Methyl salicylate is an organic compound with the formula C6H4. It is the methyl ester of salicylic acid. It is a colorless, viscous liquid with a sweet, fruity odor reminiscent of root beer, but often associatively called "minty," as it is an ingredient in mint candies. It is produced by many species of plants, particularly wintergreens. It is also produced synthetically, used as a fragrance, in foods and beverages, and in liniments.
Biosynthesis and occurrence
Methyl salicylate was first isolated in 1843 by the French chemist Auguste André Thomas Cahours, who identified it as an ester of salicylic acid and methanol. The biosynthesis of methyl salicylate arises via the hydroxylation of benzoic acid by a cytochrome P450 followed by methylation by a methylase enzyme. Methyl salicylate 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. 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. 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 and Gaultheria procumbens.
Uses
Methyl salicylate is used in high concentrations as a rubefacient and analgesicin deep heating liniments 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. Methyl salicylate is used in low concentrations 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, which can be observed by crushing wintergreen Life Savers in a dark room. It is used as an antiseptic in Listerine mouthwash produced by the Johnson & Johnson company. It provides fragrance to various products and as an odor-masking agent for some organophosphatepesticides. 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 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. Additional applications include: used as a simulant or surrogate for the research of chemical warfare agentsulfur mustard, due to its similar chemical and physical properties., in restoring the elastomeric properties of old rubber rollers, especially in printers, and as a penetrating oil to loosen rusted parts.
Safety and toxicity
Methyl salicylate is potentially deadly, especially for young children. A single teaspoon of methyl salicylate contains approximately 6 g of salicylate, which is equivalent to almost twenty 300 mg aspirin tablets. 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. The lowest published lethal dose is 101 mg/kg body weight in adult humans,. 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 died in April 2007 after her body absorbed methyl salicylate through excessive use of topical muscle-pain relief products. Most instances of human toxicity due to methyl salicylate are a result of over-application of topical analgesics, especially involving children. 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.
