In order to gain a greater understanding of what makes the ‘best’ solvent for a given reaction, one must look deeper into the physicochemical properties of the solvent, as well as considering hazards (both human and environmental) and other considerations such as recoverability, renewability and any regulatory issues. (The criteria that are taken into consideration when assessing the environmental credentials of a solvent are explored in Solvent selection guides: Criteria for Solvent Selection).
Selection of a green solvent is complex as the following constraints all need to be taken into consideration. [1] [2]
- Chemical efficiency for the reaction (as well as downstream considerations of isolation/work-up etc.);
- Safety/stability (flammability, flash point, resistivity, energy of decomposition, risk of peroxides);
- Human health issues (acute, long-term and single target organ toxicity);
- Environment (biodegradability, ecotoxicity, solubility in water, volatility, odour, life cycle analysis);
- Quality (in the case of pharmaceuticals this is related to the risk of impurities in the drug substance);
- Industrial Constraints (such as boiling point, freezing temperature, density, recoverability/recyclability);
- Cost;
- Compliance with legislation (e.g. regulations such as REACH are impacting on the use of some hazardous solvents, for example dipolar aprotics).
