Nitroanilines reduction

A curious method for determining the enzymatic activity of trypsin and of the duodenal content has been demonstrated on the cleavage of p-nitroanilides of some aminoacids [180]. The half-wave potential of p-nitroaniline reduction is more negative than that of the substituted derivatives and so the hydrolysis of the nitroanilides can be measured by the decrease of its reduction wave. 

Reduction. Reduce 0 5 g. of the nitroaniline with HCl and tin, as described on p. 385. Note that after a few minutes the original yellow colour has entirely disappeared. Cool and add 20% aqueous NaOH solution a white precipitate is formed which redissolves to give... 

It is convenient to include under Aromatic Amines the preparation of m-nitroaniline as an example of the selective reduction of one group in a polynitro compound. When wt-dinitrobenzene is allowed to react with sodium polysulphide (or ammonium sulphide) solution, only one of the nitro groups is reduced and m-nitroanUine results. Some sulphur separates, but the main reaction is represented by ... 

Compounds containing two primary amino groups attached to a benzene ring can be prepared by the reduction of dinitro compounds and of nitroanilines, usually with tin or stannous chloride and hydrochloric acid or with iron and very dilute hydrochloric acid. / ara-diamines may also be obtained by the reduction of aromatic amino-azo compounds (e.g., p-aminodimethylanihne from methyl orange, see Section IV,78). p-Phenylenediamine may also be prepared from p-nitroacetanilide reduction with iron and acid yields p-amino-acetaniUde,.which may be hydrolysed to the diamine. 

Experimental details are given for o-phenylenedlamlne, which is conveniently prepared by the reduction of o-nitroaniline in alcoholic sodium hydroxide solution with zinc powder ... 

Catalytic reduction of 1,2,4-oxadiazoles also breaks the N—O bond e.g. (264) gives (265). Benzofuroxan can be reduced under various conditions to benzofurazan (266), the dioxime (267) or o-phenylenediamine (268) (69AHC(10)l). Reduction by copper and hydrochloric acid produced o-nitroanilines (Scheme 30) (69AHC(lO)l). 

Diaminoazobenzene was reported by Nietzki to have been prepared by diazotizing -nitroaniline and coupling the product with aniline. The resulting 4-nitrodiazoaminobenzene is rearranged and the nitro group reduced. The submitters tried several times to carry out this procedure but were unsuccessful. 4,4 -Diaminoazobenzene has been prepared by the oxidation of -nitroaniline with potassium persulfate followed by the reduction of the nitro groups. ... 

The same methodology was also used starting from the ethyl 6-amino-7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate, prepared by reduction of the nitro derivative. The requisite nitro derivative was prepared by nitration of ethyl 7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate. A second isomer was prepared from 4-chloro-3-nitroaniline by reaction with diethyl ethoxymethylene-malonate, subsequent thermal cyclization, and further ethylation because of low solubility of the formed quinolone. After separation and reduction, the ethyl 7-amino-6-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate 32 was obtained. The ort/io-chloroaminoquinolones 32,33 were cyclized to the corresponding 2-substituted thiazoloquinolines 34 and 35, and the latter were derivatized (Scheme 19) (74JAP(K)4, 79CPB1). 

An analogous sequence leads to the anthelmintic agent, etibendazole (50). Reaction of the benzophenone 47, which can be obtained by acylation of o-nitroaniline with g-fluorobenzoyl chloride, with ethylene glycol leads to acetal 48. Sequential reduction of the nitro group and cyclization of the resulting diamine (49) with N,N-dicarbomethoxy-S-methylthiourea gives the benzimidazole etibendazole (50) fl6]. 

From 13.1 g of N-preduction with Raney-nickel and hydrogen, in which reaction the substance may be suspended in methanol or dissolved in methanol-ethyl acetate at normal pressure and at about 40°C with combination of the theoretical quantity of hydrogen, 12.2 g are obtained of o-emino-N-pfrom aqueous methanol hasaMPof90°C. 

The NH2 groups can be diazotized and reduced in the presence of thiosulphates and different metal ions. The effect of some metal ions, namely Fe ", Sn, Cu +, and Co on the graft yield of cotton modified with aryl diazonium groups via its reaction with 2,4-dichloro-6-(p-nitroaniline)-5-triazine in the presence of alkali and followed by reduction of nitro group was studied [4]. 

Nitroaminocompounds or Nitroamines. Compds containing both —N02 and —NH2 radicals attached to different C atoms, eg, nitroaniline, 02N.C6H4.NH2, etc. Nitroamines can be prepd either by the nitration of amines, or by partial reduction of nitrocompounds contg several —N02 groups. Another method is to treat a chloronitrocompound with ammonia, as in the prepn of dinitroaniiine... 

The hydroxyphenylbenzotriazole structure was constructed by a coupling of the diazonium salt of o-nitroaniline with 4-ethyl-phenol, followed by reduction of the nitro-azobenzene to the benzotriazole with zinc powder and NaOH. After blocking of the phenol by acetylation, bromination and dehydrobromination were performed as described earlier, and treatment with aqueous NaOH... 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

A similar approach, synthesis of a selectively substituted benzotriazole from the corresponding ortfe-nitroaniline, is depicted in Scheme 212. The process starts from a microwave-assisted substitution of the fluorine atom in 4-fluoro-3-nitrobenzonitrile 1270 by isopropylamine to give ortfo-nitroaniline 1271 in 99% yield. Reduction of the nitro group provides ortfo-phenylenediamine 1272 that is directly converted to 5-cyano-l-isopropylbenzotriazole 1273, which is isolated in 83% yield <2006JME1227>. 

The metabolism of an oral dose of 50-100 mg/kg "C-1,3-DNB was followed in rabbits (Parke 1961). Of the metabolites detected in urine, 30% were conjugated with glucuronic acid and 6% with sulfate. The major urinary metabolites of 1,3-DNB were 2,4-diaminophenol (31%), 1,3-phenylenediamine (25%), 1,3-nitroaniline (18%), and 2-amino-4-nitrophenol (14%). Other minor metabolites comprising about 20% of the label were oxidation and reduction products and azoxy dimers. 

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