[3]

Camphor /kmfr/ is a waxy, flammable, white or transparent solid with a strong aromatic odor. It
is a terpenoid with the chemical formulaC10H16O. It is found in wood of the camphor
laurel (Cinnamomum camphora), a large evergreen tree found in Asia (particularly
in Sumatra, Borneoand Taiwan) and also of Dryobalanops aromatica, a giant of the Bornean forests.
It also occurs in some other related trees in the laurel family, notably Ocotea usambarensis.
Dried rosemary leaves (Rosmarinus officinalis), in the mint family, contain up to 20% camphor. It can
also be synthetically produced from oil of turpentine. It is used for its scent, as an ingredient in
cooking (mainly in India), as an embalming fluid, for medicinal purposes, and in religious ceremonies.
A major source of camphor in Asia is camphor basil.
Norcamphor is a camphor derivative with the three methyl groups replaced by hydrogen.
Contents
[hide]

1 History

2 Production

3 Biosynthesis

4 Reactions

5 Uses

5.1 Culinary

5.2 Medicinal

5.3 Herbalism

5.4 Hindu religious ceremonies

6 Effects on the body

6.1 Small dose

6.2 Large dose toxicity

7 Regulation

8 See also

9 References

10 External links

History[edit]
The word camphor derives from the French word camphre, itself from Medieval Latin camfora,
[4]
from Arabic kafur, from Sanskrit, karpra. The term ultimately was derived from Old Malay kapur
barus which means "the chalk of Barus". Barus was the name of an ancient port located near modern
Sibolga city on the western coast of Sumatra island (today North Sumatra Province, Indonesia). This
port was initially built prior to the Indian - Batak trade in camphor and spices. Traders from India, East
Asia and the Middle East would use the term kapur barus to buy the dried extracted ooze of camphor
trees from local Batak tribesmen; in proto Malay-Austronesian language (Sanskrit adapted-Bataknese
alphabets), it is also known as kapur Barus. Even now, the local tribespeople and Indonesians in
general refer to naphthalene balls and moth balls as kapur Barus. For the local tribespeople, the use
of camphor ranges from deodorant, wood-finishing veneer, traditional rituals and non-edible

preservatives as the camphor tree itself is natively found in that region. The tree, called "Kamfer" in
[citation needed]
Indonesian, is also known for its resistance to tropical termites.

A sample of sublimed camphor

The sublimating capability of camphor gives it several uses. An early international trade in it made
camphor widely known throughout Arabia in pre-Islamic times, as it is mentioned in the Quran 76:5 as
[5]
a flavoring for drinks. By the 13th century, it was used in recipes everywhere in the Muslim world,
[6]
ranging from main dishes such as tharid and stew to desserts.
Already in the 19th century, it was known that with nitric acid, camphor could be oxidized
into camphoric acid. Haller and Blanc published a semisynthesis of camphor from camphoric acid,
which, although demonstrating its structure, would not prove it. The first complete total synthesis for
camphoric acid was published by Gustaf Komppa in 1903. Its starting materials were diethyl
oxalate and 3,3-dimethylpentanoic acid, which reacted by Claisen condensation to give
diketocamphoric acid. Methylation with methyl iodide and a complicated reduction procedure
produced camphoric acid. William Perkinpublished another synthesis a short time later. Previously,
some organic compounds (such as urea) had been synthesized in the laboratory as a proof of
concept, but camphor was a scarce natural product with a worldwide demand. Komppa realized this
and began industrial production of camphor in Tainionkoski,Finland, in 1907.

Production
Camphor can be produced from alpha-pinene, which is abundant in the oils of coniferous trees and
can be distilled from turpentine produced as a side product of chemical pulping. With acetic acid as
the solvent and with catalysis by a strong acid, alpha-pinene readily rearranges into camphene, which
in turn undergoes Wagner-Meerwein rearrangement into the isobornyl cation, which is captured by
acetate to give isobornyl acetate. Hydrolysis into isoborneol followed by oxidation
gives racemic camphor. By contrast, camphor occurs naturally as D-camphor, the (R)-enantiomer.

Biosynthesis[edit]
In biosynthesis, camphor is produced from geranyl pyrophosphate, via cyclisation
of linaloyl pyrophosphate to bornyl pyrophosphate, followed by hydrolysis to borneol and oxidation to
camphor.

Reactions[edit]
Typical camphor reactions are

bromination,

oxidation with nitric acid,

conversion to isonitrosocamphor.

Camphor can also be reduced to isoborneol using sodium borohydride.

In 1998, K. Chakrabarti and coworkers from the Indian Association for the
Cultivation of Science, Kolkata, prepared diamond thin film using camphor as the
[7]
precursor for chemical vapor deposition.
In 2007, carbon nanotubes were successfully synthesized using camphor
[8]
in chemical vapor deposition process.

Uses[edit]
Modern uses include camphor as a plasticizer for nitrocellulose (see Celluloid), as
a moth repellent, as an antimicrobial substance, in embalming, and in fireworks.
Solid camphor releases fumes that form a rust-preventative coating, and is therefore
[9]
stored in tool chests to protect tools against rust.

Some folk remedies state camphor will deter snakes and other reptiles due to its
strong odor. Similarly, camphor is believed to be toxic to insects and is thus
[10]
sometimes used as a repellent. Camphor crystals are sometimes used to prevent
damage to insect collections by other small insects. They are also used as a cough
suppressant.

Culinary[edit]
In ancient and medieval Europe, camphor was used as an ingredient in sweets. It
was used in a wide variety of both savory and sweet dishes in medieval Arabic
language cookbooks, such as al-Kitab al-abikh compiled by ibn Sayyr al[11]
Warrq in the 10th century, and an anonymous Andalusian cookbook of the 13th
[6]
century. It also appears in sweet and savory dishes in a book written in the late
[12]
15th century for the sultans of Mandu, the Ni'matnama.
Currently, camphor is used as a flavoring, mostly for sweets, in Asia. It is widely
used in cooking, mainly for dessert dishes, in India where it is known as kachha
karpooram or "pachha karpoora" ("crude/raw camphor"), in (Telugu:
),
(Tamil:

), (Kannada:

), and is available in Indian

grocery stores where it is labeled as "edible camphor". Flavored tablets of camphor

are also used as an anti-odor element and kept in clothes used on special occasions
and festivals, and also in cupboard corners as a cockroach repellent.

Medicinal[edit]
Camphor is readily absorbed through the skin and produces a feeling of cooling
similar to that of menthol, and acts as slight
local anesthetic and antimicrobial substance. There are anti-itch gelsand cooling
gels with camphor as the active ingredient. Camphor is an active ingredient (along
with menthol) in vapor-steam products, such as Vicks VapoRub.
Camphor may also be administered orally in small quantities (50 mg) for minor heart
[13]
symptoms and fatigue. Through much of the 1900s this was sold under the trade
name Musterole; production ceased in the 1990s.
Camphor has been used in ancient Sumatra to treat sprains, swellings, and
[14]
inflammation. Camphor is a component of paregoric, an opium/camphor tincture
from the 18th century. Also in the 18th century, camphor was used
[15]
by Auenbrugger in the treatment of mania. Based on Hahnemann's writings,
camphor (dissolved in alcohol) was also successfully used to treat the 1854[16]
1855cholera epidemics in Naples.

Herbalism[edit]
Camphor is available as an essential oil for aromatherapy or topical application.

Hindu religious ceremonies[edit]

Camphor is widely used in Hindu religious ceremonies. Hindus worship a holy flame
by burning camphor, which forms an important part of many religious ceremonies.
Camphor is used in theMahashivratri celebrations of Shiva, the Hindu god of
destruction and (re)creation. As a natural pitch substance, it burns cool without
leaving an ash residue, which symbolizes consciousness. Most temples in southern

India have stopped lighting camphor in the main Sanctum Sanctorum because of the
heavy carbon deposits it produces; however, open areas still burn it.
In Tamil Nadu, Andhra Pradesh, Karnataka, Kerala & Andamans, camphor is the
primary ingredient in any holy rituals. At the end of a holy ritual camphor flame
(called Aarti) is burned for the deities.
In Hindu pujas ceremonies, camphor is burned in a ceremonial spoon for
performing aarti. This type of camphor, the processed white crystalline kind, is also
sold at Indian grocery stores. It is not suitable for cooking and is hazardous to health
if eaten.

Effects on the body[edit]

It has effects similar to a muscarinic receptor agonist.

[jargon]

Small dose[edit]
Its effects on the body include tachycardia, vasodilation in skin (flushing), slower
breathing, reduced appetite, increased secretions and excretions such
[17]
as perspiration, diuretic.

Large dose toxicity[edit]

Camphor is poisonous in large doses. It produces symptoms of
irritability, disorientation, lethargy, muscle spasms, vomiting, abdominal
[18][19][20]
cramps, convulsions, and seizures.
Lethal doses in adults are in the range
50500 mg/kg (orally). Generally, two grams cause serious toxicity and four grams
[21]
are potentially lethal.

Regulation[edit]
In 1980, the U.S. Food and Drug Administration set a limit of 11% allowable
camphor in consumer products, and totally banned products labeled as
camphorated oil, camphor oil, camphorliniment, and camphorated liniment (except
"white camphor essential oil", which contains no significant amount of camphor).
Since alternative treatments exist, medicinal use of camphor is discouraged by the
FDA, except for skin-related uses, such as medicated powders, which contain only
small amounts of camphor.

See also[edit]

1,4-Dichlorobenzene

Citral

Eucalyptol

Lavender

Vaporizer

References[edit]
1.

Jump up^ The Merck Index, 7th edition, Merck & Co., Rahway, New Jersey, USA,
1960

2.

Jump up^ Handbook of Chemistry and Physics, CRC Press, Ann Arbor, Michigan,
USA

3.

Jump up^ Mann JC, Hobbs JB, Banthorpe DV, Harborne JB (1994). Natural
products: their chemistry and biological significance. Harlow, Essex, England:
Longman Scientific & Technical. pp. 30911. ISBN 0-582-06009-5.

4.

Jump up^ Camphor at the Online Etymology Dictionary

5.

Jump up^

6.

^ Jump up to:

[Quran 76:5]
a b

An Anonymous Andalusian cookbook of the 13th century,

translated from the original Arabic by Charles Perry

7.

Jump up^ Chakrabarti K,Chakrabarti R, Chattopadhyay KK, Chaudhuri S, Pal AK

(1998). "Nano-diamond films produced from CVD of camphor". Diam Relat
Mater 7 (6): 84552.Bibcode:1998DRM.....7..845C. doi:10.1016/S09259635(97)00312-9.

8.

Jump up^ Kumar M, Ando Y (2007). "Carbon Nanotubes from Camphor: An

Environment-Friendly Nanotechnology". J Phys Conf Ser. 61: 643
6. Bibcode:2007JPhCS..61..643K. doi:10.1088/1742-6596/61/1/129.

9.

Jump up^ Tips for Cabinet Making Shops

10. Jump up^ The Housekeeper's Almanac, or, the Young Wife's Oracle! for 1840!. No.
134. New-York: Elton, 1840. Print.
11. Jump up^ Nasrallah, Nawal (2007). Annals of the Caliphs' Kitchens: Ibn Sayyr alWarrq's Tenth-century Baghdadi Cookbook. Islamic History and Civilization, 70.
Leiden, The Netherlands: Brill. ISBN 978-0-415-35059-4.
12. Jump up^ Titley, Norah M. (2004). The Ni'matnama Manuscript of the Sultans of
Mandu: The Sultan's Book of Delights. Routledge Studies in South Asia. London,
UK: Routledge. ISBN 978-0-415-35059-4.
13. Jump up^ Lketietokeskus. Lkevalmisteet Pharmaca Fennica 1996, p. 814.
14. Jump up^ Miller, Charles. History of Sumatra : An account of Sumatra. p. 121.
15. Jump up^ Pearce, J M S (2008). "Leopold Auenbrugger: camphor-induced epilepsy
remedy for manic psychosis". Eur. Neurol. (Switzerland) 59 (12): 105
7. doi:10.1159/000109581. PMID 17934285.
16. Jump up^ http://www.legatum.sk/en:ahr:bayes-cholera-as-treated-by-dr-rubini-15810355 The American Homoeopathic Review Vol. 06 No. 11-12, 1866, pages 401403
17. Jump up^ Church, John (1797). An inaugural dissertation on camphor: submitted to
the examination of the Rev. John Ewing, S.S.T.P. provost ; the trustees & medical
faculty of the University of Pennsylvania, on the 12th of May, 1797 ; for the degree

of Doctor of Medicine. University of Philadelphia: Printed by John Thompson.

Retrieved January 18, 2013.
18. Jump up^ "Camphor overdose". Medline. NIH. Retrieved January 19, 2012.
19. Jump up^ Martin D, Valdez J, Boren J, Mayersohn M (Oct 2004). "Dermal
absorption of camphor, menthol, and methyl salicylate in humans". Journal of
Clinical Pharmacology 44 (10): 1151
7.doi:10.1177/0091270004268409. PMID 15342616.
20. Jump up^ Uc A, Bishop WP, Sanders KD (Jun 2000). "Camphor
hepatotoxicity". Southern Medical Journal 93 (6): 5968. PMID 10881777.
21. Jump up^ "Poisons Information Monograph: Camphor". International Programme
on Chemical Safety.

http://biocyc.org/META/new-image?type=PATHWAY&object=PWY-6991

http://www.metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6990

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess
the pathway. If an enzyme name is shown in bold, there is experimental evidence for this
enzymatic activity.
Synonyms: (R)-camphor biosynthesis
Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Terpenoids
Biosynthesis Monoterpenoids Biosynthesis Camphor Biosynthesis

Some taxa known to possess this pathway include

: Salvia officinalis

Expected Taxonomic Range: Viridiplantae

Summary:
Camphor is a bicyclic monoterpene with a characteristic pungent odor and taste. Two
enantiomers occur naturally - (+)-camphor, which is produced by several trees, including the
camphor tree (Cinnamomum camphora), and (-)-camphor, which is found in essential oils of
several plants (see (-)-camphor biosynthesis).
(+)-camphor is one of the major components of the volatile oil of sage (Salvia officinalis),
where it appears to function as a phytotoxin inhibiting the growth of competing grasses.

Immature sage leaves synthesize and accumulate camphor most rapidly, and the camphor
content of the leaves increases as they expand [Croteau81].
The first proposal for a pathway for (+)-camphor biosynthesis suggested that neryl
diphosphate was converted to (+)-borneol, which was then dehydrogenated to camphor
[Croteau76]. Subsequent studies showed that a cyclic pyrophosphate intermediate was
involved [Croteau77] and that the preferred precursor was geranyl diphosphate, rather
than neryl diphosphate [Croteau79], leading to the pathway described here.
The first pathway enzyme to be partially purifed and characterized was (+)-borneol
dehydrogenase, which catalyzes the last step in the pathway [Croteau78]. This was followed
by a partial purification of (+)-bornyl-diphosphate diphosphatase [Croteau79a] and (+)-bornyl
diphosphate synthase [Croteau79, Wise98].
Variants: (-)-camphor biosynthesis
Credits:
Created 02-Feb-2012 by Caspi R , SRI International

References
Croteau76: Croteau R, Karp F (1976). "Enzymatic synthesis of camphor from neryl pyrophosphate
by a soluble preparation from sage (Salvia officinalis)." Biochem Biophys Res Commun
72(2);440-7. PMID: 10906
Croteau77: Croteau R, Karp F (1977). "Demonstration of a cyclic pyrophosphate intermediate in the
enzymatic conversion of neryl pyrophosphate to borneol." Arch Biochem Biophys 184(1);77-86.
PMID: 921300
Croteau78: Croteau R, Hooper CL, Felton M (1978). "Biosynthesis of monoterpenes. Partial
purfication and characterization of a bicyclic monoterpenol dehydrogenase from sage (Salvia
officinalis)." Arch Biochem Biophys 188(1);182-93. PMID: 677891
Croteau79: Croteau R, Karp F (1979). "Biosynthesis of monoterpenes: preliminary characterization
of bornyl pyrophosphate synthetase from sage (Salvia officinalis) and demonstration that
Geranyl pyrophosphate is the preferred substrate for cyclization." Arch Biochem Biophys
198(2);512-22. PMID: 42356
Croteau79a: Croteau R, Karp F (1979). "Biosynthesis of monoterpenes: hydrolysis of bornyl
pyrophosphate, an essential step in camphor biosynthesis, and hydrolysis of geranyl
pyrophosphate, the acyclic precursor of camphor, by enzymes from sage (Salvia officinalis)."
Arch Biochem Biophys 198(2);523-32. PMID: 42357
Croteau81: Croteau R, Felton M, Karp F, Kjonaas R (1981). "Relationship of Camphor Biosynthesis
to Leaf Development in Sage (Salvia officinalis)." Plant Physiol 67(4);820-4. PMID: 16661761
Dehal87: Dehal SS, Croteau R (1987). "Metabolism of monoterpenes: specificity of the
dehydrogenases responsible for the biosynthesis of camphor, 3-thujone, and 3-isothujone."
Arch Biochem Biophys 258(1);287-91. PMID: 3310901
Wise98: Wise ML, Savage TJ, Katahira E, Croteau R (1998). "Monoterpene synthases from common
sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase." J Biol Chem
273(24);14891-9. PMID: 9614092

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this

Pathway
Banthorpe70: Banthorpe DV, Baxendale D (1970). "Terpene biosynthesis. 3. Biosynthesis of (+)- and
(-)-camphor in Artemisia, Salvia, and Chrysanthemum species." J Chem Soc Perkin 1 19;26946. PMID: 5532413
Jankowski08: Jankowski MD, Henry CS, Broadbelt LJ, Hatzimanikatis V (2008). "Group contribution
method for thermodynamic analysis of complex metabolic networks." Biophys J 95(3);1487-99.
PMID: 18645197
Latendresse13: Latendresse Mario (2013). "Computing Gibbs Free Energy of Compounds and
Reactions in MetaCyc." Web.
Whittington02: Whittington DA, Wise ML, Urbansky M, Coates RM, Croteau RB, Christianson DW
(2002). "Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by
a terpenoid cyclase." Proc Natl Acad Sci U S A 99(24);15375-80. PMID: 12432096

In Pathway: (-)-camphor biosynthesis

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The reaction direction shown, that is, A + B C + D versus C + D A + B, is in accordance with the
direction in which it was curated.
Mass balance status: Balanced.
is decaprenyl phosphate biosynthesis , trans, trans-farnesyl diphosphate biosynthesis , all-transfarnesol biosynthesis , geranyl diphosphate biosynthesis ,linalool biosynthesis
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Pesto Mediterranean Biochemistry

DOI: 10.1002/chemv.201200001
Author: Klaus Roth
Published Date: 03 January 2012
Source / Publisher: Chemie in unserer Zeit/Wiley-VCH
Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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When we take pesto prepared from fresh basil, fold it into steaming pasta, and allow the inimitable fragrance
to rise up, we ask ourselves: with what aromatic molecules is this plant blessing us? Here we try to uncover the
nature of this culinary-chemical marvel, and thereby come to enjoy it all the more.

Pesto (Italian for crushed) is a paste made out of pine nuts, garlic, hard cheese, olive oil, and of course
above all basil. The dish originated in Genoa, Italy, where basil played an important role as early as the Middle
Ages as a medicinal agent. In folk medicine it was deployed either fresh, dried, or as an oil for treating loss of
appetite, flatulence, fever, cough, migraine, nervousness, sleeplessness, and digestive problems.

1 Basil (Ocimum basilicum)

Every gastronome raves about herbs from the mint family, which includes such splendid representatives as
marjoram, oregano, savory, sage, thyme, mint, lemon balm, and rosemary [1]. The most beloved members of the
mint family belong to the genus Ocinum (gr. Ozein = to smell) [2], made up of over 60 species, where O.
basilicum has gained the greatest significance. It is true that the aroma of Mediterranean basil is regarded as the
most valuable, but this is an evaluation articulating European taste.

In Thailand alone, three different basil species are normally found in nearly every kitchen: horapha is a sweet
variety with a strong aniseed (also called anise) character, krapao is the tangy and peppery-tasting so-called
holy basil, and then there is manglak, the lemon basil.

In other countries one encounters many other basil varieties, including types that smell of cinnamon, cloves,
camphor, and lime. The name basil is derived from the Greek basilieus (king), presumably as an expression of
the high esteem in which the plant was held, and of its manifold applications. The German designation
Knigskraut and the French herbe royale are literal translations of the Greek.

Apart from parsley and chives, basil (Fig. 1) is today among the economically most important herbs. Much is
employed fresh, but in addition nearly 50 tons of ethereal basil oil is produced annually for introducing an
aromatic component into foods, cosmetics, and pharmaceutical products.

Figure 1. Basil in bloom (O. basilicum, Mediterranean variety).

O. basilicum exists in a great many varieties and forms. These differ in plant stature, blossom or leaf color, leaf
form and size, as well as in the composition of the related ethereal oils. Thanks to the development of new
varieties and hybrids, we find today a confusing overall picture with respect to herbal diversity [3]. In European
cuisine it is almost exclusively basil of the European type that is favored, also referred to as the Mediterranean or
Genovese type (Fig. 2). This strain is also known in English, somewhat misleadingly, as sweet basil, a term that
would actually be more appropriately reserved for certain Asiatic varieties.

Figure 2. Diversity among leaves present in the genus Ocimum. From left to right (above in each case, upper
side of the leaf; below, the corresponding underside): European or Mediterranean type (O. basilicum), African
Blue (cross between O. kilimandscharicum and O. basilicum), lemon basil (O. americanum), Mexican spice basil
or cinnamon basil (O. basilicum), Siam Queen (O. basilicum), clove basil, known in Hawaii as wild basil (O.
gratissimum).

Cultivation
As a plant, basil is an annual that grows almost by itself, to a height of ca. 3050 cm, assuming it receives
considerable sunlight as well as a regular supply of water, and is not subjected to frost.

One should regularly trim back the shoot tips so that the plant will assume a bushy form. Basil tastes best in July,
shortly before blossoms form, since after blossoming the content of its ethereal oils declines, and the leaves
become firmer and more bitter. Moreover, the best flavor is associated with basil collected early in the morning.
Blooming can be postponed by trimming off the flower buds. Should ones crop become too abundant, leaves can
be frozen in small portions.

Basil, Why Do You Smell So Good?

Except for a few minor variations, metabolism in all life forms operates on the identical chemical principles. Thus,
the basic modules necessary for maintaining metabolism and for cell construction fats, carbohydrates, amino

acids, nucleic acids are referred to as primary metabolites. Beyond this, one finds a vast array of natural
substances produced by only one or at most a small number of species. These are compounds designated
secondary metabolites.
To cite one example: only the South American cinchona tree is capable of producing quinine; no other living
organism accomplishes that!
The sole purpose of the elaborate syntheses of secondary metabolites is ensuring that the corresponding
organism gains an advantage in the daily struggle for survival [4].

Basil, too, provides its own unique smell and taste. The effort expended in the preparation of the plants' special
ethereal oil pays off in at least two ways. In the first place, the aroma attracts pollinating insects, and thus
ensures continued existence of the species. This also explains a greatly reduced synthesis of fragrant
substances after blooming occurs: the plant no longer needs to have insects visit. On the other hand, aromatic
oils also protect each individual basil plant; many plant-eating insects are unimpressed by the intense flavor of
the leaves, so they move on to find sustenance elsewhere. Basil in some cases even deploys its ethereal oil to
kill injurious microorganisms directly.

2 What Are the Chemical Compounds Responsible For Basils Aroma?

Figure 3 shows gas chromatograms from two ethereal basil oils, originating in different countries: the Comoros
Islands, which are located between East Africa and Madagascar, (Reunion type) and Egypt (Mediterranean type).
Both oils were isolated as steam distillates from O. basilicum, but they offer completely different aromas. This is
hardly surprising, since the chromatograms reveal at a glance that the two oils have very different primary
components: linalool (1) from the Mediterranean type, and methyl chavicol (3) from the Reunion type.

Figure 3. Gas chromatograms from two ethereal basil oils.

Above: Mediterranean type (country of origin, Egypt), where the principal component is linalool (1), next to which
are shown the structural formulas of a few other components. From left to right: -pinene, -pinene, 1,8-cineol
(eucalyptol) (2), linalool (1), camphor, methyl chavicol (estragole) (3), eugenol (4), -bergamotene, -cadinol.
Below: Reunion type (country of origin, Comoros), the chief component here is methyl chavicol.

An analysis of the many components (57) helps explain the properties of these ethereal basil oils: camphor,

eugenol (the chief component of clove oil), and - and -pinene. The two pinenes are in turn the chief
constituents of terpentine, which is obtained by distillation of tree resin. This resin has the function of closing
wounds in the bark, and it repels all sorts of insects, fungi, and microorganisms. Other components serve as
bactericides, fungicides, and agents to prevent infestation by worms and insects [8], protecting the plant from
such pests.

For an epicure, aroma and taste of course occupy the foreground, and here a comparison of the two basil oils
from different lands demonstrates the broad spectrum of their chemical composition. In contrast to classifying
varieties on the basis of growth, color, or size of leaf, for the epicure it is above all chemotype that is decisive:
i.e., which compounds dominate in the oil responsible for the aroma from the leaves. The following chemotypes,
listed with their chief chemical components, are distinguished commercially:
Europe (Mediterranean type, Genovese): linalool (1), with lesser amounts of 1,8-cineol [(2), eucalyptol]
and methyl chavicol [(3), estragole].
Reunion type (Comoros, Thailand, Madagascar, and Vietnam): methyl chavicol (3).
Tropical (India, Pakistan, and Guatemala): methyl cinnamate.

North African (also the former USSR): eugenol (4).

The classification above is rather crude, because the chemical contents and their relative proportions are a
function not only of geographical origin, but also of the nature of the relevant soil, the microclimate, and other
environmental factors, as well as cultivation techniques.

3 The Biosynthesis
All the components of basil oil are found in other plants as well (for details see: Seductive Aromas of the
Culinary Herbs), but basil like a professional perfumer concocts its own distinctive fragrances. As
examples, we describe here the biosyntheses of the different principal components of the Mediterranean and
Reunion chemotypes [9, 10].

Linalool (1)
This C10-compound is the principal component of the ethereal oils of both basil and coriander, and it is also found
in limited amounts in cinnamon, ginger, savory, bay leaves (laurel), marjoram, and thyme.

Figure 5. Biosynthesis of linalool (1).

Linalool (1) is a monoterpene whose carbon skeleton is seen to be composed formally of two isoprene units. Its
biosynthetic assembly involves two biochemically reactive isoprene analogues, prepared in turn from three
molecules of acetic acid by way of the intermediate mevalonic acid (5). These C5-components are themselves
converted via multiple reaction steps into linalool (1).
For details see Biosynthesis of Linalool.

Methylchavicol (Estragole)
Methyl chavicol (3) belongs to the phenylpropanoid family, whose members are derived from phenylalanine (11).

Figure 6. Biosynthesis of methyl chavicol (3).

In a first reaction step, the enzyme phenylalanine ammonia lyase (PAL) catalyzes the cleavage of ammonia, with
formation of cinnamic acid (12). Starting from cinnamic acid, the C3 side chain is modified and/or hydroxyl groups
are introduced oxidatively into the phenyl ring, the latter in turn being methylated in a stepwise fashion.
For details see Biosynthesis of Methyl Chavicol (Estragole).

I wish to express my thanks to Sensient Essential Oils, Inc., of Bremen, Germany, for samples of the various basil oils. Thanks also to G. Katzer of the HumboldtUniversitt Berlin for the rights to publish his beautiful plant photos. In addition, Katzers informative Web page greatly simplified the work of researching this article. I am
grateful to Dr. H. Bauer, Schering AG, Berlin, Germany, for valuable suggestions, and also to T. Kolrep of the Free University of Berlin for help and patience in the
recording and interpretation of the GC/MS spectra.

References
[1] The standard reference work for the herb lover: K. Greiner, A. Weber, Kruter, Grfe und Unzer, Munich,
Germany 2006. Link
[2] A. Paton, Kew Bull. 1992, 47, 403435. Link
[3] A. Paton, E. Putievsky, Kew Bull. 1996, 51, 509524. Link
[4] E. Pichersky et al., Science 2006, 311, 808811. DOI: 10.1126/science.1118510
[5] M. Marotti, J. Agric. Food Chem. 1996, 44, 39263929. DOI: 10.1021/jf9601067
[6] J. E. Simon et al. in Perspectives on new crops and new uses (Ed. J. Janick), ASHS Press, Alexandria, VA,
USA 1999. Link
[7] J. Grayer et al., Phytochemistry 1996, 43, 10331039. DOI: 10.1016/S0031-9422(96)00429-3
[8] J. E. Simon et al. in Advances in New Crops (Ed. J. Janick, J. E. Simon), Timber Press, Portland,
USA 1990. Link
[9] J. Mann, Chemical Aspects of Biosynthesis, Oxford University Press, Oxford, UK 1999. Link
[10] P. M. Dewick, Medical Natural Products, John Wiley & Sons, Chichester, UK 2002. Link
[11] W. Ternes, Naturwissenschaftliche Grundlagen der Lebensmittelzubereitung, Behrs Verlag, Hamburg,
Germany 1990. Link
[12] S. A. Goff et al., Science 2006, 311, 815819. DOI: 10.1126/science.1112614

Prof. Klaus Roth

Freie Universitt Berlin, Germany.

The article has been published in German in:

Chem. Unserer Zeit, 2006, 40, 200 206.
DOI: 10.1002/ciuz.200600388
and was translated by W. E. Russey.

Pesto Mediterranean Biochemistry Part 2

In this last part we take a look at the synthesis of the perfect pesto

Other articles by Klaus Roth published by ChemViews magazine:

In Espresso A Three-Step Preparation
Klaus Roth proves that no culinary masterpiece can be achieved without a basic knowledge of chemistry
DOI: 10.1002/chemv.201000003
In Chocolate The Noblest Polymorphism
Klaus Roth proves only chemistry is able to produce such a celestial pleasure
DOI: 10.1002/chemv.201000021
In Sparkling Wine, Champagne & Co
Klaus Roth shows that only chemistry can be this tingling
DOI: 10.1002/chemv.201000047
In Chemistry of a Hangover Alcohol and its Consequences
Klaus Roth asks how can a tiny molecule like ethanol be at the root of so much human misery?
DOI: 10.1002/chemv.201000074
In The Chemist's Fear of the Fugu
Klaus Roth shows that the chemists fear of the fugu or pufferfish extends as far as the distinctive and
intriguing poison it carries
DOI: 10.1002/chemv.201000104
In Chemistry of a Christmas Candle
Klaus Roth explains that when we light a candle, the chemistry we are pursuing is not only especially
beautiful, but also especially complex
DOI: 10.1002/chemv.201000133
Video Interview with Klaus Roth

GREEN SYNTHESIS OF CAMPHOR

The principles of Green Chemistry include working with less toxic reagents,
generating less toxic products, optimizing atom economy (minimizing
undesireable byproducts), increasing efficiency, minimizing the use of
solvents and separating agents, and minimizing the energy requirements of
the chemical process.
The oxidation of isoborneol to camphor with household bleach and glacial
acetic acid incorporates many of these principles.

Camphor is a natural product, found in the Chinese camphor tree, among

other plants, and is used in religious ceremonies as a kind of incense, as a
moth repellant and in medicinal vapor-rubs, so its toxicity is known to be
relatively low.
The oxidation of alcohols is often effected with Cr(VI) oxidizing agents,
which are known to be extremely toxic and carcinogenic. Chromium
compounds cannot be easily disposed of lest they leach into waterways.
Household bleach, on the other hand, is relatively safe and its risks to the
environment are minimal.
Finally, the isolation of camphor does not require the use of extraction
solvents, since it sublimes easily.
The active ingredient in bleach is sodium hypochlorite. Addition of acetic
acid makes hypochlorous acid, which is an oxidizing agent whose
mechanism of action is shown below:

In order to prepare for this lab, you will need to review the procedure given
below and review Mohrig's "Techniques" text on Sublimation (Technique
12, Fig 12.1a) and Infrared Spectroscopy.

Once you have read the text, you will need to prepare
your notebook with the following:
1. Purpose
2. Net Reaction
3. Table of Reactants/ Products/ Solvents

Include ALL solvents (density, bp and handling info), and any

reactants or products used in determining the Theoretical Yield

4. Theoretical Yield Calculation in grams

5. Procedure (Microscale)

The procedure for this experiment is not in your textbook, but rather
is given below. Read this carefully and then write an outline of what
you will do in your notebook.
Leave room to the right of the procedure for notes/ observations/
changes on the day of the experiment.
Under the hood if possible, combine 8.3 mmol of isoborneol with .7
mL of glacial acetic acid in a 50-mL Erlenmeyer flask. Mix in 1.7 mL
of 5.25% sodiumm hypochlorite solution (chlorox) . Measure another
15 mL of sodium hypochlorite solution into a separatory-addition
funnel, stopper the funnel, and support it over the flask. Add the
NaOCl solution to the reaction mixture in small portions with
vigourous stirring for a period of 10 minutes or more. Use a
thermoeter to monitor the temperature of the reaction mixture, and
control the rate of addition so that the temperature remains below
50C. Have an ice water bath handy to cool the reaction mixutre if its
temperature reaches 50C. When the addition is complte, seal the
flask with Paraflim and stir for 30 minutes or more.
Every 5 minutes or so, test the reaction mixture to make sure there is
an excess hypochlorite by dipping a glass rod into the solution and
touching it to a strip of strach-iodide paper. A positive test is the
presence of a purple color indicating the presence of I3- (an oxidized
form of iodine). If at any time during the 30 minutes the test is
negative, add enough sodium hypochlorite solution (about 1 mL at a
time) to the reaction mixture to give a positive test. When the
reaction period is over, test again and add enough saturated sodium
bisulfite solution dropwise to give a negative test (no color).

Cool the reaction mixture to 5C or below in and ice-water bath.

Collect the product by vacuum filtration washing it on the filter with
two portions of ice-cold water. Dry the crude product overnight at
room temperature, NOT in an oven.
The next lab period you must weigh your product and purify up to 1
gram of it by sublimation (See Figure 12.1). Weigh the sublimed
product.
Obtain an IR spectrum.

During the lab:

Remember to date every entry, record all weights, observations,

corrections and melting points IN PEN IN YOUR NOTEBOOK. You will be
marked off if I catch you recording data on scratch paper, or if you do not
have your notebook with you when you take a measurement.

Following Lab:

You must calculate the yield of your product (both crude and sublimed).
Write a discussion which includes characterization of the product from the
IR spectrum including an identification of all characteristic signals and a
comparison between the fingerprint region of your spectrum and that of
the literature spectrum. Calculate and report your percent yield. Include
copies of both your spectrum and the literature spectrum that you find
online or in the library in your final report and discuss sources of loss/
error, and reflections on how you might improve the experiment if given
the opportunity.
POST LAB STUDY QUESTIONS:
1. What evidence leads you to conclude that the solid you ended with is
different from the one you started with?
2. Calculate the atom economy = (molar mass desired
product)/(sum of molar masses of reactants) and the
reaction efficiency = (atom economy x percent yield) of this
synthesis.
3. Write a balanced chemical equation using half-reactions to determine
the number of electrons involved in the oxidation of one mole of
isoborneol with hypochlorous acid (reduced to hydrogen chloride).
4. Write another balanced chemical equation to show the use of sodium
bisulfite (NaHSO3) given that its product is sodium sulfate (Na2SO4).

Camphor and borneol are widespread bicyclic mono-terpenoids in plants. The enantiomeric
ratio of camphor has been investigated in some herbs and spices. Ravid et al. found a high
variability of enantiomeric ratio of camphor and borneol in Salvia officinalis. An excess of
(+) as well as (-) enantiomers has been observed. No characteristic distribution of those two
chiral monoterpenoids has been found in the investigated Salvia officinalis samples. In Salvia
sclarea, Salvia glutinosa and Salvia fi'uticosa an excess of (+)-camphor has been observed.
(+)-Camphor of a high enantiomeric purity has been detected in essential oils from Ocimum
basilicum, while in Coriandrum sativum (-)-camphor is the dominant enantiomer.(+)-Bomeol
has been found in lavandin and lavender oils, while (-)-bomeol has been detected in
Artemisia genus {Artemisia judaica, Artemisia arborescens, Artemisia herba alba) and
Origanum genus {Origanum vulgare, Origanum syriacum). In Chrysanthemum parthenium ()-bomeol and (-)-camphor of a high enantiomeric purity has been found.

Biosynthesis[edit]
In biosynthesis, camphor is produced from geranyl pyrophosphate, via cyclisation
oflinaloyl pyrophosphate to bornyl pyrophosphate, followed by hydrolysis to borneol and oxidation to
camphor.

Terpenoid
From Wikipedia, the free encyclopedia

Chemical structure of the terpenoid isopentenyl pyrophosphate

The terpenoids (/trpnd/ TUR-p-noyd), sometimes called isoprenoids, are a large and diverse class of
naturally occurringorganic chemicals similar to terpenes, derived from five-carbon isoprene units
assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another
not only infunctional groups but also in their basic carbon skeletons. These lipids can be found in all
classes of living things, and are the largest group of natural products.
Plant terpenoids are used extensively for their aromatic qualities. They play a role in traditional herbal
remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions.
Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, the yellow
color in sunflowers, and the red color intomatoes.[1] Well-known terpenoids
include citral, menthol, camphor, salvinorin A in the plant Salvia divinorum, the cannabinoids found
in cannabis, ginkgolide and bilobalide found in Ginkgo biloba, and the curcuminoids found
in turmeric and mustard seed.
The steroids and sterols in animals are biologically produced from terpenoid precursors. Sometimes
terpenoids are added to proteins, e.g., to enhance their attachment to the cell membrane; this is known
as isoprenylation.
Contents
[hide]

1 Structure and classification

2 Biosynthesis

2.1 Mevalonic acid pathway

2.2 MEP/DOXP pathway

3 See also

4 References

5 External links

Structure and classification[edit]

Terpenes are hydrocarbons resulting from the combination of several isoprene units. Terpenoids can be
thought of as modified terpenes, wherein methyl groups have been moved or removed, or oxygen atoms
added. (Some authors use the term "terpene" more broadly, to include the terpenoids.) Just like terpenes,
the terpenoids can be classified according to the number of isoprene units used:

Hemiterpenoids, 1 isoprene unit (5 carbons)

Monoterpenoids, 2 isoprene units (10C)

Sesquiterpenoids, 3 isoprene units (15C)

Diterpenoids, 4 isoprene units (20C) (e.g. ginkgolides)

Sesterterpenoids, 5 isoprene units (25C)

Triterpenoids, 6 isoprene units (30C) (e.g. sterols)

Tetraterpenoids, 8 isoprene units (40C) (e.g. carotenoids)

Polyterpenoid with a larger number of isoprene units

Terpenoids can also be classified according to the number of cyclic structures they contain. In the year
1995, Julius Anitnec found out that Terpenoids can be tested for using the Salkowski test[citation needed].
Meroterpenes are any compound, including many natural products, having a partial terpenoid structure

Biosynthesis[edit]

Simplified version of the steroid synthesis pathway with the terpenoid intermediates isopentenyl
pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP), and squaleneshown. Some
intermediates are omitted for clarity.

There are two metabolic pathways of creating terpenoids:

Mevalonic acid pathway[edit]

Many organisms manufacture terpenoids through the HMG-CoA reductase pathway, the pathway that also
produces cholesterol. The reactions take place in the cytosol. The pathway was discovered in the 1950s.

MEP/DOXP pathway[edit]
The 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP
pathway), also known as [non-mevalonate pathway] or mevalonic acid-independent pathway, takes place
in the plastids of plants andapicomplexan protozoa, as well as in many bacteria. It was discovered in the
late 1980s.
Pyruvate and glyceraldehyde 3-phosphate are converted by DOXP synthase (Dxs) to 1-deoxy-D-xylulose
5-phosphate, and by DOXP reductase (Dxr, IspC) to 2-C-methyl-D-erythritol 4-phosphate (MEP). The
subsequent three reaction steps catalyzed by 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP,
IspD), 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE), and 2-C-methyl-D-erythritol 2,4cyclodiphosphate synthase (YgbB, IspF) mediate the formation of 2-C-methyl-D-erythritol 2,4cyclopyrophosphate (MEcPP). Finally, MEcPP is converted to (E)-4-hydroxy-3-methyl-but-2-enyl
pyrophosphate (HMB-PP) by HMB-PP synthase (GcpE, IspG), and HMB-PP is converted to isopentenyl
pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
IPP and DMAPP are the end-products in either pathway, and are the precursors ofisoprene,
monoterpenoids (10-carbon), diterpenoids (20-carbon), carotenoids (40-carbon),chlorophylls,
and plastoquinone-9 (45-carbon). Synthesis of all higher terpenoids proceeds via formation of geranyl
pyrophosphate (GPP), farnesyl pyrophosphate (FPP), andgeranylgeranyl pyrophosphate (GGPP).
Although both pathways, MVA and MEP, are mutually exclusive in most organisms, interactions between
them have been reported in plants and few bacteria species.

Organism

Pathways

Bacteria

MVA or MEP

Archaea

MVA

Green Algae MEP

Plants

MVA and MEP

Animals

MVA

Fungi

MVA

See also[edit]

List of antioxidants in food

List of phytochemicals in food

Nutrition

Phytochemistry

Secondary metabolites

Superfruits

References[edit]
1.

Jump up^ Michael Specter (September 28, 2009). "A Life of Its Own". The New Yorker.

Menthol
From Wikipedia, the free encyclopedia

Not to be confused with methanol.

Menthol

IUPAC name[hide]
(1R,2S,5R)-2-isopropyl-5-methylcyclohexanol
Other names[hide]
3-p-Menthanol,
Hexahydrothymol,
Menthomenthol,
peppermint camphor
Identifiers

CAS number

89-78-1

ChemSpider

15803

UNII

YS08XHA860

DrugBank

DB00825

ChEBI

CHEBI:15409

ChEMBL

CHEMBL470670

RTECS number

OT0350000, racemic

Jmol-3D images

Image 1
Image 2

SMILES
[show]

InChI
[show]

Properties

Molecular formula

C10H20O

Molar mass

156.27 g mol1

Appearance

White or colorless
crystalline solid

Density

0.890gcm3, solid
(racemic or ()-isomer)

Melting point

3638 C (311 K), racemic

4245 C (318 K), ()-form ()
35-3331 C, ()-isomer

Boiling point

212 C (485 K)

Solubility in water

Slightly soluble, ()-isomer

Hazards

MSDS

External MSDS

R-phrases

R37/38, R41

S-phrases

S26, S36

Main hazards

Irritant, flammable

Flash point

93 C; 199 F; 366 K

Related compounds

Related alcohols

Cyclohexanol, Pulegol,
Dihydrocarveol, Piperitol

Related compounds

Menthone, Menthene,
Thymol, p-Cymene,
Citronellal

Supplementary data page

Structure and

n, r, etc.

properties

Thermodynamic

Phase behaviour

data

Solid, liquid, gas

Spectral data

UV, IR, NMR, MS

(verify) (what is:

/ ?)

Except where noted otherwise, data are given for materials in

their standard state (at 25 C (77 F), 100 kPa)

Infobox references

Menthol is an organic compound made synthetically or obtained from cornmint,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 andcounterirritant qualities, and it is
widely used to relieve minor throat irritation. Menthol also acts as a weak kappa opioid receptor agonist.

Contents
[hide]

1 Structure

2 Biological properties

3 Occurrence

4 Biosynthesis

5 Production

6 Applications

7 Reactions

8 History

9 Compendial status

10 Toxicology

11 See also

12 Notes and references

13 Further reading

14 External links

Structure[edit]
Natural menthol exists as one purestereoisomer, 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 group is in the trans orientation to both
the methyland 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 theircyclohexane
conformations. With the ring itself in a chair conformation, all three bulky groups can orient in equatorial
positions.
The two crystal forms for racemic menthol have melting points of 28C and 38C. Pure ()-menthol has
four crystal forms, of which the most stable is the form, the familiar broad needles.

Biological properties[edit]

Menthol crystals at room temperature. Approx. 1 cm in size.

Menthol's ability to chemically trigger the cold-sensitive TRPM8 receptors in the skin is responsible for the
well-known cooling sensation it provokes when inhaled, eaten, or applied to the skin.[1] In this sense, it is
similar tocapsaicin, the chemical responsible for the spiciness of hot chilis (which stimulates heat sensors,
also without causing an actual change in temperature).

Menthol's analgesic properties are mediated through a selective activation of -opioid receptors.[2] Menthol
also blocks voltage-sensitive sodium channels, reducing neural activity that may stimulate
muscles.[3] Menthol also enhances the efficacy of ibuprofen in topical applications via vasodilation, which
reduces skin barrier function.[4]

Occurrence[edit]
Mentha arvensis 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.[5] Japanese menthol also contains a small percentage of the 1-epimer, (+)-neomenthol.

Biosynthesis[edit]
Biosynthesis of menthol was investigated in M. x piperita, and all enzymes involved in its biosynthesis have
been identified and characterized.[6] It begins with the synthesis of the terpene limonene, followed by
hydroxylation, and then several reduction and isomerization steps.
More specifically, the biosynthesis of ()-menthol takes place in the secretory gland cells of the peppermint
plant. 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 to ()limonene. ()-Limonene-3-hydroxylase (L3OH), using O2 and NADPH, then catalyzes the allylic
hydroxylation of ()-limonene at the 3 position to ()-trans-isopiperitenol. ()-Trans-isopiperitenol
dehydrogenase (iPD) further oxidizes the hydroxy group on the 3 position using NAD+ to make ()isopiperitenone. ()-Isopiperitenone reductase (iPR) then reduces the double bond between carbons 1 and
2 using NADPH to form (+)-cis-isopulegone. (+)-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 ()-menthol.[6]

Production[edit]
As with many widely used natural products, the demand for menthol greatly exceeds the supply from
natural sources. In the case of menthol it is also interesting to note that comparative analysis of the total
life-cycle costs from a sustainability perspective, has shown that production from natural sources actually
results in consumption of more fossil fuel, produces more carbon dioxide effluent and has more
environmental impact than either of the main synthetic production routes.[7]
Menthol is manufactured as a single enantiomer (94% ee) on the scale of 3,000 tons per year by Takasago
International Corporation.[8] The process involves an asymmetric synthesis developed by a team led
by Ryji Noyori, who won the 2001 Nobel Prize for Chemistry in recognition of his work on this process:

The process begins by forming an allylic amine from myrcene, which

undergoesasymmetric isomerisation in the presence of a BINAP rhodium complex to give (afterhydrolysis)
enantiomerically pure R-citronellal. This is cyclised by a carbonyl-ene-reactioninitiated by zinc bromide to
isopulegol, which is then hydrogenated to give pure (1R,2S,5R)-menthol.
Another commercial process is the Haarmann-Reimer process. [9] [10] This process starts from mcresol which is alkylated with propene to thymol. This compound is hydrogenatedin the next step. Racemic
menthol is isolated by fractional distillation. The enantiomers are separated by chiral resolution in reaction
with methyl benzoate, selective crystallisation followed by hydrolysis.

Racemic menthol can also be formed by hydrogenation of pulegone. In both cases with further
processing (crystallizative entrainment resolution of the menthyl benzoate conglomerate) it is possible
to concentrate the L enantiomer, however this tends to be less efficient, although the higher
processing costs may be offset by lower raw material costs. A further advantage of this process is that

d-menthol becomes inexpensively available for use as a chiral auxiliary, along with the more usual lantipode.[7]

Applications[edit]
Menthol is included in many products for a variety of reasons. These include:

In nonprescription 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, it is used to relieve minor aches and pains, such as muscle cramps,
sprains, headaches and similar conditions, alone or combined with chemicals such
as camphor, eucalyptus oil or capsaicin. In Europe, it tends to appear as a gel or a cream, while in
the U.S., patches and body sleeves are very frequently used.

In decongestants for chest and sinuses (cream, patch or nose inhaler).

Examples: Tiger Balm, or IcyHot patches or knee/elbow sleeves.

Examples: Vicks VapoRub, Mentholatum, vapoRem.

In certain medications used to treat sunburns, as it provides a cooling sensation (then often
associated with aloe).

In aftershave products to relieve razor burn.

As a smoking tobacco additive in some cigarette brands, for flavor, and to reduce throat and sinus
irritation sometimes caused by smoking.

Commonly used in oral hygiene products and bad-breath remedies, such

asmouthwash, toothpaste, mouth and tongue-spray, and more generally as a food flavor agent;
e.g., in chewing gum, candy.

In a soda to be mixed with water it is used to obtain a very low alcohol drink or pure
(brand Ricqls which contains 80% alcohol in France); the alcohol is 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 honey bees.

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 Asia,
especially Japan: 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 antispasmodic and smooth muscle relaxant in upper gastrointestinalendoscopy.[11]

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
makeenantiomerically pure sulfoxides by reaction with organolithium reagents or Grignard reagents.
Menthol reacts with chiral carboxylic acids to give diastereomic menthyl esters, which are useful
for chiral resolution.

Reactions[edit]
Menthol reacts in many ways like a normal secondary alcohol. It is oxidised to menthoneby oxidising
agents such as chromic acid or dichromate,[12] 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. Phosphorus pentachloride (PCl5) gives menthyl chloride.

History[edit]
There is evidence[13] that menthol has been known in Japan for more than 2000 years, but in
the West it was not isolated until 1771, by Hieronymus David Gaubius.[14] Early characterizations were
done by Oppenheim,[15] Beckett,[16] Moriya,[17] and Atkinson.[18]

Compendial status[edit]

United States Pharmacopeia 23 [19][clarification needed]

Japanese Pharmacopoeia 15 [20][clarification needed]

Food Chemicals Codex [21][clarification needed]

This section requires expansion. (June
2009)

Toxicology[edit]

This section requires expansion. (June

2009)

Currently no reported nutrient or herb interactions involve menthol.[citation needed]

Ingesting pure menthol can be poisonous, and overdose is also possible through excess consumption
of menthol-containing products.[22] The oral LD50 has been estimated at 192mg/kg; other sources give
much higher numbers like 2900mg/kg.[23][24]

See also[edit]

Camphor

Menthol cigarettes

Pulegone

Vapor pressure

Notes and references[edit]

1.

Jump up^ R. Eccles (1994). "Menthol and Related Cooling Compounds". J. Pharm.
Pharmacol. 46(8): 618630. PMID 7529306.

2.

Jump up^ Galeottia, N., Mannellia, L. D. C., Mazzantib, G., Bartolinia, A., Ghelardini, C. (2002).
"Menthol: a natural analgesic compound". Neuroscience Letters 322 (3): 145
148.doi:10.1016/S0304-3940(01)02527-7. PMID 11897159.

3.

Jump up^ G. Haeseler, D. Maue, J. Grosskreutz, J. Bufler, B. Nentwig, S. Piepenbrock, R.

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24. Jump up^ http://www.sciencelab.com/msds.php?msdsId=9924606

Further reading[edit]

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, 1960.

Perfumer & Flavorist, December, 2007, Vol. 32, No. 12, Pages 3847