Design, Synthesis, and Antimicrobial Evaluation of Novel Pyrazoles and Pyrazolyl 1,3,4-Thiadiazine Derivatives

A novel series of pyrazolyl 1,3,4-thiadiazines 5a⁻c, 8a⁻c, 12, 15a⁻c, 17a⁻c, and 20 was prepared from the reaction of pyrazole-1-carbothiohydrazide 1a,b with 2-oxo-N'-arylpropanehydrazonoyl chloride, 2-chloro-2-(2-arylhydrazono)acetate, and 3-bromoacetylcoumarin. Moreover, the regioselective reaction of 5-pyrazolone-1-carbothiohydrazide 1a with 4-substituted diazonium salts and 4-(dimethylamino)benzaldehyde gave the corresponding hydrazones 21a⁻c and 22. The newly prepared compounds were characterized by spectroscopy and elemental analysis. Many new synthesized compounds showed considerable antimicrobial activity against tested microorganisms. Hydrazones 21a⁻c and 22 showed remarkable antibacterial and antifungal activities. 4-(2-(p-tolyl)hydrazineylidene)-pyrazole-1-carbothiohydrazide 21a displayed the highest antibacterial and antifungal activities with minimum inhibitory concentration (MIC) values lower than standard drugs chloramphenicol and clotrimazole, in the range of 62.5⁻125 and 2.9⁻7.8 µg/mL, respectively.