Kolbe–Schmitt reaction


The Kolbe–Schmitt reaction or Kolbe process is a carboxylation chemical reaction that proceeds by treating phenol with sodium hydroxide to form sodium phenoxide, then heating sodium phenoxide with carbon dioxide under pressure, then treating the product with sulfuric acid. The final product is an aromatic hydroxy acid which is also known as salicylic acid.
[image:Kolbe-Schmitt.png|500px|center|The Kolbe–Schmitt reaction]
By using potassium hydroxide, 4-hydroxybenzoic acid is accessible, an important precursor for the versatile paraben class of biocides used e.g. in personal care products.
The methodology is also used in the industrial synthesis of 3-hydroxy-2-naphthoic acid; the regiochemistry of the carboxylation in this case is sensitive to temperature.

Reaction mechanism

The Kolbe–Schmitt reaction proceeds via the nucleophilic addition of a phenoxide, classically sodium phenoxide, to carbon dioxide to give the salicylate.
The final step is the reaction of the salicylate anion with an acid to form the desired salicylic acids.

Homogeneous Kolbe-Schmitt Reaction

A modification of the classical solid-phase Kolbe-Schmitt reaction, where the solvent play a role of active media dissolving reagents and solvating cations and anions. Typical solvents for homogeneous Kolbe-Schmitt reaction are DMSO, DMF, HMPTA. Carboxylation of sodium and potassium phenoxides in solution of DMSO proceeds under milder temperature with high para-regioselectivity producing 4-hydroxybenzoic acid instead of 2-hydroxybenzoic acid. Addition into the reaction mixture of basic sodium salts like mesytolate, isopropylcarbonate, tert-butylcarbonate increase the chemical yield of a mixture 4HBA&SA up to two fold.
Screening of various metal cations, different substituted phenoxides, solvents in combination with activating additive provide a general and effective method of homogeneous carboxylation.
Particularly, rhubidium and cesium salts directed carboxylation into para-position of phenoxides with unprecedented regioselectivity. It is suggested that mechanism of the reaction involes molecular associates which responsible for decreasing of activation energy barrier of carboxylation.
Carboxylation of potassium phenoxide was shown to occur rapidly under atmospheric CO₂ pressure at 113°C in a gasometric study.