Patent GB-1362444-A (GB)
Title: 2-nitro-imidazole derivatives and methods for their preparation
IPC: C07D233/58
Filed: 1972-07-13
Abstract: 1362444 5 - Substituted - 2 - nitro - imidazoles GRUPPO LEPETIT SpA 13 July 1972 [30 July 1971] 32886/72 Heading C2C  Novel compounds I in which R is C 1-4  alkyl and Y is -CH 2 OH, -CHO, -CO-CH 3 , -CH = CH 2 , styryl, -CH=CH-CHO, substituted iminomethyl 2- benzimidazolyl or 5-amino-1,3,4-thiadiazole-2-yl are prepared, except for those in which Y is vinyl or styryl, by submitting a vinyl derivative of general Formula II in which X is hydrogen, alkyl, aryl or heterocyclic radical to oxidative cleavage with a mild oxidizing agent to form 1-(lower-alkyl)-2- nitro-5-imidazolo aldehyde and (a) when Y is required to be -CH 2 OH reducing the aldehyde with sodium borohydride, (b) when Y is required to be -CO-CH 3  reacting the 5-imidazolaldehyde with diazomethane, (c) when Y is required to be -CH=CH-CHO reacting the 5- imidazolaldehyde with acetaldehyde in the presence of a strong base, (d) when Y is required to be substituted iminomethyl reacting the 5- imidazolaldehyde with an amine, a hydrazine or a hydroxylamine derivative, (e) when Y is required to be 2-benzimidazolyl reacting the 5- imidazolaldehyde with o-phenylenediamine in the presence of a mild oxidizing agent, (f) when Y is required to be 5-amino-1,3,4-diazol-2-yl reacting the 5-imidazolaldehyde thiosemicarbazone derivative in the presence of a ferric salt. Substituted iminomethyl includes hydrazones and their functional derivatives including semicarbazones, thiosemicarbazones, guanylhydrazones, aldazines (which contain the unit), Schiff's bases, substituted hydrazones (in which the second nitrogen atom forms part of a 5-7 membered heterocyclic ring which may contain other heteroatoms selected from N, O or S) and oximes including their functional derivatives particularly nitrones. 1-(Loweralkyl) - 2 - nitro - 5 - vinyl - imidazoles are prepared by treating 1-(lower-alkyl)-2-nitro-5-(2- chloroethyl)-imidazole with a strong base preferably potassium butoxide. In the preparation of the aldehyde derivative by oxidative cleavage a novel intermediate, the corresponding 5-(1,2- dihydroxyethyl) compounds may be obtained by oxidation with potassium permanganate in a neutral solution or with osmium tetroxide. 1- (Lower - alkyl) - 2 - nitro - 5 - hydroxymethyl imidazoles are prepared by reduction of the novel 5-carbo-alkoxy derivatives with lithium borohydride and treatment of the alcohol with an oxidizing agent, preferably manganese dioxide, gives the corresponding aldehyde. 1-(C 1-4  alkyl) - 2 - nitro - 5 - styryl - imidazoles are prepared from the aldehyde by reaction with benzaldehyde in the presence of an oxidizing agent, preferably potassium butoixde. Novel starting material 1-methyl-2-nitro-5- carbethoxy imidazole is prepared by reaction of α- methylamino - α - carbethoxyacetaldehyde diethylacetal with cyanimide to form 2-amino-5 carbethoxy - 1 - methylimidazole which is oxidized to the 2-nitro derivative using sodium nitrite. Compounds I are active against grampositive and gram-negative bacteria as well as protozoa and fungi and form with a carrier a pharmaceutical composition which may be administered orally.