Green Synthesis Of Polycyclic Fused 1,5-benzazepines (1,5-benzodiazepines,1,5-benzothiazepines) By Three-component Tandem Reaction

1,5-Benzazepines（1,5-benzodiazepines,1,5-benzothiazepines）are an important central nervous system active drugs.A large number of drugs based on 1,5-benzazepines（1,5-benzodiazepines,1,5-benzothiazepines）are used to treat different mental diseases,and they are an important class of drug molecular skeletons in modern medicinal chemistry.They have various physiological activities such as anti-cancer,anti-bacterial,anti-depressant,and anti-cardiovascular diseases.Recent studies have shown that polycyclic fused1,5-benzazepines have anti-AIDS and Anti-HCV effects.Therefore,the design and green synthesis of 1,5-benzazepines（1,5-benzodiazepines,1,5-benzothiazepines）have attracted widespread attention in the field of medicinal chemistry and organic synthesis.In this paper,a series of novel and green synthesis methods were developed,and a total of 48 unreported polycyclic fused 1,5-benzodiazepines and 20 novel polycyclic fused 1,5-benzothiazepines were synthesized by different three-component tandem reactions.The specific research work is as follows:1、48 novel polycyclic fused 1,5-benzodiazepines with intra-ring and extra-ring diacyl substitution were obtained via one-pot and three-component tandem reactions at room temperature.These reactions were achieved by reacting substituted 1,2-phenylenediamines,1,3-cyclodione,2,3-butanedione or 1-phenyl-1,2-propanedione with ternary magnetic nano-loaded p-toluenesulfonic acid（Fe₃O₄@Si O₂/PTSA）made in the laboratory in the early stage as catalyst in Et OH.All the structures of target compounds were analyzed and characterized by MS,¹H NMR,¹³C NMR,IR,elemental analysis and X-ray（Vbcb）.Exploring the reaction conditions and the optimal reaction conditions were screened,and the possible reaction mechanism was proposed.The advantages of the reaction are novel reaction,good selectivity,high yield,unique compound structure.The ternary magnetic nano-supported catalyst has strong catalytic activity,can be separated by an external magnet,which has the advantage of being recyclable.2、α,β-Unsaturated carbonyl compounds were synthesized by Knoevenagel reactions using phosphotungstic acid as catalyst at room temperature.With substituted benzaldehydes,1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione as raw materials,these reactions were achieved by solvent-free grinding method.Without separation of intermediates,20 novel polycyclic fused 1,5-benzothiazepines were synthesized by tandem reaction betweenα,β-unsaturated carbonyl compounds and substituted 2-aminothiophenols in Et OH at room temperature with phosphotungstic acid as catalyst.All the structures of target compounds were analyzed and characterized by MS,¹H NMR,¹³C NMR,IR.and elemental analysis.The structures of the target products are proved to be correct.Exploring the influence of reaction conditions on the yield of the target compounds and the optimal reaction conditions were screened,and the possible reaction mechanism was proposed.This method abandons the traditional step-by-step synthesis of 1,5-benzothiazepine compounds,and realizes the one-pot synthesis of 1,5-benzothiazepine compounds by three-component tandem reactions,which provides a new green and efficient method for the synthesis of such compounds.