Methyl salicylate

Last updated
Methyl salicylate
Methyl salicylate.svg
Methyl salicylate 3D ball.png
Methyl salicylate 3D spacefill.png
Sample of methyl salicylate.jpg
Names
Preferred IUPAC name
Methyl 2-hydroxybenzoate
Other names
  • Salicylic acid methyl ester
  • Oil of wintergreen
  • Betula oil
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.925 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-317-7
KEGG
PubChem CID
RTECS number
  • VO4725000
UNII
  • InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3 Yes check.svgY
    Key: OSWPMRLSEDHDFF-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3
    Key: OSWPMRLSEDHDFF-UHFFFAOYAD
  • O=C(OC)c1ccccc1O
Properties
C8H8O3
Molar mass 152.149 g/mol
AppearanceColorless liquid
Odor Sweet, rooty
Density 1.174 g/cm3
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]
0.639 g/L (21 °C)
0.697 g/L (30 °C) [2]
Solubility Miscible in organic solvents
Solubility in acetone 10.1 g/g (30 °C) [2]
Vapor pressure 1 mmHg (54 °C) [1]
Acidity (pKa)9.8 [3]
−8.630×10−5 cm3/mol
1.538
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
Harmful
GHS labelling:
GHS-pictogram-exclam.svg [1]
Warning
H302 [1]
P264, P270, P280, P301+P312, P302+P352, P305+P351+P338, P321, P330, P332+P313, P337+P313, P362, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point 96 °C (205 °F; 369 K) [1]
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).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic compound with the formula C8H8O3. It is the methyl ester of salicylic acid. It is a colorless, viscous liquid with a sweet, fruity odor reminiscent of root beer (in which it is used as a flavoring), [4] but often associatively called "minty", as it is an ingredient in mint candies. [5] It is produced by many species of plants, particularly wintergreens. It is also produced synthetically, used as a fragrance and as a flavoring agent.

Contents

Biosynthesis and occurrence

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. [6] [7]

The biosynthesis of methyl salicylate arises via the hydroxylation of benzoic acid by a cytochrome P450 followed by reaction with a methyltransferase enzyme. [8]

Methyl salicylate as a plant metabolite

Wintergreen plants (Gaultheria procumbens) Gaultheria procumbens.JPG
Wintergreen plants ( Gaultheria procumbens )

Many plants produce methyl salicylate in small quantities. Methyl salicylate levels are often upregulated in response to biotic stress, especially infection by pathogens, where it plays a role in the induction of resistance. Methyl salicylate is believed to function by being metabolized to the plant hormone salicylic acid. Since methyl salicylate is volatile, these signals can spread through the air to distal parts of the same plant or even to neighboring plants, whereupon they can function as a mechanism of plant-to-plant communication, "warning" neighbors of danger. [9] Methyl salicylate is also released in some plants when they are damaged by herbivorous insects, where they may function as a cue aiding in the recruitment of predators. [10]

Some plants produce methyl salicylate in larger quantities, where it likely involved in direct defense against predators or pathogens. Examples of this latter class include: 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. Methyl salicylate can also be a component of floral scents, especially in plants dependent on nocturnal pollinators like moths, [11] scarab beetles, and (nocturnal) bees. [12]

Commercial production

Methyl salicylate can be produced by esterifying salicylic acid with methanol. [13] 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 two or three ethanol washes, and treated with methyl salicylate to make the surrounding tissues transparent Chick embryo in methyl salicylate.jpg
Chick embryo that was treated with methylene blue to stain the skeleton, then cleansed with two or three ethanol washes, and treated with methyl salicylate to make the surrounding tissues transparent

Methyl salicylate is used in high concentrations as a rubefacient and analgesic in deep heating liniments (such as Bengay) to treat joint and muscular pain. Randomised double blind trials report that evidence of its effectiveness is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to counterirritation. However, in the body it metabolizes into salicylates, including salicylic acid, a known NSAID. [14] [15] [16]

Methyl salicylate is used in low concentrations (0.04% and under) [17] as a flavoring agent in root beer, [4] chewing gum, mints and medicine such as Pepto-Bismol. When mixed with sugar and dried, it is a potentially entertaining source of triboluminescence, for example by crushing Wint-O-Green Life Savers in a dark room. When crushed, sugar crystals emit light; methyl salicylate amplifies the spark because it fluoresces, absorbing ultraviolet light and re-emitting it in the visible spectrum. [18] [19] It is used as an antiseptic in Listerine mouthwash produced by the Johnson & Johnson company. [20] It provides fragrance to various products and as an odor-masking agent for some organophosphate pesticides.[ citation needed ]

Methyl salicylate is also used as a bait for attracting male orchid bees for study, which apparently gather the chemical to synthesize pheromones, [21] and 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. [22] It has also been discovered that methyl salicylate works as a kairomone that attracts some insects, such as the spotted lanternfly. Unlike some other kairomone's, Methyl Salicylate attracts all stages of the spotted lanternflies life. [23]

Additional applications include: used as a simulant or surrogate for the research of chemical warfare agent sulfur mustard, due to its similar chemical and physical properties, [24] in restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers, [25] as a transfer agent in printmaking (to release toner from photocopied images and apply them to other surfaces), [26] and as a penetrating oil to loosen rusted parts.

Safety and toxicity

Methyl salicylate is potentially deadly, especially for young children who may accidentally ingest preparations containing methyl salicylate, such as an essential oil solution. A single teaspoon (5 mL) of methyl salicylate contains approximately 6 g of salicylate, [27] which is equivalent to almost twenty 300 mg aspirin tablets (5 mL × 1.174 g/mL = 5.87 g). Toxic ingestions of salicylates typically occur with doses of approximately 150 mg/kg body weight. This can be achieved with 1 mL of oil of wintergreen, which equates to 140 mg/kg of salicylates for a 10 kg child (22 lbs). [28] The lowest published lethal dose is 101 mg/kg body weight in adult humans, [29] [30] (or 7.07 grams for a 70 kg adult). It has proven fatal to small children in doses as small as 4 mL. [17] 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 (using multiple patches against the manufacturer's instructions). [31]

Most instances of human toxicity due to methyl salicylate are a result of overapplication of topical analgesics, especially involving children. Salicylate, the major metabolite of methyl salicylate, may accumulate in blood, plasma or serum which may help professionals to confirm a diagnosis of poisoning in hospitalized patients or to assist in an autopsy. [32]

Compendial status

See also

Related Research Articles

<span class="mw-page-title-main">Aspirin</span> Medication

Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.

<span class="mw-page-title-main">Listerine</span> Brand of mouthwash

Listerine is a brand of antiseptic mouthwash that is promoted with the slogan "Kills germs that cause bad breath". Named after Joseph Lister, who pioneered antiseptic surgery at the Glasgow Royal Infirmary in Scotland, Listerine was developed in 1879 by Joseph Lawrence, a chemist in St. Louis, Missouri.

<span class="mw-page-title-main">Salicylic acid</span> Chemical compound used in medicines and industry

Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or, white), bitter-tasting solid, it is a precursor to and a metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been listed by the EPA Toxic Substances Control Act (TSCA) Chemical Substance Inventory as an experimental teratogen. The name is from Latin salix for willow tree, from which it was initially identified and derived. It is an ingredient in some anti-acne products. Salts and esters of salicylic acid are known as salicylates.

<span class="mw-page-title-main">Rubbing alcohol</span> Alcohol used for germ protection

Rubbing alcohol is either an isopropyl alcohol or an ethanol-based liquid, with isopropyl alcohol products being the most widely available. The comparable British Pharmacopoeia (BP) is surgical spirit. Rubbing alcohol is denatured and undrinkable even if it is ethanol-based, due to the bitterants added.

<span class="mw-page-title-main">Menthol</span> Organic compound used as flavouring and analgesic

Menthol is an organic compound, specifically a monoterpenoid, that occurs naturally in the oils of several plants in the mint family, such as corn mint and peppermint. It is a white or clear waxy crystalline substance that is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is (−)-menthol, which is assigned the (1R,2S,5R) configuration.

A rubefacient is a substance for topical application that produces redness of the skin, e.g. by causing dilation of the capillaries and an increase in blood circulation. It has sometimes been used to relieve acute or chronic pain, but there is limited evidence as to its efficacy, and as of 2014 the best evidence does not support using gels and creams containing rubefacients for this purpose.

<span class="mw-page-title-main">Bismuth subsalicylate</span> Antacid medication

Bismuth subsalicylate, sold generically as pink bismuth and under brand names including Pepto-Bismol, Pepti-Calm and BisBacter, is a medication used to treat temporary discomfort of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea.

<span class="mw-page-title-main">Liniment</span> Ointment-like medicated topical preparation for application to skin

Liniment, also called embrocation and heat rub, is a medicated topical preparation for application to the skin. Some liniments have viscosity similar to that of water; others are lotion or balm; still others are in transdermal patches, soft solid sticks, and sprays. Liniment usually is rubbed in to the skin, which the active ingredients penetrate.

<i>Gaultheria procumbens</i> Species of flowering plant

Gaultheria procumbens, also called the eastern teaberry, the checkerberry, the boxberry, or the American wintergreen, is a species of Gaultheria native to northeastern North America from Newfoundland west to southeastern Manitoba, and south to Alabama. It is a member of the Ericaceae.

<span class="mw-page-title-main">Wintergreen</span> Small shrub in the Heath family

Wintergreen is a group of aromatic plants. The term wintergreen once commonly referred to plants that remain green throughout the winter. The term evergreen is now more commonly used for this characteristic.

<span class="mw-page-title-main">Trolamine salicylate</span> Chemical compound

Trolamine salicylate is an organic compound with the chemical formula [HN(CH2CH2OH)3]+C6H4(OH)(COO−). It is a salt of triethanolamine and salicylic acid, i.e. the compound consists of protonated triethanolamine and the conjugate base of salicylic acid, salicate.

<span class="mw-page-title-main">Ethyl salicylate</span> Chemical compound

Ethyl salicylate is the ester formed by the condensation of salicylic acid and ethanol. It is a clear liquid that is sparingly soluble in water, but soluble in alcohol and ether. It has a pleasant odor resembling wintergreen and is used in perfumery and artificial flavors.

Systemic acquired resistance (SAR) is a "whole-plant" resistance response that occurs following an earlier localized exposure to a pathogen. SAR is analogous to the innate immune system found in animals, and although there are many shared aspects between the two systems, it is thought to be a result of convergent evolution. The systemic acquired resistance response is dependent on the plant hormone, salicylic acid.

<span class="mw-page-title-main">Eucalyptus oil</span> Distilled oil from the leaf of Eucalyptus

Eucalyptus oil is the generic name for distilled oil from the leaf of Eucalyptus, a genus of the plant family Myrtaceae native to Australia and cultivated worldwide. Eucalyptus oil has a history of wide application, as a pharmaceutical, antiseptic, repellent, flavouring, fragrance and industrial uses. The leaves of selected Eucalyptus species are steam distilled to extract eucalyptus oil.

Bengay, spelled Ben-Gay before 1995, is a topical analgesic heat rub for temporary relief from muscle and joint pain associated with arthritis, bruises, simple backaches, overuse, sprains and strains.

Sodium salicylate is a sodium salt of salicylic acid. It can be prepared from sodium phenolate and carbon dioxide under higher temperature and pressure. Historically, it has been synthesized by refluxing methyl salicylate with an excess of sodium hydroxide.

<span class="mw-page-title-main">Benzyl salicylate</span> Chemical compound

Benzyl salicylate is a salicylic acid benzyl ester, a chemical compound most frequently used in cosmetics as a fragrance additive or UV light absorber. It appears as an almost colorless liquid with a mild odor described as "very faint, sweet-floral, slightly balsamic" by some, while others smell nothing at all. There is debate whether the odour is caused solely by impurities or a genetic predisposition. It occurs naturally in a variety of plants and plant extracts and is widely used in blends of fragrance materials.

<span class="mw-page-title-main">Salicylate poisoning</span> Medical condition

Salicylate poisoning, also known as aspirin poisoning, is the acute or chronic poisoning with a salicylate such as aspirin. The classic symptoms are ringing in the ears, nausea, abdominal pain, and a fast breathing rate. Early on, these may be subtle, while larger doses may result in fever. Complications can include swelling of the brain or lungs, seizures, low blood sugar, or cardiac arrest.

<span class="mw-page-title-main">Aromatherapy</span> Alternative medicine practice

Aromatherapy is a practice based on the use of aromatic materials, including essential oils and other aroma compounds, with claims for improving psychological well-being. It is used as a complementary therapy or as a form of alternative medicine, and typically is used via inhalation and not by ingestion.

<span class="mw-page-title-main">Medical uses of salicylic acid</span> Overview of a common topical medication

Salicylic acid is used as a medicine to help remove the outer layer of the skin. As such it is used to treat warts, skin tags, calluses, psoriasis, dandruff, acne, ringworm, and ichthyosis. For conditions other than warts, it is often used together with other medications. It is applied to the area affected.

References

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