Mechanism of esterification of 1,3-dimethylamino alcohols by N-acetylimidazole in acetonitrile and the influence of alkyl and geminal dialkyl substitution upon the rate

Abstract

3-(Dimethylamino)propan-1-ol and seven derivatives with alkyl substituents at the 2-position have been prepared by conventional methods, and second-order rate constants for their esterification by N-acetylimidazole in acetonitrile have been measured under pseudo-first-order conditions both by 1H NMR spectroscopy at a single temperature (23 °C) and by a UV spectroscopic method over the temperature range 25–65 °C. Evidence is presented that the intermolecular esterifications proceed via an initial rate-determining intramolecular general base catalysed formation of a cyclic tetrahedral intermediate. Effective molarities compared with the third-order reactions of simpler alcohols with acetylimidazole catalysed by triethylamine are estimated to be 13–14 mol dm–3, but alkyl substitution at the 2-position of the amino alcohol has only a modest effect upon reaction rates. All reactions have substantial negative entropies of activation and only modest enthalpies of activation as expected for concerted bimolecular reactions with highly ordered transition structures. Three structurally related carbocyclic amino alcohols constitute a short isokinetic series with the isokinetic temperature very close to the experimental range. Along this series, decreasing enthalpies of activation are almost exactly balanced in their contributions to the overall free energy of activation near room temperature by increasingly negative entropies of activation.