Enantioseparation of D/L-mandelic acid with L-phenylalanine in diastereomeric crystallization

Abstract

A mechanistic study of the chiral resolution of mandelic acid by diastereomeric crystallization with L-phenylalanine as the resolving agent was performed. Also, the efficiency of the resolving agent for chiral separation was evaluated. The carboxyl and amine groups of L-phenylalanine were hydrogen-bonded with the hydroxyl and carboxyl groups of mandelic acid for the preferential formation of a complex of L-mandelic acid-L-phenylalanine due to the stereo-configurations of the functional groups, and crystallized out as diastereomeric salt. As a result, L-mandelic acid was enriched up to 85% in the resulting diastereomeric crystals. Moreover, the chiral purity of the diastereomeric crystals depended on the molar ratio of mandelic acid to L-phenylalanine in the solution. With molar ratios ranging from 0.7 to 6.0, the purity of L-mandelic acid in the diastereomeric crystals was improved when increasing the molar ratio, while the molecular ratio of mandelic acid to L-phenylalanine in the diastereomeric crystals remained at 1:1. However, outside this range, there was no chiral separation of mandelic acid, and only racemic crystals of mandelic acid were produced. In addition, XRD and DSC analyses revealed that the structure of the resulting diastereomeric crystals was identical with that of pure L-mandelic acid-L-phenylalanine crystals. Therefore, it was concluded that L-mandelic acid was the template for the diastereomeric crystals, while D-mandelic acid was incorporated in the crystals as an impurity in a solid solution.