Studies in the development of an ibuprofen preparation suitable for use in introductory organic chemistry laboratory courses

CHED 448

Lindsey R. Edenburn, ledenburn@mymail.indstate.edu and Richard A. Kjonaas, rkjonaas@indstate.edu. Department of Chemistry, Indiana State University, Terre Haute, IN 47809
Although the chemical literature is replete with methods for the synthesis of ibuprofen, there are no reports of a method that meets the common criteria for use in an introductory organic chemistry laboratory course. Most of the reported methods for making ibuprofen involve a transition metal catalyzed aryl/alkyl coupling reaction. Although we began our study by exploring this route, we abandoned it in favor of a more student friendly Grignard route. With acetophenone as the starting material in a model study, we successfully developed a suitable 2-“day” procedure for making 2-phenylpropanoic acid using NaBH4, HCl, Mg, and CO2. Our efforts to use this procedure with p-isobutylacetophenone, however, were soon met with the realization that secondary p-alkylbenzylic halides are considerably more prone to Wurtz coupling than their unsubstituted counterparts.