Why is 4-aminophenol acetylated at the amine group rather than the phenol group?

The acetylation of 4-aminophenol preferentially occurs at the amine group due to the relative electronegativity of nitrogen compared to oxygen. Nitrogen is less electronegative than oxygen, which has a significant impact on the reactivity of the functional groups present.

Amine groups, like the one in 4-aminophenol, are basic and nucleophilic. This means they are more likely to react with electrophiles, such as acetic anhydride or acetyl chloride, which are commonly used in acetylation reactions. Because the nitrogen atom in the amine is less electronegative, it has a stronger tendency to donate its electron density, making the amine more reactive than the phenolic oxygen.

In contrast, the phenolic oxygen is more electronegative and thus holds onto its electrons more tightly, making it a less favorable site for nucleophilic attack. While the hydroxyl group (-OH) can undergo acetylation, in this case, the amine group takes precedence due to its stronger nucleophilic character. Therefore, the reaction selectively occurs at the amine group first, which explains why this choice highlights the electronegativity of nitrogen in comparison to oxygen in determining re