Vinyl nitrosamines

Another interesting class of nitrosamines are the vinyl nitrosamines. Several examples of this group have been described previously. We have however, developed two general, high yield methods, which will make these compounds available for study. 

We have just begun to explore the chemistry of these vinyl nitrosamines (which are really N-nitroso enamines) which are extremely interesting synthetic intermediates. One very exciting development has been their conversion to the corresponding epoxides. 

These epoxides are very reactive and are excellent alkylating agents. They may be the primary metabolic products of vinyl nitrosamines. One interesting reaction of the epoxides demands the intermediacy of long sought-after a-hydroxynitrosamine. 

The P450s catalyze a variety of reactions, including hydroxylation, epoxidation, peroxidation, sulfoxidation, dealkylation, deamination, etc., depending on the substrate structures. Many substrates, including alkenes, aromatic hydrocarbons, heterocycles, vinyl halides, e yl carbamate, vinyl nitrosamines, and aflatoxin Bl, have been epoxi-dized with good stereoselectivities by the membrane-boimd mammalian P450s [29]. 

Three groups of substances are regulated individually, i.e. vinyl chloride monomer in plastics (78/142/EEC), nitrosamines in rubber teats and soothers (93/11/EEC), and bisphenol A diglycidyl ether, bisphenol F diglycidyl ether, and novolac glycidyl ethers in plastics and coatings (2002/16/EC). 

Chemicals which can damage (a) the liver include carbon tetrachloride, paracetamol, bromobenzene, isoniazid, vinyl chloride, ethionine, galactosamine, halothane, dimethyl-nitrosamine (b) the kidney include hexachlorobutadiene, cadmium and mercuric salts, chloroform, ethylene glycol, aminoglycosides, phenacetin (c) the lung include paraquat, ipomeanol, asbestos, monocrotaline, sulfur dioxide, ozone, naphthalene (d) the nervous system include MPTP, hexane, organophosphoms compounds, 6-hydroxydopamine, isoniazid (e) the testes include cadmium, cyclophosphamide, phthalates, ethanemethane sulfonate, 1,3-dinitrobenzene (f) the heart include allylamine, adriamycin, cobalt, hydralazine, carbon disulfide (g) the blood include nitrobenzene, aniline, phenyl-hydrazine, dapsone. 

Metabolic activation systems—such as microsome-, cell-, and host-mediated assays—have been included in mammalian cell mutagenesis systems. Microsome-mediated assays have been used to detect many chemicals, including nitrosamines, polycyclic hydrocarbons, aflatoxins, and vinyl chloride. Cell-mediated assays seem to be a better indicator of in vivo metabolic pathways. Microsome-mediated assays seem suitable for general screening of chemicals, and cell-mediated assays are more valuable in the assessment of data. 

C8H16N202 N-butyl-N- 3-oxobutyl)nitrosamine 61734-90-5 317.85 26 700 1.2 15131 C8H160 hexyl vinyl ether 5363-64-4 416.15 35.890 1,2... 

The concept of metabolic activation developed with AAF was then apphed to PAHs, aflatoxins, nitrosamines, nitrosoureas, hydrazines, urethane, and vinyl chloride. Several metabolic activation schemes are presented in Figure 6.2. In each case a highly reactive electrophilic carbocation is formed. We now know that the concept of metabolic activation applies to many genotoxic carcinogens and helps to explain... 

In Table 33 are given the values of AH for the tautomeric change calculated from the differences in bond energies only. It is gratifying to find that these values correspond with the generally accepted opinions that, in simple cases, (1) the ketones and aldehydes are stable with respect to the vinyl alcohols, (2) the amides are stable with respect to the imidols, (3) the aldimines are stable with respect to the vinylamines, (4) the oximes are stable with respect to nitroso compounds, (5) diazohydroxy compounds are stable with respect to nitrosamines, (6) hydrazones are stable with respect to azo com-... 

Interest in alkaloids of the nicotine group appears to be on the increase. A review has appeared covering tobacco-specific nitrosamines, which may be causative factors in tobacco-related cancers. The solution conformation, and proton, deuterium, carbon-13, and nitrogen-15 n.m.r. spectra of nicotine and its 2- and 4-isomers, have been studied. A new synthesis of nornicotine and nicotine has been described, and a quantitative carbon-13 n.m.r. spectral analysis of nicotine that is labelled at positions 1, 2, and 3 with carbon-13 been presented. The synthesis and mass spectrometry of several structurally related nicotinoids have been reported. Nicotine is dehydrogenated on irradiation in benzene solution in the presence of benzophenone to l -methyl-2 -(3-pyri-dyl)pyrrole. ° Nornicotine has been synthesized in four steps from 3-bromo-pyridine and N-3-butenyl-phthalimide, using a palladium-catalysed vinylic... 

Cosmetic manufacturers may use essentially any raw material as a cosmetic ingredient insofar as it is not considered as only a drug active ingredient, and market the product without approval. The law regulates only colour additives specifically approved for cosmetics and a few prohibited and restricted ingredients (e.g. bithionol, mercury compounds, vinyl chloride, halogenated salicylanilides). Cosmetics should not be contaminated with nitrosamines, 1,4-dioxane and pesticide residues, whose potential presence is regularly checked by the FDA (see Section 2.1). 

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