Álvaro Enríquez García, Medicinal Chemist at Eli Lilly, highlighted the necessity of informed solvent selection in improving the sustainability of chemical processes. He outlined a strategy for avoiding hazardous solvents and opting for safer alternatives.
Solvents such as dichloromethane, hexane, and dioxane, were classified as hazardous or highly hazardous due to their toxic effects and environmental impact. He suggested that scientists should minimise their use and select solvents in the recommended or problematic categories such as methyl ether, ethanol, and water.
In the literature, there are many reports on solvent sustainability in manufacturing and solvent selection. However, Enríquez García wanted information relevant to medicinal chemists, so his team explored how to conduct reactions, workups, and purifications extract metrics from the Journal of Medicinal Chemistry.
His research led him to the idea of identifying key metrics related to solvent sustainability to better gauge where adjustments could be made. He aimed to write a paper with tips and tricks for medicinal chemists, guiding them on ways to enhance the sustainability of their solvent use and warn them about the risks associated with certain solvents. The principal objective of this was to gather metrics to help foster solvent sustainability in early drug discovery phases.
He identified the most popular reactions in medicinal chemistry and grouped them by recurrence, purifications, and other criteria. Heterocycle synthesis, amide formation, and BOC cleavage are examples of the most unsustainable reactions. Enríquez García and his collaborators created a comprehensive poster on how to pick safer solvents for specific reactions. Ethyl acetate was identified as a suitable solvent.
The talk then examined alternative purification methods to chromatography. Although many chemists rely on chromatography, companies still use hazardous solvents like hexane in bulk for chromatography. Instead, Enríquez García suggested alternative methods such as precipitation or telescoping reactions.
Enríquez García wrapped up his talk by directing the audience to an interactive solvent tool on the Green Chemistry Institute Pharmaceutical Roundtable website. This comprehensive tool allows users to select solvents based on various physical properties like boiling point, dielectric constant, and safety scores. Finally, automation and miniaturisation is a game-changer that allows for a quick screen for the optimisation of reactions; this can lead to increased yields and minimal waste generation.
