Intermediate products in the reduction of nitro compounds

Intermediate products in the reduction of nitro compounds (Expts 6.87 to 6.91). 

The important spectroscopic features (i.r., p.m.r., m.s., and u.v.-visible) which are observed in this varied range of nitrogen compounds are discussed descriptively under appropriate preparative sections. 

Nitrobenzene Nitrosobenzene N- Pheny Ihydroxy lamine Aniline 

The initial product, nitrosobenzene, is so easily reduced to N-phenylhydroxyl-amine that it has not been isolated from the reduction medium, but its presence has been established by reaction in solution with hydroxylamine to yield a benzenediazonium salt, which couples readily with 1-naphthylamine to form the dyestuff 2-phenylazo-1 -naphthylamine. 

Under the catalytic influence of alkali, nitrosobenzene and Af-phenylhydroxyl-amine react to yield azoxybenzene. 

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All of these substances can be reduced to benzenamine with tin and hydrochloric acid. As a result, each could be, but not necessarily is, an intermediate in the reduction of nitro compounds to amines. Formation of the bimolecular reduction products is the result of base-induced reactions between nitroso compounds and azanols or amines and possibly further reduction of the initially produced substances (see Exercise 24-18). 

The reduction of nitro compounds involves the progressive removal and replacement by hydrogen of the oxygen in the —NO2 group. The intermediate products in the reduction of nitrobenzene, whose interrelationships are shown in Fig. 5-1, are obtained by control of the reduction potential of the system. 

In the reduction of nitro compounds to amines, several of the intermediate species are stable and under the right conditions, it is possible to stop the reduction at these intermediate stages and isolate the products (see Figure 1, where R = CgHg). Nitrosoben2ene [586-96-9] C jH NO, can be obtained by electrochemical reduction of nitrobenzene [98-95-3]. PhenyUiydroxylamine, C H NHOH, is obtained when nitrobenzene reacts with zinc dust and calcium chloride in an alcohoHc solution. When a similar reaction is carried out with iron or zinc in an acidic solution, aniline is the reduction product. Hydrazobenzene [122-66-7] is formed when nitrobenzene reacts with zinc dust in an alkaline solution. Azoxybenzene [495-48-7] ... 

The reduction of nitro compounds should initially produce nitroso compounds. This area has not been systematically explored because the nitroso group can be more easily introduced by alternative methods such as direct nitrosation, condensation and oxidative procedures. - In fact, there have been few instances in which nitroso compounds have been isolated as intermediates in reductions of nitro compounds. For example, it was initially believed that w-trifluoromethylnitrobenzene produced the corresponding nitroso compound upon reduction, but subsequently the product was shown to be w-trifluoromethylazox-ybenzene. - Low yields of an intramolecular dimeric, nitroso compound, benzo[c]cinnoline dioxide (1), can be obtained by reducing 2,2 -dinitrobiphenyl with zinc or sodium sulfide (equation I). - ... 

The reduction of aromatic nitro compounds is believed to proceed to an intermediate mixture of nitroso compounds and substituted hydroxylamines which are not isolated but condense to form an azoxy compound which, in turn, is reduced to an azo compound. Contributing evidence to substantiate this mechanism is that the reduction of a mixture of two aromatic nitro compounds leads to a mixture of azo compounds consistent with that predicted if each of the nitro compounds were reduced to a nitroso compound and a hydroxylamine and these, in turn, reacted with each other in all possible combinations. This observation also implies that the bimolecular reduction of nitro compounds is practical only from the preparative standpoint for the production of symmetrically substituted azo compounds. Spectrophotometric studies of the reaction kinetics of the reduction of variously substituted nitro compounds may, however, uncover reasonable procedures for the synthesis of unsymmetrical azo compounds. 

The fundamental object of his researches differs from that of Gattermann, in that Lob undertakes to establish the separate phases of the reduction of the nitro-group. This he accomplishes by the addition of formaldehyde to the electrolyte under varying conditions, and as a result the intermediate products, at the moment of their formation, combine with formaldehyde, producing condensation compounds which do not undergo further decomposition. By regulating the potential or density of the current the reaction can at... 

Reduction of nitro compounds to amines is a synthetically important reaction (98) and is practiced since the birth of modern chemical industry—many aromatic amines are key intermediates in production of dyes and pesticides. However, the stoichiometric reductions using iron or alkali metal hydrogen sulfides or catalytic hydrogenations with heterogeneous catalysts leave room for improvements in selectivity, especially with reference to halonitro-derivatives. There are many homogeneous catalysts such as the rhodium carbonyls in the presence of amines or chelating diamines, or [Rus(CO)i2] in basic amine solutions that are... 

Formation of azo-type products might be troublesome. These by-products, arising from reduction of aromatic nitro compounds, usually are assumed to be derived from the coupling of intermediate nitroso and hydroxylamine compounds. The coupling problem is accentuated in reduction of nitroso compounds because of much higher concentrations. It can be alleviated by dropwise addition of the substrate to the hydrogenation and use of acidic media. 

A number of 5-nitro-2-furaldehyde derivatives, called nitrofurans, are used in the treatment and/or prophylaxis of microbial infections, primarily in the urinary tract. Recent evidence suggests that the reduction of the 5-nitro group to the nitro anion results in bacterial toxicity. Intermediate metabolites modify various bacterial macromolecules that affect a variety of biochemical processes (e.g., DNA and RNA synthesis, protein synthesis) this observation may explain the lack of resistance development to these drugs. Evidence also indicates that the nitro anion undergoes recycling with the production of superoxide and other toxic oxygen compounds. It is presumed that the nitrofurans are selectively toxic to microbial cells because in humans, the slower reduction by mammalian cells prevents high serum concentrations. 

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