Study On [3+2] Cycloaddition Reaction Of Hydrazone And Electron Deficient Olefins Promoted By Chloramine-T

In recent years,nitrogen-containing heterocyclic compounds have been widely used in the fields of biomedicine and functional materials.As a nitrogen-containing heterocyclic compound,pyrazole has not only pharmacological activities such as antibacterial,antitumor and antipyretic analgesia,but also is an important organic synthetic intermediate.Owing to their unique biological activity,an efficient synthesis of pyrazole is necessary.Maleimides are important building blocks in organic synthesis.They were served as synthon in Micheal addition,oxidative coupling and Diels-Alder reaction.Maleimide derivatives have become one of the hotspots in organic synthesis of N-heterocycle compounds.In the past few years,our research group has devoted to the synthesis of nitrogen-containing heterocyclic compounds based on maleimides,and its study of biological activity.On this basis,[3+2]cycloaddition of hydrazone with electron-deficient olefins such as dimethyl fumarate and maleimides promoted by chloramine-T was studied.The reaction conditions were explored,pyrazole and dihydropyrrolo[3,4-c]pyrazole compounds were synthesized in the reaction.The detailed contents include the following three aspects.Part one:[3+2]Cycloaddition of hydrazone with dimethyl fumarate promoted by chloramine-T was studied.Firstly,the reaction conditions were optimized.In the presence of hydrazone,electron-deficient olefins such as dimethyl fumarate with chloramine-T were allowed to react in glycol dimethyl ether at 70℃ for 2 h.Then we found that pyrazole compounds could be synthesized by[3+2]cycloaddition reaction of dimethyl fumarate with hydrazine and aldehyde in one-step.Part two:The substrate applicability of the reaction has been studied.In the presence of hydrazine,aldehyde,fumarate or maleate with chloramine-T were allowed to react in glycol dimethyl ether at 70℃ for 2 h,affording the corresponding pyrazole in 60～87% yields.When fumarate was used as substrate,the yield was higher than that of maleate.Besides,the cycloaddition reaction of ethyl cinnamate with phenylhydrazine and benzaldehyde was resulted in 43% yield.The possible reason was that the conjugation of benzene and olefin reduced the reactivity of ethyl cinnamate.In the presence of hydrazine,aldehyde,maleimides with chloramine-T were allowed to react in glycol dimethyl ether at 70℃ for 2 h,and dihydropyrazole were obtained in 83%～96% yields.Part three:On the basis of our experimental results and previous reports,a possible radical mechanism for[3+2] cycloaddition pyrazole of fumarate with hydrazine and aldehyde esters was proposed.Initially,hydrazone were generated in situ from hydrazine and aldehyde.Subsequently,1,3-dipole derived from hydrazone was generated by chloramine-T accompanied with the production of p-methylbenzenesulfonamide.1.3-Dipolar cycloaddition leaded to the formation of dihydropyrazole intermediate.Finally,the dihydropyrazole intermediate was oxidized by chloramine-T to afford the pyrazole derivatives.In conclusion,totally 21 compounds are synthesized,9 compounds of them have not been reported in the literature.Their structures were confirmed by melting point,IR,¹H NMR,¹³C NMR,MS and HRMS.