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Solvent Survey Reveals Trends For Pharmaceutical Manufacturing

Data suggest targets for increased use of green solvents to improve industry’s environmental footprint

by Carmen Drahl
October 6, 2014 | A version of this story appeared in Volume 92, Issue 40

GOOD NEWS AND BAD NEWS
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SOURCE: Org. Proc. Res. Dev. While use of green solvent 2-methyltetrahydrofuran is increasing, use of dichloroethane and DMF have remained constant.
Bar graphs show percent of publications reporting usage of certain solvents.
SOURCE: Org. Proc. Res. Dev. While use of green solvent 2-methyltetrahydrofuran is increasing, use of dichloroethane and DMF have remained constant.

Solvents represent roughly half the material used when pharmaceuticals are manufactured on an industrial scale, so efforts to minimize a solvent’s environmental footprint stand to make a big impact. To learn how the industry’s practices have evolved, Andrew S. Wells of Charnwood Technical Consulting teamed with coauthors at GlaxoSmithKline and Pfizer to survey solvent usage in 388 publications from the ACS journal Organic Process Research & Development, dating from the journal’s 1997 inception through 2012 (2014, DOI: 10.1021/op500276u). The survey was conducted as part of Chem21, a public-private partnership in Europe dedicated to developing environmentally sustainable drug manufacturing methods. One encouraging trend the authors noticed is that the use of many hazardous solvents decreased for processes run at scales of more than 100 kg. Another positive is increased use of 2-methyltetrahydrofuran, which is a biobased solvent derived from renewable sugars. Less encouraging is that, despite some company efforts, overall use of some solvents of concern, such as dichloromethane, remained constant. “Chemists need to avoid falling into the trap of associating certain solvents with certain reactions,” the authors say. In particular they suggest strategies for minimizing use of dipolar aprotic solvents, such as replacing dimethylformamide in nucleophilic substitution reactions with 2-methyltetrahydrofuran or ethanol.

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