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Three Ways to Improve the Sustainability of Your Lab’s Chemical Synthesis

Simple steps to implement green chemistry practices

Laboratories are some of the most energy intensive and wasteful spaces on university campuses and industrial sites alike1. In the chemical sciences, reactions are often performed with maximum yield (and/or profit) in mind, and while a lot of labs have moved toward becoming more sustainable through efforts in bringing in energy efficient equipment or recycling initiatives, many labs still perform chemistry in a wasteful way and use reagents and solvents that are hazardous to human and environmental health.

Green chemistry offers another tool in the toolbox of scientists and lab managers to reduce their environmental footprint, decrease waste, decrease exposure to hazardous chemicals, improve efficiency, and more. Green chemistry is defined by Warner and Anastas as, “the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture, and application of chemical products.”  It is not a field in and of itself but rather a holistic approach to practicing chemistry.  

The 12 Guiding Principles of Green Chemistry (Figure 1) provide the framework through which scientists can design chemical reactions and products in a more sustainable way. 

Chart of the 12 principles of green chemistry
Figure 1
Beyond Benign

Chemists may often ask themselves, “This is all well and good, but where do I start? How do I know the best approach to take?” While it can sometimes feel overwhelming when first starting on a “greener” journey, here are some simple tips and examples to help get started.

Tip #1 – Prevent waste wherever possible

There are many simple ways to prevent waste in labs, which can ultimately mitigate hazards and exposures, too. In education and teaching labs, scaling down is one of the "lowest hanging fruit" when it comes to simple changes you can make. However, this is often not possible in industrial settings (where scale-up is usually one of the key goals). In those cases, consider solvent recycling. Many solvent recycling systems exist that can allow solvents to be reused for future reactions. One-pot reactions can also help by avoiding additional workup steps between subsequent reactions including separations (columns, filtrations, liquid-liquid extractions, etc.). Of course, this is all dependent on the circumstances and reaction at hand; if the one-pot synthesis prevents kilograms of additional waste but requires the use of benzene as the solvent, a different reaction route should be considered. This is often the task of chemists looking at greener syntheses: what are the trade-offs and how can undesirable consequences be eliminated or minimized. 

Tip #2 – Use safer, alternative solvents

Over the past 20 years, a number of major pharmaceutical and industrial chemical companies have released solvent selection guides showing desirable alternatives to traditional solvents2-6. Beyond Benign, a US-based not-for-profit dedicated to transforming chemistry education for a sustainable future, has aggregated many of these guides into a simple infographic (Figure 2). Wherever possible, alternative, safer solvents should be used in place of high hazard solvents. In general, halogenated and aromatic/short-chain aliphatic hydrocarbon solvents (such as dichloromethane (DCM), dichloroethane, chloroform, benzene, toluene, hexanes, and pentane) as well as nitrogen-containing solvents (such as pyridine, N-methyl-2-pyrrolidone (NMP), propionitrile, dimethylacetamide, and dimethylformamide (DMF)) should be avoided and replaced due to their hazardous nature. 

Making these substitutions can range from being simple to more complicated. For example, if the reaction is to be done at reflux, different boiling points will impact the refluxing temperature and therefore may impact the yield or time needed for a reaction. In some cases, the solvent may participate in the reaction (such as amine-based solvents acting as bases). Again, trade-offs must be assessed carefully by the attending chemist to understand if there is greater benefit, and some testing may be required, but the rewards can be substantial. A wonderful example case study in industry is the early synthesis of Viagra, which saw a reduction in waste solvent from 1300 L per kg active pharmaceutical ingredient (API) in 1990 down to 7 L/kg API in the late 1990s7. The team was able to not only eliminate the use of chlorinated solvents in the process but also reduce the use of highly volatile solvents like methanol and diethyl ether.

Tip #3 – Measure your impact and get a baseline

Scientists love metrics. They feed off quantifiable data. And who wouldn’t? Having the numbers to rationalize a result, understand deeper meaning behind an observation, or argue for more funding are the "bread and butter" of a scientist’s daily work. Green chemistry is no exception, but there are many different metrics and tools for measuring “greenness” and choosing the right one can sometimes be daunting. There is no single metric that can evaluate all aspects of the “greenness” of a chemical product or process. However, a few quick descriptions of some of the more common metrics are available below to help give a sense of when one metric might be more appropriate than another. In fact, they are often best used in combination.

  • Yield – The quintessential measure of chemical success, yield only considers the amount of product formed but does not consider waste or other factors in the reaction.
  • Atom Economy – The percent mass of atoms from the reagents incorporated into a product. An example of a reaction with a high atom economy is a Diels-Alder reaction, while an example of a reaction with low atom economy is the production of hydrogen from benzenethiol and lithium aluminum hydride. Under the right conditions, both reactions can progress readily and produce high yields, but the second reaction incorporates only a small mass fraction of the atoms from the starting materials into the product.
  • Process Mass Intensity (PMI) – The ratio of total mass of all components used in a reaction to the mass of isolated product. The PMI can never be lower than one, whereas the E-factor (which is similar) can theoretically be as low as zero. 
  • E-Factor – The ratio of total waste mass (anything that is not incorporated into the product) to the mass of isolated product. An ideal E-factor is zero, where no waste is produced. 
  • Life Cycle Analysis (LCA) – An LCA is a much more complex analysis of a reaction product or process and must take into account metrics across a wide range of impact categories (the selection of which can vary greatly depending on the circumstance). Some examples of categories include global warming potential, acidification, terrestrial eutrophication, human toxicity, ionizing radiation, and more. 
  • DOZN – A tool developed by MilliporeSigma, this is a quantitative online green chemistry evaluator that can assess the relative greenness of chemicals and chemical processes across all twelve principles of green chemistry. 

This is just a sample and there are many more metrics available. Ultimately, using even just a few of these metrics to begin to understand how green your reaction is can lead to small changes and improvements that, over time, produce significant impact and long-term lab sustainability.

Greener Solvent Guide
Figure 2
Beyond Benign


1.    Jain, N. Integrating Sustainability into Scientific Research. Nat. Rev. Methods Primer 2022, 2 (1), 35.

2.   Byrne, F. P.; Jin, S.; Paggiola, G.; Petchey, T. H. M.; Clark, J. H.; Farmer, T. J.; Hunt, A. J.; Robert McElroy, C.; Sherwood, J. Tools and Techniques for Solvent Selection: Green Solvent Selection Guides. Sustain. Chem. Process. 2016, 4 (1), 7.

3.    Prat, D.; Pardigon, O.; Flemming, H.-W.; Letestu, S.; Ducandas, V.; Isnard, P.; Guntrum, E.; Senac, T.; Ruisseau, S.; Cruciani, P.; Hosek, P. Sanofi’s Solvent Selection Guide: A Step Toward More Sustainable Processes. Org. Process Res. Dev. 2013, 17 (12), 1517–1525.

4.   Henderson, R. K.; Jiménez-González, C.; Constable, D. J. C.; Alston, S. R.; Inglis, G. G. a.; Fisher, G.; Sherwood, J.; Binks, S. P.; Curzons, A. D. Expanding GSK’s Solvent Selection Guide – Embedding Sustainability into Solvent Selection Starting at Medicinal Chemistry. Green Chem. 2011, 13 (4), 854–862.

5.  Adams, J. P.; Alder, C. M.; Andrews, I.; Bullion, A. M.; Campbell-Crawford, M.; Darcy, M. G.; Hayler, J. D.; Henderson, R. K.; Oare, C. A.; Pendrak, I.; Redman, A. M.; Shuster, L. E.; Sneddon, H. F.; Walker, M. D. Development of GSK’s Reagent Guides – Embedding Sustainability into Reagent Selection. Green Chem. 2013, 15 (6), 1542.

6.    Taygerly, J. P.; Miller, L. M.; Yee, A.; Peterson, E. A. A Convenient Guide to Help Select Replacement Solvents for Dichloromethane in Chromatography. Green Chem. 2012, 14 (11), 3020.

7.     Dunn, P. J.; Galvin, S.; Hettenbach, K. The Development of an Environmentally Benign Synthesis of Sildenafil Citrate (ViagraTM) and Its Assessment by Green Chemistry Metrics. Green Chem 2004, 6 (1), 43–48.

Jonathon Moir, PhD

Jonathon Moir is program manager at Beyond Benign for the upcoming Green Chemistry Teaching and Learning Community (GCTLC)—an online collaboration and networking platform set to launch in 2023 that will include green chemistry education materials, collaboration spaces, events, job postings, and more. Jonathon received his B.Sc.H. from Queen’s University in 2010 and his PhD from the University of Toronto in 2016 in Inorganic Chemistry with a focus on nanomaterials and electrochemistry. Following graduate school, Jonathon transitioned to the not-for-profit sector, where he has helped manage and support the development of numerous multimillion-dollar international, interdisciplinary research programs, scientific projects, workshops, symposia and national scholarship programs across Canada and the world.

Natalie O’Neil, PhD

Natalie O’Neil is director of higher education at Beyond Benign. Natalie earned her PhD in chemistry from the University at Albany in 2017. During her graduate studies, she felt that the topics of sustainability, toxicology, and environmental hazards were missing from the traditional graduate chemistry curriculum. Therefore, she pursued a one-year certification in Green Chemistry and Chemical Stewardship and attended the American Chemical Society (ACS) Green Chemistry & Sustainable Energy Summer School. She now uses her teaching experience and her passion to empower the next generation of scientists to use sustainable approaches through green chemistry through the Beyond Benign Green Chemistry Commitment (GCC) program.

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