Synthesis,Structure Characterization And Biological Activity Of Pyrazole Formic Acids Containing 1,3,4-thiadiazole

In recent years,heterocyclic compounds have become the main direction in research and development of new drugs by virtue of the flexible structure,unique biological activity and other advantages.There exists lots of medicine and pesticide commodity with pyrazole as parent nucleus in the compounds.1,3,4-thiadiazole compounds have the biological activities of disinfection,desinsection,weeding and regulation of planting growth in agriculture,while in medicine,they are used for the production of some drug products with anticancer,antiviral and anticonvulsant effects,etc.Therefore,it is of very practical application significance of the research on compounds containing these two structural unit.Based on the review of related literature and the prophase work,Substituted aromatic acids and thiosemicarbazide are used as starting materials,through the methods of condensation,diazotization,substitution reactions,the intermediates 2-hydrazine-5-substituted-1,3,4-thiadiazoles(Ⅲ_1⁵)were obtained.By the way of condensation reaction with different substituted ketone,the intermediate s N-substituted-N’-（5-aryl-[1,3,4]thiadiazol-2-yl）-hydrazines(Ⅳ_1²5)were synthesised,and based on the methods of Vilsmeier-Haack cyclization reaction,the intermediates 3-substituted-1-（5-aryl-[1,3,4]thiadiazole-2-yl）-1-H-pyrazole-4-carbaldehydes(Ⅴ_1²5)were gained.Finally the target compounds 3-substituted-1-（5-aryl-[1,3,4]thiadiazole-2-yl）-1-H-pyrazole-4-formic acids(Ⅵ_1²5)were obtained through oxidation by potassium permanganate.So,intermediates and target products are all new compounds.Meanwhile,the organic single crystal of an intermediate compoundⅤ₁ was obtained by the solution crystallization method.The IR spectra,NMR spectra and elemental analyses were used to characterize the structure of the 50 intermediates and 25 target compounds.The structure of organic single crystal was tested and analyzed by X-ray single crystal diffraction,which belongs to the triclinic crystal system,space group P-1,further proving the correctness of its structure.Besides,preliminary bioactivity experiments were done among intermediates(Ⅴ_1²5)and all the target compounds(Ⅵ_1²5).96-well plate method was used to determine the antimicrobial activity of the intermediates and the target compounds in each gradient concentration against Escherichia coli and Staphylococcus aureus.The antibacterial activity was present in part of intermediates and almost all the target compounds,in which intermediateⅤ₁₀ and target compoundⅥ₆ were tested for the best antibacterial effect and degree of antibacterial activity was different due to different strains.For most of the target compounds,the inhibition effect against Escherichia coli was better than that of Staphylococcus aureus.