Phenols Kolbe reaction

Direct Electron Transfer. We have already met some reactions in which the reduction is a direct gain of electrons or the oxidation a direct loss of them. An example is the Birch reduction (15-14), where sodium directly transfers an electron to an aromatic ring. An example from this chapter is found in the bimolecular reduction of ketones (19-55), where again it is a metal that supplies the electrons. This kind of mechanism is found largely in three types of reaction, (a) the oxidation or reduction of a free radical (oxidation to a positive or reduction to a negative ion), (b) the oxidation of a negative ion or the reduction of a positive ion to a comparatively stable free radical, and (c) electrolytic oxidations or reductions (an example is the Kolbe reaction, 14-36). An important example of (b) is oxidation of amines and phenolate ions ... 

Carbonation Kolbe reaction Treatment of a salt of a phenol with CO2 replaces a ring hydrogen with a carboxyl group. This reaction is applied in the conversion of phenol itself into ort/io-hydroxybenzoic acid, known as salicylic acid. Acetylation of salicylic acid produces acetylsalicylic acid (aspirin), which is the most popular painkiller in use today. 

This relationship explains the similarity of the names and the fact that both are obtained from gum catechin. The reverse of the above reaction, the synthesis of protocatechuic acid from pyrocatechinol, may be accomplished by heating the phenol with ammonium carbonate and water to 1400° under pressure, which is a modification of the Kolbe reaction for synthesizing salicyclic acid (p. 716). From its constitution and by reference to the formulas on page 662 we will see its relationship to vanillin, heliotropin, eugenole, safrole, guaiacol, etc. 

Treatment of the salt of a phenol with carbon dioxide brings about substitution of the carboxyl group, COOH, for hydrogen of the ring. This reaction is known as the Kolbe reaction its most important application is in the conversion of phenol itself into o-hydroxybcnzoic acid, known as salicylic acid. Although some p-hydroxybenzoic acid is formed as well, the separation of the two isomers can be... 

If in the Kolbe reaction instead of sodium phenolate, potassium phenolate is used, the para-oxybenzoic add is obtained, and not the ortho-add. The potassium phenolate, like the sodium phenolate, first absorbs carbon dioxide, and the potassium phenyl carbonate thus formed, heated in carbon dioxide up to 150°, also yields salicylic add but if the temperature is increased, an increasingly larger quantity of the para-add is obtained, until finally at 2200 the potassium para-oxybenzoate is the only product. 

An easier method of production of p-anisic acid is methy-lation of p-hydroxy benzoic acid obtained as a co-product during manufacture of o-hydroxy benzoic acid (salicylic acid) via Kolbe reaction of phenol and CO2... 

Normally, however, we can expect the paraselectivity to be improved when the size of the cation is increased. The literature mentions at least three cases the Kolbe reaction (ref. 9), the Reimer-Tiemann reaction (ref. 10) and the hydroxymethylation of phenols in alcoholic media (ref. 11), where with hydroxide anion the para/ortho ratio is increased following the series of the cations Na+ < K+ < Cs+ < R4N+. ... 

Kolbe Reaction The phenoxide ion is even more susceptible to electrophilic aromatic substitution than phenol itself. (Why ) Use is made of the high reactivity of the phenoxide ring in a reaction called the Kolbe reaction. In the Kolbe reaction carbon dioxide acts as the electrophile. 

The Kolbe reaction is mechanistically similar to the reaction of Grignard reagents with carbon dioxide. The increased electron density at G-2 or C-4 in the phenolate ion allows either carbon atom to act as a nucleophile and attack the carbon atom of carbon dioxide. Reaction at the position ortho to the oxygen atom is shown. Tautomerization of the cyclohexadienone gives the phenol. 

Kolbe reaction Conversion of a phenolate into an orthohydroxy aromatic carboxylic acid using a high pressure of carbon dioxide. 

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-Schmltt reaction. The latter is a method for introducing a carboxyl group directly into a phenol nucleus. 

CARBOXYLATION OF PHENOLS ASPIRIN AND THE KOLBE-SCHMITT REACTION... 

Carboxylation of Phenols Aspirin and the Kolbe-Schmitt Reaction... 

The Kolbe-Schmitt reaction has been applied to the preparation of other o hydroxy benzoic acids Alkyl derivatives of phenol behave very much like phenol itself... 

Kolbe-Schmitt reaction (Section 24 10) The high pressure re action of the sodium salt of a phenol with carbon dioxide to give an o hydroxybenzoic acid The Kolbe-Schmitt reac tion IS used to prepare salicylic acid in the synthesis of as pinn... 

Alkylphenols undergo a carboxylation reaction known as the Kolbe Schmidt reaction. In the following example, the phenolate anion of /)-nonylphenol (15) reacts with carbon dioxide under pressure. Neutralization generates a sahcyhc acid (16) (10). 

Early Synthesis. Reported by Kolbe in 1859, the synthetic route for preparing the acid was by treating phenol with carbon dioxide in the presence of metallic sodium (6). During this early period, the only practical route for large quantities of sahcyhc acid was the saponification of methyl sahcylate obtained from the leaves of wintergreen or the bark of sweet bitch. The first suitable commercial synthetic process was introduced by Kolbe 15 years later in 1874 and is the route most commonly used in the 1990s. In this process, dry sodium phenate reacts with carbon dioxide under pressure at elevated (180—200°C) temperature (7). There were limitations, however not only was the reaction reversible, but the best possible yield of sahcyhc acid was 50%. An improvement by Schmitt was the control of temperature, and the separation of the reaction into two parts. At lower (120—140°C) temperatures and under pressures of 500—700 kPa (5—7 atm), the absorption of carbon dioxide forms the intermediate phenyl carbonate almost quantitatively (8,9). The sodium phenyl carbonate rearranges predominately to the ortho-isomer. sodium sahcylate (eq. 8). 

The key compound in the synthesis of aspir in, salicylic acid, is prepared from phenol by a process discovered in the nineteenth century by the German chemist Hermann Kolbe. In the Kolbe synthesis, also known as the Kolbe—Schmitt reaction, sodium phen-oxide is heated with carbon dioxide under pressure, and the reaction mixture is subsequently acidified to yield salicylic acid ... 

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