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

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the formula C₈H₈O₃. It is the methyl

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

salicylic acid 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, and has been listed by the EPA Toxic Substa ...

. It is a colorless,

viscous The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the in ...

liquid with a sweet, fruity odor reminiscent of

root beer Root beer is a sweet 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, sarsaparilla) as the ...

, but often associatively called "minty", as it is an ingredient in mint candies. It is produced by many species of

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ...

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. Mos ...

s. It is also produced synthetically, used as a

fragrance An aroma compound, also known as an odorant, aroma, fragrance or flavoring, 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 sufficiently v ...

and as a flavoring agent.

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

and

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is ...

. The biosynthesis of methyl salicylate arises via the

hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...

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. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin ...

by a

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

followed by methylation by a methylase 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. 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 The Ericaceae are a 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 c.4250 known species spread across 124 genera, making it th ...

, 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 Rosaceae (), the rose family, is a medium-sized family of flowering plants that includes 4,828 known species in 91 genera. The name is derived from the type genus ''Rosa''. Among the most species-rich genera are '' Alchemilla'' (270), ''Sorb ...

, 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, 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, from southern Maine west to southernmost Ontario, and south in the Appalachian Mounta ...

'' (sweet birch) and '' Gaultheria procumbens'' (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. They have sometimes been used to relieve acute or chronic pain, but there is ...

and

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

in deep heating

liniment Liniment (from la, linere, meaning "to anoint"), 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 oth ...

s (such as

Bengay 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. Overview Bengay was developed in France by ...

) 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 used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of the g ...

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 t ...

and mints. 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 to be caused by the separation ...

, 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 Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation ...

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 Scotland, Listerine was ...

mouthwash produced by the

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...

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 meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and la ...

. Methyl salicylate is also used as a bait for attracting male

orchid bee The tribe Euglossini, in the subfamily Apinae, commonly known as orchid bees or euglossine bees, are the only group of corbiculate bees whose non-parasitic members do not all possess eusocial behavior. Description Most of the tribe's species ...

s 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 (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...

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 that attracts some insects, such as the spotted lanternfly. Additional applications include: used as a simulant or surrogate for the research of chemical warfare agent

sulfur mustard Mustard gas or sulfur mustard is a chemical compound belonging to a family of cytotoxic and blister agents known as mustard agents. The name ''mustard gas'' is technically incorrect: the substance, when dispersed, is often not actually a gas, ...

, due to its similar chemical and physical properties, in 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), 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 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 o ...

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, 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 which aspirin is used to treat inc ...

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 Cross country running is a sport in which teams and individuals run a race on open-air courses over natural terrain such as dirt or grass. The course, typically long, may include surfaces of grass and earth, pass through woodlands and open coun ...

at Notre Dame Academy on

Staten Island Staten Island ( ) is a Boroughs of New York City, borough of New York City, coextensive with Richmond County, in the U.S. state of New York (state), New York. Located in the city's southwest portion, the borough is separated from New Jersey b ...

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 in the cir ...

, plasma or

serum Serum may refer to: * Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid *Truth serum, a drug that is likely to mak ...

to confirm a diagnosis of poisoning in hospitalized patients or to assist in an

autopsy An autopsy (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 death or to evaluate any d ...

Compendial status

* British Pharmacopoeia * Japanese Pharmacopoeia

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