Fine chemicals and pharmaceuticals are traditionally produced in batches. Switching to a flow process that generates a steady stream of such substances could offer huge benefits, notably in terms of sustainability, but this is not an easy task. Technical advances delivered by EU-funded researchers are facilitating the transition and opening up new possibilities.
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The Synflow project generated new knowledge and techniques for the production of fine chemicals and pharmaceuticals. Its outcomes could help to make the production of many high-value substances considerably more efficient and sustainable, says project coordinator Walter Leitner of RWTH Aachen University in Germany.
The key lies in a shift towards flow processing, he notes, a method by which substances are synthesised on an ongoing basis as reagents stream past an immobilised molecular catalyst. This approach contrasts with the batch processing approach traditionally used in this industrial sector, where materials are left to react in large vessels.
Compact, clean, cost-effective
Many chemical substances are already produced using flow processes, Leitner explains. However, these molecules tend to be simpler than the sophisticated compounds targeted by Synflow.
For these, batch processing remains the current standard. In contrast to a well-designed flow process, this approach tends to produce a lot of waste, Leitner notes, and it typically involves solvents, which add to the product’s environmental footprint. At the end of the process, the waste, the solvents and any catalysts used to support the reaction are still in the vessel, and so more work is required to separate and isolate the actual product.
Flow processes can be far more efficient and sustainable, Leitner explains. In line with the principles of Green Chemistry they can, for example, be designed without solvents and set up to avoid waste. The formation of unwanted side products can be avoided or reduced, catalysts are kept stationary, and so flow processing can also deliver a particularly clean product, reducing the need for purification
There are further advantages. Flow processing can help to boost safety, and it offers scope for automation. It can be initiated and interrupted flexibly. As an added bonus, the equipment is less bulky than the hardware used in batch processing, as smaller amounts of materials are processed at any given time.
Transformations on tap
That said, making the change can be difficult, particularly for the elaborate transformations involved in producing particularly complex molecules. At the current state of the art, the flow processes have to be engineered individually for every type of product, says Leitner, and every one potentially requires completely new catalysts, equipment and techniques. Synflow set out to address a number of generic challenges in a bid to take the entire field forward by providing methods to speed up this process and to deliver techniques with a broad application portfolio.
Developing suitable catalysts is one such challenge. “One of the main complications lies in immobilising the catalyst while keeping it effective,” Leitner notes. “These catalysts normally operate in solution, dissolved like sugar in coffee. When you put them into another system, they tend to get very unhappy.”
The project thus explored ways to keep their catalysts engaged. One particularly creative approach involves a catalyst-friendly coating. “It’s a solid material that looks like a powder,” Leitner explains. “You can fill it into a tube for this type of process, but every grain is covered with a thin film of liquid where the catalyst sits with a big smile on its face.”
While Synflow’s innovative solutions were initially developed to support the transition of well-established processes, they could also enable entirely new ones, Leitner notes. Further activity in the project thus focused on the wider potential of the partners’ new technologies, for example to tackle reactions that would have been hard to handle in batch operation. Such reactions notably include transformations involving reactive gases under high pressure.
The project’s findings are feeding into new developments throughout the sector, Leitner concludes. “Synflow was a wonderful project in that it laid out the methodological basis,” he explains. “The implementation of catalysis and production under continuous flow is happening as we speak in industry, and Synflow has provided a lot of input for this transition.”