Synthesis Of 2-(Alkoxylimino)-(1,2,4-Thiadiazol-3-YL)-Acetic Acid And 1,3,4-Oxadiazole

The natural organic compounds with biological activities are heterocyclic compounds, especially those containing N,O and S are applicated in many fields such as medicines, pesticides,perfurmes and electron materials.1,2,4-Thiadiazole and 1,3,4-oxadiazole are representives in five membered heterocyclic compounds which have multiple bioactivities. The synthesis of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(alkoxylimino)acetic acid was studied in the first part and the new preparation of 1,3,4-oxadiazole was successively studied in the second part.2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(alkoxylimino)acetic acid is applied in the preparation of novel cephalosprins.A reasonable synthetic route was designed in the paper, in which cyanoacetamide was starting marerial,then through oximation,alkylation, aminolysis,bromation,cyclization with postassium thiocyanate,hydrolysis in base environment to give 2-(5-amino-1,2,4-thiadiazol-3,yl)-2-(alkoxyimino) acetic acid.The reactive conditions were optimizated.For example,the yield of 2-cyano-2-(ethoxyimino)acetamide is 30%higher than literatures,the toluene solution of 2-(ethoxyimino)malononitrile was used directly and the yield of 2-cyano-2-(alkoxyimino)acetamidine is up to 62%from 57%of the literature and the workup is simpler with salting-out procedure and the last step-cyclization was realized at room temperature avoiding in lower temperature(-10～-5℃).The target compounds were confirmed by IR,NMR.The new method of preparation of 2,5-disubstituted-1,3,4-oxadiazole was studied in the second part of the paper.Twentyaromatic aldehyde N-acylhydrazones were synthezied from aldehydes and N-acylhyrazines according to the designed synthetic route. Seventeen oxadiazoles were obtained through oxidative cyclization with sodium hypochlorit as the new oxidant.The ratio between the substrate and the oxidant,the solvent,reaction time and the influence of the substitution of the moieties were respectively studied and the reaction mechanism was proposed.The new method applied choices in the preparation 2,5-disubstituted-1,3,4-oxadiazoles with biological activities and the products were confirmed through IR,NMR and MS.