α- and β-cyclodextrin complexes with n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates. A molecular mechanics study of 1:1 and 1:2 associations

Molecular mechanics (MM) methods were employed to evaluate stabilization upon formation of inclusion compounds between two different guest molecules and α- and β-cyclodextrins (CDs) for two different stoichiometries 1:1 and 1:2. The two guest molecules studied were n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates with variety of chain lengths. The computed stability for the inclusion compounds between α-CDs and n-alkyl carboxylic acids reproduced experimental data reported in the literature. The transition between 1:1/1:2 complexes occurred at an alkyl chain length of n_C=9. It was previously demonstrated by diffusion coefficients measures that a stable 1:2 stoichiometry inclusion compound could be formed between n-alkyl p-hydroxy benzoates and α-CD for the chain length n_C>4. The computed results reproduced the experimental ones. The combination between OPLS and GB/SA resulted in better agreements with experiments than those obtained with MM2 and MM3.     

Plasma chromatography of n-alkyl acetates

Plasma chromatography is a technique which permits characterization and analysis of trace constituents in a gaseous mixture at atmospheric pressure. It is especially well suited as a gas chromatographic detector. Operating at atmospheric pressure, the instrument uses either air or nitrogen carrier gas into which the sample is injected directly or through a gas chromatograph. The compounds are identified by their characteristic positive and negative mobility spectra, which consist of simple molecular and dissociative ions. Quantities as low as 10⁻⁶ to 10⁻¹² g are detectable. For use as a gas chromatographic detector, reference mobility spectra of compounds are needed. Those of n-alkanes, alcohols, ketones, halogenated aromatics, substituted nitrobenzenes, polychlorinated biphenyls, alkyl halides, aliphatic N-nitrosamines and isomeric phthalic acids have been previously reported. This study reports the reference mobility spectra produced by n-alkyl acetates. These compounds display strong positive mobility spectra but no negative mobility spectra. The spectra all show characteristic MH⁺, M(H₂O)_nH⁺ and (M₂)H⁺ along with the alkyl fragment ions.     

Structure and dynamics of rodlike polyester with long n-alkyl side chains over a wide range of temperatures by solid state C NMR

Solid state ¹³C NMR experiments on poly(p-biphenylene terephthalate) with long n-dodecyl side chains have been carried out over a wide range of temperatures, in order to elucidate conformational and dynamical behavior of the polyester in the crystalline state and thermotropic liquid crystalline state. From these experimental results, it is found that at temperatures from room temperature to 80 °C the n-alkyl side chains take both of the immobile and the mobile regions, and at temperatures above 120 °C take only the mobile region. In the immobile region the n-alkyl side chains are in the all-trans zigzag conformation and in the mobile state are undergoing fast exchange between the trans and gauche conformations. On the other hand, the terephthalate moiety of the main chain undergoes rotational motion after the melt of n-alkyl side chains as the temperature is increased.     

-Fluoro decalones as chiral epoxidation catalysts: fluorine effect

Three rigid monofluorinated trans-decalones 4a, 5e, and 6e (90% ee) have been synthesized from commercially available (−)-(R)-methyl naphthalenone (90% ee). Their structures have been fully characterized (NMR, X-ray): ketones 4a and 5e are Me,F-disubstituted to the carbonyl with the fluorine axial and equatorial, respectively, while ketone 6e is F-monosubstituted to the carbonyl with the fluorine equatorial. The use of these ketones as chiral catalysts for the epoxidation of trans-olefins (such as stilbene, β-methylstyrene and p-methoxy cinnamate) through the formation of dioxiranes shows (i) that dioxiranes with an equatorial fluorine to the dioxirane ring are less reactive and provide lower ee’s than dioxiranes with an axial fluorine and having the same chirality and (ii) that an axial methyl to the dioxirane ring is significantly less efficient than a fluorine. The results corroborate Armstrong and Houk’s theoretical model and our first hypothesis to rationalize the inverted enantioselectivities observed using -fluorinated cyclohexanones having the same chirality, i.e.: rapid ring inversion (Curtin–Hammett principle) allows the dioxirane conformation to have the fluorine axial (even if less populated than the other) to contribute significantly to the epoxidation reaction.     

Enantioselective inclusion of (R)-phenylglycyl-(R)-phenylglycine with benzyl methyl sulfoxides

A crystalline dipeptide, (R)-phenylglycyl-(R)-phenylglycine (RR-1), recognized p-halobenzyl methyl sulfoxides with high R-enantioselectivity (86–99% ee) to form inclusion compounds. The single-crystal X-ray analyses showed that RR-1 molecules are arranged in parallel and zigzags via hydrogen bonding to construct a pleated sheet. The guest molecules that form hydrogen bond with ⁺NH₃ of RR-1 are accommodated in the channel cavity between the layers. In contrast to the inclusion crystals of parent benzyl methyl sulfoxide, in which a rectangular cavity is formed, the cavity including p-halobenzyl methyl sulfoxides becomes rhomboidal. We also examine the guest exchange in these inclusion compounds and it was found that the guest exchanges occur when the host structure changes.     

-mononitroalkyl derivatives of indium

Dealkylation of trialkylindium by -mononitroalkane leads to the formation of the previously unknown -nitroalkyl derivatives of indium. An investigation of the chemical properties and of the ¹¹⁵In nuclear quadrupole resonance spectra of these compounds has been undertaken. An analysis of the data obtained from these investigations suggests the existence of intramolecular O→In coordination in the -nitroalkyl derivatives of indium.     

-(1-phenylhydrazino)-alkanone phenylhydrazones: The reaction with carbonyl compounds

The unsymmetrically disubstituted hydrazines 1 were condensed with carbonyl compounds. Some of the expected condensation products were isolated, but some were formed as unstable intermediates which underwent 1,4-elimination: The phenylhydrazone of the carbonyl compound used was obtained, together with the corresponding phenylazo-alkene 11 or alternatively, the 1,4-addition product of a different protic nucleophile to 11.     

,β-unsaturated oximes Isoxazoline formation by thermal cyclisation of compounds related to benzalacetophenone oxime and isoxazoline thermal cycloreversion reactions

At about 300° the title compounds yield fragments attributed to cyclisation to isoxazolines and subsequent cycloreversion. Isoxazolines are formed at about 200° and can usually be isolated. At 300° they yield the same products as the oximes.

Thus benzalacetophenone oxime gives 3,5-diphenylisoxazoline which then largely undergoes two distinct cycloreversions: (a) 1,3-cleavage (numbers refer to isoxazoline bonds) yielding benzonitrile and acetophenone and (b) reductive 1,4-cleavage yielding benzaldehyde and 1-phenylethylimine hydrolysis products. By-products are 2,4,6-triphenylpyridine, water and ammonium benzoate. With -methylchalcone oxime reductive 1,4-cleavage is suppressed and with β-methylchalcone oxime both modes of cleavage are suppressed and 5-methyl-3,5-diphenylisoxazole is the stable product. An analogue of -methylchalcone oxime, 2-methyl-1-phenyl-3-(2-thienyl)prop-2-ene-1-one oxime gives fragments attributed to both cleavage modes of an unisolatable and hitherto unknown isoxazoline.

Possible mechanisms for the cyclisation and cycloreversions are discussed and the reductive 1,4-cleavage is believed to be a cycloreversion of a vinyl-nitrene.     

-Cyclisation of tertiary amines. Part 4. Cyano-imidoyl substituted furans from captodative enamines and dibenzoylacetylene

-Cyano-enamines and dibenzoylacetylene lead to dienes (via [2+2] cycloaddition followed by ringopening). Their -Cyclisation to oxygen produces the title compounds.     

Electrospray ionization mass spectrometry studies of cyclodextrin‐carboxylate ion inclusion complexes

Aqueous solutions containing simple model aliphatic and alicyclic carboxylic acids (surrogates 1–4) were studied using negative ion electrospray mass spectrometry (ESI‐MS) in the presence and absence of α‐, β‐, and γ‐cyclodextrin. Molecular ions were detected corresponding to the parent carboxylic acids and complexed forms of the carboxylic acids; the latter corresponding to non‐covalent inclusion complexes formed between carboxylic acid and cyclodextrin compounds (e.g., β‐CD, α‐CD, and γ‐CD). The formation of 1:1 non‐covalent inclusion cyclodextrin‐carboxylic complexes and non‐inclusion forms of the cellobiose‐carboxylic acid compounds was also observed. Aqueous solutions of Syncrude‐derived mixtures of aliphatic and alicyclic carboxylic acids (i.e. naphthenic acids; NAs) were similarly studied using ESI‐MS, as outlined above. Molecular ions corresponding to the formation of CD‐NAs inclusion complexes were observed whereas 1:1 non‐inclusion forms of the cellobiose‐NAs complexes were not detected. The ESI‐MS results provide evidence for some measure of inclusion selectivity according to the 'size‐fit' of the host and guest molecules (according to carbon number) and the hydrogen deficiency (z‐series) of the naphthenic acid compounds. The relative abundances of the molecular ions of the CD‐carboxylate anion adducts provide strong support for differing complex stability in aqueous solution. In general, the 1:1 complex stability according to hydrogen deficiency (z‐series) of naphthenic acids may be attributed to the nature of the cavity size of the cyclodextrin host compounds and the relative lipophilicity of the guest. Copyright © 2009 John Wiley & Sons, Ltd.     

Clathrate and Inclusion Compounds. Part 13 [1]. Vibrational and NMR Spectroscopic Studies of Carboxylic Acid Guests in Urea

Infrared, Raman and solid state¹³C NMR spectra have been recorded for arange of inclusion compounds of urea containingstraight chain aliphatic carboxylic acids(butyric – decanoic) as guests. Inclusioncompounds are not formed with formic, acetic andpropionic acids. Thiourea does not forminclusion compounds with any of the C1 to C10acids. The vibrational and NMR data support theconclusion that the acids are present ashydrogen bonded dimers in the channels of thehost. The alkyl chain ¹³C chemical shiftvalues are very different from those of acidguests in the cavities formed in Dianin'scompound. These suggest that the alkyl chainsare present in the all-trans conformation,although weak bands observed in the spectrum ofthe decanoic acid inclusion compound lend somesupport to suggestions based on MM calculationsthat other conformations might be present.     

,-Difluoroketone inhibitors of HMG CoA reductase

The rationale for a new class of HMG CoA reductase inhibitors, represented by ,ga-difluoroketones 3 and 4, is described. The syntheses of 3, 4, and their nonfluorinated analogue 5 are presented.     

-Halogenoketones—XIII Chromone epoxides; their synthesis and acid-catalysed rearrangement

The chromone epoxide ring system has been synthesised. Base-catalysed cyclization and dehydrobromination of -bromo-o-acyl (aroyl) oxyacetopheones or 2-bromo-1, 3-diones yielded 3-substituted chromone epoxides. Acid-catalysed rearrangement of a 2-methylchromone epoxide in an aprotic solvent gave a 2-methylenech-romanonol, while a 3-methoxymethylchromone epoxide fragmented to chromonol under these conditions; in alchols, chromone epoxides gave 2-alkoxychromanonols.     

A New Functional Cyclophane Host. Synthesis, Complex Formation and Crystal Structures of Three Inclusion Compounds

A new macrocyclic host compound 2 having an octamethylsubstituted cyclophane structure with two intra-annular carboxylic acid functions has beensynthesized. The properties of crystalline inclusion formation are studied and X-ray crystalstructures of three inclusion complexes including acetic acid, propionic acid and acetone asthe guest molecules are reported. Inter-host channel formation with complexed guest moleculesaccommodated into the channels are typical features of the acetic acid and acetone 1 : 4 (host : guest) stoichiometric complexes being also hydrated species, while the propionicacid 1 : 2 complex is of the close packing type containing no additional water molecules.Systems of hydrogen bonds involving the host and guest functional groups are common toall structures. In the case of the acetic acid inclusion compound, a complex supramolecularhydrogen-bonded array comprising a bordering tricyclic assembly of eight molecular species exists.     

Molecular recognition in cyclodextrin complexes of amino acid derivatives. 2. A new perturbation: the room-temperature crystallographic structure determination for the N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-cyclodextrin complex

Cyclodextrins (CDs) are cyclic oligosaccharides that encapsulate various small organic molecules, forming inclusion complexes. Because CD complexes are held together purely by noncovalent interactions, they function as excellent models for the study of chiral and molecular recognition mechanisms. Recently, room-temperature crystallographic studies of both the 2:2 N-acetyl-L-phenylalanine methyl ester/beta-CD and 2:2 N-acetyl-L-phenylalanine amide/beta-CD complexes were reported. The effect of changes in carboxyl backbone functional group on molecular recognition by the host CD molecule was examined for the nearly isomorphous supramolecular complexes. A new perturbation of the system is now examined, specifically perturbation of the aromatic side chain. We report a room-temperature crystal structure determination for the 2:2 N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-CD inclusion complex. The complex crystallizes isomorphously with the two previously reported examples in space group P1; the asymmetric unit consists of a hydrated head-to-head host dimer with two included guest molecules. The crystal packing provides both a nonconstraining extended hydrophobic pocket and an adjacent hydrophilic region, where hydrogen-bonding interactions can potentially occur with primary hydroxyl groups of neighboring CD molecules and waters of hydration. The rigid host molecules show no sign of conformational disorder, and water of hydration molecules exhibit the same type of disorder observed for the other two complexes, with a few significant differences in locations of water molecules in the hydrophilic region near guest molecules. There is evidence for modest disorder in the guest region of an electron density map. In comparing this system with the two previously reported complexes of phenylalanine derivatives, it is found that the packing of the guest molecules inside the torus of the CD changes upon substitution of a methoxy group at the para position of the aromatic phenyl ring. Backbone hydrogen-bonding interactions for the guest molecules with the CD primary hydroxyls and waters also change. This structure determination is a new and revealing addition to a small but growing database of amino acid and peptidomimetic interactions with carbohydrates.     

Crystalline polysilicate magadiite with intercalated n-alkylmonoamine and some correlations involving thermochemical data

Synthesized hydrated lamellar acidic crystalline magadiite (H₂Si₁₄O₂₉·2H₂O) nanocompound was used as host for intercalation of polar n-alkylmonoamine molecules of the general formula H₃C(CH₂)_nNH₂ (n = 1–6) in aqueous solution. The original interlayer distance (d) of 1500 pm, determined by X-ray powder diffraction patterns, increases after intercalation. The values correlated with the number of aliphatic amine carbon (n_c) atoms: d = [(1312 ± 11) + (21 ± 2)]n_c. The amount of intercalated amines (N_s), decreased as n_c increased: N_s = [(5.82 ± 0.04) − (0.45 ± 0.01)]n_c. The acidic layered nanocompound was calorimetrically titrated with the amines and the thermodynamic data gave exothermic values for all guest molecules, as shown by the correlation: Δ_intH = −[(24.45 ± 0.49) − (1.91 ± 0.10)]n_c and d = [(1576 ± 16) − (10.8 ± 1.0)]Δ_intH. The negative values of the Gibbs energies and the positive entropies also presented the correlations: Δ_intG = −[(22.8 ± 0.2) − (0.2 ± 0.1)]n_c and Δ_intS = [(6 ± 1) + (5 ± 1)]n_c, respectively.     

-Halogenoketones—XIV Studies in the chemistry of 2'-hydroxyacrylophenones

An initial study of the side-chain unsubstituted 2'-hydroxyacrylophenone system shows it to have a considerably greater propensity for intermolecular addition than the comparable 2'-hydroxychalcone system, readily undergoing base-catalysed addition of, for example, alcohol and thereby diverting typical chalcone reactions requiring alcoholic alkali. 2'-Acetoxyacrylophenone dibromides and bromoalkoxides cyclize with base to chromone epoxides as do 2'-acetoxy--bromoacrylophenones in alcoholic alkali.     

New Exo-Functional Cyclophane Hosts. Synthesis and Crystal Structures of Inclusion Compounds

The new cyclophane type host compounds 1–3, containing rigid aromatic units and two exo-topic carboxylic acid functions, have been synthesized. Crystalline solvent inclusions, involving the dicarboxylic acid hosts and their corresponding ester intermediates 6 (a–c), namely 1·DMSO (1:4), 2·pyridine (1:3), 3·pyridine (1:4), 6a·pyridine (1:2) and 6a·benzene (1:2), have been prepared and studied using X-ray diffraction on single-crystals. Moreover, X-ray structure analyses of the solvent-free crystals of the 6 (a, b) intermediates were also carried out for comparison. Co-crystals of the carboxylic hosts 1–3 contained H-bonded 1:2 host-guest associates as building blocks, together with additional space-filling guests, whereas only loosely bounded space-filling solvent molecules were found in the two solid inclusion compounds of the 6a cyclophane ester host. In addition to the mentioned conventional H-bond interactions between carboxylic hosts and their guests, the crystal structures proved to be held together by relatively weak C–H…O bonds besides the ordinary van der Waals' interactions. Packing relations, and the effects of structural variations, guest molecules and anisotropic packing forces on the conformation of the semi-rigid cylcophane ring have been discussed and compared in seven crystal structures.     

Synthesis of new o-alkyl substituted arylalkylphosphanes: study of their molecular structure and influence on rhodium-catalyzed propene and 1-hexene hydroformylation

A set of new phosphane ligands designed to increase the branched-to-normal ratio of the hydroformylation reaction were prepared in the same way as the previously reported ortho-alkyl substituted arylphosphanes, which have shown increased i/n ratios in the hydroformylation of propene and 1-hexene. In order to determine the relationship between the catalytic behavior and stereoelectronic properties of the ligands, various functional alkyl groups (methyl, isopropyl, cyclohexyl) were placed on the phosphorus atom directly and in the ortho position of the phenyl ring connected to phosphorus. In the hydroformylation reaction of propene and 1-hexene a higher i/n ratio resulted with nearly all the ligands compared with that of triphenylphosphane. Additionally as the ortho-alkyl-substituent became larger, it had a favorable effect on the i-selectivity. Characterization of the ligands was carried out by NMR spectroscopy (mainly ¹H, ³¹P{¹H}, ¹³C{¹H}, HSQC/HETCOR and COSY-90). Properties of the ligands were also studied by quantum mechanical calculations and by synthesizing three Rh(acac)(CO)(PR₃) derivatives. The o-alkyl-substituent was orientated outside the ligands’ cone angle in the X-ray crystal structures of (2-cyclohexylphenyl)dicyclohexylphosphane and (2,5-dimethylphenyl)bis(4-pyridyl)phosphane, and Rh(acac)(CO)(PR₃) complex of (2-methylphenyl)dicyclohexylphosphane.     

Formation of gold-like metal-lustrous inclusion crystals from 1-phenyl-2,5-bis[5-(tricyanoethenyl)-2-thienyl]pyrrole host and an electron-donating aromatic guest

A novel pi-conjugated organic compound, 1-phenyl-2,5-bis[5-(tricyanoethenyl)-2-thienyl]pyrrole, which bears two powerful electron-withdrawing tricyanoethenyl substitutents, readily yielded gold-like metal-lustrous inclusion crystals with a series of aromatic guest molecules such as toluene, p-xylene, anisole, dimethoxybenzenes and indene. All the inclusion compounds have a common stoichiometric ratio (host/guest) of 2 : 1. X-Ray structural analyses demonstrate that the structural feature for toluene included crystal is similar to those containing p-xylene, anisole, dimethoxybenzenes and indene.