Salicylic acid (from Latin salix, willow tree) is a lipophilic monohydroxybenzoic acid, a type of phenolic acid, and a beta hydroxy acid (BHA). It has the formula C7>H6O3. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin. In addition to serving as an important active metabolite of aspirin (acetylsalicylic acid), which acts in part as a prodrug to salicylic acid, it is probably best known for its use as a key ingredient in topical anti-acne products. The salts and esters of salicylic acid are known as salicylates.
It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.
Uses
Medicine
Salicylic acid as a medication is used most commonly to help remove the outer layer of the skin. As such, it is used to treat warts, psoriasis, dandruff, acne, ringworm, and ichthyosis.
As with other hydroxy acids, salicylic acid is a key ingredient in many skincare products for the treatment of seborrhoeic dermatitis, acne, psoriasis, calluses, corns, keratosis pilaris, acanthosis nigricans, ichthyosis and warts. It is used in some shampoos to treat dandruff.
Manufacturing
Salicylic acid is used in the production of other pharmaceuticals, including 4-aminosalicylic acid, sandulpiride, and landetimide (via Salethamide).
Salicylic acid was one of the original starting materials for making acetylsalicylic acid (aspirin) in 1897.
Bismuth subsalicylate, a salt of bismuth and salicylic acid, is the active ingredient in stomach relief aids such as Pepto-Bismol, is the main ingredient of Kaopectate and "displays anti-inflammatory action (due to salicylic acid) and also acts as an antacid and mild antibiotic".
Other derivatives include methyl salicylate used as a liniment to soothe joint and muscle pain and choline salicylate used topically to relieve the pain of mouth ulcers.
Chemistry
Salicylic acid has the formula C6H4(OH)COOH, where the OH group is ortho to the carboxyl group. It is also known as 2-hydroxybenzoic acid. It is poorly soluble in water (2 g/L at 20 °C). Aspirin (acetylsalicylic acid or ASA) can be prepared by the esterification of the phenolic hydroxyl group of salicylic acid with the acetyl group from acetic anhydride or acetyl chloride. Salicylic acid can also be prepared using the Kolbe-Schmitt reaction.
Other uses
Salicylic acid is used as a food preservative, a bactericidal and an antiseptic.
Sodium salicylate is a useful phosphor in the vacuum ultraviolet, with nearly flat quantum efficiency for wavelengths between 10 and 100Â nm. It fluoresces in the blue at 420Â nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in methanol followed by evaporation.
Safety
As a topical agent and as a beta-hydroxy acid (and unlike alpha-hydroxy acids), salicylic acid is capable of penetrating and breaking down fats and lipids, causing moderate chemical burns of the skin at very high concentrations. It may damage the lining of pores if the solvent is alcohol, acetone or an oil. Over-the-counter limits are set at 2% for topical preparations expected to be left on the face and 3% for those expected to be washed off, such as acne cleansers or shampoo. 17% and 27% salicylic acid, which is sold for wart removal, should not be applied to the face and should not be used for acne treatment. Even for wart removal, such a solution should be applied once or twice a day â€" more frequent use may lead to an increase in side-effects without an increase in efficacy.
Some people are hypersensitive to salicylic acid and related compounds.
Production
Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana it can be synthesized via a phenylalanine-independent pathway.
Sodium salicylate is commercially prepared by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100 atm) and high temperature (390 K) â€" a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid:
It can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid) or methyl salicylate (oil of wintergreen) with a strong acid or base.
History
Hippocrates, Galen, Pliny the Elder and others knew that willow bark could ease pain and reduce fevers. It was used in Europe and China to treat these conditions. This remedy is mentioned in texts from ancient Egypt, Sumer and Assyria. The Cherokee and other Native Americans used an infusion of the bark for fever and other medicinal purposes.
In 2014, archaeologists identified traces of salicylic acid on 7th century pottery fragments found in east central Colorado. The Reverend Edward Stone, a vicar from Chipping Norton, Oxfordshire, England, noted in 1763 that the bark of the willow was effective in reducing a fever.
The active extract of the bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated and named by the German chemist Johann Andreas Buchner in 1828. A larger amount of the substance was isolated in 1829 by Henri Leroux, a French pharmacist. Raffaele Piria, an Italian chemist, was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.
Salicylic acid was also isolated from the herb meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as gastric irritation, bleeding, diarrhea and even death when consumed in high doses.
Dietary sources
Salicylic acid occurs in plants as free salicylic acid and its carboxylated esters and phenolic glycosides. Several studies suggest that humans metabolize salicylic acid in measurable quantities from these plants; one study found that vegetarians not taking aspirin had urinary levels of salicylic acid comparable to those of patients taking 75 mg of aspirin per day, while the non-vegetarians had levels roughly one-quarter that of vegetarians. Dietary sources of salicylic acid and their interaction with drugs such as aspirin have not been well studied. Ongoing clinical studies of patients with aspirin-induced asthma have shown some benefits of a diet low in salicylic acid. Dietary salicylic acid may be partially responsible for the health benefits of a plant-based diet.
Studies on the salicylic content of foods are sparse and have produced distinctly different results, creating controversy. Possible causes for the discrepancies include uncontrolled and often unreported factors such as cultivation area, crop species, and harvest methods, as well as inherent issues with the studies such as poor extraction and measurement procedures and limited or low-accuracy equipment. A recent study using best practice measurement methodology significantly reduced intra-sample measurement variability but has not yet been replicated or extended.
Some results have been consistently reported. Meat, poultry, fish, eggs, oils, dairy products, sugar, cereals, and flour all have little to no salicylates. Measurable levels of salicylic acid have been found in fruits, vegetables, herbs, spices, nuts, and teas.
Plant hormone
Salicylic acid (SA) is a phenolic phytohormone and is found in plants with roles in plant growth and development, photosynthesis, transpiration, ion uptake and transport. SA is involved in endogenous signaling, mediating in plant defense against pathogens. It plays a role in the resistance to pathogens by inducing the production of pathogenesis-related proteins. It is involved in the systemic acquired resistance in which a pathogenic attack on one part of the plant induces resistance in other parts. The signal can also move to nearby plants by salicylic acid being converted to the volatile ester, methyl salicylate.
See also
- Methyl salicylate
- Trolamine salicylate
- Salsalate
References
External links
- Salicylic acid MS Spectrum
- Safety MSDS data
- International Chemical Safety Cards | CDC/NIOSH
- [2] English Translation of Hermann Kolbe's seminal 1860 German article in Annalen der Chemie und Pharmacie. English title: 'On the syntheses of salicylic acid'; German title "Ueber Synthese der Salicylsäure".