How dirty are you?

I don’t feel stable! – You’re overreacting.

Green chemistry can be considered in general terms as the ‘domestic economy’ of chemistry. We, desperate housewifes of the lab, care at not to elicit too much disorder into our lab to get things done. This can be done in various ways as reducing usage of chemicals to the bare necessity and picking the less harmful path, to both environment and human health. This is also something looked after by the EU commission in the  extent to switch towards a circular economy.[1]

Surprisingly many colleagues of mine were not aware on how to properly evaluate the greenness of a reaction and how to improve their own research by changing their approach to chemistry. Herein, I would like to introduce the reader in general terms to the world of green metrics, expand his/hers view onto the exciting challenges posed by this different approach to chemistry and suggest some interesting reviews, articles and authors to follow to further extend their knowledge onto this argument.

As for green metrics, life cycle assessment (LCA) is the golden standard to have an overview onto a process. This approach is a so called “cradle-to-grave” approach because it values all the steps trough the process, from sourcing to end of life of the product. Although, life cycle assessments are not a viable alternative for everyday assessment because they require a large amount of data to be correctly implemented.[2,3] Therefore, some reaction-centred metrics were studied to allow to chemists to evaluate the greenness of a reaction. This is not anymore a cradle-to-grave but a gate-to-gate approach, as what happens before and after the reaction is not considered in the assessment. However, this is already a very powerful approach to determine the environmental footprint of a reaction, especially in terms of waste reduction.[4]

E-factor is one of the oldest and most versatile mass-based metric. This metric evaluates the amount of Kgs of waste produced against the amount of Kgs of product obtained.

In this way, as low as the E-factor is as greener the reaction becomes. A shortcoming of this metric thou is the totally absence of a qualitative assessment of the reagents and solvent used, in other words, if I use or produce a strongly human or environment endangering substance or if I produce a totally innocent one is not evaluated by the metric itself. To pose solution to this shortcoming, the metric author, Seddon, proposed to multiply the E-factor for a coefficient that would consider the noxiousness of the process. However, a cohesive framework of evaluation of environmental and human toxicity of chemicals is hardly attainable at the current state of art due to the lack of a sufficient amount of toxicity studies and data to have a coherent and cohesive evaluation framework for chemicals.

To avoid this issue, other metrics decided to exclude from the waste the substance that are certainly non-noxious as water or brine. Another interesting metric is the process mass intensity (PMI). It was adopted by the Green Chemistry Institute Pharmaceutical Round Table as metric of choice to benchmark the greenness of the production of APIs (Active pharmaceuticals ingredients). It is defined as the mass of all the materials used to make the product divided via the mass of the product.[5]

CodeCogsEqn (1)

Also here a qualitative consideration is absent this metric was choose in relation to the easiness of calculation because the amount of starting materials is often more readily available in any laboratory notebook then the amount of waste. The perfect PMI is 1 and is the case in which all the materials used ends up in the product. In this sense, E-factor and PMI can be related to each other by the following equation:

CodeCogsEqn (2)

All those metrics are of great use to determine the efficiency of processes but all of them lacks of a consideration onto the quality of the reagents and solvents used in the process.[6] Solvents are by definition the chemical present in the widest amount. Therefore, a general guideline on solvent choices is already of great help to any chemist. GlaxoSmithKline, aware of the danger and the costs posed by the post processing of noxious solvents, elaborated a wide solvent analysis suggesting a chart for the environmental footprint of a large assay of solvents in 2011[7] which was further extended in 2016[8] and complemented with a commonly used reagents guide, followed also by one of Pfizer [9,10]. The work of these pioneers is surely of great use to anyone in the field and is clear to which extent this discipline is remarkably important in both academic and industrial world. The implementation of these ‘good practices’ has been the springboard for assay studies on alternative solvents for common reactions as reductive amination[11], amide bond formation[12] or olefin metathesis[13].

Green chemistry considers also chain supply needs, pushing for an implementation of processes that source their starting materials at a sustainable consumption rate. In more simple terms, this means to switch to renewable sources, possibly available in large quantity, especially if they are already production by-products (e.g. glycerol, lignin decomposition, bioethanol).[14–17]

In conclusion, chemistry always had challenges to overcome and, in the years, many brilliant scientists followed each other opening the path and giving us strong basis to face current issues. Green chemistry is here and it is a fantastic opportunity to everyone to live in a better world and a better lab environment, reducing risk, costs and lengthy procedures by pushing further the boundaries of our knowledge. Why not stick to it?

References

[1] Clark, J. H., Farmer, T. J., Herrero-Davila, L. & Sherwood, J. Circular economy design considerations for research and process development in the chemical sciences. Green Chem. 18, 3914–3934 (2016).
[2] Sheldon, R. A. The E factor 25 years on: the rise of green chemistry and sustainability. Green Chem. 19, 18–43 (2017).
[3] Sheldon, R. a. E factors, green chemistry and catalysis: an odyssey. Chem. Commun. (Camb). 3352–3365 (2008). doi:10.1039/b803584a
[4] Andraos, J. Unification of reaction metrics for green chemistry: Applications to reaction analysis. Org. Process Res. Dev. 9, 149–163 (2005).
[5] Constable, D. J. C. et al. Key green chemistry research areas—a perspective from pharmaceutical manufacturers. Green Chem. 9, 411–420 (2007).
[6] McElroy, C. R., Constantinou, A., Jones, L. C., Summerton, L. & Clark, J. H. Towards a holistic approach to metrics for the 21st century pharmaceutical industry. Green Chem. 17, 3111–3121 (2015).
[7] Henderson, R. K. et al. Expanding GSK’s solvent selection guide – embedding sustainability into solvent selection starting at medicinal chemistry. Green Chem. 13, 854 (2011).
[8] Alder, C. M. et al. Updating and further expanding GSK’s solvent sustainability guide. Green Chem. 4, 1166–1169 (2016).
[9] Alfonsi, K. et al. Green chemistry tools to influence a medicinal chemistry and research chemistry based organisation. Green Chem. 10, 31–36 (2008).
[10] Adams, J. P. et al. Development of GSK’s reagent guides – embedding sustainability into reagent selection. Green Chem. 15, 1542 (2013).
[11] McGonagle, F. I. et al. Development of a solvent selection guide for aldehyde-based direct reductive amination processes. Green Chem. 15, 1159 (2013).
[12] MacMillan, D. S., Murray, J., Sneddon, H. F., Jamieson, C. & Watson, A. J. B. Evaluation of alternative solvents in common amide coupling reactions: replacement of dichloromethane and N,N-dimethylformamide. Green Chem. 15, 596 (2013).
[13] Skowerski, K., Białecki, J., Tracz, A. & Olszewski, T. K. An attempt to provide an environmentally friendly solvent selection guide for olefin metathesis. Green Chem. 16, 1125–1130 (2014).
[14] Chemistry, G. How renewable is renewable ? Assessing sustainable feedstocks. 24, 38–40
[15] Christensen, C. H., Rass-Hansen, J., Marsden, C. C., Taarning, E. & Egeblad, K. The renewable chemicals industry. ChemSusChem 1, 283–289 (2008).
[16] Werpy, T. and Petersen, G., Werpy, T. & Petersen, G. Top Value Added Chemicals from Biomass Volume I — Results of Screening for Potential Candidates from Sugars and Synthesis Gas Top Value Added Chemicals From Biomass Volume I : Results of Screening for Potential Candidates. Other Inf. PBD 1 Aug 2004 Medium: ED; Size: 76  pp. pages (2004). doi:10.2172/15008859
[17] Wu, L., Moteki, T., Gokhale, A. A., Flaherty, D. W. & Toste, F. D. Production of Fuels and Chemicals from Biomass: Condensation Reactions and Beyond. Chem 1, 32–58 (2016).

About The Author

My name is Giacomo Damilano, I am a green chemist from Italy and I am the ESR 8. Lately, I started my PhD studies here at KU Leuven into the synthesis of novel Ionic Liquids starting from renewable materials. Ionic liquids are marvellous materials to carry on research! They are salts liquid at about room temperature with unique proprieties as, for example, nearly non-existent vapour pressure, which avoids both financial and environmental issues related with solvents evaporation.

May you be interested to my argument of research, you are more than welcome to get in touch with me at: giacomo.damilano@gmail.com.

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