Nitroso compounds to amines

The catalytic reduction of aromatic nitroso compounds to amines is well documented. Selective reduction of nitro aromatic compounds can be achieved at room temperature and atmospheric pressure using an interlamellar montmorillonitesilylpalladium(II) complex (equation 20)." ... 

Copper salt-amine complexes can also be used for the reduction of aromatic compounds to the corresponding amine.A more general and convenient method for reducing nitroso compounds to amines involves the use of a nickel/aluminum alloy. The low cost and ready commercial availability of nickel/aluminum alloy are important features of this reduction procedure which may find wide acceptance as a preparative method. 

Nitro- and nitroso-compounds,170171 amines, and thiols induce the decomposition of diacyl peroxides in what may be written as an overall redox reaction. Certain monomers have been reported to cause induced decomposition of BPO. These include AN,172 A -vinylcarbazole,17,177 Ar-vinylimidazole178 and NVP.177... 

Oxidation of Primary Amines, Oximes, Azides, Isocyanates, or Nitroso Compounds to Nitro Compounds... 

Divalent chromium reduces triple bonds to double bonds (trans where applicable) [195], enediones to diones [196], epoxides to alkenes [192] and aromatic nitroso, nitro and azoxy compounds to amines [190], deoxygenates amine oxides [191], and replaces halogens by hydrogen [197,198],... 

The most direct way of testing the possibility that reaction of an ingested amine with nitrite can give rise to sufficient of a carcinogenic N-nitroso compound to induce tumors has been to feed the amine and nitrite simultaneously to animals for most of their lifespan. The first successful experiment of this type was that of Sander and BUrkle ( ), using the amine methyl benzyl amine, which when fed to rats with nitrite induced esophageal tumors, the same tumor induced in rats by feeding nitrosomethyl benzyl amine. Similar experiments were carried out in mice with piperazine (24), and in rats with heptamethyleneimine (25). 

In view of the various possible pathways for nitrosation of amines as well as of amine derivatives (amides, ureas, carbamates, etc. ), it is not unexpected then for N-nitroso compounds to be found in many different areas of the human environment (11). It is possible that N-nitroso compounds may represent a carcinogenic exposure which most people experience on a daily basis. The list of items that have now been demonstrated to have measurable levels of various N-nitroso compounds present within them has grown considerably over the past decade (, 11, 12). A portion of this list would include air, water, soil, cheese, meats, fish, eggs. 

Knaak, J.B., Leung, H.-W., Stott, W.T., Busch, J. Bilsky, J. (1997) Toxicology of mono-, di-, and triethanolamine. Rev. environ. Contam. Toxicol., 149, 1-86 Konishi, Y, Yokose, Y, Mori, Y, Yamasaki, H., Yamamoto, K., Nakajima, A. Denda, A. (1987) Lung carcinogenesis by V-nitrosobis(2-hydroxypropyl)amine-related compounds and their formation in rats. In Bartsch, H., O Neill, l.K. Schulte-Hermann, R., eds. Relevance ofN-nitroso Compounds to Human Cancer Exposures and Mechanisms (lARC Scientific Publications No. 84), Lyon, lARCPrexx, pp. 250-252... 

Further complications of the reduction of aromatic nitro compounds are the possibility of complete reduction to aromatic amines (which may condense with nitroso compounds to give the desired azo compounds), reduction of azo compounds to the corresponding hydrazo compounds, followed by a benzidine (or semidine) rearrangement. It is clear, therefore, that the level of reducing agent used and other reaction conditions are quite critical. 

A very flexible method of preparing unsymmetrical azo compounds makes use of the condensation of C-nitroso compounds with amines. Thionylamines have also been condensed with substituted hydroxylamines to produce azo compounds not usually accessible by other means. Treatment of dialkylsulfuric diamides with sodium hypochlorite is one means of preparing aliphatic azo compounds. Aromatic amines and aromatic nitro compounds at high temperature produce azo compounds. 

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). 

SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic and tumorigenic data. Poison by intravenous route. An eye irritant. Solutions with thorium salts are unstable explosives above 15°C. Solutions with titanium or zirconium salts are unstable explosives above 40°C. When heated to decomposition it emits very toxic NH3 and NOx. See also N-NITROSO COMPOUNDS and AMINES. 

Reductions of aromatic nitro compounds often proceed to generate mixtures of nitroso and hydroxyl-amine products which then condense to form azoxy and, eventually, azo compounds. This bimolecular reduction is practical only for the generation of symmetrically substituted azo compounds. The situation can be further complicated if the reduction continues such that aromatic amines are formed the amines may then condense with the intermediate nitroso compounds to generate hydrazo compounds which can then undergo a benzidine rearrangement. 

Nitroso compounds and hydroxylamines can be reduced to amines by the same reagents that reduce nitro compounds (19-45). Reaction with CuCl, and then phe-nylboronic acid (p. 815), also reduces nitroso compounds to the amine.A hydroxylamine can be reduced to the amine with CS2 in acetonitrile. Indium metal in EtOH/aq. NH4CI reduces hydroxylamines to the amine. V-Nitroso compounds are similarly reduced to hydrazinesm R2N—NO R2N-NH2. ... 

In mammalian systems, nitroaromatic compounds are further reduced to amines and/or hydroxylamines, which may subsequently form DNA and protein adducts. These stable metabolites may be formed by the reduced oxygen tension and high local single-electron transferring enzyme concentration, for example, P-450R in microsomes may favor the free radical dismutation over their reoxidation by oxygen (Equation 9.8). Subsequently, the nitroso compounds formed (Equations 9.7 and 9.8) will be reduced to hydroxylamines (ArNHOH) and/or amines (ArNHj). The stable metabolites may also be formed by the two-electron reduction of nitroaromatics by certain flavoenzymes. In fact, the enzymatic two-electron reduction may be considered as the four-electron reduction, since after the first two-electron (hydride) transfer, the reduction of an intermediate nitroso compound to hydroxylamine (ArNHOH) proceeds faster [55] ... 

Mow has developed the use of rotary mills using freely moving ponderous agitators, such as iron balls, for the reduction of nitro, nitroso, and azo compounds to amines with iron in aqueous emulsion in order to effect grinding action during the reduction. Such mills are also useful in the distillation of aromatic amines from the iron oxide sludges in vacuum. 

Nitro Compounds. - Catalytic hydrogenation of nitro compounds to amines takes place readily at room temperature and atmospheric pressure. The mechanism proceeds via the nitroso and hydroxylamine stages and azo, azoxy, and hydrazo compounds may also be produced. ... 

Oxidation of Aromatic Amines and Nitroso Compounds to Azo and Azoxy Compounds... 

It is based primarily on the ability of aromatic C-nitroso compounds to attach themselves to diene polymers (Figure 11). When diisocyanates are also present, the pendant secondary aromatic amine is attacked with formation of a ureido bridge (Figure 12). Since isocyanates are both toxic and abortively reactive with moisture, it is convenient to prereact them with the o-nitrosophenol so that the compounding agent, which breaks up with heat, is actually a type of diurethane species (Figure 13). 

Thus metabolic nitro reduction proceeds through a nitroso compound to a hydroxylamine, and finally to a primary amine. Occasionally, the nitroso compound and/or the hydroxylamine can be detected as a metabolite, but most commonly it is the amine that is the major metabolite of nitro... 

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