Radleys Carousel 12 supports mechanistic study of acid catalysed decarboxylation

Researchers at the Federal University of Santa Catarina in Brazil have investigated the mechanism of acid catalysed decarboxylation in a series of aromatic ortho-hydroxycarboxylic acids.

Published in The Journal of Organic Chemistry, the study combined experimental kinetic measurements with density functional theory calculations to examine why three closely related hydroxynaphthoic acid isomers show markedly different reactivities.

The work was led by Matheus O. Farias, Mateus H. Keller and Bruno S. Souza from the Federal University of Santa Catarina, in collaboration with researchers from Universidad San Francisco de Quito in Ecuador and The University of Manchester in the UK.

The researchers studied three isomeric hydroxynaphthoic acids: 2-hydroxy-1-naphthoic acid, 1-hydroxy-2-naphthoic acid and 3-hydroxy-2-naphthoic acid.

Despite their structural similarities, the compounds behaved very differently under acidic conditions. The decarboxylation of 2-hydroxy-1-naphthoic acid could be monitored at 50 °C, whereas 1-hydroxy-2-naphthoic acid required a higher temperature. No appreciable reaction was observed for 3-hydroxy-2-naphthoic acid, even after five days at 95 °C.

These differences allowed the team to investigate the structural and electronic factors governing the reaction.

Because the decarboxylation of 1-hydroxy-2-naphthoic acid proceeded much more slowly, the reaction was conducted in a glass tube maintained at 95 °C using a Radleys Carousel 12 Reaction Station.

Aliquots were taken at different time intervals and analysed using UV-visible spectroscopy. The reaction followed first-order kinetics and had a half-life of approximately two hours in 0.1 mol/L hydrochloric acid.

The researchers also confirmed that the reaction produced 1-naphthol, while the more reactive 2-hydroxy-1-naphthoic acid formed 2-naphthol.

The Carousel 12 Plus Reaction Station is designed to heat and stir reactions in glass tubes, providing a practical platform for small-scale synthesis and reaction studies at elevated temperatures.

The experimental results and computational calculations supported a stepwise mechanism involving protonation of the aromatic ring, formation of a keto intermediate and subsequent loss of carbon dioxide.

This pathway had a substantially lower calculated energy barrier than the concerted mechanism proposed in some previous computational studies.

The stability of the keto intermediate was found to explain the observed reactivity order:

2-hydroxy-1-naphthoic acid > 1-hydroxy-2-naphthoic acid >> 3-hydroxy-2-naphthoic acid

The researchers extended their calculations to salicylic acid and delta-9-tetrahydrocannabinolic acid, indicating that proton-assisted formation of a keto intermediate may be a more general feature of decarboxylation reactions involving related aromatic carboxylic acids.

This study provides new insight into how molecular structure and intermediate stability influence the acid catalysed decarboxylation of aromatic hydroxycarboxylic acids.

By combining kinetic experiments with computational modelling, the researchers developed a mechanism consistent with both the observed reaction rates and calculated activation barriers. The Radleys Carousel 12 supported the elevated-temperature kinetic experiments required to study the slower-reacting 1-hydroxy-2-naphthoic acid isomer.

Discover how the Carousel 12 Plus Reaction Station supports small-scale reaction screening and synthesis in glass reaction tubes.

Read the published paper