Chemistry 251 Laboratory -- Spring 2002
Ibuprofen Project -- Superbase Approach

This strategy uses the "superbasic" mixture of butyllithium and potassium tert-butoxide to deprotonate benzylic positions. These anions can then be used as nucleophiles. Using this strategy, p-xylene was sequentially reacted with methyl iodide, isopropyl bromide, and carbon dioxide to yield ibuprofen in 52% overall yield.

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
p-Xylene Anhydrous	Aldrich Cat. # 29,633-3	20 g	TA room
Iodomethane	Malinckrodt Cat. # 1077	10 g	Th 303? Special storage cabinet	Highly Toxic! Cancer Suspect Agent! Handle with gloves in a hood.
2-Bromopropane	Aldrich Cat. # B7, 811-4	10 g	TA room	Flammable Solid, Moisture Sensitive
Butyllithium 1.6 M solution in Hexanes	Aldrich Cat. # 18,617-1	20 mL	TA Room	Flammable liquid. Moisture sensitive. Dispense under nitrogen.
Potassium tertbutoxide	Aldrich Cat. # 15,667-1	10 g	TA room	Flammable solid. Moisture Sensitive.

A mixture of p-xylene (20 mmol), butyllithium (22 mmol), and potassium tertbutoxide (22 mmol) in hexane (15 mL) was vigorously stirred 2 h at 25 ° C. Methyl iodide (22 mmol) was introduced dropwise, in the course of 5 min, at -75 ° C. .... Then let warm to room temperature. They then went on to add more superbase and continue, but we should probably just isolate this material and see if the reaction works for us.

1. 3/28/02 -- We haven't seen the final results yet, but Aubrey and Lilian tried this reaction (p-xylene + MeI). The mixture of BuLi/KOtBu/p-xylene in hexane was a deep, bright red, probably reflecting formation of the benzyl anion. The mixture was cooled to -78 C and methyl iodide was added. The red color disappeared. The mixture was warmed to RT and quenched with sat. ammonium chloride. Then extracted with hexane. The hexanes were dried and we will look at the GC/MS to see if we got any product.



2. 4/4/02 -- The GC/MS of the crude product looks good! (They used a starting temperature of 80 degrees for 3 minutes then ramped to 150 at 10 deg/min. The p-xylene was well separated from the product ethylmethylbenzene.) There is about a 80:20 mixture of product:starting material. Aubrey and Lilian also did a distillation on the product and they will look at the GC/MS and/or NMR of the various fractions they obtained.