Synthesis of Ibuprofen in the Introductory Organic Laboratory

A method for the synthesis of ibuprofen in introductory organic chemistry laboratory courses is reported. This experiment requires two 3-h lab sessions. All of the reactions and techniques are a standard part of any introductory organic chemistry course. In the first lab session, students reduce p-isobutylacetophenone to an alcohol and then convert this alcohol to the corresponding chloride. In the second session, students convert this chloride to a Grignard reagent, which is then carboxylated and protonated to give ibuprofen. Although the final yield is modest, this procedure offers both practicability and reliability. Permanent-magnet 60 MHz (1)H NMR spectra of the final product and the two intermediates are clean and are easily interpreted by the students. Because, as previously reported, the benzylic methylene and the benzylic methine of ibuprofen have virtually identical (13)C NMR chemical shifts and cancel or nearly cancel each other in the DEPT spectrum, this synthesis provides a fitting opportunity for the introduction of HETCOR even with a permanent-magnet Fourier transform instrument.