Investigation of the Moffatt−Swern Oxidation in a Continuous Flow Microreactor System

• Published in: Organic process research & development Vol. 12; no. 5; pp. 911 - 920
• Main Authors: van der Linden, Jacobus J. M, Hilberink, Peter W, Kronenburg, Claudia M. P, Kemperman, Gerardus J
• Format: Journal Article
• Language: English
• Published: American Chemical Society 19.09.2008
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/op700228e

The Moffatt−Swern oxidation of different alcohols is performed in a continuous flow microreactor system. The microreactor process offers significant advantages over the batch process. First, because of the small reactor volume, accumulation of the labile trifluoroacetoxydimethylsulfonium salt (3) and alkoxydimethylsulfonium salt (5) is minimized. Second, because of the short residence times, which can be applied in the microreactor, the exothermic Pummerer rearrangement of the unstable intermediate 3 is limited. Because of this, the process can be operated at remarkably high temperatures in comparison with a batch reaction, viz. 0−20 °C instead of −70 °C. In the present study, a continuous flow microreactor system was optimized using reactors of different volumes allowing modulation of the residence times of labile intermediates. The efficiency of mixing was studied using different mixing devices. It has been shown that the continuous flow microreactor is an ideal tool for rapid optimization of reaction parameters. Furthermore, the scaleability and reliability of the microreactor was tested by running the system for several hours. For testosterone, the system was in process for 1.5 h without any problems, resulting in an 4-androstene-3,17-dione production rate of 64 g·h−1.