Chemistry 251 Laboratory -- Spring 2001
Racemic Ibuprofen Project Home Page

Index

• 2000 Ibuprofen Synthesis Home Page
• Students working on this project
• Table of Reagents and Amounts Available
• Notes on Step 1

Ibuprofen is the active ingredient in a number of over the counter pain relievers, e.g. Advil, Motrin, and Nuprin. It is one of the top-ten drugs sold worldwide, and, although it has been shown that only the S enantiomer has the desired biological activity, it is currently sold as the racemate. There are actually two syntheses worth exploring here. The first, a synthesis of the racemate, begins with reaction of 4-isobutylacetophenone with the sulfur ylide produced by deprotonation of trimethylsulfonium iodide to yield an epoxide. (You should look this reaction up in an advanced organic text, e.g. the one by Jerry March.) Last year we found that BF₃Et₂O catalyzed rearrangement of the epoxide to give the aldehyde worked well. What remains to be explored is the oxidation of this aldehyde to give the racemic Ibuprofen. An enantioselective synthesis of Ibuprofen could be accomplished by first performing a Wittig reaction to give the alkene and then performing an enantioselective epoxidation. The epoxide is then opened reductively by treatment with H₂ and Pd catalyst to give an alcohol that is then oxidized to the acid, Ibuprofen, using KMnO₄.

The table below lists the chemicals that we will have available for this project. If you need something that is not on this list, consult with the mentor for your project. Also note the "Amount/group" column. This is the total amount of material available for each group to use on the project.

Reagent	Source	Amount/group	Location	Comments
4-isobutylacetophenone	Lancaster Cat. # 6284	5 g	TA room
Trimethylsulfonium iodide	Aldrich Cat. #T8,048-9	4 g	TA room	Irritant
Sodium Hydride (60% dispersion in mineral oil)	Aldrich Cat. #45,291-2	5 g	TA room	Flammable Solid, Moisture Sensitive
Methyltriphenylphosphonium bromide	Aldrich Cat. #13,007-9	10 g	TA room	Irritant, Hygroscopic
Butyllithium (1.6 M in Hexanes)	Aldrich Cat. #18,617-1	20 mL	TA room	Flammable Liquid, Moisture Sensitive
DMSO (Dimethyl sulfoxide)			TA room	Wear gloves when handling DMSO. It is readily absorbed through the skin!
Boron trifluoride diethyl etherate			TA room	Caution: Toxic, corrosive, moisture sensitive. Dispense under nitrogen in the hood.