On the Role of Water in Amide Hydrolysis

Abstract

Abstract The mechanism of the water‐assisted amide hydrolysis of N ‐methylacetamide has been elucidated by Car‐Parrinello simulation and related to prior investigations of the acid‐ and the base‐catalyzed pathways. Each process was investigated in aqueous solution, and the water molecules were found to play a crucial role in the amide hydrolysis, with several reaction steps involving proton‐transfer events in which the water molecules serve as donors or acceptors. This calls for a quantum treatment of all electronic degrees of freedom, including those of the solvent molecules. A detailed analysis of the mechanisms of the amide hydrolysis pathways obtained from our simulations is given. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)