Trifluoromethyl Groups in Pharmaceuticals

The trifluoromethyl group is a component of several commonly used drugs including the antidepressant Prozac, arthritis medication Celebrex, and Januvia which is used to treat the symptoms of diabetes. Trifluoromethyl groups are also a common component of agricultural chemicals such as pesticides.

Chemists often use hydrogen fluoride to attach a trifluoromethyl group to an organic compound, but under the conditions of the reaction this might produce unwanted reaction products. MIT chemists have designed a new way to attach a trifluoromethyl group to certain compounds using a palladium catalyst. The key to the success of this catalyst has been the use of a ligand called BrettPhos. During the reaction, a trifluoromethyl group is transferred from a silicon carrier to the palladium, displacing a chlorine atom. The trifluoromethyl containing molecule is then released and the catalytic cycle begins again. The chemists have tried the synthesis with a variety of aryl compounds and have achieved yields between 70% and 94%.

Reference:
Eun Jin Cho, Todd D. Senecal, Tom Kinzel, Yong Zhang, Donald A. Watson, Stephen L. Buchwald. The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides. Science, 2010; 328 (5986): 1679-1681 DOI: 10.1126/science.1190524

Study Questions

1. Write the chemical formula for the trifluoromethyl group and for hydrogen fluoride.
2. Write a chemical equation to show the possible reaction between hydrogen fluoride and cyclohexane.
3. Write a chemical reaction to show the possible reaction between hydrogen fluoride and cyclohexene.
4. For each reaction above, assuming you start with 100g of each reactant, what mass of fluorinated product would be produced if the yield was 70%?
5. For each reaction above, assuming you begin with 25 moles of each reactant, what mass of fluorinated product would be produced if the yield were 94%?
6. For the catalytic reaction discussed in the above article, why do you think the reaction does not produce a 100% yield?