Regioselective Nitro Group Substitution. Synthesis of Isomeric 4-Amino-5-nitro- and 5-Amino-4-nitroimidazoles

Abstract

On the basis of the reactions between 4,5-dinitroimidazole derivatives(1-methyl-4,5-dinitroimidazole, 1,2-dimethyl-4,5-dinitroimidazole and ethyl 2-(4,5-dinitroimidazol-1-yl)acetate) and cyclic amines (morpholine, piperidine or pyrrolidine) in mild conditions (THF or ethanolic solution), the order of nitro group substitution has been discovered for the first time. The influence of the solvent, steric effects and possibility of hydrogen bonds formation on the reaction direction has been discussed. Also, the way of formation of diamino-substitution product and interesting isomerization process is presented.for 2,4-and 2,5-dinitroimidazoles. Introduction of an electron accepting substituent at position 5 in the 4nitroimidazole ring causes increase in cytotoxic and radiosensibiliting activity. 1 These compounds are essential especially in the treatment of diseases caused by bacteria and protozoa. The best known -Metronidazole, is effective against Bacteroides, Fusobacterium, Megasphaera, Clostridium, sometimes Peptococcus and Helicobacter pylorii. Tinidazole was found to be active against Gardnella vaginalis, Propionibacterium, Eubacterium, Campylobacter, Actinomyces and Spirochetes. Nimorazole and ornidazole have demonstrated activity against trichomoniasis. 1-4 Besides, nitroimidazoles are good radiation enhancers of hypoxic cells. From among nitroazoles, Misonidazole seems to be the best known

Crystal structure of ethyl 2-[2-(4-methylbenzoyl)-5-p-tolyl-1H-imidazol-1-yl]acetate

“…The Cambridge Structural Database (Groom & Allen, 2014) reveals only five structures of imidazole derivatives with a CH 2 COOCH 2 CH 3 substituent on nitrogen (Cai et al, 2014;Bahnous et al, 2013;Zaprutko et al, 2012). Imidazoles with benzoyl substituents are slightly more common with eight occurrences (Xue et al, 2014;Nagaraj et al, 2012;Samanta et al, 2013), while the structures of only six p-tolyl-substituted imidazoles are found (Bu et al, 1996;Fridman et al, 2006Fridman et al, , 2009.…”