1. Terpenoids
Presented By
Dr. SWATI A. GADKHE
M. Sc., Ph. D.
P.G. Department of Chemistry,
SGB AMRAVATI UNIVERSITY,
AMRAVATI,
(MS), INDIA.
1

2. Introduction
• Terpenes
• Originally the term terpene was employed to describe a mixture
of isomeric hydrocarbons of molecular formula C10H16 occuring
in terpentine and many essential oils which are obtained from the
sap and tissues of certain plants and trees.
• The oxygenated derivatives like alcohols, aldehydes, ketones at
that time were called camphors.
• As more compounds relating to terpenes and camphors were
discovered with pace of time both the terms were amalgamated
into a single term called terpenoids
• Definition
• It includes hydrocarbons of plant origin of general formula
(C5H8)n as well as their oxygenated, hydrogenated and
dehydrogenated derivatives.
• Terpenoids are composed of isoprene units therefore called as
isoprenoids.
2

3. General properties of terpenoids
• They are unsaturated compounds(open chain or cyclic with one or
more carbon atom rings) having one or more double bonds.
• Undergo addition reactions with hydrogen, halogens, halogen acids
etc.
• They undergo polymerization, also dehydrogenation in the ring.
• As they have olefinic bonds they are very easily oxidized nearly by
all oxidizing agents.
• A no. of terpenoids are labile and hence readily isomerised in
presence of acids into more stable form.
• On thermal decomposition most of the terpenoids yields isoprene
as one of the product.
3

4. Classification of terpenoids
• The terpenoids have general formula (C5H8)n and value of n or isoprene
unit is used as a basis of classification.
4
Terpenoid Isoprene unit No. of C atoms
Hemi terpenoids 1 5
Mono terpenoids 2 10
Sesqui terpenoids 3 15
Di terpenoids 4 20
Sester terpenoids 5 25
Triter terpenoids 6 30
Tetra terpenoids 8 40
• Each class of terpenoids further subdivided into subclasses according to
the no. of rings present in molecule
Acyclic terpenoids Open chain structure
Monocyclic terpenoids Contain 1 ring in molecule
Bicyclic terpenoids Contain 2 ring in molecule
Tricyclic terpenoids Contain 3 ring in molecule
Tetracyclic terpenoids Contain 4 ring in molecule

5. Important essential oils with their terpenoid constitu
ents
5
Essential oil Constituent terpenoid
Cardamom Teroineol
Camphor Camphor
Citronella Farnesol, citronellal and geraniol
Clove Eugenol
Coriandor Linalool, alpha pinene
Ginger Zingiberene
Jasmine Linalool
Lavendor Linalool
Lemon dl-limonene, citral
Peppermint Menthols
Rose Geraniol, citronellol, farnesol
Sandal wood Santalol

6. Isolation
• Due to wide occurrence in nature all terpenoids are not
separated by a general method.
• Mono and sesqui terpenoids isolated by general methods
which is carried out in two steps as follows.
1. Isolation of essential oils
2. Separation of terpenoids from essential oils.
1) Isolation of essential oils
• As plants having essential oils generally possess maximum
concentration at some perticular time.
• For ex. Jasmine at sun-set, it becomes desirable to take plant
parts having essential oil at that perticular time
a) Expression method
• This method has historical importance only. Not used now a
days.
• Plant material cut into small pieces. Then crushed to get juice
which is screened to remove larger particles.
• Then juice is centrifuged in a high speed machine. When half
of the oil is extracted and rest half remain in residue. Residue
contain inferior quality of oil which is obtained by distillation.
6

7. Isolation of essential oils
7
b) Steam distillation method
• Widely used method.
• Plant materials are macerated and steam distilled to get
essential oils into distillate from which these are extracted by
using pure organic volatile solvents like light petroleum.
• Then solvent is removed by distillation under reduced
pressure.
• Demerit- Some essential oils undergo decomposition during
steam distillation.
c) Extraction by means of volatile solvents
• Widely used in perfume industry.
• Used for such plants which yields low quantities of oil on
steam distillation.
• In this method plant material is directly treated with light
petrol at 50˚ C.
• Under these conditions oil is taken up by solvent along with
soluble colouring material.
• Then essential oils from these extract are separated by
removing solvent by distillation under reduced pressure.

8. d) Adsorption in purified fats
• This method is known as enfleurage method and widely
used in france.
• Yield of essential oil is higher by this method
• Used to extract large no of essential oils like rose and
jasmine.
• In this method fat is warmed to 50˚c in glass plates.
• Surface of fat is covered by flower petals and allowed to
kept as such for several days untill it becomes saturated with
essential oils.
• Old petals are replaced by fresh petals and it is repeated
several times.
• After removing petals, fat is digested with ethyl alcohol.
• Oil present in fat is dissolved in alcohol and some quantity
of fat is also dissolved in alcohol.
• These can be removed by cooling alcohol extract at 20˚c.
• When fat separates out, the alcoholic distillate is finally
fractionally distilled under reduced pressure to remove the
solvent.
8

9. 2) Separation of terpenoids from essential oils
9
a) Chemical methods
• These methods are not used these days.
I. Essential oils containing terpeoid hydrocarbons are treated with
nitrosyl chloride in chloroform. Crystalline adduct of hydrocarbons
having sharp melting points are obtained. These are separated and
decomposed to their corresponding hydrocarbon.
II. When essential oil containing alcohols are treated with phthalic
unhydride to form diesters. Primary alcohol react with phthalic
anhydride readily, secondary alcohols less readily and tertiary
alcohol do not react at all. After extrating diesters are decomposed
by alkali to parent terpenoid alcohol.
III. Terpenoid aldehyde and ketones are separated from essential oils
by forming their adducts with common carbonyl reagents like
NaHSO3, 2,4-dinitro phenyl hydrazine, phenylhydrazine,
semicarbazide, etc.after that these are decomposed to their
terpenoid aldehyde and ketones.
b) Physical methods
I. Fractional distillation method
II. chromatography

10. Structure determination of geraniol
10
• Geraniol occures either free or In the form of its esters in many
essential oils like rose, lemon grass, geranium, lavender and citronella.
• Geraniol is a pleasant smelling colourless liquid which boils at 229-
230˚c at 757mm pressure.
•After extracting from essential oils it is purified by crystallising it with a
complex compound with anhydrous calcium chloride
•Geraniol and its esters are mainly used in perfumary, perticulary as a
component of artificial rose scent.
• Constitution
1) Its molecular formula has been found to be C10H18O
2) As it adds on two moles of hydrogen, two moles of bromine, etc. to
form addition product. This shows that it contains two double
bonds.
C 10 H 22 O C 10 H 18 O C 10 H 18 OBr 4
H 2/N i
geraniol

11. 11
3) On oxidation it yields an aldehyde (citral a) having same no of carbon
atoms, Indicating that geraniol is a primary alcohol. The aldehyde called as
citral-a or Geranial which could be reconverted into geraniol by reduction.
Thus geraniol must be correponding alcohol of citral-a.
But the structure of citral-a is well established. Therefore the structure of
geraniol may be represented as follows:
H
CH3
CH3
C
H3
CH2OH
[O]
2[H] H
CH3
CH3
C
H3
CHO
Geranial or citral a

12. Synthesis of geraniol
12
The structure of geraniol is confirmed by its synthesis (brack and schinz,1951)
Which involves Claisen rearrangement.

13. Camphor
• introduction
• This occures in nature in camphor tree in Japan, China. It is
present in all parts of tree however, highest proportion present in
trunk
• Isolation
• When wood and leaves of camphor tree are boiled with water in
a vessel covered with dome, camphor sublimes and collects on
the surface of dome.further its purification can be done by
resublimation.
13

14. Physical properties
• Camphor is solid with charecteristic
smell and burning state.
• Melting point 180c.
• Boiling point 204 c
• It is optically active.
• (+) and (-) forms occurs naturaly.
• Recemic form is found in synthetic
product.
14

15. Uses of camphor
• As a plasticiser for the manufacture of celluloid and
photographic films.
• For manufacture of smokeless powders and explosives.
• As a mild disinfectant and stimulant for the heart muscle
• As an insect repellent
• As flavour in soaps and cosmetics.
15

16. Structure determination of camphor
• Molecular formula
• C10H16O
• Saturated characteristics.
• Camphor does not add reagents like bromine, nitrosyl chloride etc.
However it forms monosubstitution products like mono-bromocamphor,
mono-chlorocamphor, camphor-sulhonic acid. The formation of these
products reveals that camphor is a saturated compound.
• Presence of a keto group
• The nature of oxygen atom is found to be cyclic ketonic because it forms
an oxime with hydroxylamine
• It forms semicarbazone with semicarbazide
• It forms phenyl hydrazone with phenyl hydrazine.
• When camphor is distilled with iodine it yields carvacrol. The phenolic
group in carvacrol reveals the presence of ketonic group in camphor
16
C 10 H 16 O + NH 2 OH C 10 H 16 =NOH
CAMPHOR
I2
C
H 3 C H 3
C H 3
O H

17. Structure determination of camphor
• Bicyclic system
• Molecular formula of saturated parent hydrocarbon of camphor is C10H18
which corresponds to the general formula CnH2n-2 of bicyclic compounds.
Therefore camphor is bicyclic.
• Presence of CH2-CO group
• When camphor is treated with amyl nitrite and hydrochloric acid, it yields
an iso-nitroso camphor in which two hydrogen atoms have been replaced
by =NOH group. It reveals that >C=O group is directly attached to –CH2
group.
17
H14C9
CH2
CO
amyl nitrite
HCl CO
H14C9
C=NOH

18. Structure determination of camphor
• Presence of six membered ring.
• When camphor is distilled with zinc chloride or P2O5 it yields p-cymene. It
reveals that presence of six membered ring, methyl and gem-dimethyl
group in camphor.
• Nature of carbon frame in camphor.
• When camphor is oxidised with nitric acid, it yields crystalline dibasic acid,
camphoric acid C10H16O4. As camphoric acid posseses same no of
carbon atom as camphor, it means keto group must be present in one of
the ring in camphor.
• Camphoric acid further oxidised with nitric acid, camphoronic acid
C9H14O6 is obtained.
18
C10 H16 O
P2O5/ Zn
CH3
CH3
C
H3

19. Structure determination of camphor
• Structure of camphoronic acid.
• Mol formula C9H14O6. mol formula corresponding to the general formula
(CnH2n+2) for acyclic compound, indicating it is acyclic compound.
• Saturated tricarboxylic acid
• Structure of camphoric acid.
• Mol formula C10H16O4. It is saturated dicarboxylic acid.
• Camphoric acid further oxidised with nitric acid, camphoronic acid C9H14
O6 is obtained.
19
COOH
COOH
CH3
C
H3 CH3
CH3
C
C
COOH
C
H2
COOH
COOH
CH3
C
H3

20. Synthesis of camphor from
camphoric acid
• Synthesis was given by Haller(1986).
20
COOH
COOH
CH3
CO
CH2
CH3
O
COOH
CN
CH3
CH3
O
C
H3 CH3
C
H3 CH3
O
CO
CO
CH3
C
H3 CH3 C
H3 CH3
COOH
COOH
CH3
C
H3 CH3
C
H3 CH3
Ac2O
-H2O
Na-
Hg KCN
H+
OH
H+
Ca salt

camphoric acid camphoric anhydride  campholide
homocamphoric acid camphor

21. Commercial preparation of camphor
• On large scale camphor is prepared by α-pinene which is commercially a
vailable from turpentine oil.
• The reaction involves no. of wagner-meerwein rearrangement which caus
es a complete change in carbon skeleton.
21
C
H3
CH3
C
H3
CH3
Cl
H
H
CH3
Cl
C
H3 CH3
C
H2
C
H3 CH3
CH3
H
OAc
C
H3 CH3
CH3
OH
C
H3 CH3
CH3
O
C
H3 CH3
HCl
WMR
Base
-HCl
AcOH
H2SO4
NaOH C6H5NO2
 pinene  pinene hydrochloride bornyl chloride camphene
camphor

22. Synthesis of camphor from dihydro
carvone
• synthesis was given by Money et al(1969).
22
CH3
O
C
H3 CH2
C
H3 CH3
CH3
O
C
H3 CH3
CH3
O
C
H3 CH3
BF3
CH2Cl2
CH3
-
C=(CH2)2
-
OAc
TsOH

23. Squalene
• Introduction
• Acyclic triterpenoid.
• Squalene has been isolated from lever oils of sharks. It is also found in
olive oil and several other vegetable oils.
• It is a liquid which boils at 240-242˚C at 4 mm pressure.
23

24. Structure determination of squalene
• Molecular formula
• C30H50
• Unsaturated characteristics.
• When squalene is hydrogenated catalytically, it adds on six moles of
hydrogen to form perhydrosqualene C30H62. This reaction reveales that
squalene has six double bonds.
• The presence of six double bonds in squalene has been confirmed by
treating with HCl. Squalene adds on six moles of reagent and form
squalene hexachloride.
• Squalene hexachloride separated into three crystalline forms, revealing
that squalene itself is also a mixture of 3 isomers.
• The mol. Formula of perhydrosqualene is C30H62 which corresponds to
CnH2n+2 for acyclic compounds. Hencesqualene is open chain
compound.
• Since squalene cannot be reduced by sodium and amyl alcohol, it means
there are no conjugated double bonds in squalene. perhydrosqualene
C30H62
24
C 30 H 50 + 6H 2
C A T A L Y S T
N i
C 30 H 62

25. Structure determination of squalene
• When squalene is oxidised with chromyl chloride in CCl4, it yields
formaldehyde, acetaldehyde and succinic acid, revealing that squalene
contains following three fragements.
25
>C=CH 2
[O]
HCHO HCOOH
[O]
-CH=C<
[O]
CH 3CHO

26. Synthesis of squalene
• Karrer and Halfenstein(1931)
26
C
H3
CH3 CH3 CH3
OH
C
H3
CH3 CH3 CH3
X
2
2
C
H3
CH3 CH3
CH3
CH3
CH3
CH3
CH3
2 mols of farnesyl alcohol
2 mols of farnesyl bromide or chloride
squalene
Mg
-MgX
PX3
(X= Cl or Br)

27. Synthesis of squalene
• Synthesis of squalene by condensation of geranyl acetone with bis- grignard
derivative of 1,4-dibromo butane.
27
C
H3
CH3 CH3
O
CH3
2
C
H3
CH3 CH3
CH3
CH3
CH3
CH3
OH
OH
CH3
2 mols of geranyl acetone
+ Br Mg
-
CH2
-
CH2
-
CH2
-
CH2
-
Mg Br
C
H3
CH3 CH3
CH3
CH3
CH3
CH3
CH3
-2H2O
squalene

28. Synthesis of squalene
• Whiting’s synthesis: squalene is synthesized bymeans of the wittig’s reaction from
pure trans geranyl acetone and triphenylphosphorosylide.
28
C
H3
CH3 CH3
O
CH3
2
2 mols of geranyl acetone
+ PPh3=CH
-
CH2
-
CH2
-
CH=PPh3
C
H3
CH3 CH3
CH3
CH3
CH3
CH3
CH3
squalene

29. Structure determination of Abietic
acid
• Molecular formula
• C20H30O2
• Abietic acid gives effervescence with sodium bicarbonate, this shows it co
ntains a carboxylic group. Moreover as it is very difficult to esterify acid,
this shows that carboxylic group is attached to a tertiary carbon atom.
• Unsaturated characteristics.
• When abietic acid is hydrogenated catalytically, it adds on two moles of
hydrogen to form tetrahydro abietic acid. This reaction reveales that
abietic acid has two double bonds.
• If COOH group is considered as a substituent group the parent
hydrocarbon of abietic acid would be C19H34 corresponding to the general
formula CnH2n-4 for tricyclic compounds and therefore abietic acid is
tricyclic compound.
29
C 19 H 29 COOH + 2H 2
C A T A L Y S T
N i
C 19 H 33 COOH

30. Synthesis of Abietic acid
30
O
C H 3
C H 3
m ethylation
O
C H 3
C H 3
C
H 3
C H 3
C H 3
O
C H 3
C H 3
ethyl vinyl ketone
C H 3
C
H 2
O
alkylation
ethyl brom o
acetate
C H 3
C H 3
O
C H 3
H 5 C 2 OOCH 2C C H 3
S
S
C H 3
C H 3
C H 3
H 5C 2OOCH 2C C H 3
C H 3
C H 3
C H 3
H 5 C 2OOCH 2C H
Barbier wieland
degradation
C H 3
C H 3
C H 3
HOOC C H 3
Dehydoabietic acid
 tetralone
i) m ethylation
ii) desulphurisation
iii) hydrolysis
iv) hydrogenation
i) ethanediothiol
ii) hydrolysis (OH)

31. Alkaloids
• Introduction
• Alkaloids were defined as basic nitrogenous plant products, mostly
optically active and possessing nitrogen heterocycles as their
structural units with a pronounced physiological action.
• Classification of alkaloids
I. Taxonomic
II. Pharmacological
i. Analgesic alkaloid
ii. Cardioactive alkaloid
III. Biosynthetic
IV. Chemical
i. Phenylethylamine alkaloid
ii. Pyrrolidine alkaloid
iii. Pyridine or piperidine alkaloid
iv. Pyridine-pyrrolidine alkaloid
v. Tropane alkaloid
vi. Quinoline alkaloid
vii. isoquinoline alkaloid
viii. Phenanthrene alkaloid
ix. Indole alkaloid
31

32. Structure determination of
papaverine
32
• papaverine occures in opium poppy to the extent of 0.5 to 8% and
known as opium alkaloid.
• Isolation
• The dried latex obtained from unripe seed capsule of poppy is
digested with milk of lime. The alkaloids of morphine series remain
dissolved and those of papaverine series are precipitated. They are
extracted with suitable solvent like chloroform.
• properties
• Colourless solid with melting point 147˚C.
• Optically inactive tertiary base.

33. Structure determination of
papaverine
33
•Constitution
1) Its molecular formula has been found to be C20H21NO4
2) Presence of tertiary base: it adds one molecule of methyl iodide to
yield a quaternary methiodide derivative, indicating nitrogen present
in papaverine is tertiary.
3) Presence of four methoxyl group: when papaverine is heated with
constant boiling hydroiodic acid. It yields four equivalents of methyl
iodide. It reveales that papaverine contain four methoxyl group.
4) Presence of methylene(-CH2) group: when papaverine is heated
with cold dilute permanganate, it yields secondary alcohol
papaverinol. Which on more vigorous oxidation yields ketone,
papaveraldine; formation of these ketone revels that papaverinol is
secondary alcohol. Finally prolonged action of permanganate causes
oxidation of papaveraldine to papaverinic acid. papaverinic acid is
dibasic acid and also contains keto group and two methoxyl group.
All the foregoing reactions suggests that papaverine contains a
methylene group.

34. Synthesis of papaverine
34
•The structure of papaverine has been confirmed by its synthesis
given by Pictet and Games in 1909 which has been simplified,
modified and improved by Bide and Wilkinson. It is two step
synthesis.
1) Synthesis of homoveratryl amine and homoveratoryl chloride.
H3CO
H3CO
CH2O/ HCl
H3CO
H3CO
CH2Cl H3CO
H3CO
CH2CN
H3CO
H3CO
COCl
H3CO
H3CO
NH2
H2/Ni
1) hydrolysis
2) PCl5
homoveratroyl chloride
homoveratryl amine
veratrole
3,4
-
dimethoxybenzene cyanide

35. Synthesis of papaverine
35
2. Condensation of the two to form papaverine.
H3CO
H3CO
NH2
+
H3CO
H3CO
COCl

H3CO
H3CO
N
H
CO
OCH3
OCH3
Enolisation/-
H2O
P2O5
N
OCH3
OCH3
H3CO
H3CO
Dihydropapaverine
palladised asbestos 
-2H
N
OCH3
OCH3
H3CO
H3CO
papaverine

36. Structure determination of
nicotine
36
• Introduction
• Tobacco alkaloid occurring in Nicotiana tobacum L and other nicotiana
species.
•Occures in the form of its salts with malic acid and citric acid.
•It is distributed throughout the plant but highest concentration found
in leaves in varying ammounts from 0.6 to 8 percent.
• Isolation
• The leaves and stems of tobacco plants are dried and powdered and
then distilled with milk of lime. when nicotine distilles over the distillate
is extracted with ether. When solvent is evaporated nicotine is left as an
oily liquid which is further purified by fractional crystallisation of its salt
like oxalate.
• properties
• for human consumption tobacco of low alkaloid content is desirable
as nicotine is extremely toxic. Aprox. 40 mg
•When freshly prepared, it is colourless, very hygroscopic liquid. Boiling
point is 247˚C.
• natural nicotine is laevorotatory.

37. Structure determination of
nicotine
37
•Constitution
1) Its molecular formula has been found to be C10H14N2
2) Presence of tertiary nitrogen: it adds two molecules of methyl
iodide to yield a dimethiodide. Under suitable conditions, it also
form two isomeric monomethiodides, one of the tertiary nitrogen is
found to be N-methyl group.
3) when nicotine is oxidised with chromic acid or KMnO4 it forms
nicotinic acid showing that nicotine is a pyridine derivative
containing a side chain in 3-position.
4) Nature of side chain: with zinc chloride nicotine forms an addition
product nicotine zinc chloride, when distilled with soda lime, yields
pyridine, methylamine and pyrrole. This reaction reveals that
nicotine might contain a five member heterocyclic ring containing
nitrogen (ie. A pyrrolidine or a pyrrole ring). Thus, now the side
chain having N-methyl group can be extended as C4H7.NCH3
This step clearly revealed that the side chain is pyrrole derivative. But
we have already stated that the side chain is reduced and is having
one N-CH3 group, it is N-methyl pyrrolidine.
N
+
N
H
+ CH 3NH 2
C10 H14 N2.ZNCl 2.2HCl.H 2O
Lime

38. Synthesis of nicotine
38
• By spath and bretschneider(1921)
a) Synthesis of N-methyl-2-pyrrolidine
N
H
O
O
N
H
O
N
O
CH3
electrolytic
reduction
(CH3)2SO4
NaOH
Succinimide 2 pyrrolidine N methyl 2 pyrrolidine

39. Synthesis of nicotine
39
N
O
CH3
N
COOC2H5
+
C2H5ONa
N N
O
CH3
O
HCl 130 o
C
N
NH
CH3
O
COOH
-CO2
CO
N
H
CH3
Zn dust C2H5OH.NaOH
N
H
O
H
CH3
CHI
N
H
CH3
HI
100 o
C
NaOH
N
N
CH3
 keto acid
Nicotine
ethyl nicotinate
n methyl pyrrolidone
b) nicotine N-methyl-2-pyrrolidone produced in step (a) further
undergoes reactions to yield nicotine.

40. Thank you