Methyl salicylate

Methyl salicylate

Names
IUPAC name Methyl 2-hydroxybenzoate
Other names Salicylic acid methyl ester; Oil of wintergreen; Betula oil; Methyl 2-hydroxybenzoate
Identifiers
CAS Number	119-36-8
3D model (Jmol)	Interactive image
ChEMBL	ChEMBL108545
ChemSpider	13848808
ECHA InfoCard	100.003.925
IUPHAR/BPS	2431
KEGG	D01087
UNII	LAV5U5022Y
InChI InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3 Key: OSWPMRLSEDHDFF-UHFFFAOYSA-N InChI=1/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3 Key: OSWPMRLSEDHDFF-UHFFFAOYAD
SMILES O=C(OC)c1ccccc1O
Properties
Chemical formula	C8H8O3
Molar mass	152.15 g·mol^−1
Density	1.174 g/cm^3
Melting point	−8.6 °C (16.5 °F; 264.5 K)
Boiling point	222 °C (432 °F; 495 K) [1] decomposes at 340-350 °C[2]
Solubility in water	0.639 g/L (21 °C) 0.697 g/L (30°C)[2]
Solubility	miscible in diethyl ether, ethanol[2]
Solubility in acetone	10.1 g/g (30 °C)[2]
Vapor pressure	1 mmHg (54 °C)[1]
Acidity (pKa)	9.8[3]
Refractive index (nD)	1.538
Hazards
Main hazards	Harmful
GHS pictograms	[1]
GHS signal word	Warning
GHS hazard statements	H302[1]
EU classification (DSD)	Xn
R-phrases	R22
NFPA 704	1 2 0
Flash point	96 °C (205 °F; 369 K) [1]
Autoignition temperature	452.7 °C (846.9 °F; 725.8 K) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens. It is also synthetically produced, used as a fragrance, in foods and beverages, and in liniments.

The compound methyl salicylate was first isolated (from the plant Gaultheria procumbens) in 1843 by the French chemist Auguste André Thomas Cahours (1813–1891), who identified it as an ester of salicylic acid and methanol.^[4]

Natural occurrence

Wintergreen plants (Gaultheria procumbens)

This compound is probably produced as an anti-herbivore defense. If the plant is infected with herbivorous insects, the release of methyl salicylate may function as an aid in the recruitment of beneficial insects to kill the herbivorous insects.^[5] Aside from its toxicity, methyl salicylate may also be used by plants as a pheromone to warn other plants of pathogens such as tobacco mosaic virus.^[6]

Numerous plants produce methyl salicylate in very small amounts. Some plants, such as the following, produce more:

• some species of the genus Gaultheria in the family Ericaceae, including Gaultheria procumbens, the wintergreen or eastern teaberry;
• some species of the genus Betula in the family Betulaceae, particularly those in the subgenus Betulenta such as B. lenta, the black birch;
• all species of the genus Spiraea in the family Rosaceae, also called the meadowsweets;
• species of the genus Polygala in the family Polygalaceae.

Commercial production

Methyl salicylate can be produced by esterifying salicylic acid with methanol. Commercial methyl salicylate is now synthesized, but in the past, it was commonly distilled from the twigs of Betula lenta (sweet birch) and Gaultheria procumbens (eastern teaberry or wintergreen).

Uses

Chick embryo that was treated with methylene blue to stain the skeleton, then cleansed with 2 or 3 ethanol washes, and treated with methyl salicylate to make the surrounding tissues transparent

• in high concentrations as a rubefacient and analgesic in deep heating liniments (such as Bengay) to treat joint and muscular pain. Randomised double blind trial reviews report evidence of its effectiveness that is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to counter-irritation. However, in the body it metabolizes into salicylates, including salicylic acid, a known NSAID.^[7][8][9]
• in low concentrations (0.04% and under)^[10] as a flavoring agent in chewing gum and mints. When mixed with sugar and dried it is a potentially entertaining source of triboluminescence, gaining the tendency to build up electrical charge when crushed or rubbed. This effect can be observed by crushing wintergreen Life Savers in a dark room.^[11][12]

• providing fragrance to various products and as an odor-masking agent for some organophosphate pesticides.
• as a bait for attracting male orchid bees for study, which apparently gather the chemical to synthesize pheromones.^[13]
• to clear plant or animal tissue samples of color, and as such is useful for microscopy and immunohistochemistry when excess pigments obscure structures or block light in the tissue being examined. This clearing generally only takes a few minutes, but the tissue must first be dehydrated in alcohol.^[14]
• as a transfer agent, to produce a manual copy of an image on a surface.^[15]
• in small amounts, to lower the freezing point of glacial acetic acid for transport.
• a simulant or surrogate for the research of chemical warfare agent sulfur mustard, due to its similar chemical and physical properties.^[16]
• an antiseptic in Listerine mouthwash produced by the Johnson & Johnson company.^[17]
• restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers. ^[18]

Safety and toxicity

In pure form, methyl salicylate is harmful, when taken orally. A single teaspoon (5 ml) of methyl salicylate contains approximately 6 g of salicylate,^[19] which is equivalent to almost twenty 300 mg aspirin tablets (5 mL * 1.174 g/mL = 5.87 g). The lowest published lethal dose is 101 mg/kg body weight in adult humans,^[20] (or 7.07 grams for a 70-kg adult). It has proven fatal to small children in doses as small as 4 ml.^[10] A seventeen-year-old cross-country runner at Notre Dame Academy on Staten Island died in April 2007 after her body absorbed methyl salicylate through excessive use of topical muscle-pain relief products.^[21]

Most instances of human toxicity due to methyl salicylate are a result of over-application of topical analgesics, especially involving children. Some people have intentionally ingested large amounts of oil of wintergreen. Salicylate, the major metabolite of methyl salicylate, may be quantitated in blood, plasma or serum to confirm a diagnosis of poisoning in hospitalized patients or to assist in an autopsy.^[22]

Compendial status

• British Pharmacopoeia^[23]
• Japanese Pharmacopoeia^[24]

See also

• Trolamine salicylate
• Wood Lock

References

1. Sigma-Aldrich Co., Methyl salicylate. Retrieved on 2013-05-23.
2. "methyl salicylate". chemister.ru.
3. Scully, Frank E.; Hoigné, Jürg (January 1987). "Rate constants for reactions of singlet oxygen with phenols and other compounds in water". Chemosphere. 16 (4): 681–694. doi:10.1016/0045-6535(87)90004-X.
4. See:
   • Cahours, A. (1843) "Recherches sur l'huile de Gaultheria procumbens" (Investigations into the oil of Gaultheria procumbens), Comptes rendus … , 16 : 853-856.
   • Cahours, A. (1843) "Sur quelques réactions du salicylate de méthylène" (On some reactions of methyl salicylate), Comptes rendus … , 17 : 43-47.
5. D. G. James; T. S. Price (August 2004). "Field-testing of methyl salicylate for recruitment and retention of beneficial insects in grapes and hops". J. Chem. Ecol. 30 (8): 1613–28. doi:10.1023/B:JOEC.0000042072.18151.6f. PMID 15537163.
6. Vladimir Shulaev; Paul Silverman; Ilya Raskin (20 February 1997). "Airborne signalling by methyl salicylate in plant pathogen resistance". Nature. 385 (6618): 718–721. Bibcode:1997Natur.385..718S. doi:10.1038/385718a0.
7. "Topical analgesics introduction". Medicine.ox.ac.uk. 2003-05-26. Retrieved 2012-11-07.
8. Mason, L.; Moore, RA; Edwards, JE; McQuay, HJ; Derry, S; Wiffen, PJ (2004). "Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain". BMJ. 328 (7446): 995. doi:10.1136/bmj.38040.607141.EE. PMC 404501. PMID 15033879.
9. Tramer, M. R (2004). "It's not just about rubbing--topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment". BMJ. 328 (7446): 998. doi:10.1136/bmj.328.7446.998. PMC 404503. PMID 15105325.
10. Wintergreen at Drugs.com
11. Harvey, E. N. (1939). "The luminescence of sugar wafers". Science. 90 (2324): 35–36. Bibcode:1939Sci....90...35N. doi:10.1126/science.90.2324.35. PMID 17798129.
12. "Why do Wint-O-Green Life Savers spark in the dark?". HowStuffWorks.
13. Schiestl, F.P.; Roubik, D.W. (2004). "Odor Compound Detection in Male Euglossine Bees". Journal of Chemical Ecology. 29 (1): 253–257. doi:10.1023/A:1021932131526. PMID 12647866.
14. Altman, J.S.; Tyrer, N.M. (1980). "Filling selected neurons with cobalt through cut axons". In NJ Strausfeld, N.J.; Miller, T.A. Neuroanatomical Techniques. Springer-Verlag. pp. 373–402. Missing or empty |title= (help)
15. Image Transfer at Making-greeting-cards.com
16. Bartlet-Hunt, S. L.; Knappe, Detlef R. U.; et al. (2008). "A Review of Chemical Warfare Agent Simulants for the Study of Environmental Behaviour". Critical Reviews in Environmental Science and Technology. 38 (2): 112–136. doi:10.1080/10643380701643650.
17. Listerine. "Original Listerine Antiseptic Mouthwash". Retrieved 25 March 2015.
18. "MG Chemicals - Rubber Renue Safety Data Sheet" (PDF).
19. "Salicylate Poisoning - Patient UK". Patient.info. 2011-04-20. Retrieved 2013-07-01.
20. Safety data for methyl salicylate, Physical & Theoretical Chemistry Laboratory, Oxford University
21. "Muscle-Pain Reliever Is Blamed For Staten Island Runner's Death". New York Times. 10 June 2007.
22. Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1012–1014. ISBN 978-0-9626523-7-0.
23. The British Pharmacopoeia Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on 11 April 2009. Retrieved 5 July 2009.
24. "NIHS Japan". Moldb.nihs.go.jp. Retrieved 2013-07-01.

External links

• MedlinePlus - Methyl salicylate overdose
• MedlinePlus - Sports cream overdose
• CNN - Medical examiner: Sports cream caused teen's death Wayback machine link to this article
• NLM Hazardous Substances Databank – Methyl salicylate