EPR detection of nitrogen-containing radicals in dimethylamine oxidation: insights into NDMA formation†

Dimethylamine (DMA) is a key precursor for the carcinogenic N-nitrosodimethylamine (NDMA), yet the role of radical intermediates in DMA oxidation and N–N bond formation remains unclear. Using electron paramagnetic resonance (EPR), this study explored free radical generation in the DMA/NaClO and DMA/KMnO₄ systems, previously linked to NDMA formation. Without spin traps, three long-lived nitrogen-containing radicals were detected: dimethyl nitroxide radicals (DMNO˙), tetramethylhydrazine cation radicals (TMH˙⁺), and N,N-dimethylaminomethyl radicals (UDMHr). Their formation depends on pH, reaction time, and oxidant type and concentration. DMNO˙, formed via DMA oxygenation or hydrogen abstraction, is unstable at acidic pH and converts to N,N-dimethylhydroxylamine (DIMHA). TMH˙⁺ likely arises from tetramethylhydrazine (TMH) through single-electron transfer, followed by further reactions to produce UDMHr, a key NDMA precursor. This study proposes pathways for these radicals in DMA oxidation, offering direct EPR evidence of N-containing radicals and their potential role in NDMA formation.