4-Nitroimidazole chlorination

Attempted reduction of l-methyl-4-nitroimidazole with tin(II) chloride and hydrochloric acid produced some 4-chlorinated product as a result of... 

Some of the sensitizing (and cytotoxic) effects of the nitro compounds can be attributed to GSH depletion. Activated chlorine maybe replaced by GS" [reaction (89) Wardman 1982 Stratford et al. 1983)], but the reaction is much more general. For example, the 2-nitroimidazoles react with GS by N02 release. These reactions are slow, but are considerably speeded up by glutathione-S-transferase (Wardman et al. 1973). 

Other drugs studied by Moore et al. include chlorine containing photosensitizers (178), the effect of surfactants on photosensitizers (179), photosensitization by malarial drugs (180), nalidic and oxolinic acids (181), 6-mercaptopurine (182), azathioprine and nitroimidazole (183), 7-methylbenz[c]acridine and related products (184), naproxen, ben-oxaprofen and indomethacin (185), mefloquine (186), sulfamethoxazole and trimethoprim (187), benzydamine (188), photodecomposition of hydrochlorthiazide (189), tetracycline (190), frusemide (191), 6-mercaptopurine (192), 7-methylbenz[c]acridine (193), metronidazole, misonidazole and azathioprine (194), misonidazole and metronidazole (195), benzydamine (196), components in drug formulations (197) and sulfamethoxazole (198,199). 

Fluoride converts 1,2-dimethyl-4-trimethylammonio-5-nitroimidazole into the 4-fluoro derivative <87JMC150>. The 2-nitro group of 1-methyl-2,4-dinitroimidazole is replaced by bromine or chlorine when treated with 2-bromoethanol or 2-chloropropanenitrile respectively <84UC(B)363>. When benz-imidazole-2-nitrosamine is treated with dry HCl or HBr with copper metal in acetonitrile the corresponding 2-halogenobenzimidazoles are formed in 71% and 63% yields respectively <87CHE1090>. 

Chlorination of 4-nitroimidazole in an alkaline medium gives unstable 1-chloro-4-nitroimidazole 28, which decomposes in 1-2 days at 0°C (97ZOR 1847). 

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