Kinetics and equilibria of ring closure through an amide linkage. Part 2. 1-Aryl-2-pyrrolidones

Abstract

Equilibrium constants, and rate constants for forward and reverse reactions, for ring closure of several 4-(arylamino)butanoic acids to 1-aryl-2-pyrrolidones in aqueous acid, together with ionisation constants of the former group of compounds, are reported. The equilibrium constants K at 50 °C between neutral protonic forms of open-chain and ring compounds are related to the ionisation constants of the nitrogen-protonated 4-(arylamino)butanoic acids, K₁, by the equation: log K= 0.70 (pK₁)+ 1.53. The value of K for pyrrolidone itself was measured for comparison. Studies of ¹⁸O exchange reveal that (except in the case of the substrate which bears the most electron-withdrawing substituents in the aryl ring, namely 2,4-dinitro) the rate-determining step lies between the tetrahedral intermediate and the ring compound. Substituent effects and solvent deuterium isotope effects on the hydronium-ion catalysed reaction are consistent with a transition state close to the neutral tetrahedral intermediate. The effects of methyl substituents in the heterocyclic ring on rate and equilibrium constants have also been studied. The variation of K with temperature, and derived thermodynamic parameters, are reported in two cases.