Tautomerism of protonated imidazoles: A perspective from ab initio valence bond theory

The tautomerism of protonated imidazoles concerns one aromatic (1H-Imi+) and one nonaromatic (4H-Imi+) tautomers. Both experiments and computations have shown that substituents to the imidazole ring can change the relative stability of tautomers. A detailed theoretical study of the inherent mechanism would benefit the rational design of experimental syntheses related to imidazoles. In this work, we used the block-localized wavefunction (BLW) method to explore the factors governing the tautomerism between 1H-Imi+ and 4H-Imi+. While π resonance always favors the aromatic tautomer 1H-Imi+, the aromaticity noticeably reduces with electron donating groups (EDGs) as substituents due to the increased π-π repulsion, leading to the stability of 4H-Imi+ over 1H-Imi+ with EDGs such as NH2 and OH. For electron withdrawing groups (EWGs), the reduced π-π repulsion promotes the aromatic stability and favors 1H-Imi+. DFT computations were also performed to study the tautomerism mechanisms. Results show that tautomerism can hardly occur in gaseous phase, but in aqueous solution, water molecules can build hydrogen bonding network with 1H-Imi+ and facilitate the hydrogen transfers.