Base-Mediated Oxidative Degradation of Secondary Amides Derived from p-Amino Phenol to Primary Amides in Drug Molecules

Abstract

One of the most common functional groups encountered in drug molecules is the amide, and the most common degradation pathway for amides is base-mediated hydrolysis to its constituent amine and carboxylic acid. Herein, we report for the first time, a base-mediated oxidative degradation pathway of secondary amides to primary amides. This transformation also represents a novel synthetic methodology, reported for the first time in this work, in transforming secondary amides to primary amides without using any oxidative reagents. The introduction of this mechanism into the pharmaceutical literature is important given that the mechanism and required reactants are present to carry out the chemistry in dosage forms.