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

The key compound m the synthesis of aspirin salicylic acid is prepared from phe nol by a process discovered m 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 subse quently acidified to yield salicylic acid... 

Section 24 10 The Kolbe-Schmitt synthesis of salicylic acid is a vital step m the preparation of aspirin Phenols as their sodium salts undergo highly regioselective ortho carboxylation on treatment with carbon dioxide at elevated temperature and pressure... 

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... 

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. 

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. 

Perhaps the most widely known compound prepared from phenol is aspirin. If phenol, sodium hydroxide, and carbon dioxide are heated together under pressure, salicylic acid is formed (as the sodium salt) ... 

C02 is also used, to make inorganic and organic carbonates, carboxylic acids, polyurethanes and sodium salicylate. Carbon dioxide is combined with epoxides to create plastics and polymers (Figure 19). 

In pond water, carbaryl degraded very rapidly to 1-naphthol. The latter degraded, presumably by Flavobacterium sp., into hydroxycinnamic acid, salicylic acid, and an unidentified compound (HSDB, 1989). Four d after carbaryl (30 mg/L and 300 ng/L) was added to Fall Creek water, >60% was mineralized to carbon dioxide. At pH 3, however, <10% was converted to carbon dioxide (Boethling and Alexander, 1979). Under these conditions, hydrolysis of carbaryl to 1-naphthol was rapid. The authors could not determine how much carbon dioxide was attributed to biodegradation of carbaryl and how much was due to the biodegradation of 1-naphthol (Boethling and Alexander, 1979). Hydrolysis half-lives of carbaryl in filtered and sterilized Hickory Hills (pH 6.7) and U.S. Department of Agriculture Number 1 pond water (pH 7.2) were 30 and 12 d, respectively (Wolfe et al., 1978). 

CASRN 25311-71-1 molecular formula C15H24NO4PS FW 345.40 Soil. Rapidly degraded by microbes via oxidative desulfuration in soils forming isofenphos oxon (Abou-Assaf et al, 1986 Abou-Assaf and Coats, 1987 Somasundaram et al., 1989), isopropyl salicylate, and carbon dioxide (Somasundaram et al., 1989). The formation of isofenphos oxon is largely dependent upon the pH, moisture, and temperature of the soil. The degradation rate of isofenphos decreased with a decrease in temperature (35 °C >25 °C >15 °C), moisture content (22.5% >30% >15%), and in acidic and alkaline soils (pH 6 and 8). After isofenphos was applied to soil at a rate of 1.12 kg ai/ha, concentrations of 8.3, 7.2, 5.1, and 1.0 ppm were found after 5, 21, 43, and 69 d, respectively. Following a second application, 4.9, 1.55, 0.25, and 0.10 ppm of isofenphos were found after 5, 21, 43, and 69 d, respectively (Abou-Assaf and Coats, 1987). 

A pure culture of Arthrobacter sp. was capable of degrading isofenphos at different soil concentrations (10, 50, and 100 ppm) in less than 6 h. In previously treated soils, isofenphos could be mineralized to carbon dioxide by indigenous microorganisms (Racke and Coats, 1987). Hydrolyzes in soil to salicylic acid (Somasundaram et al., 1991). 

Carboxylation of sodium phenoxides with carbon dioxide, to give salicylic acid, the precursor to the synthesis of aspirin. 

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 salicylic acid was the saponification of methyl salicylate obtained from the leaves of wintergreen or the bark of sweet birch. 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 salicylic 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 07 0-isomer, sodium salicylate (eq. 8). 

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... 

Other reported syntheses include the Reimer-Tiemann reaction, in which carbon tetrachloride is condensed with phenol in the presence of potassium hydroxide. A mixture of the ortho- and para-isomers is obtained the para-isomer predominates. -Hydroxybenzoic acid can be synthesized from phenol, carbon monoxide, and an alkali carbonate (52). It can also be obtained by heating alkali salts of -cresol at high temperatures (260—270°C) over metallic oxides, eg, lead dioxide, manganese dioxide, iron oxide, or copper oxide, or with mixed alkali and a copper catalyst (53). Heating potassium salicylate at 240°C for 1—1.5 h results in a 70—80% yield of -hydroxybenzoic acid (54). When the dipotassium salt of salicylic acid is heated in an atmosphere of carbon dioxide, an almost complete conversion to -hydroxybenzoic acid results. They>-aminobenzoic acid can be converted to the diazo acid with nitrous acid followed by hydrolysis. Finally, the sulfo- and halogenobenzoic acids can be fused with alkali. 

Numerous methods for the synthesis of salicyl alcohol exist. These involve the reduction of salicylaldehyde or of salicylic acid and its derivatives. The alcohol can be prepared in almost theoretical yield by the reduction of salicylaldehyde with sodium amalgam, sodium borohydride, or lithium aluminum hydride by catalytic hydrogenation over platinum black or Raney nickel or by hydrogenation over platinum and ferrous chloride in alcohol. The electrolytic reduction of salicylaldehyde in sodium bicarbonate solution at a mercury cathode with carbon dioxide passed into the mixture also yields saligenin. It is formed by the electrolytic reduction at lead electrodes of salicylic acids in aqueous alcoholic solution or sodium salicylate in the presence of boric acid and sodium sulfate. Salicylamide in aqueous alcohol solution acidified with acetic acid is reduced to salicyl alcohol by sodium amalgam in 63% yield. Salicyl alcohol forms along with -hydroxybenzyl alcohol by the action of formaldehyde on phenol in the presence of sodium hydroxide or calcium oxide. High yields of salicyl alcohol from phenol and formaldehyde in the presence of a molar equivalent of ether additives have been reported (60). Phenyl metaborate prepared from phenol and boric acid yields salicyl alcohol after treatment with formaldehyde and hydrolysis (61). 

Oils Edible Safflower Potassium Binoxalate Ammonium Chloride Salicylic Acid Ammonium Chloride Lead Acetate Potassium Binoxalate Sodium Silicofluoride Ammonium Carbonate Fluocilicic Acid P-Dichlorobenzene Ammonium Phosphate Sec-Butyl Acetate Sec-Butyl Alcohol Calcium Phosphate Selenium Trioxide Selenium Dioxide Selenium Dioxide Selenium Dioxide Selenium Trioxide Antimony Trioxide Calcium Hypochlorite Carbaryl Cyclohexanone Charcoal... 

Salicylic acid, the major metabolite of aspirin, uncouples the electron transport chain in the mitochondria. This results in (a) increased use of oxygen and production of carbon dioxide, (b) lack of ATP, and (c) excess energy no longer utilized in ATP production. The result is increased respiration and raised temperature. The alterations in respiration lead to alkalosis followed by acidosis. The lack of ATP and loss of respiratory control will cause increased metabolic activity and hypoglycemia after an initial mobilization of glucose from glycogen. 

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