Nitrosamines alkylation

Until recently most of the mechanistic studies on nitrosation have been concerned with N-nitrosation reactions of amines, including the diazotisation reactions of primary amines. Now, work has been extended to include both O- and S-nitrosation, so that comparisons can be made. Mechanistic studies have also been extended in recent years to include reactions of nitrogen oxides, nitrosamines, alkyl nitrites, thionitrites and transition metal nitrosyl complexes. Many of these reactions have been used preparatively for a long time, but little has been known about their detailed reaction mechanisms. 

Hindered rotation occurs on the NMR time scale for numerous other systems with partial double bonds, including carbamates, thioamides, enamines, nitrosamines, alkyl nitrites, diazoketones, aminoboranes, and aromatic aldehydes. Formal double bonds can exhibit free rotation when alternative resonance structures suggest partial single bonding. The calicene 5-5, for example, has a barrier to rotation about the central bond of only 20 kcal mol . ... 

Nitrosamines, alkyl derivatives Steatosis, necrosis, carcinogenesis... 

Gas chromatography-mass spectrometry has been applied to the determination of other types of orgaruc compounds in waste waters including the following (Table 16.9) hydrocarbons, phenols, organic halogen compounds, polychlorobiphenyls, chlorophenols, chlorinated tyrosine, nitrosamines, alkyl benzene sulphonates, N,N dialkyldithio-carbamates, volatile organic compounds. 

Whatever the true details of the metabolic pathway shown in Scheme 1 might be, there are certain facts which are very secure. Among these are that the nitrosamines are oxidatively dealkylated, that electrophilic intermediates which alkylate proteins and nucleic acids are formed, and that one of the... 

Although the o-hydroxylation hypothesis has been given considerable support, it is clear that nitrosamines with alkyl side chains longer than methyl present additional possibilities for biological activation. It was stated earlier that even the o-hydroxylation hypothesis is based on considerable circumstantial evidence. This means that the other possible pathways are even more speculative, and hence, much more research needs to be carried out before some of the ideas advanced below will gain acceptance, or be put to rest. 

Nitrosamines require metabolic activation in order to produce a chemical species that will alkylate nucleophilic sites on a biomolecule such as DNA (1, . The crucial initial step in the... 

Ross and Chiarello (1979) have described a method for denitrosation of nitrosamines, such as dlalkylnitrosamines e.g. N-nitrosodimetl laminer etc., and complex aryl-alkyl nitrosamines, e.g. N-nitroso-N-(l-ethylpropyl)-3,4-dimethyl-2,6-dinitroaniline. The products of nitration and amination containing nitrosamlne as a substantial impurity are treated with an aldehyde or ketone in the presence of strong acids such as hydrochloric or hydrobromic acid. Under pressurized conditions at 105-110% for cme to two hours, the nitrosamlne is destroyed. The desired product can be recovered after neutralization of the excess acid. The equation shows the denitrosation of pendimethalin ... 

Metabolism of nitrosamines from tobacco generates a series of electrophiles that alkylate DNA, and some of the resulting adducts can also regenerate electrophilic intermediates illustrated in Scheme 9.4. This oxonium ion can be terminally quenched... 

R, R1 = alkyl, aryl, COR, CONHR Fig. 3.2 N-N restricted rotation in N-nitrosamines. 

The a-carbons of nitrosamines undergo enzymatic hydroxylation followed by oxidative cleavage leading to the formation of alkyldiazo hydroxides, alkyldiazonium ions and alkyl cations [34]. These cations are postulated to initiate the process of carcinogenesis in some cases by alkylating the base units of DNA [35, 36]. 

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