Synthesis and spectral studies of tetrazepinones

In order to develop a novel analog of the antitumour agent Mitozolomide 1, the diazotization of a variety of N-(2-aminophenyl)-N$ sp prime$-alkylureas was studied. The diazotization of N-(2-aminophenyl)-N-alkylureas of type 2a gave benzotriazole derivatives 3 (R=CONHalkyl). However, that of N-methyl-N-(2-aminophenyl)-N-alkylureas 2b gave 1,2,3,5-benzotetrazepinones 4 after the neutralization of the reaction mixture. This finding allowed the synthesis of bi- and tricyclic tetrazepinones. Electronic effects on the stability of the tetrazepinone ring system were studied by varying substituents at the benzene moiety. The stability of the tetrazepinones increased with increasing electron withdrawing character of the substituent. Variation of substituents at N5 showed that their stability decreases with increasing steric bulk of the substituents. The decomposition of benzotetrazepinones generally gave N-phenyl-N,N$ sp prime$-dimethylureas, 1-alkylbenzotriazoles and 2-hydroxy-benzimidazoles. The synthesis of stable pyrido-1,2,3,5-tetrazepinones is also described. The tetrazepinones were generally characterized by $ sp1$H and $ sp{13}$C NMR, X-ray diffraction, mass spectroscopy and microanalysis. The existence of the triazene chain was usually confirmed by $ sp{15}$N NMR spectroscopy after specific labelling of the central nitrogen (N2).(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI