119-36-8 Usage
Chemical Description
Methyl salicylate is an ester with the chemical formula C8H8O3, commonly used as a topical analgesic.
description
Natural material is found in wintergreen oil, oil of wintergreen, birch oil, green tea seed oil, clove oil, Quercetin tree oil, tuberose oil, small when medicated oil, tea oil, ylang ylang oil and cherry, apple, strawberry fruit juice. It is colorless or pale yellow, red or light yellow transparent oily liquid. A strong aroma of wintergreen oil. Relative molecular mass of 152.16. The relative density of 1.1738. Melting point-8.6 ℃. Boiling point 223.3 ℃. A flash point of 96 ℃. The refractive index of 1.5360. It is insoluble in water, soluble in alcohol, ether, acetic acid and other common organic solvents. It is easy to change when exposed in air . Rat oral LD50887mg/kg.
Salicylic acid and methanol are heated to prepare it in the presence of sulfuric acid . Or it is made of stone STSP plant holly leaf through distillation.
Methyl salicylate can be used in the formulation of flavors, mainly for the deployment of ylang ylang, tuberose, chypre, acacia, fougere, orchids. But the most common use is perfuming toothpaste. IFRA has no restrictions.
Methyl salicylate is recognized as GRAS by FEMA, FEMA number 2745, the European Council includes methyl salicylate in health artificial flavorants table which can be used in food without harm to human , the maximum amount is 8400mg/kg, ADI value is 0.5mg/kg.
Methyl salicylate can be used for food flavor formula, is a food flavor within China's GB2760-1996 provisions of the temporary use , ADI value of 0 to 0.5, is commonly used in the deployment of strawberry, vanilla, grapes and other fruit-flavor flavor for food and beer, but also flavor fructose, soft drinks.Methyl salicylate is also used as preservatives, pesticides, polishes, inks, paints, polyester dye carriers in industrial fields
application
Methyl salicylate ointment is a common dermatology drug with analgesic, anti-inflammatory, bactericidal effect. Because it can induce local irritation, it is rarely orally used.When spread in the skin,it is easily absorbed. Its liniments, ointments can be used for acute rheumatoid arthritis, low back pain and muscle pain, also itching and flavoring agents, flavoring agents, preservatives.
Uses
Different sources of media describe the Uses of 119-36-8 differently. You can refer to the following data:
1. Appropriately use it as modifiers for some floral types , such as ylang ylang, magnolia, acacia, shy flower, tuberose, gardenia, bloom, sweet clover grass.It is mainly used for medicine and hygiene products such as toothpaste, tooth powder, mouthwash, talcum powder, carminative oil. Methyl salicylate can also be used for industrial products such as glue, glue paper, card paste, paste. It can also be used for food flavor,such as strawberries, grapes, walnuts, spearmint, spicy flavor as a special green gas.
Methyl salicylate is used as high-temperature heat carrier in dyeing industry .
The product has similar-Pyrola odor ,when used as a spice, it is often used as flavoring agent for pharmaceutical drugs and the pigmentum.It also has applications in blending spices, such as Quercetin trees in general flavors. Methyl salicylate is also used as solvents and intermediates for the manufacture of pesticides, fungicides, perfumes, paints, cosmetics, ink and dye fibers such help. Methyl salicylate reacts with ammonia to make salicylamide which is used for production of antipyretic analgesics salicylaldehyde ethyl amine ,and salicylamide itself is an anti-inflammatory drug. Methyl salicylate can be obtained by acetylation using acetylsalicylic acid methyl ester (C10H10O4, [580-02-9]). Add methyl salicylate and acetic anhydride into pot ,put sulfuric acid under stirring, the reaction temperature does not exceed 60 ℃ for about 1h, the reaction is completed, the reaction is poured into ice water and precipitated crystals are filtered, washed, dried, and acetylsalicylic acid methyl ester is obtained. Acetylsalicylic acid can be prepared by cyclization to get 4-hydroxy coumarin. Methyl salicylate is used as a pharmaceutical for external application agent.
Perfumes and suntan lotion ultraviolet absorber.
2. Methyl salicylate occurs in the leaves ofGaultheria procumbens L. and in the barkof Betulaceae. It is produced by esterificationof salicylic acid with methanol. It is used inperfumery and as a flavoring agent.
3. In high concentrations as a rubefacient in deep heating liniments (such as Bengay) to treat joint and muscular pain. Randomised double blind trial reviews report evidence of its effectiveness that is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to counter-irritation. However, in the body it metabolizes into salicylates, including salicylic acid, a known NSAID. In low concentrations as a flavoring agent (no more than 0.04%; it is toxic). providing fragrance to various products and as an odor-masking agent for some organophosphate pesticides. If used excessively, it can cause stomach and kidney problems. Attracting male orchid bees, who apparently gather the chemical to synthesize pheromones; it is commonly used as bait to attract and collect these bees for study. 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. A mint flavoring in some kinds of chewing gum and candy, as an alternative to the more common peppermint and spearmint oils. It can also be found as a flavoring of root beer. It is also a potentially entertaining source of tri boluminescence ; when mixed with sugar and dried, it gains the tendency to build up electrical charge when crushed or rubbed. This effect can be observed by crushing wintergreen Life Savers candy in a dark room.
4. Methyl salicylate is used in high concentrations as a rubefacient in deep heating liniments (such as Bengay) to treat joint and muscular pain. Randomised double blind trial reviews report evidence of its effectiveness that is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to counter-irritation. However, in the body it metabolizes into salicylates, including salicylic acid, a known NSAID. It is used in low concentrations as a flavoring agent (no more than 0.04 %; it is toxic). It is also used to provide fragrance to various products and as an odor-masking agent for some organophosphate pesticides . If used excessively, it can cause stomach and kidney problems. Methyl salicylate is among the compounds that attract male orchid bees, who apparently gather the chemical to synthesize pheromones; it is commonly used as bait to attract and collect these bees for study.
5. Methyl salicylate is an organic ester that is commonly produced naturally by wintergreens. Methyl salicylate is utilize as a anti-herbivore defense system in various plants that produces it. Methyl sa
licylate is also used in high concentrations as a rubefacient to treat joint, muscular pain and acute pain. Methyl slicylate is also used as a flavoring agent and often used to provide fragrance to pr
oducts.
6. Potent inhibitor of ornithine decarboxylase
Production Method
Methyl salicylate is widespread in nature, and it is a main ingredient of wintergreen, small medicated oil . Alsoit is present in essential oils of the tuberose, Quercetin tree, ylang ylang, cloves, tea. Salicylic acid and methanol are used to make it in the presence of sulfuric acid through esterification. Salicylic acid is dissolved in methanol, add sulfuric acid, heat with stirring, the reaction time is 3h,90-100℃, cool to below 30 ℃,take oil ,wash with sodium carbonate solution to pH8 above, and then wash 1 time with water. Vacuum distillation, collect 95-110 ℃ (1.33-2.0kPa) distillate, obtain methyl salicylate. The yield is over 80%. General industrial methyl salicylate content is 99.5%. Material consumption fixed: Acid 950kg/t, methanol 400kg/t.
Description
Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester that is naturally produced by many species of plants. Some of the plants which produce it are called wintergreens, hence the common name. This compound is used as a fragrance. It is also found in liniments (rubbing ointments).
Chemical Properties
Different sources of media describe the Chemical Properties of 119-36-8 differently. You can refer to the following data:
1. Methyl Salicylate is the main component of wintergreen oil and occurs in small
quantities in other essential oils and fruits. It is a colorless liquid with a sweet,
phenolic odor.
2. Methyl salicylate has a characteristic wintergreen-like odor. May
be prepared by extraction from natural sources; or by esterification
of salicylic acid with methanol.
3. Wintergreen is an evergreen shrub with slender, creeping stems, assurgent, flowering branches with toothed leaves
clustered at the top, white, bell-shaped flowers blossoming July to August, followed by red berries (checkerberries). The plant grows
extensively in the woods of Canada and the United States (Pennsylvania). The leaves are harvested between June and September.
Wintergreen has an aromatic odor and flavor similar to methyl salicylate.
Occurrence
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. This compound is produced most likely 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.
Definition
ChEBI: A benzoate ester that is the methyl ester of salicylic acid.
Preparation
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 winter green).
Production Methods
Methyl acetate, a novel acyl acceptor for biodiesel production has been developed, and a comparative study on Novozym 435-catalyzed transesterification of soybean oil for biodiesel production with different acyl acceptors has been studied (Noureddini et al., 2005).
Figure 1 shows the effect of the molar ratio of methanol to sunflower oil on the methyl ester yield for catalytic (3% CaO) transesterification in supercritical methanol at 523 K.
Composition
The leaves of wintergreen are reported to contain arbutin, caffeic acid, ericolin, ferulic acid, gaultherase, gaultheric
acid, gaultherin, gentisinc acid, methyl salicylate (5445 to 7920 ppm) o-pyrocatachuic acid, p-coumaric acid, p-hydroxybenzoic acid,
primverose, protocatachuic acid, syringic acid, tannic acid, tannin, tricontane and vallininc acid.
Aroma threshold values
Detection: 40 ppb
Taste threshold values
Taste characteristics at 10 ppm: sweet, salicylate and root beer with aromatic and balsamic nuances
Synthesis Reference(s)
Canadian Journal of Chemistry, 61, p. 688, 1983 DOI: 10.1139/v83-127The Journal of Organic Chemistry, 40, p. 3649, 1975 DOI: 10.1021/jo00913a007Tetrahedron Letters, 37, p. 153, 1996 DOI: 10.1016/0040-4039(95)02120-5
General Description
Colorless yellowish or reddish liquid with odor of wintergreen.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Methyl Salicylate is an ester. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides. Birch-Me is incompatible with oxidizers. Birch-Me is also incompatible with strong bases. Birch-Me may react with iron salts.
Hazard
Toxic by ingestion; use in foods restrictedby FDA, lethal dose 30 cc in adults, 10 cc in chil-dren.
Health Hazard
Methyl salicylate is a highly toxic compound.The toxic symptoms in humans include nausea, vomiting, gastritis, diarrhea, respiratorystimulation, labored breathing, pulmonaryedema, convulsions, and coma. Ingestion of15 to 25 mL of this compound may befatal to humans. Application of the liquidon the skin and eyes produced severe irrita tion in rabbits. Oral, subcutaneous, or der mal administration of methyl salicylate intest animals produced specific developmen tal abnormalities affecting the eyes, ears, andcentral nervous systemToxicity of this compound is relativelymore severe in humans than in many com mon laboratory animals. The oral LD50 values in test animals were within the range800–1300 mg/kg.
Fire Hazard
Methyl salicylate is combustible.
Flammability and Explosibility
Nonflammable
Biochem/physiol Actions
Methyl salicylate plays an important role in fruit ripening. It 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. It has counter irritant and anti-inflammatory effects.
Contact allergens
This anti-inflammatory agent is found in a wide number of ointments and can induce allergic contact dermatitis.
Safety Profile
Human poison by
ingestion. Moderately toxic to humans by an
unspecified route. Moderately toxic
experimentally by intraperitoneal,
intravenous, and subcutaneous routes. An
experimental teratogen. Human systemic
effects by ingestion: flaccid paralysis without
anesthesia, general anesthesia, dyspnea,
nausea, vomiting, and respiratory
stimulation. Experimental reproductive
effects. A severe skin and eye irritant.
Ingestion of relatively small amounts has
caused severe poisoning and death.
Combustible liquid when exposed to heat or
flame; can react with oxibzing materials. To
fight fire, use CO2, dry chemical. When
heated to decomposition it emits acrid
smoke and irritating fumes.
Safety
In pure form, methyl salicylate is toxic, especially when taken internally. A single teaspoon (5ml) of methyl salicylate contains 7g of salicylate, which is equivalent to more than twenty- three 300 mg aspirin tablets. 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.[6] 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. Some people have intentionally ingested large amounts of oil of wintergreen. 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.
Synthesis
By esterification from natural sources; by esterification of salicylic acid with methanol
Carcinogenicity
Available data suggest that
methyl salicylate is not carcinogenic.
Purification Methods
Dilute the ester with Et2O, wash with saturated NaHCO3 (it may effervesce due to the presence of free acid), brine, dry MgSO4, filter, evaporate and distil it. Its solubility is 1g/1.5L of H2O. The benzoyl derivative has m 92o (b 270-280o/120mm), and the 3,5-dinitrobenzoate has m 107.5o, and the 3,5-dinitrocarbamoyl derivative has m 180-181o. [Hallas J Chem Soc 5770 1965, Beilstein 10 IV 143.]
Check Digit Verification of cas no
The CAS Registry Mumber 119-36-8 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,1 and 9 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 119-36:
(5*1)+(4*1)+(3*9)+(2*3)+(1*6)=48
48 % 10 = 8
So 119-36-8 is a valid CAS Registry Number.
InChI:InChI=1/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3
119-36-8Relevant articles and documents
Novel aroylhydrazine-amide derivatives bearing pyridine core: Synthesis, characterisations and selective colorimetric recognition properties
Li, Shaowei,Li, Huangyong,Chen, Changshui,Yue, Xiali,Cao, Xiufang,Ke, Shaoyong
, p. 384 - 392 (2013)
Four aroylhydrazine-amides receptors AR1-4 with a hydrazine spacer have been designed, synthesised and characterised as novel colorimetric chemosensors by typical spectroscopic techniques. The receptors AR1-3 exhibited certainly selectivity and sensitivity towards F- and AcO-, forming 1:1 stoichiometry complex by hydrogen-bond interaction. Furthermore, AR4 has especially shown obvious colour change in the presence of these two important biologically anions.
-
Clinton,Laskowski
, p. 3135 (1948)
-
Novel amide-type ligand bearing bis-pyridine cores: Synthesis, spectral characterizations and X-ray structure analyses
Ke, Shaoyong
, p. 91 - 97 (2016)
The novel salicylamide-type ligand containing bis-pyridine moieties, i.e. 2-((6-chloropyridin-3-yl)methoxy)-N-(2-((6-chloropyridin-3-yl)methylthio)phenyl)benzamide, which has been successfully synthesized and characterized by typical spectroscopic techniques mainly including IR, 1H NMR and ESI-MS. The structure of target compound was further determined by single crystal X-ray diffraction method and which crystallized in the monoclinic system with space group P2(1)/c.
A catalyst-free, facile and efficient approach to cyclic esters: Synthesis of 4H-benzo[d][1,3]dioxin-4-ones
Lin, Feng,Song, Qiuling,Gao, Yuyu,Cui, Xiuling
, p. 19856 - 19860 (2014)
We have developed a green and practical method to construct 4H-benzo[d][1,3]dioxin-4-one and its derivatives, which are important structural units in insecticides, and intermediates to synthesize multiple-substituted benzene derivatives of great value. The catalyst- and additive-free conditions, commercial and cheap starting materials and short reaction time, make this transformation practical and attractive.
Photocatalytic C–H activation and oxidative esterification using Pd@g-C3N4
Verma, Sanny,Nasir Baig,Nadagouda, Mallikarjuna N.,Varma, Rajender S.
, p. 248 - 252 (2018)
Graphitic carbon nitride supported palladium nanoparticles, Pd@g-C3N4, have been synthesized and utilized for the direct oxidative esterification of alcohols using atmospheric oxygen as a co-oxidant via photocatalytic C–H activation.
ON THE BIOSYNTHESIS OF BENZOIC ACID IN GAULTHERIA PROCUMBENS L. II.
GRISEBACH,VOLLMER
, (1964)
-
Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers
Alsaif, Nawaf A.,Taghour, Mohammed S.,Alanazi, Mohammed M.,Obaidullah, Ahmad J.,Al-Mehizia, Abdulrahman A.,Alanazi, Manal M.,Aldawas, Saleh,Elwan, Alaa,Elkady, Hazem
, p. 1093 - 1114 (2021)
Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in?vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC50 values ranging from 6.4 to 19.4 μM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).
Dealkylation of alklyl and aryl ethers with AlCl3-NaI in the absence of solvent
Ghiaci, Mehran,Asghari, Jila
, p. 973 - 979 (1999)
A facile synthetic procedure, for dealkylation of alkyl and aryl ethers with AlCl3-NaI in the absence of solvent is developed. We have been able to deprotect different methyl ethers in excellent yields.
Design, synthesis, and molecular docking of novel 3,5-disubstituted-1,3,4-oxadiazole derivatives as iNOS inhibitors
Koksal, Meric,Dedeoglu-Erdogan, Ayca,Bader, Marwa,Gurdal, Enise E.,Sippl, Wolfgang,Reis, Rengin,Ozgurbuz, Melda,Sipahi, Hande,Celik, Turgay
, (2021)
To obtain new anti-inflammatory agents, recent studies have aimed to replace the carboxylate functionality of nonsteroidal anti-inflammatory drugs with less acidic heterocyclic bioisosteres like 1,3,4-oxadiazole to protect the gastric mucosa from free carboxylate moieties. In view of these observations, we designed and synthesized a series of 3,5-disubstituted-1,3,4-oxadiazole derivatives as inhibitors of prostaglandin E2 (PGE2) and NO production with an improved activity profile. As initial screening, and to examine the anti-inflammatory activities of the compounds, the inhibitions of the productions of lipopolysaccharide-induced NO and PGE2 in RAW 264.7 macrophages were evaluated. The biological assays showed that, compared with indomethacin, compounds 5a, 5g, and 5h significantly inhibited NO production with 12.61 ± 1.16, 12.61 ± 1.16, and 18.95 ± 3.57 μM, respectively. Consequently, the three compounds were evaluated for their in vivo anti-inflammatory activities. Compounds 5a, 5g, and 5h showed a potent anti-inflammatory activity profile almost equivalent to indomethacin at the same dose in the carrageenan-induced paw edema test. Moreover, the treatment with 40 mg/kg of 5h produced significant anti-inflammatory activity data. Furthermore, docking studies were performed to reveal possible interactions with the inducible nitric oxide synthase enzyme. Docking results were able to rationalize the biological activity data of the studied inhibitors. In summary, our data suggest that compound 5h is identified as a promising candidate for further anti-inflammatory drug development with an extended safety profile.
Chromatography-free, Mitsunobu-triggered heterocyclizations of salicylhydroxamic acids to 3-hydroxybenzisoxazoles
Van Eker, Daniel,Chauhan, Jay,Murphy, William A.,Conlon, Ivie L.,Fletcher, Steven
, p. 5301 - 5303 (2016)
The Mitsunobu reaction has become one of the most powerful tools to alkylate acidic pronucleophiles. A significant caveat of Mitsunobu chemistry, however, is that the reaction mixture is often plagued with purification problems owing to the phosphine oxide and hydrazine dicarboxylate by-products. In addition to the development of more readily separable Mitsunobu reagents, the product's physicochemical properties may be exploited to facilitate purification. In this regard, we present a swift and efficient preparation of 3-hydroxybenzisoxazoles by the Mitsunobu-triggered heterocyclizations of salicylhydroxamic acids, which can be isolated by an acid–base work-up. As expected, a range of functional groups was compatible with the chemistry.
Synthetic method of methyl salicylate
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Paragraph 0016; 0018-0020; 0022-0024; 0026-0027, (2021/02/10)
The invention discloses a synthesis method of methyl salicylate. The method comprises the following steps: preparing sodium phenolate by using caustic soda flakes and phenol as raw materials, carryingout carboxylation reaction on the obtained sodium phenolate and carbon dioxide gas to obtain sodium salicylate, reacting the obtained sodium salicylate with chloromethane gas under the action of a phase transfer catalyst to obtain a crude methyl salicylate product containing a toluene solvent, neutralizing and washing the crude methyl salicylate product, recovering the toluene solvent at normal pressure, and carrying out vacuum distillation to obtain a finished methyl salicylate product. According to the method, a strong acid catalyst is not used, so that the wastewater amount is greatly reduced, and the corrosion to equipment and the pollution to the environment are reduced. According to the method, equipment is not seriously corroded, the wastewater amount is small, and the process is more environmentally friendly.
POLYCYCLIC AMIDES AS UBE2K MODULATORS FOR TREATING CANCER
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Paragraph 00173-00175, (2021/07/10)
Provided are compounds of Formula (I) and pharmaceutically acceptable salts and compositions thereof, which are useful for treating conditions associated with modulation of UBE2K.
