CITRAL:

Introduction:

Citral is the most important member of the acyclic monoterpenoids since the structure of
most of the other compounds in this group is based on that of citral. It finds much
industrial applications; the most important being the synthesis of β-ionone which is
frequently used in perfumery. It is optically inactive oil with lemmon like smell .It occurs
widely distributed in nature, the principal source being the lemon grass oil which has 60-
80%of citral. Citral is isolated as its crystalline bisulphate product which on hydrolysis
gives back citral.

Elucidation of structures of the Citral:

1. Its molecular formula is C10H16O

2. By the usual reactions, citral is found to have two double bonds.

3. As citral forms an oxime and reduces Fehling solution, oxygen must be present as an
aldehydic group. It is conformed by its reduction to geraniol (a primary alcohol) C10H18O,
and oxidation by silver oxide to geranic acid C10H16O, without loss of any carbon atom.

4. The presence of two double bonds and an aldehydic group in citral C10H16O led to
C10H22 as the molecular formula of its fully saturated hydrocarbon. Now as C10H22
corresponds to the general formula for acyclic compounds (CnH2n+2) citral must be
acyclic compound.

5. Citral, on heating with potassium hydrogen sulphate, gives a well known aromatic
compound p-cymene and thus the carbon skeleton and hence the relative positions of the
alkyl groups ,viz methyl and isopropyl, are established.
6. On treatment with sodium bisulphate citral forms mono as well as disulphite addition
products, this indicates that one of the double bonds is conjugated with the carbonyl
group.

The α, β-unsaturated aldehydic group in citral is conformed by its ultraviolet absorption

spectrum (λ max 238 nm)

7. The position of the other double bond and the complete structure of citral is established
by its oxidation with alkaline permagnate followed by chromic acid to give acetone,
oxalic acid and laevulic acid.

8. the above structure for citral is proved by Verley,s work ( 1897) who found that citrl
when treated with aqueous potassium carbonate solution is converted into acetaldehyde
and an unsaturated ketone which was identified as 6-methylhept-5-en2-one by its
ozonolysis to acetone and laevulinic acid .

Moreover, the structure of methylheptone has already been confirmed by synthesis

The conversion of citral to methylheptone and acetaldehyde is actually owing to the
presence of an unsaturated carbonyl group which whenever treated with alkali undergoes
the following series of reactions.

Let us the apply this reaction to citral which yield methylheptone and acetaldehyde.

CHOLESTEROL:
Introduction:

It is an animal sterol and occurs either free or as fatty esters. The main sources are brain,
spinal cord, gallstone and fish liver oils. It forms about one sixth of the dry weight of
nerve and brain tissue, and is obtained commercially by the extraction of cattle spinal
cords. As it was first of all isolated from human gallstone deposited in the bile duct, it is
known as cholesterol. Too a high concentration of cholesterol in the blood can lead to its
precipitation in the circulatory vessels, resulting in the high blood pressure and
arteriosclerosis. It is a white crystalline optically active solid with m.p.1490 and specific
rotation () D 390.
Cholesterol gives the following color reaction: 1) the salkowski reaction 2) libermann-
Burchard reaction 3) ethnolic solution of cholesterol, when treated with an ethanolic
solution of digitonin, gives a white precipitate of cholesterol digitonide.

Structural elucidation of cholesterol:

The constitution of cholesterol was elucidated by Wieland, Windaus and their co-workers
(1903-1932).
So the complete constitution of cholesterol may be dealt in the following headlines.
A) Structures of the nucleus
B) Position of the hydroxyl group and double bond
C) Nature and position of the side chain
D) Position of the angular methyl group.

A) Structures of the nucleus:

1. Molecular formula of cholesterol is C27H46O

2. On acetylation it forms monoacetate indicating the presence of the one-
hydroxyl group.
3. It adds up two bromine atoms suggesting the presence of one double bond.
4. Cholesterol on reduction gives cholestanol, which on oxidation with chromic
acid yields cholestanone.

This lead to following conclusion:

 The conversion of I to II proves the presence of the double bond.

 Oxidation of II to III (a ketone) shows that cholesterol is a secondary alcohol.
  The saturated parent hydrocarbon (cholestane C27H48IV) of cholesterol
corresponds to the general formula ( CnH2n-6) for tetracyclic compounds, hence
cholesterol is a tetracyclic alcohol.

5. On selenium distillation at 3600, cholesterol gives Diel,s hydrocarbon and

chrysene; the formation of the former compounds sugest that cholesterol has
Diel,s hydrocarbon nucleus in its structure.

B) Position of the hydroxyl group and double bond:

1) cholestanone, III on oxidation with nitric acid gives a dicarboxylic acid, V which on
pyrolysis yields a ketone, VI

Leading to the following conclusion,.

 The oxidation of III to V indicates that the ketonic group is present inside the
ring .
 The conversion of dicarboxylic acid, V to a ketone,VI indicates that V is either a
1,6-or 1,7-dicarboxylic acid. Now we see that this dicarboxylic acid is obtained
from the hydroxyl group of cholesterol which cant present in the ring D as it
would form a 1,5-dicarboxylic acid instead of 1,6-or 1, 7-dicarboxylic acid on the
above treatment. Hence the hydroxyl group may be either in the ring A,B C.

2) Position of the double bond:

Let us consider the following set of the reactions.

These reactions lead to the following conclusions.

 The convertion of I to VIII represents the hydroxylation of the double bond.

 Cholestanetriol VIII, on oxidations gives a diketone, IX< indicating that in VIII
two of the hydroxyl groups are secondary in nature and the third (resistant to
oxidation) is tertiary one.
 The oxidation of cholestanedione, X to a tetracarboxylic acid , XI, without loss of
any carbon atom suggest that the two ketonic groups in X are present in different
rings i.e. the double bond and the hydroxyl group in cholesterol are present in two
different rings and as we have seen already that the hydroxyl group of cholesterol
present in the ring A, therefore the double bond must e present either in ring B,C
or D.
 Since cholestanedione, X, can form a pyridazine derivative with hydrazine, the
two ketonic groups of X are in gama –positions with respect to each other which
is possibleonly if the double bond is present in between C5 and C6 and thus all
the abouve reactions can be written as below.
3. The position of double bond is further proved by the following set of reactions.

Which lead to the following conclusions?

i) Oxidation of XII to XIII with loss of one carbon atomindicates that keto group and
the double bond in XII are in are in the same ring. Moreover, ultraviolet absorption
spectrum of XII, max 240nm, shows that the keto group and the double bond are
conjugated. These results can be explained on the assumption that there is a migration
of the double bond of cholesterol during the formation of cholestenone, XII, which is
possible only if the double bond is present in between C5and C6.

C) Nature and the position of the side chain:

1. Cholesterol acetate on oxidation with chromic acid forms an acetate of a hydroxyl

ketone and a steam volatile ketone, isohexylmethyl ketone.
The above result shows that the isohexylmethyl ketone forms the side chain of
cholesterol and is attached to the nucleus of cholesterol trough the carbon atom
oxidized to C=O group.

2. The nature of the side chain can further be elucidated by the application of Barbier-
Wieland degradation in the following manner.
Cholesterol is converted in to 5-cholestane also known as coprostane and now if we
represent the whole of the nucleus of coprostane by R and the side chain by Cn then
the coprostane molecule will be represented by RCn. Now let us degrade the side
chain of this molecule by oxidation and B-W degradation.

These degradation reactions lead to the following conclusion:

1. The formation of the acetone from coprostane indicates that the side chain(Cn) of
the coprostane terminates in an isopropyl group.

2. The conversion of the bisnor-5-cholanic acid to the ketone ,aetiocholymethyl

ketone indicates that the -carbon atom of the acid is secondary in nature i.e, there is
an alkyl group on the -carbon atom in bisnor-5-cholanic acid.
3. Oxidation of aetiocholymethyl ketone to etianic acid with the loss of one carbon
atom suggests that alkyl group in aetiocholymethyl ketone and in bisnor-5-cholanic
is methyl.
4. The oxidation of the aetiocholanone to aetiobilianin acid without any loss of carbon
atom suggests that in the former the ketonic group is present in the ring.

Form the foregoing discussion we came to known that the coprostane contains a side-
chain of eight carbon atoms arranged in the following order.