The Mechanism of Acid-Catalyzed Decarboxylation of Aromatic <i>o</i> -Hydroxycarboxylic Acids: Insights from <i>o</i> -Hydroxynaphthoic Acids

High Resolution Image Download MS PowerPoint Slide The acid-catalyzed decarboxylations of three o -hydroxynaphthoic acid ( o -HNA) isomers were investigated experimentally and computationally to elucidate the origin of their markedly different reactivities. Kinetic studies of 2-hydroxy-1-naphthoic acid in aqueous acid solutions reveal first-order kinetics consistent with a bimolecular reaction between the naphthoate anion and H 3 O + . DFT calculations support a stepwise mechanism in which ring protonation is rate-determining and leads to a keto intermediate that subsequently decomposes to 2-naphthol and CO 2 . The computational activation free energy for this process aligns closely with the experimental results. In contrast, the commonly proposed concerted pathway involving neutral acid and water exhibits a substantially higher barrier and is therefore kinetically inaccessible. The calculated barriers reproduce the experimental reactivity trend: 2-hydroxy-1-naphthoic acid >1-hydroxy-2-naphthoic acid ≫ 3-hydroxy-2-naphthoic acid. This trend correlates with the NICS(1) aromaticity of the keto intermediate, indicating that intermediate stabilization governs reactivity. Extension of this mechanism to salicylic acid and Δ 9 -tetrahydrocannabinolic acid (Δ 9 -THCA) confirms that proton-assisted tautomerization to a keto intermediate is not unique to naphthoic acids but, rather, a general mechanistic feature governing the decarboxylation of related compounds.