Question

Draw in detail the reaction mechanism for the acid (H2SO4)-catalyzed esterification reaction between salicylic acid and acetic anhydride to form aspirin. Please include an explanation of the steps of the reaction mechanism.

Answer 1

The balanced equation for the reaction of the acid (H₂SO₄)-catalyzed esterification reaction between salicylic acid and acetic anhydride to form aspirin is

Mechanism for the reaction:

Sulphuric acid is a strong acid. So, it can donate many protons. The acid dissociation reaction is

The synthesis is acid catalyzed. First there is a reversible reaction in which the oxygen of the carbonyl of the acetic anhydride is protonated. This increases the electrophilicity of the carbon of that carbonyl. The oxygen of the phenol in salicylic acid acts as a nucleophile and attacks the carbon of the carbonyl within acetic anhydride and simultaneously breaks the π bond to oxygen. This forms a tetrahedral intermediate. A series of proton transfers occur. The electrons on the oxygen of the hydroxyl group on the tetrahedral intermediate, ultimately come down and reform a carbonyl group, this simultaneously induces an acetic acid to leave. After one additional proton transfer, the final aspirin is formed.