The synthesis of paracetamol involves the reaction of 4-aminophenol with acyl chloride or acid anhydride, where only the amino group (R-NH2) reacts, not the hydroxyl group (R-OH). The amino group is more nucleophilic, effectively attacking the acyl group and displacing chloride. The phenolic hydroxyl does not participate significantly due to the low concentration of the phenolate anion, which is a better nucleophile than free phenol. Additionally, the phenolate ester formed under basic conditions is a strong electrophile, but it is primarily amidated by the amino group, resulting in minimal ester formation.
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