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

Chirality
switching in the optical resolution of mandelic acid
(MA) using (1R,2S)-2-amino-1,2-diphenylethanol
(ADPE) in C1–C4 alcohols is demonstrated herein. Recrystallization
of the diastereomeric mixture of the MA salts from longer alcohol solvents (n-PrOH, s-BuOH, i-BuOH, and n-BuOH) produced the (R)-MA salt, whereas the (S)-MA salt was
preferentially deposited from shorter alcohol solvents
(MeOH, EtOH, i-PrOH, and t-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.