Wednesday, May 25, 2011

Strepsils - A FLurbiprofen pathway to synthesis

Recently, I caught a cold which is why I took some pills (Strepsils) for sore throat. Curious by nature, I took a glimpse at the chemical composition of the medication. What I observed, was that the active compound in the pills was a substance called Flurbiprofen. Due to the phonetical resemblance to ibuprofen, a well known pain-killer, I made some research about its nature and its uses.

Not surprisingly, it resembles very much to (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid (more shorter ibuprofen). The difference lays in the substitution of the isoproyl radical with phenyl and the hydrogen atom in ortho with a fluoride atom.


Firstly, I thought of a method to synthethise the compound from phenyl lithium and fluorobenzene as main building blocks, both of which had to be produced from benzene.

Fluorobenzene

Fluorobenzene, was to be obtained by reducing the nitration product of benzene followed by diazotation. The diazonium salt was treated with tetrafluoroboric acid. To obtain the desired compound the reaction product was put to high temperatures.


Phenyl Lithium

The phenyl lithium, is more easily available. All is needed to do in order to produce it is to bromurate benzene in a FeBr3 environment and after this to react the product with fresh lithium well kept under petrol before the reaction.


The main synthesis

The two building blocks must be first reacted in a moderate to highly acid environment. This way, biphenyl is produced. If directly available, all previous steps may not be taken into consideration, instead the usage of a more pure biphebyl reagent would be preferred.


The biphenyl will then undertake nitration in ortho. This way, when we alkylate with cloroacetic acid, the acetyl radical will be prone to go into the para position. The nitrate is then reduced with an iron and HCl mixture, next following a process similar to that in the innitial synthesis of fluorobenzene.


It is crucially important to reduce the nitro group after the alkylation due to the fact that in the opposite case, the acetyl radical would go into the ortho position yielding a totally different compound. Finally, flurbiprofen is obtained.

Generally, the sore throat medicines are made of an antiseptic and of an antiinflammatory drug. The antiseptic will reduce the microbian flora in the pharynx, while the antiinflammatory will reduce the prostaglandines and thromboxanes production, the root cause of the painful inflammation.

Despite being used for curing sore throat, its uses exceed this limited applicability. Due to the mechanism of action, flurbiprofene makes possible its use for treating the pain involved in different arthritis types of disease, a major relief for the great number of people suffering from a reumatical condition.

2 comments:

  1. This is the incorrect structure of Flurbiprofen and a more efficient method for synthesis is via the palladium catalysed suzuki-miyaura cross coupling reaction.

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