STRUCTURE ELUCIDATION OF

MENTHOL

SUBMITTED BY – SUBMITTED TO –

Abuzar Huraira Dr. Showkat R. Mir

M.Pharm Associate Professor
(1st sem) Department of
Department of P.Cognosy Pharmacognosy &
and Phytochemistry Phytochemistry
Jamia Hamdard School of Pharmaceutical
Education & Research
Jamia Hamdard
DEFINITION –

•Structure elucidation is the process of determining the

chemical structure of a compound.
•For organic compounds, it will often involve the use of nuclear
magnetic resonance spectroscopy (NMR spectroscopy).
•Other characterization techniques include mass spectrometry,
infrared spectroscopy and X-ray crystallography.
•Elucidation of molecular structure is necessary to identify or
confirm the structural identity of a chemical compound during
chemical research or product development.
• Unknown substances or impurities can be difficult to identify.

There are a number of techniques which help us to

determine the molecular structure of an unknown
compound:

•Infrared (IR) Spectroscopy.

•Ultraviolet-Visible (UV/Vis) Spectroscopy.
•Nuclear Magnetic Resonance (NMR) Spectroscopy.
•Mass Spectroscopy.
INTRODUCTION –
(MENTHOL)

Menthol is an organic compound made synthetically or

obtained from peppermint or other mint oils.

It is the major constituent of Mentha piperita Linn.

(Family - Lamiaceae)
(Common Name - Peppermint)

It is a waxy, crystalline substance, clear or white in color,

which is solid at room temperature and melts slightly above
(m.p. 41 to 43°C).

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.
OCCURENCE –

Mentha arvensis (wild mint) 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 occurs naturally in peppermint oil (along with a little

menthone, the ester menthyl acetate and other compounds),
obtained from Mentha × piperita (peppermint).

Japanese menthol also contains a small percentage of the 1-epimer

neomenthol.

STRUCTURE OF MENTHOL -

2-isopropyl-5-methylcyclohexanol
Production –

Natural menthol is obtained by freezing peppermint oil. The

resultant crystals of menthol are then separated by filtration.

Total world production of menthol in 1998 was 12,000 tonnes

of which 2,500 tonnes was synthetic.

In 2005, the annual production of synthetic menthol was

almost double.

Prices are in the $10–20/kg range with peaks in the $40/kg

region but have reached as high as $100/kg.

In 1985, it was estimated that China produced most of the

world's supply of natural menthol, although it appears that
India has pushed China into second place.
CHEMISTRY –

• The main form of menthol occurring in nature is (-)-

menthol, which is assigned the (1R, 3R, 4S) configuration.
The molecule can exist as a pair of optical isomers, though
natural menthol only contains the (-) form produced in
biosynthesis.Menthol has three asymmetric (chiral) carbon
atoms in its cyclohexane ring; it therefore occurs as four
pairs of optical isomers.
•The other isomers are known as isomenthol, neomenthol
and neoisomenthol.
In menthol, all three bulky groups [OH, CH3 and CH(CH3)2]
are in equatorial positions, making menthol more stable than
the other three isomers.
STRUCTURE ELUCIDATION –

Molecular formula was determined as C10H20O.

Molecular weight – 156.26 g/mol
B.P : 214.6 OC ; Solubility – Slightly soluble in water.
Menthol forms esters readily with acids and oxidized to yield
ketone it means that it must possess alcoholic group, which
is 2o in nature.
On dehydration followed by dehydrogenation it yields p-
cymene

Menthone on oxidation with KMnO 4 yields ketoacid

C10H18O3 which readily oxidized to 3-methyladipic acid.
These reactions can be explained by considering the following
structure of menthol.
Menthol was converted to p-Cymene, which was also
obtained by dehydrogenation of pulegone. Pulegone on
reduction yielded menthone which on further reduction
yielded menthol.

Thus the correlation of pulegone with menthol

proved the structure of menthol.
Finally the structures of menthone and menthol have been
confirmed by the synthesis given by Kotz and Hese from m-
cresol
Mass spectrum of Menthol with relative molecular structure
-

ABUNDANCE

m/z
L-MENTHOL MASS SPECTRUM -
BIOLOGICAL PROPERTIES –

• Menthol's ability to chemically trigger the cold-sensitive

TRPM8 receptors in the skin is responsible for the well-
known cooling sensation, when inhaled, eaten, or applied
to the skin.
•Menthol's analgesic properties 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.
•It used in oral hygiene products and bad-breath remedies,
such as mouthwash, toothpaste.
•As an additive in certain cigarette brands, for flavor, to
reduce the throat and sinus irritation caused by smoking.
•As an antispasmodic and smooth muscle relaxant in upper
gastrointestinal endoscopy.
•As an antipruritic to reduce itching.
REFERENCES –

•Dr. S. Mondal Lecturer Notes B. Pharm 7th Semester -

GITAM University

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