Racemic Crystals Research Articles

Resolution of optical isomers of 4-amino-p-chlorobutyric acid lactam by co-crystallization

4-Amino-p-chlorobutyric acid lactam crystallizes as racemic crystals in the monoclinic space groupP21/n, witha=5.006(2),b=6.783(2),c=27.652(2) A, β=92.25(1)°,Z=4,R=0.035 for 1618 unique reflections. As both enantiomers are present in a single crystal it is not possible to effect enantiomeric separation by crystal growth inhibition. This lactam may, however, be co-crystallized with (2R,3R)-(+)-tartaric acid forming a 2:1 complex in which only the (R) enantiomer is present. The complex crystallizes in the monoclinic space groupP21 witha=10.074(2),b=10.132(6),c=12.238(6) A, β=99.13(2)°,Z=2,R=0.036 for 2291 unique reflections. Complex formation is effected by hydrogen bonding but enantioselectivity does not involve the chiral center of the title compound directly.

Compounds of Germanium and Tin, 18. Cleavage Reactions of Hexa‐tert‐butylcyclotrigermane: Racemate versus Conglomerate Crystallization

AbstractTreatment of hexa‐tert‐butylcyclotrigermane (3) with CCl4, Br2, and I2 furnishes the correspondingly substituted 1,3‐dichloro‐ (4), 1,3‐dibromo‐ (5), and 1,3‐diiodotrigermanes (6). The symmetries of the molecules of 5 and 6 are very similar (point group C1) revealing gauche‐anti conformations and different GeGe bond lengths. However, while 5 crystallizes as a racemate, 6 forms a conglomerate of enantiomerically pure crystals. The X‐ray structure analysis of the 1,3‐dimethyltrigermane (7) derivative, derived from 6 by a sequence of metalation and methylation reactions, reveals more symmetrical molecules of the point group C2 which also crystallize as a racemate. Irradiation of 3 leads to tetra‐tert‐butyldigermene (8) and di‐tert‐butylgermylene (9) which could be trapped by addition and cycloaddition reactions with selenium, tellurium, and 3,5‐di‐tert‐butyl‐1,2‐benzoquinone.

Chiral Discrimination in the Solid and the Solution States

Abstract Crystal packing modes were compared for the active and the corresponding racemic crystals obtained for various representative compounds. In the case of 1,1′-binaphthyl, the molecular conformation itself was different in the two crystal forms. For metal complexes of D3 symmetry with three-bladed propeller shape, there appear to be only a few favoured crystal packing modes, which is in good agreement with our dispersion energy calculations. Using CD spectroscopy and X-ray crystallography, chiral discriminations of optically labile chromium complexes of D3 symmetry have been investigated in the solid and the solution states.

Polymorphism of Compound Existing as Both Racemic Compound Crystals and Mixed Crystals of Enantiomers

Abstract By recrystallization of certain racemic compound (ST), racemic compound crystals, mixed crystals of two enantiomers, or a mixture of these two types of crystals were obtained, depending on the recrystallization conditions employed. Their crystal forms were determined by X-ray diffraction of the single crystals and powdered materials. The space group and lattice parameters of the mixed crystals were identical with those of the enantiomeric crystals. This polymorphism of ST crystals would be ascribed to the small difference in the thermodynamic stability between the enantiomeric and racemic crystals. The physicochemical properties of ST are described, too.

Physicochemical properties of suplatast tosilate racemate and enantiomers

The physicochemical properties of the enantiomer and racemates of suplatast tosilate (ST) were investigated by means of infrared spectroscopy, solid-state 13C CP/MAS NMR spectroscopy, thermal analysis, and X-ray diffraction analysis, and by measuring the solubility and hygroscopy. The infrared and NMR spectra and X-ray diffraction pattern of the enantiomer were distinctly different from those of the racemate. The melting point of the enantiomer was lower than that of the racemate by 5 degrees C, while the solubility of the enantiomer was 1.3 times higher than that of the racemate. The hygroscopic rate of the enantiomer was greater than that of the racemate. These results suggested that ST was classified into a racemic compound crystal. Furthermore, by comparing the relative peak intensity ratios on X-ray diffraction patterns of the crystals with various optical purities prepared by recrystallization, it was found that a mixture of racemic compound crystals and either of racemic mixture crystals or racemic solid solutions was obtained by recrystallization of ST in the content of 0 to 64%ee, while the recrystallization of ST in the content of more than 64%ee led to the formation of racemic mixture crystals or racemic solid solutions.

Time-Resolved Diffuse Reflectance Studies of β-Phenyl Ketones in the Solid State: Conformational and Chiral Control of Triplet Lifetimes

The triplet states of ketones having a β-aryl substituent, such as 2 and 3, decay in solution by a charge transfer interaction between this aryl group and the excited carbonyl. In the solid state, this interaction also provides an efficient mode of deactivation for 3, but not for 2, reflecting the proximity between the π-ring system in 3, but not in 2, where the molecules crystallize (X-ray) in a stretched conformation. In the case of 3, the triplet lifetime in the solid state is 420 ns for the pure R or S enantiomers, but 733 ns for the racemic crystals, showing an interesting case of chiral discrimination. Powder X-ray and solid state NMR data suggest that conformational and packing differences between the enantiomers and racemic crystals are responsible for differences in the efficiency of intramolecular deactivation.

Mechanism of the Stereocomplex Formation between Enantiomeric Poly(lactide)s

Poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) crystallize into a stereocomplex with a melting point 50 °C higher than the crystals of the enantiomers. The racemic crystal is formed by packing ‚-form 31-helices of opposite absolute configuration alternatingly side by side. Single crystals of the stereocomplex exhibit triangular shape. The drastic difference of the powder patterns evidences the different packing of the ‚-form in the stereocomplex and in crystals of the pure lactides. By force field simulation of the stereocomplex and the PLLA unit cells and of their powder patterns, the reasons for the different packing could be clarified. Between the ‚-helices in the stereocomplex, van der Waals forces cause a specific energetic interaction-driven packing and, consequently, higher melting point. Helices of identical absolute configuration pack different from pairs of enantiomer ‚-helices. Packing favors R-type helication. A well-defined 103-helix has not been found. Good agreement with the experimental powder patterns proves the correctness of the simulations. On the basis of morphology, packing calculations, and atomic force microscopy, we propose a model of stereocomplex crystal growth, which explains the triangular shape of single crystals. Thus, for polymer components beyond chain folding length, the stereocomplex formation by simultaneous folding of the two types of chains is plausible. The triangular type of crystallizing offers favorable position for the polymer loops during the crystal growth. Our study of the PLA complexation mechanism may offer a chance to predict other polymeric stereocomplexes and their properties.

特集―分子性結晶ダイナミックス 結晶相不斉反応

The generation of asymmetry in a chiral crystal environment is very interesting in view point of the origin of life as well as organic syntheses. Two subjects are discussed; one is the asymmetric photoisomerization in chiral crystalline field and the other is a racemic-to-chiral transformation in a racemic crystal on exposure to visible light. Since the reactions proceed with retention of the single crystal form, the processes can be easily observed by X-ray analysis and the mechanism is explained on the basis of the reaction cavity which represents the void space around the reactive group in the crystal structure.

Helically chiral thia- and diselena-quinquephenylophanes

Helically chiral thia- and diselena-quinquephenylophanes have been synthesized starting from suitable benzene derivatives via an 8-step synthesis path. Helical thiaquinquephenylophane 9 was obtained from bis(bromomethyl)quinquephenyl 8 in cyclisation with thioacetamide under high-dilution conditions in 10% yield. The corresponding diselenaquinquephenylophane was obtained in 17% yield by using KSeCN and reduction. The M- and P-enantiomers of the thiaphane were separated by HPLC using the Okamoto resin. The CD and UV spectra of the pure M- and P-enantiomers of the thiaphane were recorded. X-Ray structure analyses of the racemic crystals were performed for both compounds. Unit-cell parameters: 9, a= 10.952(1), b= 11.896(2), c= 9.804(1)A, α= 104.19(1), β= 111.71(1), γ= 80.19(1)°, V= 1146.0(3)A3; 10, a= 10.304(2), b= 15.204(4), c= 9.128(1)A, α= 105.08(2), β= 113.72(1), γ= 93.41(2)°, V= 1242.2(5)A3. In addition, a dimeric selena-bridged [3.3]quinquephenylophane was observed, and its presence confirmed by FAB-MS and 77Se NMR spectroscopy.

Structure determination of racemic trichogin A IV using centrosymmetric crystals.

Direct methods of crystal structure solution are greatly facilitated in centrosymmetric space groups where the complexity of the phase-problem is reduced. For most peptides and proteins, crystallization in a centrosymmetric arrangement is precluded by an intrinsic dissymmetry due to the constituent chiral amino acid residues. The synthetic accessibility of peptide sequences containing amino acids of either chirality offers the possibility for co-crystallization of racemic crystals. We report here the first use of such an approach for the de novo structure determination of a medium-sized molecule, trichogin A IV, which is a constituent of a fungal lipopeptaibol mixture possessing membrane-modifying properties of biological interest.

Enantioselective Transfer of Molecules from Crystal to Crystal

Abstract When a mixture of powdered optically active host and racemic guest crystals is kept at room temperature, enantioselective transfer of guest molecule occurred from the racemic guest crystal to the host crystal and an inclusion crystal of the host and optically active guest molecules. When powdered inclusion crystal of an optically active host and a prochiral guest is mixed with powdered crystalline reagent and the mixture is kept at room temperature, enantioselective approach of the reagent to the prochiral quest molecule was occurred and optically active product was obtained.

The phenomenon of conglomerate crystallization. XXXV. The crystallization behaviour of {cis-α-Co(trien)ox]Cl}2·9H2O (1), cis-β-Co(3,2,3-tet)ox]Cl·4H2O(2), {cis-α-Co(trien)ox]NO3}2· H2O (3), and [mer-Co(dien)ox (NO2)] (4)

As expected from previous studies, the four title compounds crystallize as racemates from H2O solutions allowed to evaporate at room temperature (ca. 18° C). All four complexes have been characterized by X-ray crystallography. The outer, six-membered rings in (2) are in the chair conformation; and, in the first three species, the secondary nitrogens are chiral centres. In (1) the five-membered rings of the two cations in the asymmetric unit are characterized: Co(1), δ, δ and λ, with the chiralities of the secondary nitrogens (S) and (S); Co(2), λ, λ and δ, with secondary nitrogens (R) and (R). In (3), the five-membered rings of the two cations in the asymmetric unit are: Co(1), δ, δ and λ, with secondary nitrogens (S) and (S); Co(2), δ, λ and δ, with secondary nitrogens (S) and (S). In (2), the five-membered ring is δ and the chiralities of the secondary nitrogens are (R) and (R). In (4), the unique five-membered ring is λ and the central —NH— fragment lies at a mirror plane. Comparison of the crystallization pathways of these complexes with those of related substances are made, and suggestions as to why (1)–(4) select the racemic crystallization pathway are offered.

Optical Enrichment of Chiral Racemic Crystals on Exposure to Visible Light

Abstract The racemic complex of (1-cyanoethyl)(piperidine)cobaloxime crystallizes in an isomorphous structure to its chiral one. In either crystal one of the two crystallographically independent molecules is gradually inverted to have the opposite configuration on exposure to visible light retaining the single crystal form. This brings about optical enrichment for the crystal of racemic complex. The final structures produced by the complete irradiation for the chiral and racemic crystals are converged to the same one. The ratio of the R and S configuration of the partly inverted molecule in the final structure is not 50:50 but 60:40, which is well explained by the shape of the reaction cavities for the cyanoethyl group before and after the partial inversion. Another racemic complex crystal with pyrrolidine instead of piperidine seems to exhibit a similar optical enrichment.

Organic Reactions in Crystals.

By utilizing the phenomenon that molecules move from crystal to crystal quite easily under appropriate conditions, a new type of organic chemistry has beencontrived. The combination of the enantioselective molecular movement from racemic guest crystal to chiral host crystal with fractional distillation, leads to a process whereby enantiomeric guest molecules can be separated by distillation. Selective and efficient organic reactions can be carried out by grinding crystals of substrate and reagent.

Molecular crystal engineering by shape mimicry

Based on the high statistical preference for organics in general and true racemates in particular to pack in one of the centrosymmetric space groups, formation of molecular crystals of single enantiomers of shape-symmetric molecules was predicted to occur with approximate crystallographic symmetry. Thus, enantiomerically pure sulfoxide 1 was designed with two segments of nearly identical shape but with significantly different electron-dono/acceptor properties. Packing of 1 was predicted to occur in a near-centrosymmetric or quasicentrosymmetric fashion, with pairs of 1 arranged as would be expected for a true racemic crystal

π‐Facial hydrogen bonding in the chiral resolving agent 2,2,2‐trifluoro‐1‐(9‐anthryl)‐ethanol and its racemic modification

Abstract2,2,2‐Trifluoro‐(9‐anthryl)‐ethanol (TFAE) has been extensively used, in its pure enantiomeric forms, as a chiral solvating agent in nuclear magnetic resonance spectroscopy (NMR). It has also played an important role in the development of chiral stationary phases in liquid chromatography (LC). X‐ray crystallography of the enantiomeric and racemic crystals shows, in both cases, the formation of an intermolecular hydrogen bond between the OH and the π‐face of one of the rings of the anthracene aromatic system.1 Few examples of such hydrogen bonding have been published previously, and those that have are not as clear cut as in this case. An explanation for the hydrogen bonding is sought using molecular modelling via the PM3 analytically derived molecular electrostatic potentials. Using NMR and dynamic lineshape analysis, the barrier to rotation about the aryl‐carbon bond is estimated, indicating the CCF3 bond to be perpendicular to the anthracene axis in nonpolar solution. This conformation is identical to the conformation in the crystal. Evidence is also presented to support the formation of intermolecular π‐facial hydrogen bonding in TFAE solutions. It is thought that such hydrogen bonding may be implicated in chiral recognition using this compound. © 1994 Wiley‐Liss, Inc.

Investigation of the chirality dependence of thermal properties in chiral-racemic mixtures of the cholesteric ester CE6

Abstract A scanning adiabatic calorimetric technique has been used to study the thermal properties of the chiral and racemic liquid crystal CE6 and the phase diagram covering the cholesteric phase, the three blue phases and the isotropic phase. The purpose of this investigation is to study thermal properties of liquid crystals as a function of chirality, while all other parameters remain constant. Results for the temperature and the chirality dependence of the enthalpy and of the heat capacity are reported. The latent heats between the cholesteric phase and BPI and between the different blue phases change slightly as a function of the chirality. The total heat of transition at the isotropic phase boundary is independent of the chirality, but with decreasing chirality, we observe a large increase in the latent heat and, correspondingly, a decrease in the pretransitional contribution. These experimental facts are in qualitative agreement with the predictions of a Landau–de Gennes theory for blue phases.

The phenomenon of conglomerate crystallization. Part 34. Crystal structures of the conglomerate (–)599-K[cis-α-Λ(δλδ)-Co(edda)(No2)2] and of the racemate K[cis-α-Λ(δλδ)-Co(edda)(NO2)2]·H2O (edda = ethylenediamine-N,N′-diacetate)

A racemic solution of K[cis-α-Co(edda)(NO2)2]1(edda = ethylenediamine-N,N′-diacetate) was found to crystallize as a conglomerate in the enantiomorphic, orthorhombic space group P212121. An acidified solution of it produced racemic crystals of K[cis-α-Co(edda)(NO2)2]·H2O 2, space group P, as well as conglomerate crystals of 1. Their crystal structures and the absolute configuration of 1 were determined. In both species the anions form infinite strings which are linked to one another by the potassium cations (and/or waters, where relevant, 2). With 1 the helical strings are homochiral, while with 2 pairs of spiral strings have opposite helical chirality, as expected from the fact that they are related to one another by an inversion centre.

On the validity of Wallach's rule: on the density and stability of racemic crystals compared with their chiral counterparts

On the validity of Wallach's rule: on the density and stability of racemic crystals compared with their chiral counterparts

Fast molecular reorientations in liquid crystals.

We report investigations on fast individual molecular reorientations in isotropic, nematic (N), and smectic-A (Sm-A) phases of chiral, achiral, and racemic liquid crystals. These motions, in the ${10}^{\mathrm{\ensuremath{-}}11}$-${10}^{\mathrm{\ensuremath{-}}10}$ s range, are probed by the degenerate four-waves-mixing technique and compared to results obtained by other techniques. In homeotropic N and Sm-A phases of achiral compounds and racemic mixture, the individual reorientation time about the long molecular axis is found to be unchanged down to the Sm-A\ensuremath{\rightarrow}Sm-C transition, but increases by a factor of about 3 with a chiral compound. A quantitative comparison between theoretical prediction and experiment is presented. This result is in agreement with our previous work [Phys. Rev. Lett. 62, 3049 (1989)] and does not support the recent theoretical work by Brand et al. [Phys. Rev. Lett. 64, 1309 (1990)] as well as the results of the dielectric spectroscopy experiments of Kremer et al. [Phys. Rev. A 42, 3667 (1990)] performed at inappropriately low frequencies.