Menthol is an organic compound made synthetically or obtained from mint corn, peppermint, or other mint oil. These are crystalline, crystalline, clear or white, which are solid at room temperature and melt slightly above.
The main forms of menthol occurring in nature are (-) - mentol , which are marked (1 R , 2 S , 5 R ) configuration. Menthol has the quality of local anesthetics and counterirritant, and is widely used to relieve mild throat irritation. Menthol also acts as a weak kappa opioid receptor agonist.
Video Menthol
Structure
Menthol naturally exists as a pure stereoisomer, almost always form (1 R , 2 S , 5 R ) (bottom left corner of the diagram below). The eight possible stereoisomers are:
In natural compounds, isopropyl groups are in trans-orientation for both methyl and hydroxyl groups. Thus, it can be drawn in one of the ways shown:
The () - and (-) - enantiomers of menthol are the most stable of these based on their cyclohexane conformation. With the ring itself in a chair conformation, the three large groups can be oriented to the equator position.
The two crystalline forms for the racemic mentol have a melting point of 28Ã, Â ° C and 38Ã, Â ° C. Pure (-) - menthol has four crystalline forms, the most stable being? shape, wide familiar needle.
Maps Menthol
Biological properties
Menthol's ability to chemically trigger cold-sensitive TRPM8 receptors in the skin is responsible for the famous cooling sensations that are triggered when inhaled, eaten, or applied to the skin. In this sense, it is similar to capsaicin, the chemical responsible for the hot pepper spiciness (which stimulates heat sensors, also without causing actual temperature changes).
The analgesic properties of Menthol are mediated through selective activation of the -opioid receptor. Menthol also blocks stress-sensitive sodium channels, reducing nerve activity that can stimulate muscles. One study showed that topical absorption of ibuprofen did not increase with menthol, but did not pay attention to the complementary effects of menthol as the pain reliever itself.
Several studies have shown that menthol acts as GABA A positive allosteric modulator receptor and increases GABAergic transmission in PAG neurons. Menthol also has an anesthetic properties similar to propofol, by modulating the same site from the GABA receptor A .
Menthol is widely used in dental treatment as a topical antibacterial agent, effective against several streptococcal and lactobacillus strains.
Genesis
Mentha arvensis (wild mint) is the main species of mint used to make natural menthol crystals and natural menthol flakes. This species is mainly grown in the Uttar Pradesh region of India.
Menthol occurs naturally in peppermint oil (along with a small amount of menthone, mentile acetate ester and other compounds), obtained from Mentha ÃÆ'â € "piperita
Biosynthesis
Mentle biosynthesis has been studied in Mentha and pipeline and the enzyme involved has been identified and characterized. It begins with the synthesis of terpene limonene, followed by hydroxylation, and then some reduction and isomerization steps.
More specifically, biosynthesis (-) - menthol occurs in the secretory plant gland cells of peppermint. Geranyl diphosphate synthase (GPPS), first catalyzes the reaction of IPP and DMAPP into geranyl diphosphate. Next (-) - limonene synthase (LS) catalyzes the cyclization of geranyl diphosphate into (-) - limonene. (-) - Limonene-3-hydroxylase (L3OH), using O 2 and NADPH, then catalyzing the ally hydroxylation of (-) - limonene at 3 positions to (-) - trans-isopyperitenol. (-) - trans -Isopyperitenol dehydrogenase (iPD) further oxidizes the hydroxyl group at position 3 using NAD to make (-) - isopiperitenone. (-) - Isopiperitenone reductase (iPR) then reduces the double bond between carbon 1 and 2 using NADPH to form () - cis -measure. () - cis -Isopulegone isomerase (IPI) then isomerizes the remaining double bond to form () - pulegone. () - Pulegone reductase (PR) then reduces this double bond using NADPH to form (-) - menthone. (-) - Menthone reductase (MR) then reduces the carbonyl group using NADPH to form (-) - mentol.
Production
Natural bulbs are obtained by freezing peppermint oil. The resulting crystal crystals are then separated by filtering.
The world's total production of menthol in 1998 was 12,000 tons of which 2,500 tons were synthetic. In 2005, the annual production of synthetic menthol almost doubled. The price is in the range of $ 10-20/kg with a peak in the region of $ 40/kg but has reached as high as $ 100/kg. In 1985, it was estimated that China produces the bulk of the world's natural mentol supply, although it seems India has pushed China into second place.
Menthol is manufactured as a single enantiomer (94% e.e.) on a scale of 3,000 tons per year by Takasago International Corporation. This process involves asymmetric synthesis developed by a team led by Ry? Ji Noyori, who won the Nobel Prize in Chemistry in 2001 in recognition of his work in this process:
This process begins by forming an allylic amine of myrcene, which undergoes asymmetric isomerization in the presence of the rhodium complex BINAP to provide (after hydrolysis) a pure enantiomer R -citronellal. This is cyclized by the carbonyl reaction initiated by zinc bromide to isopulegol, which is then hydrogenated to pure (1
Another commercial process is the Haarmann-Reimer process (after the Haarmann & Reimer company, now part of Symrise) This process starts from m -cresol is alkylated with propene to thymol. This compound is hydrogenated in the next step. Racemic Mentol is isolated by fractional distillation. The enantiomers are separated by chiral resolution in reaction with methyl benzoate, selective crystallization followed by hydrolysis.
Racemic Mentol can also be formed by pulegone hydrogenation. In both cases with further processing (crystallizative entrainment resolution of the menthyl benzoate conglomerate) it is possible to concentrate L -enantiomer, but this tends to be less efficient, although higher processing costs can be offset by lower raw material costs. A further advantage of this process is that D -menthol becomes cheaper available for use as chiral auxiliaries, along with the more usual L -anipode.
Apps
Menthol is included in many products for various reasons. These include:
- In products that are not prescribed to relieve a mild sore throat and slight oral or throat irritation.
- Example: medicine balm and cough medicine.
- As an antiprurit to reduce itching.
- As topical analgesics, it is used to relieve mild pain and pain, such as muscle cramps, sprains, headaches and similar conditions, alone or in combination with chemicals such as camphor, eucalyptus oil or capsaicin. In Europe, it tends to appear as a gel or cream, whereas in the US, patches and forearms are very often used.
- Example: Tiger dressing, or IcyHot patch or knee/elbow arm.
- As a penetration enhancer in transdermal drug delivery.
- In decongestants for chest and sinuses (cream, patch or nasal inhaler).
- Example: Vicks VapoRub, Mentholatum, VapoRem.
- In certain medications used to treat sunburn, because it gives a cooling sensation (often associated with aloe vera).
- In aftershave products to relieve razor burn.
- As tobacco additives smoke in some brands of cigarettes, to taste, and to reduce the throat and sinus irritation caused by smoking. Menthol also increases nicotine receptor density, increasing the potential for addiction to tobacco products.
- Commonly used in oral hygiene products and odor drugs, such as mouthwash, toothpaste, mouth and tongue, and more commonly as a food taste agent; such as chewing gum and candy.
- As a pesticide against tracheal bee mites.
- In fragrances, menthol is used to prepare menthyl esters to emphasize floral notes (especially roses).
- In first aid products such as "mineral ice" to produce a cooling effect instead of water or electricity (bag, body/arm or cream).
- In various patches ranging from fever-lowering patches applied to the forehead of children to "patches" to alleviate many diseases (the latter is much more frequent and complicated in Asia, especially Japan: some varieties use "functional bulges" or small bumps to massage a person's feet and cool them down and cool them down).
- In some beauty products such as hair conditioner, based on natural ingredients (eg, St. Ives).
- As antispasmodic and smooth muscle relaxants in the upper gastrointestinal endoscopy.
In organic chemistry, menthol is used as a chiral auxiliary in asymmetric synthesis. For example, sulfinic esters made from sulphinyl chloride and menthol can be used to prepare enantiomerically pure sulphoxides by reaction with organolitium reagents or Grignard reagents. Menthol reacts with chiral carboxylic acids to give the diastereomic menthol ester, which is useful for chiral resolutions.
Reaction
Menthol reacts in many ways like normal secondary alcohol. It is oxidized to the menthone by oxidizing agents such as chromatic acid or dichromate, although in some conditions the oxidation may move further and open the ring. Menthol is easy to dehydrate to give especially 3-menthene, by the action of 2% sulfuric acid. Phosphorus pentachloride (PCl 5 ) provides menthol chloride.
History
In the West, menthol was first isolated in 1771, by Hieronymus David Gaubius. Initial characterization was done by Oppenheim, Beckett, Moriya, and Atkinson. Named by F. L. Alphons Oppenheim (1833-1877) in 1861.
Compendium status
- Pharmacopoeia United States 23
- Japanese Pharmacopoeia 15
- Food Codex Food
Security
The estimated dose lethal for menthol (and peppermint oil) in humans may be as low as 2 g. Survival after a dose of 8 to 9 g has been reported. Overdose effects are abdominal pain, ataxia, atrial fibrillation, bradycardia, coma, dizziness, lethargy, nausea, skin rashes, tremors, vomiting, vertigo.
See also
References
Further reading
External links
- Colacot, T. J. (2002-04-01). "2001 Nobel Prize in Chemistry: Timely recognition for chiral reactions of rhodium, ruthenium and osmium-catalysed". Rev. Metal Metals . 46 (2): 82-83.
- Ryoji Noyori Nobel lecture (2001)
- Menthol Information
- The menthol review of Science Creative Quarterly
Source of the article : Wikipedia
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