3 salicylic acid

Salicylic acid is used to treat acne, warts, dandruff, psoriasis, and similar conditions. In the treatment of acne, it slows the shedding of skin cells in hair follicles, so they do not clog the pores and cause pimples. It also has a keratolytic effect—it causes dead skin cells to slough off— which removes the top layer of skin and clears existing pore clogs. 

In treatments for warts, a stronger solution is used. Not only does this soften the wart so it can be rubbed off, but the irritation also stim- 

Salicylic acid reacts with acetic acid to produce acetylsalicylic acid the active ingredient in aspirin. It also reacts with methanol to form methyl salicylate, more commonly known as oil of wintergreen. 

Salicylic acid is common in foods such as broccoli, peppers, curry, cucumbers, and raisins, among many others. 

Salicylic acid reduces inflammation, including inflammation of the arteries. In arteries it can work to prevent hardening and narrowing. 

Salicylic Acid, CeH4 ortho-Hydroxy Benzoic Acid 

The hydroxy aromatic acids constitute an important group. They may be of the several types given in the introductory general discussion, e.g. 

Ring-hydroxy ring-carboxy acids, CeH4 Salicylic acid 

Ring-hydroxy side-chain- C6H4 f Hydroxy phenyl acetic acid 

Salicylic acid was first obtained in 1838 by Raphael Kria, by the reaction between salicylaldehyde and potassium hydroxide. 

The presently dominant process for the production of salicylic acid is based on the Kolbe-Schmitt synthesis. Hermann Kolbe and E.Lautemann described the reaction of carbon dioxide with sodium phenolate to produce sodium salicylate and its subsequent reaction with sulfuric acid to yield salicylic acid, in 1860. However, as a result of the formation of di-sodium salicylate in this process, only half the phenol was converted into salicylic acid. Rudolf Schmitt modified the synthesis in 1884, by first bringing into contact carbon dioxide with cold, dry sodium phenolate, then heating the mixture under pressure to 120 to 140 °C. 

In the process commonly used today, carbon dioxide is fed at a pressure of 6 to 7 bar and at a temperature of 100 °C over dry sodium phenolate, which is produced from phenol and 50% aqueous sodium hydroxide solution followed by vacuum evaporation of the water. The reaction mixture is then carboxylated at 150 to 170 °C until no more CO2 uptake occurs. The crude salicylic add is recovered 

The production of salicylic acid in the United States in 1985 was around 15.000t.West European production is estimated at around 20.000t the largest producers are Monsanto and Rhone Poulenc, 

Over one-half of the salicylic acid is used to manufacture acetylsalicylic acid, quantitatively one of the most important analgesic pharmaceuticals. Acetylsalicylic acid was first produced in 1853 from acetyl chloride and sodium salicylate. Its introduction as a medicament occurred in Germany in 1899 (Aspirin) and in the USA in 1900. Acetylsalicylic acid is now produced by reaction between salicylic acid and acetic anhydride in stainless steel or enamelled reactors at a temperature below 98 °C (duration of reaction 2 to 3 hours). The reaction mixture is refined by crystallization at 0 °C. 

Salicylic acid is another common organic acid that is sometimes used as a rubber retarder. It increases the scorch safety time of a nonhalogenated rubber-based compound. However, it also slows down the cure rate and may lower the ultimate cured 

Synthesis of salicylic acid from sodium phenate (phenoiate) 

Sodium phenate (sodium phenoiate) is derived from the reaction of phenol with sodium hydroxide 

Even though one million pounds a year of salicylic acid might be used worldwide by the rubber industry as a retarder, which is only a small fraction of the amount of salicylic acid used in nonrubber applications. One of its largest uses is as the principal feedstock in the manufacture of aspirin and salicylate esters. It is also used as a dyestuff intermediate and as a fungicide. 

Other retarders can probably substitute for salicylic acid with only some compound adjustments needed. 

Even the name of glutamic acid has its origin in wheat. The substance gluten occurs abundantly in high quality wheat. Glutamic acid was first prepared in a pure form from hydrolyzed gluten, hence its name. 

Properties of Salicylic Acid (SECTION 606).—(a) Salicylic acid and ferric chloride.—Add a dilute solution of ferric chloride (see note to experiment 197d, page 168) to a dilute aqueous solution of salicylic acid. To one-half of the solution add dilute hydrochloric acid, drop by drop, and to the other half dilute acetic acid. Add a drop of ferric chloride to an alcoholic solution of salicylic acid. Repeat these tests with phenol and compare the results. 

Salicylanilide is ordinarily made by reacting salicylic acid with aniline in the presence of phosphorus trichloride at an elevated temperature. The theoretical proportions of reactants are usually employed for best results, that is, one mol each of aniline and salicylic acid to a third of a mol of phosphorus trichloride. An improved process employs an inert organic solvent as a reaction diluent. 

Chemical Name 2-Hydroxyben2oic acid Common Name — 

Trade Nama Manufacturer Country Year Introduced  

and Dunlap, W.J. U.S. Patent 3,274,074 September 20, 1966 assigned to Kerr-McGee Oil Industries, Inc. 

Salicylanilide is ordinarily made by reacting salicylic acid with aniline in the presence of phosphorus trichloride at an elevated temperature. The theoretical proportions of reactants 

Chemical Name 2-HYdroxyben2oic acid Common Name — 

Sodium phenolate Bacterium Pseudomonas Carbon dioxide Naphthalene  

Initial reports (Dumer and Klessig, 1995) indicating that salicylic acid acts as an inhibitor of APX activity were later questioned (Kvaratskhelia et al., 1997a). In fact, it seems more likely that salicylic acid acts as a reducing substrate for Compound I and Compound II (second order rate constants, Jc2 and ks, of 4.0 X 10 and 1.5 x 10 M s respectively), although the nature of the radical products has not been identified (Kvaratskhelia et al., 1997a). 

Acknowledgments. The authoris own work has been supported by grants from the Royal Society, the EPSRC, the Nuffield foundation, the BBSRC 

Altschul, A. M., Abrams, R., and Hogness, T. R., 1940, Cytochrome c peroxidase, J. Biol. Chem. 136 777n794. 

Armstrong, F. A., and Lannon, A. M., 1987, Fast interfacial electron-transfer between cytochrome-c peroxidase and graphite-electrodes promoted by aminoglycosides-novel electroenzymic catalysis of HjOj reduction, J. Am. Chem. Soc. 109 7211n7212. 

Armstrong, F. A., Butt, J. N., and Sucheta, A., 1993, Voltammetric studies of redox-active centres in metalloproteins adsorbed on electrodes, Meth. Enzymol. 227 479n500. 

Salicylate synthetase was also detected in two other Mycobacterium spedes, M. tuberculosis and M. fortuitum, which contain salicylic acid in their myco-bactins. However, it was definitely absent from M. phlei, which lacks salicylic acid but has 6-methylsaIicylic acid. Furthermore, in M. phlei, salicylic acid failed to operate as a feedback control, as it did in the other three organisms. 

Other Names 171 2-Carboxyphenol 2-Hydroxybenzenecarboxylic acid 2-Hydroxybenzoic acid 311 334 337 380 51 Advanced Pain Relief Callus Removers Advanced Pain Relief Com Removers Clear away Wart Remover Compound W Dr. Scholl s Callus Removers Dr. Scholl s Com Removers Dr. Scholl s Wart Remover Kit Duofll Wart Remover Duoplant Freezone lonil lonil Plus K 537 K 557 NSC 180 Phenol-2-carboxyhc acid Psoriacid-S-Stift Retarder W Rutranex Salicylic Acid Soap Salicylic acid collodion Sahgel Salonil Stii-Dex Trans-Ver-Sal ( -Carboxyphenol o-Hydroxybenzoic acid CA Index Name Benzoic acid, 2-hydroxy-CAS Registry Number 69-72-7 Merck Index Number 8332 Chemical Structure 

Chemical/Dye Class Fluorescent Molecular Formula C7H6O3 Molecular Weight 138.12 pH Range 2.5-4.0 

Color Change at pH Nonfluorescence (2.5) to dark blue fluorescence (4.0) pKa 2.98 

Solubility Slightly soluble in water soluble in ethanol, acetone 

Borbely, L. Haasz, F. Jekkel, P. A new process for the preparation of phenolic hydroxy-substituted compounds. PCT InL Appl. WO 2006061666, 2006 Chem. Abstr. 2006,145, 62661. 

Place 10 g. of clean sodium (cut into small pieces) in a 500 ml. round bottomed flask fitted with a double surface reflux condenser. Introduce 100 g. (127 ml.) of absolute ethyl alcohol and allow the reaction to proceed as vigorously as possible if the alcohol tends to flood the condenser, cool the flask momentarily with a wet towel or by a stream of cold water. When all the sodium has reacted, add 40 g. of pure phenol. Distil ofif the 

An alternative biosynthetic pathway towards SA was hypothesized to exist after experiments with labeled benzaldehyde, benzyl alcohol, and phenylalanine resulted in lower incorporation of the label in SA than 

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C7H6O2 Oily liquid of aromatic odour b.p. 196°C. (t is prepared by the action of chloroform and caustic potash on phenol (the Reimer-Tiemann reaction) or by the oxidation of the glucoside salicin. It is easily reduced to salicyl alcohol or oxidized to salicylic acid. 

When the phenol contains a carboxylic acid group, e.g., m- or p-hydroxy-benzoic acid, the acetylated derivative will of course remain in solution as the sodium salt, but is precipitated when the solution is subsequently acidified. Salicylic acid, however, cannot be acetylated under these conditions. 

Required Salicylic acid, 10 g. pyridine, 7 ml. acetyl chloride. 

Dissolve 10 g. of salicylic acid (o-hydroxybenzoic acid) in 7 ml. of dry pyridine contained in a too ml. conical flask. Then without delay (since this solution if allowed to stand tends to become a semi-solid mass) run in 7 5 ml. (8 3 g.) of acetyl chloride, adding about i ml. of the chloride at a time, and shaking the mixture continuously during the addition. The heat of the reaction causes the temperature of the mixture to rise rapidly ... 

It should be emphasised that salicylic acid can be readily acetylated by Method 1, and that the above preparation of acetylsalicyclic acid is given solely as an illustration of Method 2. To employ Method 1, add 10 g. of salicylic acid to 20 ml. of a mixture of equal volumes of acetic anhydride and acetic acid, and boil gently under reflux for 30 minutes. Then pour into about 200 ml. of cold water in order to precipitate the acetylsalicylic acid (11 g.) and finally recrystallise as above. Method 2, however, gives the purer product. 

Reactions of Aspirin, (i) Distinction from Salicylic acid. Shake up with water in two clean test-tubes a few crystals of a) salicylic acid, (0) aspirin, a very dilute aqueous solution of each substance being thus obtained. Note that the addition of i drop of ferric chloride solution to (a) gives an immediate purple coloration, due to the free —OH group, whereas (b) gives no coloration if the aspirin is pure. 

In the following experiment, salicylic acid is reduced to o-hydroxybenzyl alcohol (or saligenin), which being crystalline is readily isolated the excess of hydride is destroyed by the addition of undried ether, and the aluminium hydroxide then brought into solution by the addition of sulphuric acid. 

Required Salicylic acid, 6 0 g. lithium aluminium hydride, 2 5 g. dry ether, 165 ml. 

Now cool the mixture thoroughly in ice-water, and run in over a period of 45 minutes a solution of 6 o g. of dry salicylic acid in 75 ml. of dry ether. When the addition of the acid to the stirred solution is complete, heat the mixture under reflux on the water-bath for 15 minutes to ensure completion of the reduction. Then thoroughly chill the mixture in ice-water, and hydrolyse any unused hydride by the slow addition of 50 ml. of ordinary undried ether, followed similarly by 75 ml. of dilute sulphuric acid. 

Violet coloration. (Note however that a dilute solution of salicylic acid will give this coloration without any preliminary neutralisation.)... 

I. Methyl salicylate test. Heat i ml. of methanol with 0 5 g. of sodium sdicylate (or free salicylic acid) and a few drops of cone. H2SO4 gently for i minute. Cool, pour into a few ml. of cold water in a boiling-tube, and shake. Note the odour of methyl salicylate (oil of wintergreen). 

Many of the reactions of phenols are frequently given also by their derivatives, e.g.f salicylic acid (p. 352) beha es like phenol towards a number of reagents. 

Salicylaldehyde gives a yellow coloration and forms salicylic acid very slowly. Cannizzaro s reaction is also given by formaldehyde but, owing to the difficulty in isolating the products, is not used as a test. 

Oxidation to acids. Varm together in a small conical flask on a water-bath for lo minutes a mixture of 0 5 ml. of benzaldehyde or salicylaldehyde, 15 ml. of saturated KMn04 solution, and 0-5 g. of NajCOj. Then acidify with cone. HCl, and add 25% sodium sulphite solution until the precipitated manganese dioxide has redissolved. On cooling, benzoic or salicylic acid crystallises out. 

Action of sodium hydroxide. Does not undergo the Cannizzaro reaction. It dissolves in dil. NaOH solution, giving a yellow solution from which the aldehyde is precipitated unchanged on acidification. If heated with cone. NaOH solution, salicylaldehyde slowly undergoes atmospheric oxidation to salicylic acid. 

Salicylic Acid. Ester has strong odour of oil of wintergreen. 

The methyl ester formed by substituting methanol for ethanol in the above reaction has an even stronger odour and should be prepared if salicylic acid is suspected. 

Acetylation. Boil i g. of salicylic acid with 4 ml. of an acetic anhydride-acetic acid mixture (equal volumes) under reflux for 10 minutes. Pour into water. Filter off the aspirin (p. 111), wash with water and recrystallise from aqueous acetic acid (1 1) m.p. l36 ... 

Phthalein formation Fuse together carefully in a dry test-tube a few crystals of salicylic acid or of a salicylate with an equal quantity of phthalic anhydride rnoistened with 2 drops of cone. HjSO. Cool, dissolve in water and... 

It is important to note that in these reactions salicylic acid is functioning as a phenol. 

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. 

Phenolic carbolic) odour. Many phenols, some derivatives of salicylic acid e.g., salicylaldehyde). 

Substances suitable for the estimation acetanilide, sucrose, glucose, cinnamic acid, diphenyl amine, salicylic acid, vanillin, />"bromoacetanilide, toluene p-sul phonamide. 

Choice of solvent for recrystallisation. Obtain small samples (about 0 5 g.) of the following compounds from the storeroom (i) salicylic acid, (Li) acetanilide, (iii) m-dinitrobenzene, (iv) naphthalene, and (v) p-toluene-sulphonamide. Use the following solvents distilled water, methylated spirit, rectified spirit, acetone, benzene and glacial acetic acid. 

Optional or alternative experiments are the recrystaUisation of 3-0 g. of crude benzoic or salicylic acid from water. 

Salicylic acid, however, cannot be acetylated under these conditions. 

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. 

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