in male and ≥19 IU/L in female \[[@B12]\], while Assy *et al.*2009 reported ALT ≥ 30 IU/L in male and ≥ 19 IU/L in female along with HBV DNA levels ≥ 100000 copies/mL can classify a patient into the active carrier state \[[@B22]\]. Although, serum AST levels are not thought to be incredibly useful predictor of HBV disease, we also evaluate their performance either they are useful or not for discriminating HBeAg (-) chronic active from inactive patients. Previous studies reported raised serum ALT levels from ULN can predict liver dysfunction with 90% specificity and 56% sensitivity \[[@B29]\], but according to Kim *et al.*prior testing of ELISA along with ALT level can better predict liver function as compared to only ALT levels \[[@B30]\]. This is particularly important because without performing PCR and liver biopsy, the decision as to predict HBeAg (-) chronic inactive is difficult. ROC curve analysis was performed to find out an accurate cutoff value for ALT, AST and HBV DNA load to guess HBeAg (-) inactive chronic patients from active (Table [2](#T2){ref-type="table"} and [3](#T3){ref-type="table"}). Serum ALT, AST and HBV DNA levels were found to be highly significant with immense AUROC. Their performance was assessed by using different cut off values irrespective of patient\'s gender. We observed same results as described by Prati *et al.*\[[@B12]\] and Assy *et al.*\[[@B23]\]. ALT ≤30 IU/L and HBV DNA load ≤ 100,000 copies/mL showed high sensitivity, specificity, PPV and NPV to differentiate HBeAg (-) inactive chronic patients from active. In combination (ALT and HBV DNA levels) we observed higher sensitivity (98%) and NPV (94%) than previously described \[[@B22]\] (92% and 86%, respectively) (Table [3](#T3){ref-type="table"}). Although Borg *et al.*found AST level as an important predictor during same circumstances \[[@B31]\], and in our study single AST value (≤ 20 IU/L) also showed high sensitivity and specificity, its prognostic ability was not better than serum ALT and HBV DNA. Our results are in agreement with Assay *et al*\[[@B22]\]. that the new baseline value for ALT levels (30 IU/L for male and 19 IU/L for female) notably perform well than AST as given in Table [3](#T3){ref-type="table"}. We detect HBV DNA in all patients. By using new cut off value of ALT, HBV DNA cut off values 50, 000 and 100,000 copies/mL showed same investigative performance and were better than 2000, 5000 and 20,000 copies/mL. These results indicate that NIH proposed HBV DNA levels limits are useful, and our findings are according to the study by Assy *et al.*\[[@B22]\] as given in Table [3](#T3){ref-type="table"}. As HBV DNA load and liver damage appears to be different in HBeAg (+) and negative patients. In HBeAg (+) patients, no correlation was found between severity of liver damage and HBV DNA load \[[@B32]-[@B34]\]. In recent study by Kim *et al.*(2011) validate the performance of ALT and HBV DNA, and found that these markers may also used for discriminating patients with HBeAg (-) active carriers from inactive \[[@B35]\]. In our study, HBV DNA load was five times higher in chronic active patients. We also observed a positive significant correlation between HBV DNA levels and ALT in chronic active patients (Figure [2](#F2){ref-type="fig"}) leading to the conclusion that inflammation increases in patients with elevated HBV DNA levels as HBeAg has immunomodulatory action \[[@B36]\]. Recent studies showed that for HBeAg (-) patients, low HBV DNA levels are associated with less liver damage although some studies were unable to observe such relationship \[[@B37],[@B38]\]. These findings suggest that HBV DNA load and ALT are most convenient techniques to predict active chronic HBV in HBeAg (-) patients. Although, there are some limitations in our study like absence of liver biopsy data, HBV genotyping and/or a short period of follow up; yet the population size in this study is far larger than reported by others. In conclusion, we verified the new cut off value of ALT and found better results than previously described and also found AST as good predictor. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= BI, WA and FTJ contributed equally to this work. BI, WA, SG, FTJ and SH designed the study, analyze the data and wrote paper. They also checked the revised manuscript thoroughly and confirmed all the data given in manuscript. All work was performed under supervision of SH. We all authors read and approved the final manuscript. Authors\' information ===================== Bushra Ijaz (M Phil Molecular Biology), Waqar Ahmad (M Phil Chemistry) and Gull S (MSc Biochemistry) are Research Officer; Javed FT is Head Pathology Department Jinnah Hospital, Lahore; while Sajida Hassan (PhD Molecular Biology) is Principal Investigator at CEMB, University of the Punjab, Lahore Acknowledgements ================ Financial support by Prime Minister program for prevention of hepatitis (2005-10) is highly acknowledged.

PubMed Central

2024-06-05T04:04:19.015111

2011-2-27

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052190/", "journal": "Virol J. 2011 Feb 27; 8:86", "authors": [ { "first": "Bushra", "last": "Ijaz" }, { "first": "Waqar", "last": "Ahmad" }, { "first": "Fouzia T", "last": "Javed" }, { "first": "Sana", "last": "Gull" }, { "first": "Sajida", "last": "Hassan" } ] }

PMC3052191

Background ========== Aplastic anemia, acquire or congenital anemia associated with hypoplastic \"fatty or empty\" bone marrow and global dyshematopoiesis, has been first described by Paul Ehrlich in year 1888 \[[@B1]\]. The pathophysiology is believed to be idiopathic \[[@B2]\] or immune-mediated phenomenon with active destruction of haematopoietic stem cells \[[@B3]\]. The abnormal immune response may be elicited by environmental exposures, such as to chemicals, drugs, viral infections and endogenous antigens generated by genetically altered bone marrow cells \[[@B4]\]. A small fraction of the genes involved in pancytopenia has been represented by the congenital BM failure syndromes (relatively rare) which lately develop in clinical syndromes as Fanconi\'s anemia, Dyskeratosis Congenita, and Shwachman-Diamond syndrome \[[@B5],[@B6]\]. Hepatitis-associated aplastic anemia (HAAA) is a well recognized and distinct variant of clinical syndrome, acquired aplastic anemia, in which an acute attack of hepatitis leads to the marrow failure and pancytopenia \[[@B7]-[@B9]\]. HAAA has been first reported in two cases by Lorenz and Quaiser in 1955 \[[@B8]\] and the number of the cases increase up to value of 200 by the year 1975 \[[@B10]-[@B12]\]. However, this syndrome has been reported in 2-5% cases of west and 4-10% in area of more prevalent to hepatitis and Human Immunodeficiency Viruses (HIV) in the Far East \[[@B12],[@B13]\], it belongs to the area of low socioeconomic status \[[@B14],[@B15]\]. HAAA is not considered relative to age, sex and severity of hepatitis \[[@B14]\], predominantly it has been found in children \[[@B13]\], adolescent boys and in young aged men \[[@B10],[@B16]\]. The onset of syndrome, pancytopenia, usually takes two to three months \[62 days: ranging from 14 to 225) after attack of acute hepatitis \[[@B12],[@B14]\]. Hepatitis associated with aplastic anemia may be acute and chronic \[**7**\], mild and transient \[[@B16]\], self-limiting and fulminant and the development of AA is always fatal if not treated on time \[[@B7],[@B10]\]. Majority of the cases have been found as fulminant where the mortality rate reaches up to 85% \[[@B17]\]. Aetiology of the syndrome has been attributed to various agents and factors \[**7**\] which may include pathogenic viruses, autoimmune responses, liver transplantation procedure \[[@B18]\] bone marrow transplantation, radiation \[[@B19]\] and drugs administered to control the viral replication \[[@B14]\]. Aplastic anemia associated hepatitis viruses ============================================ Several hepatitis viruses such as Hepatitis A \[[@B20]\], B \[[@B21],[@B22]\], C \[[@B23]\], and E, G \[[@B24]\] have been anticipated to be associated with this set of symptoms \[[@B7]\]. No association has been found with blood transfusion, toxins and drugs \[[@B17]\]. In one study Safadi and co-workers (2001) found out that sera of eight of the patients had the existence of Hepatitis Bc IgG and/or anti-HBs antibodies which was suggested due to past exposure and immunizing effect and they were unable to establish any direct relation with acute hepatitis B \[[@B14]\]. As non-A, non-B hepatitis agents are usually responsible for the hepatitis associated aplastic anemia; the prevalence of anti-hepatitis C virus antibodies is similar in HAAA and aplasia of other origins \[[@B25]\]. HCV seropositivity has been observed in the patients developing cytopenia following non-A non-B hepatitis (NANBH). HCV viremia has been frequently observed without detecting anti-HCV antibodies in patients\' blood reflecting the transfusion associated HCV infection \[[@B25],[@B26]\]. However, it has also been reported that HCV is not generally implicated as a causative agent of hepatitis preceding aplastic anemia \[[@B27]\]. Hepatitis G virus (HGV) has been reported as a possible etiological agent of acute hepatitis, chronic liver dysfuntioning, and fulminant hepatitis and hepatitis associated aplastic anemia. A relation of Hepatitis G virus with hepatitis subsequently developing in the aplastic anemia has been seen in a 24 years old person by measuring the hematological, biochemical, serological and virological parameters and detecting HGV RNA in his serum by PCR and electro-immunoassay \[[@B24]\]. The development of aplastic anemia generally found to occur in hepatitis not caused by the hepatitis A and hepatitis B viruses commonly known as the non-A and non-B hepatitis associated aplastic anemia which were reported in above than 80% of the cases of hepatitis preceding severe cytopenia \[[@B28],[@B29]\]. Viruses other than hepatitis associated with aplastic anemia ============================================================ Viruses other than the hepatitis viruses have also been implicated as a causative agent of AA \[[@B1],[@B5]\] which include parvovirus B19 \[[@B19],[@B30],[@B31]\], Cytomegalovirus, Epstein bar virus \[[@B19],[@B31],[@B32]\], Echovirus 3 \[[@B33]\], GB virus-C \[[@B34]\], Transfusion Transmitted virus (TTV) \[[@B35]\], SEN virus and non-A-E hepatitis virus (unknown viruses) \[[@B7]\]. Parvovirus B19, an under recognized hepatotrophic virus, is documented as an offending agent of HAAA. Its infection cause hepatic manifestation ranging from abnormal liver functioning to Fulminant Hepatic failure and aplastic anemia \[[@B30]\]. The primary site of infection of this virus is erythroid progenitor cell in which it halts the erythropoises and leads to the anemia in immunocompromised hosts. The DNA of this virus has been detected in liver of fulminant hepatic failure manifested with bone marrow aplapsia and in the serum of fulminant hepatitis children of unknown origin \[[@B36],[@B37]\]. Association of Torque Teno virus, single stranded circular DNA has liver as a susceptible host as well as various other tissues including bone marrow. It has been firstly reported in 12 years old Japanese boy suffered from cytopenia following acute hepatitis by detecting Torque Teno virus DNA of genotype 1a and IgM antibodies against this virus in peripheral blood and bone marrow mononuclear cells which precludes that acute bone marrow failure majorly concerns with infection of TTV virus to haemopoietic progenitor cells. However, other studies have also been done on assessing the TTV as an etiological agent of HAAA \[[@B33],[@B38]\]. In a study a 6-year-old boy was experienced aplastic anemia two months after the onset of acute hepatitis associated with echovirus-3 \[[@B33]\]. As idiopathic aplastic anemia is associated with the increased level of secretion of INF-γ and TNF-α from T cells which inhibit the hematopoietic cell proliferation \[[@B39]\], similar increased level of serum INF-γ and TNF-α was found in the patient four weeks after the onset of aplastic anemia \[[@B33]\]. Similarly varying degrees of cytopenia has been related to the HIV infection and severe aplastic anemic conditions develop after subsequent attack of HSV-6 \[[@B17],[@B40]\]. Epstein Bar virus infection, involved in hepatitis, manifests the pathogenesis of marrow aplasia \[[@B40]\]. The pathogenic mechanism involve in the EBV infection is direct cytotoxity or mediates the immune response of host \[[@B7],[@B17],[@B14],[@B41]\]. Immunopathogenesis of HAAA ========================== Aplastic anemia can be acquired or congenital \[[@B1],[@B42]\]. As the aplastic anemia following the hepatitis has been elucidated as a severe bone marrow failure with an episode of acute hepatitis, following lymphocyte variations occur during the course of the syndrome: activation of circulating cytotoxic T cells increase, tend to accumulate in the liver, broad skewing patter of T cell reportrie in peripheral blood of the patient forms, a large number of T cell infiltration from liver parenchyma occurs \[[@B13],[@B26],[@B43],[@B44]\] defective monocyte to macrophage differentiation \[[@B45]\] and decreased circulating level of interleukin-1 occur \[[@B46]\]. Various Immunological abnormalities have been accountable for the development of aplastic anemia following hepatitis. The immunological abnormalities with HAAA show that CD8+ kupffer cells detecting by liver biopsies appear as a mediator of this syndrome. In a study it has been reported that patient showed a decreased ratio of CD4/CD8 cells and a high percentage of CD8 cells which can be cytotoxic and myleopoietic during the in vitro study of aplastic anemia \[[@B10],[@B20]\]. The residing of CD8 cells in bone marrow during HAAA produces a high level of interferon gamma (INF-γ) and cells derived from bone marrow locating in liver may activate these cytotoxic T cells causing their intrahepatic accumulation strongly affected by the Tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) causing the onlooker damage to liver cell of genetically modified mouse model. However, it has also been shown in several studies that increased level of soluble IL-2 receptor forms the major reason of non specific inflammation of HAAA \[[@B47],[@B48]\]. The pathogenesis of HAAA in children has been suggested to relate with the interruption in balance of lymphocyte sub-populations and T lymphocyte activation \[[@B49]\]. Genetic Vulnerability of HAAA ============================= Being an acquired disease, severe HAAA has also been presented as a Familial Bone Marrow Failure Syndrome (FBMFS) in a study while finding the family donor of HSCs transplant for treatment of idiopathic fulminant liver failure patient who has developed myelodysplastic syndrome after onset of severe aplastic anemia. The donor sibling also found to be developed the acute lymphoblastic leukemia after diagnosing the hypocelluarity of bone marrow. The event of finding these two familial cases shows the bone marrow failure syndrome to be inherited \[[@B50]\]. HAAA has not been clarified with any genetic tendency \[[@B18]\]. Mutation in genes of the telomere repair complex, *TERC*(the gene for the RNA component of telomerase) and *TERT*(the gene for the telomerase reverse transcriptase catalytic enzyme), reduce the marrow regenerative capacity, making genes mutation carriers susceptible to the development of aplastic anemia once it has been started \[[@B42]\]. Clinical features ================= Most of the clinical features relating to aplastic anemia following the hepatitis include: Pallor and multiple skin bleeding \[[@B11]\], lymphocytopenia, hypogammaglobulin \[[@B51]\] low number of CD8/T cell ratio \[[@B12]\] and increased number of cytotoxic cells \[[@B48]\] Neutropenia, fever \[[@B17]\]. Bacterial and fungal infection may emerge as secondary in presenting the disease \[[@B2]\]. Later complications may develop especially involving myelodysplasia \[[@B4]\]. The victims of severe aplastic anemia following the hepatitis experience a severe immune deficiency that might be either due to the hepatitis or aplastic anemia that is yet to be discovered \[[@B51]\]. Diagnosis of hepatitis associated aplastic anemia ================================================= On a course of HAAA, hepatitis can be detected on some of the following parameters: subsequent increase in serum Alanine Trasnaminase (ALT), Aspartate Transaminase (AST), by at least three times above the normal values which are 6 to 41U/l, 9-34U/l, 5-58U/L for ALT and AST respectively \[[@B12],[@B18],[@B30],[@B35],[@B36],[@B43],[@B52],[@B53]\], increase in serum Alkaline phosphatase (ALP), gamma glutaryl transferase (GGT) and billirubin (39-117U/l, 5-58 U/l, and 2-7 micromol/L, respectively). Peripheral blood count can be determined by Flow cytometry analysis with directly conjugated monoclonal antibodies for CD2, CD3, CD4, CD8, CD19 and HLA-DR, whereas haematopoietic failure with bone marrow hypocellularity can be elucidated in terms of absolute neutrophil count (less than 500 per mm^3^), Platelet count (less than 20,000 per mm3), Reticulocyte count (less than 60,000 per mm^3^) \[[@B53]\] and Protrombin Index (%): normal value 70-100% \[[@B24]\]. To establish the onset of pancytopenia following hepatitis, hypocelluarity of bone marrow below 50% might be obtained by bone marrow aspiration \[[@B14]\] and trephine biopsy \[[@B11]\]. Various virological and serological markers are available for the detection of hepatitis A, B, C, D, E, G, TTV and parvovirus. Among these tests, anti-HAV Ig total antibodies, HBsAg, HB core antigen, HBsIgG antibodies, various HCV recombinant antigens and hepatitis E virus IgM and IgG are being in use. However, to determine causative nature of all hepatitis viruses, RNA genome of RNA containing viruses such as HCV, HDV, HEV and HGV can be qualitatively detected by RT-PCR reaction and DNA of parvovirus B19 and TTV can be detected by Nested PCR \[[@B14],[@B53]\]. IgG antibody for Cytomegalovirus, EBV and parvovirus has been found a useful tool for the diagnostic purposes \[[@B18]\]. However, serological and virological parameters for hepatitis A, B, and C were found negative in majority of the HAAA cases reported in several studies \[[@B17],[@B23],[@B27]\]. Treatment ========= The standard therapy which is employed for the treatment of HAAA is allogenic bone marrow (BM) transplantation treatment from HLA matched siblings \[[@B13],[@B54]\]. HAAA is mostly occurring in children and it would be easier to find the HLA matched donor. As HAAA shows poor prognosis, most often it has been treated by hematopoietic stem cell transplantation \[[@B26],[@B55]\]. Immunosuppressive therapy has proved effective after BM transplantation. Various immunosuppressive drugs named Antithymocyte Globulin (ATG) and Cyclosporine have been administered without eliciting any acute side effects. Steroids such as Glucocorticoids have also been employed in combination with immunosuppressive medications for the treatment of the HAA patients \[[@B26]\]. A durable remission from HAA has been achieved by the administrating high dose of Cyclophosphamide (CY), a highly immunosuppressive, which elicits its effect by readily destroying the lymphocytes and committed myeloid cells. The haemopoietic stem cells are not susceptible to the toxic effects of the CY due to releasing the aldehyde dehydrogenase enzyme which inactivates the drug. However, restoration of haematopoesis process may achieved by high dose of CY which mediates autoimmune attack on haematopoiectic stem cells HSCs \[[@B13]\]. Patients irresponsive to the IST are prone to be cured by unrelated donor bone marrow transplantation \[[@B18]\]. Immunosuppressive therapy might have proved as a safe and alternative treatment for HAAA after of bone marrow or haemotopoietic stem cell transplantation \[[@B55]\]. Several studies showed that Parvovius induced aplastic anemia improves by the administration of retroviral therapy \[[@B21],[@B56]\]. Antiviral therapy for treating hepatitis B associated HAAA has been unknown yet; however it has been tested by administrating the nucleoside analogs, lamiviudine, against the aplastic anemic secondary to hepatitis B virus infection and remission occurs from the severe aplastic anemia accompanied with the hepatitis B viral infection. Interferon, an effective therapy for the hepatitis B and C viral infections, cannot be employed as a potential approach for the HAAA because of its mylosuppressive effects \[[@B21]\]. Acyclovir has been used for the treatment of aplastic anemia caused by the Epstein Bar virus \[[@B32]\]. The blood count comes to the normal range after five years of treatment \[[@B55]\], however, chances of recovery from hepatitis associated acquired aplastic anemia is rare \[[@B57]\]. Growth factors deficiencies have been found to be responsible for the majority of the aplastic anemic cases \[[@B1]\]. As these growth factors released by stromal cells are essential for the survival, proliferation and differentiation of hematopoietic stem cells \[[@B58],[@B59]\], a transient increase in granulocytes has been found effective in most aplastic anaemic trials by administrating the erythropoietin, growth factors, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, interleukin-3 \[[@B1]\] and androgens \[[@B5]\]. The limiting factors in success of immunosuppressive therapy are found to be the extent to which organ has been destructed, tissue regeneration capacity and most importantly pharmacology effect of drugs that is not sufficient for uncontrolled potent immune response \[[@B1]\]. The survival of the patients treated with hematopoietic cell transplantation and response rate to immunosuppressive therapy found to be 85% and 70% respectively \[[@B7]\]. Children response better than the adults to bone marrow transplantation and survival rate with Bone marrow transplantation from HLA matched donors is found to be similar as that for the non hepatitis associated aplastic anemia \[[@B14]\]. It has also been reported that parameters of liver dysfunctioning tend to improve when pancytopenia starts presenting itself \[[@B18],[@B28]\]. Although majority of the patients survives after aplastic anaemia tends to have complete recovery, the mortality rate is yet very high \[[@B52]\]. The mean survival rate after developing the severe bone marrow aplasia has been 2 months and fatality rate ranges from 78-88% \[[@B28],[@B60],[@B61]\]. Conclusion ========== HAAA is a well documented and diverse variant of clinical syndrome of aplastic anemia, in which an acute attack of hepatitis leads to the marrow failure and pancytopenia that may be acute or chronic. This disorder has been reported in 2-5% cases in West, 4-10% in Far East and high in area of low socioeconomic status. HAAA is not related to age, sex and severity of hepatitis, predominantly it has been found in children, adolesecent boys and in young aged men. A number of hepatitis viruses manifest the disease symptoms. Amongst the hepatitis viruses, HBV, HCV and HGV seropositivity has been mostly commonly observed in reported cases of HAAA. The causative agent of HAAA can be detected using hematological, biochemical, immunological and virological markers. The clinical features relating to HAAA are pallor and multiple skin bleeding, lymphocytopenia, hypogammaglobulin, low number of CD8/T cell ratio and increased number of cytotoxic cells, neutropenia and fever etc. For HAAA, immunosuppressive therapy is more effective after BM transplantation. Abbreviations ============= AA: Aplastic anemia; HAAA: hepatitis associated aplastic anemia; HCV: hepatitis C virus; NANBH: non-A non-B hepatitis; HGV: hepatitis G virus; HBV: hepatitis B virus; HAV: hepatitis A virus; HDV: hepatitis delta virus; HEV: hepatitis E virus; ELISA: enzyme linked immunosorbant assay; PCR: polymerase chain reaction; TTV: transfusion transmitted virus; INF-γ: interferon gamma; TNF-α: tumor necrosis factor alpha; Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= BR reviewed the literature, and wrote the manuscript. MI & SARS edited the manuscript. SB, AMB, AH, IR, MA, LA and SB helped BR in literature review. All the authors read and approved the final manuscript.

PubMed Central

2024-06-05T04:04:19.017300

2011-2-28

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052191/", "journal": "Virol J. 2011 Feb 28; 8:87", "authors": [ { "first": "Bisma", "last": "Rauff" }, { "first": "Muhammad", "last": "Idrees" }, { "first": "Shahida Amjad Riaz", "last": "Shah" }, { "first": "Sadia", "last": "Butt" }, { "first": "Azeem M", "last": "Butt" }, { "first": "Liaqat", "last": "Ali" }, { "first": "Abrar", "last": "Hussain" }, { "first": "Muhammad", "last": "Ali" } ] }

PMC3052192

Introduction ============ Retinitis pigmentosa (RP) is clinically characterized by loss of predominantly rod photoreceptor function as well as loss of peripheral vision. The classic clinical triad is considered to be the presence of bone spicule pigmentation in the peripheral retina, arteriolar attenuation, and waxy disc pallor. Cataracts, most commonly of the posterior subcapsular type, are often found in all forms of retinitis pigmentosa. Ectopia lentis and lens dislocation are known risk factors for those with RP, presumably secondary to zonular fiber weakness and vitreous degeneration \[[@B1],[@B2]\]. The post-operative complication of lens dislocation following cataract extraction in RP patients has also been documented \[[@B2]\]. In this report, we describe a spontaneous late posterior chamber intraocular lens subluxation secondary to severe capsular bag contraction in a patient with RP. Case presentation ================= A 58-year-old Hispanic woman presented to our clinic with blurred vision. She had been diagnosed with RP two years prior to presentation. Her best corrected visual acuity (BCVA) was 20/70 in the right eye and 20/25 in the left. Slit-lamp examination revealed anterior subcapsular as well as nuclear cataracts in both eyes, but worse in the right eye. No phacodonesis or iridodonesis was noted. Dilated fundus examination revealed bone spicule pigmentation in the retinal periphery, arteriolar attenuation, and optic disc pallor in both eyes, but which was more prominent in her right eye than in her the left. She had severe field loss of peripheral visual in the right eye (measured by Humphrey visual field. Humphrey Field Analyzer, Zeiss Ophthalmic, Dublin, CA, USA), leaving only the central 10°. Her left eye was found to have only mild loss of peripheral vision nasally. Electroretinography demonstrated an isoelectric potential in her right eye consistent with the diagnosis of RP. In her left eye, there was a generalized decrease in amplitude. She underwent an uncomplicated cataract extraction by phacoemulsification of the right eye. A continuous curvilinear capsulorrhexis was performed without any zonular stress observed. The capsulorrhexis was approximately 6 mm in diameter. A foldable acrylic intraocular lens (Tecnis Abbott Medical Optics Inc. Santa Ana, CA, USA) was inserted and observed to be well-centered at the end of the case. Post-operatively, her BCVA improved to 20/40 in the right eye. The intraocular lens was well-positioned within the capsular bag. However, three months after the surgery, she again presented to the clinic with blurry vision. She denied any history of trauma or fall. At this time her BCVA was 20/100 in the right eye and 20/25 in the left eye. On slit-lamp examination, the edge of the intraocular lens was displaced nasally and the capsular bag was displaced temporally (Figure [1](#F1){ref-type="fig"}). There were prominent capsular bag folds indicating severe bag contraction. Fundus examination again revealed changes from RP that were stable compared to previous examination. She was offered surgery, but declined it ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Capsular bag contraction and intraocular lens subluxation**. ::: ![](1752-1947-5-65-1) ::: Discussion ========== There is a strong association between RP and zonular fiber weakness, anterior capsule contraction, and extensive vitreous degeneration \[[@B2],[@B3]\]. In one case study of a Korean patient with RP, intraocular lens dislocation into the anterior chamber occurred six years after phacoemulsification of the left eye and eight years after extracapsular cataract extraction of the right eye \[[@B4]\]. Hayashi, in a 2007 study, documented the possible predisposing factors for late in-the-bag or out-of-the-bag intraocular lens dislocation after intraocular lens placement \[[@B3]\]. RP was found to be associated with an increased incidence of in-the-bag lens dislocation. One case study reported a posterior lens dislocation in an RP patient one year following posterior Nd-YAG laser capsulotomy \[[@B5]\]. Although there is the possibility of zonular disruption having been inflicted during surgery in our patient, the lens was well-positioned and stable for more than 10 weeks post-operatively. Nonetheless, it is likely that the turbulent forces of the phacoemulsification process further disrupted an already weak set of zonular fibers. Dehiscence of these fibers and the fibrotic changes found in the anterior capsule are likely to have contributed to the development of severe capsule contraction and intraocular lens subluxation in this patient. Again, it is possible that a tear in the posterior capsule was created during surgery or from asymmetrical placement of the intraocular lens. However, no tear was detected visually and there was no prolapse of vitreous into the posterior chamber. Additionally, the correct placement of the intraocular lens was confirmed intra-operatively as well as on multiple post-operative visits. Thus, severe capsular contraction combined with anterior vitreous degeneration and zonular fiber weakness provides the most plausible mechanism of lens subluxation. Conclusion ========== Although the occurrence of posterior lens subluxation following phacoemulsification and intraocular lens placement is not a common event \[[@B3]\], it is a complication that should be discussed with patients with RP undergoing cataract surgery given its ability to cause dramatic consequences. Furthermore, careful slit-lamp examination is essential preoperatively to detect any zonular weakness or loss. If this weakness is present, consideration should be given as to the method of cataract extraction that would best preserve zonule fiber integrity and limit the risk of posterior capsule tears. For example, a chopping technique may be preferred to reduce zonular stress. In addition, gentle hydrodissection can also be employed to decrease stress on the zonules during surgery. Consideration should be given to using a capsular tension ring prophylactically in the fellow eye in order to help prevent a similar event. Consent ======= Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= DN gathered the data, performed the literature review, and edited the manuscript. FT and AI were major contributors in writing the manuscript. All authors read and approved the final manuscript.

PubMed Central

2024-06-05T04:04:19.019273

2011-2-14

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052192/", "journal": "J Med Case Reports. 2011 Feb 14; 5:65", "authors": [ { "first": "Dany M", "last": "Najjar" }, { "first": "Ann O", "last": "Igbre" }, { "first": "Frank F", "last": "Tsai" } ] }

PMC3052193

Introduction ============ Extremity casts are frequently applied for routine immobilization for many acute fractures. The period of immobilization varies according to the patient and the fracture. For example, a non-operatively treated tibial fracture is rarely immobilized for longer than six months. Total contact casting has been used in the treatment of Charcot\'s neuropathy for periods of up to one year \[[@B1]\]. We report a case of a below knee cast removal after 28 months. Case presentation ================= When she was 40 years old, a Caucasian woman underwent bunion surgery for pain whilst ambulating. The wounds healed without complication but she went on to develop mechanical allodynia, intermittent swelling and a bluish discoloration of the foot, consistent with a diagnosis of type 1 complex regional pain syndrome. She received many different treatments for continued pain over the subsequent years. Drug therapies using pregabalin, strong opiates and epidural analgesia were not fully successful and she was offered a below knee cast as a temporizing measure. There was no pre-existing psychiatric diagnosis but the patient developed a psychological dependence upon this cast. She was reluctant to have it removed, believing that her pain remained inadequately treated. She failed to attend several appointments at the pain clinic. When she did return, the anesthetists asked for orthopaedic assistance to remove her cast. By this point she was 45 years old and had spent the previous 28 months in the same below knee cast. She was no longer taking regular analgesia but was unable to tolerate anyone touching her leg and therefore received a general anesthetic to facilitate the cast removal. The cast was found to be intact, despite having been worn for such a long period. This can be explained by the fact that she had been using crutches and the plaster was reinforced with a heel stirrup. The resin surface was filthy (Figure [1](#F1){ref-type="fig"}). The toes were swollen and erythematous with thick scales in the web spaces; the toenails showed evidence of onychocryptosis and onychogryphosis and had not been cut. The deep cotton bandages were intact but appeared soiled on removal of the cast. The exposed leg was covered in thick yellow skin scales (Figure [2](#F2){ref-type="fig"}) which were easily exfoliated by hand (Figure [3](#F3){ref-type="fig"}). There were no significant areas of skin loss with integument intact over bony protuberances. Dense heel callosities were removed with a sharp blade. Closer inspection of the skin surface revealed small pitted ulcers 1-2 mm in diameter replacing the normal skin pores. Healthy pink granulation tissue was seen at the base of these ulcers which appeared clean and were not infected (Figure [4](#F4){ref-type="fig"}). They did not bleed on palpation and required no dressing. Some superficial telangiectasia were also noted on the anterior aspect of the ankle joint which were not present elsewhere on her limbs. There was no change in skin pigmentation. The leg circumferences were reduced by 5.5 cm at the calf and 1.5 cm at the ankle when compared to the normal leg. Passive dorsiflexion was symmetrically zero degrees. Passive plantar flexion was 30° in the cast leg and 40° in the normal leg. Her passive knee movements were normal. Doppler ultrasound showed good flow at the dorsalis pedis and posterior tibial pulses. Swabs, skin and toenails sent at time of the removal of the cast showed no growth of any organisms or fungal species. ::: {#F1 .fig} Figure 1 ::: {.caption} ###### **Photograph of below knee cast prior to removal**. ::: ![](1752-1947-5-74-1) ::: ::: {#F2 .fig} Figure 2 ::: {.caption} ###### **Photograph demonstrating the appearance of leg after cast removal**. ::: ![](1752-1947-5-74-2) ::: ::: {#F3 .fig} Figure 3 ::: {.caption} ###### **Photograph showing yellow scales being exfoliated by hand**. ::: ![](1752-1947-5-74-3) ::: ::: {#F4 .fig} Figure 4 ::: {.caption} ###### **Photograph of showing small skin pits with pink granulation tissue following removal of scales**. ::: ![](1752-1947-5-74-4) ::: She was later reviewed in the pain clinic. Her skin was healthy but her allodynia remained symptomatic. At this stage she was reluctant to pursue any further treatment. Discussion ========== Cast immobilization is a routine orthopedic treatment which is administered for short periods of time in order to limit its complications. Total contact casts are used for longer time periods but are changed quite often in order to monitor for complications \[[@B1]\]. A patient found to have been wearing the same cast for 28 months is extremely rare and there have been no previous cases reported in the literature. Patients who are known to be wear casts occasionally fail to attend for cast removal. In this scenario an awareness of the extent of potential complications is useful for this less compliant patient group. Halanski and Noonan \[[@B2]\] reviewing plaster cast complications describe joint stiffness, muscle atrophy, cartilage degradation, ligament weakening and disuse osteoporosis. Joint stiffness was present in this case but was relatively insubstantial with only 10° of relative reduction in passive plantar flexion. This finding suggests that any stiffness observed after cast removal may be attributable to capsular stretch pain. Muscle atrophy as a consequence of cast immobilization has been described \[[@B3]\] and was observed in this case where the leg circumference was substantially reduced. Research has attributed this change to an increase in both the resting inorganic phosphate concentration in skeletal muscle \[[@B4]\] and a change in the neural command of muscle contraction \[[@B5]\] with immobilization. Skin complications have been described following plaster cast immobilization. Ulceration occurs where there is insufficient padding over bony protuberances and excoriation is known to occur particularly in casts worn by children which have become soiled \[[@B6]\]. One case describes skin atrophy and hyperpigmentation thought to be a variant of stasis dermatitis \[[@B7]\]. In this case the skin under the dense scales was relatively healthy. The small and regularly distributed pitted ulcers occurred where each individual skin pore had become blocked. The tissue at the base of these pits was healthy. Conclusion ========== Prolonged cast immobilization is extremely rare and occurs in non compliant patients. This case demonstrates muscle atrophy which was anticipated. The stiffness of the ankle joint was not marked. Skin changes were minor with no substantial areas of ulceration or stasis dermatitis. Where patients choose to remain in their cast for prolonged duration the complications may only be minor. Competing interests =================== The authors declare that they have no competing interests. Consent ======= Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Authors\' contributions ======================= CFY and DWE reviewed the patient and performed the operation. SE researched for previous case reports and evidence. HI documented and described the findings. HI, SE and DWE contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript.

PubMed Central

2024-06-05T04:04:19.020013

2011-2-22

{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052193/", "journal": "J Med Case Reports. 2011 Feb 22; 5:74", "authors": [ { "first": "Helen", "last": "Ingoe" }, { "first": "Sarah", "last": "Eastwood" }, { "first": "David W", "last": "Elson" }, { "first": "Claire F", "last": "Young" } ] }