Three-component,one-pot Synthesis Substituted 3-benzylidene-2,4-dimethyl-1,5-benzodiazepine Compoundsand Synthesis Study About 3-acyl-1,5-benzodiazepine

1,5-benzodiazepines and its derivatives gain remarkable attention because of its applications in pharmaceuticals. These compounds have been known for their analgesic, anti-anxiety, hypnotic, anticonvulsant, and so on, which have resulted in numerous recent studies pertaining to their syntheses. Most of the synthesis methods of benzodiazepines reported in articles are multi-step transformations. There are drawbacks in these methods such as using toxic organic solvents, low yields, and harsh reaction conditions. Therefore, the eco-friendly, solvent-free, multi-component, one-pot reactions have gained significant importance as a tool for the synthesis of 1,5-benzodiazepines. An one-pot, three-component methodology for the synthesis of the substituted 3-benzylidene-2,4-dimethyl-1,5-benzodiazepine compounds was proposed. And all the products were characterized. This paper also studied the synthesis reaction about 3-acyl-1,5-benzodiazepine. These reactions were discussed by DFT method on B3LYP/ 6-31 G level. The reaction mechanisms were explained from micro perspective.The main content and innovation of the thesis:1. Three-component, one-pot synthesis: For the first time, this paper reports an efficient one-pot, three-component methodology for the synthesis of the substituted 3-benzylidene-2,4-dimethyl-1,5-benzodiazepine compounds. 15 kinds of products were obtained via the condensation reaction of the substituted 1, 2-phenylenediamines, acetyl acetone and substituted benzaldehyde without solvent under room temperature. And 5 were novel, 10 were known. The three-component, one-pot reaction has a lot of advantages: The program was more easy and flexible and higher yields(80%). The reaction was carried out avoiding the use of toxic solvents and catalysts. The reaction conditions are more mild and eco-friendly.2. Optimization conditions and detection: After optimizing on the reaction conditions of the 3-benzylidene-2,4-dimethyl-1,5-benzodiazepine compounds, the optimal conditions are solvent-free, without catalysis, and room temperature. And the highest yield is 80%. The structures of the novel 3-benzylidene-2,4-dimethyl- 1,5-benzodiazepine compounds(VIII) were characterized by 1H NMR, 13 C NMR、MS and elemental analysis. And the compound of 2,4-dimethyl-3-(4-bromo-benzylidene)- 1,5-benzodiazepine(VIIIc) was determined by X-ray diffraction. The mechanism of three-component, one-pot reaction was proposed and validated through detecting the intermediates(V) by X-ray diffraction.3. Synthesis study about 3-acyl-1,5-benzodiazepine: A 3-ester-1,5-benzodiazepine was regarded as the guide compound. After the research on the guide compound and reference literatures, the synthesis study of two 3-acyl-1,5-benzodiazepines was executed. There are three synthetic routes designed for 3-COCH3 substituted 1,5-benzodiazepine and two routes designed for 3-CH2COCH3 substituted 1,5-benzodiazepine. And all the designed routes were researched by the experimental studies. Based on the experimental facts, all the designed routes and real reaction routes were discussed by DFT method on B3LYP/ 6-31 G level. One of the influence factors about the synthetic reaction progress, electronic effects, was studied quantitatively in theory theoreticall. And the features of these reactions were clarified visually. The reaction mechanisms were explained from micro perspective. And these consequences provide basis for the later synthesis research.