Investigation of Stability and Structure in Three Homochiral and Heterochiral Crystalline Forms of 3-Phenyllactic Acid

Abstract

3-Phenyllactic acid (3PLA) is a new example of a chiral compound that can form a conglomerate or a racemic crystal upon crystallization of racemic 3PLA. In this study, homochiral crystals (1), heterochiral racemic crystals (2) (reported here for the first time), and conglomerates (3) of 3PLA were prepared, and the thermal stability, crystal structures, and spectroscopic properties of 1À3 were investigated. Crystals of 1 and 3 formed from aqueous solution as needles (orthorhombic, P2 1 2 1 2 1 ), while crystals of 2 formed from 3:1 hexanesÀethyl acetate as rectangular blocks (monoclinic, P2 1 /c). The pure enantiomer and conglomerates are unusual in that they exhibit slightly greater thermodynamic stability than the racemic form (Δ(ΔH fus ) = 4.0 kJ/mol) despite having considerably lower density (ΔF calc = 3.7%) and less efficient molecular packing in accordance with Wallach's Rule. Considering that molecules of 3PLA adopt essentially identical conformations in the homochiral and heterochiral crystals, the higher stability in crystals of pure enantiomer (1 and 3) results from stronger hydrogen-bonding interactions via homochiral packing as compared to heterochiral packing in racemic crystals (2). 3PLA therefore provides a unique test system to investigate the influence of surface energetics and solvation in biasing homochiral vs heterochiral nucleation to develop methods for enantioseparation via crystallization.

Spontaneous Resolution of Chiral 3-(2,3-Dimethylphenoxy)propane-1,2-diol under the Circumstances of an Unusual Diversity of Racemic Crystalline Modifications

“…The crystallization of diol 1 discussed herein has much in common with the crystallization of 3-phenyllactic acid, studied in the Navare and MacDonald paper . In both cases, racemic conglomerate and several polymorphs of racemic compound can crystallize from the racemic feed material depending on the conditions.…”

“…The crystallization of diol 1 discussed herein has much in common with the crystallization of 3-phenyllactic acid, studied in the Navare and MacDonald paper. 13 In both cases, racemic conglomerate and several polymorphs of racemic compound can crystallize from the racemic feed material depending on the conditions. In both cases, Wallach's rule is formally observed, and homochiral crystals are less dense than racemic crystals; however, the firsts melt at higher temperatures.…”

“…Polymorphism is an evergreen theme for researchers of molecular crystals. , Current interest in this problem is largely supported by the needs of pharmaceutical science and industry. , In recent years, chiral compounds are increasingly becoming objects of the research. − An additional feature of chiral systems that is absent in the case of achiral substances is the possible interconversion of homochiral (scalemic, enantiopure) and heterochiral (mainly racemic) crystalline forms. − In the strict sense of the word, conglomerate homochiral crystals are not polymorphic with respect to any racemic solid. However, like ordinary polymorphs, those and others can be formed from a common feed medium (solution or melt) and can transform into each other both as a result of solid-phase transitions and as a result of contact with the common liquid phase .…”

Bioorganic Research of Galactites tomentosa Moench. Honey Extracts: Enantiomeric Purity of Chiral Marker 3‐Phenyllactic Acid

“…The (-)-enantiomer possess known (S) absolute configuration. 18 All chromatograms of the extracts unequivocally showed the predominant presence of (-)-3-phenyllactic acid enantiomer, while the opposite (+)-enantiomer was not detected in any sample. Because of polarimetric detector sensitivity, enantiomeric excess was estimated to be >95%.…”

Сhiral and Racemic Fields Concept for Understanding of the Homochirality Origin, Asymmetric Catalysis, Chiral Superstructure Formation from Achiral Molecules, and B-Z DNA Conformational Transition

“…Also, data on solubility and some other physical properties show that racemates tend to be slightly more stable than pure enantiomers. The simplest explanation of Wallach's phenomenon is associated with a difference in hydrogen bonding energies of "true" racemates and pure enantiomers [253][254][255][256][257][258][259][260]. Opponents of this concept validity believe that "true" racemates and pure enantiomers with analogous H-bonding are not rare in occurrence [261][262][263][264][265][266].…”