bluuebunny/crossref_metadata_2025 huggingface dataset:
Iodine‐doped “crowned” phthalocyanines
Authors: Sielcken O. E. , Nolte R. J. M. , Schoonman J.
Published: September 2010

In this paper, we describe the effect of iodine doping on the structure and electrical properties of crown‐ether‐substituted phthalocyanines. For the doped phthalocyanines, a layered two‐dimensional structure was found. A.c. impedance spectroscopy revealed that doping strongly increases the bulk electronic conductivity of the “crowned” phthalocyanines and their alkali‐metal picrate complexes. The intermolecular barriers for conductivity were not affected by the iodine dopant.
Orbital control in the reductive cleavage of tris(methoxyphenyl)phosphines
Authors: Budzelaar Peter H. M. , van Doom Johannes A. , Meijboom Nico
Published: September 2010

The character of the LUMO of (methoxyphenyl)phosphines determines the reductive cleavage of the C‐P bond; a high LUMO energy prevents reduction whereas a small coefficient at the C‐P carbon atom leads to a poor cleavage.
The lithiation of N,N,N′,N″,N″‐Pentamethyldlethylenetriamine (PMDTA)
Authors: Schakel M. , Aarnts M. P. , Klumpp G. W.
Published: September 2010

The title compound is easily lithiated at its NMe groups by alkyllithiums dissolved in alkanes.
Rigid etheno‐bridged metopon analogues from Diels‐Alder reaction of 5‐methylthebaine. (Chemistry of opium alkaloids, Part XXXII)
Authors: Woudenberg R. H. , Lie T. S. , Maat L.
Published: September 2010

Diels‐Alder reaction of 5‐methylthebaine (2) with ethyl acrylate, methyl vinyl ketone or p‐benzoquinone yielded ethyl 4,5α‐epoxy‐3,6‐dimethoxy‐5,N‐dimethyl‐6α,14α‐ethenoisomorphinan‐7α‐carboxylate (3), 7α‐acetyl‐4,5α‐epoxy‐3,6‐dimethoxy‐5,N‐dimethyl‐6α,14α‐ethenoisornorphinan (4), and 4,5α‐epoxy‐3,6‐dimethoxy‐5,N‐dimethyl‐6α,14α‐ethenobenzo[7,8]isomorphinan‐3′,6′‐diol (5b), respectively.

Both ester 3 and ketone 4 were converted into 4,5α‐epoxy‐3,6‐dimethoxy‐α,α,5,N‐tetramethyl‐6α,14α‐ethenoisomorphinan‐7α‐methanol (7) with methylmagnesium iodide. The 3‐methoxy group was hydrolysed to give 4,5α‐epoxy‐3‐hydroxy‐6‐methoxy‐α,α,5,N‐tetramethyl‐6α,14α‐etheno‐isomorphinan‐7α‐methanol (8). Demethylation of 3 with boron tribromide afforded ethyl 4,5α‐epoxy‐3,6‐dihydroxy‐5,N‐dimethyl‐6α,14α‐ethenoisomorphinan‐7α‐carboxylate (6). Structure elucidation was mainly based on1H and13CNMR spectroscopy. It is remarkable that, in all cases, β‐face approach of the diene system of 2 has taken place. The new rigid metopon analogues 6, 7, and 8, will be tested for biological activity**.

magnified image
An overlooked short entry to 2‐ alkyliden‐1,3‐dioxolanes. Highly reactive ketene acetals
Authors: Aben R. W. M. , Scheeren J. W.
Published: September 2010

2‐Alkyliden‐1,3‐dioxolanes can be prepared surprisingly easily from the corresponding 2‐bromoacetals by dehydrobromination with potassium tert. butoxide. The method has a wide scope and gives access to ketene acetals which cannot be prepared by other methods. The application of mono substituted cyclic ketone acetals in the lewis acid catalyzed stereoselective formation of cis oxetanes from aldehydes is illustrated.
Sulfonation of norbornene with sulfur trioxide
Authors: Bakker B. H. , Schonk R. M. , Cerfontain H.
Published: September 2010

Sulfonation of norbornene 1 with the SO3‐dioxane complex affords the β‐sultone 2, which rearranges at room temperature to the γ‐sultone 3. Reaction of 1 with 2 equiv of SO3‐nitromethane yields the carbyl sulfate 4. Carbocations are not involved in the formation of either the β‐sultone or the carbyl sulfate.
The oxygenation of cyclopalladated N,N‐dimethylbenzylamine derivatives with tert‐butyl hydroperoxide
Authors: Alsters Paul L. , Teunissen Herman T. , Boersma Jaap , van Koten Gerard
Published: September 2010

Cyclopalladated N,N‐dimethylbenzylamine complexes can be oxygenated with tert‐butyl hydroperoxide to the corresponding phenolates in good yield (> 80%); the rate of oxygenation is highly enhanced by increasing the nucleophilicity of the metal center or by addition of a vanadium catalyst.
The effect of pH and temperature on the periodate oxidation of sucrose
Authors: de Wit D. , van Rantwijk F. , Maat L. , Kieboom A. P. G.
Published: September 2010

The oxidation of sucrose with periodate was studied at different pH and temperature. Open‐chain di‐ and tetraaldehydes thus obtained were analyzed using HPLC. The ratio of singly oxidized glucose rings to doubly oxidized glucose rings proved to be dependent on the pH. This behaviour of the glucose ring in sucrose was compared with that of methyl α‐D‐glucopyranoside. At higher temperatures, the direction of the oxidation shifted to the glucose part of sucrose. At 95°C and pH 7, sucrose appeared to be oxidized selectively to the dialdehyde GOO‐F.
Towards a rational design of resolving agents. Part II: Correlation between resolution results and physical properties of diastereomeric salts
Authors: van der Haest A. D. , Wynberg H. , Leusen F. J. J. , Bruggink A.
Published: September 2010

Six closely related cyclic phosphoric acids (1a‐f) were compared with respect to their resolving ability towards ephedrine. Variation of the aromatic substituent in the phosphoric acids significantly influences this ability. Studying the results of the resolution experiments as a function of some physico‐chemical properties of the diastereomeric salts reveals a relationship between the resolving ability of a particular phosphoric acid and the difference in heat of fusion of its diastereomeric salts.
Reactions of cyclopalladated compounds and alkynes: New pathways for organic synthesis?
Authors: Pfeffer Michel
Published: September 2010

Cyclometallated compounds, obtained by direct intramolecular C–H activation of a ligand by transition metals, are fairly reactive [especially those derived from palladium(II)] towards insertion of internal alkynes into their metal‐carbon bond. This reaction leads to either new organometallic compounds by inclusion of one to three alkynes into the M‐C bond, or organic compounds which are either carbocyclic or heterocyclic, their nature depending upon the alkyne substituents as well as upon the cyclometallated ligand.
Analogues of uridine 5′‐diphosphate glucose and guanosine 5′‐diphosphate mannose
Authors: Broxterman H. J. G. , Kooreman P. A. , van den Elst H. , Roelen H. C. P. F. , van der Marel G. A. , van Boom J. H.
Published: September 2010

One‐pot coupling of 2′,3′‐di‐O‐benzoyl‐uridine and 4,5,6,8‐tetra‐O‐acetyl‐3,7‐anhydro‐2‐deoxy‐D‐glycero‐D‐ido‐octitol with appropriate bifunctional phosphoro‐, phosphono‐ and thiophosphonylation reagents gave, after removal of the base‐labile protecting groups, analogues of UDP‐Glc containing charged phosphate, neutral alkyl‐ and arylphosphonate and phosphonothioate linkages. In an analogous manner, GDP‐Man analogues, in which guanosine and octitol units are similarly linked via phosphate, alkyl phosphate or phosphotriester bonds, were prepared.
Stereospecific synthesis of partially protected 2‐azido‐2‐deoxy‐D‐glucosyl D‐myo‐inositol: Precursor of a potential insulin mimetic and membrane protein anchoring site
Authors: Verduyn R. , Elie C. J. J. , Dreef C. E. , van der Marel G. A. , van Boom J. H.
Published: September 2010

Racemic and partially protected myo‐inositol derivative 5 was coupled stereospecifically with the 2‐azido‐2‐deoxy‐glucosyl trichloroacetimidate donor 8. Optical resolution of the thus obtained diastereoisomeric mixture of dimers by silica gel column chromatography, and further protective group manipulations, afforded the suitably protected title compound 14.
Conditions for modified fischer glycosidations with n‐pentenol and other alcohols
Authors: Konradsson Peter , Roberts Carmichael , Fraser‐Reid Bert
Published: September 2010

Various O‐glycosides were prepared directly from the corresponding aldoses by use of 3 molar equivalents of an alcohol with catalytic amounts of trifluoromethanesulfonic acid (triflic acid) in dimethyl sulfoxide.
Synthesis and properties of two pyrromethenium salts; one with a rigid Z‐syn structure and another with a rigid E‐anti structure
Authors: Koek J. H. , van der Hoef K. , Roodenburg L. , Lugtenburg J. , Fokkens R.
Published: September 2010

1,3,7,9‐Tetramethyldipyrrolo[1,2‐c:2′,1′‐f]pyrimidinium methanesulphonate (1) and 2,3,5,6,8,8‐hexamethyl‐8H‐benzo[1,2‐b:4,5‐b']dipyrrolium methanesulphonate (2) have been prepared via simple reaction schemes. The first has a rigid Z‐syn pyrromethenium structure, the second a rigid E‐anti structure. The E‐anti compound has a larger λmax value, higher extinction, higher fluorescence intensity and larger Stokes shift than the corresponding Z‐syn compound. Mobile pyrromethenium salts do not show appreciable fluorescence. Both systems react rapidly with nucleophiles at the central carbon of the conjugated system to form colourless non‐fluorescent tricyclic pyrromethane systems. Upon intravenous injection into rats, the title compounds lead to rapid death, in contrast to a related purromethene‐BF2 complex, which is completely harmless upon intravenous injection.
Synthesis of serine analogues to be used as modified phospho acceptor sites in substrates of protein kinase C
Authors: Broxterman H. J. G. , Liskamp R. M. J.
Published: September 2010

Serine and threonine analogues (compounds 2‐6) are readily accessible by reaction of the anion of N,N‐dibenzylglycine ethyl ester (1) with an appropriate carbonyl compound. These analogues will be incorporated into Protein Kinase C (PKC) substrates. The serine aldehyde derivative 7 was used for the preparation of the corresponding diethyl acetal 9. This compound was the starting material in the synthesis of the suicide precursor 8, featuring a reductive amination leading to 12 and a Lewis‐acid‐catalysed cyclization giving 8.
Shape effects in the conversion of ethanol to hydrocarbons over alkaline‐free synthesised ZSM‐5 and alumina ted silicalite‐1 crystals
Authors: Voogd P. , Sollie J. C. , Doelwijt A. , van Bekkum H.
Published: September 2010

Diffusion effects on conversion rates and product distributions in the ethanol to gasoline reaction on zeolite H‐ZSM‐5 were investigated. A sample of large ZSM‐5 crystals (Si/Al47) having a narrow particle‐size distribution was hydrothermally synthesised in an alkaline‐free medium, applying ammonium cations. X‐ray data indicate considerably heterogeneous aluminium distribution throughout the large ZSM‐5 crystals.

In the ethanol conversion, comparison with conventional small H‐ZSM‐5 crystallites revealed that compounds having small critical diameters predominated in the product mixture when using large crystals. This is caused by their high relative mobility in the ZSM‐5 channels. As to xylene and ethyltoluene formation, high para selectivities were found, especially at low contact times. Large ZSM‐5 crystals deactivate rather quickly, mostly within 24 hours, because of coke deposition on the outer crystal surface.

Large silicalite‐1 crystals, subjected to a post‐synthesis treatment with AlCl3 at high temperatures, showed comparable shape effects in the ethanol conversion. Unexpectedly, deactivation rates are not dissimilar from those of directly synthesised H‐ZSM‐5.
Oxidative debromination in a binuclear copper (I) complex
Authors: Gelling O. J. , Feringa Ben L.
Published: September 2010

The binuclear copper (I) complex Cu2 (2,6‐BPB‐1‐Br)(BF4)21.8CH3CN (8) undergoes at 20°C with O2 a rapid oxidative arene debromination.
Synthesis of vitamin‐K derivatives with different lengths of the alkyl side chain
Authors: Liu Benli , Gu Lianquan , Zhang Jingling
Published: September 2010

The radical alkylation of 1,4‐naphthoquinone with various lengths of fatty acids [H(CH2)nCO2H] in the presence of (NH4)2S2O8 and AgNO3 was studied. A simple and effective method was found for the synthesis of vitamin‐K derivatives with different lengths of alkyl side chain. Two types of vitamin‐K derivatives were synthesized. The first type, 2‐alkyl‐1,4‐naphthoquinones, was synthesized by a single step of radical alkylation of 1,4‐naphthoquinone with different lengths of fatty acids. The second type, 2‐alkyl‐3‐methyl‐1,4‐naphthoquinones, was synthesized by radical alkylation of 2‐methyl‐ 1,4‐naphthoquinone using the same reaction as for the first type, or by radical methylation of the first type. Our results show that the former method is suitable for the synthesis of long‐side‐chain (n > 11; n, number of carbon atoms in chain of the fatty acid) vitamin‐K derivatives, whereas the latter method is better for the synthesis of short‐side‐chain (n < 11) vitamin‐K derivatives. The structures of these newly synthesized vitamin‐K derivatives were identified by UV, IR, 1H NMR and MS spectra.
Stereospecific conversion of a racemic pantoyl lactone to D‐(‐)‐pantoyl lactone through microbial oxidation and reduction reactions
Authors: Kataoka Michihiko , Shimizu Sakayu , Yamada Hideaki
Published: September 2010

A novel enzymatic process for the synthesis of D‐(‐)‐pantoyl lactone from a racemic mixture of pantoyl lactone is described. The process involves two stereospecific enzymatic reactions, i.e., stereospecific oxidation of L‐(+)‐pantoyl lactone to ketopantoyl lactone by Nocardia asteroides and asymmetric reduction of ketopantoic acid, which is formed through the spontaneous hydrolysis of ketopantoyl lactone, to D‐(‐)‐pantoic acid by Agrobacterium radiobacter without any modification of the remaining D‐(‐)‐pantoyl lactone. With 80 mg/ml of racemic pantoyl lactone as the substrate, the amount of D‐(‐)‐pantoyl lactone synthesized reached 71.3 mg/ml (82.8% ee; molar conversion yield, 89.1%).
Asymmetric epoxidation of allyl alcohol derivatives by ω‐hydroxylase from Pseudomonas oleovorans
Authors: Fu Hong , Shen Gwo‐Jenn , Wong Chi‐Huey
Published: September 2010

This paper described the application of non‐heme monooxygenase system from Pseudomonas oleovorans to the syntheses of chiral 3‐(benzyloxy)‐, 3‐(allyloxy)‐, 3‐(butyloxy)‐ and 3‐(aryloxy)‐1,2‐epoxypropanes (6) from their corresponding allyl alcohol derivatives. The epoxides were determined to be R forms with good enantiomeric excess. The specificities of the enzymatic epoxidation of olefines and hydroxylation of the radical probe trans‐2‐phenyl‐1‐methylcyclopropane were discussed with regard to the reaction mechanism.
Lipophilic diaza crown ethers in supported liquid membranes; influence of pH on transport rates and membrane stability
Authors: Nijenhuis Wilma F. , Walhof Judith J. B. , Sudhölter Ernst J. R. , Reinhoudt David N.
Published: September 2010

Lipophilic diaza‐18‐crown‐6 derivatives are used to transport potassium cations through supported liquid membranes. The influence of the pH of the aqueous phases on the rate of transport and membrane stability has been studied. At pH values lower than 10, the flux is reduced significantly because the ionophores are protonated and leach out of the membrane phase. With these carriers, proton‐driven transport is possible. The length of the alkyl chain attached to the carrier has a pronounced effect on membrane stability. Carriers having two n‐pentyl chains leach out to the aqueous phases at pH 10, whereas carriers with two n‐decyl or n‐tetradecyl chains result in a stable membrane system. Model calculations show that di‐n‐decyldiaza‐18‐crown‐6 forms a 1:1 complex with potassium cations (K 3.1 · 106 l ṁ mol−1) in 2‐nitrophenyl n‐octyl ether (NPOE). The calculated diffusion coefficient of the complex in NPOE is the same as the diffusion coefficient of the dibenzo‐18‐crown‐6 potassium cation complex in NPOE (1.1 · 10−3 cm2·h−1). This means that the higher potassium fluxes for diaza crown ethers compared to dibenzo crown ethers are due to stronger complexation in the membrane phase with potassium cations. Very high carrier concentrations (and, therefore, very high fluxes) can be obtained using these lipophilic diaza crown ethers.
Synthesis and spectroscopic properties of 14‐, 15‐, 15′ ‐ and 14′ ‐monodeutero‐ and 15,15′ ‐dideuterospheroidenes
Authors: Gebhard R. , van Dijk J. T. M. , Boza M. V. T. J. , van der Hoef K. , Lugtenburg J.
Published: September 2010

The high‐yield synthesis of four mono‐ and one dideutero‐labelled spheroidene, the carotenoid bound in the reaction centre ofRhodobacter sphaeroides 2.4.1, is described. The all‐Eisomers (14′‐2H)‐, (15′‐2H)‐, (15‐2H), (14‐2H)‐ and (15,15′‐2H2)spheroidenes have been prepared in high purity with more than 95%2H incorporation from C2H3CN and/or Dibal‐2H. The spectroscopic properties of the labelled compounds are discussed; the mass spectra reveal that toluene elimination from spheroidene is restricted to a single location in the molecule.
Synthesis and Structure of [Me4N][Ni(dmise)2]2, the first Conductor based on the Ni(C3S4Se)2 system
Authors: Cornelissen Joost P. , Reefman Derk , Haasnoot Jaap G. , Spek Anthony L. , Reedijk Jan
Published: September 2010

Electrochemical oxidation of [Bu4N][Ni(dmise)2] in the presence of Me4NPF6 yields [Me4N][Ni(dmise)2]2, the selenone derivative of the superconducting [Me4N][Ni(dmit)2]2. The X‐ray structure of [Me4N][Ni(dmise)2]2 reveals a non‐stacking arrangement of paired anions. The [Ni(dmise)2]2 diads are connected along the c‐axis via a short intermolecular Se…Se contact of 3.277(3) Å. Preliminary conductivity measurements show a room temperature conductivity of 20 S cm−1 with a metallic behavior down to 140 K, at which point a metalinsulator transition occurs.
An improved method for the N‐alkylation of benzotriazole and 1,2,4‐triazole
Authors: Katritzky Alan R. , Kuzmierkiewicz Wojciech , Greenhill John V.
Published: September 2010

The N‐alkylation of benzotriazole and 1,2,4‐triazole with alkyl halides proceeds efficiently in the presence of sodium hydroxide in N,N‐dimethylformamide (DMF).
A convenient synthesis of DNA fragments nitrogen‐15 labeled at the exocyclic cytosine amino group
Authors: Kellenbach E. R. , van den Elst H. , Boelens R. , van der Marel G. A. , van Boom J. H. , Kaptein R.
Published: September 2010

A convenient method is described for the synthesis of oligodeoxynucleotides 15N labeled at the exocyclic amino group of cytosine. The 4‐triazolide derivative of deoxyuridine is used as a building block in the solid phase synthesis of the oligodeoxynucleotide. Deprotection and cleavage from the solid support is achieved by treatment with 15N labeled NH4OH. This treatment also substitutes the 4‐triazolide group of the deoxyuridine by an 15N labeled amino group to yield 4‐15N cytosine. The method was applied to a DNA fragment corresponding to a glucocorticoid response element. The oligomer was characterised by 1H‐15N coherence spectroscopy.
Synthesis of 5β‐methyl‐6‐demethoxythebaine and its Diels‐Alder reaction to 6α,14α‐ethenoisomorphinans and 6β,14β‐ethenomorphinans (Chemistry of Opium Alkaloids, Part XXXV
Authors: Woudenberg R. H. , Piet D. P. , Sinnema A. , Lie T. S. , Maat L.
Published: September 2010

Deprotonation of 6‐demethoxythebaine (1) with butyllithium, followed by reaction of the anion with dimethyl sulfate, gave the non‐conjugated diene 4 as the major product and title compound 5β‐methyl‐6‐demethoxythebaine (5) only in low yield. Therefore, 5 was prepared from 5β‐methylthebaine (6), which was converted into 5β‐methylcodeinone (7) and then reduced to 5β‐methylcodeine (8). Mesylation of 8 yielded 6‐O‐mesyl‐5β‐methylcodeine (9). Reaction of 9 with lithium bromide gave 5β‐methyl‐bromocodide (10) as the major product, together with 5. When 10 was treated with potassium tert‐butoxide, the desired 5 was obtained in good yield. Short treatment of 10 gave the intermediate 8‐bromo‐5‐methyl‐desoxycodeine‐A (11), which reacted further to 5 after prolonged treatment.

Diels‐Alder reaction of 5 with ethyl acrylate yielded two products, ethyl 6α,14α‐ethenoisomorphinan‐7α‐carboxylate 13 and ethyl 6β,14β‐ethenomorphinan‐8β‐carboxylate 14, due to β‐face and α‐face approach, respectively. Similarly, with 3‐buten‐2‐one as the dienophile, a mixture of 7α‐acetyl‐6α,l4α‐ethenoisomorphinan 15 and 8β‐acetyl‐6β,14β‐ethenomorphinan 16 was obtained. Diels‐Alder reaction of 5 with maleic anhydride, followed by esterification of the adducts, yielded dimethyl 6α,l4α‐ethenoisomorphinan‐7β,8β‐dicarboxylate 19 and dimethyl 60,140‐ethenomorphinan‐7β,8β‐dicarboxylate 20 in a 7 : 3 ratio. The results of the Diels‐Alder reaction are discussed in connection with the substituents in the 5β‐ and 6‐position.
Reductive cleavage of the carbon‐phosphorus bond with alkali metals. I. Cleavage of functionalised triphenylphosphines; formation of secondary and primary phosphines
Authors: Budzelaar Peter H. M. , van Doorn Johannes A. , Meijboom Nico
Published: September 2010

The reductive cleavage reaction of functionalised triphenylphosphines 1–34 with Na/NH3 and Li/THF depends strongly on the nature of the functionality and on the reducing agent. No reduction occurs with 11, 24, 30, 31 and 32 in Na/NH3. Compounds 3, 4, 5, 10, 12, 13, 15, 19, 23, 25, 26 and 27 cleave to give the secondary phosphide in high yield with Na/NH3, whereas 2, 7 and 9 give a high yield with Li/THF. Reduction occurs but cleavage is poor with 6, 7, 14, 29 and 34 and Na/NH3, or with 11 and Li/THF. Primary ortho‐functionalised phenyl phosphines are obtained by a double cleavage reduction from 2, 5, 12, 25, 26 and 27 with Na/NH3. This unprecedented reaction proceeds via the secondary phosphine, which is formed by protonation of the corresponding phosphide with NH3. It occurs when the aryl group contains a strongly electron‐donating substituent. Multiple cleavage of aryl groups with extended π systems occurs with 7 and 34 when they are made to react with Li/THF. Halogens are cleaved from the phenyl group (16, 17, 18, 28 and 33, with Na/NH,), whereas SCH, groups are converted to the corresponding mercapto group (20, 21 and 22). Birch reduction (2 and 10) can take place in NH, but not in the aprotic solvent THF; it occurs only when other reactions are slow. Sodium amide is obtained via reaction of 8 in Na/NH,. Restricted Hartree‐Fock calculations were carried out for a number of substituted phenylphosphines. From the correlation between the energies and coefficients of the LUMO (always an aryl π* orbital) and the experimental cleavage data, it was concluded that there are three requirements for successful cleavage. The LUMO energy should be neither too high (no reduction) nor too low (radical anion too stable) and, further, the coefficient of the LUMO on the carbon attached to phosphorus must be large.
Non‐linear optical and electro‐optical polymers
Authors: Staring Emiel G. J.
Published: September 2010

In this review, we present a general overview of organic molecules and materials for non‐linear optics, with emphasis on materials for frequency doubling and for the Pockels or electro‐optic effect. After a short introduction on the molecular basis of second‐order non‐linearity, we shall discuss the relevant materials aspects of three important classes of organic non‐linear optical materials: organic crystals, Langmuir‐Blodgett films and poled polymers. The latter class of materials is, in our opinion, the most versatile of these three. We shall present some representative and recent examples of various types of poled polymer materials, their synthesis and their non‐linear optical properties.
Substituent effects. 14. Anomalous dissociation constants in water‐organic solvent mixtures: Benzylammonium ions and related systems
Authors: Hoefnagel A. J. , de Vos R. H. , Wepster B. M.
Published: September 2010

Thermodynamic dissociation constants in various water‐organic solvent mixtures are given for benzylammonium, benzyldialkylammonium, and (2‐phenylethyl)ammonium ions. Deviations from the Hammett equation (Eqn. 1) are similar to those observed for carboxylic acids, but of opposite sign. The extended Hammett equation (Eqn. 3), containing the hydrophobic constant, π, yields good correlations. Derived secondary normal sigma values are exemplified.
Photochemistry of α‐bis(methoxyimino)alkanes
Authors: Stunnenberg Frank , Cerfontain Hans
Published: September 2010

The photochemistry of the α‐bis(methoxyimino)alkanes 1–5 and the, structurally related, conjugated dihydro(methoxyimino)isoxazoles 6 and 7 was studied. Triplet‐photosensitized irradiation of 1–7 leads only to stepwise E‐Z isomerization. Photostationary‐state (pss) ratios for 1,6 and 7 are reported for the various applied triplet sensitizers. Direct irradiation with 254 nm leads to both E‐Z isomerization (which is the dominant reaction) and formation of products resulting from initial N‐O homolysis of the excited singlet ππ* state. Mechanisms for the formation of the various products are proposed and the relative importance of the various steps is indicated and discussed. For the α‐bis(methoxyimino)alkanes 1 and 3, only the (E,Z)‐isomer undergoes N‐O homolysis. With the (methoxyimino)isoxazolines 6 and 7, only the exocyclic NO bond exhibits homolysis and not the strained endocyclic bond.
Carbodiimides as important intermediates in the reaction of isocyanates with carboxylic acids
Authors: Schotman A. H. M. , Mijs W. J.
Published: September 2010

The reaction between isocyanates and carboxylic acids is known to lead to amides. We have studied the mechanism of catalysis of this reaction by phospholene oxides.

The reaction between phenyl isocyanates and benzoic acid was monitored under various conditions using High‐Pressure Liquid Chromatography. It was found that the catalyst reacts with the iso‐cyanate under formation of a carbodiimide. The carbodiimide reacts with the carboxylic acid to form amide and isocyanate via an N‐acylurea as intermediate. The catalyst is partly deactivated by the acid. The phospholene catalyst was only found effective in reactions with aromatic isocyanates.
Synthesis of two branched heptopyranoside‐ (L,D‐Hepp)‐containing trisaccharides of the inner‐core region ofCitrobacter PCM1487
Authors: Boons G. J. P. H. , Overhand M. , van der Marel G. A. , van Boom J. H.
Published: September 2010

The diastereogenic addition of (phenyldimethylsilyl)magnesium chloride to methyl 3‐O‐allyl‐2,4‐di‐O‐benzyl‐α‐D‐manno‐hexodialdo‐1,5‐pyranoside gave a L‐glycero‐D‐manno‐heptopyranoside (L,D‐Hepp) derivative having at C‐7 the phenyldimethylsilyl function as a hydroxy‐masking group. The L,D‐Hepp) derivative was converted into two acceptors which could be applied successfully for the preparation of the trisaccharides L‐α‐D‐Hepp)‐(1→3)‐O‐[L‐α‐D‐Hepp‐(1→7)]‐L‐α‐D‐Hepp/‐O‐Me20and α‐D‐Glcp‐(1→3)‐O‐[L‐α‐D‐Hepp‐(1→7)]‐L‐D‐Hepp‐O‐Me26.
Synthesis of (12,13‐13C2)retinal and (13,1413C2)retinal: A strategy to prepare multiple‐13C‐labeled conjugated systems
Authors: Groesbeek M. , Rood G. A. , Lugtenburg J.
Published: September 2010

(12,13‐13C2)Retinal, (13,14‐13C2)retinal, (19‐13C)retinal and (20‐13C)retinal (1) were prepared in a simple fashion in high yield via a consecutive strategy. The key step is the reaction of a N‐methoxy‐N‐methylamide with an alkyllithium or a Grignard reagent. The preparation of the required N‐methoxy‐N‐methylamide is discussed. In this scheme, only three commercially available 13C‐labeled starting materials (ethyl bromoacetate, acetonitrile and methyl iodide) are sufficient to construct retinals with any possible combination of 13C labeling in the conjugated tail end. This strategy is applicable to the preparation of many other conjugated systems, such as retinoids, carotenoids and polyenes.
Synthesis of sparsomycin derivatives, addressing its binding to the large ribosomal subunit
Authors: van den Broek L. A. G. M. , Antonisse A. J. J. , Ottenheijm H. C. J. , Felix A. San , Lázaro E. , Ballesta J. P. G. , Lelieveld P.
Published: September 2010

The syntheses of compounds 14–19, 6‐methyluracilacryloyl derivatives, and 27–29, photoreactive aryl azide analogs of the antitumor antibiotic sparsomycin (1) are described. All of the modifications in the 6‐methyluracilacryloyl part of 1 were achieved by selective reduction or by selective N‐ and O‐methylation of 6 (Scheme 2). The key step in the synthetic scheme to the photo‐affinity analogs is the reaction of the chloromethyl sulfoxides 20 and 21 with the properly protected cystamine 22 in liquid ammonia, to give the sparsomycin N‐protected amines 23 and 24, respectively (Scheme 4). Subsequently, the photoreactive groups, viz. a p‐azidosalicylyl and a 4‐azido‐2‐nitrophenyl group, were coupled with these amines. For an evaluation of the biological activity of the compounds prepared, inhibition of protein biosynthesis in two cell‐free assays, cell‐growth inhibition of E. coli in liquid medium and inhibition of murine leukemia L1210 colony formation in soft agar were studied. All variations introduced in the “western A” fragment of 1 render the drug biologically inactive. Apparently, the uracil ring plays an important role in the interaction of sparsomycin with the ribosomal peptidyl transferase and its unmodified presence is crucial for displaying activity. The photoprobes, carrying modifications in the “eastern C” fragment of 1, do interact with the ribosome, but less effectively than sparsomycin itself.
Pressure effects as mechanistic probes for homolytic thermal cobaltcarbon bond cleavage of cobalamins
Authors: Gamelkoorn H. J. , de Bolster M. W. G. , Balt S.
Published: September 2010

The effect of pressure on the rates of anaerobic thermal homolytic scission of the CoC bond in alkylcobalamins (RB12, R = adenosyl, methyl and neopentyl) has been determined in different solvents of varying viscosities. Homolytic fission is compared to bond breaking using βH elimination (isopropylcobalamin in ethylene‐glycol + water mixtures) and heterolysis. These two mechanisms are characterized by a volume of activation that is close to zero, whereas homolysis shows a substantial positive value (18.5 cm3 ṁ mol−1 for AdoB12, 17.0 cm3 ṁ mol−1 for MeB12 and 7.9 cm3 ṁ mol−1 for neopentylB12, all in ethylene glycol) for this parameter. Consequently, pressure effects can be used, with caution, as mechanistic probes to identify CoC bond fission mechanisms for the reactions studied.
Reactions of β‐sultones and carbyl sulfates with nucleophiles
Authors: Bakker Bert H. , Schonk Ruud M. , Cerfontain Hans
Published: September 2010

Ring opening of the octane‐β‐sultones 1a‐c by methanol gives the β‐methoxyoctane‐sulfonic acids 2a‐c by SN2 substitution at C‐O with inversion of the configuration. Hydrolysis of cis‐ and trans‐4,5‐octanesultones 1a‐b under acidic conditions is stereospecific and leads to threo‐ [(RR,SS)‐4u] and erythro‐5‐hydroxy‐4‐octanesulfonic acid [(RS,SR)‐4u], respectively, by a similar SN2 reaction on the carbon of the CO bond. Hydrolysis of 4,5‐octanesultones 1a‐b with base proceeds by attack at the sulfur atom of the β‐sultone ring to provide 5‐hydroxy‐4‐octanesulfonates (4v) with retention. Reaction of carbyl sulfates 5a‐b with methanol gives the methyl esters of 5‐hydroxy‐4‐octanesulfonic acid 7a‐b in a stereospecific way with retention of configuration by attack of methanol at the sulfonate sulfur atom.
A convenient synthesis of a lipopeptide containing a diacylglycerol moiety: Preparation of a potential inhibitor of protein kinase C
Authors: de Bont H. B. A. , van Boom J. H. , Liskamp R. M. J.
Published: September 2010

The synthesis of a dimyristoylglycerol peptide is reported. Starting from 1,2‐diisopropylidene‐sn‐glycerol, a 1,2‐dimyristoyl‐sn‐glycerol derivative has been synthesized which has been coupled to an immobilized peptide. After deprotection and cleavage from the resin, a diacylglycerol‐moiety‐containing lipopeptide was obtained which can be considered as a potential inhibitor of protein kinase C.
A preliminary appraisal of selected problems in computer‐assisted organic synthesis
Authors: Hippe Z. S. , Fic G. , Mazur M.
Published: September 2010

Some basic problems of contemporary computer‐assisted organic synthesis are briefly dealt with. The discussion (led from the point of view of computer science) mainly concerns the question of a solution space in organic synthesis and methods of artificial intelligence used to search it. Some features of systems assisting in organic synthesis, regarded as dedicated expert systems, are also commented on. An interactive strategy for development of an optimum synthetic tree is proposed. Finally, expected future trends in computer‐assisted organic synthesis and simulation (modeling) of organic reactions are briefly summarized.
Synthesis of mitosenes from N‐aryl‐2‐(diphenylphosphinyl)pyrrolidines
Authors: van der Gen A. , Zorgdrager J. , van der Steeg M. , Schreurs H.
Published: September 2010

A new route for the construction of the mitosene skeleton was developed using 2‐(diphenylphosphinyl)pyrrolidine (2) and 2‐methoxy‐3‐methyl‐1,4‐benzoquinone (3) as starting materials. Regioselective oxidative addition of 2 to 3 gave 5‐substituted pyrrolidinylbenzoquinone 4. Protection of the quinone function by reduction, followed by in‐situ reaction with benzyl bromide, gave the bis‐benzylated product 5. Using a recently developed route to pyrrolo[1,2‐a]indoles, 5 was converted into the protected mitosenes 8. Debenzylation and subsequent oxidation of 8 produced the mitosenes 1 in good yields.
Synthesis of chiral 4‐pyrazolol derivatives starting from D‐glucose
Authors: de Wit D. , van Unen L. M. A. , van Rantwijk F. , Maat L. , Kieboom A. P. G.
Published: September 2010

The condensation of protected and unprotected 3‐ketoglucose (1) with hydrazines to 4‐pyrazolols has been investigated. 3‐ (5) and 5‐(D‐erythro‐1,2,3‐trihydroxypropyl)‐4‐pyrazolol (4) were obtained from 1 in high yield, as a mixture of these two isomers. A regioselective route starting from protected 1 in two steps yielded a mixture of diastereomers as a result of epimerization in the side chain.
Mechanism of enantioselective ester cleavage by histidine‐containing peptides at a micellar interface. 2. Effect of changing peptide chain length
Authors: Cleij Marco C. , Drenth Wiendelt , Nolte Roeland J. M.
Published: September 2010

Chiralp‐nitrophenyl esters derived from the amino acid phenylalanine are cleaved by various histidine‐containing tripeptides and higher oligopeptides as catalysts at a micellar interface. It is assumed that the oligopeptides adopt an internally hydrogen‐bonded C7conformation when they dissolve into the micellar hydrocarbon phase. Chiral recognition is attributed to the formation of a hydrogen bond in the micellar hydrocarbon phase between one enantiomer of the ester and the peptide. It is important for the activity that the imidazolyl NH moiety of the His residue remains in the aqueous phase. The hydrophilic/hydrophobic balance, which determines the location of each of the amino acid residues of the peptide in the two‐phase system, can be controlled by varying the length and stereochemistry of the peptide chain and by attaching hydrophobic groups. The most selective catalyst is a tripeptide with the structure C4H9OC(O)‐L‐Phe‐L‐His‐L‐Leu. It cleaves thep‐nitrophenyl esters of N‐protected L‐ and D‐phenylalanine with an enantioselective ofkI/kD≈︁ 40. Further lengthening of the peptide chain with L‐Leu and L‐Ala residues and lengthening of the N‐protecting group of the catalyst decreases the enantioselectivity down tokI/kD≈︁ 6 for the penta‐peptide C12H25OC(O)‐L‐Phe‐L‐His‐(L‐Leu)3. The origin of these effects is discussed.
Synthesis of 20‐oxo steroids
Authors: van Leusen Daan , van Echten Erik , van Leusen Albert M.
Published: September 2010

The synthesis is described of a series of eighteen 16‐dehydro‐20‐isocyano‐20‐sulfonylpregnanes (5 and 8–14) by C‐20 alkylation of 17‐[isocyano(sulfonyl)methylene]androstanes 1–3. The geminal isocyano and sulfonyl groups at C‐20 (compounds 5, 8–14) are removed by acid hydrolysis to provide a new entry into 20‐oxo steroids (6, 15–19). The C‐20 alkylation also includes halomethylation and alkoxymethylation to form 21‐halo‐ and 21‐alkoxy‐16‐dehydro‐20‐oxopregnanes, respectively. As an attractive alternative to acid hydrolysis, the isocyano group is first oxidized with Pb(OAc)4 to an isocyanato group prior to hydrolysis (of the geminal isocyanato and sulfonyl groups) to the same 20‐oxo steroids. The latter conversion is carried out under non‐acidic conditions at room temperature in a slurry of alumina in dichloromethane.
Supramolecular encapsulation of C60 in a water soluble calixarene; A core‐shell charge transfer complex
Authors: Williams René M. , Verhoeven Jan W.
Published: September 2010

A calix[8]arene derivative has been found to form a water soluble complex with fullerene‐C60, but not with C70, which allows extraction of C60 from e.g. toluene into the aqueous phase. Charge transfer character of the complex is evident from strong charge transfer absorption around 440 nm measured in water. Molecular modeling calculations indicate a core‐shell structure for the complex.
Synthesis and spectroscopy of nine isomeric methylacephenanthrylenes
Authors: Mulder Patrick P. J. , Boere Ben B. , Baart Arthur , Cornelisse Jan , Lugtenburg Johan
Published: September 2010

The synthesis of nine isomeric methyl‐substituted acephenanthrylenes is described. Three different approaches were used. 1‐, 2‐, And 6‐methylacephenanthrylene (1a, 1c and 1f) were prepared by formylation of acephenanthrene (2) and 4,5,7,8,9,10‐hexahydroacephenanthrylene (17), followed by Wolff‐Kishner reduction and dehydrogenation. 4‐, 5‐, 7‐ And 10‐methylacephenanthrylene (1d, 1e, 1g and 1j) were synthesized by treating the corresponding acephenanthrenones with methyllithium, followed by dehydration and, in the case of 1g and 1j, dehydrogenation. 8‐ And 9‐methylacephenanthrylene (1h and 1i) were prepared by a Haworth synthesis starting with the reaction of methylsuccinic anhydride with acenaphthene. The spectroscopic properties of acephenanthrylene and its methyl derivatives were investigated with mass spectrometry, 1H NMR and UV‐VIS spectroscopy. According to the 1H NMR spectra, steric hindrance between the methyl group and nearby protons decreases in the following order: 1, 10 > 6 > 7 > 3 > 4, 5, 8, 9.
CCK‐A Agonists: Endeavours involving structure‐activity relationship studies
Authors: Hermkens Pedro H. H. , Ottenheijm Harry C. J. , van der Werf‐Pieters Jane M. L. , Broekkamp Chris L. E. , de Boer Thijs , van Nispen Jan W.
Published: September 2010

The design cycle of peptidomimetics having CCK‐A agonistic activity is discussed. The phases of this strategic approach are discussed briefly and results obtained either in our laboratories or by other groups are elaborated in this framework.

Most of the CCK‐A agonists prepared until recently still consist of six or more amino acid residues. Several conclusions can be drawn from studies in which one single amino acid has been exchanged against other residues. Studies involving the exchange of Tyr(SO3H) (amino acid 2) indicate that rather than the presence of the aromatic ring, the correct positioning of an acidic function is responsible for activity. The third amino acid (Met) probably acts as spacer residue. Amino acid 4 (Gly) can only be exchanged by D‐amino acids containing small side chains (D‐Ala). Replacement of Trp (amino acid 5) almost always results in decrease of actvity. Changes in position 6 indicate that the side‐chain is involved in hydrophobic interactions with the receptor site and replacement of Asp (amino acid 7) demonstrates that the acidic function of the side chain is of importance for activity. The aromatic ring of amino acid 8 (Phe) may be substituted by a bulky alkyl or cycloalkyl moiety without considerable loss of activity.

Isosteric replacements of protease‐sensitive amide bonds enhancing the metabolic stability are permitted.

Two new classes of cyclic peptides were found with conserved CCK‐A activity. A start has been made with these peptides to determine the active CCK‐A topology by means of molecular modeling and NMR studies.
Conformational analysis of 1‐arylpiperazines and 4‐arylpiperidines
Authors: Dijkstra Gerard D. H.
Published: September 2010

A conformational analysis of 1‐arylpiperazines and 4‐arylpiperidines is presented using molecular‐mechanics and semi‐empirical calculations. It has been found that electronic effects of substituents on the aryl ring determine the conformational behaviour of 1‐arylpiperazines. Steric effects play a minor role. Electron‐withdrawing substituents on the aryl moiety increase the conjugation between the anilino nitrogen lone pair and the π electrons of the aryl group and direct the orientation between the aryl and heterocycle towards the same plane. Electron‐releasing substituents have the opposite effect and reduce the energy difference between a coplanar and perpendicular orientation between the rings. 4‐Arylpiperidines prefer a perpendicular orientation between the rings.
Electrochemistry of potentially bioreductive alkylating quinones. Part 4. Qualitative and quantitative structure‐activity relationships of aziridinylquinones
Authors: Driebergen R. J. , Moret E. E. , Janssen L. H. M. , Beijnen J. H. , Holthuis J. J. M. , Kelder S. J. Postma , Verboom W. , Reinhoudt N. D. , Lelieveld P.
Published: September 2010

The concept of bioreductive alkylation as a mechanism of action of aziridinylquinoid anticancer agents has been investigated. The influence of quinone substituents on quinone reduction, on protonation of the aziridines prior to and following quinone reduction and on partitioning properties of the compound was examined. Parameters obtained from a combined electrochemical, chemical‐stability and lipophilicity study describing these processes were determined and correlated quantitatively in a Hansch‐type QSAR study with biological data obtained from three experimental tumor models. Poor quantitative correlations between cytotoxicity in a L1210 clonogenic assay and the parameters were obtained. Good linear relationships, however, between antitumor activity in vivo (vs. L1210 leukemic mice and vs. B16 melanoma‐bearing mice) and the lipophilic properties of the quinone were found. These relationships, showing a negative correlation between antitumor activity and lipophilicity, can be used to predict the activity of new, unknown compounds. No trend was evident between antitumor activity and other parameters, although some indications for potential importance of electronic and steric properties of the substituents and of their ability to form hydrogen bonds were found.
Synthesis of dicyclopenta‐fused derivatives of phenanthrene
Authors: Mulder Patrick P. J. , Boere Ben B. , Cornelisse Jan , Lugtenburg Johan
Published: September 2010

The synthesis of cyclopent[hi]acephenanthrylene (CPAP), a dicyclopenta‐fused derivative of phenanthrene, is described. The 4,5‐dihydro and 4,5,6,7‐tetrahydro derivatives of CPAP were also prepared. These novel compounds are characterized by means of 1H‐NMR, UV‐VIS and mass spectrometry.
Macrocyclic carriers in supported liquid membranes
Authors: van Straaten‐Nijenhuis Wilma F. , de Jong Feike , Reinhoudt David N.
Published: September 2010

Macrocyclic receptor molecules can be designed to selectively bind a variety of host molecules, including metal cations and neutral molecules. This property can be uniquely exploited in separation processes, by using these compounds as carriers in transport through liquid membranes.

The various types of liquid membrane systems are briefly discussed, and the attractive features of the supported (by a microporous polymer film) liquid membrane (SLM) are explained. The mechanical stability of the SLMs is dependent on several factors, including the type of polymer support, membrane solvent, and hydrophobicity of the carrier used.

The rates and selectivity of transport are discussed in terms of membrane geometry, membrane solvent type, structure and concentration of the carrier, and the type and concentration of cations, and anions in both the source and receiving phases. Existing mathematical models in which these parameters have been incorporated, are compared with experimental data. Apart from a concentration gradient of the metal cation over the membrane, other driving forces, such as anion concentration, proton counter‐transport and redox‐active transport, are discussed.
Convergent functional groups XIV. Synthesis and binding studies of new molecular clefts for recognition and catalysis
Authors: Pieters Roland J. , Rebek Julius
Published: September 2010

Two new molecular clefts have been synthesized, both containing an adenine receptor portion and a metal‐binding site. The binding of adenine derivatives was evaluated in CDCl3, acetone‐d6 and water using NMR titrations. Base‐paired hydrogen‐bonded complexes are formed in all three solvents, but structural differences in the complexes are also observed. The CuII binding ability was established using UV spectroscopy.
Alkali‐metal‐ion‐assisted BAL2 cleavage of 2‐(methoxycarbonyl)‐1,3‐xylylene‐18‐crown‐5 by benzenemethanethiolate anion
Authors: Cacciapaglia R. , Mandolini L. , Castelli V. Van Axel
Published: September 2010

BAL2 demethylation of 2‐(methoxycarbonyl)‐1,3‐xylylene‐18‐crown‐5 by benzenemethanethiolate anion in dimethylformamide (+ 1.6M water) at 35°C is significantly promoted by alkali‐metal counterions, the efficiency order being Na+ > K+ > Cs+ > Li+. The contrasting behaviour of the model compound, methyl 2,6‐dimethylbenzoate, whose demethylation reaction is in fact slightly inhibited by metal ions, points to the crucial role played by the polyether bridge of the crown ether substrate. In line with previous work from this laboratory, selective transition‐state stabilisation in the metal‐ion‐promoted cleavage of the crown‐ether substrate is ascribed to a favourable combination of electrostatic binding of the metal ions with the negative charge being transferred from the nucleophile to the convergent methoxycarbonyl group and coordinative binding to the neutral donors of the polyether bridge.
The effect of chemical structure upon the thermodynamics of micellization of model alkylarenesulphonates. Prediction of micellar properties with the Poisson‐Boltzmann model
Authors: Bijma Koos , Engberts Jan B. F. N.
Published: September 2010

This paper describes how the theory of the “dressed micelle”, which is based on the nonlinear Poisson‐Boltzmann equation, can be used to calculate a number of thermodynamic quantities for micellization of sodium p‐alkylbenzenesulphonates. From the Gibbs energy of micellization, the enthalpy of micelle formation is calculated and compared with calorimetric enthalpies. A number of other thermodynamic quantities, such as the degree of counterion binding, the electrostatic surface potential of a micelle, and the entropy of micelle formation, have also been calculated as a function of temperature and surfactant structure and, where possible, compared with experimental data. In general, the calculated thermodynamic parameters obtained using the model show the same trend with respect to temperature and structure as the experimental quantities. The absolute values, however, differ from the experimental quantities. Finally a comparison is made between the Poisson‐Boltzmann model, the phase‐separation model and the mass‐action model.
X‐ray structure of a molecular basket. Origin of its poor binding properties
Authors: Martens C. F. , Sijbesma R. P. , Gebbink R. J. M. Klein , Nolte R. J. M. , Spek A. L.
Published: September 2010

X‐ray analysis and 1H‐NMR data in solution show that the entrance of the cavity of receptor 1c is blocked by benzyl groups, preventing the binding of substrate molecules.
Preparation and characterization of novel cage‐type cyclophanes having a helically twisted and cylindrical internal cavity
Authors: Murakami Yukito , Hayashida Osamu , Matsuura Sadahiko
Published: September 2010

An asymmetric character of the internal cavities provided by novel cage‐type cyclophanes, two triaza[3.3.3]paracyclophanes linked with three chiral bridging components, was clarified by means of circular dichroism (CD) spectroscopy and a computer‐aided molecular modeling study based on molecular mechanics conformational search.