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

Abstract

A novel series of pyrazolyl 1,3,4-thiadiazines <b>5a</b>⁻<b>c</b>, <b>8a</b>⁻<b>c</b>, <b>12</b>, <b>15a</b>⁻<b>c</b>, <b>17a</b>⁻<b>c</b>, and <b>20</b> was prepared from the reaction of pyrazole-1-carbothiohydrazide <b>1a</b>,<b>b</b> with 2-oxo-<i>N</i>'-arylpropanehydrazonoyl chloride, 2-chloro-2-(2-arylhydrazono)acetate, and 3-bromoacetylcoumarin. Moreover, the regioselective reaction of 5-pyrazolone-1-carbothiohydrazide <b>1a</b> with 4-substituted diazonium salts and 4-(dimethylamino)benzaldehyde gave the corresponding hydrazones <b>21a</b>⁻<b>c</b> and <b>22</b>. The newly prepared compounds were characterized by spectroscopy and elemental analysis. Many new synthesized compounds showed considerable antimicrobial activity against tested microorganisms. Hydrazones <b>21a</b>⁻<b>c</b> and <b>22</b> showed remarkable antibacterial and antifungal activities. 4-(2-(<i>p</i>-tolyl)hydrazineylidene)-pyrazole-1-carbothiohydrazide <b>21a</b> 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.