| Salicylic acid |
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| Identifiers |
| CAS number |
69-72-7 Y |
| PubChem |
338 |
| ChemSpider |
331 Y |
| UNII |
O414PZ4LPZ Y |
| EC number |
200-712-3 |
| DrugBank |
DB00936 |
| KEGG |
D00097 Y |
| ChEBI |
CHEBI:16914 Y |
| ChEMBL |
CHEMBL424 Y |
| RTECS number |
VO0525000 |
| ATC code |
A01AD05,B01AC06 D01AE12 N02BA01 S01BC08 |
| Jmol-3D images |
Image 1 |
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InChI=1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10) Y
Key: YGSDEFSMJLZEOE-UHFFFAOYSA-N Y
InChI=1/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10)
Key: YGSDEFSMJLZEOE-UHFFFAOYAQ
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| Properties |
| Molecular formula |
C7H6O3 |
| Molar mass |
138.12 g mol−1 |
| Appearance |
colorless to white crystals |
| Odor |
odorless |
| Density |
1.443 g/cm3 [1] |
| Melting point |
158.6 °C, 432 K, 317 °F
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| Boiling point |
211 °C, 484 K, 412 °F (20 mmHg[1])
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| Solubility in water |
2 g/L (20 °C) |
| Solubility |
soluble in ether, CCl4, benzene, propanol, acetone, ethanol, oil of turpentine, toluene |
| log P |
2.26 |
| Acidity (pKa) |
2.97[2] |
| Refractive index (nD) |
1.565[1] |
| Thermochemistry |
Std enthalpy of
formation ΔfHo298 |
-589.9 kJ/mol |
| Related compounds |
| Related compounds |
Methyl salicylate,
Benzoic acid,
Phenol, Aspirin,
4-Hydroxybenzoic acid,
Magnesium salicylate,
Choline salicylate,
Bismuth subsalicylate,
Sulfosalicylic acid |
| Hazards |
| MSDS |
Oxford MSDS |
| EU Index |
200-712-3 |
| EU classification |
Harmful (Xn) |
| R-phrases |
R22 R36 R38 R61 |
| S-phrases |
S22 S26 S36 S37 S39 |
| NFPA 704 |
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| Flash point |
157 °C |
Autoignition
temperature |
545 °C |
| LD50 |
480 mg/kg |
Y (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
| Infobox references |
Salicylic acid (from Latin salix, willow tree, from the bark of which the substance used to be obtained) is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. 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 being 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 in anti-acne treatments. The salts and esters of salicylic acid are known as salicylates.
Contents
- 1 Chemistry
- 2 Plant hormone
- 3 Production
- 4 History
- 5 Dietary sources
- 6 Medicinal and cosmetic uses
- 7 Mechanism of action
- 8 Other uses
- 9 Safety
- 10 See also
- 11 Footnotes
- 12 External links
Chemistry[edit]
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).[3] 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.
Plant hormone[edit]
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 also induces specific changes in leaf anatomy and chloroplast structure. SA is involved in endogenous signaling, mediating in plant defense against pathogens.[4] It plays a role in the resistance to pathogens by inducing the production of pathogenesis-related proteins.[5] It is involved in the systemic acquired resistance (SAR) 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.[6]
Production[edit]
Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana it can also 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 (390K) -a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid:
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It can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid)[7] or methyl salicylate (oil of wintergreen) with a strong acid or base.
History[edit]
Main article: History of aspirin
White willow (
Salix alba) is a natural source of salicylic acid
The Greek physician Hippocrates wrote in the 5th century BC about a bitter powder extracted from willow bark that could ease aches and pains and reduce fevers.[citation needed] This remedy was also mentioned in texts from ancient Sumer, Lebanon, and Assyria.[citation needed] The Cherokee and other Native Americans used an infusion of the bark for fever and other medicinal purposes for centuries.[8] The medicinal part of the plant is the inner bark and was used as a pain reliever for a variety of ailments. 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.[9]
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 1826. A larger amount of the substance was isolated in 1828 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.[10]
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[edit]
Unripe fruits and vegetables are natural sources of salicylic acid, particularly blackberries, blueberries, cantaloupes, dates, raisins, kiwi fruits, guavas, apricots, green pepper, olives, tomatoes, radish and chicory; also mushrooms. Some herbs and spices contain quite high amounts, although meat, poultry, fish, eggs and dairy products all have little to no salicylates. Of the legumes, seeds, nuts, and cereals, only almonds, water chestnuts and peanuts have significant amounts.[11]
Medicinal and cosmetic uses[edit]
Salicylic acid is known for its ability to ease aches and pains and reduce fevers. These medicinal properties, particularly fever relief, have been known since ancient times, and it is used as an anti-inflammatory drug.[12]
In modern medicine, salicylic acid and its derivatives are used as constituents of some rubefacient products. For example, methyl salicylate is used as a liniment to soothe joint and muscle pain, and choline salicylate is used topically to relieve the pain of mouth ulcers.
Cotton pads soaked in salicylic acid can be used to chemically exfoliate skin
As with other beta hydroxy acids, salicylic acid is a key ingredient in many skin-care products for the treatment of seborrhoeic dermatitis, acne, psoriasis, calluses, corns, keratosis pilaris, and warts.[13] The standard treatment for calluses is a 6% aspirin suspension in petroleum jelly, applied on the callus for one hour and then removed with washing. It works as a keratolytic, bacteriocide and comedolytic agent by causing the cells of the epidermis to shed more readily, opening clogged pores and neutralizing bacteria within, preventing pores from clogging up again by constricting pore diameter, and allowing room for new cell growth.[14] Because of its effect on skin cells, salicylic acid is used in several shampoos to treat dandruff. Use of concentrated solutions of salicylic acid may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock.[15][16]
Bismuth subsalicylate, a salt of bismuth and salicylic acid, is the active ingredient in stomach relief aids such as Pepto-Bismol.[citation needed]
Mechanism of action[edit]
Salicylic acid has been shown to work through several different pathways. It produces its anti-inflammatory effects via suppressing the activity of cyclooxygenase (COX), an enzyme that is responsible for the production of pro-inflammatory mediators such as the prostaglandins. It does this not by direct inhibition of COX like most other non-steroidal anti-inflammatory drugs (NSAIDs) but instead by suppression of the expression of the enzyme (via a yet-unelucidated mechanism).[17] Salicylic acid has also been shown to activate adenosine monophosphate-activated protein kinase (AMPK), and it is thought that this action may play a role in the anticancer effects of the compound and its prodrugs aspirin and salsalate. In addition, the antidiabetic effects of salicylic acid are likely mediated by AMPK activation primarily through allosteric conformational change that increases levels of phosphorylation.[18] Salicylic acid also uncouples oxidative phosphorylation, which leads to increased ADP:ATP and AMP:ATP ratios in the cell. As a consequence, salicylic acid may alter AMPK activity and subsequently exert its anti-diabetic properties through altered energy status of the cell. Even in AMPK knock-out mice, however, there is an anti-diabetic effect, demonstrating that there is at least one additional, yet-unidentified action of the compound.[19]
Other uses[edit]
Although toxic in large quantities, salicylic acid is used as a food preservative and as bactericidal and an antiseptic.[20] For some people with salicylate sensitivity, even these small doses can be harmful.[citation needed]
Sodium salicylate is a useful phosphor in the vacuum ultraviolet, with nearly flat quantum efficiency for wavelengths between 10 to 100 nm.[21] It fluoresces in the blue at 420 nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in methanol followed by evaporation.
Safety[edit]
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, making it capable of causing moderate chemical burns of the skin if at very high concentrations. It is capable of damaging the lining of pores in such cases if the solvent is alcohol, acetone, or an oil. Over-the-counter limits are set at 2% for topical left on the face and 3% for those expected to be washed off, such as acne cleansers or shampoo. Caution should be exercised when handling large volumes of salicylic acid, and protective gloves are recommended for any repeat, prolonged exposure. Seventeen percent and 27% salicylic acid, which is often 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 only twice a day – more frequent use may lead to an increase in side-effects without an increase in efficacy.[22]
When ingested, salicylic acid has a possible ototoxic effect by inhibiting prestin.[23] It can induce transient hearing loss in zinc-deficient individuals. This finding is based on clinical studies with rats. An injection of salicylic acid induced hearing loss in zinc-deficient rats, while a simultaneous injection of zinc reversed the hearing loss. An injection of magnesium in the zinc-deficient rats did not reverse the salicylic acid-induced hearing loss.
There are no studies specifically looking at topical salicylic acid in pregnancy. Oral salicylic acid has not been associated with an increase in malformations if used during the first trimester, but use in late pregnancy has been associated with bleeding, especially intracranial bleeding.[24] The risks of aspirin late in pregnancy are probably not relevant for a topical exposure to salicylic acid, even late in the pregnancy, because of its low systemic levels. Topical salicylic acid is common in many over-the-counter dermatological agents, and the lack of adverse reports suggests a low teratogenic potential.[25]
Salicylic acid overdose can lead to salicylate intoxication, which often presents clinically in a state of metabolic acidosis with compensatory respiratory alkalosis. In patients presenting with an acute overdose, a 16% morbidity rate and a 1% mortality rate are observed.[26]
Some people are hypersensitive to salicylic acid and related compounds.
The United States Food and Drug Administration recommends the use of sun protection when using skincare products containing salicylic acid (or any other BHA) on sun-exposed skin areas.[27]
There is data that supports an association between exposure to salicylic acid and Reye's Syndrome. The National Reye's Syndrome Foundation cautions against the usage of these substances, and other substances similar to aspirin, on children and adolescents.
Epidemiological research has shown an association between the development of Reye's Syndrome and the use of aspirin (a salicylate compound) for treating the symptoms of influenza-like illnesses, chicken pox, colds, etc.
The U.S. Surgeon General, the Food and Drug Administration, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics recommend that aspirin and combination products containing aspirin not be given to children under 19 years of age during episodes of fever-causing illnesses, because of a concern about Reye's Syndrome.[28]
See also[edit]
- Methyl salicylate
- Trolamine salicylate
[edit]
- ^ a b c Haynes, William M., ed. (2011). CRC Handbook of Chemistry and Physics (92nd ed.). CRC Press. p. 3.306. ISBN 1439855110.
- ^ Salicyclic acid. Drugbank.ca. Retrieved on 2012-06-03.
- ^ "Salicilyc acid". inchem.org. Retrieved 2008-10-13.
- ^ Hayat, S. and Ahmad, A. (2007). Salicylic acid – A Plant Hormone. Springer. ISBN 1-4020-5183-2.
- ^ Van Huijsduijnen, R. A. M. H.; Alblas, S. W.; De Rijk, R. H.; Bol, J. F. (1986). "Induction by Salicylic Acid of Pathogenesis-related Proteins and Resistance to Alfalfa Mosaic Virus Infection in Various Plant Species". Journal of General Virology 67 (10): 2135. doi:10.1099/0022-1317-67-10-2135.
- ^ Taiz, L. and Zeiger, Eduardo (2002) Plant Physiology, 3rd Edition, Sinauer Associates, p. 306, ISBN 0878938230.
- ^ "Hydrolysis of ASA to SA". Retrieved July 31, 2007.
- ^ Hemel, Paul B. and Chiltoskey, Mary U. Cherokee Plants and Their Uses – A 400 Year History, Sylva, NC: Herald Publishing Co. (1975); cited in Dan Moerman, A Database of Foods, Drugs, Dyes and Fibers of Native American Peoples, Derived from Plants. [1] A search of this database for "salix AND medicine" finds 63 entries.
- ^ Stone, E (1763). "An Account of the Success of the Bark of the Willow in the Cure of Agues". Philosophical Transactions 53: 195–200. doi:10.1098/rstl.1763.0033.
- ^ Jeffreys, Diarmuid (2005). Aspirin : the remarkable story of a wonder drug. New York: Bloomsbury. pp. 38–40. ISBN 978-1-58234-600-7.
- ^ What is Salicylic acid and in which foods does it occur?. Food-Info.net. Retrieved on 2012-06-03.
- ^ Mackowiak, Philip A. (2000). "Brief History of Antipyretic Therapy". Clinical Infectious Diseases, 31: 154–156. doi:10.1086/317510. PMID 11113017.
- ^ Steele, K.; Shirodaria, P.; O'Hare, M.; Merrett, J.D.; Irwin, W.G.; Simpson, D.I.H.; Pfister, H. (1988). "Monochloroacetic acid and 60% salicylic acid as a treatment for simple plantar warts: effectiveness and mode of action". British Journal of Dermatology 118 (4): 537–43. doi:10.1111/j.1365-2133.1988.tb02464.x. PMID 3377974.
- ^ Salicylic Acid Essential Actives, KAVI.
- ^ Grimes, P.E. (1999). "The Safety and Efficacy of Salicylic Acid Chemical Peels in Darker Racial-ethnic Groups". Dermatologic Surgery 25 (1): 18–22. doi:10.1046/j.1524-4725.1999.08145.x. PMID 9935087.
- ^ Roberts, W. E. (2004). "Chemical peeling in ethnic/dark skin". Dermatologic Therapy 17 (2): 196–205. doi:10.1111/j.1396-0296.2004.04020.x. PMID 15113287.
- ^ "Anti-Inflammatory Activity of Aspirin – It's All About Salicylic Acid". American Chemical Society.
- ^ Hawley, S. A.; Fullerton, M. D.; Ross, F. A.; Schertzer, J. D.; Chevtzoff, C.; Walker, K. J.; Peggie, M. W.; Zibrova, D. et al. (2012). "The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase". Science 336 (6083): 918–22. doi:10.1126/science.1215327. PMC 3399766. PMID 22517326.
- ^ Raffensperger, Lisa (2012-04-19). "Clues to aspirin's anti-cancer effects revealed". New Scientist
- ^ "Definition of Salicylic acid". MedicineNet.com.
- ^ Samson, James (1976). Techniques of Vacuum Ultraviolet Spectroscopy. Wiley, .
- ^ salicylic acid 17 % Topical Liquid. Kaiser Permanente Drug Encyclopedia. Accessed 28 Sept 2011.
- ^ Wecker, H.; Laubert, A. (2004). "Reversible hearing loss in acute salicylate intoxication". HNO (in German) 52 (4): 347–51. doi:10.1007/s00106-004-1065-5. PMID 15143764.
- ^ Rumack, CM; Guggenheim, MA; Rumack, BH; Peterson, RG; Johnson, ML; Braithwaite, WR (1981). "Neonatal intracranial hemorrhage and maternal use of aspirin". Obstetrics and gynecology 58 (5 Suppl): 52S–6S. ISSN 0029-7844. PMID 7312229.
- ^ Acne and Pregnancy. Fetal-exposure.org. Retrieved on 2012-06-03.
- ^ Salicylate Toxicity. Emedicine.medscape.com. Retrieved on 2012-06-03.
- ^ "Beta Hydroxy Acids in Cosmetics". Archived from the original on 2007-12-21. Retrieved 2007-11-23.
- ^ "Aspirin / Salicylates and Reye's Syndrome". reyessyndrome.org. Retrieved 2009-05-22.
External links[edit]
- Safety MSDS data
- International Chemical Safety Cards | CDC/NIOSH
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Acne-treating agents (D10)
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| Antibacterial |
- Azelaic acid
- Benzoyl peroxide#
- Hydroxyquinoline
- Blue light therapy
- Tea tree oil
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| Keratolytic |
- Glycolic acid
- Salicylic acid#
- Sulfur
- Benzoyl peroxide#
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| Anti-inflammatory |
- Nicotinamide
- Ibuprofen
- Aspirin
- Red light therapy
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| Antibiotics |
- Clindamycin
- Dapsone
- Erythromycin
- Sulfacetamide
- Tetracyclines (Lymecycline
- Minocycline
- Doxycycline)
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| Hormonal |
- Antiandrogens
- Contraceptives
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| Retinoids |
- Adapalene
- Isotretinoin
- Motretinide
- Tazarotene
- Tretinoin
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| Other |
|
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| Combinations |
- Adapalene/benzoyl peroxide
- Benzoyl peroxide/clindamycin
- Clindamycin/tretinoin
- Erythromycin/isotretinoin
- Sulfacetamide/sulfur
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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noco/cong/tumr, sysi/epon
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Ancient anaesthesia
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| Plants / animals |
- Aconitum (aconite)
- Atropa belladonna (belladonna)
- Cannabis
- Castoreum
- Coca
- Conium (hemlock)
- Datura inoxia (thorn-apple)
- Datura metel (devil's trumpet)
- Hyoscyamus niger (henbane)
- Lactucarium
- Mandragora officinarum (mandrake)
- Opium
- Saussurea (saw-wort)
- Willow
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| People |
- Abulcasis
- Avenzoar
- Avicenna
- Celsus
- Dioscorides
- Galen
- Hippocrates
- Rhazes
- Sabuncuoğlu
- Sushrutha
- Theophrastus
- Zhang
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| Compounds |
- Aconitine
- Atropine
- Cocaine
- Coniine
- Δ9-THC
- Hyoscyamine
- Morphine
- Salicylate
- Scopolamine
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Antifungals (D01 and J02)
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Wall/
membrane |
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Ergosterol
inhibitors
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Azoles
(lanosterol 14
alpha-demethylase inhibitors) |
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Imidazoles
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- topical: Bifonazole
- Butoconazole
- Clomidazole
- Clotrimazole#, Croconazole
- Econazole
- Fenticonazole
- Ketoconazole
- Isoconazole
- Miconazole#, Neticonazole
- Omoconazole
- Oxiconazole
- Sertaconazole
- Sulconazole
- Tioconazole
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Triazoles
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- topical: (Fluconazole#, Fosfluconazole
- Terconazole)
- systemic: (Fluconazole
- Hexaconazole
- Isavuconazole†, Itraconazole
- Posaconazole
- Voriconazole)
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Thiazoles
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topical: (Abafungin)
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Polyene antimycotics
(ergosterol binding)
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- topical: (Hamycin
- Natamycin
- Nystatin#)
systemic: (Amphotericin B#, Hamycin)
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Allylamines
(squalene monooxygenase
inhibitors) |
- topical: (Amorolfine
- Butenafine
- Naftifine
- Terbinafine)
systemic: (Terbinafine)
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β-glucan synthase
inhibitors
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- echinocandins (Anidulafungin
- Caspofungin
- Micafungin)
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| Intracellular |
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Pyrimidine analogues/
Thymidylate synthase inhibitors
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Mitotic inhibitors
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| Others |
- Bromochlorosalicylanilide
- Methylrosaniline
- Tribromometacresol
- Undecylenic acid
- Polynoxylin
- Chlorophetanol
- Chlorphenesin
- Ticlatone
- Sulbentine
- Ethylparaben
- Haloprogin
- Salicylic acid
- Selenium sulfide#
- Ciclopirox
- Amorolfine
- Dimazole
- Tolnaftate
- Tolciclate
- Sodium thiosulfate#
- Whitfield's ointment#
- Potassium iodide#
- Taurolidine
- Tea tree oil
- citronella oil
- lemon grass
- orange oil
- patchouli
- lemon myrtle
- PCP: Pentamidine
- Dapsone
- Atovaquone
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Plant hormones
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- Abscisic acid
- Auxins
- Cytokinins
- Ethylene
- Gibberellins
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- Brassinosteroids
- Florigen
- Jasmonates
- Karrikins
- Plant peptide hormones
- Polyamine
- Salicylic acid
- Strigolactones
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Salicylates
|
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- Salicylic acid
- Aspirin
- Aloxiprin
- Methyl salicylate
- Magnesium salicylate
- Ethyl salicylate
- Bismuth subsalicylate
- Sodium salicylate
- Salicylamide
- Salicin
- Benorilate
- Salsalate
- Ethenzamide
- Diflunisal
- Trolamine salicylate
- Homosalate
- Salicylmethylecgonine
- Octyl salicylate
- Aluminon
- Benzyl salicylate
- Copper aspirinate
- Potassium salicylate
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Phenolic acids and their glycosides
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| Monohydroxybenzoic acids |
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Aglycones
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- 3-Hydroxybenzoic acid
- 4-Hydroxybenzoic acid
- Salicylic acid
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Glycosides
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- p-Hydroxybenzoic acid glucoside
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| Dihydroxybenzoic acids |
- 2,3-Dihydroxybenzoic acid (Hypogallic acid)
- 2,4-Dihydroxybenzoic acid
- 2,6-Dihydroxybenzoic acid
- 3,5-Dihydroxybenzoic acid
- Ethyl protocatechuate
- Gentisic acid
- Homogentisic acid
- Orsellinic acid
- Protocatechuic acid
|
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| Trihydroxybenzoic acids |
- Bergenin
- Chebulic acid
- Ethyl gallate
- Eudesmic acid
- Gallic acid
- Norbergenin
- Phloroglucinol carboxylic acid
- Syringic acid
- Theogallin
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