Introduction :- A large group of plants used in medicine or veterinary practice for

therapeutic or prophylactic purpose. This practice has existed since prehistoric times. There are
three ways in which plants have been found useful in medicine.

First, they may be used directly as teas or in other extracted forms for their natural chemical
constituents.

Second, they may be used as agents in the synthesis drugs.

Finally, the organic molecules found in plants may be used as models for synthetic drugs.

The therapeutic properties of medicinal plants are conditioned by the presence in their organs of
active substance, such as alkaloids, flavonoids, glycosides, vitamins, tannins, and coumarin
compounds, which physiologically affect the bodies of humans and animals or which are
biologically active in relation to the causative agents of various diseases. A special group of
medicinal plants are antibiotics. Harvested medicinal plants are usually dried in special crop dryers,
in lofts, or in the shade. To obtain essential oils and juices from certain medicinal plants only
freshly harvested material can be used. Dried medicinal plants are used in pharmaceutical practice
( for the preparation of infusion and decoctions ), in galenics production ( for the manufacture of
tinctures, extracts, and other neogalenicals and galenicals ), and in the chemical and
pharmaceutical industry ( for the most part to obtain pure active substance ).the composition and
quantity of active substance found in different organs of medicinal plants vary and change in the
course of the year as a result of the aging of the plants and habits conditions. Those parts of the
plants in which the largest quantity of these substance accumulates are collected first. Some
important medicinal plants are such as Atropa belladonna, Conium maculatum,
Cymbopogon, Meyer lemon
 Mentha peppermint :-

Peppermint (Nepali: पपपपपप) was first described in 1753 by Carl Linnaeus from specimens that had
been collected in England; he treated it as a species, but it is now universally agreed to be a hybrid. It is
a herbaceous rhizomatous perennial plant growing to 30–90 cm (12–35 in) tall, with smooth stems, square
in cross section. The rhizomes are wide-spreading, fleshy, and bare fibrous roots. The leaves are from 4–
9 cm (1.6–3.5 in) long and 1.5–4 cm (0.59–1.57 in) broad, dark green with reddish veins, and with an acute
apex and coarsely toothed margins. The leaves and stems are usually slightly fuzzy. The flowers are purple,
6–8 mm (0.24–0.31 in) long, with a four-lobed corolla about 5 mm (0.20 in) diameter; they are produced in
whorls (verticillasters) around the stem, forming thick, blunt spikes. Flowering is from mid to late summer.
The chromosome number is variable, with 2n counts of 66, 72, 84, and 120 recorded. Peppermint is a fast-
growing plant; once it sprouts, it spreads very quickly.
Occurrence:- 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 occurs naturally in peppermint oil (along with a little menthone, the ester menthyl acetate and
other compounds), obtained from Mentha x piperita.[6]Japanese menthol also contains a small percentage of
the 1-epimer, (+)-neomenthol

Extraction of menthol from peppermint oil:-

Chemical Constituents:- Peppermint has a high menthol content. The oil also contains menthone and
menthyl esters, particularly menthyl acetate. Dried peppermint typically has 0.3–0.4% of volatile oil
containing menthol (7–48%), menthone (20–46%), menthyl acetate (3-10%), menthofuran (1–17%) and 1,8-
cineol (3–6%). Peppermint oil also contains small amounts of many additional compounds
including limonene, pulegone, caryophyllene and pinene.

Menthol
Menthol is an organic compound made synthetically or obtained from corn mint,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 counterirritantqualities, and it is
widely used to relieve minor throat irritation. Menthol also acts as a weak kappa opioid receptor agonist
 Menthol A macro photograph of menthol crystals. Menthol crystals at room temperature.

IUPAC name - (1R,2S,5R)-2-Isopropyl-5-methylcyclohexanol.

Other names - 3-p-Menthano, Hexahydrothymol, Menthomenthol.

Chemical formula -C10H20O Molar mass - 156.27 g·mol−1 Density- 0.890 g·cm−3, solid(racemic or (−)-isomer) Melting point-36 to 38 °C (97

to 100 °F; 309 to 311 K)

Appearance:- White or colorless crystalline solid

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 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
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 28 °C and 38 °C. Pure (−)-menthol has four
crystal forms, of which the most stable is the α form, the familiar broad needles.

Biosynthesis :-
Biosynthesis of menthol was investigated in M. x piperita, and all enzymes involved in its
biosynthesis have been identified and characterized. 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.

Chemical Investigation of menthol:-

(1) Molecular formula, as determined by elemental analysis and molecular weight determination,
is C10H20O.
(2) It is a saturated compound. On heating with Se (selenium) it gives p-cymene
(1-methyl-4-isopropyl benzene). Menthol on reduction with HI gives p-menthene as the only
products. This also confirmed that menthol has p-menthene skeleton.

(3) Nature of oxygen :- (i) Menthol on acetylation with acetic anhydride and pyridine at room
temperature forms a monoacetate. Formation of monoacetate shows that oxygen is present in the
form of a hydroxyl group. Acetylation at room temperature shows that hydroxyl group of menthol is
either a primary or a secondary but not a tertiary in nature.
(ii) Menthol on oxidation with chromic acid forms a carboxyl compound which is identified as a
ketone (Menthone

Formation of a ketone shows that the hydroxyl group is secondary in nature.

(4) Position of Hydroxyl group :- Menthol on oxidation with chromic acid gives a ketone. Menthone,
C10H20O. Menthone (II) on oxidation with KMnO4 gives a keto acid, C10H18O3 (III). This keto acid (III) is
identified by 6-keto-3, 7-dimethyloctaoic acid commonly known as ketomenthylic acid (III). Ketomenthylic acid
(III) is readily oxidation to give 3-methylhexanedioic acid (IV) and acetone.

Formation of compound (III) shows that the keto group in menthone is present in p-menthene
skeleton. Thus menthol is p-menthene-3ol and menthone is p-menthan-3-one.
 Structure of menthone is also supported by the fact that pulegone on reduction yields menthol
and since the structure of pulegone is known to be (V), it therefore follows that menthol must be (I).

Finally the structure of menthol has been confirmed by its synthesis:

Stereochemistry of menthol

Menthol has three chiral carbons (1, 3, and 4) and hence it forms four pairs (eight optically
active forms) of enantiomers. These are

(+_) Menthol

(+_) isomenthol

(+_) neomenthol;
(+_) neoisomenthol

The configuration of these are as follows :

Application :-
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.Examples: Tiger Balm, or IcyHot patches or
knee/elbow sleeves.
 In decongestants for chest and sinuses (cream, patch or nose inhaler).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 caused by smoking. Menthol also increases nicotine receptor density, increasing the
addictive potential of tobacco products.
 Commonly used in oral hygiene products and bad-breath remedies, such as mouthwash, 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 Ricqlès 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 gastrointestinal endoscopy.[12]
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 reacts with chiral carboxylic acids to give diastereomic menthyl esters, which are useful
for chiral resolution.