What is the mechanism of catalysis of ester aminolysis by weak amine bases? Comparison of experimental studies and theoretical investigation of the aminolysis of substituted phenyl esters of quinoline-6- and -8-carboxylic acids

The mechanisms of aminolysis of substituted phenylquinoline-8- and -6-carboxylates (Q-8 and Q-6) were evaluated using AM1 semiempirical and HF/6-31+G(d) ab initio quantum mechanical methods to study the ammonolyses of the model systems vinyl cis-3-(methyleneamino)acrylate (M1), cis-2-hydroxyvinyl cis-3-(methyleneamino)acrylate (M2), and vinyl trans-3-(methyleneamino)acrylate (M3). Both experimental and computational results support the formation of a tetrahedral intermediate in the reaction. The imine nitrogens of the Q-8, M1, and M2 esters are in position to catalyze aminolysis of the esters, whereas the imine nitrogens of the Q-6 and M3 esters are not. Ammonia attack on the M1 and M2 esters occurs at a hydrogen bonding distance above the imine nitrogen. This hydrogen bond prevails in the tetrahedral intermediate and during alkoxide departure. In a sequential step prior to diffusion apart, the very acidic N-protonated amide protonates the leaving alkoxide. Abstraction of the proton from the -NH3+ substituent of the zwitterionic tetrahedral intermediate by imine nitrogen is thermodynamically highly unfavorable. The previously proposed proton slide mechanism involving catalysis by the imine nitrogen of intramolecular proton migration converting R-C(OR')(O-)(NH3+) to R-C(OR')(OH)(NH2) is not supported by the present study. The results of this study are fully consistent with the experimental observations for the aminolyses of substituted Q-8 and Q-6 esters.