METHYL SALICYLATE
METHYL SALICYLATE
Methyl salicylate = MeSA = Synthetic Wintergreen Oil = Salicylic acid, methyl ester
CAS Number: 119-36-8
EC Number: 204-317-7
Chemical formula: C8H8O3
Molar mass: 152.149 g/mol
Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic compound with the formula C6H4(OH)(CO2CH3).
Methyl salicylate is the methyl ester of salicylic acid.
Methyl salicylate 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.
Methyl salicylate is produced by many species of plants, particularly wintergreens.
Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.
Methyl salicylate is also produced synthetically, used as a fragrance and as a flavoring agent.
Methyl salicylate is a liquid methyl ester of salicylic acid with a distinct characteristic odor.
Methyl salicylate is colorless or light pale in color, and commonly known as synthetic oil of wintergreen (made from the distillation of wintergreen leaves).
Over-thecounter methyl salicylate preparations can be found in cosmetics, flavorings, and perfumes.
The most familiar medicinal use of methyl salicylate is as a counter-irritant, analgesic, and local anesthetic for relief of aches, pain, and stiffness in muscles, joints, and tendons.
Methyl salicylate is used in low concentrations (0.04% and under) as a flavoring agent in chewing gum and mints.
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.
Methyl salicylate is used as an antiseptic in Listerine mouthwash produced by the Johnson & Johnson company.
Methyl salicylate provides fragrance to various products and as an odor-masking agent for some organophosphate pesticides.
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.
Methyl salicylate 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, due to its similar chemical and physical properties., in restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers, and as a penetrating oil to loosen rusted parts.
Methyl salicylate has a long history of use in consumer products as a counterirritant and as an analgesic in the treatment and temporary management of aching and painful muscles and joints.
Methyl salicylate is also used in suntan lotions (as an UV-absorber) and perfumery as a modifier of blossom fragrances.
The pesticidal uses of methyl salicylate include vertebrate repellent on terrestrial and greenhouse food crops and as an insect repellent when incorporated into a coating on the internal and outer surfaces of cartons used to store consumer products like human and pet foods, animal feeds and nonfood items such as clothing and textiles.
What is methyl salicylate?
Methyl salicylate is an external analgesic available in over-the-counter (OTC) medicines that temporarily relieve minor body aches and muscle and joint pain associated with backache, arthritis, strains, sprains, and bruises.
Methyl salicylate can be found in topical pain medicines (e.g., creams or ointments) that contain more than one external analgesic active ingredient.
What is methyl salicylate used to treat?
Relieves minor body aches
Relieves muscle and joint pain
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.
What is methyl salicylate topical?
Methyl salicylate topical (for the skin) is used for temporary relief of minor aches and pains caused by strains, sprains, arthritis, bruising, nerve pain, simple backache, or pain in the lower spine.
Methyl salicylate topical may also be used for purposes not listed in this medication guide.
Preferred IUPAC name
Methyl 2-hydroxybenzoate
Other names
Salicylic acid methyl ester
Oil of wintergreen
Betula oil
This product is used to treat minor aches and pains of the muscles/joints (such as arthritis, backache, sprains).
Menthol and methyl salicylate work by causing the skin to feel cool and then warm.
These feelings on the skin distract you from feeling the aches/pains deeper in your muscles and joints.
This product should not be used by children younger than 18 years without a doctor’s advice.
Check the ingredients on the label even if you have used the product before.
The manufacturer may have changed the ingredients.
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-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, 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, scarab beetles, and (nocturnal) bees.
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).
Methyl salicylate is an aromatic ester whose principal natural source is wintergreen (Gaultheria procumbens) and sweet birch (Betula lenta) plants.
Methyl salicylates history is intertwined with that of salicylic acid and its other derivatives, all of which were recognized by early man as having theraputic values (see sidebar).
Methyl salicylates organoleptic nature is viewed positively in North America.
Wintergreen is still referred to as “mountain tea” in some areas of the US.
Methyl salicylates use as a refreshing and medicinal beverage carried over into that country’s popular soft drinks: birch beer, root beer and sarsaparilla.
With the demise of sassafras oil (due to its safrole content), methyl salicylate was employed to re-construct America’s uniquely flavored national beverages.
In the world’s soft drink market, North America is the only place where these three beverages are consumed.
Outlanders usually find the taste of these soft drinks repulsive.
This different attitude toward methyl salicylate reflects itself in differences in organoleptic description of this aroma chemical, depending on whether the describer is an American or a European cousin.
These cultural orientations have resulted in wintergreen-based oral hygiene products finding acceptance in North America and the Philippines, and to a lesser extent in Great Britain, while the rest of the world shuns them.
Almost 50% of the North American toothpaste flavor market is wintergreen-based, versus nil in the rest of the world.
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.
The biosynthesis of methyl salicylate arises via the hydroxylation of benzoic acid by a cytochrome P450 followed by methylation by a methylase enzyme.
Salicylic acid, methyl salicylate, and other molecules that are derived from salicylic acid belong to a group of molecules called salicylates.
While these structures may appear to be very similar, they actually perform radically different effects on various tissues of the body.
Let’s first examine Salicylic acid.
The chemical structure of Salicylic acid (C7H6O3) includes a benzene ring with an alcohol (-OH) and a carboxylic acid (-COOH) functional group attached to it (see image attached here).
The image attached shows the full chemical and skeletal formulas of salicylic acid.
Chemists use skeletal formulas as a shortcut when drawing chemical structures.
In a skeletal formula, each line indicates a bond, and a carbon is represented by two lines coming together at an angle.
In the case of a benzene ring, there are three lines and three double lines indicating three single bonds and three double bonds.
There are six corners, which indicate six carbon atoms.
Hydrogen atoms that are bonded to carbons are not shown in skeletal formulas.
However, hydrogens are included if they are bonded to an oxygen or another non-carbon atom (as in the case of alcohols and carboxylic acids).
Salicylic acid is naturally derived from the bark of white willows or the leaves of wintergreens, like the methyl salicylate we see in Wintergreen essential oil.
Because salicylic acid isn’t a volatile aromatic compound, Methyl salicylate isn’t found in the essential oils of these plants.
However, salicylic acid is an important ingredient in many skin care products for its exfoliating and cleansing properties.
Another well-known salicylate is acetylsalicylic acid, commonly referred to as aspirin.
The chemical structure of aspirin differs from salicylic acid in that the aspirin structure replaces the alcohol functional group in salicylic acid with an ester functional group.
While this may seem like a minor change in structure, Methyl salicylate results in very different properties.
Over-the-counter aspirin is commonly used to treat minor pain and to help manage inflammation.
Methyl salicylate also can inhibit some of the pathways involved in platelet aggregation (blood clotting) and is commonly used as a blood thinner.
Methyl Salicylate
When you open a bottle of Wintergreen essential oil, you will immediately notice its crisp, minty aroma.
What you’re smelling is actually just one very special chemical constituent: methyl salicylate.
Similar to salicylic acid, methyl salicylate (C8H8O3) is constituted of a benzene ring with an alcohol functional group attached.
However, instead of a carboxylic acid group like in the case of salicylic acid, methyl salicylate contains a methyl ester functional group in its place.
Many over-the-counter ointments and salves for acute joint and muscular discomfort contain methyl salicylate as the active (working) ingredient.
Methyl salicylate can be soothing to fatigued or strained muscles and joints.
This is part of the reason why applying diluted Wintergreen essential oil or Deep Blue rub to these tissues after exercise can be so beneficial.
CAS Number: 119-36-8
CHEBI:31832
ChEMBL: ChEMBL108545
ChemSpider: 13848808
ECHA InfoCard: 100.003.925
EC Number: 204-317-7
IUPHAR/BPS: 2431
KEGG: D01087
PubChem CID: 4133
RTECS number: VO4725000
UNII: LAV5U5022Y
CompTox Dashboard (EPA): DTXSID5025659
How much methyl salicylate can you take?
Different types of products containing this active ingredient have different strengths.
That’s why Methyl salicylate is always important to read and follow the Drug Facts label.
Most medicines warn against use of an active ingredient for longer than 7-10 days.
Stop use and ask a doctor if symptoms persist.
Methyl salicylate produces the familiar odor and flavor of oil of wintergreen.
This chemical relative of aspirin also relieves the inflammation that causes headaches and muscle pain.
Concentrated methyl salicylate is toxic, especially to children, but small amounts may be used as flavorings and in topical creams.
Chemical formula: C8H8O3
Molar mass: 152.149 g/mol
Appearance: Colorless 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)
Decomposes at: 340–350 °C
Solubility in water:
0.639 g/L (21 °C)
0.697 g/L (30 °C)
Solubility: Miscible in organic solvents
Solubility in acetone: 10.1 g/g (30 °C)
Vapor pressure: 1 mmHg (54 °C)
Acidity (pKa): 9.8
Magnetic susceptibility (χ): −8.630×10−5 cm3/mol
Refractive index (nD): 1.538
Safety guide for methyl salicylate
Methyl salicylate is approved by the U.S. Food and Drug Administration (FDA) and is safe and effective when used according to the Drug Facts label.
You should not use more of the medicine or for longer than the label says.
Safe use tips:
You should only apply the medicine to your skin.
You should not tightly bandage the treated area.
A tight bandage can trap too much of the active ingredient against your skin.
You should not use a heating pad on the treated area.
Ask a healthcare provider before use if:
You are allergic to aspirin or salicylates.
You have redness over the affected area.
You are pregnant or breastfeeding.
Talk to a healthcare provider before using an OTC topical pain reliever containing methyl salicylate or trolamine salicylate in a child age 12 and under.
Methyl Salicylate (Wintergreen oil) is a topical analgesic and anti-inflammatory agent.
Also used as a pesticide, a denaturant, a fragrance ingredient, and a flavoring agent in food and tobacco products.
A systemic acquired resistance (SAR) signal in tobacco.
A topical nonsteroidal anti-inflammatory drug (NSAID).
Methyl salicylate lactoside is a COX inhibitor.
Synonym(s):
Oil of wintergreen, Wintergreen oil, 2-Hydroxybenzoic acid methyl ester, Methyl 2-hydroxybenzoate
methyl salicylate
Methyl 2-hydroxybenzoate
119-36-8
Wintergreen oil
Gaultheria oil
Betula oil
Teaberry oil
Sweet birch oil
OIL OF WINTERGREEN
Analgit
Spicewood Oil
2-Carbomethoxyphenol
Methyl salicylate (oil of wintergreen) is a chemical that smells like wintergreen.
Methyl salicylate is used in many over-the-counter products, including muscle ache creams.
Methyl salicylate is related to aspirin.
Methyl salicylate overdose occurs when someone swallows a dangerous amount of a product containing this substance.
Methyl salicylate can be by accident or on purpose.
Where is methyl salicylate found?
Methyl salicylate is used as a flavoring agent to provide fragrance to various products, and as an odor masking agent.
Methyl salicylate is found in household products, gum, candy, root beer, and mouthwashes.
How can you avoid contact with methyl salicylate?
Avoid products that list any of the following names in the ingredients:
•2-(Methoxycarbonyl)phenol
•2-Carbomethoxyphenol
•2-Hydroxybenzoic acid methyl ester
•4-10-00-00143 (Beilstein Handbook Reference)
•AI3-00090
•Analgit
•BRN 0971516
•Benzoic acid, 2-hydroxy-, methyl ester
•Betula
•Betula Lenta
•Betula oil
•CCRIS 6259
•Caswell No. 577
•EINECS 204-317-7
•EPA Pesticide Chemical Code 076601
•Exagien
•FEMA No. 2745
•FEMA Number 2745
•Flucarmit
•Gaultheria oil
•Gaultheria oil, artificial
•Gaultheriaoel
•HSDB 1935
•Methyl 2-hydroxybenzoate
•Methyl o-hydroxybenzoate
•Methyl salicylate
•Methyl salicylate (natural)
•Methylester kyseliny salicylove
•Methylester kyseliny salicylove [Czech]
•Metylester kyseliny salicylove
•Metylester kyseliny salicylove [Czech]
•NSC 8204
•Natural wintergreen oil
•Oil of wintergreen
•Salicylic acid, methyl ester
•Spicewood Oil
•Sweet birch oil
•Synthetic wintergreen oil
•Teaberry oil
•Wintergreen oil
•Wintergreen oil, synthetic
•Wintergruenoel
•o-Anisic acid
•o-Hydroxybenzoic acid, methyl ester
What are some products that may contain methyl salicylate?
-Household Products
-Liquids
-Pet Care
CAS Number: 119-36-8
Molecular Weight: 152.15
Beilstein/REAXYS Number: 971516
EC Number: 204-317-7
MDL number: MFCD00002214
PubChem Substance ID: 24897111
NACRES: NA.25
Chemical name (IUPAC): 2-Hydroxy-benzoic acid methyl ester
INCI: Methyl salicylate
Synonyms: Hydroxybenzoic acid, Oil of wintergreen (ca. 98% methyl salicylate)
CAS No.: 119-36-8
EINECS No.: 204-317-7
Molecular formula: C8H8O3
Physiochemical properties Appearance: colourless, yellowish or reddish oily liquid; characteristic
odour of wintergreen.
Boiling point (BP): 220 – 224 ºC
Melting point (MP): -8.6 ºC
LogKow: 2.55
Solubility: 0.74 g/l at 30ºC in water; also soluble in most common
organic solvents.
VP: The vapor pressure is 0.0343 mmHg at 25ºC
References: cited in Hansen et al., 2006; IUCLID, 2000)
Methyl salicylate is used as a flavoring agent and smoothing agent in oral care such as toothpastes, mouthwashes and breath fresheners, per the SCCS.
Methyl salicylate is also used in perfumery; bath products such as soaps, detergents and oils; body and hand preparations and mud packs; skin care; foot powders; and hair products such as shampoo and conditioners.
Functions according to CosIng database:
– Denaturants, Fragrance (Methyl salicylate has the characteristic odor of wintergreen, and is used in perfumery).
Other:
– Easing and removing sore muscles and joints caused by increased physical activity level.
– Flavoring agent
Concentrations of Methyl salicylate being applied Methyl salicylate is used in cosmetics as warming-up agent;
rubefacient in sport-massage products, at concentrations in the range of 3 – 9% in the European market.
Methyl salicylate is used in perfumery as a modifier in blossom fragrance and as a mild antiseptic in oral hygiene products;
as a denaturant and flavouring agent at concentrations in the range 0.0001% to 0.6%;
as a flavouring agent in toothpastes up till 1%.
The prime purpose of the sports cream/massage products is to alleviate certain discomforts arising occasionally in connection with sports and physical exercises.
Although not claimed because this would have placed these products under the medicinal products regulations, they in fact remove aching in the muscles due to anti-inflammatory properties.
Saloons providing so-called aroma treatment (aromatherapy) also use wintergreen oil that contains methyl salicylate up till 98%. Wintergreen oil is an “essential oil”.
According to their workingcodex essential oils are blended with other “base” oils and the concentrations are in the range 0.5 – 5%.
2-Hydroxybenzoic acid methyl ester
Gaultheriaoel
Wintergruenoel
Flucarmit
Betula
Exagien
Methyl o-hydroxybenzoate
2-(Methoxycarbonyl)phenol
methylsalicylate
Natural Wintergreen Oil
Betula Lenta
BIRCH-ME
How to use Methyl Salicylate 10 %-Menthol 3 % Topical Patch
Use this medication on the skin only.
Clean and dry the affected area.
Remove the backing from the patch and apply the patch to the affected area.
Do not apply the patch to skin that is injured or irritated (such as skin that is cut, scraped, sunburned, infected, or has a rash).
Leave the patch on the affected area for up to 12 hours.
Use this medication as directed by your doctor or follow all directions on the product package.
If you have any questions, talk to your doctor or pharmacist.
Only use 1 patch at time and do not use more than 2 patches in a 24-hour period.
Do not bandage or wrap the area where the patch is applied unless directed to do so by the doctor.
Heat can increase the risk of side effects.
Do not apply this medication immediately before, during, or after activities that increase skin temperature (such as bathing in hot water, swimming, sun bathing, heavy exercise) or in hot/humid weather.
Wait until your skin has cooled before applying the medication.
Do not use a sunlamp/tanning bed, hot water bottle, or heating pad on the treated area.
Wash your hands well after handling the patch.
Avoid getting this medication in your eyes, nose, or mouth.
If you do get the medication in those areas, flush with plenty of water.
After removing each patch, fold the used patch with the sticky sides together, and throw away in the trash away from children and pets.
Tell your doctor if your condition lasts for more than 3 days, or if it gets worse, or if it keeps returning.
If you think you may have a serious medical problem, get medical help right away.
Salicylic acid, methyl ester
Benzoic acid, 2-hydroxy-, methyl ester
Synthetic Wintergreen Oil
Gaultheria oil, artificial
Wintergreen Oil, synthetic
o-Hydroxybenzoic acid, methyl ester
Birch oil, sweet
Salicylic Acid Methyl Ester
MFCD00002214
FEMA No. 2745
NSC 8204
2-Hydroxybenzoic acid, methyl ester
UNII-LAV5U5022Y
Metylester kyseliny salicylove
methyl hydroxybenzoate
2-Hydroxy-benzoic acid methyl ester
68917-75-9
Benzoic acid, hydroxy-, methyl ester
LAV5U5022Y
CHEBI:31832
NSC-8204
NCGC00091106-02
Background
Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens.
Methyl salicylate was first extracted and isolated from plant species Gaultheria procumbens in 1843.
Methyl salicylate can be manufactured synthetically and Methyl salicylate used as a fragrance, in foods, beverages, and liniments.
Methyl salicylate forms a colorless to yellow or reddish liquid and exhibits a characteristic odor and taste of wintergreen.
For acute joint and muscular pain, methyl salicylate is used as a rubefacient and analgesic in deep heating liniments.
Methyl salicylate is used as a flavoring agent in chewing gums and mints in small concentrations and added as antiseptic in mouthwash solutions.
Methyl salicylate, 99%
DSSTox_CID_5659
DSSTox_RID_77872
DSSTox_GSID_25659
Caswell No. 577
Methyl2-Hydroxybenzoate
Panalgesic
Theragesic
PredaLure
FEMA Number 2745
Anthrapole ND
Ben Gay
Methyl salicylate (natural)
General description
Methyl salicylate (MeSA) is a natural herbivore-induced plant volatile.
Methyl salicylate is a naturally occurring product in vegetables, and berries, and the primary constituent of the oil of wintergreen.
Methyl salicylate Applications
Methyl salicylate has been used:
-as a component of clarifying solution for treating Mongolian gerbil cochlea intact for immunofluorescence analysis
-as a plant elicitor to test its effect on reducing the whitefly population from tomato plants
-in the hyalinization of tissues for pulmonary angiography
-in clearing tissues
Methyl salicylate sometimes called as wintergreen oil which is a sweet smelling member of the aspirin family is one of the most widely used as counterirritant.
Methyl salicylate is the ester of salicylic acid in which the acidic carboxylate moiety is methylated but the phenolic hydroxyl is unchanged.
Methyl salicylate is very similar in structure to salicylic acid.
Salicylic acid is found in copious amounts in the bark of willow bark that could ease aches and reduce fever.
CAS-119-36-8
CCRIS 6259
HSDB 1935
WINTER GREEN OIL
EINECS 204-317-7
EPA Pesticide Chemical Code 076601
Metylester kyseliny salicylove [Czech]
Methylester kyseliny salicylove [Czech]
Pharmacodynamics
Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow.
Methyl salicylate is pharmacologically similar to aspirin and other NSAIDs but as a topical agent Methyl salicylate primarily acts as a rubefacient and skin irritant.
Counter-irritation is believed to cause a soothing sensation of warmth.
Mechanism of action
Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves 5.
This is thought to mask the underlying musculoskeletal pain and discomfort.
When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where Methyl salicylate reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.
Absorption
Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH.
Dermal bioavailability is in the range of 11.8 – 30.7%.
For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% 9.
Volume of distribution
After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes.
Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus.
The drug readily crosses the placental barrier.
Molecular FormulaC8H8O3
Average mass152.147 Da
Monoisotopic mass152.047348 Da
ChemSpider ID13848808
Protein binding
Degree of albumin binding depends on the plasma concentration of the compound
Metabolism
Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate.
Methyl salicylate is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes.
Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites.
BRN 0971516
Methyl salicylate [JAN:NF]
Methylester kyseliny salicylove
AI3-00090
methyl-salicylate
Methylis salicylas
salicylic acid methyl
1-O-methylsalicylate
Salonpas (Salt/Mix)
salicylate methyl ester
Methyl salicylate (oil of wintergreen) is a chemical that smells like wintergreen.
Methyl salicylate is used in many over-the-counter products, including muscle ache creams.
Methyl salicylate is related to aspirin.
Methyl salicylate overdose occurs when someone swallows a dangerous amount of a product containing this substance.
This can be by accident or on purpose.
Biochem/physiol Actions
Methyl salicylate plays an important role in fruit ripening.
Methyl salicylate is known to attract natural enemies of herbivores.
MeSA inhibits the activity of aminocyclopropane-1-carboxylic acid synthase (ACC synthase) and aminocyclopropane-1-carboxylic acid oxidase (ACC oxidase) in plums and tomatoes, it can inhibit fungal infections and reduce chilling injury symptoms in fruits like pomegranates.
This oil of wintergreen is of great interest in the tobacco industry as a flavorant.
Methyl salicylate has counter irritant and anti-inflammatory effects.
Methyl Salicylate,(S)
Theragesic (Salt/Mix)
ACMC-1BSKR
Methyl salicylate (TN)
Methyl salicylate, 8CI
methyl-2-hydroxybenzoate
Enamine_001611
Methyl salicylate, 98%
Methyl salicylate, BioXtra
salicylic-acid methyl ester
Route of elimination
Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).
Half-life
The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses.
The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication.
This product is used to treat minor aches and pains of the muscles/joints (e.g., arthritis, backache, sprains).
Menthol and methyl salicylate are known as counterirritants.
They work by causing the skin to feel cool and then warm.
These feelings on the skin distract you from feeling the aches/pains deeper in your muscles, joints, and tendons.
Some products should not be used on children younger than 12 years without a doctor’s advice.
Check the label carefully before using on children between 2 and 12 years old.
Do not use on children younger than 2 years.
WLN: QR BVO1
EC 204-317-7
SCHEMBL5312
Betula oil, Wintergreen oil
ZINC490
4-10-00-00143 (Beilstein Handbook Reference)
BIDD:ER0323
Wintergreen oil, China origin
CHEMBL108545
Follow all directions on the product package.
If you have any questions, ask your doctor or pharmacist.
This medication is for use on the skin only.
Do not apply near the eyes, mouth, nose, or genitals, and be careful not to touch those areas while the medication is on your hands.
If you do get the medication in those areas, flush with plenty of water.
Wash your hands well before inserting contact lenses.
If you are using the lotion, spray, or foam, shake the bottle well before using.
Apply a thin layer of medication to the affected area no more than 3 to 4 times a day. Rub in gently and thoroughly.
After applying the medication, wash your hands unless you are using this medication to treat the hands.
If treating the hands, wait at least 30 minutes after applying the medication to wash your hands.
Do not apply this medication to skin that is injured or irritated (e.g., cut, scraped, sunburned).
Do not bandage or tightly wrap the affected area.
Doing so may increase the risk of side effects.
You may cover the area loosely to protect clothing.
Ask your pharmacist for more details.
Methyl salicylate is an organic ester responsible for the minty smell of wintergreen.
This procedure will use starting materials that can be found at a supermarket including aspirin, antifreeze, and drain cleaner.
The synthesis is broken down into two parts: hydrolysis of the aspirin and esterification.
Our starting material is aspirin (acetylsalicylic acid).
In the first step, water is used to break the ester bond.
This hydrolysis reaction can be accomplished through either acid or base catalysis.
This removes the acetate from the aspirin.
Quenching with water will leave both acid products in their protonated form.
If base-catalyzed hydrolysis is used, both acids will likely be deprotonated, and acid will need to be added to separate the salicylic acid (water insoluble) from the acetic acid (water soluble).
The second step is a standard Fisher esterification.
This reaction will connect the salicylic acid to the methanol with concentrated sulfuric acid as the catalyst.
Heat can increase the risk of side effects.
Do not apply this medication immediately before, during, or after activities that increase skin temperature (e.g., bathing in hot water, swimming, sun bathing, heavy exercise) or in hot/humid weather.
Wait until your skin has cooled before applying the medication.
Do not use a sunlamp/tanning bed, hot water bottle, or heating pad on the treated area.
Methyl salicylate is available in different strengths and with different ingredients but with product names that sound similar.
Read the label carefully to make sure you have the right product for you.
Ask your pharmacist if you have any questions.
Tell your doctor if your condition persists for more than 7 days, if Methyl salicylate worsens, or if Methyl salicylate keeps returning.
If you think you may have a serious medical problem, seek immediate medical attention.
GTPL2431
Methyl salicylate (JP17/NF)
DTXSID5025659
FEMA 2745
NSC8204
HMS1398J05
HMS2089H12
HMS3885C04
BCP29151
CS-B1799
HY-Y0189
In methyl salicylate (oil of wintergreen), the COOH group of salicylic acid is esterified with methanol (CH3OH), whereas in acetylsalicylic acid (aspirin) the acid component of the ester is acetic acid, and salicylic acid contributes the phenolic ―OH group.
Methyl salicylate is available over-the-counter for topical use as an antiinflammatory and analgesic agent.
Methyl salicylate is used externally because of its irritating effect on gastrointestinal mucosa.
Methyl salicylate can either be synthesized or extracted from the leaves of Gaultheria procumbens (Ericaceae) and bark of Betula lenta (Betulaceae) Sweetman (2003).
Methyl salicylate is rapidly hydrolyzed to salicylic acid, which has analgesic, antipyretic, and antiinflammatory effects.
Methyl salicylate is used topically as a counter-irritant.
When applied topically, sufficient methyl salicylate is absorbed to provide pain relief for those suffering with rheumatic conditions, painful muscles, or joints.
Esterases in the skin rapidly hydrolyze salicylate esters to the active salicylic acid in both the epidermis and dermis.
Methyl ester 2-hydroxy-benzoic acid
Tox21_111081
Tox21_201543
Tox21_300137
ANW-17321
BBL010504
s3756
SBB053705
STK397388
Other names:
Benzoic acid, 2-hydroxy-, methyl ester
Salicylic acid, methyl ester
O-Hydroxybenzoic acid, methyl ester
Analgit
Betula
Betula oil; Betula Lenta; Exagien; Flucarmit; Gaultheria oil; Gaultheria oil, artificial; Gaultheriaoel; Methyl o-hydroxybenzoate
Methyl 2-hydroxybenzoate; Oil of Wintergreen; Spicewood oil; Sweet birch oil; Teaberry oil; Wintergreen oil; Wintergruenoel; 2-(Methoxycarbonyl)phenol
2-Hydroxybenzoic acid, methyl ester; Natural wintergreen oil; Synthetic wintergreen oil; Wintergreen oil, synthetic
Methyl ester of 2-hydroxy-benzoic acid; 2-Carbomethoxyphenol; NSC 8204; Salonpas; Theragesic; 8022-86-4; 648434-07-5; 8024-54-2
2-Hydroxy methyl ester benzoic acid; Methyl ester 2-hydroxy-benzoic acid
Quality Level: 100
vapor density: 5.26 (vs air)
vapor pressure: 1 mmHg ( 54 °C)
product line: ReagentPlus®
assay: ≥99% (GC)
form: liquid
autoignition temp.: 847 °F
refractive index: n20/D 1.536 (lit.)
bp: 222 °C (lit.)
mp: −8-−7 °C (lit.)
density: 1.174 g/mL at 25 °C (lit.)
SMILES string: COC(=O)c1ccccc1O
InChI: 1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3
InChI key: OSWPMRLSEDHDFF-UHFFFAOYSA-N
Methyl salicylate is a major component of oil of wintergreen (prepared by distillation from wintergreen leaves).
Methyl salicylate has an analgesic effect and is used in many over-the-counter analgesic creams or gels designed only for topical use.
Methyl salicylate, if ingested, is very poisonous.
Although aspirin is acetyl salicylate that is structurally close to methyl salicylate, after ingestion Methyl salicylate is rapidly broken down into salicylic acid by blood and liver esterase; very little methyl salicylate is broken down to salicylic acid by the esterase in blood.
Methyl salicylate is a relatively common cause of poisoning in children, and ingestion of one teaspoon of oil of wintergreen can be fatal.
The popular topical ointment Bengay® contains 15% methyl salicylate while Bengay Muscle Pin/Ultra Strength contains 30% methyl salicylate.
Many Chinese medicines and medicated oils contain high amounts of methyl salicylate.
Poisoning from methyl salicylate can occur due to abuse of topical creams containing methyl salicylate.
Salicylate can be detected in blood after excessive topical application of creams containing methyl salicylate.
Bell and Duggin reported the case of a 40-year-old man who became acutely ill after receiving treatment from an unregistered naturopath (herbal skin cream treatment for psoriasis).
The herbal cream contained methyl salicylate, and in this case transcutaneous absorption of methyl salicylate was enhanced due to psoriasis.
A lot of us know how bad Methyl salicylate feels to have constant body pain.
Methyl salicylate ruins our mood, gets us off track of whatever we are focusing on, Methyl salicylate stunts our progress throughout the day, and Methyl salicylate is just very debilitating in general.
If you have suffered from constant body pain before, you have probably explored the wide array of different body rubs that are available on the market.
You probably didn’t know, however, that one of the most common ingredient among all of these body rubs is something called Methyl Salicylate.
Methyl Salicylate is both an anti-irritant and an NSAID that works great against body pain but is Methyl salicylate right for you? Read on to find out.
Fast Relief Against Body Pain
Because Methyl Salicylate is a topical pain reliever, Methyl salicylate can definitely be a lot better than orally taken medicines if the pain is caused by localized trauma.
If you got your body pain because you bumped that part of your body into something for example, an orally taken pain reliever would not act fast because Methyl salicylate is impossible for Methyl salicylate to isolate the pain and act on it specifically.
The same limitations do not apply for topical pain relievers because you can just rub Methyl salicylate into that exact area and watch Methyl salicylate act fast on that area alone.
Methyl salicylate, analytical standard
AKOS000118977
CCG-266225
DB09543
MCULE-5398249325
Methyl ester of 2-hydroxy-benzoic acid
NE10156
Methyl salicylate, >=98%, FCC, FG
NCGC00091106-01
NCGC00091106-03
NCGC00091106-04
NCGC00091106-05
NCGC00254104-01
NCGC00259093-01
Many over-the-counter products are available to treat common musculoskeletal aches and pains.
Often these products are in the form of ointments, liniments, and rubefacients.
Methylsalicylate is an active ingredient in many of the over-the-counter rubefacients.
Methylsalicylate-containing rubefacients have been reported to cause salicylate poisoning after ingestion, topical application to abnormal skin, and inappropriate topical application to normal skin.
Many over-the-counter products contain methylsalicylate because of its mild analgesic and anti-inflammatory properties.
These over-the-counter products may contain up to 30% methylsalicylate.
In the United States, drug preparations containing >5% methylsalicylate must bear a label warning against misdirected use and that the product should be kept out of the reach of children.
We present a unique case of salicylate poisoning caused by genital exposure to a methylsalicylate-containing rubefacient used to facilitate masturbation in a teenager.
68917-50-0
8024-54-2
90045-28-6
AC-11584
AK105942
H364
TS-02010
DB-012808
FT-0612582
FT-0622968
FT-0695782
FT-0698844
Methyl salicylate, natural, 98%, FCC, FG
ST50715363
Methyl salicylate, puriss., 99.0-100.5%
Methyl salicylate (MeSA) is a volatile organic compound synthesized from salicylic acid (SA) a plant hormone that helps to fight against plant disease.
Seed treatment with MeSA, is an encouraging method to the seed industry to produce more growth and yield.
The aim of our study is to find out the growth, development and disease tolerance of rice seed treated with different concentrations of MeSA.
Also the seed treatments were studied to determine whether they directly influenced seedling emergence and growth in rice (Oryza sativa L) cultivars ‘IR 20, IR 50, IR 64, ASD 16, ASD 19 and ADT 46’ under greenhouse condition.
MeSA seed treatments at 25, 50, 75 and 100 mg/L significantly increased seedling emergence.
Effects were stronger in IR 50, and IR 64 and the effects were dose dependent, although the relationship between dose and effect was not always linear.
MeSA seed treated rice plant against bacterial blight were analyzed.
Bacterial blight was more effectively controlled by the seed treated with 100 mg/L than others.
These results suggest that seed treatment with MeSA alters plant physiology in ways that may be useful for crop production as well as protection.
1929-EP2272835A1
1929-EP2272844A1
C12305
D01087
Methyl salicylate, SAJ first grade, >=98.0%
Methyl salicylate, tested according to Ph.Eur.
Salicylic acid (SA) is a critical signal for the activation of plant defense responses against pathogen infections.
We recently identified SA-binding protein 2 (SABP2) from tobacco as a protein that displays high affinity for SA and plays a crucial role in the activation of systemic acquired resistance to plant pathogens.
Here we report the crystal structures of SABP2, alone and in complex with SA at up to 2.1-Å resolution.
The structures confirm that SABP2 is a member of the α/β hydrolase superfamily of enzymes, with Ser-81, His-238, and Asp-210 as the catalytic triad.
SA is bound in the active site and is completely shielded from the solvent, consistent with the high affinity of this compound for SABP2.
Our biochemical studies reveal that SABP2 has strong esterase activity with methyl salicylate as the substrate, and that SA is a potent product inhibitor of this catalysis.
Modeling of SABP2 with MeSA in the active site is consistent with all these biochemical observations.
Our results suggest that SABP2 may be required to convert MeSA to SA as part of the signal transduction pathways that activate systemic acquired resistance and perhaps local defense responses as well.
23256-EP2277848A1
23256-EP2289892A1
23256-EP2298735A1
23256-EP2305250A1
23256-EP2305688A1
23256-EP2308867A2
23256-EP2308870A2
23256-EP2311824A1
23256-EP2311842A2
23256-EP2314584A1
AB01275470-01
Plants are one of the basic staple food, for all forms of life.
We depend on plants for food and medicine, plant derivatives, regulation of the hydrologic cycle.
Plants are essential to the balance of nature.
For more than half of the world’s population “Rice is life”.
Rice is an economic crop for the farmers and major food staple for the world.
Rice provides the main source of food energy for at least one third of the world’s population.
Rice is an essential part of the daily meal in Southern and Eastern parts of India and Asia.
However most the rice plant are affected by the Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) and Methyl salicylate is one of the most important bacterial diseases of rice.
Heavy yield losses due to X. oryzae was reported during last one decade.
Seed germination is one of the early and vital stages in the plant life cycle.
Improved germination of seeds is one process which can improve the economic success of crop by ultimately enhancing the yield.
The process of seed germination may be regulated by external factors, including temperature, light, soil moisture and salinity, metal or mineral composition.
Treatments of seed include applications of chemical agents, biological substances, or physical processes, to increase agricultural production.
The seed treatment helps to protect seedlings from insects and disease which pose devastating consequences to crop production during critical growth stages.
The application of treatments to seeds promotes stronger and healthier roots, leading to uniform seedling emergence, with improved crop performance.
Seed priming is a method of pre-sowing treatments that exposes seeds to a certain solutions that allows partial hydration until the germination process begins.
Various seed priming techniques have been reported to enhance germination and allow for more uniform seed emergence, increasing nutrient reserves through increased physiological activities and increased yield in the crop14.
Various common methods utilized for priming seeds includes: hydro priming, (soaking in water); osmopriming (soaking seed in osmotic solutions); thermopriming (treatment of seed with low or high temperatures); solid matrix priming (treatment of seed with solid matrices); and bio priming (hydration using biological compounds).
Halo priming (soaking seed in salt solutions), and priming with plant growth hormones are also performed along with thermo priming, and on-farm priming.
The mechanism of rice seed priming techniques which uses plant growth regulators may enhance rice performance.
Plant hormones or bio-stimulants are also known to improve plant population and increase productivity.
Presoaking seeds with optimal concentrations of plant growth hormones, such as auxin (IAA), gibberellins (GA), abscisic acid, ethylene (ET), Salicylic acid (SA) and Jasmonic acid (JA) have been shown to benefit germination performance and yield of some crop species growth under both normal and stress conditions.
The effects of seed priming by soaking seeds of sorghum, rice, or wheat in water, are reported to enhance germination rates.
Some strategies for more vigorous plants report improved seedling emergence under induced stress conditions.
SA is a natural phenolic compound that plays a role in the regulation of physiological and biochemical processes.
SA is chemically known as 2-hydroxy benzoic acid is a member of phenolic compounds, containing of an aromatic ring bearing a hydroxyl group which is synthesized by the plant.
These hydroxyl groups are involved in lignin biosynthesis; others serve as allelopathic compounds, regulate plant responses to abiotic stress and disease resistance by inducing antimicrobial defense compounds termed phytoalexins or by signaling defense activation.
Exogenous application of SA act as potential antioxidant capacity inducers, also increase the levels of hydrogen peroxide in plants.
These pathways also regulate many physiological processes in plants, such as increased germination rate, cell growth, stomatal opening, photosynthesis and ion uptake.
Methyl salicylate (MeSA) is a volatile organic compound which is synthesized from SA.
MeSA is associated with induced resistance plant defense which has been used in effective disease control methods28,29,30.
Seed treatment with MeSA can be used to enhance rice seed germination and seedling growth.
We studied the performance of rice seed priming with different concentrations of MeSA (0, 25, 50, 75 and 100 mg/L).
Variables assessed include: germination rate, growth of root and shoot heights (cm), biomass of fresh and dry weights of the shoots and roots (mg) disease incidence, mean lesion lengths, disease index and disease incidence of different rice varieties under greenhouse conditions.
Generic name:
Methyl salicylate/menthol – topical
Pronunciation
(METH-ill-sal-ISS-ill-ate/MEN-thall)
Brand name(s)
BenGay , Icy Hot
Methyl salicylate 100 microg/mL in Acetonitrile
Methyl salicylate, ReagentPlus(R), >=99% (GC)
Methyl salicylate, Vetec(TM) reagent grade, 99%
Q407669
Salicylic acid is a cellular poison that indiscriminately impairs cellular metabolism in overdose.
The clinical presentation of salicylate poisoning is related to stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration.
Symptoms can include hyperpnea, tachypnea, tinnitus, hyperpyrexia, and diaphoresis.
Additional signs are dehydration, electrolyte disturbances, serum glucose abnormalities, and mixed acid-base disturbances.
More severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death.
Treatment of salicylate poisoning consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations.
Enhanced elimination of salicylate is achieved by a sodium bicarbonate infusion with maintenance of serum potassium homeostasis or hemodialysis if the bicarbonate infusion is ineffective or cannot be performed.
Methylsalicylate, also known as oil of wintergreen, is widely available in many over-the-counter ointments, lotions, and salves for the relief of musculoskeletal aches and pains.
The table provides examples of products that contain various concentrations of methylsalicylate.
In vivo, methylsalicylate is hydrolized to salicylic acid.
Five milliliters of oil of wintergreen is approximately equal to 7,000mg of salicylate or twenty-two 325mg aspirin pills.
Topical salicylates rarely produce systemic toxicity when used appropriately; however, methylsaliclyate can be absorbed through intact skin.
Exercise and heat exposure can enhance percutaneous absorption of methylsaliclyate.
At least one death has been reported in an athlete using an excessive amount of a methylsalicylate-containing rubefacient.
There can be increased absorption of methylysalicylate with abnormal skin such as psoriasis, erythroderma, and burns.
There can also be increased aborption of methylsalicylate when applied to large areas of skin, if other products (such as menthol or camphor) are used concurrently, or if an occlusive dressing is used.
Scrotal skin has been shown to have up to a 40-fold greater absorption of certain substances compared to other dermal regions.
SR-05000001473
Q-100939
SR-05000001473-1
Z19703590
2-[Hydroxy(methoxy)methylene]-3,5-cyclohexadiene-1-one
F0001-0306
6-[(E)-Methoxyhydroxymethylene]-2,4-cyclohexadiene-1-one
Methyl salicylate, United States Pharmacopeia (USP) Reference Standard
Methyl salicylate, Pharmaceutical Secondary Standard; Certified Reference Material
Gaultheria oil pound>>Wintergreen oil pound>>2-Hydroxy-benzoicacimethylester pound>>Methyl 2-hydroxybenzoate
Hydrolysis of Methyl Salicylate and Synthesis of Acetylsalicylic Acid
Objectives
Many naturally occurring chemicals can be used isolated and used to make other compounds.
Methyl salicylate is a naturally occurring compound that we will use to produce salicylic acid, which will then be used to make the wonder drug aspirin (acetylsalicylic acid).
This is not the source of salicylic acid in the industrial synthesis of aspirin, but it is, nevertheless, a good one for laboratory use.
Two different chemical techniques will be employed.
First is hydrolysis, which is the breaking of a bond with water.
Esters are quite easily hydrolyzed into their two starting components, an acid and an alcohol.
Then, we perform an ester synthesis for the formation of aspirin.
Equilibrium favors hydrolysis, but using acetic anhydride as the acid source prevents this backward reaction, since water is not produced during ester formation.
Both salicylic acid and aspirin are easily isolated.
Background
Methyl salicylate (an ester) can be hydrolyzed to produce salicylic acid.
The two different functional groups on the aromatic ring are utilized in this lab.
First, the free carboxylic acid group will be produced when we hydrolyze the methyl salicylate.
Methanol is the alcohol which is released by hydrolysis.
Second, the hydroxyl group on salicylic acid will be used in ester formation to produce aspirin.
When we performed an ester synthesis previously, we took special precautions to prevent water from being produced (we included a dessicant in the reaction mixture and had a drying tube affixed on top of the reflux column).
Acetic anhydride will be used in this experiment so that when ester is formed, water is not produced.
As a result, the thermodynamic equilibrium will now be for the formation of an ester instead of its hydrolysis.
Cas No.: 119-36-8
Purity: ≥98%
Formula: C8H8O3
Formula Wt.: 152.15
Chemical Name: 2-Hydroxybenzoic acid methyl ester
IUPAC Name: methyl 2-hydroxybenzoate
Synonym: Wintergreen Oil, Betula Oil, Sweet Birch Oil
Melting Point: -8.6°C
Solubility: Sparingly soluble in water. Soluble in chloroform and ether.
Appearance: Clear, Colorless Liquid
Before proceeding with the experiment you should review several items.
First, you should be familiar with the ester functional group.
Esters are formed when an acid and an alcohol combine.
You should be able to quickly identify an ester by looking at the structural formula.
There are only three types of compounds which have an oxygen located between two carbons.
These are ethers, esters and acid anhydrides.
Can you identify the differences?
Second, we will perform a hydrolysis reaction.
Hydrolysis occurs when water is used to break a bond.
Hydrolysis can occur in either basic or acidic conditions.
We will learn later the actual mechanisms, but in both cases we produce one chemical which is an alcohol and the other chemical will be a carboxylic acid when esters are hydrolyzed.
Third, we will produce an ester.
Methyl salicylate should be noted that ester formation cannot occur in the presence of base, only acid.
During the first day of this lab, we will produce salicylic acid.
This acid will then be used to make aspirin.
The synthesis of aspirin is a multi-billion dollar a year chemical.
While salicylic acid as some therapuetic value, it is not as effective as aspirin in reducing inflammation and other common medical conditions for which aspirin can be used.
Aspirin is part of a large group of chemicals classified as Non-Steriodal Anti-Inflammatory Drugs (NSAIDS).
Procedure
This experiment is composed of two parts.
The first involves the hydrolysis of methyl salicylate in order to produce salicylic acid (Day 1).
The salicylic acid produced in this part of the experiment will be used to prepare acetylsalicylic acid (aspirin) (Day 2).
The aspirin must be very pure, so you will do a second purification of the aspirin on the third day.
Day 1: Hydrolysis of Methyl Salicylate
Many esters have familiar odors.
Methyl salicylate, an ester derived from the combination of salicylic acid and methanol, is also known as the oil of wintergreen.
Methyl salicylate was first isolated in pure form in 1843 by extraction from wintergreen plant (Gaultheria).
It was soon found that this compound had analgesic and antipyretic character almost identical to that of salicylic acid when taken internally.
This medicinal effect probably results from the ease with which methyl salicylate is hydrolyzed to salicylic acid under the alkaline conditions found in the intestinal tract.
Methyl salicylate can be taken internally or absorbed through the skin, hence its use in some liniment preparations.
When applied to the skin, it produces a mild burning or soothing sensation, which is probably due to the action of its phenolic hydroxyl group.
Methyl salicylate also has a pleasant odor, and it is used as an extract for flavoring purposes.
Esters can be hydrolyzed into their carboxylic acid and alcohol components under either acidic or basic conditions in the presence of heat.
In this experiment, methyl salicylate, an ester also known as oil of wintergreen because of its natural source and odor, is treated with aqueous base and heated.
Since, in our experiment, hydrolysis occurs in the presence of base (instead of acid), the carboxylic acid and phenolic -OH groups on salicylic acid are ionized and this compound exists as the sodium salt of salicylic acid, sodium salicylate.
The reaction mixture is subsequently acidifed using sulfuric acid, which converts this anion into the fully protonated acid, salicylic acid.
The alcohol is methanol.
The salicylic acid, which is mostly insoluble, is a solid and can be isolated and purified by crystallization.
As mentioned above, the phenolic hydroxyl group, which is also acidic, would be ionized and exist as the sodium salt during the basic hydrolysis, just like the carboxylic acid group, but it is not shown ionized in this figure because we are concerned with the ester hydrolysis.
As the following figure shows, the phenolic -OH, as well as the carboxylic acid group, will be protonated during the acidification step following the addition of the sulfuric acid.
The hydrolysis of methyl salicylate will be performed using the following setup.
Obtain about 25 mL of freshly prepared 5 M NaOH (or, alternatively, you can dissolve 5.0 g of sodium hydroxide pellets in 25 mL of water).
Pour into a 100-mL round bottom flask (always use a funnel; never pour chemicals through a ground-glass opening).
Add 7.5 g (0.050 mol; 50 mmol) of methyl salicylate (a liquid) to the 100-mL round-bottomed flask containing the NaOH. (a white solid may form, but it will dissolve quickly when the mixture is heated.)
Add ~3-4 boiling stones to prevent bumping (which is the production of a large gas bubble when heated) or uneven boiling.
Attach a reflux condenser to the top of the flask and turn on the cooling water.
Heat the reaction mixture to boiling using a heating mantel.
Allow the mixture to reflux (with cooling) for about 20 minutes.
The liquid mixture should be continually boiling for the entire reflux time.
After a 20 min reflux, transfer the reaction mixture to a 250-mL beaker.
Add 50 mL of DI water to the reaction contents in your beaker.
Either add a stirring bar or vigorously stirr the solution with a glass stirring rod as you add acid in the next step.
Carefully add enough 3 M H2SO4 to make the solution acidic to litmus paper (pHydroin paper) to a pH of 1.
Note: It is best to add the acid slowly with stirring to mix the contents rather than just pouring the acid into the beacker.
Stirring and adding slowly should prevent sodium salicylate from becoming entrapped in the solid salicylic acid.
You may need to add more than 25 mL of 3 M sulfuric acid (for example, you will need more than 20 mL just to neutralize the NaOH used in the reaction).
Solid salicylic acid should form as the neutralization proceeds.
After pHydroin paper shows a pH of 1, add 1-2 mL more of the 3M sulfuric acid to ensure all the salicylic acid precipitates.
The mixture will be acidic, but too much acid will not be a problem: Acid stays acid in acid.
Cool the mixture in an ice-water bath to about 0oC. Let beaker stay in the ice bucket for about 15 min while allowing the crystals to settle.
The salicylic acid must must be a slurry before you do the filtration.
So, if the solid is not freely flowing in the beaker, add enough water so that the solid is suspended and a liquid slurry appearance.
Collect the crystals by vacuum filtration, using a Büchner funnel and filter paper.
The filtration can be conducted most easily by decanting off most of the supernatant liquid through the Büchner funnel before adding the mass of crystals.
Carefully wash the beaker with ice cold water, if necessary, to transfer all the crystals to the funnel.
Store the salicylic acid crystals in an evaporating dish or beaker in the drying oven until the next lab period.
Since your collected crystals from an acid solution, you cannot store your filter paper with your chemical.
STOP AND STORE THIS PART OF THE EXPERIMENT UNTIL THE NEXT LAB PERIOD!
Day 2: Procedure for the preparation of aspirin
When the crystals are thoroughly dry, weigh them and determine the percent yield, based on the amount of starting material.
Remember, 1 mol of methyl salicylate yields 1 mol of salicylic acid).
Determine the melting point of your purified salicylic acid (m.p. 159-160oC) and compare it to a sample of pure salicylic acid from the stockroom.
Aspirin is a trade name for acetylsalicylic acid, a common analgesic.
Acetylsalicylic acid is an acetic acid ester derivative of salicylic acid.
The earliest known uses of the drug can be traced back to the Greek physician Hippocrates in the fifth century B.C. He used powder extracted from the bark of willows to treat pain and reduce fever.
Salicin, the parent of the salicylate drug family, was successfully isolated in 1829 from willow bark.
Sodium salicylate, a predecessor to aspirin, was developed along with salicylic acid in 1875 as a pain reliever.
Sodium salicylate was not often popular though, as it has a habit of irritating the stomach.
However, in 1897, a man named Felix Hoffman changed the face of medicine forever.
Hoffman was a German chemist working for Bayer.
He had been using the common pain reliever of the time, sodium salicylate, to treat his father’s arthritis.
The sodium salicylate caused his father the same stomach trouble it caused other people, so Felix decided to try and concoct a less acidic formula.
His work led to the synthesis of acetylsalicylic acid, or ASA.
This soon became the pain killer of choice for physicians around the globe.
Scientists never really understood the inner workings of the drug however.
It wasn’t until the 1970’s, when British pharmacologist John Vane, Ph.D. began work on aspirin that people began to understand how aspirin really works.
Vane and his colleagues found that aspirin inhibited the release of a hormone like substance called prostaglandin.
This chemical regulates certain body functions, such as blood vessel elasticity and changing the functions of blood platelets.
Thus can aspirin affect blood clotting and ease inflammation.
The reaction for synthesis of acetylsalicylic acid is shown in the following figure.
Salicylic acid, prepared from the hydrolysis of methylsalicylate is reacted with acetic anhydride producing the ester product, acetylsalicylic acid.
In a previous experiment, we have used the Fischer esterification reaction to produce isopentyl acetate from an acid (acetic acid) and an alcohol (isopentyl alcohol).
The current experiment uses the carboxylic acid derivative, acetic anhydride, for ester formation.
The advantage of using acetic anhydride is that you do not produce water which can be used for hydrolysis of the newly formed ester.
Concentrated sulfuric acid will be used to keep everything in the protonated state.
Acetic anhydride is the preferred acid derivative to synthesize aspirin commercially because the acetic acid produced in this reaction (a reaction by-product) can be used again, by converting it back into acetic anhydride.
If you recovered less than 3.5 g of salicylic acid, you will need to adjust the quantities of reagents used in this protocol.
However, if you recovered at least 3.5 g salicylic acid, use the quantities of reagents listed below (remember, if you recovered more than 3.5 g of salicylic acid, use only 3.5 g salicylic acid regardless of how much you recovered).
If you recovered less than 3.5 g salicylic acid, just proportion the amounts of the other reagents for this reaction.
Initiate the aspirin synthesis reaction:
Preheat 60-90 mL of water in a 400-mL beaker to boiling.
Place about 3.5 g of salicylic acid into a 125-mL Erlenmeyer flask (do no use more salicylic acid, even if you isolated more)
Add 3.5 mL of acetic anhydride (density is 1.08 g/mL) using a pipettor (if you reset the pipettor to a different value, please reset it back to the 3.5 mL value so other students don’t use the wrong amount).
Add about 4 or 5 drops of concentrated (18 M) sulfuric acid [or 85% phosphoric acid] to the mixture (some heat may be generated).
This addition of acid allows the carbonyl carbon of acetic anhydride to be more electrophilic.
Heat the flask containing your reactants by placing it into a beaker of boiling water for five or six minutes.
Stir the mixture by gently swirling the flask.
During this time, the solid should dissolve completely.
Isolation of aspirin
Remove the flask from the boiling water bath, and add 15 mL of ice water to it.
(The ice [or ice/water mixture] hydrolyzes the unreacted anhydride and keeps the mixture cool.
Can you write the equation of this hydrolysis reaction?)
Thoroughly cool the flask to complete the initial crystallization of aspirin.
Remember that when a solution becomes cloudy, that is a solid forming and this would be the crystals of aspirin you desire.
If crystals are slow in forming, you may need to scratch the inside of the Erlenmeyer flask with a glass rod, which will speed up crystal formation by seeding, or initializing the formation of crystals.
Collect your aspirin via vacuum filtration, and let air continue to be drawn over the solid for about 10 minutes to evaporate most of the water surrounding the solid.
The aspirin product will be analyzed using HPLC (High Pressure Liquid Chromatography).
The HPLC resolves the aspirin from the salicylic acid. For your analysis, weight out precisely 0.0100 grams of sample and place in a clean test tube.
To this test tube, add five mL methanol, and swirl to dissolve aspirin.
Then, add 5 mL Milli-Q water (ultra purified) to facilitate dissolving.
This dissolved material will be given to an IA who will run your sample on the HPLC and give you a copy of the chromatogram of your crude aspirin.
Characterization of aspirin by re-crystallization and solubility
Take about 2 grams of your slightly moist aspirin isolated above and add to a small beaker.
Add either 5 mL of methanol or 5 mL of acetone and gently swirl to dissolve the solid.
You may need to warm slightly, but do not boil the mixture.
All of the aspirin should dissolve in the warm solvent.
Remove the beaker containing the aspirin-solvent mixture and let it cool to room temperature on the bench.
When it is about room temperature (the beaker will feel slightly cool to the touch), place the beaker in an ice bucket to continue to produce crystals.
After about 15 minutes on ice, collect by vacuum filtration your crystals (do not use water to wet the filter paper, but use the same solvent to wet the filter paper prior to collecting crystals).
Let the vacuum continue to be drawn through the Buchner funnel for about 15 minutes to thoroughly evaporate the solvent.
At this point, your filter paper and your crystals should be dry.
Weigh your sample to determine your yield of re-crystalized aspirin.
For HPLC analysis of your re-crystallized aspirin, weigh out about 0.0100 grams of your re-crystalized aspirin and add 5 mL of the anhydrous methanol, dissolve and then add 5 mL Mili-Q water to dissolve your solid.
Slight warming should not be necessary.
Do a yield, percent yield, and melt temp of your re-crystallized aspirin.
Be sure to have your aspirin samples analyzed via HPLC.
Caution: Aspirin decomposes in boiling water (therefore, do not boil the aspirin) or when dissolved in solutions of alkali hydroxides and carbonates.
Inorganic salts of acetylsalicylic acid are soluble in water (especially the Calcium salt, but are decomposed quickly.
The purpose of re-crystallization is to get rid of contaminating chemicals, such as salts.
So, even if you do not fully dissolve all your aspirin, you could still effect a purification by adding a certain amount of water.
After adding some water (e.g., up to 100 mL water), heat the mixture up to 50-60oC and let as much aspirin dissolve as possible.
Then, cool the mixture and let the crystals form, even though not all the solid may have gone solution.
This method effectively washes the crystals and lets the contaminants get diluted into the solvent.
After cooling, collect the crystals by vacuum filtration.
You can take advantage of the high solubility in one solvent and the lower solubility in another.
For example, if your solid dissolves easily in ethanol, but not well in water (check the solubilities above), first dissolve your solid in as little ethanol as possible, perhaps at a slightly elevated temperature. Then, add a large excess of water (e.g., 100 mL of water), and let your sample stand on ice for 10-15 min.
Collect the crystals as normal.