Vegetable Oils as Green Solvents

By Jose Jimenez Santiago, a graduate student in the Song Group at the University of Toronto

The problem with solvents

Solvent has been defined as a “liquid that has the property to dissolve, dilute, or extract other materials without causing a chemical modification of these substances or itself”1. In chemical sciences and industry, most solvents come from the petrochemical industry. In 2020, the production of organic solvents surpassed 28 million metric tons2. This intensive consumption of solvents comes with a large concern with respect to sustainability, environment, safety, and health.  For instance, in the pharmaceutical industry, solvents can double the total mass of reagents and additives needed to produce a target compound. In this regard, the solvent of choice accounts for the environmental impact of a pharmaceutical product2-4.

How to select a good solvent

The 5th green chemistry principle promotes the use of Safer Solvents and Auxiliaries3.  Ideally, alternatives to petroleum-based solvents should fulfill the following requirements: 1) does not emit volatile organic compounds (VOCs); 2) be low toxicity for humans; 3) have a limited impact on the environment (i.e, be eco-friendly); 4) be obtained from renewable sources; 5) have high dissolving power, and 6) be easy to recover4.

There has been a huge effort to mitigate the negative impact of solvents. In this context, “sustainable” or “green” solvents describe those that are eco-friendly, non-toxic, or biodegradable5. Green solvents can be classified into seven categories: 1. bio-based solvents (from renewable sources), 2. eco-friendly (good health and safety risk profile), 3. water (renewable and non-toxic), 4. liquid polymers (non-volatile, non-toxic), 5. fluorinated solvents (non-flammable and non-toxic), 6. ionic liquids (non-volatile, thermally stable), 7. supercritical fluids like CO2 (inert, recyclable)5,6.

Vegetable oils as green solvents

Regarding the different green solvent classes, vegetable oils belong to the bio-based solvent class (category 1). These oils have the advantage of offering a positive impact on the environment and human health because they are biodegradable, non-toxic, and non-volatile. Vegetable oils, commonly produced from plant seeds or fruits (e.g., rapeseed, sunflower, olive, etc.), are non-polar and lipophilic systems whose composition is variable and complex depending on the origin and production method. The main components in vegetable oils are triglycerides, which are composed of three fatty acid molecules esterified into one glycerol molecule and constitute between 95-98% of the oil (Figure 1). The physical and chemical properties of each oil are determined by the proportion and position of fatty acids on the glycerol backbone and the ratio of these triglycerides in the oil7,8. In the next section, some recent innovative applications of this new class of solvents are discussed.

Figure 1. Major components in different vegetable oils1.

Applications of Vegetable Oils as Green Solvents

  1. Innovative Techniques for Extraction of Bioactive Compounds

Bioactive compounds from plants, algae, yeast, and fungi are usually extracted with petrochemical-based solvents in the pharmaceutical industry. However, the energy employed for distillation and the large amount of solvent used require innovative techniques. In this context, the solvent property of vegetable oils in combination with ultrasound has helped to achieve a greener extraction procedure. For example, the ultrasound-assisted extraction (UAE) of carotenoids from fresh carrots was recently achieved using sunflower oil as the solvent (Figure 2). Surprisingly, the extraction times have been reduced by more than half compared to conventional solvent extraction9.

Figure 2. Ultrasound-assisted extraction (UAE) of carotenoids with sunflower oil9.

2. Reaction Media for Multicomponent Synthesis

In 2021, a research article in the Green Chemistry Journal10 demonstrated the effectiveness of palm oil in a multicomponent reaction. The Biginelli reaction (Figure 3) is one of the most popular multicomponent reactions involving the condensation of urea, an aldehyde, and a β-keto ester to give dihydropyrimidinones (DHPMs). Typically, this reaction is performed in conventional non-renewable, petroleum-based solvents such as cyclohexane, THF, dioxane, toluene, and hexanes. In this study, the yield of the reaction did not decrease when using palm oil over cyclohexane. Moreover, using waste palm oil was possible without a considerable decrease in yield. Finally, the study showed that it is possible to recover the solvent (palm oil) and reuse it for at least 5 additional reactions without losing its effectiveness (Figure 4).

Figure 3. Model reaction for solvent screening10.
Figure 4. Reusability study for palm oil as a green solvent10.

3. Reaction Media for Catalytic Coupling Reactions

Another recent application of vegetable oils in organic synthesis has been as a solvent in metal-catalyzed cross-coupling reactions11. Carbon-carbon bond formations are among the most frequently used transformations in modern chemistry, patent literature, and the fine chemical industry. In 2021, a study demonstrated that food-grade and waste lipids are excellent solvents for homogeneous catalysis11. A variety of oils were tested (Figure 5) and the model reaction was the Suzuki-Miyaura coupling catalyzed by palladium (Pd) (Chart 1).

Figure 5. Vegetable, semisynthetic, and animal-based oil evaluated in this study11.

The results are shown in Chart 1 with the optimized conditions for a variety of oils tested. Semisynthetic oils (green) were as effective as traditional solvent used in homogeneous catalysis (red). Most of the vegetable oils (orange) were efficient for the transformation. Triglycerides originating from animals like butter and fish oil (blue) worked well as the reaction media as well as some natural waxes (pink). In this study, the exceptional performance of vegetable oil and related lipids as solvents was further confirmed for several other important Pd-catalyzed transformations including the Hiyama, Stille, Sonogashira and Heck cross-coupling reactions.

Chart 1. Model cross-coupling reaction and catalytic results of different oils and solvents screened11.

In a very recent study12, a protocol for the more challenging carbon-nitrogen bond coupling reaction was developed. The model reaction, the Buchwald-Hartwig amination, is shown in Chart 2. This reaction is sensitive to the solvent used and even petroleum-based solvents gave low yields in this reaction (red). Nevertheless, semisynthetic oils give excellent yields for the reaction (green) but vegetable oils dramatically reduce the catalytic performance (orange). Animal oils and natural waxes (pink and blue) gave a high yield in catalysis. Current research is focused on expanding the substrate scope for this reaction with the best solvents and using them for other important catalytic reactions like carbon-oxygen bond formation.

Chart 2. Model cross-coupling reaction and catalytic results of different oils and solvents screened12.

In conclusion, vegetable oils have emerged as a potential sustainable replacement for petroleum-based solvents. Great progress has been done in using them for the extraction of bioactive compounds and purification. Vegetable oils have the potential to be an ecological and economic solution and alternative to petroleum-based solvents and other hazardous solvents. Future scientific innovations will make them attractive at the large scale in the pharmaceutical and fine chemical industries.

References

  1. Yara-Varón, E.; Li, Y.; Balcells, M.; Canela-Garayoa, R.; Fabiano-Tixier, A.; Chemat, F. Molecues 2017, 22, 1474-1498.
  2. Constable, D. J. C.; Jimenez-Gonzalez, C.; Henderson, R. K. Org. Process Res. Dev. 2007, 11, 133-137.
  3. https://www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-green-chemistry.html
  4. Chemat, F.; Vian, M. Alternative Solvents for Natural Product Extraction; Springer: Heidelberg, Germany, 2014; pp. v-vi, ISBN 978-3-662-43627-1.
  5. Reichardt, C. Org. Process Res. Dev. 2007, 11, 105-113.
  6. Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.; Johnson, T. A.; Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D. A. Green Chem. 2008, 10, 31-36.
  7. Kerton, F.; Marriot, R. Alternative Solvents for Green Chemistry, 2nd ed.; RSC Publishing: Cambridge, UK, 2013; pp. 149-171, ISBN 978-1-84973-595-7.
  8. Chen, B.; McClements, D. J.; Decker, E. A. Crit. Rev. Food Sci. Nutr. 2011, 51, 901-916.
  9. Li, Y.; Fabiano-Tixier, A. S.; Tomao, V.; Cravotto, G.; Chemat, F. Ultrason. Sonochem. 2013, 20, 12-18.
  10. Noppawan, P.; Sangon, S.; Supanchaiyamat, N.; Hunt, A. J. Green Chem. 2021, 23, 5766-5774.
  11. Gevorgyan, A.; Hopmann, K.; Bayer, A. Green Chem. 2021, 23, 7219-7227.
  12. Gevorgyan, A.; Hopmann, K.; Bayer, A. Organometallics https://doi.org/10.1021/acs.organomet.1c00517