DFT Studies on Mechanism of Organocatalytic Metal-Free Click 32CA Reaction for Synthesis of NH-1,2,3-triazoles.

The mechanism of enamine-mediated organocatalytic [3 + 2] cycloaddition (32CA) reaction of Hagemann's ester to p-toluenesulfonyl azide in the present L-proline as a catalyst has been investigated using M06-2X functional with the 6-31+G(d) basis set. The effects of the different solvents were studied with a 6-311+G(d,p) basis set. In addition, the effects of the keto ester substitutions: one model system M1 (R₁ = CH₃ and R₂ = H) and two real systems R2 (R₁ = R₂ = Me) and R3 (R₁ = Et and R₂ = Me) also studied in this work. DFT results indicated that the different solvents show the same effect, which leads to a decrease in the ΔG₂₉₈ along the reaction pathway compared to the gas phase. Moreover, the model system M1 has a lower activation free energy (17.5 kcal/mol) than real systems R2 and R3 by about 3.8 and 3.2 kcal/mol in the solution phase (DMSO), respectively. Analysis of the global and local reactivity indices of the reactants was performed in the gas and solution phases. [ABSTRACT FROM AUTHOR]