Chemistry 251 Laboratory -- Spring 2000
Ibuprofen Project Home Page

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Last updated on 4/12/00


Synthesis of Ibuprofen

Faculty Mentor: John Hanson

Reference: Cleij, M.; Archelas, A.; Furstoss, R. J. Org. Chem. 1999, 64, 5029-5035.

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. The synthesis 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.) 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.

Students Working on This Project

Lab Day Name E-mail
Monday Randy Baca
Monday Mark Allen
Monday Kat Corkum
Tuesday Sarah Hesseltine
Tuesday Jayme Takahashi
Wednesday Jenny Anguiano
Wednesday Erin Haney
Thursday Krista Prescott
Thursday Mari Gantner
Thursday II Joy Manning
Thursday II Kathleen White
Friday Ty Koch
Friday Steve Russell

Table of Reagents and Amounts Available for this Project

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!
Pd, powder, submicron Aldrich
Cat. #32,666-6
0.2 g TA room

Step 1: Epoxide Formation using Trimethylsulfonium Iodide

  1. The NaH comes as a dispersion in oil. It looks like a grey powder. Be sure not to expose it to air for any significant amount of time. NaH is usually washed with hexane to remove the oil before it is used. Here is a wash procedure that I used when I was doing a reaction that required 2 g of NaH (it was also a 60% dispersion in oil).

  2. Since the NaH is a 60% dispersion in oil, you will have to weigh out 1.67 times the amount you would need if it was pure.

  3. Is it possible to use NaHMDS instead of NaH? This worked OK, but still some starting material.

  4. Sarah and Jayme got BEAUTIFUL results using 1.5 eq. of NaH, 1.2 eq. of the trimethylsulfonium iodide. They washed the NaH once with hexane, then did the reaction normally. After workup the NMR looked perfect -- no starting material present. No need to do any purification! Click here to see the NMR.