Synthesis Of 1,5-benzodiazepines Via Domino Reaction Catalyzed By Cerium/copper Supported On Magnetic Nanoparticles

1,5-Benzodiazepines constitute an important class of biological active benzos seven-membered nitrogen heterocyclic compounds,which are utilized in diverse domain such as drug synthesis,biochemistry,organic chemistry.Recently,numerous methods have been reported for the synthesis 1,5-benzodiazepine derivatives.It mainly uses liquid acids as catalysts,which has disadvantages such as non-renewable,cumbersome separation,poor selectivity,and unfriendly environment.Thence,it is necessary to develop new and efficient green catalysts that are reusable and easy to separate to solve the current problems.The characteristic of magnetic nano-supported catalyst is distinctive,such as reusability,large specific surface area,easy separation,high stability,safety and nontoxicity.It shows excellent catalytic performance in organic chemical reactions.Some magnetic nano-supported catalysts have been reported,and their active centers are simply attached to the surface of magnetic nanoparticles,which are easily lost during the reaction,resulting in waste of resources and environmental pollution.Therefore,in this paper,two magnetic nano-supported catalysts with novel structures,stable properties and chemical bonds were designed and prepared,and their structures were characterized and analyzed.The two catalysts were applied to different reaction systems for catalyzing synthesis of 1,5-benzodiazepine compounds,and their catalytic activity and recycling performance were studied.The specific research work is as follows:1.A novel magnetic nano-supported cerium catalyst Co Fe2O4@Si O2@APTES@ATA-Ce Cl3 with both Br?nsted acid sites and Lewis acid sites was successfully prepared.The catalyst uses magnetic nanoparticles Co Fe2O4 as a carrier,the surface of which is coated with Si O2,connected by a silane coupling agent(APTES),fixed by 2-aminoterephthalic acid and coordinated by cerium trichloride.The structure,composition and morphology of the catalyst were characterized and analyzed.The catalyst was applied to the one-pot synthesis of benzyl/phenethyl substituted 1,5-benzodiazepines by three-component domino reaction,o-phenylenediamine,1,3-dicarbonyl compounds and phenylacetaldehyde/phenyl-propionaldehyde as raw materials,its catalytic activity and recycling performance was evaluated,the reaction conditions were optimized,the substrate expansion was carried out,and the catalytic mechanism was proposed.The double acid site of the catalyst synergistically activates the carbonyl group of the reactant and the imine double bond of the reaction intermediate,and 24 kinds of 1,5-benzodiazepine compounds that have not been reported in literature have been synthesized with high catalytic activity.The yield of the reaction was up to 94%.After studying the recycling performance of the catalyst,it was found that it could be recycled 6 times without notable decrease in activity.2.On the basis of amino-functionalized magnetic nanoparticles Co Fe2O4@Si O2@APTES,3-hydroxy-2-picolinic acid was anchored on the magnetic nanoparticles through the formation of amide bonds,and further coordinated with Cu(OAc)2 to obtain magnetic nano-supported copper catalyst Co Fe2O4@Si O2@APTES@HO-PBA@Cu(OAc)2.After the new catalyst was fully characterized,its catalytic activity and recycling performance was investigated in the one-pot synthesis of diester/methyl substituted 1,5-benzodiazepines via threecomponent domino reaction,which take advantage of o-phenylenediamine,1,3-dicarbonyl compound,and diethyl acetylenedicarboxylate/propiolic acid as reactant.After the optimization of reaction conditions and the expansion of substrates,this catalyst has synthesized 24 kinds of diester/methyl substituted 1,5-benzodiazepine compounds with high catalytic activity,which have not been reported in literature,and the highest yield of the reaction can reach 90%.The catalytic mechanism was proposed.The active component of the catalyst,copper acetate,not only acts as the carbonyl group of the Lewis acid activation reactant,but also promotes the C-C coupling and cyclization of the enamine-enamine intermediate which is difficult to cyclize to form the target compound with a seven-membered ring structure.After studying the recycling performance of the catalyst,it was found that it can be recycled7 times without obvious loss of activity.