V-Nitrosoamines

A characteristic property of most diazotizations of aminoazoles is the occurrence of a relatively stable transient intermediate (probably the /V-nitrosoamine), in contrast with the diazotization of carbocyclic aromatic amines, where /V-nitrosoamines have been considered to be unstable intermediates. 

Westin, J.B., Spiegelhalder, B., Preussmann, R. Shani, J. (1990) Assay of suntan lotions for the carcinogenic, non-volatile V-nitrosoamine V-nitrosodiethanolamine. Cancer Lett., 50, 157-160... 

The ease with which diazo compounds are formed in these reactions should constitute reasonable warning that the nitrosation of all amines is fraught with considerable hazard. Not only can the unstable diazo compounds be formed, but also the intermediate /V-nitrosoamines themselves may be explosive in nature. Therefore each particular case must be carefully examined with all caution. As a matter of fact, even though reactions may have been run successfully at one time or another, this does not necessarily imply that the reaction is indeed safe (see safety note in Redemann et al. [18a]). 

B-14. Which compound yields an /V-nitrosoamine after treatment with nitrous acid (NaNOz, HC1) ... 

The initial product is a salt of hydrazinesulfonic acid, which is converted to the hydrazine by acid treatment. Diazonium salts can also be reduced to arenes (19-69). V-Nitrosoamines can be denitrosated to secondary amines by a number of reducing agents, including H2 and a catalyst,BF3—THF—NaHCOa, and NaBH4-TiCl4, as well as by hydrolysis. 

Reactions of these compounds with the secondary and tertiary amines contained in many foods lead to the known carcinogens. V-nitrosoamines ... 

Certain species of Enterobacteriaceae, especially 0. proteus, could utilise nitrates as electron acceptors for anaerobic respiration, resulting in reduction of nitrate into nitrite. Nitrite further could possibly react with secondary amines present in the wort, forming (V-nitrosoamine (Figure 8.2). A -nitrosomines are carcinogenic in nature (Smith, 1994). Hence, a considerable amount of apparent total N-nitroso compounds (ATNCs) represents a possible risk to health, and consequently their concentration is strictly monitored and limited to 20 gg/1 (Maiguerite and Walker, 2002). Because of the risk of W-nitroso compounds, the Enterobacteriaceae species related to brewery environments are monitored. 

Indoor and outdoor exposure to many chemical substances (formaldehyde, asbestos, PVC, many metals, like Cr, As, Be, Ti, V, pesticides and nitrosoamines) can also spur the development of cancer. Here we can only state that the International Agency for Research of cancer has identified 60 environmental agents that can aggravate cancer for humans during exposure to polluted urban air (Misch, 1994). 

On treatment of certain other tertiary aromatic amines with nitrous acid, it has been found that either C-nitroso compounds, nuclear nitro compounds, or jV-nitrosoamines are formed with loss of an alkyl group. In the case of the nitrodimethylanilines, the latter two types of reaction may occur. The formation of nitro-jV-nitrosomethylanilines predominate at room temperature, whereas the formation of polynitro compounds predominates at more elevated temperatures. The formation of nitrosoamines from iVW-dimethylanilines appears to be particularly favored when both ortho positions are occupied by nitro groups, although /V-nitroso compounds were also obtainable from other nitrodimethylanilines. The product of the reaction, of course, is an /V-nitroso secondary amine. 

The reaction, called diazotization of an amine goes as follows Nitrous acid is pro-tonated by a strong acid to form the nitrosonium ion, Nitrosonium ion reacts with the primary amine to form AAnihosoammomum, an unstable compound., V-ni-trosoammonium deprotonates to form AAnitrosoamine. W-nitrosoamine tautomerizes to diazenol. In die presence of acid, diazenol dehydrates to diazonium... 

Similar reactions occur with TV-nitrosoamines R2-NNO and /V-nitrosoamides RC0(R )NN0.70 Apart from the intramolecular hydrogen atom transfer, diverse intramolecular radical additions (cyclizations) and other rearrangements have also been used to obtain cross-reaction products between NO and the radicals resulting from the transformation of the primarily formed R to another radical R. 69 70 Giving evidence for the persistent radical effect, the yields of the desired products are large and those of the selftermination of the transient intermediates are low,... 

Khudoley V, Malaveille C, Bartsch H. 1981. Mutagenicity studies in Salmonella tvnhimurium on some carcinogenic N-nitrosoamines in vitro and in the host-mediated assay in rats. Cancer Res 41 3205-3210. 

Nitrosoamines or nitrasamines are derivatives of amines, containing V-nitroso groups ( N—N=0)- Typically, a nitrosamine is formed by the reaction of an amine with a nitrite. These substances are also produced by the action of nitrate-reducing bacteria. Nitrosoamines occur in trace quantities in tobacco smoke, processed food, meat products, and salted fish. Many nitrosoamines are used as gasoline and lubricant additives, antioxidants, stabilizers, and softeners for copolymers. These compounds are noncombustible liquids or solids at ambient temperature. The hazardous properties of nitrosoamines are different from those of their parent aliphatic or aromatic amines. 

Archibald TG, Barnard JC, Harlan RF (1998) Continuous process for diazomethane from an N-methyl-N-nitrosoamine and from methylurea through V-methyl-V-nitrosourea (Aerojet General Corporation). US Patent 5,854,405... 

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