AB-INITIO MOLECULAR-ORBITAL STUDY ON THE MECHANISM OF AMIDE HYDROLYSIS DEPENDENT ON LEAVING GROUPS

The alkaline hydrolysis of amides, N-methyl acetamide 1, acetanilide 2 , and N-acetyl imidazole 3, was investigated by use of ab initio molec ular orbital calculations. A detailed analysis was performed for two p ossible mechanisms, Path 1 and 2. Path 1, similar to ester hydrolysis, releases CH,COOH and RNH whereas Path 2 contains the RNH group that e xtracts the H atom from the OH fragment in the tetrahedral intermediat e. In this mechanism, carboxylate ion and an amine directly form. It w as ascertained that Path 2 is a better route to decompose the TD inter mediate than Path 1 for 1 and 2 in the gas phase. The stability of the leaving group RNH determines which route, Path 1 or 2, is preferred i n the gas phase. The solvent effect was estimated for the two mechanis ms by using the SCRF calculations of the IPCM model. (C) 1997 Elsevier Science Ltd.