Kinetic solvent isotope effects and activation parameters for the intramolecular addition–elimination between amino and amide groups in 1-amino-8-trifluoroacetylnaphthalene under acidic conditions

Abstract

Rates of the reaction of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine in the presence of acid have been measured in 70%(v/v) Me2SO–H2O over a range of temperatures and in 70%(v/v) Me2SO–D2O. The dependence of the first-order rate coefficient on hydronium ion concentration has been fitted to the expression k=(k0H+kH[H3O+])/(1 +KH[H3O+]) in which the terms k0H and kH correspond respectively to spontaneous and hydronium ion catalysed reactions of the neutral form of 1-amino-8-trifluoroacetylaminonaphthalene and KH is the equilibrium constant between 1-amino-8-trifluoroacetylaminonaphthalene and its protonated form which is unreactive. Solvent isotope effects and thermodynamic parameters for the individual terms in the rate expression are explained by a mechanism in which 1-amino-8-trifluoroacetylaminonaphthalene reacts by intramolecular addition of the amino group to the amide carbonyl to give a zwitterionic tetrahedral intermediate which undergoes rate-limiting protonation by hydronium ion at the diffusion-limited rate and undergoes a rate-limiting proton switch with participation by water. In particular the kinetic solvent isotope effect on the hydronium ion catalysed reaction is low (kH/kD 1.41) as expected for a diffusion-controlled reaction. The standard entropy change for the intramolecular addition is unfavourable (ΔS°– 81 J K–1 mol–1) and the entropy of activation for the solvent-mediated proton switch is also large and negative (ΔS‡– 61 J K–1 mol–1).