Study On The Synthesis Of Five-membered Heterocyclic Compounds Containing Nitrogen And Oxygen Atoms By Oxidative Dehydrogenation And Decarburization

Benzoxazole and 1,3,4-oxadiazoles are five-membered heterocyclic compounds containing nitrogen and oxygen atoms,which have antibacterial and anti-inflammatory activity.These compounds showed a broad spectrum of biological characteristics in medicine and agricultural chemicals.In this paper,a new synthetic method for the preparation of benzoxazole has been developed by oxidative dehydrogenation cyclization reaction and a new synthetic method for the preparation of 1,3,4-oxadiazoles have been developed by oxidation decarburization cyclization reaction,respectively.The first part involved oxidative dehydrogenation and cyclization of o-hydroxyaniline.First of all,2-（2-nitrophenyl）methyl amino phenol was used as the reaction substrate,the oxidizing agent,reaction temperature and solvent were screened by the conditions tests.The optimum reaction condition has been determined to be:Ph（OAc）₂as the oxidant,with a reaction substrate molar ration of 2.2:1;oxidation reaction solvent is chloroform and reaction temperature is room temperature.The corresponding imine was obtained by the reaction of amino phenol and aromatic aldehyde and twenty aromatic amines were obtained by reduction reaction of sodium borohydride.All of these amines have been successfully oxidized to the corresponding benzoxazole and the yields are from17%up to 99%.When the substrates contain tert-butyl,the yield of the target product is generally higher than that of the substituent bearing nitryl and hydrogen substituent.When benzaldehyde,p-nitrobenzaldehyde or aromatic aldehyde containing thiophene ring and furyl ring were used,the yield of the target product is higher.The second part involved oxidative decarburization and cyclization of acylhydrazone.First of all,acetophenone N-benzoyl hydrazone has been used as the reaction substrate,the oxidizing agent,reaction temperature and solvent were screened by the conditions tests.The optimum reaction condition has been determined to be:Cu（OAc）₂ as the oxidant,oxidation reaction solvent is dimethyl sulfoxide and reaction temperature is 120℃.The corresponding acylhydrazone was obtained by the reaction of aromatic ketone and acylhydrazine and the corresponding 1,3,4-oxadiazole was prepared by the oxidation reaction of acylhydrazone.In addition,the structure of products or intermediates were confirmed by ¹H NMR,¹³C NMR,IR.The corresponding oxidation mechanisms has been proposed respectively through capturing the intermediate in the oxidation reaction process.