Menthol
Encyclopedia
Menthol is an organic compound
made synthetically or obtained from peppermint
or other mint
oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature
and melts slightly above. The main form of menthol occurring in nature is (−)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic
and counterirritant
qualities, and it is widely used to relieve minor throat irritation
. Menthol also acts as a weak kappa Opioid receptor
agonist
.
In the natural compound, the isopropyl
group is in the trans
orientation to both the methyl and hydroxyl
groups. Thus it can be drawn in any of the ways shown:
The (+) and (–) enantiomers of menthol are the most stable among these based on their cyclohexane conformation
s. With the ring itself in a chair conformation, all three bulky groups can orient in equatorial positions.
There are two crystal forms for racemic
menthol; these have melting points of 28 °C and 38 °C. Pure (−)-menthol has four crystal forms, of which the most stable is the α form, the familiar broad needles.
receptors in the skin is responsible for the well-known cooling sensation that it provokes when inhaled, eaten, or applied to the skin. In this sense it is similar to capsaicin
, the chemical responsible for the spiciness of hot peppers (which stimulates heat sensors
, also without causing an actual change in temperature).
Menthol has analgesic
properties that are mediated through a selective activation of κ-opioid receptors. Menthol also blocks voltage sensitive sodium channels, reducing neural activity that may stimulate muscles. Menthol also enhances the efficacy of ibuprofen
in topical applications via vasodilation
, which reduces skin barrier function.
is the primary species of mint
used to make natural menthol crystals and natural menthol flakes. This species is primarily grown in the Uttar Pradesh
region in India
.
(−)-Menthol (also called l-menthol or (1R,2S,5R)-menthol) occurs naturally in peppermint oil (along with a little menthone
, the ester menthyl acetate
and other compounds), obtained from Mentha x piperita
. Japanese menthol also contains a small percentage of the 1-epimer
, (+)-neomenthol.
Biosynthesis of menthol was investigated in M. x piperita, and all enzymes involved in its biosynthesis have been identified and characterized.
(94% ee
) on the scale of 3,000 tons per year by Takasago International Corporation
. The process involves an asymmetric synthesis developed by a team led by Ryōji Noyori
:
Image:Menthol synthesis.png|
rect 6 14 131 92 myrcene
rect 136 46 201 63 diethylamine
rect 468 110 628 180 citronellal
rect 387 112 458 135 zinc bromide
desc bottom-left
The process begins by forming an allylic amine from myrcene, which undergoes asymmetric isomerisation
in the presence of a BINAP
rhodium
complex to give (after hydrolysis
) enantiomerically pure R-citronellal
. This is cyclised by a carbonyl-ene-reaction initiated by zinc bromide
to isopulegol which is then hydrogenated to give pure (1R,2S,5R)-menthol.
Racemic
menthol can be prepared simply by hydrogenation of thymol
, and menthol is also formed by hydrogenation of pulegone
.
In organic chemistry
, menthol is used as a chiral auxiliary
in asymmetric synthesis. For example, sulfinate ester
s made from sulfinyl chlorides and menthol can be used to make enantiomerically pure
sulfoxides by reaction with organolithium reagent
s or Grignard reagents
. Menthol reacts with chiral carboxylic acids to give diastereomic menthyl esters, which are useful for chiral resolution
.
by oxidising agents such as chromic acid
or dichromate, though under some conditions the oxidation can go further and break open the ring. Menthol is easily dehydrated to give mainly 3-menthene, by the action of 2% sulfuric acid
. PCl5 gives menthyl chloride.
for more than 2000 years, but in the West
it was not isolated until 1771, by Hieronymus David Gaubius
. Early characterizations were done by Oppenheim, Beckett, Moriya, and Atkinson.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
made synthetically or obtained from peppermint
Peppermint
Peppermint is a hybrid mint, a cross between the watermint and spearmint . The plant, indigenous to Europe, is now widespread in cultivation throughout all regions of the world...
or other mint
Mentha
Mentha is a genus of flowering plants in the family Lamiaceae . The species are not clearly distinct and estimates of the number of species varies from 13 to 18. Hybridization between some of the species occurs naturally...
oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature
Room temperature
-Comfort levels:The American Society of Heating, Refrigerating and Air-Conditioning Engineers has listings for suggested temperatures and air flow rates in different types of buildings and different environmental circumstances. For example, a single office in a building has an occupancy ratio per...
and melts slightly above. The main form of menthol occurring in nature is (−)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
and counterirritant
Counterirritant
A counterirritant is a substance which creates inflammation in one location with the goal of lessening the inflammation in another location. They can be used as antipruritics. This strategy falls into the more general category of counterstimulation....
qualities, and it is widely used to relieve minor throat irritation
Throat irritation
Throat irritation is a common complaint in individuals of all ages. Throat irritation means different things to different people. Some people may mean a dry cough; others describe it as a scratchy feeling at the back of the throat and others simply mean a sensation of something stuck at the back of...
. Menthol also acts as a weak kappa Opioid receptor
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
.
Structure
Natural menthol exists as one pure stereoisomer, nearly always the (1R,2S,5R) form (bottom left corner of the diagram below). The eight possible stereoisomers are:In the natural compound, the isopropyl
Isopropyl
In organic chemistry, isopropyl is a propyl with a group attached to the secondary carbon. If viewed as a functional group an isopropyl is an organic compound with a propyl group attached at its secondary carbon.The bond is therefore on the middle carbon....
group is in the trans
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
orientation to both the methyl and hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
groups. Thus it can be drawn in any of the ways shown:
The (+) and (–) enantiomers of menthol are the most stable among these based on their cyclohexane conformation
Cyclohexane conformation
A cyclohexane conformation is any of several three-dimensional shapes that a cyclohexane molecule can assume while maintaining the integrity of its chemical bonds....
s. With the ring itself in a chair conformation, all three bulky groups can orient in equatorial positions.
There are two crystal forms for racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
menthol; these have melting points of 28 °C and 38 °C. Pure (−)-menthol has four crystal forms, of which the most stable is the α form, the familiar broad needles.
Biological properties
Menthol's ability to chemically trigger the cold-sensitive TRPM8TRPM8
Transient receptor potential cation channel subfamily M member 8 , also known as the cold and menthol receptor 1 , is a protein that in humans is encoded by the TRPM8 gene.-Function:...
receptors in the skin is responsible for the well-known cooling sensation that it provokes when inhaled, eaten, or applied to the skin. In this sense it is similar to capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
, the chemical responsible for the spiciness of hot peppers (which stimulates heat sensors
TRPV1
The transient receptor potential cation channel subfamily V member 1 ', also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene...
, also without causing an actual change in temperature).
Menthol has analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
properties that are mediated through a selective activation of κ-opioid receptors. Menthol also blocks voltage sensitive sodium channels, reducing neural activity that may stimulate muscles. Menthol also enhances the efficacy of ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
in topical applications via vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
, which reduces skin barrier function.
Occurrence
Mentha arvensisMentha arvensis
Mentha arvensis is a species of mint with a circumboreal distribution. It is native to the temperate regions of Europe and western and central Asia, east to the Himalaya and eastern Siberia, and North America.It is a herbaceous perennial plant growing to 10–60 cm tall...
is the primary species of mint
Mentha
Mentha is a genus of flowering plants in the family Lamiaceae . The species are not clearly distinct and estimates of the number of species varies from 13 to 18. Hybridization between some of the species occurs naturally...
used to make natural menthol crystals and natural menthol flakes. This species is primarily grown in the Uttar Pradesh
Uttar Pradesh
Uttar Pradesh abbreviation U.P. , is a state located in the northern part of India. With a population of over 200 million people, it is India's most populous state, as well as the world's most populous sub-national entity...
region in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
.
(−)-Menthol (also called l-menthol or (1R,2S,5R)-menthol) occurs naturally in peppermint oil (along with a little menthone
Menthone
Menthone is a naturally occurring organic compound with a molecular formula C10H18O. l-Menthone , shown at right, is the most abundant in nature of the four possible stereoisomers. Menthone is a monoterpene and a ketone...
, the ester menthyl acetate
Menthyl acetate
Menthyl acetate is a natural monoterpene which contributes to the smell and flavor of peppermint. It is the acetate ester of menthol. Menthyl acetate constitutes 3-5% of the volatile oil of mentha piperita....
and other compounds), obtained from Mentha x piperita
Peppermint
Peppermint is a hybrid mint, a cross between the watermint and spearmint . The plant, indigenous to Europe, is now widespread in cultivation throughout all regions of the world...
. Japanese menthol also contains a small percentage of the 1-epimer
Epimer
In chemistry, epimers are diastereomers that differ in configuration of only one stereogenic center. Diastereomers are a class of stereoisomers that are non-superposable, non-mirror images of one another....
, (+)-neomenthol.
Biosynthesis of menthol was investigated in M. x piperita, and all enzymes involved in its biosynthesis have been identified and characterized.
Production
As with many widely-used natural products, the demand for menthol greatly exceeds the supply from natural sources. Menthol is manufactured as a single enantiomerEnantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
(94% ee
Enantiomeric excess
The enantiomeric excess of a substance is a measure of how pure it is. In this case, the impurity is the undesired enantiomer .-Definition:...
) on the scale of 3,000 tons per year by Takasago International Corporation
Takasago International Corporation
is a major international producer of flavors and fragrances headquartered in Japan, with presence in 22 countries worldwide and net sales of $900 million in . Major competitors include Firmenich, International Flavors and Fragrances, Givaudan and Symrise.-History:...
. The process involves an asymmetric synthesis developed by a team led by Ryōji Noyori
Ryoji Noyori
is a Japanese chemist. He won the Nobel Prize in Chemistry in 2001. Noyori shared half of the prize with William S. Knowles for the study of chirally catalyzed hydrogenations; the second half of the Prize went to K. Barry Sharpless for his study in chirally catalyzed oxidation reactions...
:
Image:Menthol synthesis.png|
rect 6 14 131 92 myrcene
rect 136 46 201 63 diethylamine
Diethylamine
Diethylamine is a secondary amine with the molecular structure CH3CH2NHCH2CH3. It is a flammable, strongly alkaline liquid. It is miscible with water and ethanol. It is a colorless liquid which often appears brown due to impurities...
rect 468 110 628 180 citronellal
Citronellal
Citronellal or rhodinal or 3,7-dimethyloct-6-en-1-al is a monoterpenoid, the main component in the mixture of terpenoid chemical compounds that give citronella oil its distinctive lemon scent....
rect 387 112 458 135 zinc bromide
Zinc bromide
Zinc bromide is a inorganic compound with the chemical formula ZnBr2. It is a colourless salt that shares many properties with zinc chloride , namely a high solubility in water forming acidic solutions, and solubility in organic solvents...
desc bottom-left
- Notes:
- Details on the new coding for clickable images is here: mw:Extension:ImageMap
- This image editor was used.
The process begins by forming an allylic amine from myrcene, which undergoes asymmetric isomerisation
Isomerisation
In chemistry isomerisation is the process by which one molecule is transformed into another molecule which has exactly the same atoms, but the atoms are rearranged e.g. A-B-C → B-A-C . In some molecules and under some conditions, isomerisation occurs spontaneously...
in the presence of a BINAP
BINAP
BINAP is an abbreviation for the organophosphorus compound 2,2'-bis-1,1'-binaphthyl. This chiral ligand is widely used in asymmetric synthesis. It consists of a pair of 2-diphenylphosphinonaphthyl groups linked at the 1 and 1´ positions. This C2-symmetric framework lacks stereogenic atom, but...
rhodium
Rhodium
Rhodium is a chemical element that is a rare, silvery-white, hard and chemically inert transition metal and a member of the platinum group. It has the chemical symbol Rh and atomic number 45. It is composed of only one isotope, 103Rh. Naturally occurring rhodium is found as the free metal, alloyed...
complex to give (after hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
) enantiomerically pure R-citronellal
Citronellal
Citronellal or rhodinal or 3,7-dimethyloct-6-en-1-al is a monoterpenoid, the main component in the mixture of terpenoid chemical compounds that give citronella oil its distinctive lemon scent....
. This is cyclised by a carbonyl-ene-reaction initiated by zinc bromide
Zinc bromide
Zinc bromide is a inorganic compound with the chemical formula ZnBr2. It is a colourless salt that shares many properties with zinc chloride , namely a high solubility in water forming acidic solutions, and solubility in organic solvents...
to isopulegol which is then hydrogenated to give pure (1R,2S,5R)-menthol.
Racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
menthol can be prepared simply by hydrogenation of thymol
Thymol
Thymol is a natural monoterpene phenol derivative of cymene, C10H14O, isomeric with carvacrol, found in oil of thyme, and extracted from Thymus vulgaris and various other kinds of plants as a white crystalline substance of a pleasant aromatic odor and strong antiseptic properties...
, and menthol is also formed by hydrogenation of pulegone
Pulegone
Pulegone is a naturally occurring organic compound obtained from the essential oils of a variety of plants such as Nepeta cataria , Mentha piperita, and pennyroyal. It is classified as a monoterpene....
.
Applications
Menthol is included in many products for a variety of reasons. These include:- In non-prescription products for short-term relief of minor sore throat and minor mouth or throat irritation
- Examples: lip balmLip balmLip balm or lip salve is a wax-like substance applied topically to the lips of the mouth to relieve chapped or dry lips, angular cheilitis, stomatitis, or cold sores. Lip balm often contains beeswax or carnauba wax, camphor, cetyl alcohol, lanolin, paraffin, and petrolatum, among other ingredients...
s and cough medicineCough medicineA cough medicine is a medicinal drug used in an attempt to treat coughing and related conditions. For dry coughs, treatment with cough suppressants may be attempted to suppress the body's urge to cough...
s
- Examples: lip balm
- As an antipruriticAntipruriticAntipruritics, also known as anti-itch drugs, are medications that inhibit the itching that is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those from mosquitoes, fleas, and mites, and contact dermatitis and...
to reduce itching - As a topical analgesic to relieve minor aches and pains such as muscle cramps, sprains, headaches and similar conditions, alone or combined with chemicals like camphorCamphorCamphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...
, eucalyptus oilEucalyptus oilEucalyptus oil is the generic name for distilled oil from the leaf of Eucalyptus, a genus of the plant family Myrtaceae native to Australia and cultivated worldwide. Eucalyptus oil has a history of wide application, as a pharmaceutical, antiseptic, repellent, flavouring, fragrance and industrial uses...
or capsaicinCapsaicinCapsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
. In Europe it tends to appear as a gel or a cream, while in the US patches and body sleeves are very frequently used- Examples: Tiger BalmTiger BalmTiger Balm is the trade name for a heat rub manufactured and distributed by Haw Par Healthcare in Singapore.- History :It was originally developed in the 1870s by a herbalist, Aw Chu Kin, in Rangoon, Burma, who asked his sons Aw Boon Haw and Aw Boon Par on his deathbed to perfect the...
, or IcyHotIcyHotIcyHot is a topical rubefacient heat rub meant for relieving pains such as arthritis, backache, muscle strains, sprains, bruises, and cramps. IcyHot, produced and marketed by Chattem, now a subsidiary of Sanofi-Aventis, is known for its dual action pain relief, claiming it is "Icy to dull the...
patches or knee/elbow sleeveSleeveSleeve is that part of a garment which covers the arm, or through which the arm passes or slips. The pattern of the sleeve is one of the characteristics of fashion in dress, varying in every country and period...
s
- Examples: Tiger Balm
- In decongestantDecongestantA decongestant or nasal decongestant is a type of drug that is used to relieve nasal congestion.-Pharmacology:The vast majority of decongestants act via enhancing norepinephrine and epinephrine or adrenergic activity by stimulating the α-adrenergic receptors...
s for chest and sinuses (cream, patch or nose inhaler)- Examples: Vicks VaporubVicksVicks is a line of over-the-counter medications owned by the American company Procter & Gamble. Vicks manufactures NyQuil and its sister medication, DayQuil. The Vicks brand also produces Formula 44 cough medicines, cough drops, VapoRub, and a number of inhaled breathing treatments...
, MentholatumMentholatumThe Mentholatum Company, Inc., founded in 1889 by Albert Alexander Hyde, is a maker of non-prescription health care products. It was bought out by Rohto Pharmaceutical Co., a Japanese health care company, in 1988...
, vapoRem
- Examples: Vicks Vaporub
- In certain medications used to treat sunburnSunburnA sunburn is a burn to living tissue, such as skin, which is produced by overexposure to ultraviolet radiation, commonly from the sun's rays. Usual mild symptoms in humans and other animals include red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. An excess of UV...
s, as it provides a cooling sensation (then often associated with aloeAloeAloe , also Aloë, is a genus containing about 500 species of flowering succulent plants. The most common and well known of these is Aloe vera, or "true aloe"....
) - As an additive in certain cigarette brandsMenthol cigaretteA menthol cigarette is a cigarette flavored with the compound menthol, a substance which triggers the cold-sensitive nerves in the skin without actually providing a drop in temperature....
, for flavor, to reduce the throat and sinus irritation caused by smoking. - Commonly used in oral hygieneOral hygieneTeeth cleaning is part of oral hygiene and involves the removal of dental plaque from teeth with the intention of preventing cavities , gingivitis, and periodontal disease. People routinely clean their own teeth by brushing and interdental cleaning, and dental hygienists can remove hardened...
products and bad-breath remedies like mouthwashMouthwashMouthwash or mouth rinse is a product used to enhance oral hygiene. Some manufacturers of mouthwash claim that antiseptic and anti-plaque mouth rinse kill the bacterial plaque causing cavities, gingivitis, and bad breath. Anti-cavity mouth rinse uses fluoride to protect against tooth decay...
, toothpasteToothpasteToothpaste is a paste or gel dentifrice used with a toothbrush as an accessory to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it serves as an abrasive that aids in removing the dental plaque and food from the teeth, assists in suppressing...
, mouth and tongue-spray, and more generally as a food flavor agent; e.g., in chewing gumChewing gumChewing gum is a type of gum traditionally made of chicle, a natural latex product, or synthetic rubber known as polyisobutylene. For economical and quality reasons, many modern chewing gums use rubber instead of chicle...
, candyCandyCandy, specifically sugar candy, is a confection made from a concentrated solution of sugar in water, to which flavorings and colorants are added... - In a sodaSoft drinkA soft drink is a non-alcoholic beverage that typically contains water , a sweetener, and a flavoring agent...
to be mixed with water to obtain a very low alcohol drink or pure (brand RicqlèsRicqlèsRicqlès is a French soft drink. The brand Ricqlès was created in 1838 in Uzès, France, and was originally a medicinal mint spirit. In 1954 the company introduced the soft drink version of the beverage....
which contains 80% alcohol in France). The alcohol is also used to alleviate nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, in particular motion sicknessMotion sicknessMotion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
, by pouring a few drops on a lump of sugar. - As a pesticide against tracheal mites of honey beeHoney beeHoney bees are a subset of bees in the genus Apis, primarily distinguished by the production and storage of honey and the construction of perennial, colonial nests out of wax. Honey bees are the only extant members of the tribe Apini, all in the genus Apis...
s - In perfumery, menthol is used to prepare menthyl esters to emphasize floral notes (especially rose)
- In first aid products such as "mineral ice" to produce a cooling effect as a substitute for real ice in the absence of water or electricity (Pouch, Body patch/sleeve or cream)
- In various patches ranging from fever-reducing patches applied to children's foreheads to "foot patches" to relieve numerous ailments (the latter being much more frequent and elaborate in AsiaAsiaAsia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, especially JapanJapanJapan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
: some varieties use "functional protrusions", or small bumps to massage ones feet as well as soothing them and cooling them down) - In some beauty products such as hair-conditioners, based on natural ingredients (e.g. St. Ives)
- As an antispasmodicAntispasmodicAn antispasmodic is a drug or a herb that suppresses muscle spasms.-Smooth muscle spasm:One type of antispasmodics is used for smooth muscle contraction, especially in tubular organs of the gastrointestinal tract...
and smooth muscleSmooth muscleSmooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
relaxant in upper gastrointestinal endoscopyEndoscopyEndoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
.
In organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
, menthol is used as a chiral auxiliary
Chiral auxiliary
A chiral auxiliary is a chemical compound or unit that is temporarily incorporated into an organic synthesis so that it can be carried out asymmetrically with the selective formation of one of two enantiomers...
in asymmetric synthesis. For example, sulfinate ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s made from sulfinyl chlorides and menthol can be used to make enantiomerically pure
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
sulfoxides by reaction with organolithium reagent
Organolithium reagent
An organolithium reagent is an organometallic compound with a direct bond between a carbon and a lithium atom. As the electropositive nature of lithium puts most of the charge density of the bond on the carbon atom, effectively creating a carbanion, organolithium compounds are extremely powerful...
s or Grignard reagents
Grignard reaction
The Grignard reaction is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides add to a carbonyl group in an aldehyde or ketone. This reaction is an important tool for the formation of carbon–carbon bonds...
. Menthol reacts with chiral carboxylic acids to give diastereomic menthyl esters, which are useful for chiral resolution
Chiral resolution
Chiral resolution in stereochemistry is a process for the separation of racemic compounds into their enantiomers. It is an important tool in the production of optically active drugs...
.
Reactions
Menthol reacts in many ways like a normal secondary alcohol. It is oxidised to menthoneMenthone
Menthone is a naturally occurring organic compound with a molecular formula C10H18O. l-Menthone , shown at right, is the most abundant in nature of the four possible stereoisomers. Menthone is a monoterpene and a ketone...
by oxidising agents such as chromic acid
Chromic acid
The term chromic acid is usually used for a mixture made by adding concentrated sulfuric acid to a dichromate, which may contain a variety of compounds, including solid chromium trioxide. This kind of chromic acid may be used as a cleaning mixture for glass. Chromic acid may also refer to the...
or dichromate, though under some conditions the oxidation can go further and break open the ring. Menthol is easily dehydrated to give mainly 3-menthene, by the action of 2% sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
. PCl5 gives menthyl chloride.
History
There is evidence that menthol has been known in JapanJapan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
for more than 2000 years, but in the West
Western world
The Western world, also known as the West and the Occident , is a term referring to the countries of Western Europe , the countries of the Americas, as well all countries of Northern and Central Europe, Australia and New Zealand...
it was not isolated until 1771, by Hieronymus David Gaubius
Hieronymus David Gaubius
Hieronymus David Gaubius was a German physician and chemist.-Life:He was a native of Heidelberg. He studied medicine and sciences at the Universities of Harderwijk and Leiden, where he was a pupil of Hermann Boerhaave and Bernhard Siegfried Albinus...
. Early characterizations were done by Oppenheim, Beckett, Moriya, and Atkinson.
Compendial status
- United States PharmacopeiaUnited States PharmacopeiaThe United States Pharmacopeia is the official pharmacopeia of the United States, published dually with the National Formulary as the USP-NF. The United States Pharmacopeial Convention is the nonprofit organization that owns the trademark and copyright to the USP-NF and publishes it every year...
23 - Japanese Pharmacopoeia 15
- Food Chemical Codex
Toxicology and MSDS data
Currently no reported nutrient or herb interactions involve menthol. (−)-Menthol has low toxicity: Oral (rat) LD50: 3300 mg/kg; Skin (rabbit) LD50: 15800 mg/kg.Further reading
- E. E. Turner, M. M. Harris, Organic Chemistry, Longmans, Green & Co., London, 1952.
- Handbook of Chemistry and Physics, 71st edition, CRC Press, Ann Arbor, Michigan, 1990.
- The Merck Index, 7th edition, Merck & Co, Rahway, New Jersey, USA, 1960.
- Perfumer & Flavorist, December, 2007, Vol. 32, No.12, Pages 38–47
External links
- Colacot T. J. Platinum Metals Review 2002, 46(2), 82-83.
- Ryoji Noyori Nobel lecture (2001)
- Menthol Information
- Cooler than Menthol
- A review of menthol from the Science Creative Quarterly