Theoretical Analysis of the Mechanism of the 1,3-Dipolar Cycloaddition of Benzodiazepine with N-Aryl-C-ethoxycarbonylnitrilimine

In this work, the mechanism and regio- and no-periselectivity of the 1,3-dipolar cycloaddition reaction of 2,4-dimethyl-3H-1,5-benzodiazepine with N-aryl-C-ethoxycarbonylnitrilimine have been studied using the DFT method at the B3LYP/6-31G(d) level of theory. IRC calculations and activation energies show that this reaction follows an asynchronous concerted mechanism. The two C=N sites of 2,4-dimethyl-3H-1,5-benzodiazepine are easily reached by the dipole, and the energy barrier between the reagents and the transition states is too weak. The secondary barriers are traversed by the heat released in the reaction medium after the crossing of the first TS, which facilitates the addition reaction and does not require high energy. The obtained results of this study are in good agreement with experimental outcomes.