Tautomeric behavior of 1,2,4-triazole derivatives: combined spectroscopic and theoretical study

1,2,4-Triazole is a popular scaffold in drug design. According to chemical nature, the triazole ring tends to prototropic tautomerism. Tautomeric phenomena are important for studying the chemical reactivity and interaction of drugs based on triazole with biomolecules in the human body. Theoretical modeling was used to assign structures of newly synthesized 2-(3-hetaryl-1,2,4-triazol-5-yl)anilines. The procedure included quantum-chemical SMD/M06-2X/6–311++G(d,p) calculation of the relative stability for possible tautomers, simulation of UV/vis spectra for the most stable forms, and comparison of the resulting curves with the experimental spectral data taking into account the Boltzmann weighting. The influence of the substituents in triazole ring on tautomeric equilibrium was elucidated. NBO charge distribution, dipole moment, molecular electrostatic potential, and HOMO/LUMO gap for the most stable tautomers were analyzed.