Ibuprofen Goes With The Flow

Using a three-step continuous-flow process, chemists at Florida State University have prepared the popular nonsteroidal anti-inflammatory drug ibuprofen (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200903055). Such continuous-flow syntheses could lead to safer, cheaper, and more efficient pharmaceutical production, according to D. Tyler McQuade and Andrew R. Bogdan, who spearheaded the work. Their synthesis makes use of a simplified microreactor—a device in which reactions are carried out in microchannels or narrow-bore tubing. The system gives chemists precise control over heat transfer and mixing and also eliminates the need to purify any intermediates. To make ibuprofen, McQuade and Bogdan’s team had to design a reaction sequence in which all excess reagents and by-products were compatible with downstream reactions. Their scheme begins with a Friedel-Crafts acylation of isobutylbenzene, followed by a 1,2-aryl migration, and concludes with a saponification. With less than 500 cm of tubing and five syringe pumps, the chemists were able to produce crude ibuprofen at a rate of 9 mg/minute. They note that a continuous, high-throughput synthesis of the drug could be easily achieved by adding parallel reactors or by lengthening the channels combined with alternative pumping mechanisms.