Solvent Sustainabilityin Drug Discovery: Where AreWe Now, and How Can We Improve?

Abstract Solvent selection plays a critical role in promoting synthetic chemistry reactions. Metrics from the ACS-GCIPR have led to an estimate that solvents utilized contribute 80–90% of the waste streams of pharmaceutical manufacturing processes. The medicinal chemistry team of the ACS-GCIPR has performed a systematic study of the most common transformations (over 400k reactions) utilized in the drug discovery phase examining the solvents in which these reactions are performed. Specifically, we have focused on the use of several solvents that are undesirable based on their hazardous nature and/or known adverse effects on human health. The data have shown that in over 40% of cases, the reactions profiled are conducted in what is an undesirable solvent with the use of methylene chloride and N,N-dimethylformamide being particularly prevalent. The perspective further discusses strategies and resources available to medicinal chemists to enable the selection of more sustainable reaction media.