Extraction of salicin from willow park

Preparation of acetylsalicylic acid (aspirin)


Background:
In 1763 the use of willow tree bark was reported in more specific terms by Reverend Edward Stone in a lecture to the Royal Society in London. He used its extracts to treat the fever resulting from malaria (then common in Britain; there are some marshes in the UK where the malarial mosquito still persists). He also found that it helped with ‘the agues’, probably what is now called arthritis. Other common medicines of the time included opium to relieve pain and Peruvian cinchona bark for fevers (it contained quinine).
In the early part of the 1800s chemists in Europe took willow leaves and boiled them with different solvents to try to extract the active ingredients. In 1825 an Italian chemist filtered such a solution and evaporated away the solvent. He obtained impure crystals of a compound containing some of the active ingredient. Repeated recrystallization and refinement of his experimental technique produced a pure sample of the unknown material (Figure:1)


(Figure :1)
In 1828 Buchner in Germany managed to obtain some pure white crystals of a compound by repeatedly removing impurities from an extract of willow bark. He called it ‘salicin’ (Figure 1.2). It had a bitter taste and relieved pain and inflamma¬tion. This same compound was extracted from a herb called meadowsweet by other chemists. Analysis of salicin showed it to be the active ingredient of willow bark joined to a sugar, glucose.

In the body, salicin is converted into salicylic acid (Figure 1.3) and it was this that was thought to be the active ingredient that relieved pain, but it had such a very bitter taste that it made some people sick. Some patients complained of severe irritation of the mouth, throat and stomach.
The extraction process for making the salicin also proved long and tedious and wasteful of trees: from 1.5 kg of willow bark only 30g of salicin could be obtained.3,4 Once the formula was known for salicylic acid, a group of chemists tried to work out how to make it artificially by a less expensive and tedious process.