Synthesis, Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by 1H NMR, 13C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.