Nitrosamine derivatives

This property has been exploited in syntheses of /V-nitrosamine derivatives by the reaction of electrophiles (E) with a-Hthiated intermediates. These intermediates are prepared by hydrogen—Hthium exchange using Hthium dusopropylamide [4111-54-0] (LDA) (76,77). 

Mutagenicity. The AJ-nitrosamines, in general, induce mutations in standard bacterial-tester strains (117). As with carcinogenicity, enzymatic activation, typically with Hver microsomal preparations, is required. Certain substituted A/-nitrosamine derivatives (12) induce mutations without microsomal activation (31,33,34). Because the a-acetoxy derivatives can hydroly2e to the corresponding a-hydroxy compounds, this is consistent with the hypothesis that enzymatic oxidation leads to the formation of such unstable a-hydroxy intermediates (13) (118). However, for simple /V-nitrosamines, no systematic relationship has been found between carcinogenicity and mutagenicity (117,119—123). 

V-Alkylpipera ines and PIP can react with nitrosating agents such as nitrogen oxides, nitrites or nitrous acid to form nitrosamine derivatives (61,62). Piper a2ine dihydrochloride [142-64-3] reacts with aqueous sodium nitrite and HCl to give the dinitrosamine that melts at 156—158°C (61). 

Bioassay in Strain A Mice of Nitrosamines Derived from Nicotine... 

V-Nitrosodiethanolamine has been found in many complex matrices such as cutting and grinding fluids and cosmetics. Analysis for V-nitrosodiethanolamine is complicated by the matrix and a clean-up technique with derivatization is typically required before quantitation of the analyte to achieve adequate sensitivity and selectivity. Ammonium sulfamate may be added to the sample to prevent the artifactual formation ofV-nitrosamines. Derivatives of V-nitrosodiethanolamine have been prepared by acylation, trifluoroacylation, trimethylsilylation and methylation. The derivatives have been analysed by gas chromatography using flame ionization and mass spectro-metric detectors (Occupational Safety and Health Administration, 1990). 

Kamataki, T. et al. (2002) Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine derivatives application of genetically engineered Salmonella expressing human CYP. Drug Metab. Rev, 34 (3), 667-676. 

Fig. 31. Relation of half-wave potentials (at pH 11) for the oxidation of cyclic -phenylenediamines to half-wave potentials in 0.1 M NaOH for the reduction of nitrosamines derived from the same cyclic amines...

In the second degradation shown for dihydrolythrine (see Scheme 1) both lythrine and vertine were converted to /V-nitrosamine derivatives (38) and an... 

Compounds (165) are unstable, the 3-methyl derivative being completely decomposed after one day standing at room temperature. They are also very unstable towards strong bases. The acetyl derivatives, however, are more stable. Nitrosamine derivatives of (165a) have also been prepared. 

Nitrosamines form as a result of the reaction of nitrosating agents with secondary amines in the rubber. One of the main sources of secondary amines is a number of the accelerators that are used in sulphur-based cure systems, the amines being breakdown products produced as a result of the chemical reactions taking place during vulcanisation. Specific examples of these accelerators, their secondary amine products (i.e. the nitrosatable compounds) and the nitrosamines derived from them, are given in Table 12.7. 

The nitrosamine (121) and especially diazonium salts (122) prepared from it, as well as their alkyl and aryl derivatives, are important synthetic intermediates (b-76MI4i200, p. 325). For conditions that decide between nitrosamine function or diazotization see (73jcS(P1)13S7). At room temperature or in concentrated hydrochloric acid nitrosamines derived from triazoles are unstable, and their decomposition products include chlorotriazoles (63LA(665)144) 5-nitrosamino-3-phenyl-l,2,4-triazole affords the 5-bromo compound with hydrobromic acid at 0 °C and reacts violently with hydroiodic acid (05lA(343)i). Thermal arylation with triazole nitrosamines is possible (73jcs(pi)i357). 

Eernandez-Marcote, M.S.M. Mochon, M.C. Sanchez, J.C.J. Perez, A.G. Electrochemical reduction of prilocaine as its V-nitrosamine derivative at the mercury electrode. Electroanalysis 1998, 10, 492-496. 

The saliva of betel nut chewers contains nitrosamines derived from areca nut alkaloids (4), and the use of areca nuts has been widely imphcated in the development of oral cancers. 

An apparent geometrical dependence of the 37(15N-N—C-H) coupling constants of some N-nitrosamine derivatives, [83] (Table XXXIV,... 

It has long been known that nitrosamines derived from nicotine and certain of its metabolites are carcinogenic to experimental animals and the possibility exists that nitrosation could occur in vivo particularly in areas of high environmental nitrite/ nitrate. At present, there seems to be no evidence that implicates this process in smoking cessation programmes. However, it is important that evidence of addiction, cardiovascular diseases and carcinogenesis are carefully monitored in populations exposed to "medicinal" nicotine for long periods. 

Nitrosamines derived from 5-amino-1,2,4-thiadiazoles are readily accessible stable compounds.3 Thermolysis of the substituted 5-nitrosoimino-1,2,4-thiadiazolines (48574 and 486383) produces the corresponding 5-ketones (487, 488) with evolution of nitrogen almost quantitatively. Their photolysis, involving n- n excitation, proceeds less uniformly. Irradiation of 486 in various solvents yields, as primary products, Hector s base (14b) and phenyl-cyanamide subsequent changes produce their 1 1-adduct, as well as 3,5-dianilino-l,2,4-thiadiazole, phenylurea, and other compounds, all in variable moderate yield. The photolytic fragmentation is more complex than that of comparable heterocyclic nitrosimines.384... 

Hecht, S.S. and A.R. Tricker Nitrosamines derived from nicotine and other tobacco alkaloids Chapter 11 in Analytical determination of nicotine and related compounds and their metabohtes, edited by J.W. Gorrod and P. lacob III, Elsevier, New York NY (1999) 421 88. Hecht, S.S., T.C. Tso, and D. Hoffmann Approaches to the reduction of nitrosamines and aromatic amines in Modifying the risk for the smoker. Proc. 3rd World Conf. on Smoking and Health, edited by E.L. Wynder, D. Hoffmann, and G.B. Gori, 1975, DHEW Publ. No. (NIH) 76-1221 (1976) 535-545. 

The use of accelerators based on secondary amines is being reduced or eliminated. This is because secondary amines can react with nitrogen oxides to form suspected carcinogenic nitrosamines. This is especially a problem with dithiocarbamate-type accelerators. Proposed accelerators that do not give carcinogenic nitrosamine derivatives include... 

From the aspect of chemical carcinogenity the polarographic determination of N-nitrosamines become important. These compounds may be present in food, beverages and atmosphere, occasionally they can be formed in the body by nitrosation of amines, especially in the stomach. There were many papers published describing the determination of various nitrosamines (derivatives of proline, pyrolidine, piperidine, etc.) in different matrices[26]. The most important problem in their analysis (as with the... 

Centralite is hydrolysed with 60 per cent sulphuric acid, and the N-ethylaniline formed can again be determined after nitrosation. The half-wave potentials of nitrosamines derived both from diphenylamine and phenylethylamine are in the neighbourhood of —0-65 V (at pH about 2). 

Oyumi, Y. and Brill, T.B. Thermal Decomposition of Energetic Materials 5. High-Rate, In Situ, Thermolysis of Two Nitrosamine Derivatives of RDX by FTIR Spectroscopy Combustion and Flame 62, 233-241. 

In Summary Nitrous acid attacks amines, thereby causing N-nitrosation. Secondary amines give Ai-nitrosamines, which are notorious for their carcinogenicity. Ai-Nitrosamines derived from primary amines decompose through SnI or Sn2 processes to a variety of products. Ai-Nitrosation of N-methylamides results in the corresponding N-nitrosamides, which liberate diazomethane upon treatment with hydroxide. Diazomethane is a reactive substance used in the methylesterification of carboxylic acids and as a source of methylene for the cyclo-propanation of alkenes. 

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