Kolbe-Schmitt method

The carboxylation of phenols is a well established process for synthesis of salicylic acid according to the Kolbe-Schmitt method (Table 4, entry 39). The exothermic reaction is carried out at slightly elevated temperatures around 150 °C and pressures of approximately 5 bar. Batch processes are still mainly used. The main task is to exclude water from the reaction mixture, because this would release the alkali metal hydroxide from the phenoxide salt. 

Salicylic acid is prepared today exclusively by the Kolbe-Schmitt method, in which absolutely dry sodium phenolate is treated with dry carbon dioxide, first at ordinary temperature, then at 125° under a pressure of 4 to 7 atmospheres. The reaction proceeds quantitatively if the salt is completely dry and pulverized to a dust. This fine subdivision is achieved by drying and grinding in a vacuum. 

Manufacture. Several methods have been described for the preparation of -hydroxyben2oic acid. The commercial technique is similar to that of salicylic acid, ie, Kolbe-Schmitt carboxylation of phenol. The modification includes the use of potassium hydroxide in place of caustic (51). The dried potassium phenate is heated under pressure, 270 kPa (2.7 atm) or more, with dry carbon dioxide at 180—250°C. The potassium salt [16782-08-4] of Nhydroxyben2oic acid forms almost quantitatively and can be converted to free acid by using a mineral acid. 

Salicylic acid. The preparation of salicylic acid by passing carbon dioxide into dry sodium phenoxide at 170-190° is the classical example of the Kolbe-Schmitt reaction. The latter is a method for introducing a carboxyl group directly into a phenol nucleus. 

Current Methods. The general outline of the Kolbe-Schmitt reaction, as it is employed in the 1990s, is as follows. In the first step, phenol and hot aqueous caustic are mixed to produce the sodium phenate which is taken to dryness. Next, the phenate and dry carbon dioxide are introduced into the carbonator. Air is excluded to minimize oxidation and the formation of colored compounds. The gas—solid mixture is agitated and heated, first at low temperature, followed by several hours at higher temperatures, to complete the formation of sodium salicylate. Variations of this reaction have been noted in the literature and are still being investigated (10,11). One reported scheme produces salicylic acid or substituted salicylic acids by reaction of a granulated alkali metal salt of the respective phenolic compound with C02 in a fluidized bed at 20—130°C until at least 50—80% of the metal salt has been converted to... 

Phenol readily couples with diazonium salts to yield coloured compounds. The latter can be nsed for the photometric detection of phenol as in the case of diazotized 4-nitroaniline. Sahcylic acid (2-hydroxybenzoic acid) can be prodnced by the Kolbe-Schmitt reaction (stndied by the density functional method ) from sodinm phenolate and carbon dioxide, whereas potassium phenolate gives the para compound. Alkylation and acylation of phenol can be carried out with aluminium chloride as catalyst methyl groups can also be introduced by the Mannich reaction. Diaryl ethers can only be produced under extreme conditions. 

There are many other approaches to industrial applications of flash chemistry, although available information is limited. Let us briefly touch on some examples. The Kolbe-Schmitt synthesis serves as a useful standard method to introduce a carboxyl group into phenols (Scheme 10.6). The Kolbe-Schmitt synthesis has been widely used in industry, and there are many variants of this transformation. Microflow systems can be used for conducting the Kolbe-Schmitt synthesis under aqueous high-pressure conditions.A decrease in reaction times by an order of magnitude (a few tens of seconds instead of minutes) and increase in space-time yields by orders of magnitude can be attained using a microflow system. For example, a microflow system composed of five parallel capillaries (inner volume 9 ml) has a productivity of 555 g/h, whereas the productivity of a macrobatch reactor (IL flask) is 28 g/h. 

Aromatic hydroxycarboxylic acids, especially salicylic acid, have a wide range of applications, for example, as valuable raw materials and intermediates in the production of pharmaceutical chemicals. Originally, salicylic acid was synthesized by the Kolbe-Schmitt reaction [57], which consists of two steps (1) the synthesis and purification of alkali metal phenoxides and (2) carboxylation (Scheme 4.4). Another possible synthetic method is via the attack of a trichloromethyl cation (generated by a copper catalyst from carbon tetrachloride) on the phenoxide anion, followed by hydrolysis of the C—Cl bonds with concentrated sodium hydroxide, because it is fairly difficult to replace an aromatic hydrogen with carboxyl functionality [58]. 

Since, in Kolbe s synthesis, as here described, the mono-sodium salicylate reacts to some extent with unchanged sodium phenoxide, producing the di-sodium salt, part of the phenol is liberated and excluded from the reaction. The reaction proceeds to completion if the sodium phenoxide is heated to about 150° for a long time, with carbon dioxide under pressure in the autoclave. This is the technical method of Schmitt. 

A modification of the Kolbe synthesis which permits the immediate conversion of all the phenol into salicylic acid is known as Schmitt s synthesis. According to this method, as in the other, the sodium phenyl carbonate is first prepared this is then further heated in an... 

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