A New Mechanism for Amide Hydrolysis

PREVIOUS work on acid-catalysed amide hydrolysis has indicated that the reaction is bimolecular: in the rate-determining step the conjugate acid of the amide is attacked by a water molecule 1 . This conclusion is derived from three types of evidence. It has been shown that in concentrated aqueous acid solutions the rate of hydrolysis of a number of simple amides increases with the proportion of water in the solvent 2 ; that polar substituents in the acyl part of the amide molecule have very little effect on the rate 3 ; and that the rate is substantially diminished by groups, for example, ortho substituents in benzamides, which shield the reaction centre from attack by other molecules 3 4 .