Cyrhetrenyl and ferrocenyl 1,3,4-thiadiazole derivatives: Synthesis, characterization, crystal structures and in vitro antitubercular activity

A new series of cyrhetrenyl and ferrocenyl 1,3,4-thiadiazoles (TDZs) were designed, synthesized and characterized. The condensation-cyclization reaction of organometallic-cyanide with the corresponding thiosemicarbazide produces the ferrocenyl-TDZs (3a-c) and cyrhetrenyl analogues (4ac). The structures of all products were inferred from their elemental analysis, H-1 and C-13 NMR spectra and MS. The molecular structures of 3b and 4b were confirmed using X-ray crystallography. The electronic effects of cyrhetrenyl (4a-c) and ferrocenyl (3a-c) bound directly to the thiadiazole ring have been correlated with the chemical shift of the exocyclic amine proton and C-13 shift of the carbon at the 5-position. The X-ray crystal structure of 3b and 4b indicates that the rhenium compound 4b possesses a more extensive conjugated pi-system. The activity of the new organometallic-TDZs was evaluated in vitro against Mycobacterium tuberculosis. The incorporation of any organometallic fragment into the thiadiazole skeleton showed a comparable but lower antitubercular activity than isoniazid. (C) 2015 Elsevier B.V. All rights reserved.