Chiral Host Compounds Research Articles

The effect of dopant chirality on the properties of self-assembling materials with a ferroelectric order.

A series of achiral hockey stick-shaped molecules forming a tilted smectic I liquid crystal phase as well as one non-mesogenic chiral bistereogenic analogue were synthesized and characterized. Herein, we report an example of an achiral hockey stick-shaped compound exhibiting a smectic I phase with a direct transition to the isotropic phase for the first time. This occurrence was confirmed via polarized light microscopy, dielectric spectroscopy, and XRD studies. Homologues with an odd number of carbon atoms in the oligomethylene spacer chain exhibit a lower clearing point than members posessing an even number of carbon atoms in this chain; thus, a characteristic odd-even effect has been observed. The influence of the synthesized compounds with different degrees of chirality and similar chemical structures on the properties of the host compound with a chiral smectic C phase was investigated. A chiral compound forming a wide-temperature chiral smectic C phase without any additional mesophase and having a short helical pitch was selected as the host material for the creation of two bicomponent systems. The mesomorphism of each binary mixture was characterized using optical microscopy and differential scanning calorimetry. The helical pitch of every binary mixture, forming a chiral smectic C phase, was studied within its full phase temperature range. As expected, the chiral host compound in the smectic C* phase doped with the hockey stick-shaped mesogen exhibited a longer helical pitch and lower spontaneous polarization than the chiral host material. On the other hand, for the chiral host compound doped with a non-mesogenic analogue containing two chiral centres, the helical pitch was shorter, and the spontaneous polarization was higher. These results should be potentially applicable for the design of advanced functional multi-component mixtures useful for various applications. The mesogenic behaviour of one binary mixture, forming both the chiral smectic I and titled chiral smectic C phases, was deeply studied via X-ray diffraction and dielectric spectroscopy techniques.

Scalable Enantioseparation of Amino Acid Derivatives Using Continuous Liquid−Liquid Extraction in a Cascade of Centrifugal Contactor Separators

Using a cascade of six centrifugal contactor separators in a countercurrent liquid−liquid extraction mode allowed the separation of one of the enantiomers of 3,5-dinitrobenzoyl-leucine in 55% yield and 98% ee using a catalytic amount of a chiral host compound based on a cinchona alkaloid. This method allows the preparation of kilograms of enantiopure material in table-top-sized equipment that can be operated in a fume cupboard. The methodology can be easily scaled up to ton amounts as large-volume centrifugal contactor separators are commercially available as well.

Continuous Separation of Racemic 3,5‐Dinitrobenzoyl‐Amino Acids in a Centrifugal Contact Separator with the Aid of Cinchona‐Based Chiral Host Compounds

Resolution through revolution: It is possible to extract 3,5-dinitrobenzoyl-protected amino acids enantioselectively with the aid of a table-top centrifugal contact separator and a catalytic amount of a chiral host compound based on the Cinchona alkaloids. Enantioselectivities of up to 80 % could be reached in a single pass. This allows the development of a process for the continuous separation of racemates.The resolution of racemates is mostly performed by crystallisation of diastereomeric salts. Direct physical separation could be much more efficient, but so far most concepts, with the exception of SMB, have proven to be non-scaleable. Here we report the first scalable process for the resolution of N-protected amino acid derivatives through selective extraction, with the aid of a catalytic amount of a chiral host compound based on Cinchona alkaloids. The method hinges on the use of centrifugal contact separators (CCSs) for fast mixing and separation. Although the highest ee obtained was only 80 %, the concept can be extended through the use of a series of CCSs in countercurrent mode to effect full separation.

Separation of (S)-(−)-3-Methyl-2-pyrrolidinone as an Inclusion Complex with (R)-(+)-4,4′,6,6′-Tetrachloro-2,2′-bis(hydroxydiphenylmethyl)-1,1′-biphenyl Host and its X-ray Structural Study

By inclusion complexation with the chiral host compound (R)-(+)-4,4′,6,6′-tetrachloro-2,2′-bis(hydroxydiphenylmethyl)-1,1′-biphenyl, racemic 3-methyl-2-pyrrolidinone was resolved and its (S)-(−)-enantiomer was isolated as a 1:1 inclusion complex, which crystallises in the orthorhombic crystal system in the space group P212121 (a = 14.1163(2) A, b = 14.7140(3) A, c = 17.2025(3) A). By the inclusion complexation, the keto–enol equilibrium of the guest was frozen and the keto-form was isolated in a pure form. By X-ray structural study of the complex, the guest molecule included was elucidated to be the keto-form and its absolute configuration was determined to be (S). By inclusion complexation with (R)-(+)-4,4′,6,6′-tetrachloro-2,2′-bis (hydroxydiphenylmethyl)-biphenyl, racemic 3-methyl-2-pyrrolidinone was resolved and its (S)-(−)-enantiomer isolated and in addition the keto–enol equilibrium of the guest was frozen and the keto-form isolated.

Resolution of α-aminolactams by inclusion complexation with chiral host compounds

3-Aminopiperidin-2-one and α-amino-ε-caprolactam were efficiently resolved by inclusion complexation with a chiral host compound, ( R, R)-(−)- trans-4,5-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.5]decane. The amino substituent on the lactam ring was found to play an important role in efficient chiral recognition in the inclusion crystals.

Inclusion Properties of 11b‐Substituted 2,3,5,6,11,11b‐Hexahydro‐3‐oxo‐1H‐indolizino[8,7‐b]indole‐5‐carboxylic Acid Esters. New Chiral Host Compounds Derived from L‐Tryptophan.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Resolution of 4-oxoazetidin-2-yl benzoate by inclusion crystallization with an optically active host compound

4-Oxoazetidin-2-yl benzoate was resolved efficiently by an inclusion complexation with a chiral host compound, ( R, R)-(−)- trans-4,5-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.5]decane. The phenyl substituent on the β-lactam ring was found to play an important role in an efficient chiral recognition in the inclusion crystals.

Inclusion Properties of 11b-Substituted 2,3,5,6,11,11b-Hexahydro-3-oxo-1H-indolizino[8,7-b]indole-5-carboxylic Acid Esters. New Chiral Host Compounds Derived from l-Tryptophan

Abstract New chiral host compounds have been prepared from l-tryptophan and 3-aroylpropionic acids. These hosts show broad inclusion and sorption abilities toward solvent and racemic molecules, and are characterized by X-ray crystallographic analysis, which clarify the one-dimensional channel structures of the hosts, the helical arrangements of the guests, and the occurrence of weak interactions such as C–H···O and C–H···Cl between the hosts and the guests. The TG and DTA data show the high cohesion of the hosts, and the PXRD patterns indicate that the crystal structures of the hosts remain ordered after removal of the guest molecules. These hosts have potential usefulness in the optical resolution of racemic guest molecules such as s-butyl chloride and 4-methylcyclohexene.

Optical Resolution of Acyclic α-Hydroxy Ketone Derivatives by Inclusion Complexation

Abstract A new method for the preparation of optically active acyclic α-hydroxy ketone derivatives by thermodynamic resolution using a chiral host compound is described. We examined the resolution of racemic 2-benzyloxy-3-pentanone with chiral host compounds in various solvents. After optimization of the reaction conditions, it has become apparent that the optical resolution could occur only under certain strict conditions about solvents, host compounds, and the concentration of the substrate. Stirring the suspension of the ketone with (−)-TADDOL bearing a cyclohexyl ring, derived from ethyl l-tartrate, in MeOH–H2O (1:1) at room temperature produces the inclusion complex with high enantioselectivity to give (S)-ketone with up to 99% ee. On the other hand, the ee of (R)-ketone obtained from the filtrate could be improved by the same procedure using (+)-TADDOL; finally, both enantiomers of the ketone as an almost optically pure form were afforded. Analysis of the formed complex by ESI-TOFMS supposed that the host–guest ratio would be 1:1. This resolution procedure was also applied to other substrates to afford the corresponding optically active ketones.

Crystal engineering for molecular dynamics

Molecules of some achiral compounds are arranged in a chiral form in their own crystals. When achiral molecules cannot be arranged in a chiral form in the crystal, they can be arranged in a chiral form in inclusion complex crystals with a chiral host compound. Reaction of the inclusion complex in the solid state gives the optically active compound. Some new examples of these enantioselective reactions will be discussed. By inclusion complexation with a host compound, molecules can be accommodated in one form in inclusion crystals. By this method, tautomerism and equilibrium can be frozen and one tautomer and configurational or conformational isomer may be isolated in a pure state. X-Ray analytical and CD spectral studies of these isolated isomers will also be discussed.

Enantiomeric recognition of chiral 3,3-bridged-1,1'-binaphthol dimer toward alpha-phenylethylamine and alpha-amino acid ester.

The 1,1'-binaphthol-based dimers with p-phenylenebis(2-ethynyl) spacer, (+)-6 and (+)-2, were synthesized as chiral host compounds. (1)H NMR, UV-vis, and fluorescent titration were used to evaluate the enantiomeric recognition abilities of the chiral host dimers toward the guest amine 7 and alpha-amino acid ester 8. The chiral BINOL-based dimers were found to have good enantiomeric recognition ability. The computer simulation of the host-guest complex molecules was carried out to describe the conformational changes of both naphthyl ring in the molecule of chiral host dimer after complexation with the guest molecule.

Synthesis of Enantiomerically Pure 1,5,7-Trimethyl-3-azabicyclo[3.3.1]nonan-2-ones as Chiral Host Compounds for Enantioselective Photochemical Reactions in Solution

The synthesis of the title compounds is described. As common starting material, 1,5,7-trimethyl-2,4-dioxo-3-azabicyclo[3.3.1]-nonan-7-carboxylic acid chloride (4) was employed which is in turn available from cis,cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid (Kemp’s triacid). For the synthesis of the diastereomeric menthyl esters 1 and 2, the chloride 4 was initially substituted by (-)-menthol and its imide part was subsequently reduced to an amide by consecutive treatment with sodium borohydride and triethylsilane. The enantiomerically pure hosts 3a and 3b were obtained from the racemate by resolution of their N-menthoxycarbonyl derivatives. The racemic compounds rac-3a and rac-3b were prepared from the acid chloride 4 and the ortho-hydroxyanilines 9a and 9b via amide formation, condensation to the oxazole and reduction. Structural data are provided which prove the absolute configuration of compound ent-3b and the relative configuration of compound rac-3a.

ChemInform Abstract: Single-Crystal-to-Single-Crystal Enantioselective [2 + 2] Photodimerization of Coumarin, Thiocoumarin and Cyclohex-2-enone in the Inclusion Complexes with Chiral Host Compounds.

Abstract Single-crystal-to-single-crystal enantioselective [2+2] photodimerization reactions of coumarin (1a), thiocoumarin (1b) and cyclohex-2-enone (2) were found to proceed efficiently in inclusion complexes with (R,R)-(−)-trans-bis(hydroxydiphenylmethyl)-2,2-dimethyl-1,3-dioxacyclopentane (3a), (R,R)-(−)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.4]nonane (3b), and (−)-1,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenylprop-1-ynyl]benzene (4), respectively. Through these reactions, (−)-anti-head-to-head dimer 6a, (+)-anti-head-to-head dimer 6b and (−)-syn-trans dimer 10 were obtained in 100, 100 and 48% ee, respectively.

Single-Crystal-to-Single-Crystal Enantioselective [2+2] Photodimerization of Coumarin, Thiocoumarin and Cyclohex-2-enone in the Inclusion Complexes with Chiral Host Compounds

Single-crystal-to-single-crystal enantioselective [2+2] photodimerization reactions of coumarin (1a), thiocoumarin (1b) and cyclohex-2-enone (2) were found to proceed efficiently in inclusion complexes with (R,R)-(−)-trans-bis(hydroxydiphenylmethyl)-2,2-dimethyl-1,3-dioxacyclopentane (3a), (R,R)-(−)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.4]nonane (3b), and (−)-1,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenylprop-1-ynyl]benzene (4), respectively. Through these reactions, (−)-anti-head-to-head dimer 6a, (+)-anti-head-to-head dimer 6b and (−)-syn-trans dimer 10 were obtained in 100, 100 and 48% ee, respectively.

Resolution of hydrocarbons by inclusion complexation with a chiral host compound

Some racemic unsaturated hydrocarbons, 3- and 4-methyl and 4-vinylcyclohexene, bicyclo[4.3]nonane-2,5-diene, and 3-chloro- and 3,4-dichloro-1-butene were resolved as inclusion complex crystals with a chiral host compound derived from tartaric acid. The inclusion complexation, purified by repeating recrystallization from ether twice and decomposed by heating in vacuo, gave optically active hydrocarbons of 28–75% ee by distillation. The optical resolution by inclusion complexation in a water suspension medium and by fractional distillation in the presence of a chiral host was also applied to these hydrocarbons.

Resolution of omeprazole by inclusion complexation with a chiral host BINOL

Both ( S)-(−)- and ( R)-(+)-enantiomers of omeprazole were directly resolved by inclusion complexation with a chiral host compound ( S)-(−)- or ( R)-(+)-2,2′-dihydroxy-1,1′-binaphthyl in high enantiomeric excess (>99% e.e.).

Enantioselective Single-Crystal-to-Single-Crystal Photodimerization of Coumarin and Thiocoumarin in Inclusion Complexes with Chiral Host Compounds

An intermolecular enantioselective photoreaction by a single-crystal-to-single-crystal transformation has been carried out for the first time, as is evident from X-ray structure analysis and X-ray powder diffractometric studies. This reaction, the dimerization of the title compound to cyclobutane derivative 1 (X=O, S), provides a good example for studying the mechanism of topochemical reactions in the crystal.

Enantioselective Single-Crystal-to-Single-Crystal Photodimerization of Coumarin and Thiocoumarin in Inclusion Complexes with Chiral Host Compounds

An intermolecular enantioselective photoreaction by a single-crystal-to-single-crystal transformation has been carried out for the first time, as is evident from X-ray structure analysis and X-ray powder diffractometric studies. This reaction, the dimerization of the title compound to cyclobutane derivative 1 (X=O, S), provides a good example for studying the mechanism of topochemical reactions in the crystal.

ChemInform Abstract: Enantioselective Photochemical Reactions of N‐Phenyl Enaminones in Inclusion Complex Crystals Using a Chiral Host Compound.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective Photochemical Reactions of N-Phenyl Enaminones in Inclusion Complex Crystals Using a Chiral Host Compound.

Enantioselective reaction of N-methyl-N-phenyl-3-amino-2-cyclohexen-1-one derivatives to the corresponding N-methylhexahydro-4-carbazolones has been accomplished by photolysis in a water suspension of 1:1 inclusion compounds of the starting material with optically active host compounds derived from tartaric acid. 3-(N-Methylanilino)-2,5,5-trimethyl-2-cyclohexen-1-one formed two kinds of dimorphous crystals, and one of these gave an optically active carbazolone derivative by photolysis, but the other one was photochemically inert. X-ray structure analysis showed that two reaction centers, the phenyl and cyclohexenone groups of the reactant, are located in close and distant positions respectively in these two inclusion compounds.