Reactivities of N‑Nitrosamines Against Common Reagents and Reaction Conditions

The knowledge of the reactivity of N-nitrosamines (NSAs) with common organic reagents in synthesis is essential in determining their presence in pharmaceutical products, if formed and retained during synthesis. In this study, we carried out a comprehensive survey of the Reaxys database for all reactions in which the NSA functional group is consumed. Very different reactivities for different classes of NSAs, e.g., N,N-dialkylnitrosamines and N,N-diphenylnitrosamine, were identified, suggesting substrates which should be included in any future reactivity screening. A classification of NSAs based on their reactivities, and corresponding reagents and transformations, was drawn up based on the data. Furthermore, the survey identified missing areas in the reported reactivities of NSAs with different reagents. This led to an experimental reactivity screening of 8 commercial NSAs with common synthetic reagents in the Mirabilis tool for purge assessment. The results showed Na2S2O4 in 1 M aqueous NaOH at 50 °C to be highly effective at destroying NSAs without damaging other organic compounds.