Synthesis Of Multi-ester Groups-containing 1,5-benzodiazepines Or Fused 1,5-benzodiazepines By One-pot Tandem Reactions

1,5-benzodiazepines exhibit high physiological activities and pharmacological activities,which are widely used,especially in the fields of sedatives,antiviral,antidepressants,and anti-inflammatory drugs.Therefore,the synthesis of 1,5-benzodiazepines has always been a research hotspot in organic chemistry and drug synthesis.In addition,one-pot synthesis1,5-benzodiazepines via the tandem reactions can obtain the target products without separation and purification of intermediates,which is a green and efficient synthesis method.Therefore,our group has been committed to the synthesize of novel 1,5-benzodiazepines by one-pot tandem reactions.1,5-benzodiazepines are a class of compounds formed by the fusion of a benzene ring and a seven-membered nitrogen-containing heterocyclic ring.There are multiple reaction sites on the seven-membered ring structure,which can connect different substituents to make1,5-benzodiazepines have different physiological activities and pharmacological activities.Studies have shown that ester group is a drug active group with high hydrophobicity and lipid solubility,and the introduction of ester group can enhance the biological activity of the target products.Indanone compounds are also an active structural unit with a wide range of biological activities,such as antioxidant activity,antibacterial activity,anti-allergic activity and so on.Therefore,this paper aims to synthesize novel multi-ester groups-containing1,5-benzodiazepines or indanone fused 1,5-benzodiazepines by introducing ester groups or indanone structures into the active seven-member ring structure of 1,5-benzodiazepins.The main work of this paper is as follows:1、A method for one-pot synthesis of 2,3-diester-1,5-benzodiazepines catalyzed by a magnetic nano-supported catalyst via the tandem reactions has been developed.With substituted 1,2-phenylenediamines,ethyl benzoylacetate andα-carbonyl ester compounds（ethyl glyoxylate,ethyl pyruvate,ethyl benzoylformate）as the raw materials,18 novel2,3-diester-1,5-benzodiazepines with enamine or imine structure are obtained by one-pot tandem reactions in the presence of magnetic nano-supported p-toluenesulfonic acid（Fe₃O₄@Si O₂-Ts OH）made in laboratory in ethanol.The optimal reaction conditions are obtained by optimizing the conditions of the tandem reactions.Under the optimal reaction conditions,the scope of substrate applicability is studied and the target products with single isomer are obtained.The target products are characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis to determine their structures.The structures of the target products are proved to be correct by the X-ray single crystal diffraction patterns of compound Vcb and compound Vfb.Furthermore,a reasonable reaction mechanism is proposed for the tandem reactions.This synthesis method has many advantages,such as no need to separate and purify the intermediate,easy operation and environmental friendliness.In addition,the catalyst can be easily separated and recovered.2、A method for one-pot synthesis of indanone fused 1,5-benzodiazepines catalyzed by a magnetic nano-supported catalyst via the tandem reactions has been developed.30 novel indanone fused 1,5-benzodiazepines with enamine structure are obtained by reacting starting materials of substituted 1,2-phenylenediamine,1,3-indanedione,α-dicarbonyl compounds or aromatic aldehyde（ethyl glyoxylate,ethyl pyruvate,pyruvic acid,2,3-butanedione,4-chlorobenzoic aldehyde,2-thiazolecarboxaldehyde）by one-pot tandem reactions in the presence of Fe₃O₄@Si O₂-Ts OH made in laboratory in ethanol.The optimal reaction conditions are obtained by optimizing the conditions of the tandem reactions.Under the optimal reaction conditions,the scope of substrate applicability is studied and the target products with single isomer are obtained.The target products are characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis to determine their structures.Furthermore,a reasonable reaction mechanism is proposed for the tandem reactions.The synthesis method has the advantages of environmental friendliness,mild reaction conditions,and the catalyst is easily separated and recoverable,which is of great significance in organic synthesis and drug development.