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Here, we analyse 1.3 million classified reactions from 40 years of patent data, distinguishing for the first time between reaction, workup, purification, and analytical solvents. Despite decades of awareness of solvent hazards and the publication of influential solvent selection guides, we find no net reduction in the proportion of hazardous solvents used as reaction media. Dichloromethane usage has grown, and rising trifluoroacetic acid consumption intensifies concerns over per\u2010 and polyfluoroalkyl substances. Where regulations have removed specific solvents, chemists have defaulted to lateral substitution, replacing one hazardous solvent with another rather than adopting greener alternatives. We identify the reaction classes most dependent on each problematic solvent, providing a data\u2010driven framework for prioritising targeted intervention over blanket regulation. Crucially, these findings expose systemic biases in historical datasets that threaten to turn AI solvent\u2010prediction models into engines for proliferating outdated, hazardous practices rather than advancing sustainable chemistry.<\/jats:p>","DOI":"10.1002\/anie.1677569","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:45:50Z","timestamp":1789616750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Stubborn Persistence of Toxic Solvents in Chemical Synthesis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-8569","authenticated-orcid":false,"given":"Maarten R.","family":"Dobbelaere","sequence":"first","affiliation":[{"name":"Laboratory For Chemical Technology Department of Materials Textiles and Chemical Engineering Ghent University  Gent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-7692","authenticated-orcid":false,"given":"Helen F.","family":"Sneddon","sequence":"additional","affiliation":[{"name":"Green Chemistry Centre of Excellence Department of Chemistry University of York  York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurpub\/ckaa165.843"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202420719"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/op060170h"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02978570"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.3c01494"},{"key":"e_1_2_8_7_1","volume-title":"Green Chemistry Theory and Practice","author":"Anastas P. 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