Phenol Kolbe-Schmitt reaction

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... 

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 ... 

Carbon dioxide reacts with phenolates 1 to yield salicylate 2 with less reactive mono-phenolates, the application of high pressure may be necessary in order to obtain high yields. This reaction, which is of importance for the large scale synthesis of salicylic acid, is called the Kolbe-Schmitt reaction ... 

The Kolbe-Schmitt reaction is limited to phenol, substituted phenols and certain heteroaromatics. The classical procedure is carried out by application of high pressure using carbon dioxide without solvent yields are often only moderate. In contrast to the minor importance on laboratory scale, the large scale process for the synthesis of salicylic acid is of great importance in the pharmaceutical industry. 

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. 

The applicability of the Reimer-Tiemann reaction is limited to the formylation of phenols and certain reactive heterocycles like pyrroles and indoles. Yields are usually below 50%. In contrast to other formylation procedures, the Reimer-Tiemann reaction is orf/to-selective it is therefore related to the Kolbe-Schmitt reaction. 

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... 

Kolbe-Schmitt reaction 6.4.-.- phenol carboxylase Aresta, 1998... 

Carboxylation reactions based on carbon dioxide have a great interest as the direct introduction of the carboxylic functionality represents, wth respect to the conventional synthetic methodologies, a way for both saving energy and reducing the production of wastes. Despite such aspects, that have a positive environmental impact, the only "direct carboxylation" process exploited at the industrial level is the more-than-one-hundred-years old Kolbe-Schmitt reaction. This process converts phenol (in the form of a Group 1 element salt) and carbon dioxide into a mixture of o- and p-OH-benzoic acid. The major product depends on the reaction conditions and the metal used (Na or K, respectively). This reaction has been recently reviewed [4] by several research groups and extended to other substrates. 

The Kolbe-Schmitt reactions of polyhydroxy phenols such as resorcinol, pyrogallol and phloroglucinol are exceptionally carried out in aqueous solution.[6] Any explanation has not yet been given to the reason of the exception. Kinetic studies on the carboxylation of resorcinol (ROH) with hydrogencarbonate (KHCO-O were carried out in aqueous solutions. 

Phenols that have more than one hydroxyl group may be carboxylated with CO2 at atmospheric pressure under basic conditions. The research team of Y.-C. Gao synthesized 3,5-di-fert-butyl-y-resorcylic acid from 4,6-di-fert-butyl resorcinol using the Kolbe-Schmitt reaction under these conditions. The resorcylic acid derivative was needed in order to prepare ternary complexes of lanthanide(lll)-3,5-di-fert-butyl-Y-resorcylate with substituted pyridine-A/-oxide. 

Kolbe-Schmitt reaction Synthesis of salicylic acid der. from phenols and CO2. 248... 

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. 

The keto tautomers of monohydric phenols are frequently invoked as reactive intermediates in many reactions, such as the Reimer-Tiemann and Kolbe-Schmitt reactions , electrophilic substitution (e.g. bromination i) s well as the photo-Fries rearrangement (see Section IV.D and also Refs. 16-18 cited in Reference 7). In certain cases the keto... 

It was in 1860 that Kolbe first produced salicylic acid by heating a mixture of phenol and sodium in the presence of carbon dioxide at atmospheric pressure. In the years that followed, the importance of C02 pressure, temperature of the system and the role of water was highlighted. Consequently, this reaction, that is often known as the Kolbe Schmitt reaction has given rise to several variants ... 

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