Tautomerism in pyridazin-3(2H)-one: a theoretical study using implicit/explicit solvation models.

The tautomeric conversion of pyridazin-3(2H)-one 1 into pyridazin-3-ol 2 has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-311++G** level. Two mechanisms have been considered for this process: (i) one in which the hydrogen is directly transferred through TS12; and (ii) another one in which a double hydrogen transfer takes place via TS1122 upon formation of the corresponding dimer. The former requires a very high activation energy of 42.64kcal/mol as a consequence of the strain associated with the formation of the four-membered TS12, while the latter requires a much lower activation energy, 14.66kcal/mol. Implicit, explicit, and a combination of both implicit and explicit solvation models, using both protic and aprotic polar solvents, have been considered for the first mechanism. This study allows the establishment of the requirement to use protic polar solvents in order to reduce the high activation energy associated with TS12.