Quantum Chemical Consideration of Substituent Effects on Tautomeric Properties of 2-Pyridones–2-Pyridinols

Abstract The tautomeric properties of 2-pyridones–2-pyridinols exerted by the substituent effect were discussed on the basis of quantum chemical quantities deduced from molecular orbital (MO) calculations. A substituent at the 6-position has the greatest stabilizing effect. The magnitude of this effect was greater on the 2-pyridinol form than the 2-pyridone form, irrespective of the nature of the substituent. This led to a large predominance of the 2-pyridinol form on the 6-polar-substituted derivatives to such an extent that it was observed by conventional UV measurements at ambient temperature. In the 6-methyl derivative, the 2-pyridinol form was not observed by a similar measurement due to the weak substituent effect. The association ability is still an important factor in determining tautomeric equilibrium in a solution, resulting in a strong lability to the molecular environment. The substituent effects on the stabilities of both tautomers were shown to be correlated with the N-atomic charges and ring structural modifications of the tautomers.