Chirality Switching in Optical Resolution of Mandelic Acid in C1–C4 Alcohols: Elucidation of Solvent Effects Based on X‑ray Crystal Structures of Diastereomeric Salts

Abstract

Chirality switching in the optical resolution of mandelic acid (MA) using (1<i>R</i>,2<i>S</i>)-2-amino-1,2-diphenylethanol (ADPE) in C1–C4 alcohols is demonstrated herein. Recrystallization of the diastereomeric mixture of the MA salts from <i>longer</i> alcohol solvents (<i>n</i>-PrOH, <i>s</i>-BuOH, <i>i</i>-BuOH, and <i>n</i>-BuOH) produced the (<i>R</i>)-MA salt, whereas the (<i>S</i>)-MA salt was preferentially deposited from <i>shorter</i> alcohol solvents (MeOH, EtOH, <i>i</i>-PrOH, and <i>t</i>-BuOH). Thermogravimetric analysis and ¹H NMR spectroscopy showed that all the solvents employed were incorporated in the diastereomeric salts and the stability of the incorporated alcohols increased with an increase in the effective surface area of their alkyl chains. The X-ray crystal structures of the eight solvated diastereomeric salt pairs revealed that the type of hydrogen-bonding network (sheetlike or columnar) and the arrangement of the columnar structures were controlled by the length of the included alcohol. By comparison of the two diastereomeric MA salt crystal structures, their relative stability to display chirality switching was investigated