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.