Acidity and Basicity of Indazole and its N-Methyl Derivatives in the Ground and in the Excited State

The tautomeric equilibrium between 1H- and 2H-indazoles both in the ground (S0) and in the excited state (S1) have been investigated by photophysical and thermochemical techniques, as well as by theoretical calculations. In the excited state indazole is 3.8 pKa units more acid (pKa* = 10.10) and 1.8 pKa units more basic (pKa* = 2.87) than in the ground state. The complete thermodynamical cycle connecting the ground and excited states in the gas and condensed phases for 1-methyl- and 2-methylindazoles has been built, allowing us to discuss the relative stability of the 1H- and 2H-indazole tautomers. Our results indicate that the 1H tautomer is more stable than the 2H tautomer and that the difference in energy between them (2.3 kcal mol-1) is the same in the ground and the excited states. The theoretical calculations performed at 6-31G//6-31G level show that this trend is only attenuated but never reversed by the solvation effect of either two water molecules or one formic acid molecule. Both experimental and theoretical results lead to the conclusion that 1-methylindazole is 3.2 kcal mol-1 more stable than 2-methylindazole. However, in order to adequately reproduce the relative stability of benzazoles, the ab initio calculations must include correlation effects (MP2/ /6-31G**//6-31G*).