Synthesis and structural studies of 3,6-disubstituted-bis-1,2,4-triazolo-[4,3-b][3′,4′-f]pyridazines

Abstract

Synthesis of a series of 3,6-disubstituted-bis-1,2,4-triazolo-[4,3-b][3′,4′-f]pyridazines (4) was accomplished by the oxidative intramolecular cyclization of 6-arylidenehydrazino-3-aryl-1,2,4-triazolo[4,3-b]pyridazine (3) using iodobenzene diacetate (IBD), as a green oxidant, in dichloromethane at room temperature. The compounds 3 and 4 were characterized by IR, NMR (1H and13C), mass spectral data and elemental analyses. X-ray crystal analysis of sterically strained 3,6-di-(2′-fluorophenyl)-bis-1,2,4-triazolo-[4,3-b][3′,4′-f]pyridazine 4f and 3,6-di-(4′-fluorophenyl)-bis-1,2,4-triazolo-[4,3-b][3′,4′-f]pyridazine 4g indicated that pyridazine ring has twisted conformation leading to nonplanar tricyclic core. Both compounds crystallized in orthorhombic P212121 space group, containing one single molecule per asymmetric unit. The studies reveal that the compound 4f is associated with weak, centrosymmetric F⋯F interactions (distance of 2.882(3) Å), with cis geometry, between adjacent molecules which are responsible for the formation of chains along a axis. Additionally, compounds 4 were screened for their cytotoxic activity against the human cervical carcinoma (HeLa) cell line using MTT assay, however, with not much significant activity.