Electrophilic heteroaromatic substitutions. 8. Studies on the mechanism of the alfa-side-chain aminomethylation and hydrogen/deuterium isotope exchange reactions of alfa-methylpyrroles

A kinetic investigation of the acid-mediated a-side-chain (dimethy1amino)alkylation and hydrogenldeuterium isotope exchange reactions of ethyl 1,3,4,5-tetramethylpyrrole-2-carboxylat(e1 ) and ethyl 4-bromo-1,3,5-trimethylpyrrole- 2-carboxylate (2) in aqueous acetonitrile has been carried out. The effect of a number of variables, such as nature and concentration of the catalyzing acid, amount of water in the reaction medium, and concentration and type of the electrophile, on the reaction rate indicates that both processes are subject to general acid catalysis and that their limiting step is electrophilic attack on an a-methylenepyrroline. The influence on the rate of the Mannich reaction of the nuclear substituent adjacent to the side chain undergoing attack is also discussed. The conditional dissociation constants of acetic and formic acid in 95% aqueous acetonitrile have been measured