Solvent effects in the excited-state tautomerization of 7-azaindole: a theoretical study

The solvent effect often changes the mechanism of a chemical reaction. Experimental studies of the excited-state tautomerization of 7-azaindole (7AI) suggested that the intrinsic reactions occur via the concerted triple and double proton transfer mechanisms in the gas and liquid phases, respectively. Theoretical study is required to understand how the solvent effect changes the mechanism; however, such studies have rarely been performed in the excited-state. In this study, systematic quantum mechanical calculations were performed to study the excited-state tautomerization of 7AI in methanol. Electronic structures and energies for the reactant, transition state, and product were computed at the complete active space self-consistent field levels with the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The IEFPCM and SM8 methods were used to include solvent effect in the excited and ground-state calculations, respectively. The excited-state double proton transfer (ESDPT) in 7AI-CH(3)OH and the triple proton transfer (ESTPT) in 7AI-(CH(3)OH)(2) both occur via a concerted but asynchronous mechanism. The ESTPT barrier was smaller than the activation energy of solvent reorganization; however, the amount of 7AI-(CH(3)OH)(2) in methanol is very small because the complex formation is entropically very unfavorable. Therefore, the ESTPT is not an important path. The MRPT2 barrier of ESDPT was 2.8 kcal/mol, which agrees very well with the experimental value. The MRPT2 barrier of deuterium (D) transfer is larger than the activation energy of solvent reorganization; therefore, the intrinsic D transfer is rate-limiting, while the proton transfer must compete with solvent reorganization. The time-dependent density functional theory (TDDFT) was also used for comparison. Most TDDFT methods used in this study failed to predict transition state structures or barriers of the excited-state tautomerization. Additionally, the TDDFT levels failed to predict correct dipole moments in the excited-state, which produced an unreliable solvent effect on barrier heights.