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Menthol

2007 Schools Wikipedia Selection. Related subjects: Chemical compounds

                               Menthol
                (-)-Menthol (-)-Menthol (-)-Menthol
                               General
           Systematic name                     2-(2-Propyl)-5-methyl-
                                                       1-cyclohexanol
    for racemic (−)-isomer             (2R)-(2-Propyl)-(5S)-methyl-
                                                    (1R)-cyclohexanol
               Other names                 3-p-Menthanol,
                                            Hexahydrothymol,
                                              Menthomenthol,
                                                   peppermint camphor
         Molecular formula                                C[10]H[20]O
                    SMILES                        CC1CCC(C(C1)O)C(C)C
                Molar mass                               156.27 g/mol
                Appearance                         White or colorless
                                                    crystalline solid
                CAS number                         [89-78-1], racemic
                                              [2216-51-5], (−)-isomer
                             Properties
         Density and phase                        0.890 g/cm^3, solid
                                              (racemic or (−)-isomer)
       Solubility in water               Slightly soluble, (−)-isomer
In ethanol, diethyl ether,
       acetone, chloroform
       acetic acid, hexane                                    Soluble
             Melting point   36-38 °C (311 K), racemic
                                42-45 °C (318 K), (−)-form (α)
                                              35-33-31 °C, (−)-isomer
             Boiling point                             212 °C (485 K)
    Chiral rotation [α][D]              -50° at 18 °C, 10% EtOH soln.
                               Hazards
                      MSDS                              External MSDS
              Main hazards                        Irritant, flammable
                  NFPA 704

                          2
                          1
                          0

               Flash point                                      93 °C
             R/S statement                       R37/38, R41 S26, S36
              RTECS number                         OT0350000, racemic
                                            OT0700000, (−)-enantiomer
                       Supplementary data page
    Structure & properties                              n, ε[r], etc.
        Thermodynamic data                            Phase behaviour
                                                   Solid, liquid, gas
             Spectral data                            UV, IR, NMR, MS
                          Related compounds
          Related alcohols                     Cyclohexanol, Pulegol,
                                            Dihydrocarveol, Piperitol
         Related compounds      Menthone, Menthene,
                                             Thymol, p- Cymene,
                                                          Citronellal
          Except where noted otherwise, data are given for
                materials in their standard state (at 25°C, 100 kPa)
                                    Infobox disclaimer and references

   Menthol is a covalent organic compound made synthetically or obtained
   from peppermint or other mint oils. It is a waxy, crystalline
   substance, clear or white in colour, 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.

History and occurrence

   There is evidence that menthol has been known in Japan for more than
   2000 years, but in the west it was not isolated until 1771, by Gambius.
   (-)-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.

Structure

   Natural menthol exists as one pure enantiomer, nearly always the
   (1R,2S,5R) form (bottom left of diagram below). The other seven
   stereoisomers are:

   Structures of menthol isomers

   In the natural compound, the isopropyl group is oriented trans-
   orientation to both the methyl and alcohol groups. Thus it can be drawn
   in any of the ways shown:

   Menthol chair conformation

   In the ground state all three bulky groups in the chair are equatorial,
   making (-)-menthol and its enantiomer the most stable two isomers out
   of the eight.

   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.

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 balms and cough medicines
     * As an antipruritic 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 products like Camphor or Capsicum. 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 Balm IcyHot patches or knee/elbow sleeves
     * In decongestants for chest and sinuses (cream, patch or nose
       inhaler)
          + Examples: Vicks Vaporub
     * In certain medications used to treat sunburns, as it provides a
       cooling sensation (then often associated with Aloe)
     * As an additive in certain cigarette brands, for flavor, to reduce
       the throat and sinus irritation caused by smoking and arguably to
       reduce the bad-breath smokers experience and possibly improve the
       smell of second-hand smoke.
     * Commonly used in oral hygiene products and bad-breath remedies like
       mouthwash, toothpaste, mouth and tongue-spray, and more generally
       as a food flavor agent e.g. in chewing-gum, candy
     * In a soda as well as in a syrup to be mixed with water to obtain a
       very low alcohol drink or (brand Rickles in France). The syrup
       is/was also used to alleviate nausea, in particular motion
       sickness, by pouring a few drops on a lump of sugar.
     * As a pesticide against tracheal mites of honeybees
     * In perfumery, menthol is used to prepare menthyl esters to
       emphasise 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 Asia, esp.
       Japan: some variety use `functional protrusion' i.e. 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 (ex: St Ives)

   Some supporters of the homeopathic theory of pharmacology believe that
   menthol interferes with the effects of homeopathic remedies. Its use is
   strongly discouraged for those seeking homeopathic cures, to the point
   of prohibiting the use of mint-flavored toothpaste. Currently no other
   reported nutrient or herb interactions involve menthol. Menthol is
   available as a dietary supplement or natural medicine in the form of
   peppermint oil. It is used in Eastern medicine to treat indigestion,
   nausea, sore throat, diarrhoea, colds, and headaches. (-)-Menthol has
   low toxicity: Oral (rat) LD50: 3300 mg/kg; Skin (rabbit) LD50: 15800
   mg/kg).

   In organic chemistry, menthol is used as a chiral auxiliary in
   asymmetric synthesis. For example, sulfinate esters made from sulfinyl
   chlorides and menthol can be used to make enantiomerically pure
   sulfoxides by reaction with organolithium reagents or Grignard
   reagents. Menthol is also used for classical resolution of chiral
   carboxylic acids, via the menthyl esters.

Synthesis

   As with many widely-used natural products, the demand for menthol
   greatly exceeds the supply from natural sources. Menthol is
   manufactured as a single enantiomer (94% ee) by Takasago International
   Co. on a scale of 400 000 tonnes per year. The process involves an
   asymmetric synthesis developed by a team led by Ryoji Noyori:

   Manufacturing process for menthol

   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. For preparation of
   other isomers such as neomenthol, see ref. 1.

Chemical properties

   Menthol reacts in many ways like a normal secondary alcohol. It is
   oxidised to menthone by oxidising agents such as chromic acid, 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. PCl[5] gives menthyl chloride.

   Reactions of menthol

Biological properties

   Menthol's ability to chemically trigger cold-sensitive receptors in the
   skin is responsible for the well known cooling sensation that it
   provokes when inhalated, eaten, or applied to the skin. It should be
   noted that Menthol does not cause an actual drop in temperature. . In
   this sense it is similar to capsaicin, the chemical responsible for the
   spiciness of hot peppers (which stimulates heat sensors, also without
   causing actual temperature rise).
   Retrieved from " http://en.wikipedia.org/wiki/Menthol"
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   with only minor checks and changes (see www.wikipedia.org for details
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