TAUTOMERISM OF HYDROXY-PYRIDAZINES : THE N-OXIDES

Abstract We present a comprehensive theoretical study of the structure and tautomerism of the four isomeric hydroxy-pyridazine N -oxides, as well as pyridazine-1,2-dioxide. Gas-phase properties are modelled with high-level ab initio calculations employing large basis sets (6-311++G(3df,3pd)) and quadratic configuration interaction treatment of electron correlation (QCISD(T)). Since these acidic heterocycles are of interest as novel carboxylate bio-isosteres, their anionic conjugate bases are also examined. Aqueous solution-phase properties are investigated using the isodensity polarised continuum model (IPCM), and the semi-empirical AM1–SM2 and PM3–SM3 models, and relative acidities compared. The calculated properties are generally in good agreement with existing experimental data, indicating that the 1-hydroxy tautomer predominates both in the gas phase and in solution in the case of the 6-substituted system, and that hydroxy-1-oxide tautomers predominate in the 3- and 5-substituted systems. The behaviour of the 4-substituted isomer is less clear, with non-planar 1-hydroxy and planar 4-hydroxy tautomers being similar in stability.