Synthetic Organic chemists are wasteful. There, I’ve said it. On a daily basis around the globe, the pharmaceutical and supporting industries use vast quantities of reagents and solvents, the majority of which are derived from fossil resources; catalysts, many of which are based on rare precious metals; and purification media, where a linear economy is in operation. These consumables are used and discarded – heading to the incinerator and contributing huge quantities of carbon dioxide to the earth’s atmosphere and playing a role in the growing climate emergency.
This is an especially pressing issue for manufacturing campaigns of complex active pharmaceutical ingredients (APIs) which typically require 6-10 chemical steps to furnish kilogram quantities, in the process generating an unsustainable amount of waste. Due to the complexities of drug discovery, most of these APIs never even get approved for clinical use. This cannot continue.
But change is coming. We, Malvern Panalytical, are on a journey. A journey to Net Zero and we are committed to achieving this by 2040. Our target is aligned with the Paris Agreement and limiting global heating to 1.5°C above pre-industrial levels and has been validated by the Science Based Targets initiative. But how are we going to achieve this? By unleashing our greatest asset – our people. By engaging our workforce – through our engineering skills and scientific mindset we will use an enhanced consciousness of our environmental footprint to empower our employees to be part of the solution. We are on a road to Net Zero. We are also on the road to becoming more sustainable. Synthetic organic chemists are wasteful – but we’re doing something about it.
The way we do organic Chemistry hasn’t changed much in over 100 years. Sure, there have been some technological advances in purification and analytical techniques but we still use round bottom flasks, Erlenmeyer flasks and separating funnels. Indeed, most of the innovation in organic chemistry has taken place at the atomic level, how to make and break specific chemical bonds and how to interconvert between functional groups. Now into the third decade of the twenty-first century, we are beginning to see paradigm-shifting developments that are changing the way we think about organic chemistry. These advances will allow us to become more sustainable and less wasteful. But this alone is not enough. The central aspect of the synthetic chemistry environmental footprint is the solvent problem. Adopting new working practices is one part of the solution, the other is conscientious solvent selection and minimization – and will be a recurring theme throughout.
One of the key enabling technologies for sustainability is flow chemistry, a chemical reaction run in a continuous flow stream. Flow has been widely adopted by the organic chemistry community and is a crucial component in many GMP manufacturing campaigns. The benefits of utilizing flow are varied and include increased reproducibility and safety, in addition to supporting sustainability. Protocols can reduce waste by minimizing solvent use via avoiding workups with laborious washing and extraction steps, and facilitating solvent recycling. Flow can also reduce energy consumption with more efficient heating and cooling, and promote re-use of heterogeneous catalysts, which are commonly packed into a reactor bed before the reaction is initiated, thereby eliminating any barrier to re-use.
Nature’s ability to convert carbon dioxide and water into carbohydrates via photosynthesis is the pinnacle of sustainable chemistry – and organic chemists have taken notice. In the laboratory, photoredox catalysis uses light to generate single electron species which can then combine with other organic derivatives in novel and interesting ways. This technique has been much heralded and implemented, facilitating hitherto impossible chemical reactivity and selectivity with significant sustainable credentials. Light can be free and energy-efficient avoiding the use of stoichiometric reagents and photoredox chemistry can proceed without the use of rare-earth metals and instead utilize the more abundant copper and nickel. In addition, more direct synthetic routes to arrays of complex lead-like compounds by a late-stage functionalization strategy reduces step count and reduces the subsequent solvent and reagent waste. The major drawback of photoredox catalysis to date concerns scalability, as light can be unable to fully penetrate the reaction medium. One pragmatic solution is to carry out these types of reactions in a flow reactor, giving rise to flow photochemistry and conferring the additional benefits discussed above.
Synthetic organic electrochemistry has been around since the 19th century and has been employed in the manufacture of bulk chemicals. It is only in the last 5 years, however, that electrochemistry has found widespread use in synthesis labs. The game-changer has been the development of a standard preparative electrolysis apparatus suitably designed for the organic chemist, negating the need for a build-your-own approach. The field is relatively immature for this reason. Despite this, synthetic electrochemistry is an inherently sustainable approach to carrying out redox-type reactions because electrical current, which can be from renewable resources, is used in place of stoichiometric oxidants and reductants.
Another method to avoid the use of stoichiometric reagents is to use more atom economical catalytic alternatives. The gold standard surely has to be biocatalysis. Thanks to advances in biotechnology and recombinant DNA technology, enzymes can be designed, isolated (and immobilized) in an acceptable timeframe and cost. Furthermore, enzymes are produced from renewable resources and are biodegradable – a truly closed-loop economy. Enzymatic chemical reactions can offer unique approaches to targets, reduced step counts by avoiding protecting group strategies, and reduce solvent and energy usage as most reactions are performed in aqueous systems at ambient temperature.
Flow chemistry, photochemistry, electrochemistry and biocatalysis are beginning to offer more sustainable options to the synthetic organic chemist. But to have a meaningful impact, these technologies need to be adopted together with minimizing the use of greener, more sustainable solvents. Join us for our upcoming webinar series: The future of sustainable chemistry where we will explore the benefits of these four technologies and discuss how they are being embraced by organic chemists to deliver novel synthetic routes to candidate drugs.
Click here to sign up to the first in the series – The future of sustainable chemistry: Electrochemistry
Further reading
- Nobel prize in chemistry awarded for research on lithium-ion batteries
- Are you ready to embrace the green fuels of the future?
- Closing the gap – how to solve the battery market’s sustainability problem
- GMP: More than meets the (chemistry) eye!
