A theoretical study of the protomeric equilibrium of 6-chloro-2-hydroxypyridine in the gas phase and in solution

Abstract

The equilibrium between 6-chloro-2-hydroxypyridine and 6-chloro-2-pyridone has been studied theoretically in the gas phase, in water and in carbon tetrachloride using a combination of electronic structure calculations, including geometry optimization and electron correlation, and molecular dynamics simulations. The use of a 6–31G** basis with correlation, correctly predicts the increased stability of the enol form upon chlorine substitution at the 6 position and, at the MP4 level, yields agreement with the gas phase energetics to within 1.5 kcal mol^–1. The accuracy of the computer simulations in predicting the differential free energy of solvation of the two tautomers in water is also ca. 1.5 kcal mol^–1, whilst for solvation in carbon tetrachloride the corresponding accuracy is ca. 0.2 kcal mol^–1.