WM5 The synthesis of salicylic acid and aspirin

Synthesis is better than harvesting Chemists can synthesise (artificially produce) compunds, once the structure is known. Phenol’s germicidal properties were well known by the end of 19 th Century. Phenol (a product from heating coal) was readily available. 2-hydroxybenzoic acid has 1 extra functional group, compared to phenol.

How is phenol converted into 2- hydroxybenzoic acid? Draw the structures of phenol and 2- hydroxybenzoic acid. What extra atoms need to be added to phenol? What conditions and reagents are needed? (research this).

Kolbe –Schmitt synthesis Kolbe (1874) produced salicylic acid from dry sodium phenoxide in a stream of carbon dioxide at 150 – 160 °C. He found that the yield was only 50%. Schmitt (1884) increased the yield to 90% by increasing the pressure to 5 bar (7atm), until no more CO 2 was taken up.

On an industrial scale… Felix Hoffmann developed process for the Bayer company. Unpleasant side-effects on mouth, gullet and stomach. Hoffmann modified the structure and tested products on his rheumatic father! 1898 – 2-ethanoylhydroxybenzoic acid (aka acetylsalicylic acid OR aspirin) produced

Aspirin: made by esterification Aspirin is an ester O Functional group R-C-O-R’ Alcohol + acid  ester Aspirin is not very soluble in water so it became the first medicine to be sold as tablets. You can read about esters and esterification in CI 13.4.