Solvent Selection from the Green Perspective

In recent years, analytical chemists have increasingly adopted a sustainability viewpoint. Yet, at the same time, they still use traditional organic solvents for extractions and other procedures. In this installment of Sample Preparation Perspectives, we will look at solvent selection from green considerations. Trends on solvent use are presented, followed by a discussion on what makes a green solvent. Finally, the CHEM21 Solvent Selection Guide is examined as representative of tools for selecting green solvents for use in analytical methods and other chemical processes.

Chromatographers have been concerned with their use of organic solvents for decades. For example, in the inaugural LCGC sample preparation trends survey (1) in 1992, over a third of respondents considered modifying their procedures to reduce their solvent use, despite the fact that 42.4% did not consider reduction of laboratory waste an issue. This was during the early stages of the research and commercialization of supercritical fluid extraction (SFE), which created some of the initial interest in dealing with solvent use in analytical sample preparation. Sample preparation was still in the beginning stages of awareness in the minds of chromatographers and other analysts. These concerns were also prior to the rise in popularity of what is now termed “green chemistry.”

Knowledge of the environmental and health effects of the worst solvents has limited the use of chemicals like benzene and carbon tetrachloride since the beginning of our careers. Over this time, government regulations have restricted some use of traditional solvent use, dating back to the Montreal Protocol on Substances that Deplete the Ozone Layer in 1989 (2) and continuing through the more recent prohibition by the U.S. Environmental Protection Agency on the use of methylene chloride (3). Nowadays, with the establishment of green chemistry and sustainability, along with growing concerns over climate change and other environmental maladies, solvent use is at the forefront. In our most recent sample preparation trends survey (4), the top response (42.4%) to an open-ended question on areas of improvement in the field of sample preparation was the development of green techniques. Additionally, nearly all respondents (88.6%) claimed a concern with the health, safety, and environmental consequences of the solvents they use. Of these analysts, only 10% would consider switching to nontraditional solvents like supercritical fluids, ionic liquids, deep eutectics solvents, or others. This finding supports survey results from Jessop (5), who asked researchers, “If the adoption of greener solvents over the next 20–30 years will reduce environmental damage from human activities, then the adoption of what class of solvents will be responsible for the greatest reduction in environmental damage?” Water, carbon dioxide, and “carefully selected” traditional organic solvents combined for about three quarters of the total responses. Responses to Jessop’s question are shown in Figure 1.

What is a Green Solvent?

As analytical chemists, we have gained knowledge of solvent properties. From our earliest chemistry education, we learned of solubility and “like dissolves like.” With experience in liquid chromatography, we gathered an appreciation for the role of solvent properties like viscosity. But as we move to adopt more green principles in our work, we must additionally ask ourselves, “what is a green solvent?” And in addressing traditional organic solvents (where we are most familiar), the question becomes, “will we recognize a green solvent when we see one?”

In this installment of “Sample Prep Perspectives,” we will limit this treatment to organic solvents only, as nontraditional solvents are still finding their place in chemical analysis. Of course, no solvent, reagent, or other chemical is truly 100% green. We can only discuss the greenness of a solvent relative, or in comparison, to other solvents. This can be seen graphically by looking at two approaches to discussing green chemistry. Figure 2 shows a number of solvents explored by a life-cycle assessment (LCA) approach and an environmental health and safety (EHS) approach (6). An LCA looks at the material and energy inputs and outputs over the life cycle of a product. In Figure 2, to be considered green, a solvent would have a low score, located on the left of the abscissa in the diagram. Thus, solvents like heptane, hexane, and diethyl ether would be considered the most green of this solvent set. Looking at the EHS treatment, again, a low score would be the greenest, represented by acetates or 1-propanol. Combining these somewhat disparate approaches, the greenest solvents would be in the lower left quadrant of Figure 2, where we see nothing.

Over the past 25 or so years since green chemistry has been developed, several “green solvent selection guides” have been developed. These guides tend to be somewhat similar, based on EHS approaches to solvent characterization. Given the plethora of such tools for choosing solvents, which should be used? While each selection guide has its merits, this discussion will focus on the CHEM21 Guide. We choose to present this guide for three major reasons: (1) the EHS approach is similar to other solvent guides, (2) alignment with the Global Harmonization System, (3) its development by a consortium of researchers based on survey of other solvent guides, and (4) implied endorsement by professional groups like the American Chemical Society’s Green Chemistry Institute.

CHEM21 Selection Guide

Not to be overlooked in the selection of a green solvent system is the CHEM21 selection guide of classical and less classical solvents (7). It is a survey of publicly available solvent guides for the pharmaceutical industry. However, the system can be extended and applied to a broader industry base (agricultural chemistry and consumer products, for example) and their most likely solvent systems with the consideration of its principles. The system scores the safety, health, and environmental impact of any solvent. The scoring assigns a rank of three categories: recommended, problematic or hazardous. This scoring is aligned with the Global Harmonized System and the scores can be assigned based on available physical property data and toxicological and eco-toxicological data available in the solvent’s REACH (European Registration, Evaluation, Authorization, and Restriction of Chemicals regulation) dossiers.

CHEM21 stems for the Innovative Medicines initiative (IMI)-CHEM21 public-private partnership and is a European consortium to promote sustainable methodologies both in biology and chemistry.Ultimately, the initiative is to compare the greenness of chemical processes, to that end solvents which equal at least half of the material used in the process must also be evaluated. An abbreviated version of rankings for some of these solvents can be found in Table I where a few of the most common solvents involved in chromatography and sample preparation are given with their CHEM21 rating.

For the safety score, the importance of the combination of the flash point and the boiling point by delineating solvents into three sub-categories. A score of 1 for a flash point greater than 60 ^oC, of 3 with a flash point of 24 to 60 ^oC, of 4 for flash temperatures of 23 to 0 ^oC, of 5 for -1 to -20 ^oC, and 7 for less than -20 ^oC.Additional points can be added to the score for auto-ignition temperatures less than 200 ^oC, resistivity greater than 10⁸Ώ m, the ability to form peroxides, or any solvent with a high energy of decomposition for example, greater than 500 J/g.

For the health score, exposure limits are suggested as the best system to be used, but there is limited availability of that data except for very common solvents. Instead, the CHEM21 system uses scoring from the Classification and Labelling/Global Harmonization System, CLP/GHS.The key to those used in Table I is:

After assigning a score from CLP/GHS system, 1 point is added to the health score if the boiling point of the solvent is less than 85 ^oC.

Contained in the environmental score should be a solvent’s environmental toxicity to both valuable insect and aquatic populations; environmental impact on soils, aquatic systems and the air; carbon footprint in terms of both CO₂ generation as well as recycling potential. For this score a 10-point criteria is used with the highest score dictating the final score. Only three values are used, 3, 5 and 7. The environmental score is based on boiling point. For solvents with a boiling range of 70 to 139 ^oC, the score is 3 and there is no H4xx value assigned. For those with a boiling range 50 to 69 ^oC or 140 to 200 ^oC, the GHS-assigned values are H412 and H413 and the environmental score in CHEM21 is 5. Finally, a score of 7 is given to solvents that boil at less than 50 ^oC or greater than 200 ^oC, these solvents would have GHS values of H400, H410 and H411. Work towards a metric that yields the CO₂ footprint (in kg/kg) or the cumulative energy demand (CED, in MJ/kg) has been undertaken by other green chemistry roundtables (8).

Conclusions

Green solvent considerations are taking increasing importance in analytical chemistry. But most analysts are not aware of how to select such a solvent. Since the greenness of a chemical is relative, solvent selection guides are useful tools in this endeavor. These guides are typically based on impacts on the environment, human health, and safety. The CHEM21 Solvent Selection Guide, coupled with the Global Harmonization System, is presented as an example of a myriad of such tools.

References

1. Majors, R. E.Trends in Sample Preparation. LCGC1992, 10 (12), 912-928.
2. Environmental Protection Agency. Risk Management for Methylene Chloride under TSCA. https://www.epa.gov/
3. United Nations Environmental Programme (UNEP), Handbook for the Montreal Protocol on Substances That Deplete the Ozone Layer, ninth ed., Nairobi, 2012.
4. Raynie, D. E. Trends in Sample Preparation, Part 1: Current State of the Field. LCGC North Am. 2023, 41 (9), 374–380, 393. DOI: 10.56530/lcgc.int.mn3284n6
5. Jessop, P. G. Searching for Green Solvents. Green Chem. 2011, 13, 1391–1398. DOI: 10.1039/C0GC00797H
6. Capello, C.; Fischer, U.; Hungerbuhler, K. What is a Green Solvent? A Comprehensive Framework for the Environmental Assessment of Solvents. Green Chem.2007, 9, 927–934. DOI: 10.1039/B617536H
7. Prat, D.; Wells, A.; Hayler, J.; Sneddon, H.; McElroy, C. R.; Abou-Shehada, S.; P. Dunn, P.CHEM21 Selection Guide of Classical- and Less Classical-Solvents. Green Chem. 2016, 18, 288–296. DOI: 10.1039/C5GC01008J
8. American Chemical Society. Green Chemistry & Sustainability in the Chemical Industry: Industry Roundtables. https://www.acs.org/green-chemistry-sustainability/industry-roundtables.html (accessed 2025-02-05).

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