Nitrosoimmonium ion

The above scheme satisfies much of the metabolic data however, some of it is speculative, and it is certainly incomplete. The evidence for the formation of the a-hydroxylated intermediate is circumstantial. The acetate ester of a-hydroxylated dimethylnitrosamine has been prepared (12.13) and has been found to be a potent, directly acting carcinogen (14). Other esters of a variety of a-hydroxylated nitros-amines have also been prepared (15). While it has been shown that DMN acetate is hydrolyzed to hydroxymethylmethyl-nitrosamine by an esterase enzyme, it has been pointed out that these derivatives of the a-hydroxylated nitrosamines also dissociate to N-nitrosoimmonium ions (15 16). 

Wiessler (15) suggested that the nitrosoimmonium ion could act as the electrophile which alkylates cellular nucleophiles. 

Since N-nitrosoimmonium ions seem to be involved in the hydrolysis of a-acetates, it should be possible to isolate such species as stable salts. For this purpose, we selected a system such as XVII in which the phenyl group should provide further stabilization of such a carbonium ion. After the reaction of nitrosyl chloride with the corresponding imines, addition of antimony pentachloride resulted in the precipitation of pale yellow solids these could be isolated and stored under nitrogen for several days at room temperature. ... 

In summary our study of a-substituted nitrosamines has given us a very interesting view of the chemical reactivity of this class of compounds. We have been able to show that the chemical behavior is governed by the intermediate existence of N-alkyl N-nitrosoimmonium ions in the thermal and solvolytic reactions. The significance of these N-alkyl N-nitrosoimmonium ions in the biological activity of dialkyInitrosamines is not clear at the moment. 

These ions are presumably so reactive that they are able to alkylate their own anion. The stronger the acid, the better the dissociation and the easier the rearrangement. At present, we are investigating the mechanistic details of this self-alkylation. One can imagine that a stronger nucleophile which comes from outside could be alkylated by the nitrosoimmonium/anion complex ... 

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