Using Microreactors in Chemical Synthesis: Batch Process versus Continuous Flow - Pharmaceutical Technology

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Using Microreactors in Chemical Synthesis: Batch Process versus Continuous Flow
The authors discuss the advantages of microreactors and flow chemistry for various reaction types in achieving improved process economics and reaction efficiency.


Pharmaceutical Technology


Grignard reactions


Figure 7: Grignard microreaction with two subsequent quench modules. (FIGURE COURTESY OF SAFC)
Accelerated and economic process development for large-scale synthesis. Microreactors have simple and pragmatic advantages over traditional batch vessels. They take up less space on the factory floor, but can be used to make large quantities of product. 2-Benzoyl pyridine is an important building block and has annual demand of about 15 metric tons. It is synthesized through a Grignard reaction (see Figure 7). In a microreactor, this reaction takes less than one minute. The Grignard microreaction is followed by two on-line quench modules. Precise reaction control leads to a highly pure crude product, thereby making a distillation step unnecessary, as would be the case for purification of the lower quality batch product.

This reaction was performed in a stainless-steel plate reactor (ART, Alfa Laval, Lund, Sweden). The reactor took up only 30 X 50 cm of space on the bench. Rapid flow rates were achieved with this reactor, thus allowing the continuous production of 200–300 kg of 2-benzoyl pyridine per day.

Conclusion

These reactions show the versatility and utility of microreactor technology and flow chemistry in chemical synthesis. Such an approach offers many advantages over traditional batch-mode manufacturing. Depending on the reaction, improved process economics, greater reaction efficiency, and waste reduction may be achieved. Problems inherent in scale-up are eliminated or reduced, making microreactor technology a viable tool in the synthesis of APIs.

Andreas Weiler*, PhD, is global business director of SAFC Pharma, Industriestrasse 25, 9470 Buchs, Switzerland, tel. 41 81 755 2405, fax 41 81 755 2584,
. Matthias Junkers, PhD, is product manager of chemistry at Sigma-Aldrich.

*To whom all correspondence should be addressed.

References

1. T. Schwalbe, V. Autze, and G. Wille, "Chemical Synthesis in Microreactors," Chimia 56 (11), 636–649 (2002).

2. T. Schwalbe et al., "Novel Innovation Systems for a Cellular Approach to Continuous Process Chemistry from Discovery to Market," Org. Process Res. Dev. 8 (3), 440–454 (2004).


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