MENTHOL

MENTHOL Basic information
Product Name:MENTHOL
Synonyms:3-p-Menthol;4-Isopropyl-1-methylcyclohexan-3-ol;5-methyl-2-(1-methylethyl)-,(1.alpha.,2.beta.,5.alpha.)-(+-)-Cyclohexanol;5-methyl-2-(1-methylethyl)-,(1alpha,2beta,5alpha)-(+/-)-cyclohexano;cis-1,3-trans-1,4-(+-)-mentho;Cyclohexanol, 5-methyl-2-(1-methylethyl)-, (1alpha,2beta,5alpha)-(±;cyclohexanol,5-methyl-2-(1-methylethyl)-,(1-alpha,2-beta,5-alpha);d,1-menthol
CAS:15356-70-4
MF:C10H20O
MW:156.27
EINECS:239-388-3
Product Categories:MEA - MESAnalytical Standards;Alphabetic;M;NMR Reference Standards;NMRStable Isotopes;Spectroscopy;Biochemistry;Monocyclic Monoterpenes;Terpenes
Mol File:15356-70-4.mol
MENTHOL Structure
MENTHOL Chemical Properties
Melting point 34-36 °C(lit.)
Boiling point 216 °C(lit.)
density 0.89 g/mL at 25 °C(lit.)
vapor pressure 0.8 mm Hg ( 20 °C)
FEMA 2665 | MENTHOL RACEMIC
refractive index 1.4615
Fp 200 °F
storage temp. 2-8°C
solubility Practically insoluble in water, very soluble in ethanol (96 per cent) and in light petroleum, freely soluble in fatty oils and in liquid paraffin, very slightly soluble in glycerol.
form cryst.
color White
InChIKeyNOOLISFMXDJSKH-UHFFFAOYSA-N
CAS DataBase Reference15356-70-4(CAS DataBase Reference)
Safety Information
Hazard Codes Xn,Xi
Risk Statements 37/38-41-48/20/22-40-38-22
Safety Statements 36/37/39-36-26
RIDADR UN 1888 6.1/PG 3
WGK Germany 2
RTECS OT0525000
HS Code 29061100
MSDS Information
ProviderLanguage
SigmaAldrich English
ACROS English
ALFA English
MENTHOL Usage And Synthesis
Chemical PropertiesFree-flowing or agglomerated, crystalline powder or prismatic or acicular, colourless, shiny crystals
Chemical PropertiesRacemic menthol is a mixture of equal parts of the (1R,2S,5R)- and (1S,2R,5S)-isomers of menthol. It is a free-flowing or agglomerated crystalline powder, or colorless, prismatic, or acicular shiny crystals, or hexagonal or fused masses with a strong characteristic odor and taste. The crystalline form may change with time owing to sublimation within a closed vessel. The USP 32 specifies that menthol may be either naturally occurring l-menthol or syntheti-cally prepared racemic or dl-menthol. However, the JP XV and PhEur 6.0, along with other pharmacopeias, include two separate monographs for racemic and l-menthol.
Chemical PropertiesMenthol has three asymmetric carbon atoms in its cyclohexane ring and, therefore, occurs as four pairs of optical isomers.The configurations of four of these isomers are given; the other four are their mirror images.(1R,3R,4S)-(?)-Menthol,,; (1R,3S,4S)-(+)-neomenthol,; (1R,3S,4R)-(+)- isomenthol,; (1R,3R,4R)-(+)-neoisomenthol,. (?)-Menthol is the isomer that occurs most widely in nature. It is the main component of peppermint and cornmint oils obtained from the Mentha piperita and Mentha arvensis species. Esterified menthol also occurs in these oils (e.g., as the acetate and isovalerate).Other menthol stereoisomers may be present in these oils as well.
Physical propertiesPhysical Properties. The eight optically active menthols differ in their sensory properties. (?)-Menthol has a characteristic peppermint odor and also exerts a cooling effect. The other isomers do not possess this cooling effect and are, therefore, not considered to be “refreshing.” Racemic menthol occupies an intermediate position; the cooling effect of the (?)-menthol present is distinctly perceptible.
The enantiomeric menthols have identical physical properties (apart from their specific rotations), but the racemates differ from the optically active forms in, for example, theirmelting points.Although the differences between the boiling points are small, the (racemic) stereoisomers can be separated by fractional distillation. Boiling points (in °C at 101.3 kPa) are as follows:
rac-neomenthol, 211.7
rac-neoisomenthol 214.6
rac-menthol, 216.5
rac-isomenthol, 218.6
Other physical constants of commercially available levorotatory and racemic menthols are as follows: (?)-menthol, mp 43 °C, [α]20 D ?50° (ethanol, 10%); racemic menthol, mp 38 °C.
Chemical Properties. Hydrogenation of menthols yields p-menthane; oxidation with chromic acid or catalytic dehydrogenation yields menthones. Dehydration under mild conditions yields 3-p-menthene as the main product. Reaction with carboxylic acids or their derivatives yields menthyl esters, which are used mainly as aroma substances and in pharmaceutical preparations and formulations. The esterification of menthols with benzoic acid is used on an industrial scale in the resolution of racemic menthol.






OccurrenceHas apparently not been reported to occur in nature
PreparationBy hydrogenation of thymol followed by separation from its other isomers.
IndicationsMenthol, a cyclic alcohol (derived from peppermint, other mint oils, or prepared synthetically), relieves itching by generating a cool sensation. It is usually used in 0.25% to 2% concentrations but is present in concentrations as high as 16% in some OTC products.
DefinitionChEBI: P-menthan-3-ol is any secondary alcohol that is one of the eight possible diastereoisomers of 5-methyl-2-(propan-2-yl)cyclohexan-1-ol. It has a role as a volatile oil component. It is a p-menthane monoterpenoid and a secondary alcohol.
Production MethodsMenthol occurs widely in nature as l-menthol and is the principal component of peppermint and cornmint oils obtained from the Mentha piperita and Mentha arvensis species. Commercially, lmenthol is mainly produced by extraction from these volatile oils. It may also be prepared by partial or total synthetic methods.
Racemic menthol is prepared synthetically via a number of routes, e.g. by hydrogenation of thymol.
Toxicity evaluationThe acute oral LD50 in rats has been reported as 3180 mg/kg by Jenner, Hagan, Taylor, Cook & Fitzhugh (1964) and as 2900 mg/kg by Herken (1961). The acute oral LD50 in cats was reported to be 1500-1600 mg/kg (Flury & Seel, 1926). The sc LD50 in the mouse was reported as 1400-1600 mg/kg (Flury & Seel, 1926) and the ip LD50 as 750 mg/kg in the rat (Herken, 1961) and 1500-1600 mg/kg in the cat (Flury & Seel, 1926). In rabbits, the ip LD50 was reported to be approximately 2000 mg/kg (Herken, 1961), while the acute dermal LD50 exceeded 5000 mg/kg (Levenstein, 1973).
Pharmaceutical ApplicationsMenthol is widely used in pharmaceuticals, confectionery, and toiletry products as a flavoring agent or odor enhancer. In addition to its characteristic peppermint flavor, l-menthol, which occurs naturally, also exerts a cooling or refreshing sensation that is exploited in many topical preparations. Unlike mannitol, which exerts a similar effect due to a negative heat of solution, l-menthol interacts directly with the body’s coldness receptors. d-Menthol has no cooling effect, while racemic menthol exerts an effect approximately half that of l-menthol.
When used to flavor tablets, menthol is generally dissolved in ethanol (95%) and sprayed onto tablet granules and not used as a solid excipient.
Menthol has been investigated as a skin-penetration enhancer and is also used in perfumery, tobacco products, chewing gum and as a therapeutic agent. When applied to the skin, menthol dilates the blood vessels, causing a sensation of coldness followed by an analgesic effect. It relieves itching and is used in creams, lotions, and ointments. When administered orally in small doses menthol has a carminative action.

Safety ProfileModerately toxic by ingestion, intraperitoneal, and subcutaneous routes. An eye and skin irritant. K%en heated to decomposition it emits acrid smoke and irritating fumes. See also MENTHOL and 1-MENTHOL.
SafetyAlmost all toxicological data for menthol relate to its use as a therapeutic agent rather than as an excipient. Inhalation or ingestion of large quantities can result in serious adverse reactions such as ataxia and CNS depression,hypersensitivity reactions, severe abdominal pain, nausea, vomiting, vertigo, drowsiness, and coma.Although menthol is essentially nonirritant there have been some reports of hypersensitivity following topical application. In a Polish study approximately 1% of individuals were determined as being sensitive to menthol.There have been reports of apnea and instant collapse in infants after the local application of menthol to their nostrils.
The WHO has set an acceptable daily intake of menthol at up to 0.4 mg/kg body-weight.
LD50 (rat, IM): 10.0 g/kg
LD50 (rat, oral): 3.18 g/kg
targetGABAA receptor
MetabolismRabbits are said to eliminate 59% of dl-menthol as glucuronide (Williams, 1938).
storageA formulation containing menthol 1% w/w in aqueous cream has been reported to be stable for up to 18 months when stored at room temperature.
Menthol should be stored in a well-closed container at a temperature not exceeding 25°C, since it sublimes readily.
IncompatibilitiesIncompatible with: butylchloral hydrate; camphor; chloral hydrate; chromium trioxide; b-naphthol; phenol; potassium permanganate; pyrogallol; resorcinol; and thymol.
Regulatory StatusIncluded in the FDA Inactive Ingredients Database (dental preparations, inhalations, oral aerosols, capsules, solutions, suspensions, syrups, and tablets; also topical preparations). Included in nonparenteral medicines licensed in the UK. Accepted for use in foods and confectionery as a flavoring agent of natural origin. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
MENTHOL Preparation Products And Raw materials
MENTHOL BOLD CRYSTAL Silicic acid tetra-menthol ester Menthol octadecanoate MENTHOL-BETA-CYCLODEXTRIN COMPLEX Menthol, acetate, cis-1,3,trans-1,4- Menthol, fumarate (2:1), (1R,3R,4S)- (+)-MENTHOL,MENTHOL, (+)-,(1S)-(+)-mentho l-Menthol acetate Menthol tridecanoate 1-(1'(R)-ALPHA-METHYLBENZYL)-AZIRIDINE-2(R)-CARBOXYLIC ACID (-)-MENTHOL ESTER 1-(1'(R)-ALPHA-METHYLBENZYL)-AZIRIDINE-2(S)-CARBOXYLIC ACID (-)-MENTHOL ESTER menthol,isovalerat l-Menthol formate MENTHOL ACETATE Menthol octanoate Menthol heptanoate Menthol hexanoate Menthol pentanoate

Email:[email protected] [email protected]
Copyright © 2024 Mywellwork.com All rights reserved.