THEORETICAL STUDY OF THE MOLECULAR MECHANISM AND REGIOSELECTIVITY OF THE (3+2) CYCLOADDITION REACTION BETWEEN BENZONITRILE OXIDE AND 2,4-DIMETHYL-2<i>H</i>-1,2,3-TRIAZOLE AND MOLECULAR DOCKING STUDIES OF THE OBTAINED CYCLOADDUCTS

Abstract

Reaction pathways for (3+2) cycloaddition between 2,4-dimethyl-2H-1,2,3-triazole and benzonitrile oxide were explored in detail at the B3LYP/6-31G(d) level of theory. This cycloaddition reaction proceeds through nonconcerted mechanism. Analysis of the relative energies associated with the competitive reaction pathways shows that the cycloaddition reactions of 2,4-dimethyl-2H-1,2,3-triazole and benzonitrile oxide are highly regioselective. The electronic structures of the reactants and products formed were analyzed using the electron localization function (ELF). The energy profiles of the four regioisomeric reaction pathways, as well as the ELF topology of the transition state structures, were examined to elucidate the origin of regioselectivity in these (3+2) cycloaddition reactions. A subsequent docking analysis is conducted on four cycloadducts in relation to the main protease of SARS-CoV-2 (6LU7), alongside 1HSG of HIV-1 ligand.