Hodgin George A, Burns Michael J, Deadman Benjamin J, Roberts Christopher S, Hii King Kuok Mimi, Nguyen Bao N
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, U.K.
Lhasa Ltd., Granary Wharf House, 2 Canal Wharf, Leeds LS11 5PS, U.K.
Org Process Res Dev. 2024 Sep 18;28(10):3837-3846. doi: 10.1021/acs.oprd.4c00217. eCollection 2024 Oct 18.
The knowledge of the reactivity of -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., ,-dialkylnitrosamines and ,-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 NaSO in 1 M aqueous NaOH at 50 °C to be highly effective at destroying NSAs without damaging other organic compounds.
了解亚硝胺（NSAs）在合成过程中与常见有机试剂的反应活性，对于确定其在药品中的存在至关重要（如果在合成过程中形成并保留下来）。在本研究中，我们对Reaxys数据库中所有消耗NSA官能团的反应进行了全面调查。我们发现不同类别的NSAs，如α,β-二烷基亚硝胺和α,β-二苯基亚硝胺，具有非常不同的反应活性，这表明在未来任何反应活性筛选中都应纳入的底物。基于这些数据，根据NSAs的反应活性、相应的试剂和转化反应进行了分类。此外，该调查还确定了NSAs与不同试剂反应活性报道中存在的缺失领域。这导致在用于净化评估的Mirabilis工具中，对8种商业NSAs与常见合成试剂进行了实验性反应活性筛选。结果表明，在50℃下于1 M氢氧化钠水溶液中的亚硫酸钠能高效破坏NSAs，而不会损害其他有机化合物。
