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.
Figure 7: Grignard microreaction with two subsequent quench modules. (FIGURE COURTESY OF SAFC)
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.
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, Andreas.Weiler@sial.com
. Matthias Junkers, PhD, is product manager of chemistry at Sigma-Aldrich.
*To whom all correspondence should be addressed.
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).