Synthesis Study Of Antineoplastic Intermediates1,3,4-Thiadiazole And Derivatives

Tumor is a large class of diseases which is the cell abnormal proliferatedand metastasized. Tumor incidence and mortality rates have been rising, itis becoming the first killer of mankind.1,3,4-thiadiazole compounds werehad a many of biological activity,like anti-tumor,anti-bacterial,anti-HIV,lowering blood glucose and lipid. In recent years,1,3,4-thiadiazolecompounds studied in terms of anticancer drugs has become a focus ofattention of many researchers.in this study,we were synthesized5-substituted-2amino-1,3,4-thiadiazole compounds with the malonate,diethyl malonate, succinic anhydride as materials.and then synthesizedthiadiazole derivatives by modifing the amino-group to provide a referencefor preparing the novel1,3,4-thiadiazole as antineoplastic.All the compoun-ds were characterized by mass spectra, IR and1H NMR.The main work isas follows:1.A synthetic route was identified that5-substituted-2amino-1,3,4-thiad-iazole compounds was synthesized from diethyl malonate and succinicanhydride by the single ethyl esterification, acylation, and cyclization withthiosemicarbazide under the catalysis of the MsOH.There is a characteristicof the synthetic route with available raw materials, operated easy and betteryield.2. To select the best condition for cyclizating reaction process by theorthogonal design.The result indicated that,when the ratio of thiosemicarb- azide to chloride is1:2, the ratio of thiosemicarbazide to methane sulfonicacid is1:3, stirred for1hour and the temperature as110℃, the averageyield was52.76%, increased by16.57%compared with the literature（37%）.3.We were synthesized twelve new compounds by modifing theamino-group of5-substituted-2amino-1,3,4-thiadiazole compounds witharomatic chloride, ethyl acetoacetate and acetylacetone as raw materials.To sum up, twelve novel1,3,4-thiadiazole derivatives were synthesizedby the malonate, diethyl malonate, succinic anhydride and thiosemicarbaz-ide which is to provide a reference basis for studing the1,3,4-thiadiazolecompounds of antineoplastic drugs.