Methyl salicylate (oil of wintergreen or wintergreen oil) is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula C₈H₈O₃. It is the methyl

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a active metabolite, metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been lis ...

. It is a colorless,

viscous Viscosity is a measure of a fluid's rate-dependent resistance to a change in shape or to movement of its neighboring portions relative to one another. For liquids, it corresponds to the informal concept of ''thickness''; for example, syrup h ...

liquid with a sweet, fruity odor reminiscent of

root beer Root beer is a North American soft drink traditionally made using the root bark of the sassafras tree '' Sassafras albidum'' or the vine of '' Smilax ornata'' (known as sarsaparilla; also used to make a soft drink called sarsaparilla) as the ...

(in which it is used as a flavoring), but often associatively called "minty", as it is an ingredient in mint candies. It is produced by many species of

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

s, particularly

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

s. It is also produced synthetically, used as a

fragrance An aroma compound, also known as an odorant, aroma, fragrance, flavoring or flavor, is a chemical compound that has a smell or odor. For an individual chemical or class of chemical compounds to impart a smell or fragrance, it must be sufficien ...

and as a flavoring agent.

Biosynthesis and occurrence

Methyl salicylate was first isolated (from the plant ''

Gaultheria procumbens ''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 sou ...

'') in 1843 by the French chemist

Auguste André Thomas Cahours August André Thomas Cahours (1813–1891) was a French chemist and scientist whose contribution to organic chemistry was one of the greatest in history. He discovered, among other things, the processes of synthesis of several chemical molecules, i ...

(1813–1891), who identified it as an

and

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

. The biosynthesis of methyl salicylate arises via the

hydroxylation In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

benzoic acid Benzoic acid () is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. The benzoyl group is often abbreviated "Bz" (not to be confused with "Bn," which ...

by a

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

followed by reaction with a methyltransferase enzyme.

Methyl salicylate as a plant metabolite

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. 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, notably

hoverflies Hoverflies, also called flower flies or syrphids, make up the insect family (biology), family Syrphidae. As their common name suggests, they are often seen Hover (behaviour), hovering or nectaring at flowers; the adults of many species feed main ...

, lacewings, and lady beetles. 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 ''Gaultheria'' is a genus of about 283 species of shrubs in the family Ericaceae. The name commemorates Jean François Gaultier of Quebec, an honour bestowed by the Scandinavian Pehr Kalm in 1748 and taken up by Carl Linnaeus in his '. These pl ...

'' in the family

Ericaceae The Ericaceae () are a Family (biology), family of flowering plants, commonly known as the heath or heather family, found most commonly in acidic and infertile growing conditions. The family is large, with about 4,250 known species spread acros ...

, including ''

'', the wintergreen or eastern teaberry; some species of the genus ''

Betula A birch is a thin-leaved deciduous hardwood tree of the genus ''Betula'' (), in the family Betulaceae, which also includes alders, hazels, and hornbeams. It is closely related to the beech- oak family Fagaceae. The genus ''Betula'' contains 3 ...

'' in the family

Betulaceae Betulaceae, the birch family, includes six genera of deciduous nut-bearing trees and shrubs, including the birches, alders, hazels, hornbeams, hazel-hornbeam, and hop-hornbeams, numbering a total of 167 species. They are mostly natives of ...

, particularly those in the subgenus ''Betulenta'' such as ''B. lenta'', the black birch; all species of the genus ''

Spiraea ''Spiraea'' , sometimes spelled spirea in common names, and commonly known as meadowsweets or steeplebushes, is a genus of about 80 to 100 species

'' in the family

Rosaceae Rosaceae (), the rose family, is a family of flowering plants that includes 4,828 known species in 91 genera. The name is derived from the type genus '' Rosa''. The family includes herbs, shrubs, and trees. Most species are deciduous, but som ...

, also called the meadowsweets; species of the genus ''

Polygala ''Polygala'' is a large genus of flowering plants belonging to the family Polygalaceae. They are commonly known as milkworts or snakeroots. The genus is distributed widely throughout much of the worldPolygalaceae. Methyl salicylate can also be a component of

floral scent Floral scent, or flower scent, is composed of all the volatile organic compounds (VOCs), or aroma compounds, emitted by floral tissue (e.g. flower petals). Other names for floral scent include, aroma, fragrance, floral odour or perfume. Flower sce ...

s, especially in plants dependent on nocturnal pollinators like moths, scarab beetles, and (nocturnal) bees.

Commercial production

Methyl salicylate can be produced by esterifying

with

. Commercial methyl salicylate is now synthesized, but in the past, it was commonly distilled from the twigs of ''

Betula lenta ''Betula lenta'' (sweet birch, also known as black birch, cherry birch, mahogany birch, or spice birch) is a species of birch native to eastern North America. Description ''Betula lenta'' is a medium-sized deciduous tree reaching tall, except ...

'' (sweet birch) and ''

'' (eastern teaberry or wintergreen).

Uses

Methyl salicylate is used in high concentrations as a

rubefacient 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 limi ...

and

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

in deep heating

liniment Liniment (from , meaning "to smear, Anointing, anoint"), also called embrocation and heat rub, is a medicated topical preparation for application to the skin. Some liniments have a viscosity similar to that of water; others are lotion or balm; s ...

s (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 Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

. Methyl salicylate is used in low concentrations (0.04% and under)Wintergreen
at Drugs.com as a

flavoring A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive that is used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of ...

agent in

chewing gum Chewing gum is a soft, cohesive substance designed to be chewed without being swallowed. Modern chewing gum is composed of gum base, sweeteners, softeners/plasticizers, flavors, colors, and, typically, a hard or powdered polyol coating. Its tex ...

mints A mint or breath mint is a food item often consumed as an after-meal refreshment or before business and social engagements to improve breath odor. Mints are commonly believed to soothe the stomach, given their association with natural byproducts ...

and

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

such as Pepto-Bismol. When mixed with sugar and dried, it is a potentially entertaining source of

triboluminescence Triboluminescence is a phenomenon in which light is generated when a material is mechanically pulled apart, ripped, scratched, crushed, or rubbed (see tribology). The phenomenon is not fully understood but appears in most cases to be caused by the ...

, for example by crushing Wint-O-Green

Life Savers Life Savers (stylized as LifeSavers) is an American brand of ring-shaped hard and soft candy. Its range of mints and fruit-flavored candies is known for its distinctive packaging, coming in paper-wrapped aluminum foil rolls. Candy manufacturer ...

in a dark room. When crushed, sugar crystals emit light; methyl salicylate amplifies the spark because it fluoresces, absorbing

ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...

light and re-emitting it in the visible spectrum. It is used as an antiseptic in

Listerine Listerine (, ) is an American 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 United Kingdom, L ...

mouthwash produced by the

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational pharmaceutical, biotechnology, and medical technologies corporation headquartered in New Brunswick, New Jersey, and publicly traded on the New York Stock Exchange. Its common stock is a c ...

company. It provides

to various products and as an odor-masking agent for some

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

pesticides Pesticides are substances that are used to pest control, control pest (organism), pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for a ...

. Methyl salicylate is also used as a bait for attracting male orchid bees for study, which apparently gather the chemical to synthesize pheromones, and to clear plant or animal tissue samples of color, and as such is useful for microscopy and

immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

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. It has also been discovered that methyl salicylate works as a

kairomone A kairomone is a semiochemical released by an organism that mediates interspecific interactions in a way that benefits a different species at the expense of the emitter. Derived from the Greek καιρός, meaning "''opportune moment""kairomon ...

that attracts some insects, such as the spotted lanternfly. Unlike some other kairomone's, Methyl Salicylate attracts all stages of the spotted lanternflies life. Other niche uses include: * as a simulant or surrogate for the research of chemical warfare agent

sulfur mustard Mustard gas or sulfur mustard are names commonly used for the organosulfur chemical compound bis(2-chloroethyl) sulfide, which has the chemical structure S(CH2CH2Cl)2, as well as other species. In the wider sense, compounds with the substituen ...

, due to its similar chemical and physical properties; * restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers; * as a transfer agent in printmaking (to release toner from photocopied images and apply them to other surfaces); * as a historical substitute for

cedar oil Cedar oil, also known as cedarwood oil, is an essential oil derived from various types of Pinophyta, conifers, most in the Pinaceae, pine or Cupressaceae, cypress List of trees and shrubs by taxonomic family, botanical families. It is produced fro ...

as an immersion oil in microscopy, given its refractive index (1.538) being close to that of crown glass (1.515) and being less prone to

drying Drying is a mass transfer process consisting of the removal of water or another solvent by evaporation from a solid, semi-solid or liquid. This process is often used as a final production step before selling or packaging products. To be consider ...

than cedar oil; * 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 An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the ...

solution. A single teaspoon (5 mL) of methyl salicylate contains approximately 6 g of salicylate, which is equivalent to almost twenty 300 mg

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

tablets (5mL × 1.174g/mL = 5.87g). 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 140mg/kg of salicylates for a 10kg child (22lbs). The lowest published lethal dose is 101 mg/kg body weight in adult humans, (or 7.07 grams for a 70 kg adult). It has proven fatal to small children in doses as small as 4 mL. A seventeen-year-old cross-country runner at Notre Dame Academy on

Staten Island Staten Island ( ) is the southernmost of the boroughs of New York City, five boroughs of New York City, coextensive with Richmond County and situated at the southernmost point of New York (state), New York. The borough is separated from the ad ...

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). 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 Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

, plasma or serum which may help professionals to confirm a diagnosis of poisoning in hospitalized patients or to assist in an

autopsy An autopsy (also referred to as post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of deat ...

Compendial status

British Pharmacopoeia The ''British Pharmacopoeia'' (''BP'') is the national pharmacopoeia of the United Kingdom. It is an annually published collection of quality standards for medicinal substances in the UK, which is used by individuals and organisations involve ...

Japanese Pharmacopoeia The is the official pharmacopoeia of Japan. It is published by the . The first edition was published on 25 June 1886, with revisions being issued from time to time. The current revision is number 18, issued electronically on 7 June 2021. An off ...

References

External links

MedlinePlus – Methyl salicylate overdose

ttps://web.archive.org/web/20070610200503/http://www2.cnn.com/2007/US/06/09/musclecream.death.ap/index.html Wayback machine link to this article
NLM Hazardous Substances Databank – Methyl salicylate
{{DEFAULTSORT:Methyl Salicylate Commercialization of traditional medicines Flavors Methyl esters Salicylate esters 3-Hydroxypropenals Sweet-smelling chemicals Substances discovered in the 19th century

Biosynthesis and occurrence

Methyl salicylate as a plant metabolite

Commercial production

Uses

Safety and toxicity

Compendial status

See also

References

External links