7V-Nitrosamines

The ease of preparation of 7V-nitrosamines makes their reduction to N,N-disubstituted hydrazines an attractive route to the latter. A major diflSculty in effecting this reduction has been the ease with which both the nitrosamine and the resulting hydrazine are cleaved to the parent amine. The use of a titanium(n) reagent has now been found to circumvent this problem, and provides N,N-disubstituted hydrazines in good yield (Scheme 42). ... 

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. 

Oxygenation of lithiated dialkyInitrosamines in THF at —78°C is fast and gives good yields of the 7V-alkyl-N-(l-hydroperoxyalkyl)nitrosamines. If oxygenation is too prolonged, poor yields and explosive by-products result. 

Treatment of 3-amino-5,6-dihydro-2-thioxo-l,3-thiazin-4(3//)-ones (75) with nitrous acid results in oxidative desulfurization and the formation of the corresponding diones (76). However, if the N-amino substituent bears two methyl groups the reaction can proceed further and monodemethylation and 7V-nitrosation may take place, leading to the nitrosamine (77) (Scheme 9) <86AP521>. 

Hecht, S.S., J.D. Adams, and D. Hoffmann HPLC-TEA of tobacco-specific nitrosamines in Environmental carcinogens. Selected methods of analysis. Vol. 6.7V-Nitroso componnds, edited by H. Egan, R. Preussmann, G. Eisenbrand, T. Spiegelhalder, I.K. O Neill, and H. Bartsch, lARC, Lyon, Erance, lARC Sci. Publ. No. 45 (1983)429-436. 

Studies on the metabolism of cyclic nitrosamines in organ culture systems have been carried out on NPYR, NPIP, NNN, and A, 7V -dinitrosopiperazine (DNP). In cultured human bronchi, NPYR, NPIP, and, to a lesser extent, DNP, were metabolized to CO2 178). All three nitrosamines were bound to protein and DNA of the bronchial explants. In cultured human colon, NPYR and DNP were metabolized to CO2 and were bound to DNA and protein (75). Low levels of binding were observed for NNN and NPIP. 

Nitrosating agents such as nitrous acid, dinitrogen trioxide, dinitrogen tetraox-ide, nitrosyl chloride, and alkyl nitrites are sources of NO (nitrosonium ion), which react with secondary amines to yield the corresponding A-nitrosamines. Similarly, secondary amides yield their corresponding A-nitrosoamides, ureas yield 7V-nitrosoureas, and carbamates, the 7V-nitrosocarbamates. 

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