Enantiomer separation of 2‐halomandelic acids via diastereomeric salt formation with chiral N‐substituted 2‐amino‐2‐phenylethanols

Abstract

AbstractChiral N‐substituted secondary 1,2‐aminoalcohols have been developed for the enantioseparation of ortho‐halomandelic acids (o‐X‐MAs) via diastereomeric salt formation. Two structural isomers, N‐methyl‐2‐amino‐1,2‐diphenylethanol and N‐benzyl‐2‐amino‐2‐phenylethanol, showed high separation abilities for o‐X‐MAs (X = Cl, Br, I). The chiral recognition mechanism was elucidated by crystallographic analysis of the less‐soluble salts. The substituents on the nitrogen atom of the resolving agents and the inclusion of the crystallization solvent stabilized the salt and enhanced their separation ability.