13.16:
Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids
Carboxylic acids bearing a keto group at the β position to the carboxyl group are called β-keto acids. When heated, these acids can readily undergo decarboxylation to lose CO2 gas while simultaneously generating a ketone.
The decarboxylation mechanism begins with the intramolecular hydrogen bonding between the β-keto oxygen atom and the hydrogen atom of the carboxyl group, which generates a reactive conformation.
As the partially protonated keto-oxygen is highly electrophilic, it leads to an internal electron transfer, proceeding through a six-membered cyclic transition state.
Consequently, a C–C bond cleavage results in the formation of an enol, along with the evolution of CO2 as gas.
Finally, the enol undergoes facile keto-enol tautomerism to yield more stable ketones.
13.16:
Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids
Carboxylic acids, upon heating, undergo a decarboxylation reaction by releasing carbon dioxide gas. Monocarboxylic acids do not undergo decarboxylation easily. However, a silver salt of carboxylic acid reacts with bromine or iodine under high temperature to release carbon dioxide gas and forms halide with one less carbon. This reaction is called the Hunsdiecker reaction.
Unlike monocarboxylic acids, ꞵ-keto acids bearing a keto group at the β position to the carboxyl group, readily undergo decarboxylation under an acid medium to form a ketone and releases carbon dioxide gas.
Decarboxylation reaction is biologically relevant while oxidizing food materials in the tricarboxylic acid (TCA) cycle. In this cycle, oxalosuccinic acid is formed as an intermediate that bears three carboxyl groups and one carbonyl group. However, as the carbonyl group is at the ꞵ-position to only one carboxyl group, only one of the three carboxyl groups undergoes decarboxylation to produce α-ketoglutaric acid by losing CO2.
