Racemization during aminolysis of mixed and symmetrical anhydrides of N‐alkoxycarbonylamino acids by amino acid anions in aqueous dimethylformamide

Abstract
Racemization attending the aminolysis of symmetrical (Sy) and mixed (Mx) anhydrides (An) of N‐alkoxycarbonylamino acids by amino acid anions in aqueous dimethylformamide has been examined by reversed phase high‐performance liquid chromatography analysis of the N‐protected dipeptides produced. Racemization occurred in most cases when the anion was generated using 1 equiv. sodium hydrogen carbonate, in most cases for MxAn reactions when the base was sodium carbonate, and only in a few cases for SyAn reactions when the base was sodium carbonate. Less racemization was associated with MxAn reactions when the chloroformate of a secondary alcohol had been used for their generation. The change in chirality is explained on the basis of the formation and racemization of the 2‐alkoxy‐5(4H)‐oxazolone, which is greater in the presence of the weaker base because of incomplete deprotonation of the amino acid zwitter‐ion.