Anilide formation from an aliphatic ester. The mechanism of cyclisation of methyl 3-(2-aminophenyl)propionate

Abstract

The cyclisation of methyl 3-(2-aminophenyl)propionate to dihydroquinolone is both general acid and general base catalysed. General base catalysis involves the diffusion-controlled, rate-determining removal of a proton from a zwitterionic tetrahedral intermediate, as observed for reactions with more basic amines. But the general acid catalysed proton transfer is concerted with heavy atom reorganisation, and a mechanism involving the rate-determining breakdown of a neutral tetrahedral intermediate is proposed. The kinetics require independent routes to the two tetrahedral intermediates, and it is shown that the cyclisation of the conjugate acid of the amino-ester is an important pathway for ester aminolysis by weakly basic amines.