119-36-8 Usage
Chemical Description
Methyl salicylate is an ester with the chemical formula C8H8O3, commonly used as a topical analgesic.
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.
New highly selective turn-on fluorescence receptor for the detection of copper (II)
Nan, Qian,Rong, Pu,Jiang, Yunbao,Yang, Rui
, p. 307 - 315 (2017)
Three new receptors (1a–c) bearing a p-dimethylaminobenzamide fluorophore have been synthesized and evaluated in terms of their fluoroionophoric properties towards various metal ions. Notably, receptors 1a and 1c exhibited dramatic fluorescent enhancement towards Cu2?+ in acetonitrile. Subsequent investigations revealed that the highly selective behavior of these receptors towards Cu2?+ could be attributed to the Cu2?+-mediated oxidative cyclization of these compounds to the corresponding 1,3,4-oxadiazoles. Solvent effects and quantum calculations indicated that 1a and 1c both possessed an intramolecular charge transfer channel, which could be obstructed by the oxidative cyclization of these receptors. Receptor 1a was successfully applied to the determination of the Cu2?+ in drug sample with a low detection limit of 2.2?×?10??8?mol?L??1.
Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses
Barman, Sanmitra,You, Lei,Chen, Ran,Codrea, Vlad,Kago, Grace,Edupuganti, Ramakrishna,Robertus, Jon,Krug, Robert M.,Anslyn, Eric V.
, p. 81 - 90 (2014)
A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl) ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
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.
Synthesis of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole moiety: Their in vitro evaluation against PDE4B
Rao, Raja Mohan,Luther, Bethala Jawahar,Rani, Chekuri Sharmila,Suresh, Namburi,Kapavarapu, Ravikumar,Parsa, Kishore V.L.,Rao, Mandava V. Basaveswara,Pal, Manojit
, p. 1166 - 1171 (2014)
A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling-cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using 10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target compounds. All the synthesized compounds were tested for their PDE4B inhibitory potential in vitro using a cell based cAMP reporter assay. Some of them showed fold increase of the cAMP level when tested at 30 μM. A representative compound showed encouraging PDE4B inhibitory properties that were supported by its docking results.
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.
Anticancer activity ofwater-soluble olsalazine-pamam-dendrimer-salicylic acid-conjugates
Cortez-Maya, Sandra,Pedro-Hernández, Luis Daniel,Martínez-Klimova, Elena,Ramírez-ápan, Teresa,Martínez-García, Marcos
, (2019)
Improving the activity and selectivity profile of anticancer agents will require designing drug carrier systems that employ soluble macromolecules. Olsalazine-PAMAM-dendrimer-salicylic acid-conjugates with dendritic arms of different lengths have shown good stability regarding the chemical link between drug and spacer. In this study, the drug release was followed in vitro by ultraviolet (UV) studies. Evaluation of the cytotoxicity of the olsalazine-PAMAM-dendrimer-salicylic acid-conjugates employing a sulforhodamine B (SRB) assay in PC-3 (human prostatic adenocarcinoma) and MCF-7 (human mammary adenocarcinoma) cell lines demonstrated that conjugate 9 was more active as an antiproliferative agent than cisplatin, and no cytotoxicity towards the African green monkey kidney fibroblast (COS-7) cell line was observed in any of the conjugates synthesized in the present work.
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.
