Systematic study of chiral discrimination upon crystallisation. Part 2.1 Chiral discrimination of 2-arylalkanoic acids by (1R,2S)-2-amino-1,2-diphenylethanol

Abstract

The resolution of 2-arylalkanoic acids by (1R,2S)-2-amino-1,2-diphenylethanol has been studied. It has been found that the position of a substituent on the aromatic group of the acids affects resolution efficiency to a considerable extent. Crystal structure analysis of the diastereomeric salts has revealed that a columnar hydrogen-bond network is commonly formed in the diastereomeric salts studied. A detailed analysis of the hydrogen-bond networks formed in the diastereomeric salts has enabled clear elucidation of the correlation between crystal structure and efficiency of resolution; differential stability of the crystals of less- and more-soluble salts, which results in large differences in solubility and subsequently in resolution efficiency, is found to arise from the inclusion of water molecules in the less-soluble salt, reinforcing the columnar hydrogen-bond network by strong hydrogen bonds, and from the absence of such water molecules in the more-soluble salt. On the other hand, when the resolution gave poor efficiency, such a remarkable difference in stability between the pairs of diastereomeric salts is not observed.