Manufacture of Aspirin (AQA A-Level Chemistry): Revision Notes

7.3.6 Manufacture of Aspirin

Manufacturing of Aspirin

Aspirin, a widely used pharmaceutical, is synthesised via an acylation reaction involving salicylic acid and ethanoic anhydride. This reaction is a key application of acylation in the pharmaceutical industry, with similar acylation reactions also used in other sectors, such as textiles (e.g., making cellulose acetate).

Reaction Overview:

The synthesis of aspirin from salicylic acid and ethanoic anhydride proceeds as follows:

$${Salicylic acid} + \text{Ethanoic anhydride} \rightarrow \text{Aspirin} + \text{Ethanoic acid}$$

1. Reactants:

• Salicylic Acid: Provides the phenolic group that undergoes acylation.
• Ethanoic Anhydride: Serves as the acylating agent, transferring an acyl group to salicylic acid.

2. Products:

• Aspirin: The desired pharmaceutical product, which is an ester.
• Ethanoic Acid: A by-product that is relatively mild and non-corrosive.

Industrial Advantages of Using Ethanoic Anhydride over Ethanoyl Chloride

In aspirin manufacturing, ethanoic anhydride is preferred over ethanoyl chloride for several reasons:

3. Cost-Effectiveness:

• Ethanoic anhydride is generally cheaper to produce than ethanoyl chloride, making it more economical for large-scale production.

4. Controlled Reactivity:

• Ethanoic anhydride is less reactive than ethanoyl chloride, allowing for a more controlled reaction process. This control minimises the risk of unwanted side reactions and excessive heat release, which can be challenging to manage industrially.

5. By-Products:

• The reaction with ethanoic anhydride produces ethanoic acid as a by-product, which is relatively safe and non-corrosive. In contrast, the reaction of ethanoyl chloride would produce hydrogen chloride gas, a highly corrosive and hazardous by-product that requires careful handling.

6. Reaction Conditions:

• Reactions with ethanoyl chloride tend to be very fast and highly exothermic, making them harder to control, particularly on an industrial scale. Ethanoic anhydride, being less reactive, allows for a milder, more easily managed reaction environment.