FAR 113/3

ORGANIC CHEMISTRY

PRACTICAL 3 : SYNTHESIS OF TETRAHYDROCARBAZOLE
BY FISCHER INDOLE SYNTHESIS

GROUP : A6


NAME : CHOO MEI YONG ( 119057 )
CHOW YAN NING ( 119058 )
CHOY WENG YAN ( 119059 )


LECTURER : PROF. CHAN KIT LAM

DATE : 22/ 10 / 2013







OBJECTIVES :

1. To determine the percentage yield of tetrahydrocarbazole.
2. To determine the weight and melting point of tetrahydrocarbazole.
3. To understand the mechanism of the formation of tetrahydrocarbazole from cyclohexanone.

INTRODUCTION :

Indole is a fused-ring heterocycle contain a pyrolle ring fused to a benzene ring. The
Fischer Indole synthesis is a chemical reaction that produces the aromatic heterocycle indole
from a (substituted) phenylhydrazine and an aldehyde or ketone (with the exception of
formaldehyde and acetaldehyde) under acidic conditions. Zinc chloride, hydrochloric acid or
glacial acetic acid may be used, but polyphosphoric acid is often preferred. The reaction was
discovered in 1883 by Hermann Emil Fischer. It is an important general method of preparing
substituted indoles. Naturally, indoles occur in some flower oils, like Jasmine and Orange
Blossom and are therefore used in perfumery.

In this experiment, tetrahydrocarbazole is synthesized by heating phenylhydrazine and
cyclohexanone in the present of glacial acetic acid which acts as an acid catalyst. Initially, the
reaction of the phenylhydrazine with cyclohexanone forms a phenylhydrazone which undergoes
isomerization to become enamine (or 'ene-hydrazine'). After protonation, a cyclic [3,3]-
sigmatropic rearrangement occurs producing an imine. The resulting imine forms a cyclic
aminoacetal or aminal, which under acid catalysis eliminates NH
3
, resulting in the energetically
favorable aromatic indole (tetrahydrocarbazole).







PROCEDURE :

1. 2.2g or 2.3mL of cyclohexanone, 20mL of glacial acetic acid and 2mL of phenylhydrazine is
placed in 100mL round-bottom flask.

2. A reflux condenser is attached and the mixture is heated under reflux for 20-30 minutes.

3. It is cooled to room temperature and further in the cold water to precipitate the product.

4. The precipitate is filtered by pump and finally the solid is washed with 30mL of cold water.

5. The solid is recrystallized to solid from 95% ethanol: water (4:1), (40mL).

6. The crystal is filtered by pump and then it is washed with a little cold water and the final
product is dried in the oven at 100

C overnight.


RESULTS :

Weight of tetrahydrocarbazole produced = 1.0705g
Relative molecular weight of tetrahydrocarbazole, C
12
H
13
N
= (12 x 12.0107) + (13 x 1.00794) + 14.00674
= 171.2384 g/mol

No. of mole of tetrahydrocarbazole produced
= Weight of tetrahydrocarbazole produced
Relative molecular weight of tetrahydrocarbazole
= 1.0705g
171.2384 gmol
-1
= 0.00625 mol

Weight of cyclohexanone used = 2.2 g or 2.3 ml
Relative molecular weight of cyclohexanone, C
6
H
10
O used
= (6 x 12.0107) + (10 x 1.00794) + 15.9994
= 98.143 g/mol
No. of mole of cyclohexanone used
= weight of cyclohexanone
relative molecular weight of cyclohexanone
= 2.2 g
98.143 gmol
-1
= 0.0224 mol

Volume of phenylhydrazine used = 2 ml
Density of phenylhydrazine = 1.10 g/ml
Weight of phenylhydrazine used
= Volume of phenylhydrazine used x Density of phenylhydrazine
= 2 ml x 1.10 g/ml
= 2.2 g
Relative molecular weight of phenylhydrazine, C
6
H
8
N
2

= (6 x 12.0107) + (8 x 1.00794) + (2 x 14.00674)
= 108.1412 g/mol

No. of mole of phenylhydrazine used
= weight of phenylhydrazine used
Relative molecular weight of phenylhydrazine
= 2.2g
108.1412 gmol
-1
= 0.0203 mol

Theoretically, from the equation above, we know that 1 mol of cyclohexanone and 1 mol of
phenylhydrazine will produce 1 mol of cyclohexanone phenylhydrazone. Then, 1 mol of
cyclohexanone phenylhydrazone will subsequently be synthesized into 1 mol of
tetrahydrocarbazole.
In this experiment, cyclohexanone presents in excess. So, phenylhydrazine is the limiting
reagent for this reaction.
From calculation, there is 0.0203 mol of phenylhydrazine presents. Hence, it will produce
0.0203 mol of tetrahydrocarbazole.
However, the experimental result show that only 0.00625 mol of tetrahydrocarbazole is
produced.

Hence, the percentage yield of product
= No. of mole of phenylhydrazine used x 100%
No. of mole of tetrahydrocarbazole produced
= 0.00625 mol x 100%
0.0203 mol
= 30.79%

Melting point of tetrahydrocarbazole produced = 116 - 118
o
C


EXERCISE :
1. Record the weight and calculate the percentage yield of your product.
Weight of product is 1.0705g whereas percentage yield of the product is 30.79%. The
calculation has been shown above.

2. Record the melting point of your recrystallized product.
The melting point of the recrystallized product is between 116C to 118C.




3. Give the full mechanisms the formation of tetrahydrocarbazole starting from
cyclohexanone.
(i) Nucleophilic attack by nucleophile on electrophile due to the presence of lone pair
electron of phenylhydrazine.


(ii) Oxygen accepts a proton from nitrogen, yielding a neutrl carbinolamine.




(iii) Acid catalyst protonates the hydroxyl oxygen.




(iv) Elimination of a water molecule occurs due to the lone pair electron of nitrogen.





(v) Loss of H
+
from nitrogen then gives rise to imine product.

(vi) Reaction of imine product with glacial acetic acid and produces 1,2,3,4
tetrahydocarbazole.














DISCUSSION :

The Fischer Indole synthesis is a chemical reaction that produces the aromatic
heterocyclic indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic
conditions. Indole is an aromatic heterocyclic organic compound which has a bicyclic structure,
consisting of a six-member benzene ring fused to a five-member nitrogen-containing pyrrole
ring. Indole is a solid at room temperature.

The Fischer Indole synthesis requires a suitable acid and therefore the choice of an acid
catalyst is very important. Generally, various catalysts can be used to catalyse the Fisher Indole
Synthesis. Among them are Bronsted-Lowry acids such as HCl, H
2
SO
4
, polyphosphoric acid and
p-toluenesulfonic acid or Lewis acids such as BF
3
, ZnCl
2
, FeCl
3
and AlCl
3
. Polyphoshoric acid
(a polyprotic acid) is often much preferred due to the presence of many phosphoric units. Each
phosphoric unit provides an extra unit of proton for catalyzing the reaction. This will increase the
rate of reaction greatly in the experiment. However, glacial acetic acid is used in this experiment.
This is because if polyphosphoric acid is to be used, it must be firstly hydrolyzed to eliminate
water from the compound. Therefore, glacial acetic acid which can be used readily without any
hydrolysis is much more convenient compared to polyphosphoric acid. Besides, polyphosphoric
acid is unstable in aqueous form and the disposal of phosphoric acid residue can have some
considerable environmental impact.

The Fisher Indole synthesis involves the heating of phenylhydrazone of an aldehyde or
ketone (with the exception of formaldehyde and acetaldehyde) in the presence of an acid
catalyst. In this experiment, the ketone that is used is cyclohexanone. When the reaction started,
the cyclohexanone and phenylhydrazine is being heated and then refluxed with the help of a
condenser in the presence of glacial acetic acid as catalyst. As a result of that, phenlhydrazone is
formed via the intramolecular condensation reaction with the elimination of ammonia.
Intramolecular condensation is actually the formation of a cyclic compound during the fusion of
two moieties of single molecules. The phenylhydrazone is then obtained by using crystallisation
method. The crystals of phenyhydrazone is then heated again in 95% ethanol to form 1,2,3,4-
tetrahydrocarbazole with the elimination of ammonia. The product is then recrystallised to obtain
the pure 1,2,3,4-tetrahydrocarbazole.

The weight of the final product is 1.0705g with results in 30.79% of percentage yield for
the reaction. The percentage yield is much lesser from the theoretical yield and this might be due
to several factors which include the following:

a) The refluxing period is too short thus causing incomplete reaction to occur.
b) The recrystallization period is not long enough to allow for the complete precipitation of crystals.
c) Wet filtered product remaining on the filter paper might not be completely transferred, resulting
the mass of the tetrahydrocarbazole to become less.
d) The product may stick on the conical flask and is not being rinsed properly to yield the product.
Last but not least, the melting point of the final product from the experiment is between
116C to 118C. The range of melting point for the final product is near the actual melting point
of the 1,2,3,4-tetrahydrocarbazole. Therefore, we can conclude that the final product is 1,2,3,4-
tetrahydrocarbazole.


PRECAUTIONS :
1. All the apparatus used in the experiment must be dry.
2. Boiling chips must be added into the round bottom flask before the reflux and must be
removed before the recrystallization process using a spatula.
3. Round bottom flask is cooled with running tap water before putting it into an ice bath to
prevent the flask from breaking due to rapid temperature change.
4. A conical flask is used instead of a beaker during recrystallization to minimize the evaporation
of ethanol.
5. Excessive amount of 95% ethanol must be avoided for recrystallization.


CONCLUSION :
The weight of tetrahydrocarbazole obtained is 1.0705g. The melting point of tetrahydrocarbazole
is in the range of 116C to 118C. The percentage yield of the product obtained is 30.79%.


REFERENCES :
1) FAR 113/3 Organic Chemistry Practical Manual
2) Janice Gorzynski Smith, Organic Chemistry 2
nd
Ed., Mc Graw Hill International Edition,
2008.