Ab initio mechanistic study of the protection of alcohols and amines with anhydrides

Abstract

The acetylation of methanol and methylamine with acetic anhydride was investigated with ab initio calculations in the gas phase using RHF, B3LYP and MP2 with the 6-31+G(d,p) basis set. A six-membered cyclic transition state of acetic anhydride with the reagent was found, thereby indicating that the reaction, in contrast with existing theory, occurs as a concerted process in which acetyl formation and the loss of a proton from the alcohol oxygen or amine nitrogen atom occurs simultaneously. The same mechanism holds for other anhydrides, e.g. t-Boc anhydride, as well as for secondary amines. The energy of activation for these reactions was calculated and both reactions should occur at room temperature.