Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide

The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA.