Synthesis, structure and in vitro cytotoxicity testing of some 1,3,4‐oxadiazoline derivatives from 2‐hydroxy‐5‐iodobenzoic acid

The syntheses of nine new 5-iodo­salicylic acid-based 1,3,4-oxa­diazo­line derivatives starting from methyl salicylate are described. These compounds are 2-[4-acetyl-5-methyl-5-(3-nitro­phen­yl)-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6a), 2-[4-acetyl-5-methyl-5-(4-nitro­phen­yl)-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6b), 2-(4-acetyl-5-methyl-5-phenyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl)-4-iodo­phenyl acetate, C19H17IN2O4 (6c), 2-[4-acetyl-5-(4-fluoro­phen­yl)-5-methyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate, C19H16FIN2O4 (6d), 2-[4-acetyl-5-(4-chloro­phen­yl)-5-methyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate, C19H16ClIN2O4 (6e), 2-[4-acetyl-5-(3-bromo­phen­yl)-5-methyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6f), 2-[4-acetyl-5-(4-bromo­phen­yl)-5-methyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6g), 2-[4-acetyl-5-methyl-5-(4-methyl­phen­yl)-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6h) and 2-[5-(4-acetamido­phen­yl)-4-acetyl-5-methyl-4,5-di­hydro-1,3,4-oxa­diazol-2-yl]-4-iodo­phenyl acetate (6i). The compounds were characterized by mass, 1H NMR and 13C NMR spectroscopies. Single-crystal X-ray diffraction studies were also carried out for 6c, 6d and 6e. Compounds 6c and 6d are isomorphous, with the 1,3,4-oxa­diazo­line ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C—H⋯O, C—H⋯π and I⋯π inter­actions. For 6e, the 1,3,4-oxa­diazo­line ring is almost planar. In the packing, Cl⋯π inter­actions are observed, while the I atom is not involved in short inter­actions. Compounds 6d, 6e, 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep-G2, with IC50 values of 0.9–4.5 µM.