Salicylic acid, and its salts

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. 

Salicylic acid and its salts (it is monobasic, although diatomic) are extensively used in medicine, both externally as antiseptics and internally in the treatment of rheumatism, etc. It is not aitbout caustic properties, and hence, when taken internally, it ahould be largely diluted. 

The efficacy of salicylic acid is in first line directed against yeasts and moulds, but its activity against bacteria is also worth a mention as it is more pronounced than that of benzoic acid. However, because of its low piQ value salicylic add can only be used for the preservation of highly acidic products. As a food preservative it has been abandoned because of its toxicity. Still of some importance is the application of salicylic acid for the protection of cosmetics and pharmaceutical products. In the EC list of preservatives allowed for cosmetics, salicylic acid and its salts are mentioned with a maximum authorized concentration of 0-5%. 

Other Derivatives of SaUcylic Acid. p-Aminosalicylic acid and its salts have been used in the treatment of tuberculosis. / -Aminosalicylic add can be prepared by the caiboxylation of in-amiuoplienol. Metliylene-5,5-disalicylic acid, produced by heating two parts salicylic acid with 1-1.5 parts of 30-40 wt % formaldehyde in the presence of an add catalyst, is used as an intermediate in the production of bacitracin me thy le ne di salicy la te. 

A) Acetylsalicylic Add (Aspirin). Salicylic acid and its derivatives were among the first synthetic organic compounds to be used for therapeutic purposes. The sodium salt of salicylic acid, the methyl and phenyl esters, and the acetyl derivative of salicylic acid are extensively used to diminish pain (as analgesics) and to reduce the temperature of the body (as antipyretics). The most widely used is the acetyl derivative which is sold under the name aspirin. Salicylic acid is prepared industrially by the carbonation of sodium phenoxide, at 180-200° at atmospheric pressure or 120-130° at a pressure of a few atmospheres. 

Late in the last century, a beginning was made in the task of simplifying the molecular structure of natural products while retaining the therapeutic action. It was hoped in this way to obtain substances which coiild be more easily synthesized and which might be free from toxic side effects introduced by unwanted parts of the molecule. The introduction of salicylic acid into medicine in 1875 was one of the earliest results of this endeavour, and this acid and its salts and derivatives such as aspirin replaced the use of willow bark, and the glucoside of salicyl alcohol which this bark contained. 

Yasunaga, T. Satoi, Y Igarashi, M. Bird repellents containing salicylic acid or its salts or esters and application method. Jpn. Kokai Tokkyo Koho JP 2006257017, 2006 Chem. Abstr. 2006, 145, 350199. 

Examples of organic adds used as preservatives are dehydroacetic acid, sorbic acid, salicylic acid, propionic acid and their salts also benzoic acid and its salts and alkyl esters. 

The only practical methods for the preparation of o-chloro-benzoyl chloride to be found in the literature consist in the treatment of o-chlorobenzoic acid with phosphorus penta-chloride1 or thionyl chloride.2 It has, however, also been formed by distilling salicylic acid or its sodium salt with phosphorus pentachloride,3 and by heating the dichloride of o-sulfobenzoic acid.4... 

Both salicylic acid and sodium salicylate (its sodium salt) were widely used analgesics in the nineteenth century, but both had undesirable side effects. Salicylic acid irritated the mucous membranes of the mouth and stomach, and sodium salicylate was too sweet for most patients. Aspirin, a synthetic compound, was first sold in 1899 after Felix Hoffman, a German chemist at Bayer Company, developed a feasible commercial synthesis. Hoffman s work was motivated by personal reasons his father suffered from rheumatoid arthritis and was unable to tolerate the sweet taste of sodium salicylate. 

Potentiation of salicylate activity by simultancoas administration of />-aminobcn7.oic acid or its. salts has been the basis for the introduction of numerous products of this kind. Sala.ssa and cow orkers have shown that this effect is due to the inhibition of both. salicylate metabolism and excretion in the urine.This effect has been proved amply, provided that the ratio of 24 g of p-aminobcn/oic acid to 3 g of salicylate per day is observed. There is no. strung evidence, however. to substantiate any significant elevation of plasma. salicylate levels when less /7-aminoben/oic acid is u.sed. 

In solution, particularly in the presence of stxiium bicarbonate. the salt will darken on standing (see salicylic acid). This darkening may be lessened by the addition of sodium sulfite or sodium bisulfite. Also, use of recently boiled distilled water and dispensing in amber-colored bottles lessens color change. Sodium salicylate forms a eutectic mixture with antipyrine and produces a violet coloration with iron or its salts. Solutions of the compound must be neutral or slightly basic to prevent precipitation of free salicylic acid. The USP salt forms neutral or acid solutions, however. 

Complexation. It has been well established in the literature that complexation is an effective way to solubilize hydrophobic compounds. Nicotinimide is known to complex with aromatic drugs through tt donor-7r acceptor interaction (101). Similar tt-tt interaction also occurs between salts of benzoic acid or salicylic acid and drugs containing aromatic rings such as caffeine (102).Obviously, aromaticity is an important factor in this type of complexation. Unfortunately, from a safety perspective the use of these types of complex-ing agents for products is not really very viable. 

Materials that have been used in pyrotechnic mixtures include nitrocellulose, polyvinyl alcohol, stearic acid, hexamethylenetetramine, kerosene, epoxy resins, and unsaturated polyester resins such as Laminae . Salts of benzoic acid and its derivatives, such as potassium benzoate and sodium salicylate, also can serve as energetic fuels that are high melting and quite stable. The properties of most of these fuels can be found in a handbook prepared by the U.S. Army. Table 3.6 contains information on a variety of organic compounds that are of interest to the high-energy chemist. 

Salicylic acid (from the Latin Sahx meaning willow tree) is a biosynthesized, organic, beta hydroxy acid that is often used. Sodium salicylate is converted by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure and temperature. Acidification of the product with sulfuric acid gives salicylic acid. Alternatively, it can be prepared by the hydrolysis of Aspirin (acetylsahcyhc acid) or Oil of Wintergreen (methyl salicylate) with a strong acid or base. 

An additional useful test is to distil the acid or its sodium salt with soda lime. Heat 0.5 g. of the acid or its sodium salt with 0 2 g. of soda lime in an ignition tube to make certain that there is no explosion. Then grind together 0 5 g. of the acid with 3 g. of soda lime, place the mixture in a Pyrex test-tube and cover it with an equal bulk of soda hme. Fit a wide dehvery tube dipping into an empty test-tube. Clamp the tube near the mouth. Heat the soda lime first and then the mixture gradually to a dull-red heat. Examine the product this may consist of aromatic hydrocarbons or derivatives, e.g., phenol from salicylic acid, anisole firom anisic acid, toluene from toluic acid, etc. 

Reactive clay is used today principally in European countries, though it was once used worldwide. Zinc salt of salicylic acid derivatives and zinc-modified phenolic resin are used in Japan and the United States, respectively. The synthetic coreactants have a special feature giving stable recorded images. 

As the following pages of this section will show, there is hardly a new method of analysis which is not immediately tried for the determination of aspirin as such, or in formulations and biological fluids. The analysis of aspirin is intricately interwoven with that of salicylic acid, its precursor and degradation product. From the very first, residual salicylic acid was determined by the convenient reaction with ferric salts — typical for phenols — which give a violet complex with salicylic acid. 

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