A-Nitrosamides

Treatments in the presence of alkaline reagents may evolve diazoalkanes, which are toxic gases and at least one of which (diazomethane) induces tumours in mice and rats. These methods, which were highly recommended for use with iV-nitrosamines, could not therefore be used for degradation of iV-nitrosamides. 

A third denitrosation method involved use, as for A-nitrosamines, of the action of hydrobromic acid in glacial acetic acid. The reaction was very fast - less than 10 min were required to achieve better than 99.9% degradation - but re-formation was observed and it was necessary to remove the nitrosylbromide. After investigation of several possible chemical reagents, flushing out with nitrogen was found to be the most 

Waste category Recommended destruction method no. (in order of preference)  

Solutions in volatile organic solvents, including dichloromethane and  

Method 1 Destruction of A-nitrosamides in laboratory wastes using sulfamic acid in hydrochloric acid solution  

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Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

Under appropriate condition, the peptide bond may react with aqueous nitrous acid to form a nitrosamide (32). It has been shown (33, 34, 35) in model systems that N-substituted amines can be formed by reaction between free amines and triglycerides. 

A reagent composed of tetra-n-butylammonium nitrate and TFAA in methylene chloride has been used to nitrate a series of A-alkyl and A-aryl amides (40-90 %). The formation of significant amounts of A-nitrosamides was noted. Tetra-n-butylammonium nitrate and triflic anhydride in methylene chloride has been used to successfully nitrate a variety of heterocyclic amides, imides and ureas (66). ... 

Aside from the explosive hazard of A-nitrosamides, it also has been observed that many A-nitroso compounds have a serious physiological effect on mucous membranes and on the skin. Apparently, this corrosive action is not observed in the case of A,A -dinitroso-A,A -dimethyloxalamide [37a, b]. Even so, considering that some A-nitroso compounds are reputed to be carcinogenic, due care should be exercised in the handling of all nitroso compounds. 

Recent advances in chromatography have made it possible to employ microbore HPLC for the determination of NOC. Its main advantage is that it uses a very low mobile-phase flow (20-100 /rl/min). This might make the TEA compatible with a reversed-phase system. Massey et al. (73), in fact, have successfully used reversed-phase chromatography for the HPLC-TEA determination of V-nitroso-V, 7V -di methylpiperazinium iodide. A 500-mm X 1-mm microbore ODS column and a mobile phase consisting of 0.1 M ammonium heptane-sulfonate in methanol water (70 30) (flow rate 20 /zl/min) was used for the HPLC separation. In another study, Riihl and Reusch (74) used a microbore Spherisorb 3 SW column for HPLC-TEA determination of volatile V-nitrosamines. The mobile phase was a mixture of 2-propanol and n-hexane (2.5 97.5). Further application of such techniques for the determination of various polar NOC, especially A-nitrosamides, in foods is desirable. 

Another drawback of the TEA (both in the GC and HPLC modes) is that A-nitrosamides give extremely poor yields ( 1%) of NO upon pyrolysis. When heated, these compounds, instead of splitting into NO and the parent amides, rearrange to yield diazoalkenes and nitrogen. Recently reported modifications of the TEA have somewhat improved this deficiency in the GC mode, but the corresponding improvements in the HPLC mode are yet to be worked out (78). 

The preceding method worked well for the determination of several A-nitrosamides, including streptozotocin. Because of the high dead volume of the system, however, considerable peak broadening occurred, especially for the late-eluting peaks. The technique was applied to the determination of NMU in fried bacon (detection limit 10 ppb) (Table 1). 

The next pesticide analyzer is described by Singer, et al (6) and used post-column derivatization for a nitrosamide-specific reaction. Following chromatographic separation and UV detection, the stream was air-segmented and treated with the Griess Reagent (Figure 11). The... 

Many N-unsubstituted pyrazoles 80 can be obtained from A-allyl-A-nitrosamides 79 (Scheme 46) <1990H(30)789>. Cyclocondensation of -alkoxyvinyl trifluoromethyl ketones 81 with thiosemicarbazide under mild conditions affords 4,5-dihydro-l//-pyrazole-l-thiocarboxamides 82, which can be easily dehydrated with concomitant thiocarboxamide group hydrolysis in concentrated sulfuric acid to give N-unsubstituted pyrazoles 83 (Scheme 47) <1998JFC(92)23>. 

A-nitrosamides behave in acid solution like A-nitrosamines they are reduced to acylated hydrazines. In this way alkylhydrazines may be prepared from primary amines by the following reactions [216]. 

A kinetic model was proposed by Turco et al. [53] with a nitrosamide as an intermediate compound and vanadyl groups were supposed to be the active sites. 

In this section, all the reactions have in common the formation of an N—C bond as the last step in the synthesis of pyrazoles and indazoles. First, pyrazoles and then indazoles are discussed. Pyrazole itself and many other N f-pyrazoles have been obtained from A-allyl-A-nitrosamides <90H(30)789> to illustrate the reaction. Scheme 6 represents the case of pyrazole (7). The reaction of... 

When mixed with the equimolar solution of amides R C(0)NHR (41) in CHCI3, complex 38 reacted quickly at room temperature, yielding up to 95% of A-nitrosamides (42, Fig. 17) (76). Dark-blue solutions of 38 lost their color upon addition of the substrates, which is a reasonable visual test for the reaction. Among the variety of amides (41), only those possessing A-Me substituents were transformed to the corresponding A-nitrosamides (42). No reaction occurred for substrates with bulkier groups. Consequently, no color discharge... 

Nitrate and nitrate salts naturally occur in vegetable, fish and meats, are in food for their preservative properties and are present in pesticide and drug residues in food. They react with other chemicals in the body to produce NNAs and A-nitrosamides. 

Sen, N.P. and S. Seaman On-line combination of high-performance liquid chromatography and total A-nitroso determination apparaffis for the determination of A-nitrosamides and other A-nitroso compounds and some recent data on the levels of A-nitrosoproline in foods and beverages in A-Nitrosocompounds Occurrence, biological effects and relevance to human cancer, edited by I.K. O Neill, R.C. von Borstel, C.T. Miller, J. Long, and H. Bartsch, LARC, Lyon, France, lARC Sci. Publ. No. 57 (1984) 137-143. 

Diazomethane reacts rapidly with unesterified fatty acids in the presence of a little methanol, which catalyses the reaction, to form methyl esters. The reagent is generally prepared as a solution in diethyl ether by the action of alkali on a nitrosamide, e.g. N-methyl-/V-nitroso-p-toluene-sulfonamide (Diazald, Aldrich Chemical Co., Milwaukee, U.S.A.). Solutions of diazomethane are stable for short periods If stored refrigerated in the dark over potassium hydroxide pellets. If they are kept too long, polymeric byproducts form which may interfere with the subsequent GC analysis. 

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