Equilibrium and activation thermodynamic parameters of the tautomerism of 6-methoxy-2-pyridone in water

Abstract

In neutral water, the interconversion of the two tautomers of the lactim–lactam equilibrium of 6-methoxy-2-pyridone occurs essentially via a pH-independent process. The influence of temperature on the position and on the dynamics of this tautomeric equilibrium has been studied by temperature-jump relaxation kinetics. The equilibrium and activation thermodynamic parameters obtained (ΔH° 26.8 kJ mol^–1, ΔS° 58 J K^–1 mol^–1; lactam → lactim, ΔH_c^‡ 46 kJ mol^–1, ΔS_c^‡–40 J K^–1 mol^–1) indicate a high value for the kinetic entropy term. These results indicate that the interconversion mechanism is ionic (rather than concerted) and involves the anionic form of the substrate in a cyclic transition state. In this transition state, at least two solvent molecules would temporarily ensure a hydrogen bond connection between the sites which undergo tautomerism.