Atropin

e
 Atropine:

 Atropine is the racemic form of

l-hyoscyamine which readily
racemises to atropine when warmed
in an ethanol alkaline solution, thus
atropine is (±)- or dl-hyoscyamine.
Isolation:
 Atropine is extracted either from belladona roots or
from the juice of datura plant.

Belladona roots Datura plant

 In practice, the juice which also contains hyoscyamine

is heated with potassium carbonate solution when
hyoscyamine is racemised to atropine.
 Then, the atropine is extracted with chloroform.
The solvent chloroform is evaporated and the alkaloid
is then extracted with dilute sulphuric acid.

The extracted acidic solution is made alkaline with

potassium carbonate when atropine is precipitated
out.

 The alkaloid may be purified by crystallization.

Properties:

 Atropine is a crystalline compound (m.p. 115-116

°C ) with sharp bitter taste.
Owing its dilating action on pupils of the eyes,
atropine is used in ophthaquinology, for this purpose
one part of atropine in 130,000 parts of water is
sufficient to dilate the pupil of the eye.
 Atropine has also been used to relieve the night
sweats which are a distressing feature of tuberculosis
and to diminish the activity of the salivary and gastric
glands. When taken internally atropine first stimulates
and then depresses the central nervous system.
Constitution:
1) Molecular Formula:
From the analytical data and molecular weight
determination, it follows that the molecular formula of
atropine is C17H23NO3
2) Atropine as an ester :
When atropine is warmed with barium hydroxide
solution, it undergoes hydrolysis to yield a racemic acid,
(±)-tropic acid (C9H10O3) and an optically inactive
alcohol, tropine (C8H15NO) (tropine tropate – an ester)
 This reaction reveals that atropine is the tropeine, an
ester of tropic acid i.e., it can be named as
tropine tropate.

Lanenberg further confirmed, that atropine is a tropine

tropate ester, by evaporating a mixture of tropine and
tropic acid in presence of hydrochloric acid and obtained
atropine.

Further, atropine cannot be amide because tropine, the

product of hydrolysis, is a tertiary base
3) Structure of Tropic acid: The structure of this acid
is based on the following evidences:
Its molecular formula has
been found to be C9H10O3

As tropic acid consumes one equivalent of alkali and

does not add on bromine, it is a saturated monobasic
acid.

Tropic acid, when acetylated, forms a monoacetate,

indicating that it must contain one hydroxyl group.
 When tropic acid is heated strongly, it loses a molecule of
water to yield an optically inactive unsaturated acid, called
atropic acid C9H8O2. Therefore, the hydroxyl group must
be an alcoholic group.
Atropic acid when oxidised, yields benzoic acid. The
formation of benzoic acid reveals that atropic acid and
hence tropic acid both will contain at least one benzene
nucleus with a side chain containing a carboxylic group in
their structure.
 As atropic acid is an unsaturated acid, it means that
atropic acid may be either (I) or (II).

Since, however, structure (I) is known to be cinnamic

acid, structure (II) must be atropic acid. This is confirmed
by the fact that atropic acid on oxidation with
permanganate yields phenylglyoxal.
 As atropic acid is formed by the dehydration of tropic acid, it
means that addition of a molecule of the water to the former
would therefore give tropic acid, consequently, must be either
(III) or (IV) which is confirmed by synthesis.
 Tropic acid has been shown to be (IV) by synthesis,
{e.g., Mackenzie and Wood synthesised tropic acid (IV)
from acetophenone.
 Structure (III) is called atrolactic acid which on
dehydration is converted into structure (II), thus
confirming the structure of atropic acid as IV.
4) Structure of Tropine (Tropanol):
 Tropeine is the generic name for the esters of
tropine.
Its structure is established as:
i) Its molecular formula has
been found to be C8H15NO
ii) When tropine is treated with methyl iodide, it yields
a crystalline compound. This reaction reveals that the
nitrogen atom in tropine is tertiary.
iii) When fused with alkali, tropine yields methyl amine,
indicating that it must contain a N-methyl, i.e., >N-CH3
group. This is also confirmed by the fact that tropine when
heated with hydrogen iodide at 150 °C (Herzig-Meyer
method) yields one mole of methyl iodide.

iv) As tropine forms a monoacetate and a monobenzoate,

this indicates that it must contain a hydroxyl group.
v) When tropine is oxidised with chromic acid, it
yields a tropinone, C8H13NO, which gives
characteristic reactions of a ketone. Therefore, the
hydroxyl group must be secondary alcoholic
(-CHOH-) group.
vi) Finally the structure of tropine has been confirmed
by its synthesis. Robinson assumed that the skeleton of
tropinone, when subjected to hydrolysis, would be
broken down into the three units, namely,
succindialdehyde, methylamine and acetone.

Tropinone
 Furthermore, Robinson was of the opinion
that these three units must be joined by means
of double Mannich reaction to form tropinone
in a single step.

Tropinone
5) Structure of Atropine:
We already know that atropine is a tropine tropate ester.
On this basis, it is assigned (V). This structure has been
confirmed by synthesis from tropine and tropic acid; this
has been done by heating these two together in presence
of HCl. (Fischer-Speier esterification)
6) Stereochemistry Tropines:
When tropinone is reduced, it yields two alcohols,
tropine and Ψ- tropine(psedotropine). However, the
relative amounts of two alcohols are dependent upon the
nature of reducing agents employed.
Tropine and Ψ- tropine are considered to be epimers. In
one of these epimers, the nitrogen bridge and the hydrogen
of the secondary alcoholic group are on the same side(A)
while in the other epimer, these are on the opposite
side(B).

(A) (B)