Phenyl salicylic acid

Methyl, ethyl, n-propyl, isopropyl, n-hutyl, benzyl, cyclohexyl esters of formic, acetic, oxalic, succinic, tartaric, citric, benzoic, salicylic (and other substituted benzoic acids), phthalic and cinnamic acids phenyl esters of acetic, benzoic and salicylic acids. 

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

Salicyl-u-toluide has been prepared only by the action of phosphorus oxychloride upon a mixture of salicylic acid and o-toluidine. The useful methods of preparation of salicylanilide are by the interaction of salicylic acid and aniline in the presence of phosphorus trichloride, by heating phenyl salicylate and aniline, and from o-hydroxybenzamide and bromobenzene in the presence of small amounts of sodium acetate and metallic copper. A number of these and other anilides have been described. ... 

Xanthone (Coll. Vol. i, 537) In nearly quantitative yields by distillation in vacuo of the acid chloride formed by the action of thionyl chloride on the phenyl ether of salicylic acid. Lock and Kempter, Monatsh. 67, 24 (1936). 

Decomposition of salicin (2-(hydroxymethyl)phenyl-/ -D-glucopyranoside) yields two alcohols glucose (a compound with numerous 1°, 2°, and a 3° hydroxyl functionalities, Fig. 13.4.6) and l-0H-2-CH20H-benzene (a 1° alcohol, Fig. 13.4.7). Further oxidation of l-0H-2-CH20H-benzene leads to the formation of salicylic acid ... 

Replacement of the hydroxyl group on the phenyl ring with a carboxyl group forms a molecule of benzoic acid. Addition of a hydroxyl at the 2-position on a benzoic acid molecule forms 2-hydroxybenzoic acid or salicylic acid. The slightly more complex phenylpropanoid skeleton contains a linear three-carbon chain (the propanoic group) added to the benzene ring (the phenyl group). Addition of ammonia to carbon 2 of this three-carbon side chain yields the amino acid phenylalanine (Fig. 3.3). Phenylalanine... 

Phenyl-1 -propanone 1 - Pheny 1-2-propanone Phenyl salicylate Phenyl vinyl ether Phthalamide 1.3- Phthalic acid 1.4- Phthalic acid Phthalic anhydride Phthalonitrile Piperidine 14.85... 

Another source pressure cooked the peyote in acidic water 15 minutes at 15 lbs. and poured off the liquid. This process was repeated 5 more times and the combined water extracts evaporated slowly to a tar which is cooled until able to be formed into small pills. The pills are dipped in Salol (phenyl salicylate), which has been liquified by heating, and allowed to dry. This forms an enteric coating which is said to allow ingestion without nausea. Others... 

Salicylic acid is manufactured on a large scale. In the dye industry it serves for the production of valuable azo-dyes which exhibit great fastness. To some extent these dyes are applied to mordanted fibres. In addition, the acid and its derivatives are widely used in pharmacy. Being a phenolcarboxylic acid it has a powerful disinfecting action (preservative). It has further proved itself an important antirheumatic and an analgetic. The derivative in which the phenolic hydroxyl group is acetylated (aspirin) has become especially popular. The first medicament of the series was the phenyl ester of salicylic acid, salol, which is produced as a by-product in the technical process. The preparation of salicylaldehyde has been described above (p. 235). 

Uses Antiseptic and disinfectant pharmaceuticals dyes indicators slimicide phenolic resins epoxy resins (bisphenol-A) nylon-6 (caprolactum) 2,4-D solvent for refining lubricating oils preparation of adipic acid, salicylic acid, phenolphthalein, pentachlorophenol, acetophenetidin, picric acid, anisole, phenoxyacetic acid, phenyl benzoate, 2-phenolsulfonic acid, 4-phenolsulfonic acid, 2-nitrophenol, 4-nitrophenol, 2,4,6-tribromophenol, 4-bromophenol, 4-/ert-butylphenol, salicylaldehyde, and many other organic compounds germicidal paints laboratory reagent. 

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). 

Phenyl salicylate (salol) is manufactured by heating salicylic acid and phenol in the presence of phosphoms oxychloride for 4—5 hours at 110—115°C. The molten product is separated, mixed with water, dried, and distilled under vacuum. Another process involves the transesterification of a salicylate such as methyl, with phenol in the presence of an alkali or alkaline-earth phenate. Medicinally, phenyl salicylate was formerly used as an intestinal antiseptic. However, the main applications of phenyl salicylate have been related to the ability to absorb uv light over the wavelengths of 290—325 nm. As an effective uv-light absorber, phenyl salicylate was incorporated in alkyd paints, waxes, and polishes, but has been largely replaced in this application by less extractable, more effective compounds. The May 1996 price was 10.60/kg (18). 

Amino salicylic acid and its salts have been used in the treatment of tuberculosis. />-Amino s alicylic acid can be prepared by the carboxylation of, w-amino phenol (32). Aminosalicylic acid USP assays not less than 98.5% and not more than 100.5%, calculated on the anhydrous basis. The antitubercular agents are likely to be used as the more tolerated salts calcium [133-15-3], potassium [133-09-5], sodium [133-10-8], and the ethyl [6069-17-2] and phenyl [133-11-9] esters of aminosalicylic acid. 

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). 

To a mixture of 138.1 g. (1 mole) of salicyclic acid and 128.6 g. (1 mole) of -chlorophenol in a 2-1. round-bottomed flask fitted with a thermometer reaching to the bottom of the flask and a reflux condenser with a drying tube (Note 1) is added 58.3 g. (0.38 mole) of phosphorus oxychloride. The mixture is heated with occasional swirling, and the temperature is maintained at 75-80°. At the end of 4 hours the reactants have been reduced to a molten mass, and this is poured slowly, with vigorous stirring, into a solution of 120 g. of sodium carbonate in 800 ml. of water. The precipitated ester is collected on a filter and washed with four 200-ml. portions of water. The yield of crude, air-dried, p-chloro-phenyl salicylate is 174-189 g. (70-76%) m.p. 65-66°. Recrystallization from absolute ethanol yields 136-154 g. (55-62%) of pure product m.p. 69.5-70.5°. A second crop may be obtained by concentration of the filtrate from the first crop or by the addition of water (Note 2). 

Substituted phenyl salicylates can be prepared by heating salicylic acid and the appropriate phenol in the presence of phosphorus oxychloride,34 5 phosphorus trichloride,4 5 phosphorus pentachloride,4 6 phosgene,4 or thionyl chloride,4 or by heating the phenol and salol.7... 

It is an interesting fact that if potassium phenolate is used in the Kolbe synthesis para-hydroxy benzoic acid is obtained, especially at high temperatures. Potassium phenyl carbonate is first formed, and heated up to 150° yields salicylic acid, but if the temperature be further raised, the para-acidis produced in increasing quantities until at 220° potassium para-hydroxy-benzoic acid is the sole product. 

It will have been noted that in the formation of salicylic acid, only one half of the phenol is converted the rest is obtained unchanged. Schmitt (Dingier s Polyteehnisches Journal, 255, 259) succeeded in modifying the synthesis to obviate this defect, and his is the method always used industrially, although the other is more convenient in the laboratory. In Schmitt s synthesis sodium phenyl carbonate is prepared by heating up to 120°—140° dry sodium phenolate with carbon dioxide in autoclaves under pressure. Complete transformation of the intermediate sodium phenyl carbonate to mono-sodium salicylate then occurs on further heating. The carbon dioxide may be led in from a cylinder under pressure, or liquid or solid carbon dioxide may be mixed directly with the sodium phenolate in the autoclave. If preferred, the sodium phenyl carbonate can be prepared at ordinary pressures at 110° and then heated under pressure at 140°. 

Other solvents tried and the liquid temperatures of the refluxing mixtures are stearic acid (340-365°), di- -butyl phthalate (320-325°), phenyl salicylate (290°). The first two solvents are unsatisfactory because of side reactions consuming some of the tetraphenylcyclopentadienone, the third because the addition reaction is too slow. 

The cross-bridge of ASBA provides a reasonably long spacer (16.3 A). The phenyl azide portion is constructed from a salicylic acid derivative and thus possesses a ringactivating hydroxyl group. The presence of this group allows radioiodination of the ring prior to cross-linking (Chapter 8, Section 4.5). 

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