119-36-8 Usage
Chemical Description
Methyl salicylate is an ester with the chemical formula C8H8O3, commonly used as a topical analgesic.
Description
Methyl salicylate, also known as oil of wintergreen, is an organic ester that is naturally produced by many species of plants, particularly those called wintergreens. It is a colorless or pale yellow, red or light yellow transparent oily liquid with a strong aroma of wintergreen. Methyl salicylate is used as a fragrance and has various applications in different industries due to its unique properties.
Uses
Used in Perfumery:
Methyl salicylate is used as a modifier for some floral types, such as ylang ylang, magnolia, acacia, shy flower, tuberose, gardenia, bloom, and sweet clover grass. It is also used in the formulation of flavors, mainly for the deployment of ylang ylang, tuberose, chypre, acacia, fougere, and orchids.
Used in Medicine and Hygiene Products:
Methyl salicylate is used in medicine and hygiene products such as toothpaste, tooth powder, mouthwash, talcum powder, and carminative oil. It is recognized as GRAS (Generally Recognized As Safe) by FEMA and is included in the European Council's health artificial flavorants table, which can be used in food without harm to humans.
Used in Industrial Products:
Methyl salicylate can also be used for industrial products such as glue, glue paper, card paste, and paste. It is also used as a high-temperature heat carrier in the dyeing industry.
Used in Food Flavor:
Methyl salicylate is used as a flavoring agent for food, providing a mint flavor 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 and is used in the deployment of strawberry, vanilla, grapes, and other fruit-flavor flavors for food and beer.
Used in Pharmaceutical Drugs:
Methyl salicylate is used as a pharmaceutical for external application agents, such as methyl salicylate ointment, which is a common dermatology drug with analgesic, anti-inflammatory, and bactericidal effects.
Used in Solvents and Intermediates:
Methyl salicylate is used as solvents and intermediates for the manufacture of pesticides, fungicides, perfumes, paints, cosmetics, ink, and dye fibers.
Used in Attracting Male Orchid Bees:
Methyl salicylate is among the compounds that attract male orchid bees, who gather the chemical to synthesize pheromones. It is commonly used as bait to attract and collect these bees for study.
Used as a Rubefacient:
In high concentrations, methyl salicylate is used as a rubefacient in deep heating liniments (such as Bengay) to treat joint and muscular pain. It metabolizes into salicylates, including salicylic acid, a known NSAID.
Used as a Clearing Agent:
Methyl salicylate can be used to clear plant or animal tissue samples of color, making it useful for microscopy and immunohistochemistry when excess pigments obscure structures or block light in the tissue being examined.
Used as a Flavoring Agent:
In low concentrations, methyl salicylate is used 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.
Used as a Preservative:
Methyl salicylate is also used as a preservative in the food industry, with an ADI (Acceptable Daily Intake) value of 0 to 0.5 mg/kg.
Used in the Production of Antipyretic Analgesics:
Methyl salicylate reacts with ammonia to make salicylamide, which is used for the production of antipyretic analgesics such as salicylaldehyde ethyl amine. Salicylamide itself is an anti-inflammatory drug.
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.
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.
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
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)
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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)
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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.
POLYCYCLIC AMIDES AS UBE2K MODULATORS FOR TREATING CANCER
-
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.
Design, modification of phyllanthone derivatives as anti-diabetic and cytotoxic agents
Nguyen, Ngoc-Hong,Vo, Van-Giau,Phan, Hoang-Vinh-Truong,Ngo, Thanh-The,Sichaem, Jirapast,Nguyen, Thi-Phuong,Nguyen, Huu-Hung,Pham, Duc-Dung,Nguyen, Tien-Cong,Nguyen, Van-Kieu,Duong, Thuc-Huy
supporting information, p. 371 - 378 (2020/07/13)
Twelve benzylidene derivatives, one Baeyer-Villiger oxidative, six imine derivatives were successfully designed and synthesised from phyllanthone. In the search for potential new anti-diabetic agents, phyllanthone along with its benzylidene and oxidation analogues were evaluated for enzyme inhibition against α-glucosidase. In the benzylidene series, most analogues displayed stronger activity than the mother compound. Compound 1c revealed the strongest activity, outperforming the acarbose positive control with an IC50 value of 19.59 μM. Phyllanthone and its derivatives were then tested for cytotoxic activity against the K562 cell line. The imine analogues displayed the most powerful cytotoxic activity with 3cand 3d having IC50 values of 57.55 and 68.02 μM, respectively.
