Study On The Oxidative Cycloaddition Reaction Of Hydrazone

Hydrazone is a compound with C=N-NH four atom bond in the molecule.Hydrazone and its derivatives have attracted extensive attention due to their unique chemical properties,biological activities and unique application prospects.The role of hydrazone compounds in the treatment of tuberculosis is well known.Polysubstituted hydrazones have antispasmodic,anti leukemia and anti-tumor activities.They also have anti-inflammatory,analgesic,antipyretic and antibacterial activities.Hydrazones formed in situ from α-halohydrazones are usually used as active dienes to construct various five-,six-,seven-,or seven membered heterocyclic compounds.Hydrazone has been widely used in[4+1],[4+2]and[4+3]cycloaddition reactions to obtain nitrogen-containing heterocyclic compounds with various values.A series of nitrogen heterocyclic compounds have been successfully synthesized by hydrazone cycloaddition reaction.1.The aza-Diels-Alder reaction of phenylhydrazone with active double bond compounds was studied.Spiro[indoline-3,3’-pyridazine]and spiro[indene-2,3’-pyridazine]were successfully synthesized by the reaction of phenylhydrazone with 3-arylidene indole ketone and 2-arylidene-1,3-indanedione in good yield and high diastereoselectivity.The results clearly show that the reaction is an aza Diels alder reaction with normal electron demand.Compared with the previous reports,the[4+2]cycloaddition reaction was carried out by removing a molecule of hydrogen halide from α-haloacylhydrazone to generate azoolefins in situ.The reaction is more atom economical and does not need metal catalyst,and the reaction has high diastereoselectivity.The cycloaddition reaction of aldhydrazone with active double bond compounds was studied.In the reaction of aldehyde hydrazone and 3-arylmethylene indolinone,while the solvent was acetonitrile,we obtained a multi-substituted pyrazole derivative,the expected spiro ring is destroyed,and TEMPO(2,2,6,6-Tetramethylpiperidine oxide)part wai cited.Under the same conditions,while the solvent was 1,4-dioxane,a spiro ring[indoline-3,3’-pyrazole]wass obtained.In the reaction of aldhydrazone with 2-arylmethylene-1,3-indandione and arylenebarbituric acid,we successfully obtained spirocyclic pyrazole derivatives.All products were characterized by IR,1H NMR,13C NMR,HRMS spectroscopy.The twelve single crystal structures of were determined by X-ray diffraction method.2.The cycloaddition reaction of keto hydrazone and 3-arylmethylene indole ketone was studied,and spiro[cinolin-3,3’-indoline]and spiro[indoline-3,3’-pyridazine]compounds were successfully synthesized.The reaction products of hydrazone and 3-arylmethylene indole ketone condensed by cyclohexanone and arylhydrazine are usually a mixture of two diastereomers.Keto hydrazones synthesized from cyclopentanone,cyclohexanone,4-tert-butylcyclohexanone,tetrahydronaphthalene ketone and arylhydrazine can react with 3-arylidene indole ketones to form six membered spiro compounds.The yield of 4-tert-butylcyclohexanone and tetrahydronaphthalene ketone is obviously lower than that of cyclohexanone and cyclopentanone.However,2-tert-butylcyclohexanone can not react smoothly.The results show that the steric hindrance of keto hydrazone has a significant effect on the reaction.Tempo as an oxidant has a very high substrate universality,which provides an efficient and simple synthesis scheme for nitrogen-containing six membered cyclic compounds.3.The cycloaddition reaction of aldehyde hydrazone with active double bond compounds was studied.In the reaction of aldehyde hydrazone with 3-arylidene indole ketone,when the reaction solvent is acetonitrile,we get polysubstituted pyrazole derivatives,tempo(2,2,6,6-tetramethylpiperidine oxide)takes part in the reaction;under the same conditions,when the solvent is 1,4-dioxane,spiro[indoline-3,3’-pyrazole]is obtained.In the reaction of aldehyde hydrazone with 2-arylidene-1,3--indanedione and arylidene barbituric acid,spiro pyrazole derivatives were obtained successfully.Therefore,when the reaction substrate is aldehyde hydrazone synthesized by condensation of phenylacetaldehyde and arylhydrazine.Finally,[3+2]cycloaddition reaction takes place to form pyrazole derivatives.This reaction provides a more convenient synthesis scheme for complex pyrazole derivatives,and has important guiding significance for pharmaceutical chemistry and synthetic chemistry.