Green Synthesis Of 1,5-Benzoxazapines (Diazepines) Catalyzed By Magnetic Nanoparticles

1,5-benzoxazepines and 1,5-benzodiazepines are a class of benzo-fused seven-membered heterocyclic compounds containing heteroatoms(N,O),which are widely used in the field of medicinal chemistry.It is often used as anticonvulsant,anti-inflammatory,analgesic and hypnotic drugs.Most of the reported synthetic methods of 1,5-benzazepines(oxynitride,diazonium)have the disadvantages of cumbersome steps,harsh reaction conditions and low yields.Therefore,the synthesis of novel 1,5-benzodiazepines(oxynitrogen and diazepine)by efficient and green methods is of great significance in the fields of pharmaceutical chemistry and organic synthesis.Multicomponent domino reaction is an efficient synthetic method.It can obtain complex products with high atomic economy in a reaction system,which is in line with the chemical strategy of sustainable development.Magnetic nanocatalyst is a new type of heterogeneous catalyst,which has the advantages of high catalytic activity,strong stability and easy separation.It is an important field of catalyst development in the future.In view of this,this paper developed two kinds of magnetic nanocatalysts to catalyze the synthesis of three-component domino reaction,and synthesized 28 fused polycyclic 1,5-benzodiazepines and 25 novel1,5-benzodiazepines.The specific research contents are as follows:1.A novel method for the green synthesis of 1,5-benzoxazepines catalyzed by magnetic nano-supported p-toluenesulfonic acid(CoFe2O4@SiO2-PTSA)was developed.This method used substituted o-aminophenol,1,3-indandione,aromatic aldehydes or ethyl pyruvate as raw materials,and self-made CoFe2O4@SiO2-PTSA as catalyst to synthesize 28 fused polycyclic 1,5-benzoxazepines via three-component domino reaction.All the obtained products were characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis,and confirmed the correctness of the structure of the target compounds.This method abandons the traditional synthesis method of dehydrohalogenation using strong bases,and adopts a recyclable magnetic nano-supported catalyst(CoFe2O4@SiO2-PTSA)to synthesize fused polycyclic1,5-benzoxazepines via three-component domino reaction,which provides a new idea for the green synthesis of benzoxazepines.2.A novel method for the synthesis of 25 1,5-benzodiazepines with acyl,carboxyl,aryl,benzyl and other substitutions was developed by magnetic nanoparticles(CoFe2O4)catalyzed via three-component domino reaction.This method used substituted 1,2-phenylenediamine,3-butyn-2-one and aldehyde compound or pyruvate as raw materials,ethanol as solvent and magnetic nanoparticles cobalt ferrite(CoFe2O4)as catalyst,25 kinds of 1,5-benzodiazepines with acyl,carboxyl,aryl,benzyl and other substitutions were synthesized via three-component domino reaction.The obtained products were characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis.Combined with the X-ray single crystal diffraction pattern of the target compound ?-4dd,the correctness of the structure of target compounds was confirmed.The reaction underwent Michael addition,nucleophilic addition-dehydration,intramolecular cyclization,proton transfer and other reaction processes,and realized the construction of a seven membered nitrogen heterocycle and four new chemical bonds(two C-N bonds,one C=C bond and one C-C bond)in the reaction system.The method has the advantages of novel synthesis method,atomic economy,high reaction selectivity,short time and recyclable catalyst.