PHC464

PHARMACEUTICAL ORGANIC CHEMISTRY

TITLE : MONONITRATION OF TOLUENE AND

ESTERIFICATION

LECTURER : PROFESSOR DR SADIA SULTAN AND

DR NURUL IZZATI OSMAN

PREPARED BY :

NAME ID STUDENT

1
2
3
PRACTICAL 1 : Mononitration of Toluene

Objectives
To understand the mono subtitution of Toluene

Discussion
The electrophilic aromatic substitution in toluene is the subject of this experiment.
Methylbenzene was treated with nitric acid, HNO3 and sulphuric acid, H2SO4 to produce the
nitro-substituted toluene. As a result, 2-nitromethylbenzene and 4-nitromethylbenzene are
formed. Thus, sulphuric acid acts as a catalyst to increase the rate of reaction. During the
experiment, precautions must be taken, such as gently swirling the flask containing the
HNO3 and H2SO4 respectively, under running tap water to ensure that it does not cool below
room temperature. Then, the product was collected by filtration before undergoing
recrystallization. The purpose of the recrystallization process is to obtain a pure product that
is free from any impurities.

● Mechanism

In this reaction, the electrophile is the nitronium ion (NO2+), which is produced from
concentrated nitric acid and sulphuric acid.

Toluene is nitrated when the electron-rich benzene ring attacks the nitronium ion.
Methyl is an electron donor and a weakly activating group; hence, it will function as both a
para and ortho director. This is because the resonance form of the carbocation has a close
proximity to the methyl, releasing electrons to make it more stable and conducive to
synthesis. Existing sulfuric acid acts as a catalyst. As methyl is not a substantial side chain,
ortho products will produce more than para products.
 ● Percentage yield

The percentage yield of the reaction is 47.516%. The reaction carried out in this
experiment results in a low yield which could be due to practical errors during preparation,
solubility factor of the product, and the practical losses during filtration and recrystallisation.

In the experiment, a practical error during preparation occurred when we overlooked

the procedure step where the manual specified that we must measure nitric acid and sulfuric
acid using the same cylindrical measure without washing, and slowly pour the H2SO4 into
HNO3. We, instead, used separate cylindrical measures and did not use a dropper when
adding sulfuric acid. This may result in less effective interaction between the acids, causing
reduced concentration of nitronium ion to undergo reaction with toluene.

The product (nitrotoluene) solubility may cause product loss depending on agitation
before filtration. Mononitration of toluene produces a mixture of nitrotoluene isomers, where
p- and m-nitrotoluenes are insoluble in water as yellow liquids, but o-nitrotoluene is soluble
although very poorly (0.07g/100mL at 20°C). Some quantity might dissolve when much ice is
added to solidify the product and scraped to break lumps and washed with water. The
dissolved o-nitrophenol is filtered out when the vacuum pump pulls water from the solid
product.

Practical losses of product occur during filtration and recrystallisation. Prior to

filtration, the reaction mixture is cooled in ice bath to solidify the product, together with
scraping. However, too much agitation and scraping breaks the product into small lumps that
can pass through the Buchner funnel when the vacuum pump is turned on for too long.
During recrystallisation, product dissolved in methanol in a test tube is allowed to cool.
Disturbing the solution during cooling may break up seed crystals starting to grow, resulting
in less formation of product crystals. This may have been the case when the test tube is
constantly moved when we were trying to monitor the formation of crystals.

Precautions to minimise product loss include being vigilant for certain specifications
in the experiment procedure that are easily overlooked; such as using the same cylindrical
measure when obtaining HNO3 and H2SO4, and allowing solution to cool (without agitation)
before putting in ice bath. Understanding the importance of each step in the procedure may
help with this precaution. Another precaution is to avoid excessive agitation in water if
product is somewhat water-soluble. Lastly, using a dropper when a substance is supposed
to be added slowly.
Calculation

C7H8 + HNO3 -> C7H7NO2 + H2O

Toluene (3 ml) Nitric acid (8 ml)

Mass No. of mole

C7H8 : 3 ml x = 2.61 g 2.61 g x = 0.02833 mol C7H8

(limiting reactant)

HNO3 : 8 ml x = 11.36 g 11.36 g x = 0.1803 mol HNO3

C7H7NO2 : Based on equation :

0.02833 mol C7H7NO2 x = 1 mole of C7H8 : 1 mole of C7H7NO2

3.885 g Thus,

0.02833 mol C7H8 = 0.02833 mol C7H7NO2

Theoretical yield : 3.885 g C7H8

Actual yield : 1.846 g C7H7NO2

Percentage yield = x 100%

= x 100%

= 47.516 %

Conclusion

Nitrotoluene can be prepared from toluene by substituting the methyl group attached
to a benzene ring in toluene with a nitro group, where concentrated H2SO4 is used as
catalyst and starting material. This reaction is an electrophilic aromatic substitution where
nitronium ion NO2+ (electrophile) is attacked by electron-rich benzene ring (nucleophile) in
toluene to form a benzenium ion which will be deprotonated by hydrogen sulfate HSO4-. The
mass of nitrotoluene filtered and collected is 1.846g which is 47.516% yield. This low yield is
due to practical errors during preparation, solubility factor of the product, and the practical
losses during filtration and recrystallisation. Precautions to minimise such loss include
understanding the importance of each step in the procedure, avoiding excessive agitation if
product is in the slightest water-soluble, and using a dropper to add a substance slowly.
PRACTICAL 2 : Esterification

Objectives

To study about synthesis and distillation techniques in the esterification process.

Discussion

The synthesis of an ester when a carboxylic acid reacts with an alcohol in the
presence of an acid catalyst is called esterification, involving elimination of water molecule
from a molecule of carboxylic acid and a molecule of alcohol; by removing hydroxyl -OH
group from carboxylic acid and a H atom from alcohol. Catalyst and heat provide energy to
remove -OH from carboxylic acid. The product ester is an organic compound with a pleasant
odour which is poorly soluble in water but highly soluble in nonpolar organic solvents.
Therefore, the reaction mixture will form 2 liquid phases, an organic layer and an aqueous
layer. In this experiment, acetic acid CH3COOH and isoamyl alcohol C5H11OH will react to
yield isoamyl acetate CH3COOC5H11 and water, catalysed by sulfuric acid H2SO4.
CH3COOC5H11 is an ester with a banana-like odour, in which acetate group from acid and
isopentyl group from alcohol is combined by an ester linkage. The reaction was carried out in
a reflux. The condenser prevents loss of volatile reactant (alcohol) and the ester product.
H2SO4 acts as catalyst by increasing rate of reaction by lowering activation energy, and as a
dehydrating agent by removing water to force equilibrium position to the right for greater
yield. Boiling chips in flask provide nucleation sites to prevent bumping or superheating. The
reaction mixture is washed with 5% aqueous bicarbonate solution to neutralise the
unreacted carboxylic acid and H2SO4 dissolved in the organic layer. Anhydrous sodium
sulfate, an adsorbing agent, dries the organic layer by removing traces of water. Complete
removal of water is indicated by formation of big clumps by the anhydrous Na2SO4.
 ● Mechanism

In step 1 of the foregoing method, carbonyl oxygen of acetic acid is protonated by

sulfuric acid. This reaction will then generate two reversible resonance structures, one of
which is a carbocation. Carbon's electron density is repelled, increasing the electrophilicity of
carbonyl carbon and activating it for nucleophilic assault. Carbonyl groups are attacked by
alcohol groups. In step 3, the conjugate bases of acid and deprotonated oxygen produce a
molecule containing two alcohol groups. As seen in step 4, one of these alcohol groups will
then be deprotonated using the remaining sulphuric acid. In step 5, oxygen from alcohol
forms phi bonds and produces water as the leaving group. The conjugate base of sulphuric
acid will be protonated to create isopentyl acetate ester.

● Percentage yield

Besides, percentage yield was calculated in this experiment to know how much the
reactant reacts to form ester as the product. In theory, the higher the percentage yield, the
more effective the chemical process. Thus, the percentage yield that we obtained is 69.9%
with the actual mole 0.0321 mole and theoretical mole 0.0459 mole. As a result, we can see
that the reaction may be incomplete as the 30.1% was lost. It is due to experimental error
and improper technique during handling the experiment. For instance, when washing the
mixture, some of the organic layer may be eliminated from the separatory funnel and the
product may also lost when improper transferring the product into Erlenmeyer flask in order
to weigh them.
Calculation

Conclusion

The purpose of this lab was to produce esters from the acid catalyzed reaction
between an alcohol and a carboxylic acid. We were successful in achieving this goal as the
product has dinstict “banana” smell which indicates the presence of esters. The ester
obtained from this experiment is isoamyl acetate via the Fischer esterification method, with a
percentage yield of 69.9 % due to sample loss during the filtration or heating processes.
References

Sandtorv A. (n. d.). 2.1: Recrystallization, as cited in PDX Open publishing initiative.
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TORY_TECHNIQUES/2.01%3A_RECRYSTALLIZATION

Robert J. Ouellette, J. David Rawn. (2014). Organic Chemistry, as cited in ScienceDirect.

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form%20hydrogen%20bonds,less%20soluble%20than%20carboxylic%20acids.

Nichols L. (n. d.). 1.4B: Controlled Boiling. Retrieved from

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Shammi T., P. S. T. Sai (2009). Esterification of ethanol with sulfuric acid: A kinetic study.
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