Carcinogen Chemistry. I. Reactions of Protonated Dialkylnitrosamines Leading to Alkylating and Aminoalkylating Agents of Potential Metabolic Significance

Summary

Three distinct modes of protolytic dialkylnitrosamine fragmentation were observed when we followed the time dependence of the nuclear magnetic resonance (NMR) spectra of seven nitrosamines in superacid solution: 1) In equimolar HSO₃F: SbF₃ (“magic acid”), dimethylnitrosamine was cleaved to the protonated Schiff base of formaldehyde and methylamine, and diethylnitrosamine was similarly converted to the protonated acetaldehyde-ethylamine Schiff base. 2) By contrast, of the five dipropyl- and dibutylnitrosamines we studied, all cleaved non-oxidatively under these conditions (with loss of nitrogen gas) to the corresponding propyl or butyl cations. The carbocations thus produced underwent condensation and fragmentation to form the tert-butyl cation as the principal product ultimately observable by NMR. 3) The third fragmentation mechanism, which involved denitrosation to the dialkylammonium ion, was observed only as a minor pathway in the sulfuric or fluorosulfuric acid protolysis of dimethylnitrosamine. The mechanisms that are postulated for these cleavage reactions, if functioning in vivo, could account for several metabolic observations that have proved difficult to reconcile with previous conceptions of nitrosamine metabolism.