LABORATORY REPORT

Subject : Chemistry Lab

Lecturer : Mr. Tabligh Permana, S.Si
Instructor(s) : Said
Rizal
Faculty : Life Science & Technology
Date of Experiment : 8 April 2019
Date of Lab Report Submission : 22 April 2019
Semester :2

Experiment: PREPARATION OF ASPIRIN

PARTICIPANTS:
1. Charishaa Laturiuw 11805004
2. Felicia Nathalie 11805003
3. Flavia Aurelia 11805002
I. Objective
Synthesis of a simple drug.
II. Introduction
Salicylic-acid-containing compounds derived from willow bark have been in use for hundreds
of years as antipyretic (fever-reducing), analgesic (pain killing), and anti-inflammatory agents. It
was eventually discovered that salicylic acid is the portion of these molecules responsible for the
therapeutic effect. Two ester derivatives of this acid, synthesized as shown,

that are currently used in common medicine are: methyl salicylate (oil of wintergreen) for external
applications and acetylsalicylic acid (aspirin) for internal consumption. The particular derivatives
are chosen for their effectiveness in penetrating the physiological environment in the respective
application - the skin or the intestines. Once within the body tissue, both compounds are hydrolysed
to a salicylic acid, the active agent. This experiment will demonstrate the preparation of aspirin.
Aspirin is superior to salicylic acid for oral dosage in that the latter is very bitter, and causes
stomach upset. The aspirin possesses these properties to a markedly lesser degree and passes
through the stomach largely unchanged, undergoing hydrolysis only in the small intestine and after
absorption in the bloodstream. This temporarily masking of physiologically active compound, to
facilitate oral ingestion or prevent decomposition during transport to the site of activity compound,
to facilitate oral ingestion or prevent decomposition during transport to the site of activity within
the body, is a very common strategy in drug design. The esterification reactants written above do
not proceed fully to completion. A convenient way to obtain complete reaction in the preparation
of an acetate ester is to use acetic anhydride.
 The reaction is catalysed by concentrated phosphoric acid. Excess acetic hydride may be used
in this reaction as the un-reacted portion is hydrolysed after reaction is complete with water.

The acetic acid is produced is removed by filtration of the acetic acid- water solution to yield aspirin
crystals. Trace amounts of salicylic remaining are removed by recrystallization from an
ethanol/water solvent pair.

Purification of a solid by crystallization from a solvent-pair

Occasionally a mixture of two solvents (solvent-pair) is more satisfactory than a single solvent for
recrystallization. Such solvent-pairs are made up of two miscible liquids, one of which dissolves
the substance readily and another which dissolves it very sparingly. example s of solvent-pairs are:
ethanol and water is to dissolve the substance in ethanol at the boiling-point and add water drop
wise, with shaking or stirring, until a faint turbidity persists in the hot solution. A few drops of
ethanol are then added until the solution clears. The hot solvent mixture is then not quite saturated
with the solute and is treated subsequently in the usual way, such as decolorized with charcoal (if
necessary), filtered hot (if treated with charcoal), cooled, filtered, and washed.

III. Equipments and Chemicals Used

- Hot plate with water bath and stirrer. - Acetic Anhydride
- Round necked flask - H₂SO₄ concentrated
- Beakers - Ethanol 96% (cold)
- Reflux unit - FeCl₃
- Distillation unit - Salicylic Acid
- Ice bath - Boiling chips/ Magnetic Stirrer
- Pipette - Filter Paper
- Vacuum filtration system

IV. Procedure
1. The cold water bath and water bath for boiling was prepared.
2. 1 g of Salicylic Acid was weighed and put into a round-necked flask.
3. 1.5 mL of Acetic anhydride and 0.5 mL of H2SO4 was added into the round necked flask in that
order.
4. The reagents was mixed, attached to the condenser and heated for 15 minutes with continuous
stirring of the magnetic stirrer.
5. The solution was then poured into a beaker glass and 50 mL of cold water was added into the
solution.
6. The beaker glass was put into the ice water bath and stirred until the solution eventually turns
white from transparent.
 7. A filter paper was cut and put into the büchner funnel that was connected to the vacuum flask and
pump.
8. The solution was poured into the vacuum filtration unit.
9. The residue obtained on the filter paper should contain salicylic and aspirin. To dissolved the
salicylic, cold ethanol was used and poured into the filter paper.
10. If the aspirin is present, white powder will be seen on the filter paper.

V. Observation and Analysis

1. 1 gram of Salicylic Acid was weighed and put into a round necked flask.

2. 1.5 mL of Acetic anhydride was added to the
round necked flask. The purpose of the
addition of Acetic anhydride is to react with
the salicylic acid so that aspirin can be
synthesized. This is because aspirin is an ester
3. 0.5 mL of H2SO4 was added to the round
necked flask using a dropper. 1 drop of pipette
equals to 0.05 mL so, 10 drops was added and the
solution was then mixed. H2SO4 was added to the
mixture as a catalyst for the salicylic acid and
and esters are formed by esterification of an
alcohol and a carboxylic acid. Salicylic acid
has a phenol group that acts as the alcohol.
Acetic anhydride was used instead of acetic
acid (a carboxylic acid) because reaction of
salicylic acid and acetic anhydride supposedly
reacts faster and has a higher yield.
acetic anhydride reaction. The H⁺ found from the
acid is needed for the first step of the mechanism
of the forward reaction. Once acetic acid is
formed, salicylic acid can also react with acetic
acid to form aspirin and water. H2SO4 is present
as a hygroscopic compound to absorb the water
formed to ensure a forward reaction.

Salicylic Acid + Acetic Acid (+H2SO4 catalyst) ⇄Aspirin + Acetic Acid

4. The solution was heated on a hot plate and
stirred using a magnetic stirrer. A condenser was
also used in this step. This is called a reflux
reaction. The heating step was done because the
reaction is endothermic, meaning it absorbs heat
energy from the surrounding, and hence reaction
5. The solution was poured into a beaker glass
and cold water was added to the solution. This
water is to react with the excess acetic
anhydride so it breaks down into acetic acid.
The beaker was then put into an ice bath and
continuously stirred. After the reflux, now the
moves forward better when heat is supplied to the solution contains acetic anhydride, salicylic
system. This is according to Le Chatelier’s acid, aspirin, water and H2SO4 because they all
principle that if the forward reaction is exist in an equilibrium reaction. To separate the
endothermic, heat must be supplied to cause pure aspirin, we let the solution to cool down so
equilibrium to shift to the right. However, fumes that aspirin and crystallize. The stirring helps
of acetic anhydride can be irritative so the reaction the release of heat so that cooling down is
is done with a condenser so that little to no fumes faster.
escape, also ensuring the availability of the
reactants. According to Le Chatelier’s principles
again, for the equilibrium to shift to the right, the
concentration of reactants in the solution must be
high.

6. The solution was poured into a 7. To ensure all solids formed has been transferred onto
vacuum filtration unit to separate the the filter paper, the beaker was rinsed with cold ethanol
solid aspirin from the rest of the which will be added again after this.
solution. The vacuum filtration unit was
used to make the speed up the drainage
of the solution and to ensure that all
moisture is separated from the solid
formed.
8. Cold ethanol was poured into the vacuum Result after the ethanol dilution: There was no
filtration system. The residue obtained any remains seen on the filtration paper this
should have aspirin and solid salicylic acid means that the aspirin is not present on the
as salicylic acid becomes solid again in cold filtration paper. According to the module, we
temperature. To get rid of salicylic acid, the were supposed to test whether the solid formed
residue was poured with cold ethanol in pure aspirin or not, however we were not able
because salicylic acid has a hydroxyl group to do this as no solid was formed.
so it is soluble in alcohols, in this case
ethanol. However, aspirin can also dissolve
slightly in ethanol, therefore we use cold
ethanol, decreasing the solubility of aspirin
in ethanol.

The experiment above was not able to achieve the objective mention. This may be due to errors in the
experiment.
The first reason may be that the addition of cold water might have induced the hydrolysis of aspirin
back into alcohol and carboxylic acid. In the esterification reaction of salicylic acid and acetic acid,
aspirin can be formed and water is formed as a by-product. So if water and aspirin is both present in
the solution, the equilibrium may shift to the left and having a backward reaction will decrease the
aspirin present. Furthermore, the water added into the solution is cold water, this lowers the
temperature and becomes more suitable for an exothermic reaction. In this case, because the forward
reaction is endothermic, the backward reaction is exothermic and will be promoted in cold
temperature. Hence there is a decrease in the amount of aspirin formed. A possible solution for this
may be to do the procedures at a faster pace to prevent more loss of aspirin and recalculating the
amount of time the solution was heated and cooled down to ensure the largest yield of the reaction.
Second, only 1g of salicylic acid was used. This is equal to 7.246 mmol of salicylic acid. Even if all
salicylic acid was reacted in excess acetic anhydride, the amount of aspirin produced will only be 1.3g
 which is a small amount. In this case, because the reaction is in equilibrium, not all the salicylic acid
is reacted so the amount of aspirin formed is also not maximum. Also, because the power of the
vacuum pump, the filter paper used might have ripped a little bit. This might have caused the escape
of aspirin back into the solution. The solutions to these problems are to use more salicylic acid so that
the amount of expected aspirin can be more and to use 2 layers of filter paper to ensure the filtering
process.

VI. Conclusion
The objective of this experiment is to synthesize aspirin, a simple drug. However, we were not able
to synthesize any aspirin despite knowing the suitable reactants to produce it. We know that to form
aspirin, an ester, we need salicylic acid (alcohol) and acetic anhydride (carboxylic acid substitute) in
the presence of acid catalyst. This will be an equilibrium reaction and hence we use Le Chatelier’s
principles to ensure the highest yield of aspirin formed. The general steps for this reaction is the
synthesis of aspirin and the crystallization of aspirin. Even with the theoretical knowledge of
synthesis of aspirin, we were not able to produce any aspirin so practice and further improvements
mentioned in the discussion might be needed for future try-outs of this experiment.

VII. References
- https://labmonk.com/synthesis-of-aspirin-from-salicylic-acid-using-acetic-anhydride
- http://www.lahc.edu/classes/chemistry/arias/exp%205%20-%20aspirinf11.pdf