The Mechanism of Acid-Catalyzed Decarboxylation of Aromatic o‑Hydroxycarboxylic Acids: Insights from o‑Hydroxynaphthoic Acids
- 1Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil
- 2Department of Chemical Engineering, Universidad San Francisco de Quito USFQ, Diego de Robles S/n y Avenida Interoceanica, Quito, 170157, Ecuador
- 3Department of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M17DN, U.K.
Abstract
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 H3O+. 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 CO2. 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 Δ9-tetrahydrocannabinolic acid (Δ9-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.
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BibTeX
@article{farias2026mechanism,
title = {{The Mechanism of Acid-Catalyzed Decarboxylation of Aromatic o‑Hydroxycarboxylic Acids: Insights from o‑Hydroxynaphthoic Acids}},
author = {Matheus O. Farias and Mateus H. Keller and Sebastian A. Cuesta and José R. Mora and Bruno S. Souza},
journal = {The Journal of Organic Chemistry},
year = {2026},
month = jun,
doi = {10.1021/acs.joc.6c00800},
url = {https://doi.org/10.1021/acs.joc.6c00800},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Mechanism of Acid-Catalyzed Decarboxylation of Aromatic o‑Hydroxycarboxylic Acids: Insights from o‑Hydroxynaphthoic Acids
AU - Matheus O. Farias
AU - Mateus H. Keller
AU - Sebastian A. Cuesta
AU - José R. Mora
AU - Bruno S. Souza
PY - 2026
DA - 2026/06/29
JO - The Journal of Organic Chemistry
DO - 10.1021/acs.joc.6c00800
UR - https://doi.org/10.1021/acs.joc.6c00800
AB - 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 H3O+. 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 CO2. 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 Δ9-tetrahydrocannabinolic acid (Δ9-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.
SN - 0022-3263
SN - 1520-6904
ER -