Ibuprofen Chemistry

Ibuprofen is a commonly used pain reliever. Its chemical properties include:

Ibuprofen has a poor water solubility with less than 1 mg of ibuprofen dissolving in 1 ml water. It is more soluble in aqueous alcohol mixtures.

Stereoisomerism

Ibuprofen has a stereocenter in the α-position of the propionate moiety. There are two possible enantiomers of ibuprofen and each of these has different biological effects and metabolism within the body. The mirror images or setreoisomers are non-superimposable, much like the left and the right hand.

The two optical isomers of ibuprofen are identified by the prefixes R- and S+. The stereoisomers are similar in properties such as melting point, boiling point and solubility. The S+ form is the more pharmacologically active form and the R- form has no anti-inflammatory effect.

For example dexibuprofen or (S) ibuprofen or (+) ibuprofen is active both in vitro and in vivo. In vivo testing has revealed that an enzyme called the 2-arylpropionyl-CoA epimerase converts (R)-ibuprofen into the active (S)-enantiomer. Due to the presence of this isomerise, most ibuprofen preparations available on the market are in the form of (R)-ibuprofen, as making and manufacturing the (S)-enantiomer form is more difficult and expensive.

Synthesis of ibuprofen

Ibuprofen was originally synthesized by Boots in a process which involved six steps. The first step was the Friedel-Crafts acetylation of isobutylbenzene. Next, the Darzens reaction was used to give the α, β-epoxy ester which was then hydrolyzed and decarboxylated to the aldehyde. Interaction with hydroxylamine then gave an oxime which can be converted to nitrile and hydrolyzed to the correct acid.

Now, the synthesis is a shortened three-step process developed as a joint initiative between Boots and the company Hoechst Calanese (BHC).

Further Reading

• What is Ibuprofen?
• Ibuprofen Mechanism
• Ibuprofen Side Effects
• Ibuprofen Toxicology