Synthesizing pharmaceuticals, cosmetic ingredients and other valuable fine chemicals can involve complex sequential reactions, use of toxic solvents and often low yields. But imagine if you could simply blend solid powder reactants and extrude the desired product with 100% yield and no waste. Impossible? Not according to recent ground-breaking work in COST Action CA18112 ‘Mechanochemistry for Sustainable Industry (MechSustInd)’.
The concept of bringing solid reactants together in close contact to produce products is known and the Action initially used laboratory-scale ball-mills to grind together materials to make active pharmaceutical ingredients (APIs) such as the antibiotic nitrofurantoin.
Dr Evelina Colacino is an organic chemist at the University of Montpellier, France, and Chair of the COST Action. “Specifically, the action looked to use mechanochemistry to form covalent bonds and avoid conventional organic chemistry lab synthesis,” she explains. “Using mechanochemistry can avoid excessive use of solvents, heating, or the need to adjust pH.”
This initial work demonstrated the potential of mechanochemistry as an alternative route, but the ultimate aim was to develop a continuous process, which could reduce costs and the environmental footprint of fine chemicals production.
Above: A photo of an extruder, the equipment used in the synthesis of the compounds
Notable first
This is where the expertise of Dr Deborah Crawford at the University of Bradford, United Kingdom, and Leader of the Action’s Working Group 3 on engineering perspectives came in. “Extrusion processes are well established in fine chemicals production, but normally only in terms of the final formulation of products,” says Deborah. “So, the equipment is found on site in chemical production plants.” The technology is also used to make or shape food products, such as pasta, and plastics.
A twin-screw extrusion device was used to mix and grind together two solid reactants to synthesize APIs continuously without the use of solvents. Following optimisation of the temperature and rotational speed of the screws, the process was able to generate 0.23 grams of nitrofurantoin per minute with complete conversion to a desired isomer form and with no need for additional purification steps.
This is a notable first and was reported in a paper in ACS Sustainable Chemistry & Engineering in summer 2020 and as a news highlight in Chemical & Engineering News.
Next steps
“A final objective of the Action was to show scale up of API production by extrusion,” says Evelina. “But thanks to the work with Deborah we have accelerated the project.” The Action is now focusing on further optimising conditions, life cycle analysis of the process, and issues such as Good Manufacturing Practice (GMP) certification.
The Action is also looking to involve pharmaceutical manufacturers to collaborate in further scaling up the process. “The Action has demonstrated a straightforward method to obtain generic drugs that is much more cost effective than conventional solution synthesis and is less polluting – it is a truly sustainable chemistry,” says Deborah.
Evelina sees a big added value to COST Actions. “It is fantastic to interact with scientists across Europe and beyond,” she says. “It is like having a multi-centred, virtual lab where you can access every skill, a huge range of equipment and knowledge.”
Deborah agrees saying: “COST Actions are brilliant for early career researchers. They allow you to make the connections and establish the collaborations you need to remain research active as you start an academic career.”
Read more about COST Action ‘Mechanochemistry for Sustainable Industry’
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