Salicylic acid

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Salicylic acid
Skeletal formula of salicylic acid
Ball-and-stick model of salicylic acid
Salicylic acid
Names
Preferred IUPAC name
2-Hydroxybenzoic acid[1]
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.648 Edit this at Wikidata
EC Number
  • 200-712-3
KEGG
RTECS number
  • VO0525000
UNII
  • InChI=1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10) checkY
    Key: YGSDEFSMJLZEOE-UHFFFAOYSA-N checkY
  • InChI=1/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10)
    Key: YGSDEFSMJLZEOE-UHFFFAOYAQ
  • O=C(O)c1ccccc1O
Properties
C7H6O3
Molar mass 138.122 g/mol
Appearance Colorless to white crystals
Odor Odorless
Density 1.443 g/cm3 (20 °C)[2]
Melting point 158.6 °C (317.5 °F; 431.8 K)
Boiling point 200 °C (392 °F; 473 K) decomposes[3]
211 °C (412 °F; 484 K)
at 20 mmHg[2]
Sublimes at 76 °C[4]
  • 1.24 g/L (0 °C)
  • 2.48 g/L (25 °C)
  • 4.14 g/L (40 °C)
  • 17.41 g/L (75 °C)[3]
  • 77.79 g/L (100 °C)[5]
Solubility Soluble in ether, CCl4, benzene, propanol, acetone, ethanol, oil of turpentine, toluene
Solubility in benzene
  • 0.46 g/100 g (11.7 °C)
  • 0.775 g/100 g (25 °C)
  • 0.991 g/100 g (30.5 °C)
  • 2.38 g/100 g (49.4 °C)
  • 4.4 g/100 g (64.2 °C)[3][5]
Solubility in chloroform
  • 2.22 g/100 mL (25 °C)[5]
  • 2.31 g/100 mL (30.5 °C)[3]
Solubility in methanol
  • 40.67 g/100 g (−3 °C)
  • 62.48 g/100 g (21 °C)[3]
Solubility in olive oil 2.43 g/100 g (23 °C)[3]
Solubility in acetone 39.6 g/100 g (23 °C)[3]
log P 2.26
Vapor pressure 10.93 mPa[4]
Acidity (pKa)
  1. 2.97 (25 °C)[6]
  2. 13.82 (20 °C)[3]
UV-vismax) 210 nm, 234 nm, 303 nm (4 mg/dL in ethanol)[4]
−72.23·10−6 cm3/mol
1.565 (20 °C)[2]
2.65 D
Thermochemistry
−589.9 kJ/mol
3.025 MJ/mol[7]
Pharmacology
A01AD05 (WHO) B01AC06 (WHO) D01AE12 (WHO) N02BA01 (WHO) S01BC08 (WHO)
Hazards
Safety data sheet MSDS
GHS pictograms GHS05: CorrosiveGHS07: Harmful[8]
GHS Signal word Danger
H302, H318[8]
P280, P305+P351+P338[8]
Eye hazard Severe irritation
Skin hazard Mild irritation
NFPA 704 (fire diamond)
2
1
0
Flash point 157 °C (315 °F; 430 K)
closed cup[4]
540 °C (1,004 °F; 813 K)[4]
Lethal dose or concentration (LD, LC):
480 mg/kg (mice, oral)
Related compounds
Related compounds
Methyl salicylate,
Benzoic acid,
Phenol, Aspirin,
4-Hydroxybenzoic acid,
Magnesium salicylate,
Choline salicylate,
Bismuth subsalicylate,
Sulfosalicylic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
Infobox references

Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone.[9] The name is from Latin salix for willow tree. It is an ingredient in some anti-acne products. Salts and esters of salicylic acid are known as salicylates.

Uses[edit]

Medicine[edit]

Cotton pads soaked in salicylic acid can be used to chemically exfoliate skin.

Salicylic acid as a medication is used commonly to remove the outer layer of the skin. As such, it is used to treat warts, psoriasis, acne vulgaris, ringworm, dandruff, and ichthyosis.[10][11][12][13]

Similar to other hydroxy acids, salicylic acid is an ingredient in many skincare products for the treatment of seborrhoeic dermatitis, acne, psoriasis, calluses, corns, keratosis pilaris, acanthosis nigricans, ichthyosis, and warts.[14]

Uses in manufacturing[edit]

Salicylic acid is used in the production of other pharmaceuticals, including 4-aminosalicylic acid, sandulpiride, and landetimide (via salethamide).

Salicylic acid has long been a key starting material for making acetylsalicylic acid (aspirin).[9] Aspirin (acetylsalicylic acid or ASA) is prepared by the esterification of the phenolic hydroxyl group of salicylic acid with the acetyl group from acetic anhydride or acetyl chloride.

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".[15]

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.

Other uses[edit]

Salicylic acid is used as a food preservative, a bactericide, and an antiseptic.[16]

Sodium salicylate is a useful phosphor in the vacuum ultraviolet spectral range, with nearly flat quantum efficiency for wavelengths between 10 and 100 nm.[17] 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.

Mechanism of action[edit]

Salicylic acid modulates COX-1 enzymatic activity to decrease the formation of pro-inflammatory prostaglandins. Salicylate may competitively inhibit prostaglandin formation. Salicylate's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms.

Salicylic acid works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with nicotinamide adenosine dinucleotide and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid to the phenolic acceptor.

The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis.[6]

Safety[edit]

If high concentrations of salicylic ointment are applied to a large percentage of body surface, high levels of salicylic acid can enter the blood, requiring hemodialysis to avoid further complications.[18]

Production and chemical reactions[edit]

Biosynthesis[edit]

Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana, it can be synthesized via a phenylalanine-independent pathway.

Industrial synthesis[edit]

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 (115 °C) – a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid:

Salicylic-Acid General Synthesis V.2.svg

It can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid)[19] or methyl salicylate (oil of wintergreen) with a strong acid or base.

Reactions[edit]

Upon heating, salicylic acid converts to phenyl salicylate:[20][9]

2 HOC6H4CO2H → C6H5O2C6H4OH + CO2 + H2O

Further heating gives xanthone.[9]

Salicylic acid as its conjugate base is a chelating agent, with an affinity for iron(III).[21]

Salicylic acid slowly degrades to phenol and carbon dioxide at 200–230 °C:[22]

C6H4OH(CO2H) → C6H5OH + CO2

History[edit]

White willow (Salix alba) is a natural source of salicylic acid.

Hippocrates, Galen, Pliny the Elder, and others knew that willow bark could ease pain and reduce fevers.[23] It was used in Europe and China to treat these conditions.[24] This remedy is mentioned in texts from Ancient Egypt, Sumer, and Assyria.[25] The Cherokee and other Native Americans use an infusion of the bark for fever and other medicinal purposes.[26]

In 2014, archaeologists identified traces of salicylic acid on seventh-century pottery fragments found in east-central Colorado.[27] 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.[28]

The active extract of the bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated and named by German chemist Johann Andreas Buchner in 1828.[29] A larger amount of the substance was isolated in 1829 by Henri Leroux, a French pharmacist.[30] Raffaele Piria, an Italian chemist, was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.[31][32]

Salicylic acid was also isolated from the herb meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839.[33] 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]

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.[34] High-salicylate beverages and foods include beer, coffee, tea, numerous fruits and vegetables, sweet potato, nuts, and olive oil.[35] Meat, poultry, fish, eggs, dairy products, sugar, and breads and cereals have low salicylate content.[35][36]

Some people with sensitivity to dietary salicylates may have symptoms of allergic reaction, such as bronchial asthma, rhinitis, gastrointestinal disorders, or diarrhea, so may need to adopt a low-salicylate diet.[35]

Plant hormone[edit]

Salicylic acid is a phenolic phytohormone, and is found in plants with roles in plant growth and development, photosynthesis, transpiration, and ion uptake and transport.[37] Salicylic acid is involved in endogenous signaling, mediating plant defense against pathogens.[38] It plays a role in the resistance to pathogens (i.e. systemic acquired resistance) by inducing the production of pathogenesis-related proteins and other defensive metabolites.[39] Exogenously, salicylic acid can aid plant development via enhanced seed germination, bud flowering, and fruit ripening, though too high of a concentration of salicylic acid can negatively regulate these developmental processes.[40]

The volatile methyl ester of salicylic acid, methyl salicylate, can also diffuse through the air, facilitating plant-plant communication.[41] Methyl salicylate is taken up by the stomata of the nearby plant, where it can induce an immune response after being converted back to salicylic acid.[42]

Signal transduction[edit]

A number of proteins have been identified that interact with SA in plants, especially salicylic acid binding proteins (SABPs) and the NPR genes (Nonexpressor of pathogenesis related genes), which are putative receptors.[43]

History[edit]

In 1979, salicylates were found to be involved in induced defenses of tobacco against tobacco mosaic virus.[44] In 1987, salicylic acid was identified as the long-sought signal that causes thermogenic plants such as the voodoo lily, Sauromatum guttatum, to heat up.[45]

See also[edit]

References[edit]

  1. ^ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 64. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  2. ^ a b c Haynes, William M., ed. (2011). CRC Handbook of Chemistry and Physics (92nd ed.). Boca Raton, FL: CRC Press. p. 3.306. ISBN 1-4398-5511-0.
  3. ^ a b c d e f g h "Salicylic acid". Archived from the original on 2014-05-24. Retrieved 2014-05-23.
  4. ^ a b c d e CID 338 from PubChem
  5. ^ a b c Atherton Seidell; William F. Linke (1952). Solubilities of Inorganic and Organic Compounds: A Compilation of Solubility Data from the Periodical Literature. Supplement. Van Nostrand.
  6. ^ a b Wishart, David S.; Djombou Feunang, Yannick; Guo, An Chi; Lo, Elvis J.; Marcu, Ana; Grant, Jason R.; Sajed, Tanvir; Johnson, Daniel; Li, Carin; Sayeeda, Zinat; Assempour, Nazanin; Iynkkaran, Ithayavani; Liu, Yifeng; Maciejewski, Adam; Gale, Nicola; Wilson, Alex; Chin, Lucy; Cummings, Ryan; Le, Diana; Pon, Allison; Knox, Craig; Wilson, Michael. "Salycylic acid | DrugBank Online". DrugBank. 5.0.
  7. ^ "Salicylic acid". Archived from the original on 2017-02-15. Retrieved 2014-08-17.
  8. ^ a b c Sigma-Aldrich Co., Salicylic acid. Retrieved on 2014-05-23.
  9. ^ a b c d Boullard, Olivier; Leblanc, Henri; Besson, Bernard (2000). "Salicylic Acid". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a23_477. ISBN 3527306730.
  10. ^ "Salicylic acid". Drugs.com. Archived from the original on 18 January 2017. Retrieved 15 January 2017.
  11. ^ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 310. hdl:10665/44053. ISBN 9789241547659.
  12. ^ "SALICYLIC ACID - National Library of Medicine HSDB Database". toxnet.nlm.nih.gov. Archived from the original on 2018-08-21. Retrieved 2018-08-21.
  13. ^ salicylic acid 17 % Topical Liquid. Kaiser Permanente Drug Encyclopedia. Accessed 28 Sept 2011.
  14. ^ Madan RK; Levitt J (April 2014). "A review of toxicity from topical salicylic acid preparations". J Am Acad Dermatol. 70 (4): 788–92. doi:10.1016/j.jaad.2013.12.005. PMID 24472429.
  15. ^ "Bismuth subsalicylate". PubChem. United States National Institutes of Health. Archived from the original on 1 February 2014. Retrieved 24 January 2014.
  16. ^ "Definition of Salicylic acid". MedicineNet.com. Archived from the original on 2011-12-09. Retrieved 2010-10-12.
  17. ^ Samson, James (1976). Techniques of Vacuum Ultraviolet Spectroscopy. Wiley, .
  18. ^ Péc, J.; Strmenová, M.; Palencárová, E.; Pullmann, R.; Funiaková, S.; Visnovský, P.; Buchanec, J.; Lazarová, Z. (October 1992). "Salicylate intoxication after use of topical salicylic acid ointment by a patient with psoriasis". Cutis. 50 (4): 307–309. ISSN 0011-4162. PMID 1424799.
  19. ^ "Hydrolysis of ASA to SA". Archived from the original on August 8, 2007. Retrieved July 31, 2007.
  20. ^ Kuriakose, G.; Nagaraju, N. (2004). "Selective Synthesis of Phenyl Salicylate (Salol) by Esterification Reaction over Solid Acid Catalysts". Journal of Molecular Catalysis A: Chemical. 223 (1–2): 155–159. doi:10.1016/j.molcata.2004.03.057.
  21. ^ Jordan, R. B. (1983). "Metal(III)-Salicylate Complexes: Protonated Species and Rate-Controlling Formation Steps". Inorganic Chemistry. 22 (26): 4160–4161. doi:10.1021/ic00168a070.
  22. ^ Kaeding, Warren W. (1 September 1964). "Oxidation of Aromatic Acids. IV. Decarboxylation of Salicylic Acids". The Journal of Organic Chemistry. 29 (9): 2556–2559. doi:10.1021/jo01032a016.
  23. ^ Norn, S.; Permin, H.; Kruse, P. R.; Kruse, E. (2009). "[From willow bark to acetylsalicylic acid]". Dansk Medicinhistorisk Årbog (in Danish). 37: 79–98. PMID 20509453.
  24. ^ "Willow bark". University of Maryland Medical Center. University of Maryland. Archived from the original on 24 December 2011. Retrieved 19 December 2011.
  25. ^ Goldberg, Daniel R. (Summer 2009). "Aspirin: Turn of the Century Miracle Drug". Chemical Heritage Magazine. 27 (2): 26–30. Archived from the original on 20 March 2018. Retrieved 24 March 2018.
  26. ^ 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] Archived 2007-12-06 at the Wayback Machine A search of this database for "salix AND medicine" finds 63 entries.
  27. ^ "1,300-Year-Old Pottery Found in Colorado Contains Ancient 'Natural Aspirin'". Archived from the original on 2014-08-13. Retrieved 2014-08-13.
  28. ^ Stone, Edmund (1763). "An Account of the Success of the Bark of the Willow in the Cure of Agues". Philosophical Transactions of the Royal Society of London. 53: 195–200. doi:10.1098/rstl.1763.0033.
  29. ^ Buchner, A. (1828). "Ueber das Rigatellische Fiebermittel und über eine in der Weidenrinde entdeckte alcaloidische Substanz (On Rigatelli's antipyretic [i.e., anti-fever drug] and on an alkaloid substance discovered in willow bark)". Repertorium für die pharmacie…. Bei J. L. Schrag. pp. 405–. Noch ist es mir aber nicht geglückt, den bittern Bestandtheil der Weide, den ich Salicin nennen will, ganz frei von allem Färbestoff darzustellen." (I have still not succeeded in preparing the bitter component of willow, which I will name salicin, completely free from colored matter
  30. ^ See:
  31. ^ Piria (1838) "Sur de neuveaux produits extraits de la salicine" Archived 2017-07-27 at the Wayback Machine (On new products extracted from salicine), Comptes rendus6: 620–624. On page 622, Piria mentions "Hydrure de salicyle" (hydrogen salicylate, i.e., salicylic acid).
  32. ^ Jeffreys, Diarmuid (2005). Aspirin: the remarkable story of a wonder drug. New York: Bloomsbury. pp. 38–40. ISBN 978-1-58234-600-7.
  33. ^ Löwig, C.; Weidmann, S. (1839). "III. Untersuchungen mit dem destillierten Wasser der Blüthen von Spiraea Ulmaria (III. Investigations of the water distilled from the blossoms of Spiraea ulmaria). Löwig and Weidman called salicylic acid Spiräasaure (spiraea acid)". Annalen der Physik und Chemie; Beiträge zur Organischen Chemie (Contributions to Organic Chemistry) (46): 57–83.
  34. ^ Malakar, Sreepurna; Gibson, Peter R.; Barrett, Jacqueline S.; Muir, Jane G. (1 April 2017). "Naturally occurring dietary salicylates: A closer look at common Australian foods". Journal of Food Composition and Analysis. 57: 31–39. doi:10.1016/j.jfca.2016.12.008.
  35. ^ a b c "Low salicylate diet". Drugs.com. 19 February 2019. Archived from the original on 16 December 2019. Retrieved 16 December 2019.
  36. ^ Swain, AR; Dutton, SP; Truswell, AS (1985). "Salicylates in foods" (PDF). Journal of the American Dietetic Association. 85 (8): 950–60. doi:10.1016/S0002-8223(21)03743-3. ISSN 0002-8223. PMID 4019987. Archived (PDF) from the original on 2019-04-05. Retrieved 2019-12-16.
  37. ^ Vlot, A. C; Dempsey, D. A; Klessig, D. F (2009). "Salicylic Acid, a multifaceted hormone to combat disease". Annual Review of Phytopathology. 47: 177–206. doi:10.1146/annurev.phyto.050908.135202. PMID 19400653.
  38. ^ Hayat, S. & Ahmad, A. (2007). Salicylic Acid – A Plant Hormone. Springer. ISBN 978-1-4020-5183-8.
  39. ^ 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 or Resistance to Alfalfa Mosaic Virus Infection in Various Plant Species". Journal of General Virology. 67 (10): 2135–2143. doi:10.1099/0022-1317-67-10-2135.
  40. ^ Koo, Young Mo; Heo, A Yeong; Choi, Hyong Woo (February 2020). "Salicylic Acid as a Safe Plant Protector and Growth Regulator". The Plant Pathology Journal. 36 (1): 1–10. doi:10.5423/PPJ.RW.12.2019.0295. ISSN 1598-2254. PMC 7012573. PMID 32089657.
  41. ^ Taiz, L. and Zeiger, Eduardo (2002) Plant Physiology Archived 2014-03-05 at the Wayback Machine, 3rd Edition, Sinauer Associates, p. 306, ISBN 0878938230
  42. ^ Chamowitz, D. (2017). What a plant knows: a field guide to the senses. Brunswick, Vic.: Scribe Publications.
  43. ^ Kumar, D. 2014. Salicylic acid signaling in disease resistance. Plant Science 228:127–134.
  44. ^ Raskin, I. 1992. Salicylate, A New Plant Hormone. Plant Physiol 99:799–803.
  45. ^ Raskin, I., A. Ehmann, W. R. Melander, and B. J. Meeuse. 1987. Salicylic Acid: a natural inducer of heat production in arum lilies. Science 237:1601–1602.

Further reading[edit]

External links[edit]