Carboxylation of phenols

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

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

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. 

Ca.rhoxyla.tlon, This is the process of iatroduciag a carboxyUc acid group iato a phenol or naphthol by reaction with carbon dioxide under appropriate conditions of heat and pressure. Important examples are the carboxylation of phenol and 2-naphthol to give sahcyhc acid and 2-hydroxy-3-naphthoic acid, respectively. 

Phenol is an important intermediate in the anaerobic degradation of many complex and simple aromatic compounds. Tschech and Fuchs proposed that the carboxylation of phenol to 4-hydroxybenzoate is the first step in the degradation of phenol under denitrifying conditions. However, 4-hydroxybenzoate is not detected in the cultures or cell extracts of the denitrifying Pseudomonas species in the presence of CO2 and phenol, but it is detected if phenol is replaced by phenolphosphate. In contrast, 4-hydroxybenzoate is readily detected as an intermediate of phenol degradation in the iron-reducing bacterium GS-15, and 4-hydroxybenzoate may prove to be a common intermediate in the anaerobic transformation. Thus, in anaerobic degradation of phenolic compounds, it has been postulated that carboxylation reactions may play important roles. 

Figure 3 Possible reaction mechanism of carboxylation of phenol via...

It can be concluded from these observations that whereas benzoate produced by the carboxylation of phenols can be degraded, dehydroxylation with the formation of substituted benzoates may produce stable terminal metabolites. 

Calusterone, 154 Cambendazole, 353 c-AMP, 464 Canrenone, 174 Catpipramine, 416 Capobenic acid, 94 Carbadox, 390 Carbencillin, 437 Carbidopa, 119 Carbinoxamine, 32 Carbiphene, 78 Carboxylation of phenols, 86... 

The use of C02 in chemistry normally requires its interaction with metal centers of catalysts one such example is the Kolbe-Schmitt carboxylation of phenol to produce salicylic acid. The potential of C02 as a raw material in the synthesis of carboxylates, carbonates, or carbamates is rather limited. A future aim is the economically attractive synthesis of carboxylic acids, or optically... 

In this chapter attention will be focused on the chemical transformations of C02 to yield carboxylic acids and related molecules (e.g., cyclic esters), while natural carboxylations reactions such as those dealing with RuBisCO (ribulose-1,5 bis(phosphate) carboxylase/oxidase) and its genetic engineering or the carboxylation of phenol via a phenol phosphate intermediate by the phenol-carboxylase enzyme, will be left aside. 

A base-promoted carboxylation of phenols that allows the synthesis of salicylic acid derivatives. 

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. 

Rahim, M. A., Matsui, Y., Matsuyama, T., Kosugi, Y. Regioselective carboxylation of phenols with carbon dioxide. Bull. Chem. Soc. Jpn. 2003, 76, 2191-2195. 

Carboxylation of phenols has been demonstrated under a number of conditions and this reaction is presumably analogous to that demonstrated in pure cultures of Desulfobacterium anilini during metabolism of aniline and in denitrifying bacteria during metabolism of phenol (Section 6.7.3.1). The following examples are used to illustrate some important details of these... 

Iijima and Yamaguchi published an efficient and regioselective carboxylation of phenol in supercritical carbon dioxide in the presence of aluminum bromide to form salicylic acid (Equation 4.31) [59]. They also reported the K2C03-catalyzed direct synthesis of salicylic acid from phenol and scC02 [60]. 

AG°r is positive and increases as a function of temperature this shows that the direct carboxylation of phenol is impossible it is essential to perform the reaction using a phenate. 

In the reworking of an old method, 4-hydroxybenzoic acid has been derived in high yield by the copper-catalysed carboxylation of phenol in alkaline solution with carbon tetrachloride (ref.30). The author recalls preparing 4-hydroxy-3-methylbenzoic acid precisely by this route in 1947. 

The work presented here describes initial fundamental research efforts aimed at the generation of a co-metabolic process intended to replace the Kolbe-Schmitt carboxylation of phenol. At present a prototype organism has been constructed utilizing enzymes from multiple aromatic catabolic pathways encoding for toluene and p-cresol metabolism (13,14). Recombinant P. putida EM2878 catalyzes the conversion of toluene to HBA in a single processing step. Central to the conversion... 

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