Computational Study of Regioselectivity in Synthesis of Substituted 1,2,3-Triazoles from Click Reaction of Azides with Propiolates Using Quantum Chemistry Methods

Click synthesis of 1,4 and 1,5-disubstituted 1,2,3triazoles from benzyl azide and ethyl propiolate has been studied by means of Density Functional Theory (DFT) from the structural and thermochemical viewpoints in the gas phase and in presence of three different solvent, water, dioxane and tetrahydrofuran (THF) using polarized continuum model. On the basis of calculated thermodynamical results, it has been demonstrated that the production of 1,4-disubstituted regioisomer is more favorable than 1,4-disubstituted regioisomer. Moreover, a significant decrease in the computed values of the reaction enthalpy and free energy changes was obtained in the three solution phases in comparison with the gas phase. Furthermore, the thermodynamical preference in using water as the solvent was obtained in comparison with dioxane and THF to that is in agreement with experimental observations. In next step, electronic and structural origins of regioselectivity were investigated via analysis of variations in the calculated values of some key bond lengths and bond orders. Finally, to present a more concise interpretation on the regioselectivity, we performed the topological analysis of electronic indices via Quantum Theory of Atoms in Molecule (QTAIM) approach.