FAR 113/3

ORGANIC CHEMISTRY

PRACTICAL III
SYNTHESIS OF TETRAHYCROCARBAZOLE BY
FISCHER INDOLE SYNTHESIS

NAME:

LOW KAH JUN (127920)

NAVIN KUMAR A/L THAMILARAJAN (127933)
FOONG PEI PEI (127899)
LYDIA ADILA BINTI ISKANDAR (127339)
NUR KHADIJAH BINTI BASHARUDIN (127946)

LECTURER:
DATE:

PROF. DR. AMIRIN SADIKUN

Experiment 3: Synthesis of Tetrahydrocarbazole by Fischer Indole Synthesis

OBJECTIVE
1. To synthesis tetrahydrocarbazole through Fischer indole synthesis of
cyclohexanone phenylhydrazone in presence of glacial acetic acid as catalyst.
2. To determine the weight and melting point of tetrahydrocarbazole produced.
3. To determine the percentage yield of tetrahydrocarbazole.
4. To discuss the mechanism of formation of cyclohexanone phenylhydrazone
from cyclohexanone and phenylhydrazine.
5. To discuss the mechanism for Fischer indole synthesis of tetrahydrocarbazole.
INTRODUCTION
Indole is a fused-ring heterocycle contain a pyrolle ring fused to a benzene
ring. An important general method of preparing substituted indoles, known as the
Fischer indole synthesis, consists of heating the phenylhydrazone of an aldehyde or
ketone (with the exception of formaldehyde and acetaldehyde) in the presence of an
acid catalyst. Zinc chloride, hydrochloric acid or glacial acetic acid may be used, but
polyphosphoric acid is often preferred.
In this experiment, you will be preparing tetrahydrocarbazole (1,2,3,4tetrahydrocarbazole) involving phenylhydrazine, cyclohexanone and glacial acetic

acid as a catalyst.

PROCEDURE
1. 2.2g or 2.3 mL of cyclohexanone, 20 mL of glacial acetic acid and 2 mL of
phenylhydrazine were placed in a 100 mL round-bottom flask.
2. Boiling chips were added into the mixture.
3. A reflux condenser was attached to the round-bottom flask and heated under
reflux for 20 to 30 minutes.
4. The mixture was allowed to cool to room temperature and immersed in the
cold water for the precipitation of the product.
5. The precipitate was filtered by using the pump. At the same time, the solid was
washed with 30 to 50 mL of cold water.
6. The precipitate was then transferred to 250 mL conical flask. 40 mL of the
solution of hot 95% ethanol: water (4:1) was added into the conical flask. The
mixture in the conical flask was heated on a hot plate until all of the
precipitate dissolved.
7. Another conical flask was prepared with a filter paper on it. 20 mL of hot
solution of ethanol: water (4:1) was added to wet the filter paper. The 20mL
solution was then removed from the conical flask.

8. The hot mixture from step 6 was added quickly into the conical flask. Then,
the conical flask was left to cool by immersing it in ice bath to get the
recrystallized product.
9. The crystals were filtered by using the pump. At the same time, the crystals
were washed with 30mL of cold water.
10. The final product obtained was transferred to an evaporating dish and dried in
the oven at 100 overnight.
11. The product was then collected in the next day. The weight and the melting
point of the product were recorded.
RESULTS
1. 1,2,3,4-tetrahydrocarbazole (
Weight of

C12 H 13 N

C12 H 13 N

produced = 1.8992g
C12 H 13 N

Relative molecular weight of

= (12 12.0107) + (13 1.00794) + 14.00674

= 171.2384 g/mol
No. of mole of

C12 H 13 N

produced

Weigh t of C12 H 13 N produced

Relative molecular weigh t of C 12 H 13 N

1.8992 g
171.2384 g / mol

= 0.011 mol

Cyclohexanone (
Weight of

C6 H 10 O

C6 H 10 O

used = 2.2g or 2.3mL

Relative molecular weight of

C6 H 10 O

used

= (6 12.0107) + (10 1.00794) + 15.9994

= 98.143 g/mol

No. of mole of

C6 H 10 O

used =

Weight of C6 H 10 O
Relative molecular weight of C6 H 10 O

2.2 g
98.143 g /mol

= 0.02242 mol

Phenylhydrazine (

C6 H 8 N 2

Volume of

C6 H 8 N 2

Density of

C6 H 8 N 2

Weight of

C6 H 8 N 2

used = 2 ml
= 1.10 g/mL
used = Volume of

C6 H 8 N 2

used density of

C6 H 8 N 2
= 2 mL 1.10g/mL
= 2.2g
C6 H 8 N 2

Relative molecular weight of

= (6 12.0107) + (8 1.00794) + (2 14.00674)

= 108.1412 g/mol

No. of mole of

C6 H 8 N 2

used =

Weight of C 6 H 8 N 2 used
Relative mol ecular weight of C 6 H 8 N 2

2.2 g
108.1412 g/ mol

= 0.02034 mol

1 mol of

C6 H 10 O

1 mol of C6 H 8 N 2

1 mol of C12 H 13 N

In this experiment, phenylhydrazine is the limiting reagent of the reaction as

cyclohexanone present in excess.
1 mol of

C6 H 8 N 2

0.02034 mol of

1 mol of C12 H 13 N

C6 H 8 N 2

0.02034 mol of C12 H 13 N

Theoretical yield (theoretical weight of 1,2,3,4-tetrahydrocarbazole produced)

= no. of mole of 1,2,3,4-tetrahydrocarbazole relative molecular weight of 1,2,3,4tetrahydrocarbazole
= 0.02034 mol 171.2384 g/mol
= 3.4830g
However, the experimental result shows that only 1.8992g of 1,2,3,4tetrahydrocarbazole is produced.
Percentage yield

Actual yield
Theoretical yield

1.8992 g
3.4830 g

= 54.53%

100%

100%

2. Melting point of 1,2,3,4-tetrahydrocarbazole produced: 114 - 116

3. Mechanism of the formation of 1,2,3,4-tetrahydrocarbazole from
cyclohexanone and phenylhydrazine in the presence of glacial acetic acid as
catalyst through Fischer indole synthesis.
It is a nucleophilic addition reaction which involves cyclohexanone
that react with phenylhydrazine in the presence of glacial acetic acid as acid
catalyst. Oxygen atom has higher electronegativity compared to carbon atom
and hydrogen atom. So, the electronegative oxygen atom tends to withdraw
2
electro from the sp carbon which is attached to it, making the relative

sp 2 carbon atom becoming positively charged and the oxygen atom

becoming negatively charged. The nitrogen atom of the phenylhydrazine
contains a lone pair electron, acted as a nucleophile and it attacked the
positively charged carbon. The end product formed in this process is
phenylhydrazone by removing one molecule of water.

Glacial acetic acid, which is an acid catalyst, will release hydrogen ion
in solution. The hydrogen ion is used to protonate the phenylhydrazone. The
end product formed in this process is the tautomeric form of phenylhydrazone,
enamine.

Enamine interconvert within itself rapidly and causing the proton

shifting. The process is continued with the switching of adjacent conjugated
double bond. Meanwhile, by migrating the pi-bond to another carbon, the
sigma bond is also undergoes transformation. In other words, the enamine
undergoes sigmatropic [3,3] rearrangement. A very unstable molecule with
carbon-nitrogen double bond is formed, namely imine, due to the
intramolecular rearrangement of bonding.

The high unstability of the

NH 2

group causes the protons shift to

the C-N double bond. This results in formation of C-N bond and aminoacetal
is formed.

An ammonia group is eliminated and finally producing

tetrahydrocarbazole, a very stable compound.

DISCUSSION
The Fischer indole synthesis is a organic reaction used to convert
phenylhydrazine and an aldehyde or ketone to an aromatic heterocycle indole under
acidic conditions. In this experiment, we used phenylhydrazine and cyclohecanone

(ketone) with glacial acetic acid (which acts as acid catalyst) to produce
tetrahydrocarbazole (aromatic heterocycle indole).
The Fischer indole synthesis is accelerated an acidic environment. Both protic
and Lewis acids have been shown to help breaking the nitrogen-nitrogen bond in the
sigmatropic shift. Hydrochloric acid, sulphuric acid (Brnsted acids), zinc chloride,
and iron chloride (Lewis acids) have been used successful. However, the synthesis is
not completely dependent on an acid. Indolization can also occur under thermal
conditions without a catalyst in solvents such as ethylene glycol, diethylene, glycol,
sulfolane or pyridine.
The full mechanism of the Fischer indole synthesis starts with an enolizable
N-aryl hydrazone, which is a hydrazone with an -hydrogen and an N-aryl group. The
tautomer undergoes a [3,3]-sigmatropic rearrangement with heating and under acidic
condition, to form a non-aromatic, unstable intermediate.
Next, tautomerization restores aromaticity, in which intramolecular addition of
the aniline nitrogen onto an imine forms a new ring. Loss of ammonia aromatizes the
second ring, forming a tetrahydrocarbazole. This completes the indole synthesis.
1,2,3,4- tetrahydrocarbazole obtained in this experiment is an cyclohexane attached to
an indole.
Adding the boiling chips is to prevent bumping in the flask during heating.
After recrystallize the tetrahydrocarbazole, it is washed with 95% ethanol. This is
important to not wash it using a lot of ethanol because the tetrahydrocarbazole is not
stable in ethanol. So it will dissolve in excess of ethanol.
The percentage of product formed is 54.53% and its melting point is about
114 - 116C. The physical appearance of the product is faint yellowish white and
shiny crystals. Our groups product is totally white and shiny crystals, and the melting
point range is lower than the theoretical range. This shows the presence of impurities.
The low percentage yield was due to the loss of the product along the experiment by
factors such as:
a)

Some of the product was lost during transfer between apparatus and some

product was left in the containers.

b)

The product dissolved in excess ethanol.

c)

Leakage in the filter paper during filtration using a pump.

d)

To quicken the process of recrystallization, the conical flask containing the

solution was immersed into cold water, so impurities were precipitated as well.
e)

Insufficient time for recrystallization of all the products to take place.

f)

Contaminated containers

Precautions
1. The flow of tap water is from the bottom to the reflux condenser to ensure
proper condensation when the reflux process is carried out.
2. The duration of reflux (counted when condensation first started) must be kept
between 20-30 minutes to ensure the reaction is complete.
3. The crystallized product should not be washed with excessive cold ethanol to
prevent the crystals from dissolving in it.
4. The product obtained must be completely dry while determining its melting
point. The presence of water in the crystals will affect the melting point
reading obtained.
5. Protective goggles should be worn throughout the experiment to protect our
eyes from the fumes of chemicals, especially when we were dealing with
strong acids and during boiling of chemicals.
6. The boiling chips should be placed into the round-bottom flask before starting
the reflux process to prevent unnecessary explosion.
7. The solution should be cooled in room temperature during crystallization to
obtain fine and nicely-figured crystals, instead of putting the conical flask
directly into the cool water bath immediately after filtration.
8. During recrystallization, tetrahydrocarbazole should be completely dissolved
and the solution should be left for an adequate time to ensure that more crystal
would be formed in order to get the maximum yield product.

Conclusion

The weight of tetrahydrocarbazole obtained in this experiment is 1.8992g,

resulting in the percentage yield of 54.53%. The range of melting point for the
tetrahydrocarbazole obtained is around 114-116C. This experiment proved that
tetrahydrocarbazole can be synthesized by the Fischer indole synthesis method, which
involves the heating of the phenylhydrazone of a cyclohexanone under reflux in the
presence of an acid catalyst.

References
1. Practical Manual FAR 113/3 Organic Chemistry I. School of Pharmaceutical
Sciences, Universiti Sains Malaysia, 2015.
2. Organic Chemistry, Robert T. Morrison, Robert N. Boyd and Robert K. Boyd,
6th edition, Benjamin Cummings, 1992.
3. http://www.users.miamioh.edu/gungbw/pdfs/Model_report.pdf
4. http://www.name-reaction.com/fischer-indole-synthesis