Reactivities of <i>N</i>‑Nitrosamines\nagainst Common Reagents and Reaction Conditions

The knowledge of the reactivity of <i>N</i>-nitrosamines\n(NSAs) with common organic reagents in synthesis is essential in determining\ntheir presence in pharmaceutical products, if formed and retained\nduring synthesis. In this study, we carried out a comprehensive survey\nof the Reaxys database for all reactions in which the NSA functional\ngroup is consumed. Very different reactivities for different classes\nof NSAs, e.g., <i>N</i>,<i>N</i>-dialkylnitrosamines\nand <i>N</i>,<i>N</i>-diphenylnitrosamine, were\nidentified, suggesting substrates which should be included in any\nfuture reactivity screening. A classification of NSAs based on their\nreactivities, and corresponding reagents and transformations, was\ndrawn up based on the data. Furthermore, the survey identified missing\nareas in the reported reactivities of NSAs with different reagents.\nThis led to an experimental reactivity screening of 8 commercial NSAs\nwith common synthetic reagents in the Mirabilis tool for purge assessment.\nThe results showed Na<sub>2</sub>S<sub>2</sub>O<sub>4</sub> in 1 M\naqueous NaOH at 50 °C to be highly effective at destroying NSAs\nwithout damaging other organic compounds.