Synthesis of some substituted 1,3,4-oxadiazoles, thiadiazoles and 1,2,4-triazoles

In this paper the synthesis of some substituted 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles is reported. Ethyl methacrylate was treated with hydrazine hydrate in ethanol to give the corresponding hydrazide (1). The hydrazide was converted to 1-acyl thiosemicarbazide (2) byits reaction with ammonium thiocyanate, which was treated with sodium hydroxide solution and with concentrated sulfuric acid to give 5substituted-1,2,4-triazoles-3-thiol (3) and 2-substituted-5-amino-1,3,4Synthesis of some substituted 1,3,4-oxadiazoles, thiadiazoles and ... 30 thiadiazole (4) respectively. The acid hydrazide (1) was treated with benzaldehyde or substituted benzaldehyde to give hydrazones (7-12), the hydrazones were then cyclized with lead dioxide to 2-subtituted-5-phenyl 1,3,4-oxadiazole (14). The reaction of the hydrazide (1) with formic acid gave 1-formyl-2-acyl hydrazine (6) and the cyclization of (6) by phosphorus pentaoxide gave monosubstituted-1,3,4-oxadiazoles (13). Acid hydrazide (1) was treated with phenyl isothiocyanate to give substituted thiosemicarbazide (5). The structure of the synthesized compounds were confirmed by physical and spectral means. INTRODUCTION 1,3,4-oxidiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles and their derivatives are associated with various biological activities such as anticonvulsant (1) , antifungal (2,3) , anticancer (4,5) , anti-inflammatory (6,7) and antibacterial properties (8-10) . The therapeutic effect of these compounds have been well studies for a number of pathological cases including inflammation (11) , pain (12) or hypertension (13) . These biological data promoted many researchers to synthesized substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole by using a number of starting materials and methods. 1,3,4-Oxadiazoles were synthesized from acid hydrazides by their reaction with carbon disulfide in ethanolic potassium hydroxide (14,15) . 1,2-Diacyl hydrazine was treated with thionyl chloride to give substituted 1,3,4-oxdiazole, such as compound (I) (16) . Whereas oxidation of substituted thiosemicarbazide with lead oxide (17) or potassium iodide/iodine (18) gave substituted 1,3,4-oxadiazoles. Treatment of carboxylic acids with hydrazine in the presence of polyphosphoric acid gave 1,3,4-oxdiazolee as compound (II). O