Synthesis of Novel 1-(5-(Benzylsulfinyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene)-thiourea/urea Derivatives and Evaluation of Their Antimicrobial Activities

A new series of 1-(5-(benzylsulfinyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene)-thiourea/urea derivatives (1a-j) were designed and synthesized. For the first time, (i) a new process was developed for N-methylation of 1,3,4-thiadiazole moiety using dimethyl carbonate an environmentally benign reagent in presence of N,N,N ',N '-tetramethylethylenediamine and (ii) the sulfide was selectively oxidized to sulfoxide in higher yield by using chlorine (g) in aqueous acetic acid media under mild reaction condition. The synthesized compounds (1a-j) were investigated for their antimicrobial activities. The tested compounds (1a-j) were exhibited moderate to excellent antibacterial activities against both Gram-positive and Gram-negative bacterial strains. The same compounds exhibited good antifungal activities against selected fungal strains. Particularly, the compounds 1b, 1d, 1h, and 1i were proved to be promising leads exhibiting both antibacterial and antifungal activities compared with standard drugs, ciprofloxacin, and fluconazole. The presence of 1,3,4-thiadiazole moiety has a significant role in the display of antimicrobial activity. In addition, the presence of both sulfinyl and thiourea or urea functionalities has enhanced the activity as per obtained antimicrobial activity data.