citronellol, geraniol, nerol, linalool, Menthol (Para-menthane-3-ol), a-terpineol, Borneol, isoborneol, Bisabolol, Santalol and Benzyl alcohol

1. Phytochemistry
Volatile oils
Terpene Alcohols
By
Dr. Mostafa Mahmoud Hegazy ( PH.D.)

2. Oxygenated Terpene Compounds
Characters:
1- Odor-carrying compounds.
2- Better solubility in dilute alcohol than hydrocarbons.
3- They have great stability against oxidizing influences.
If the terpene hydrocarbons were removed from the oil
(terpenless) volatile oil. It is more soluble in alcohol, more stable
and have much stronger odor.

3. Removal of terpenoid hydrocarbons
(Terpeneless oils of dill, lemone and orange)
Oils rich in terpenoid hydrocarbons are liable to rapid deterioration on storage through oxidation
and polymerization to yield bad smelling (generally with turpentine-like odor) and resinified
products.
The process of elimination of terpenoid hydrocarbons could be considered as a specific
procedure for rectification. Thus a considerable amount of the terpenoid hydrocarbons could be
removed by any of the following methods to produce "terpeneless-oils":
1- Fractional distillation under reduced pressure; hydrocarbons have lower boiling points than
oxygenated compounds and therefore, distill first and are discarded.
2- Column chromatography on silica gel, by eluting hydrocarbons with n-hexane then oxygenated
compounds with absolute alcohol.
3- Selective extraction of the oxygenated components with dilute alcohol followed by distillation.
Terpeneless oils are more expensive than natural oils, and
are characterized by being:
1- Richer in oxygenated compounds.
2- More soluble in low-strength alcohols.
3- Employed in smaller quantities to give the same strength of odor.
4- More stable being less liable to deterioration

4. Oxygenated Terpene Compounds
(1) Terpene Alcohols (2) Phenols and Phenolic Ethers
(3) Terpene Aldehydes (4) Terpene Ketones
(5) Esters (6) Monoterpene Oxides
(7) Monoterpene peroxides

5. TERPENE ALCOHOLS
Aliphatic
Saturated Unsaturated
Aromatic Alicyclic
e.g. Santalol
e.g.
Citronellol
Geraniol
Nerol
Linalol
Benzyl alcohol
Monocyclic
Bicyclic
Sesquiterpene
e.g. Menthol and Terpeniol
e.g. Borneol

6. CH3CH2OH
CH2OH CH2OH
H
H
CH2OH
HO
CH2OH
OH
Saturated alcohols:
ALIPHATIC ALCOHOLS
Unsaturated alcohols:
Methyl alcohol Ethyl alcohol
Citronellol
Acyclic monoterpenoids
Acyclic sesquiterpenoids
Farnesol
(+)-Linalool
Nerolidol
nerol Geraniol
CH3OH

7. OH OH
H
OH
OH
CH2OH
ALICYCLIC TERPENOID ALCOHOLS
Monoterpenoids Sesquiterpenoids
(-)-Menthol a-Terpineol (-)-Borneol Carotol Santalol
Monocyclic Bicyclic Tricyclic
CH2OH CH2CH2OH CH=CHCH2OH
AROMATIC ALCOHOLS
Benzyl alcohol Phenyl ethyl alcohol Cinnamyl alcohol

8. Isolation of terpenoid alcohols

Fractional distillation.

Counter current extraction.

Chromatography.

Derivatization.
Derivatization of terpenoid alcohols
Used for identification and/or isolation and quantitation are
based on either Reactions due to
1- unsaturation (similar to terpenoid hydrocarbons.),
or
2- the presence of functional OH groups.

9. Methods Used in Preparation of Derivatives of Terpene Alcohols
1- Reactions similar to terpenoid hydrocarbons:
These are due to unsaturation. They are addition reactions such as
hydration, hydrogenation and halogenation or degradation reactions such
as oxidation.
2- The derivatives employed for identification of the alcohol are those, which
characterize the functional group (OH).
The most commonly derivatives are:
1. Dehydration Products.
2. CalciumChloride Addition Products.
3. Esters.
Examples for such esters are:
a) Borates. b) Phthalates c) Benzoates d) Urethanes

10. Reactions due to hydroxyl group: the reactivity is dependent on the
type of alcoholic group (primary, secondary or tertiary).
1-Dehydration reactions
yields the corresponding unsaturated hydrocarbons.Tertiary alcohols are the
most reactive (3ry > 2ry). 1ry resist dehydration except geraniol (that is
dehydrated with ZnCl2).
2- Esterification:
The esterification speed
1- acid anhydrides :1ry > 2ry > 3ry alcohols → corresponding esters.
2- halogen acids e.g. HBr :3ry > 2ry > 1ry alcohols → alkyl bromides.

11. Boric acid esters (borates)
1ry and 2ry alcohols react easily to give the corresponding borates, while 3ry
do not react. Boric acid and boric anhydride are weakly acidic and do not
affect other sensitive constituents in the oil.The reaction is used mainly to
separate both 1ry
and 2ry
from 3ry
alcohols.
Phthalic acid esters (phthalates)
1ry alcohols react under less drastic conditions than 2ry alcohols, 3ry alcohols
do not react.
primary alcohols are heating at 100 o
C (water bath), with phthalic anhydride,
in dilute benzene solutions → acid phthalates esters, on shaking with dilute
aqueous alkalis, the water-soluble salts are obtained.
Secondary alcohols need higher temperature 120-130 o
C.
The reaction is used for
1- Isolation, purification and identification of primary and secondary alcohols.
2- It is used for separation of 1ry
from 2ry
and 3ry
alcohols.
3- It is quantitative for primary alcohols and can be used for their estimation.
ROH + O
O
O
OR
O
O
OH
OK
O
O
ONa
OR
O
O
ONa ROH
Na HCO3
Alcoholic
KOHHeat
+
Saponification
Phthalic
anhydride
Alcohol
Acid phthalate
monoester
Sodium phthalate
monoester
Sodium
Potassium
phthalate
Alcohol

12. Carbamic acid esters (urethans or carbamates)
The reaction is used for derivatization of 1ry and 2ry alcohols but not for ? 3ry alcohols
rapidly dehydrated under the reaction conditions. Traces of moisture interfere with the
reaction, and results in the formation of diaryl amines (e.g. diphenyl urea derivatives).
N=C=ON=C=O
O2N
α−Naphtyl
isocyanate
p-nitrophenyl
isocyanate
N=C=O
Phenyl
isocyanate
COOH
Carbamic acid
H2N
ROH +
N=C=O N
H
COOR
Alcohol
Phenyl
isocyanate
Phenyl urethan
Calcium chloride addition products
Certain 1ry alcohols (R-CH2OH) when shaken with powdered anhydrous CaCl2 in
absolute ether or benzene form complex crystalline compounds. The original alcohol is
easily regenerated by the addition of water to the separated CaCl2 complex .

13. Determination of alcohol content in volatile oils
I- General method:
This is based on acetylation of the oil sample using acetic anhydride, and
determination of the ester value of the oil before and after acetylation. The alcohol
content is then obtained by calculation. The method is suitable for determination of 1ry
and 2ry alcohols. estimation of the resulting acetate by hydrolysis with alcoholic KOH.
The major drawbacks of the method are:
1-Tertiary alcohols do not react quantitatively as they are easily dehydrated.
2- Certain aldehydes, ketones and phenols are converted to compounds that can be
acetylated.
II- Determination of 1ry alcohols.
Oils containing 1ry alcohols are refluxed with phthalic anhydride at 100 o
C, to yield the
corresponding acid phthalates. The excess phthalic anhydride is back titrated against
standard alkali.
2ry alcohols react under more drastic conditions.

14. III- Determination of 3ry alcohols.
Modification of the acetylation method:
3ry alcohols undergo partial or complete break down and dehydration when
treated with acetic anhydride. This is overcome by dilution of the reaction
mixture with xylene or oil of turpentine to decrease the dehydrating effect of
acetic anhydride.
Dehydration method:
This is carried by catalytic dehydration of 3ry alcohols using ZnCl2 or I2,
followed by determination of the amount of water released from the reaction,
which is equivalent to the amount of 3ry alcohol present.
IV- Special method for determination of citronellol (formylation)
Most of the terpene alcohols are dehydrated by strong formic acid (100%)
i.e. they are not esterified. On the other hand, only citronellol resists
dehydration and is quantitatively converted to the corresponding formate.

15. Unsaturated Aliphatic Terpene Alcohols
Citronellol
CH2OH
Citronellol
2
3
4
5
6
7
8
Occurrence:
1- d-form in oil of citronella, (Cymopogon nardus).
2- l-form ( β-rhodinol or levocitrol) from oil of geranium (35 - 40 %) and oil of
rose (20 - 35 %).
3- dl-form (dihydrogeraniol) is probably an artefact formed during
hydrodistillation.
Properties: Citronellol is a stable..? only one double bond in the molecule
(c.f. geraniol and nerol, 2 double bonds)., colorless liquid with rose-like odor.
•It is not affected by: 1- Heating in presence of water at 250 o
C or boiling with
alkalies. 2- Treatment with phosphorus pentachloride on the cold. 3- Heating
with dilute acids e.g. H2SO4.
•It polymerizes on heating with strong acids.

16. Isolation:
1- fractional distillation (fraction with boiling points 225-226 °C)
2- Formation of the acid phthalate by heating with phthalic anhydride at 200°C.
The citronellol acid phthalate will be purified by decomposition with alcoholic
KOH and extraction with ether. The geraniol present in the oil will decompose
giving hydrocarbons.
3- semisynthesis: the racemic form obtained by catalytic hydrogenation of
geraniol or nerol.
Identification: derivatization and m.p. determination by Preparation of
1- acid phthalate silver salt 2- citronellyl pyruvate semicarbazone
3- citronellal semicarbazone 4- bromoderivatives
Uses: It used widely in preparations of cosmetics, perfumes, soaps and as
substitute for rose oil
Citronellol Citronellal
[O]
Citronellal semicarbazone

17. Geraniol and Nerol
CH2OH H
H CH2OH
Geraniol
(trans form)
Nerol
(cis form)
Occurrence:
• Geraniol and its esters are present in palmerosa (95 %), geranium (40 - 50
%), citronella (30 - 40 %) and rose .
• Nerol and its esters are obtained from oils of neroli, petitgrain, bergamot,
and generally occur together with geraniol and its esters.
Properties:
• Both compounds have rose-like odor, lighter than water.
• Because of the presence of two olefinic double bonds, geraniol is highly
reactive.

18. Geraniol
5% H2SO4
Terpine hydrate
Geraniol and Nerol are sensitive to mineral acids and dehydrating agents
Geraniol
dehydrating
agent Dipentene or
mix. of terpenoid hydrocarons
Conc H3PO4
or heating with
K bisulfste
Geraniol
oxidation
Citral
CHO
H

19. Separation of Geraniol fromNerol
• Only geraniol forms crystalline additive compound with CaCl2,
which is insoluble in ether, and benzene and regenerated by
warming with H2O.
Geraniol
anhydrous
CaCl2
Geraniol-CaCl2
Warm H2O
• Only geraniol forms a crystalline acid phthalate ester, while
Nerol doesn’t.

20. Identification:
Geraniol can be identified by determination of the melting points of its
derivatives:
1- Diphenyl urethane (m.p. 82-83 °C)
2- α-naphthyl urethane (m.p. 47-8 °C)
3- 3-nitrophthalate (m.p. 109 °C)
Nerol can be characterized by its derivatives:
1- tetrabromide (m.p. 116-118 °C),
2- diphenyl urethane (m.p. 52-53 °C).
Uses:
It is used in manufacturing of perfumes, soap, and flavor industry.

21. (+)-Linalool
Occurrence:
• Linalol is unsaturated tertiary alcohol.
• It occurs either free in d- and l-isomers or in the form of esters
(usually acetate).
• d-form occurs in oils of rose wood, nutmeg, sweet orange and
coriander.
• l-form occurs in oils of lavender, lemon, salvia and rose.
• Linalyl acetate occurs in oils of Lavender, bergamot.
Isolation: By careful distillation of the saponified volatile oil, since it
doesn’t form any definite crystalline derivatives.
HO
*
( + )- Linalool

22. Action of acids:
1) Because it is a tertiary alcohol, linalool isomerizes easily to geraniol by action of acids.
2) It is easily oxidized by chromic acid or formic acid (cold) to citral.
(+)-Linalool
OH
acid reagents oxidation
Chromic acidH
Geraniol
CHO
Citral
CH2OH
3) Upon esterification with glacial acetic acid and acetic anhydride
Properties:
(+)-Linalool
OH
mixture of acetate
derivatives of
H
Geraniol
CH2OH
CH2OH
Nerol
H
α-terpineol
OH

23. Identification:
By preparation of the phenyl urethane and α–naphthyl urethane
derivatives.
Uses:
It is widely used in perfumes, cosmetics, soap, and flavor industries.
4) It converted to terpin hydrate with 5% H2SO4.
(+)-Linalool
OH
hydration
5% H2SO4
OH
OH
terpin hydrate
5) With halogen acids yields the corresponding halides
(e.g. Linalyl chloride and Linalyl bromide)

24. CH2OH
Aromatic Alcohol
(Benzyl alcohol)
• Occurrence: as ester of benzoic and cinnamic acids in
balsam Peru, balsam Tolu, and ester of acetic acid (benzyl
acetae) in oil of Jasmin.
• Isolation: By fractional distillation of original or saponified oil,
or through additive derivatives with CaCl2 , which regenerated
by water.
• Uses:
– Perfumes, cosmetics and soap industry.
– Synthesis of flower oil (Jasmin).

25. Alicyclic terpene alcohols
They can be classified as following:
Monocyclic (e.g. menthol, terpineols)
Bicyclic (e.g. borneol, Isoborneol)
Sesquiterpene (e.g. santalol)

26. Monocyclic Monoterpene Alcohols
Menthol (p-menthane-3-ol)
Occurrence:It exists in the nature only in
the l-form in different Peppermint oils.
Isolation:
It is isolated from Japanese mint oil (Mentha arvensis) Or Peppermint oils
(Mentha piperita)
Characters: Menthol is a crystalline 2ry alcohol. It possesses a
powerful peppermint like odor and a cooling taste.
• It is easily oxidized with dichromate solution into menthone.
• Dehydration with ZnCl2 gives p-menthene.
• Reduction with HI produces p-menthane.
OH
(-)-Menthol

27. Pippermint oil
cooling at 15 o
C, centrifuge
Liquid oilMenthol-crystals
cooling at 5 o
C, centrifuge
Liquid oilMenthol-crystals
Liquid oil
(Menthone + Menthol)
Menthol-crystals
cooling at 10 o
C, centrifuge
Oxime + Menthol
ether dil.H2SO4
ethereal layer
(Menthol)
aqueous layer
(Oxime)
NH2OH.HCl

28. Synthesis: Menthol can be synthesized by hydrogenation
(reduction) of thymol using copper chromite catalyst.
OH
Thymol
OH
Menthol
H2
copper chromite
(-) Menthol
O
K2Cr2O7
soln
Menthone
ZnCl2
p-menthene p-cymene
HI/reduction
p-menthane

29. Identification:
Color tests:
1) Menthol + few drops of conc. H2SO4 + few drops of vanillin-
H2SO4 → orange yellow color.
2) No color with conc. H2SO4+ HNO3 (thymol gives green color).
Uses:
• Menthol is widely used in many pharmaceutical preparations.
1- It can be applied as a counter-irritant on the skin and mucous
membranes.
2- It used as antiseptic in toothpaste and mouth washes.
3- It serves as flavoring agent for certain medicinal preparations, candies,
and chewing gums.

30. α-terpineol
• d-form in oil of Neroli and petit grain (bitter orange)
• l-form in oil of camphor
• Crystalline compound
• Gives oily dibromide derivatives with bromine
• Prepared by fractional distillation and as phenylurethane
• Estimation:
– By the acetylation method because acetic anhydride on the
hot will abstract water giving dipentene.
• Uses:
– Cosmetic, soap because of its lilac-like odor.
OH

31. • α-terpineol is a 3ry unsaturated cyclic alcohol. It easily losses water with
some reagents, e.g.
OH
α-terpineol
Dipentene
KHSO4
Terpinolene
H3PO4
α-Terpinene
Formic acid
Terpinolene

32. Monocyclic sesquiterpenoid alcohols
α -Bisabolol
H OH
(-)α -Bisabolol
Source
Four optically active isomers of bisabolol are possible. (-)α-Bisabolol is the
most common.
It is a monocyclic tertiary alcohol that constitutes together with bisabolol
oxides the major components (about 50%) of the volatile oil of the flowers of
German chamomile (Matricaria chamomilla).
Pharmacological effect
The bisabolol type constituents were found responsible of the ulcer-protective
properties of chamomile

33. Bicyclic Monoterpene Alcohols
• Borneol occurs as d- or l- isomer free or as ester mainly the acetate.
• d-Borneol (borneo-camphor) is present in Dryobalanops sp. Trees, nutmeg
and lavender
• l-Borneol (Nagi-camphor) is present in oil of citronella and coriander.
• Bornyl acetate is present in pine needle oils
• Readily oxidized to camphor
OH
H
(-)-Borneol
H
OH
OH
H* * **
Borneol Isoborneol

34. Isolation
Pine oil
Saponification of the oil (hydrolysis of esters)
Fractional distillation to remove
hydrocarbons, then cooling
Borneol crystals Liquid oil
Acid phthalate derivative of borneol

35. Synthetically from
O
Camphor
Reduction
HO HO
Borneol Isoborneol
Not in nature
Na/alcohol
HO
Cl
Cl
HCl gas
- 10 o
C
isomerization KOH
(+)-α-Pinene Pinene HCl Bornyl chloride
(white ppt.)
Borneol
(pinnane to camphane)
O
Camphor
HNO3
Oxid.
α-pinene therefore used for preparation of synthetic Camphor
molecular
rearrangment

36. Separation of Borneol from Camphor
O
HO
Camphor
Borneol
Phthalic anhydride
heat
HO
Borneol acid phthalate ester
NaHCO3
Sodium salt
Soluble in
water

37. O
HO
Camphor
Borneol
Benzoic acid
boil
Bornyl benzoate
(Non-volatile)
Steam distillation
(volatile Camphor)

38. O
HO
NH2OH.HCl
HON
Camphor oxime
Extracted with
25%H2SO4
Borneol
Camphor
Separation of borneol fromisoborneol
- By heating with zinc chloride in benzene (dehydration)only isoborneol
(unstable) is converted into the solid terpene hydrocarbon camphene.
Isoborneol
ZnCl2/ benzene
Heat
Camphene
HO

39. Uses
• Scenting room sprays, inhales and soap.
• Bornyl esters are used in pharmaceutical preparations
Characters of borneol
• 2ry alcohol with camphor-like odor.
• Volatile at ordinary temperature.
• It is readily oxidized to camphor (by distillation, over copper
oxide, or by action of chlorine.
• It is stable to the effect of dehydrating agents. (c.f. isoborneol)

40. Sesquiterpene alcohols
α-Santalol
It as e.g. of a tricyclic Sesquiterpene alcohols
• In oil of Sandal wood (Santalum album)
• Fractional distillation
• Viscous yellowish liquid
• The medicinal value of Sandalwood is due to santalols
CH2OH

41. For more educational lectures
cognosy4all.blogspot.com

42. cognosy4all.blogspot.com
Pharmacognosy and Herbal Medicine Dr. Mostafa