Ascorbic acid mediated N-dealkylation and N-deoxygenation of N,N'-dimethylaniline N-oxide

Article abstract of DOI:10.1021/ja00114a001

Ascorbic acid (AscH^-), commonly known as vitamin C, is an antioxidant and radical scavenger present in many human and animal tissues. There is much current interest in the protective roles of antioxidants against degenerative tissue damage associated with aging and chronic diseases. We demonstrate that ascorbic acid mediates the facile N-deoxygenation and N-dealkylation of N,N-dimethylaniline N-oxide (DMAO) at room temperature to produce N,N-dimethylaniline (DMA), N-methylaniline (MA), and formaldehyde, respectively. The relative rates of N-dealkylation and N-deoxygenation were found to be dependent on both DMAO and AscH^- concentrations in the reaction medium, and N-deoxygenation was somewhat faster than N-dealkylation under standard reaction conditions. Quantitative analysis of the products from DMAO/AscH^- reaction mixtures indicated that the rate of N-deoxygenation is identical to the rate of AscH^- consumption for at least the first 60 min of the reaction. Trapping experiments with mercaptoethanol and N,N,N',N'-tetramethylphenylenediamine (TMPD) provided evidence that the AscH^--mediated N-deoxygenation and N-dealkylation of DMAO is initiated by a single electron transfer process. A chemical mechanism for the AscH^--mediated N-deoxygenation and N-dealkylation of DMAO is proposed, which entails initial formation of a nitrogen cation radical and a subsequently-formed carbon-centered radical species. Steady state kinetic studies were carried out, and the kinetic results support the proposed mechanism. The possible physiological significance of these reactions with regard to the metabolism of xenobiotic aromatic amines as well as the biological role of vitamin C in normal and disease states is discussed.