HETEROCYCLES, pp.2023-2029, Vol.68 (2006)

SYNTHESIS AND PROPERTIES OF OLIGOCARBOXAMIDE
MOLECULAR STRANDS CONTAINING 1,8-NAPHTHYRIDINE AND
PYRIDINE GROUPS

Hisakazu Miyamoto,*,a Takahiro Ikeuchi,a Atsushi Fujioka,a Jean-Marie
Lehn,*,b Shigeru Ohba,*,c and Yohji Misakia
a Department of Applied Chemistry, Faculty of Engineering, Ehime

University, Matsuyama, Ehime 790-8577, Japan
E-mail: miyamoto@eng.ehime-u.ac.jp
b Laboratoire de Chimie Supramoleculaire, ISIS-ULP
8, allee Gaspard Monge, BP70028
F-670834 Strasbourg cedex,Francec Department of Chemistry, Keio University, Hiyoshi 4-1-1, Kohoku-ku,
Yokohama 223-8521, Japan

Abstract – Oligocarboxamide molecular strands based on carboxamide between
1,8-naphthyridine and pyridine, pyridine and pyridine, 1,8-naphthyridine andbenzene, and pyridine and benzene have been prepared. They have afforded
various inclusion complexes with organic solvents. Structural features of theinclusion complexes determined by X-Ray crystal structure analyses aredescribed.

Supramolecular chemistry has developed as the chemistry of the entities generated via intermolecularnoncovalent interactions.1 Supramolecules, well-defined oligomolecular species, result from the specificintermolecular association of a few components.2 In particular, helicity codons based on speciallydesigned sequences of heterocyclic units enforce the self-organization multiturn helical entities.3 A new
family of oligocarboxamide strand (1) (Scheme 1) derived from 2,6-diaminopyridine and2,6-pyridinedicarboxylic acid has recently been reported.4-7 This compound not only self-organizes intoa single helical monomer, but it reversibly assembles, giving rise to a double-helical dimer. A new typeof oligomeric strand (2) (Scheme 1) composed of alternating pyrimidine and 1,8-naphthyridine
heterocycles has also been reported.8 Compound (2) also self-organizes into a helical monomer.
Compound (1) can include H2O in the helical internal space. Compound (2) can include a cesium ion in
the helical internal space. Oligocarboxamide molecular strands containing 1,8-naphthyridine andpyridine groups are expected to include other molecules. We now report preparation of the strands
containing 1,8-naphthyridine-pyridine ring (3a, b), pyridine rings (3c-e, 4), 1,8-naphthyridine andbenzene ring (5a, b), and pyridine and benzene ring (5c-e) with carboxamide linkage (Scheme 2), as wellas the ability of these molecules to form inclusion complexes.

OC10H21
H
N

O

H
N

N

O

H
N

N
O

OC10H21

OC10H21
H
N

N

O

H
N

N

H
N

N

O

O

H
N

N
O

H
N

N

O

O
O

1Ar
N

N

N

N

N

N
N

N
N
N

N

Ar

N
N

N

Ar

2Scheme 1R1H
N

R2

X

H
N

O

H
N

NOX

H
N

O

a: R1=OC10H21, R2=t-BuO, X=1,8-naphthyridine groupb: R1=H, R2=t-BuO, X=1,8-naphthyridine groupc: R1=OC10H21, R2=t-BuO, X=pyridine groupd: R1=H, R2=t-BuO, X=pyridine groupe: R1=OC10H21, R2=C6H5CH2O, X=pyridine group

R2O

3HN
HNO

H
N

NO

N

H
N

NO

O

N

1,8-naphthyridine group:O

N

N
pyridine group:O
4HNO

H
N

H
N

O

XX
O

H
NO

OO

a: m-, X=1,8-naphthyridine groupb: p-, X=1,8-naphthyridine groupc: o-, X=pyridine groupd: m-, X=pyridine groupe: p-, X=pyridine group5

Scheme 2
Syntheses.
Syntheses of the new molecular strands (3~5) have been achieved according to Schemes 3-6.
2,7-Diamino-1,8-naphthyridine (6) 9-11 was monoprotected by treatment with di-tert-butyl dicarbonate(Boc2O) to give tert-butyl N-(7-aminonaphthyridin-2-yl)carbamate (7), which reacted withpyridine-2,6-bis(carbonyl chloride) derivatives (9a, b) prepared from the corresponding
pyridine-2,6-dicarboxylic acid derivatives (8a6, b) to give 3a, b in 58 and 37% yields, respectively. 12Boc2O
H2NN

N

O

NH2 THF

6H2N

N

N

N
H

7R1R1SOCl2HOOCO

7 / Et3N

N

COOH

8a: R1=OC10H21
b: R1=H

ClOC

N

3a, b

COCl

THF

9Scheme 39a, b / Et3N

O
H2N

Boc2O

N
10N
H

3c, dO
THF

11

THF
H2NN

NH2
C6H5CH2OCOCl / NEt3
H2N

THF

9a / Et3N

O
N

N
H3eO
THF

12

Scheme 42,6-Diaminopyridine (10) was monoprotected by treatment with di-tert-butyl dicarbonate (Boc2O) to givetert-butyl N-(6-aminopyridyl)carbamate (11) (Scheme 4).
The monoamine (11) reacted withpyridine-2,6-bis(carbonyl chloride) derivatives (9a, b) to give 3c, d in 66 and 54% yields, respectively.
2,6-Diaminopyridine (10) was also monoprotected by treatment with benzyloxycarbonyl chloride to give
benzyl N-(6-aminopyridyl)carbamate (12), which reacted with 4-decyloxypyridine-2,6-bis(carbonylchloride) (9a) to give 3e in 66% yield (Scheme 4).
The monoamine (11) reacted with pyridine-2,5-bis(carbonyl chloride) (13)13 to give 4 in 59% yield(Scheme 5).
COCl

11 / Et3N4ClOCN

THF

13

Scheme 5
The monoamine (7) reacted with 14b, c to give 5a, b in 57 and 40% yields, respectively (Scheme 6).
The monoamine (11) reacted with 14a, b, c to give 5c, d, e in 23, 55, and 77% yields, respectively(Scheme 6).
7, 11 / Et3N
COClClOC
14a: o-, b: m-, c: p-5a, b, 5c-e

THF

Scheme 6
Formation and characterization of inclusion complexes.
The ability of the molecular strands synthesized here to form inclusion complexes with various organic
solvent molecules was investigated. These complexes were obtained according to the following generalprocedure. Oligocarboxamide molecular strands were heated and solved with organic solvents.

Table 1 Host-guest Ratio of Inclusion Complex of 3-5
guest

3a3b3c3d3e

45a5b5c5d5e

acetonemethanoltoluenecyclopentanone

1:1

1:1

1:1

cyclohexanone

1:1

1:1

1:1

1:2

1:1

1:2

1:2 1:1 1:1

1:1

1:2

1:1

1:1 1:1 1:2

1:1 3:1

1:2

1:2

1:1

1:1 1:1 1:2

1:3

1:2

1:2

1:1

1:1 1:2

2:1
1:1 1:1 1:1
1:1

1:1

AcOEt
THF

1:1

dioxane

1:1

DMF

1:1

DMSO

1:1

1:1

1:2

1:1
1:1

CH2Cl2pyridine

1:1
1:2

1:1

The solution was kept at room temperature to allow the formation of inclusion complexes (Table 1).
Table 1 shows the host-guest ratio for the inclusion complexes formed by 3a-e, 4, 5a-e, with typicalorganic solvents. The host-guest ratio was determined by 1H NMR spectra or TG. It should be notedthat the p-substituted carboxamide hosts (4), (5b), and (5e) displayed significant ability to form suchinclusion complexes. This ability may be due to the host’s formation of a supramolecular zigzag chain
in the crystal lattice, as indicated by X-Ray study14 for complexes of 5e, with guest molecules being
accommodated between the chains.
X-Ray crystal structure analyses14 have been carried out for the inclusion complexes, 3c•pyridine•0.5H2O
and 5e•2DMF in order to reveal the site of the host molecule where the guest molecules are connected.
Crystals were grown from corresponding pyridine and DMF solutions by slow evaporation at room
temperature. In 3c•pyridine•0.5H2O, the host molecule (3c) can be described as having a lobster shape,
the head of which is the pyridine ring containing N12, with the two arms catching the guest molecule andthe tail being formed by the aliphatic chain (Figure 1).

Figure 1. (a) The molecular structure of 3c•py•0.5H2O,
and (b) The side view.

Figure 2. The crystal structure of 3c•py•0.5H2O
projected along the a axis.

The dihedral angles of the pyridine rings N10/C22-C26 and N14/C34-C38 in the arms of the host (3c)with respect to the head pyridine plane (N12/C28-C33) are 14.5(1)° and 8.3(1)°, respectively, and thedihedral angle between the arm pyridine rings is 22.0(1)°. The N11-H11 and N13-H13 moieties of theamide groups form intramolecular hydrogen bonds with the head N12 atom. The water O8 atom islocated between the two arms of the host (3c), and is connected to both N9 and N15 atoms via N-H•••Ohydrogen bonds. The guest pyridine molecule is connected to one of the arms of the host (3c) by anN15-H15•••N16 hydrogen bond, but the pyridine ring is nearly perpendicular to and shifted away fromthe plane of the arm. In the crystal, there are π-π stacking interactions between one of the arms of thehost, where the N12 and N14 pyridine rings and amide groups C27/N11/O3 and C33/N13/O5 areinvolved. These moieties are stacked along the a axis to form a column (Figure 2). However, theoverlap of the aromatic rings in the column is relatively poor.
In 5e•2DMF, the host (5e) shows an extended and slightly curved structure, having a local inversion
center (Figure 3). The dihedral angles between the amide moiety and the aromatic ring, to which theamide group is connected, are 12.0(4)-32.2(3)°, except for the 1.3(3)° angle between the amide
O3/C27/N11 and pyridine ring (N10/C22-C26). The dihedral angles between the central benzene(C28-C33) and the pyridine rings (N10/C22-C26 and N13/C35-C39) are 26.7(4)° and 16.3(4)°,respectively, and that between the two pyridine rings is 16.5(4)°. The guest DMF molecules areconnected to the host molecule (5e) by N11-H11•••O7 and N12-H12•••O8 hydrogen bonds. In thecrystal, the host molecules are connected by N9-H9•••N13i (symmetry code (i) 3/2-x, 1/2+y, 1/2+z) andN10•••H14i-N14i hydrogen bonds, forming a polymer chain (Figure 4). A side view of the chain can beseen in Figure 5, where the host molecules (5e) look like rods, with both ends being bound together via
hydrogen bonds, forming zigzag chains along the [011] direction. The guest DMF molecules areconnected to the host by hydrogen bond and are located in the cavity between the chains.

Figure 3. The molecular structure of 5e•2DMF. The broken lines show
N-H•••O hydrogen bonds between the host and guest molecules.

Figure 4. The molecular chain of the host 5e
Figure 5. The crystal structure of 5e•2DMF
connected via N-H•••N hydrogen bonds.
projected along the b axis.

Further studies of the relationship of the inclusion ability and the crystal structures for theoligocarboxamide molecular strands are now in progress.
ACKNOWLEDGEMENTS
This work was supported by the Yamada Science Foundation.
REFERENCES AND NOTES
1.
2.

J.-M. Lehn, Supramolecular Chemistry-Concepts and Perspectives. Weinheim: VCH, 1995.
J.-M. Lehn, Supramolecular Polymers; Chapter 14, A. Ciferri. Ed., Marcel Dekker, Inc., New-York,2000.
3. a) G. Hanan, J.-M. Lehn, N. Kyritsakas, and J. Fischer, J. Chem. Soc., Chem Commun., 1995, 765.
b) M. Ohkita, J.-M. Lehn, G. Baum, and D. Fenske, Chem. Eur. J., 1999, 5, 3481. c) L. A. Cuccia,J.-M. Lehn, J. C. Homo, and M. Schmutz, Angew. Chem. Int. Ed., 2000, 39, 233. d) K. M. Gardinier,R. G. Khoury, and J.-M. Lehn, Chem. Eur. J., 2000, 6, 4124.
4. V. Berl, I. Huc, R. G. Khoury, M. J. Krische, and J.-M. Lehn, Nature, 2000, 407, 720.
5. V. Berl, M. J. Krische, I. Huc, J.-M. Lehn, and M. Schmutz, Chem. Eur. J., 2000, 6, 1938.
6. V. Berl, I. Huc, R. G. Khoury, M. J. Krische, and J.-M. Lehn, Chem. Eur. J., 2001, 7, 2798.
7. V. Berl, I. Huc, R. G. Khoury, M. J. Krische, and J.-M. Lehn, Chem. Eur. J., 2001, 7, 2810.
8. A. Petitjean, L. A. Cuccia, J.-M. Lehn, H. Nierengarten, and M. Schmutz, Angew. Chem. Int. Ed.,
2002, 41, 1195.
9. G. R. Newkome, S. J. Garbis, V. K. Majestic, F. R. Fronczek, and G. Chiari, J. Org. Chem., 1981, 46,833.
10. A. E. M. Boelrijk, T. X. Neenan, and J. Reedijk, J. Chem. Soc., Dalton Trans., 1997, 4561.
11. J.-P. Collin and M.-T. Youinou, Inorg. Chimi. Acta, 1992, 201, 29.
12. Typical syntheses: tert-Butyl N-(7-aminonaphthyridin-2-yl)carbamate (7)Di-tert-butyl dicarbonate (2.72 g, 12.5 mmol) dissolved in THF (10 mL) was added dropwise to
2,7-diamino-1,8-nphthyridine (6) (2.0 g, 12.5 mmol) dissolved in THF (40 mL). The mixture washeated for 10 h at 60 °C. The mixture was evaporated, separated by column chromatography (silicagel, 9/1 EtOAc/methanol) to give 7 as a colorless powder (2.01 g, 62% yield). Compound (7): mp
198.7 °C (decomp); IR (KBr): νmax 3318, 3190, 1728, 1602 cm-1; 1H NMR (300 MHz, CDCl3):
δ 7.98 (d, J = 8.78 Hz, 1H), 7.91 (d, J = 8.78 Hz, 1H), 7.79 (d, J = 8.78 Hz, 1H), 7.41 (br s, 1H), 6.64
(d, J = 8.78 Hz, 1H), 4.97 (br s, 2H), 1.55 (s, 9H); FAB-MS: m/z (%): 261.1 (100) [MH+].
2,6-Bis[N-(7-tert-butoxycarbonylaminonaphthyridin-2-yl)carbamoyl]-4-decyloxypyridine (3a)4-Decyloxypyridine-2,6-dicarboxylic acid (8a) (0.5762 g, 1.78 mmol) and thionyl chloride (1.2 mL)
were refluxed for 1 h. After evaporation, the residue was used in the next step. tert-Butyl
N-(7-aminonapthyridin-2-yl)carbamate (7) (0.9275 g, 2.56 mmol) and triethylamine (0.3964 g, 0.547mL, 3.918 mmol) were dissolved in dry THF (7 mL), and previously prepared
4-decyloxypyridine-2,6-bis(carbonyl chloride) (9a) (0.6413 g, 1.78 mmol) in dry THF (0.75 mL)
was added dropwise at room temperature. The reaction was allowed to proceed for an additional 1
h at room temperature. The mixture was filtered and separated by column chromatography (silicagel, 1/1 EtOAc/hexane) to give 3a as a colorless powder (0.8311 g, 58% yield). Compound (3a):mp 273.0 °C (decomp); IR (KBr): νmax 3312, 1733, 1613 cm-1; 1H NMR (300 MHz, CDCl3): δ 10.55(s, 2H), 8.61 (d, J = 8.78 Hz, 2H), 8.12-8.28 (m, 6H), 8.01 (s, 2H), 7.54 (s, 2H), 4.22 (t, J = 6 Hz,2H), 1.88 (m, 2H), 1.55 (s, 18H), 1.20-1.54 (m, 14H), 0.88 (br s, 3H); FAB-MS: m/z (%): 808.6(100) [MH+].
13. M. Matsuzaki, H. Okabe, and S. Tanaka, Jpn. Kokai Tokkyo Koho, 1977, JP52033677.
14. X-Ray Analyses. Crystal structures of the two compounds were determined by the single-crystal
X-Ray diffraction method. The crystals of 3c•py•0.5H2O and 5e•2DMF were sealed in capillaries

to avoid efflorescence. X-Ray intensity data were measured on a Rigaku-AFC7R four-circle
diffractometer with Mo Kα radiation. Intensity decays of the standard reflections were 6% and11%, respectively. Structure analyses were carried out with the programs SIR92, SHELXL97, andTEXSAN. For 3c•py•0.5H2O: the occupation factor of the guest water molecule was assumed to50% based on the displacement parameter of the O atom. The H atoms were positioned
geometrically except for the water molecule. Crystallographic data have been deposited at theCCDC, 12 Union Road, Cambridge CB2 1EZ, UK and copies can be obtained on request, free ofcharge, by quoting the publication citation and the deposition numbers CCDC 247689-247690.
3c•py•0.5H2O: Chemical formula C42H57N8O7.5, Formula weight 793.96, Crystal systemTriclinic,
Space group P -1, a/Å 9.915(4), b/Å 10.365(4), c/Å 22.163(4), α/°94.23(2), β/°91.30(2),γ/°94.73(3), V/Å3 2263(1), Z 2, Dcalcd/g cm-3 1.165, μ/mm-1 0.081, Crystal size/mm 0.5×0.5×0.4, Temperature/K 299, Reflections measured 8943, Reflections independent 7984,
Reflections with I>2σ(I) 3751, Reflections used 7984, R(F)/Rw(F2) 0.058/0.202.
5e•2DMF: Chemical formula C34H46N8O8, Formula weight 694.79, Crystal system
Orthorhombic, Space group Pna21, a/ Å 17.304(7), b/ Å 10.002(6), c/ Å 21.924(8), V/ Å 33795(3), Z 4, Dcalcd/g cm-3 1.216, μ /mm-1 0.088, Crystal size/mm 0.55 × 0.3 × 0.2,
Temperature/K 293, Reflections measured 5074, Reflections independent 3434, Reflections
with I>2σ(I) 1122, Reflections used 3434, R(F)/Rw(F2) 0.060/0.191.