Elucidating chemoselectivity and unraveling the mechanism of 1,3-dipolar cycloaddition between diphenyl nitrilimine and (isoxazol-3-yl)methylbenzimidazole through molecular electron density theory

The reaction between diphenyl nitrilimine and 2-[(5-methylisoxazol-3-yl)methyl]-1-propargyl-1H-benzimidazole was examined using molecular electron density theory at the DFT/B3LYP/6-311+G(d,p) computational level. Energy profiles suggest that the chemoselective and regioselective pathway, particularly involving the imine function of the benzimidazole ring, is kinetically controlled and irreversible due to its exothermic nature. Weak noncovalent Van der Waals interactions stabilize the transition state. Geometric analysis reveal an asynchronous mechanism, with the shortest bond involving nitrogen atom N3 with the highest negative charge. Wiberg bond index and bond formation percentages are applicable for the more advanced bond in an asynchronous reaction. The inclusion of THF solvent delays the reaction without affecting chemoselectivity, polarity, or the mechanism. Despite diphenyl nitrilimine zwitterionic structure, the reaction mechanism is classified between a pseudo(mono)radical and a carbene-like mechanism, slightly favoring the latter.