Tautomerism of oxopyridines and oxopyrimidines: Theoretical study with complete optimization of geometry

The semiempirical MINDO /3 method is employed to calculate the energies of various tautomers of model tautomeric compounds— 2-oxo- and 4-oxopyridines and pyrimidines. The results are compared with experimental data in the gas phase, where the solute–solvent interactions not included in theoretical calculations are absent. Although the relative energies obtained by the MINDO /3 method appear to be superior to other semiempirical and ab initio calculations, the accuracy of the method was determined to be as low as 3–4 kcal/mol. It indicates that it is exceedingly difficult to account theoretically for intrinsic stabilities of the tautomers. The importance of various factors influencing calculated free-energy differences is discussed. Particular attention is paid to the problem of geometry optimization.