Synthesis, Characterization, Crystal Structure, and Theoretical Calculations of Novel 1,5-Benzodiazepine Derivatives Obtained via 1,3-Dipolar Cycloaddition Reactions

A series of triazolo-benzodiazepine derivatives were synthesized by the condensation of 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine (BZD) 1 with nitrilimine analogs (N-aryl-C-ethoxycarbonyl-nitrilimines and diarylnitrilimines). The newly synthesized cycloadducts were well-characterized by various spectroscopic techniques (¹H, ¹³C NMR, and HRMS). The structure of single-crystal was characterized using a single-crystal X-ray technique. A theoretical study of the chemo and regioselectivity has been performed by density functional theory at the B3LYP/6-311G(d,p) level of theory. A comprehensive theoretical study of the reaction mechanism was performed. The geometry of the different reactants and products were analyzed, the transition states were located and the corresponding reaction paths were determined and characterized by the intrinsic reaction coordinate. Computational results show that the reactions were completely chemo and regioselective, the mechanism of reactions was non-concerted and explained the effect of aryl groups on the reaction yield.