What Factors Are Taken Into Consideration When Selecting a Solvent?

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 consider hazards (both human and environmental) and other considerations such as recoverability, renewability, and any regulatory issues.

The 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 and worker safety (acute, long-term, and single target organ toxicity)
• Environment (biodegradability, ecotoxicity, solubility in water, volatility, odor, life cycle analysis)
• Quality (e.g., 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)
• Disposal
• Cost
• Compliance with legislation and regulatory guidelines (e.g., regulations such as REACH are impacting the use of some hazardous solvents, for example, dipolar aprotics)
• Corporate responsibility – drive for sustainable manufacturing

Specific classes of solvents may have their own considerations as well. For example, the environmental impact of volatile organic compounds (VOCs), including:

• Harmful effects on human health (e.g., 1,2-dichloroethane and DMF)
• Harmful effects on natural ecosystems (e.g. hexanes)
• Damage to materials (e.g., acids)
• Stratospheric ozone depletion (e.g., carbon tetrachloride)
• Tropospheric photochemical oxidant formation (e.g., xylene, toluene)
• Global climate change
• Odor (e.g., amines such as pyridine, triethylamine; dimethyl sulfide)

The criteria taken into consideration when assessing the environmental credentials of a solvent are explored in Solvent Selection Guides: Criteria for Solvent Selection. As with all chemicals, solvents and their use are subject to legislation (for more information, see Environmental Legislation in the Process Design topic).