CONTENTS

• ALKALOIDS DEFINITION
• CLASSIFICATION
• EXTRACTION
• GENERAL STRUCTURAL ELUCIDATION
• IDENTIFICATION TESTS
• EXAMPLES OF THE ALKALOIDS
• REFERENCES

1
 ALKALOIDS
• DEFINITION:
Alkaloids are a group of naturally occurring
chemical compounds which are basic in nature and
contains nitrogen atom in its heterocyclic ring.

• Alkaoidal content of plant varies with the season, age and

its localty.

2
CLASSIFICATION OF ALKALOIDS

• Phenylethylamine alkaloids eg:Ephedrine,Pseudoephedrine

• Pyrrolidine alkaloids eg: Hygrine, Coca species
• Pyridine or piperidine alkaloids eg: Arecoline, Coniine
• Pyridine-Pyrrolidine alkaloids eg: Nicotine
• Phenanthrene alkaloids eg: Papaverine
• Indole alkaloids eg: Ergometrine, Reserpine
• Quinoline alkaloids eg: Quinine, Cinchonine
• Isoquinoline alkaloids eg: Morphine, Codeine
• Tropane alkaloids eg: Atropine, Cocaine
• Tropolone alkaloids eg: Colchicine

3
 EXTRACTION OF ALKALOIDS
Powdered drug

Alkaloids are freed as bases by rendering with the solution of

ammonia or sodium carbonate

Total extract was concentrated and shake with successive

quantity of inorganic acid

Residue organic fraction Aqueous acid

solution
(like pigments,fats very weak
bases or CHC/3 soluble
alkaloidal sulphates)

4
Organic solutions of alkaloidal Make alkaline and extract
Bases alkaloid with immiscible solvents
(alkaloidal salts)

Crude alkaloid mixture was obtained

By the removal of solvent

Residual
Purification by fractional crystallization aqueous fraction
Chromatographic separation etc

Structural identification by modern

analytical techniques like uv, Mass,
NMR, IR spectroscopy etc
5
 STRUCTURAL ELUCIDATION OF
ALKALOIDS
• Determination of molecular formula and optical activity
• Determination of unsaturation
• Cleavage of alkaloids into fragments
• Identification of fragments, linkage of fragment to fragment
• Determination of oxygen includes methoxyl, alcoholic, phenolic,
carboxylic, carbonylic, acetoxy, benzoxy
• Determination of nitrogen
• Determination of C-methyl group
• Degradation of alkaloids
– Hofmann exhaustive methylation
– Emde’s degradation
– Van Braun’s method
– Oxidation
– Zinc Distillation/Reductive Degradation
– Alkali fusion
– Dehydrogenation
• Physical Methods
• Synthesis
6
Determination of molecular formula and optical activity:
Molecular formula calculation is based upon the simple fact that
introduction of a double bond or cyclisation of the chain decreases
the molecular formula by two hydrogen atoms relative to its
corresponding aliphatic hydrocarbons.
If alkaloid is optically active, its specific rotation is measured.

Determination of unsaturation:
Unsaturation can be determined by using
-reducing agents like LiAlH4 and NaBH4
-bromination
-by using halogen acids or alk.KMnO4

Cleavage of alkaloids into fragments:

Alkaloid are cleaved into fragments either by hydolysis with
water, acid or alkali.
These fragments can be examined separately.
Eg: Piperine on hydrolysis gives piperidine or piperic acid shows
that they are linked With an acid amide linkage.

7
Functional group analysis:
Infra red examination can reveal the nature of functional group present.

Functional nature of oxygen:

a) Hydroxyl group:
by the formation of acetate on treatment with
Acetic anhydride
Acetyl chloride
by the formation of benzoate on treatment with
Benzoyl chloride
The no. of hydroxyl group can be determined by
Zerewintoff’s method in which it can
Quantitatively can be estimated by treating with methyl magnesium iodide
and measuring mathane so formed.

b) Phenolic hydroxyl group: It is characterized by

-Alkali solubility followed by reprecipitation by carbon dioxide
-Color reactions with ferric chloride
-Acylation to an ester
-Alkylation to an ether

8
c) Alcoholic hydroxyl group:
Generally by acylation reaction and negative tests for phenolic
group.
Confirmation by dehydration, oxidation, absorption spectrum in the
IR region.
i) Primary alcoholic group: On oxidation

Primary alcohol aldehyde carboxylic acid

(same no. of (same no. of
carbon atoms) carbon atoms)
ii) Secondary alcoholic group: On oxidation
secondary alcohol ketone carboxylic acid
(same no. of (less no. of
carbon atoms) carbon atoms)
iii) Teritiary alcoholic group on oxidation gives ketone and further
gives acids with less no. of carbon atoms.

d) Carboxylic group: can be determined by

i. Carboxylic group + alcohol ester
ii. By its solubility in aqueous Na2CO3/NH3
Its no. of Carboxylic group can be determined volumetrically by titration
against a Standard Ba(OH)2 solution using phenolphthalein indicator. 9
Gravimetrically by silver salt method
e) Alkoxyl group: Alkoxyl group can be determined by Zeisel method.
1260C AgNO3
-OCH3 + HI -OH + CHI3 AgI
The no. of moles of silver iodide indicates the number of alkoxylic
groups in the treatment.

f) Carbonyl groups: Carbonyl groups can be determined by reaction with

Hydroxyl amine, phenyl hydrazine or 2,4-dinitrophenyl hydrazine.

g) Ester group: Ester groups can be detected by their hydrolysis with water,
dilute acids, alkali to the hydroxyl and acidic compounds. The nature is
established by knowing the nature of the acid.
-COOR + NaOH -COONa + ROH
-CONH2 + NaOH -COONa + NH 3

10
Functional nature of nitrogen:
The nature of nitrogen in an alkaloid can be determined by the reaction with
acetic anhydride, methyl iodide and nitrous acid.
Secondary amines gives nitroso product on reaction with nitrous acid and it
can be acetylated and benzoylated.
Alkylation of secondary amines requires 2 moles of alkyl halides.
Teritiary amines requires one mole of alkyl halides for alkylation and are
converted into amine oxides on treatment with 20%H2O2.

The N-alkyl group can be estimated by Herzig-Meyer method

HI 150-300 AgNo3/C2H5OH
N-CH3 NH + CH 3I AgI
NMR spectroscopy is also used for the detection of N-methyl and N-ethyl
groups.
-On distillation of an alkaloid with aqueous KOH gives methylamine,
dimethylamine/ trimethylamine indicates that 1,2,3 alkyl groups
respectively attached to the nitrogen atom, if ammonia is formed it
indicates the presence of a free amino group.
N-alkyl group can also be detected by the distillation of an alkaloid with
soda lime when methyl amine is obtained,
11
Estimation of C-methyl group;
C-methyl groups are estimated by the Kuhn-Roth oxidation in
C-CH3 + K2Cr2O7/H2SO4 HOOC.CH 3

Degradation of alkaloids:
Based on the changes during the degradation we can easy to know the
structure of an original molecule.
a) Hofmann exhaustive methylation:
By this method heterocyclic rings are opened with the elimination
nitrogen from the nature of the remaining carbon skeleton, the nature
of heterocyclic ring can be ascertained.
Hofmann exhaustive methylation fails
With unsaturated heterocyclic rings
When there is no beta hydrogen atoms
With tetrahydroquinoline
MeI Heat
CH3CH2CH2NMe2 Ag2O CH3CH2CH2N+Me3OH CH3CH=CH2
200OC
QUARTENARY AMMONIUM
HYDROXIDE + Me3N + H2O

12
 N
H2/Ni 2MeI

NH
N+
PYRIDINE PIPERIDINE
Me2I-
DIMETHYL
PIPERIDINIUM
IODIDE
Moist
Ag2O

HEAT MeI
H20 HEAT
Ag2O
H2O
N+
N N
Me3OH - Me2
DIMETHYL Me2OH
PIPERIDINIUM
HYDROXIDE

+ Me3N ISOMERISES

PIPERYLENE

13
b) Emde’s degradation: can be applied for those compounds which do
not contain Beta hydrogen atoms.
In this final step involves reductive cleavage of quartenary ammonium
salts either with sodium amalgam or sodium in liquid ammonia or by
catalytic hydrogenation.

N Na,C2H5OH N MeI,AgOH

ISOQUINOLINE
1,2,3,4-TETRAHYDRO
ISOQUINOLINE

N+Me2OH-
HEAT
-H2O
CH2NMe2

MeI
AgOH

EMDE'S
DEGRADATION + Me3N
Na/Hg,
H2O-C2H5OH
CH2N+Me3I- CH3
NOTE:Here beta hydrogen is absent
o-METHYL STYRENE
14
c) Von Braun method: Includes two types:
i) Von Braun cyanogen method: The bond between N and CH3 gr.is cleavage by cyanogen bromide to
give cyanamide and methyl bromide. The cyanamide is treated with acid secondary amine is obtained.

BrCN

N N+ CH2Br

R CN Br_ N
R

R CN

CH2Br

H
R

15
Von Braun second method is for the compounds with the secondary cyclic
dist. under
amines PBr5 reduced pressure
+ C6H5CN
N N CH2Br CH2Br
C6H5
COC2H5 C
1,5-DIBROMO
Br Br
PENTANE
N-BENZOYL INTERMEDIATE
PIPERIDINE

d) Reductive degradation: The pyridine/piperidine nuclei in some cases

can be eliminated as ammonia and n-pentane by heating with hydroiodic
acid at 300oc.
N
HI
+ NH3
O
300 C CH3 CH3

PYRIDINE n-PENTANE

Zinc dust distillation: Distillation of an alkaloid or its product over hot zinc
dust degrades to its aromatic derivative.
Zn dust
Morphine phenanthrene

e) Alkali fusion: gives information about the type of nuclei present 16

in
the molecule by the fusion with solid KOH.
 f) Oxidation: Gives information about the fundamental structure of alkaloid
and the Position and nature of some of the functional groups or side chains
such as –CHOH etc.
HO COOH
KOH
ADRENALINE
FUSION

HO

PROTOCATECHUIC ACID

Mild oxidation eg: H2O2, I2 in ethanolic solution, alk.K4[Fe(CN)6]

Moderate oxidation eg: acid or alkali KMnO4 or Cr2O3 in acetic acid
Vigorous oxidation eg: K2Cr2O7/H2SO4, Cr2O3/H2SO4, Con.HNO3, MnO2/H2SO4
g) Dehydrogenation : In this method the alkaloid is distilled with a catalyst
such as Sulphur, selenium/palladium to form relatively simple and easily
recognisable product Generally used to determine the gross structure of the
alkaloid. During dehydrogenation peripheral groups such as hydroxyl and
c-methyl groups can be estimated.

Physical Methods: used for determining the gross structure of an alkaloid and
used to clarify the compound stereochemistry.
17
 •Ultraviolet spectroscopy
•Infrared spectroscopy
•Nuclear Magnetic Resonance spectroscopy
•Mass spectroscopy
•Optical rotatory dispersion and circular dichorism
•Confirmational analysis
•X-ray diffraction

Synthesis:
The final confirmation of the structure can be made by its synthesis.

18
 IDENTIFICATION TESTS OF ALKALOIDS
REAGENT CHEMICAL COLOUR
Dragendroff’s Potassium Reddish brown
reagent bismuth iodide precipitate
solution
Mayer’s Potassium Cream
reagent mercuric iodide precipitate
solution
Wagner’s Iodine in Reddish brown
reagent potassium Iodide precipitate
solution
Hager’s reagent Solution of picric Yellow
acid in water precipitate
19
 EPHEDRINE
• SOURCE:Ephedrine occurs along with five other alkaloids namely
pseudoephedrine, methylephedrine, methylpseudoephedrine,
norephedrine and norpseudoephedrine obtained from the genus
Ephedra.
• It is a protoalkaloid.
• It belongs to phenylethylamine alkaloid.
USES:
•Shows sympathomimetic in action.
•Used successfully in the treatment of bronchial asthma,
hay fever and mydriatic action.
•Used in the treatment of allergic reactions.
•Also have hypotensive effects

20
 CONSTITUTION OF EPHEDRINE:

1. Its molecular formula is C10H15NO.

2. Presence of a secondary amino group
3. On benzoylation , it gives dibenzoyl derivative which means oxygen
atom is present as hydroxyl group since one benzoyl group is
introduced at NH group and other at OH group.
4. On oxidation ephedrine gives benzoic acid suggesting that it is
monosubstituted benzene.
5. On treatment with hydrochloric acid it gives methylamine,
propiophenone.

C10H15NO CH3NH2 C6H5COCH2CH3

HCI

21
 This reaction suggests either of the following two structures of ephedrine .
NH
NH

OH
OH
I II
6.Ephedrine hydrochloride on heating, undergo hydramine fission to form
Propiophenone phenylacetone and methylamine.
NH

CH3NH2 C6H5COCH2CH3 C6H5CH2COCH3

HCI
OH

7.The above structure of ephedrine is supported by its Hofmann

exhaustive methylation to syn-methylphenylethylene oxide.

NH
HOMe3N
CH3I
heat
AgOH C6H5CH CHCH3 Me3N
OH O
OH

22
 8.The structure proposed by degradative means is further confirmed by
its synthesis and optical isomerism
Synthesis:
NH

C6H5.CO.CHO.CH3 CH3OH H2-Pt

C6H5.CO.C.CH3

NH2.CH3 N.CH3 OH
EPHEDRINE

Isomerism: The racemic ephedrine is resolved into optically active ephedrine

by means of mandelic acid.

ISOMERS OF EPHEDRINE:
CH3 CH3

H C NHCH3 H3CHN C H

H C OH HO C H

C6H5 C6H5
(- )-EPHEDRINE (+ )-EPHEDRINE

23
 NICOTINE
• Source: Nicotine is obtained from the leaves of Nicotiana
tobaccum
• It belongs to pyridine-pyrrolidine alkaloid.
• It is a type of tobacco alkaloid.
• It is the one of the toxic alkaloid known and its fatal dose for
human being is 40 mg.

24
 CONSTITUTION OF NICOTINE

1. Its molecular formula is C10H14N2

2. Nature of nitrogen atoms: tertiary and one was the N-methyl group

3. Nicotine on oxidation gives nicotinic acid indicating that it is 3-substituted

O OH

C10H14N2

4. Position and nature of side chain: Nicotine absorbs only three moles of
hydrogen form hexahydro derivative suggesting that side chain is saturated.
N NH

Na-C2H5OH

C5H10N C5H10N
25
 -When nicotine is heated with concentrated hydroiodic acid at 150 0c
and forms methyl iodide, thus side chain has N-methyl group

N NH
lime
C10H14N2.ZnCl2.HCLH2O
CH3NH2
Nicotine zinc chloride
PYRIDINE pyrrole
Above reaction indicates that, as side chain is pyrrole derivative. The
point of attachment of side chain to the 3-position of pyridine nucleus is
CH3 CH3

N N
C5H10N
or

On treatment with methyliodide, it gives nicotine isomethiodide which on

oxidation with potassium ferricyanide followed by dichromate oxidation gives
N-methylproline.
CH3

HI CrO3 N O
C10H14N2 C10H14N2CH3I C10 H13 N2OCH3
CH3I K3Fe(CN)6
OH 26
N-METHYLPROLINE
5. Nicotine on treatment with bromine in acetic acid affords HBr per bromide
along with other products on treatment with H2SO4.Hydobromide perbromide is
converted to dibromocotinine which gives 3- acetyl pyridine, oxalic acid,
methylamine on heating with a mixture of sulphurous and H2SO4 at 130-1400

N Br2-CH3CH3OO H2SO3 NH
N CH3NH2 COOH
N H2SO3 H2SO4
N
O
COOH
NICOTINE COCH3
Br Br

Nicotine on treatment with bromine in presence of hydrobromic acid

gives dibromoticonine which on heating with barium hydroxidegives
nicotinic acid , melonic acid and methyl amine.

Br2 NH COOH
N N CH3NH4
N HBr N
Ba(OH)2 H2C
O COOH
NICOTINE HO
COOH
Br Br

The structure of nicotine was finally prepared by the synthesis of nicotine.

27
 MORPHINE

• SOURCE: It is extracted from the dried leaves of Papaver

somniferum plant with at high conc.(23%).
• It belongs to a class of opium alkaloids and a subclass of morphine
alkaloids.
• This belongs to a class of papaverine alkaloids i.e. it contains
phenanthrene ring.
• It is a colorless solid insoluble inether, water but most soluble in
alcohol. It is leavorotatory alkaloid with a specific rotation of 131.
USES:
•Analgesic
•Hypnotic and sedative
•Potent analgesic due to its central narcotic effect
•CTZ stimulation in the medulla

28
 CONSTITUTION OF MORPHINE

1.Its molecular formula is C17H19O3N

2.Its nature of nitrogen is tertiary in nature
CH3I
[C17H19O3] N [C17H19O3] N CH3
Morphine quaternary salt

3.Its nature of oxygen atom

I. Presence of 2 hydroxyl groups
Acetylation
C17H17ON[OH]2 C17H17ON(OCOCH3)2
morphine

C17H17ON(OCOC6H5)2

ii) Nature of hydroxyl groups:-

With FeCl3 gives characteristic color
treating with aq.NaOH gives soluble mono sodium salt of morphine
reconverted into morphine with CO2
Note:- one of the two hydroxyl groups is phenolic in nature
29
iii) With halogen acid gives monohalogen derivative that is one –OH
group is replaced by halogen acid this reaction is characteristic of
alcohol. Hence second –OH group is alcoholic in nature (secondary
alcohol)
iv) From the unreactivity of third oxygen and by degradation studies it
is revealed that third oxygen is in ether linkage
Presence of ethylenic bond:-
morphine on acid hydrolysis gives epomorphine..
Presence of benzene nucleus:- Bromination :-gives mono bromo
derivatives it reveals that morphine contain benzene ring.
Presence of phenanthrene ring:-
with zinc dust :- gives phenanthrene moiety –contain phenanthrene
moiety
Presence of cyclic tertiary base system:-
confirmed by that codeine when subjected to exhaustive methylation, yield
-codeine , the formula of which contains one more CH 2 than codeine itself
and the nitrogen atom remains intact i.e., it is not lost.
If codeine possess a cyclic t-amino system, then the product obtained
would posses lesser number of carbon atoms and there also occurs loss of
nitrogen.
If codeine contains a tertiary cyclic base system, the result are than readily
30
explained by the following reactions:-
 CH3I heat
Ag2O
N N OH N

H3C CH3 H3C CH3

CH3

Structure of methyl morphol:-

By pschorr synthesis;-
-codeimethine Heating with codeimethine
alkali

Morphol
Methyl morphenol morphenol
HBr Na\C2H5OH
Na\C2H5OH

HBr
Methyl morphol
Presence of CH2CH2NCH3 group:-
codiemethiodide and codinenemethiodide on heating separately
with a mixture of AC2O-ACONa gives 3-methoxy 4-acetoxy phenanthere
and 3-methoxy-4,6-diacetoxy phenanthrene along with dimethyl amino
ethanol respectivel which reveals the presence of CH2CH2NCH3 group 31
 H3CO

AC2O
codeimethiodide ACO + Me2NCH2CH2OH
ACONa

3-methoxy-4-acetoxy phenanthrene

H3CO

AC2O
codeinenemethiodide ACO Me2NCH2CH2OH
ACONa +

CAO
3-methoxy-4,6-diacetoxy phenanthrene

Methyl morphol further confirmed by its synthesis.

32
Presence N-Methyl groups:-
By herzig-mayer method one >N-CH3 group is present
Presence of third oxygen atom and ether linkage:-
HO
HO

HO KOH
O
HO

HO
3,4,5,6 tetrahydroxyl mophenol
phenanthrene

The above reaction explains the placing two oxygen atoms in the form of
–OH present at c-3 and C-6. And the second oxygen is ether linkage
between C-4 and C-5 of phenanthrene nucleus
Structure of morphine:-by the above information we can know
that the presence of following groups
HO

O + NMe-CH2-CH2 + One double bond

33
HO
Position of double bond:-codeine on treating with PCl5 gives chlorocodide
further Hydrolysis with acetic acid gives mixture of codeine, isocodeine,
psuedocodeine, and allopsuedocodeine. In which psuedocodeine on oxidation
gives pseudocodinone ( -C=O group at C-8 Position). By above results the
double bond is present as:-

O
OH

Formation of 9-amino phenanthrene indicates the N-CH3 group of

morphine is attached to C-9. Further position of N-CH 3group at 9th
position is supported by Steric view

34
 O O

several
(O) reactions +
C17H19O3N

morphine
9,10 phenanthroquinone
H3C

N CH2

H2C

9-ethyl methyl amino

phenanthrene

After several chemical reactions the tertiary nitrogen attached through

ethylene bridge and attached to C-13.And hence the mophine
structure can be given as:-
HO
Further confirmed by synthesis:-GATES synthesis

NCH3
35
HO
 ATROPINE
• SOURCE:- Atropine is obtained from the leaves of atropa
belladona (deadly night shade) and from the thorn plant datura
stromanium,
• In plants available as L-hyoscyamine
• Hyoscyamine on heating gives + hyoscyamin and recemic mixture
of hyoscyamin is known as atropine.
• USES:
– Anticholinergic agent
– Smooth muscle relaxant – antispasmodic
– Pupil dialation. A single drop of solution containing one part of
atropine in 40,000 parts of water is sufficient to dilate the pupil
of the eye
– Atropine has also been used to relive the night sweats which
are a distressing
– feature of tuberculosis and to deminish the activity of salivary
and gastric glands

36
 CONSTITUTION OF ATROPINE:

Molecular formula:- C17H23NO3

Atropine structure is established by hydrolytic degradation
process tropine tropate
H-OH
C17H23NO3 C9H10O3 + C8H15NO
Ba(OH)2
Atropine tropic acid tropine

Determination of structure of tropic acid:-

Mol.Formula:-C9H10O3
1. absence of double bond
C9H10O3 + NaOH [C9H9O3] Na
tropic acid monosodium salt
of tropic acid
2. single carboxylic acid
Absence of phenolic OH group

From 1 and 2 it can be predicted that tropic acid is saturated mono

carboxylic acid
37
 COOH

C9H10O3 -H2O KMnO4

C9H8O2
tropic acid heat

BENZOIC ACID

atropic acid and in turn tropic acid consists of benzene molecule

with a substituent – from the above reaction.
C3H5O3 C3H3O2

HEAT

-H2O

tropic acid Atropic acid

4. presence of hydroxyl group

5.Further structure of atropic acid is confirmed oxidising tropic acid in KMnO 4

O O

KMnO4 C C OH
Tropic acid
38
Phenyl glyoxal
 CH2OH O

C C OH
CH2 O

I H
C C OH + H OH

CH3 O

atropic acid
C C OH

OH
II

As the tropic acid consists of primary alcohol functional group the

probable structure of tropic acid will be

CH2OH O

C C OH

I H

Further structure of the tropic acid is established by its synthesis

(Mekenje and Wood )
The tropic acid formed is recemic mixture.
39
Determination of structure of tropine:-
mol.formula:-C8H15NO
Tropine reacts with bromine no decolorisation is seen hence it is a
saturated Comp. Tropine when reacts with methyl iodide it consumes 1
mole to give a quaternary ammonium salt

C8H15ON + CH3I [C8H15ON] CH3IH

It indicates that nitrogen atom in tropine is tertiary in nature Detection

of presence of N-Methyl group:- herzig meyer method
Nature of oxygen atom:- Indicates presence of OH group

C8H14N(OH) + Cl C
-HCl
tropine benzoyl chloride
C8H14N(OCOC6H5)
mono benzoyl derivative

Detection of basic nucleus:-

Tropine on oxidation gives ketone it indicates presence of
secondary alcohol tropinone on oxidation gives tropinic acid which
on further oxidation gives N-methyl succinamide it reveals that
presence of N-methyl pyrollidine ring in tropinone and hence in 40
tropine
Tropic acid on HEM yields an unsaturateed dicarboxylic acid which on
reduction gives pimelic acid.
CH2CH2COOH
H.E.M Reduction
C8H13NO4 C7H8O4 H2C
CH2CH2COOH
tropinic acid unsaturated acid
Pimelic acid
Tropinic acid also contains seven carbon atoms..
HC C CH2
H2SO4 H reduction
HEM
tropine tropidine
CH

H
HC C CH

H2
H2C C CH2

CH2

H2
H2C C CH2

Cycloheptane

another reaction for knowing the structure of tropine.

HI [H] distill.HCl
C8H15NO C H
8 14 NI C H
8 15 N
<1500 tropine iodide
tropine dihydro tropidine

Zn-dust distill.
CH3Cl + C7H14N C7H9N
nordihydro tropidine 2-ethyl pyridine 41
By the above discussion conclusions are:
Tropine possess a 7 membered carbon ring.
It contains a reduced pyridine ring in the structure
It possess reduced pyrrole (pyrollidine) ring in the structure
It possess N-Methyl group
As tropine contains only one nitrogen atom it means that this should also
remain common to pyrollidine and piperidine( reduced pyridine ) rings
and it should be as N- CH3 group
H H H
H2C C CH2COOH H2C C CH2 H2C C CH2

NCH3 NCH3 C O NCH3 CHOH

H2C C COOH H2C C CH2 H2C C CH2

H H H
Tropinic acid Tropinone Tropine

Atropine structure was confirmed by synthesis:-

1
2 O CH2OH
7
NCH3 3 OC C

6
4 H
5
ATROPINE 42
 RESERPINE
SOURCE: Reserpine is obtained from the leaves of Rauwolfia
serpentina and R.vomitaria.Other important alkaloids present
are yohimbine, ajmalicine and ajmaline.It is an indole alkaloid .

CONSTITUTION OF RESERPINE:
• Its molecular formula is C33H40N2O9
• Presence of 5 methoxyl group
• Nature of N atom
• Hydrolysis of reserpine gives a mixture of methyl
alcohol,trimethoxybenzoic acid, reserpic acid.
COOH

NaOH
C33H40N2O9 + 2H2O Hydrolysis + CH3OH

OMe OMe

OMe
3,4,5- Trimethoxy benzoic acid

+ C22H28N2O5
Reserpic acid 43
Conclusions based on the above reaction:
•No –COOH or –OH group
•Reserpine is a diester

Structure of reserpic acid:

•Its molecular formula is C22H28N2O5.
•Presence of one carboxyl group- by silver salt method
•Presence of one –OH group – by halogen acids
•Presence of two methoxyl group- by ziesel method
•Presence of two N atoms-
•Reduction of Resepic acid with LiAlH4 yields resepic alcohol,
one –OH, two –OCH3, one CH2OH groups.
•Oxidation of Reserpic acid
COOH
C22H28N2O5 KMnO4
Oxidation

OMe
NHCO

COOH
4-methoxy N- oxalyl anthranilic acid

44
•Fusion with KOH:
COOH

KOH Ac2O
C22H28N2O5
FUSION
HOOC OH HOOC OH

•Dehydrogenation: On dehydrogenation of reserpic acid gives the

molecular formula C19H16N2 as one of the principal product.
This hydrocarbon is also obtained by dehydrogenation of yohimbine with
selenium and named as yobyrine.
•Structure of yobyrine:
•With zinc distillation:
H
N
Zn dust +
C19H16N2
distillation
N
Yobyrine

C2H5 Isoquinoline
3-Ethylindole

45
With oxidation:
CH3

COOH
COOH
Chromic acid KMnO4
C19H16N2
COOH

Toulic acid Pthalic acid

Yobyrine on condensation gives products with aldehydes suggests the

presence of pyridine ring with a CH2 substituent adjacent to the nitrogen.
As yobyrine is formed from the reserpic acid the structure of reserpic acid
is given as
H
N

OCH3

HOOC OH

Reserpic acid OCH3

46
Structure of reserpine: As reserpine is a diester of reserpic acid that
the strucuture of Reserpine is given as

H
N

OCH3

OCH3

OCO OCH3
HOOC

OCH3
OCH3

Reserpine

47