Synthesis and in Vitro Antimicrobial Activity of 6-Substituted 2H-1,3,5-Thiadiazine-2,4(3H)-diones

A series of 6-substituted 2H-1,3,5-thiadiazine-2,4(3H)-diones (1a–m) was prepared by treatment of alkyl, aryl, and heterocyclic primary thioamides with phenoxycarbonyl isocyanate to give N-(phenoxycarbonyl)-N^′-thioacylureas, which gave 1 upon heating in refluxing xylene solution or upon treatment with aqueous sodium carbonate solution followed by acidification. ¹H NMR and infrared spectral evidence indicates that the 6-alkyl derivatives 1a,b,1,m exist predominately in the exocyclic alkylidene tautomeric form. The major product obtained from alkaline and acid hydrolysis of the 6-phenyl derivative 1c was found to be benzoic acid and benzoylurea, respectively. The majority of compounds 1a–m exhibited in vitro antifungal activity against Candida albicans and Trichophyton mentagrophytes. Several derivatives, 1b–d,h j, displayed minimum inhibitory concentration values below 2 µg/mL against Trichophyton mentagrophytes. Four derivatives, 1c,e,g,h, inhibited the growth of Seratia marcesens, Staphylococcus aureus, and Staphylococcus epidermis in an in vitro sensitivity disk assay. 2-Furyl derivative 1h displayed antileukemic activity against P-388 lymphocytic leukemia.