Synthesis And Selectivity Of Aromatic (Hetero) Ring-Substituted 1,5-Benzodiazepine Compounds

1,5-benzodiazepines are a kind of nitrogen-containing heterocyclic compounds and have both important pharmacological activities and bioactivities. They process antianxiety, anticonvulsant and sedative. It is said that 1,5-benzodiazepines and derivatives have good antibacterial activity. Therefore, the design and synthesis of 1,5-benzodiazepines have been broad concernIn the present study, according to different design directions, 36 2-aromatic heterocyclic-4-phenyl-1,5-benzodiazepines were designed and systhesized through Aldol-condensation, aza-Michael addition and cyclization, where o-phenylenediamine, acetophenone and aromatic formaldehyde are the raw materials. Herein, 36 2-aromatic heterocyclic-4-phenyl-1,5-benzodiazepines were characterized by 1H NMR,13 C NMR,IR,MS and single crystal diffraction analysis. In addition, in the course of the synthesis of two newly compounds, we also did further modification and obtained the optimum conditions.Through the study on the regioselectivity of 18 4-phenyl-2-thiophen-2-yl-1,5-benzodiazepines and 6 4-phenyl-2-thiophen-3-yl-1,5-benzodiazepines, the possible mechanism for the synthesis was proposed. Quantatived calculation of the raw materials and parts of target products were made through the Gaussian03 quantum chemistry package, density functional theory(DFT) at the B3 LYP method, in the 6-31 G basis set level. We obtained the structure parameter, such as(zero-point energy, Internal energy, thermodynamic enthalpy, Gibbs free energy)charge and other parameters, through calculation of compounds. According to structure parameter, we gave the theoretical explanation for the reaction mechanism and regioseletive.Antibacterial activity of these novel compounds was evaluated in vitro against bacterial including clinical cryptococcus neoformans, cryptococcus neoformans, candida albicans and staphylococcus aureus, escherichia coli, by filter paper method. The results show that the target compounds have no antibacterial activity. Comparing with 1,5-benzodiazepines which was synthesized by our group, we further illustrated the reason that these compounds was inactivated.