Solvents are critical components in chemical production. They can be used to promote chemistry, dissolve reactants, modify solute properties, remove impurities/byproducts, isolate products, etc.
How Solvents Relate to Green Chemistry
The extensive use of solvents, however, may increase environmental burden and health risks because many organic solvents are flammable, volatile, and even toxic. An analysis report by the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (the Roundtable) suggests that typically >70% of pharmaceutical wastes are solvent-related (i.e., solvent and water consumption). Therefore, solvent choice is a key factor when trying to conduct green chemistry.
The selection of solvents should follow the principles of green chemistry to minimize waste and improve safety. The directly related principles are
- Safer Solvents and Auxiliaries
- Inherently Safer Chemistry for Accident Prevention
- Eliminate and Minimize Hazards and Pollution
Selection Guide
Prat et al. published CHEM21 selection guide based on health, safety, and environmental criteria, which includes not only classical solvents, but also emerging solvents, such as bio-derived solvents.
Solvents are defined as
- Recommended: solvents to be tested first in a screening exercise, if of course there is no chemical incompatibility in the process conditions.
- Problematic: these solvents can be used in the lab, but their implementation in the pilot plant or at the production scale will require specific measures, or significant energy consumption
- Hazardous: the constraints on scale-up are very strong. The substitution of these solvents during process development is a priority
- Highly Hazardous: solvents to be avoided, even in the laboratory
Full lists of solvent selection guide are shown below.
CHEM 21 solvent guide of classical solvents
| Family | Solvent | Ranking |
| Water | Water | Recommended |
| Alcohols | MeOH | Recommended |
| EtOH | Recommended | |
| i-PrOH | Recommended | |
| n-BuOH | Recommended | |
| t-BuOHc | Recommended | |
| Benzyl alcohol | Problematic | |
| Ethylene glycol | Recommended | |
| Ketones | Acetone | Recommended |
| MEK | Recommended | |
| MIBK | Recommended | |
| Cyclohexanone | Problematic | |
| Esters | Methyl acetate | Problematic |
| Ethyl acetate | Recommended | |
| i-PrOAc | Recommended | |
| n-BuOAc | Recommended | |
| Ethers | Diethyl ether | Highly Hazardous |
| Diisopropyl ether | Hazardous | |
| MTBE | Hazardous | |
| THF | Problematic | |
| Me-THF | Problematic | |
| 1,4-Dioxane | Hazardous | |
| Anisole | Recommended | |
| DME | Hazardous | |
| Hydrocarbons | Pentane | Hazardous |
| Hexane | Hazardous | |
| Heptane | Problematic | |
| Cyclohexane | Problematic | |
| Me-cyclohexane | Problematic | |
| Benzene | Highly Hazardous | |
| Toluene | Problematic | |
| Xylenes | Problematic | |
| Halogenated | DCM | Hazardous |
| Chloroform | Highly Hazardous | |
| CCl4 | Highly Hazardous | |
| DCE | Highly Hazardous | |
| Chlorobenzene | Problematic | |
| Aprotic polar | Acetonitrile | Problematic |
| DMF | Hazardous | |
| DMAc | Hazardous | |
| NMP | Hazardous | |
| DMPU | Problematic | |
| DMSOc | Problematic | |
| Sulfolanec | Hazardous | |
| HMPA | Highly Hazardous | |
| Nitromethane | Highly Hazardous | |
| Miscellaneous | Methoxy-ethanol | Hazardous |
| Carbon disulfide | Highly Hazardous | |
| Acids | Formic acid | Problematic |
| Acetic acid | Problematic | |
| Ac2O | Problematic | |
| Amines | Pyridine | Hazardous |
| TEA | Hazardous |
CHEM 21 solvent guide of emerging solvents
| Family | Solvent | Ranking |
| Alcohols | i-Butanol | Recommended |
| i-Amyl alcohol | Recommended | |
| 1,3-Propane diol | Problematic | |
| Glycerol | Problematic | |
| Esters | i-Butyl acetate | Recommended |
| i-Amyl acetate | Recommended | |
| Glycol diacetate | Recommended | |
| γ-Valerolactone | Problematic | |
| Diethyl succinate | Problematic | |
| Ethers | TAME | Recommended |
| CPME | Problematic | |
| ETBE | Problematic | |
| Hydro-carbons | D-Limonene | Problematic |
| Turpentine | Problematic | |
| p-Cymene | Problematic | |
| Aprotic polar | Dimethyl carbonatec | Recommended |
| Ethylene carbonated | Problematic | |
| Propylene carbonate | Problematic | |
| Cyrene | Problematic | |
| Miscella-neous | Ethyl lactate | Problematic |
| Lactic acid | Problematic | |
| TH-furfuryl alcohol | Hazardous |
Selection Tool
The guide above provides a quick selection of green solvents. We have to recognize, however, that some solvents offer unique properties that are vital for some classes of reaction and therefore, the need from a solvent may vary.
This interactive tool - Solvent Selection Tool, created by the Roundtable, allows you to select greener and safer solvents from 272 solvents in the database based on the Principal Component Analysis (PCA) of the solvent's 70 physical properties.After filtering by Functional Groups, Physical Properties, Engineering, International Conference on Harmonization (ICH), Safety, Health and Environment (SHE) based on the process needs, solvent shortlist will be available.
Looking forward, more comprehensive selection guide may be developed and employed as the promotion of green solvents is a trend due to the development of green chemistry, and the increasing regulation as well.
Reference:
- American Chemical Society
- Prat, D., Wells, A., Hayler, J., Sneddon, H., McElroy, C.R., Abou-Shehada, S. and Dunn, P.J., 2015. CHEM21 selection guide of classical-and less classical-solvents. Green Chemistry, 18(1), pp.288-296.
- Diorazio, L.J., Hose, D.R. and Adlington, N.K., 2016. Toward a more holistic framework for solvent selection. Organic Process Research & Development, 20(4), pp.760-773.
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