Synthesis and characterization of 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives from substitued aminoacid hydrazide

Five-membered heterocyclic rings as especially thiadiazole, triazole, and oxadiazole are in the structure of many compounds used in medicine today. These rings are variety isomers according to the location of connected heteroatoms. But, 1,3,4-thiadiazole, 1,2,4-triazole and 1,3,4-oxadiazole derivatives within these isomers are biologically highest active. The five-membered ring compounds have a wide range biological activity such as anticancer activity, then antibacterial, antifungal, anti-HIV, antitumor, antiviral, antidepressant, antiinflammatory, antituberculosis, diuretic, antipyretic, antihypertension, antidiabetic, plant growth regulators, blood vessel expander, antilipidemic, analgesic, insecticidal etc.In this study, 1,3,4-thiadiazole, 1,2,4-triazole-3-thione and 1,3,4-oxadiazole derivatives from five-membered rings were synthesized. First, appropriate starting material and L-phenylalanine ethyl ester containing amine group was reacted with compound 4-fluorobenzoyl chloride and was converted to amide derivative [I] and the ester part is treated to hydrazine hydrate and was obtained its hydrazide derivative [II]. The hydrazide derivative was reacted with substituted isothiocyanate to obtain thiosemicarbazide derivatives [IIIa-d]. The synthesized thiosemicarbazides were cyclizated 1,3,4-thiadiazole [IVa-d] in sulfuric acid medium, 1,2,4-triazole-3-thione [Va-d] in sodyum hydroxide medium and 1,3,4- oxadiazole [VIa-d] ring in the presence of KI/I2.All of reactions was monitored by Thin Layer Chromatography (TLC). The structures of synthesized compounds were elucidated by spectroscopy methods as UV-Vis, FT IR, ¹H NMR, 13C NMR and elemental analysis (C, H, N, S) as well as of physical and chemical methods.