Aspirin:

Unknown: - 19.5/20

Introduction: (1.5)
Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle
aches, toothaches, common cold, and headaches. It is used worldwide as a 'blood thinner' and to
relieve inflammation, pain, and fever. Aspirin is known as a salicylate and a nonsteroidal anti-
inflammatory drug (NSAID) or 2-acetoxybenzoic acid (not a name for aspirin, it is acetyl
salicylic acid -0.5). Aspirin was first produced 110 years ago, but the natural form, salicylic acid,
found in plants (i.e. the willow and myrtle) has been used for thousands of years. But due to huge
demand, it is now being synthetized. Aspirin synthesis is accomplished via an esterification
(acetylation) reaction: the reaction between salicylic acid and acetic anhydride with hydrochloric
acid (or any strong mineral acid) as a catalyst produces the ester aspirin, or acetylsalicylic acid.

Aim: (1)
The objective of this experiment is to synthesize aspirin from salicylic acid and acetic anhydride,
collect it after vacuum filtration, determine its yield, and checking the reaction completion (or
purity) by means of FeCl3 reagent (flare (flare?) the presence of salicylic acid by the observation
of a purple color).

Experimental: (2)
Equipment:
• Plastic dropper
• Buchner funnel
• Filter paper
• Balance
• Ice bucket
•
Glassware:
• Beakers
 • 125 ml Erlenmeyer flask
• Graduated cylinder
• Spatula
• Test tubes (x2)
• Watch glass
• Pasteur pipette
• Glass rod

Chemicals Used:

Structure Molar Safety hazards

Chemicals weight Amount
(g/mol)
Salicylic acid Causes severe eye irritation. Causes
138.121 3g skin and respiratory tract irritation. May
C7H6O3
be harmful if swallowed. Light sensitive.
May cause central nervous system effects.
May cause reproductive and fetal effects.
Target Organs: Kidneys, central nervous
system, pancreas.
Acetic anhydride Causes burns by all exposure routes.
102.09 6 mL Flammable liquid and vapor. Harmful if
C4H6O3
inhaled or swallowed. Lachrymator
(substance which increases the flow of
tears). Moisture sensitive.
Target Organs: Eyes, skin, mucous
membranes.
hydrochloric acid 10 drops Causes eye and skin burns. Causes
36.45
HCl (~1 mL) digestive and respiratory tract burns. May
be fatal if inhaled or swallowed. Repeated
or prolonged exposure may cause erosion
of exposed teeth. Corrosive to metal.
Target Organs: Respiratory system,
gastrointestinal system, teeth, eyes, skin.
Iron (III) chloride Harmful if swallowed. Causes eye and
162.2 few mL skin irritation and possible burns. May
FeCl3
cause respiratory and digestive tract
 irritation. May cause blood abnormalities.
May cause liver and kidney damage.
Target Organs: Blood, kidneys, liver.
Acetylsalicylic (product Harmful if swallowed, causes skin
180.157 irritation, causes serious eye irritation,
acid C 9 H 8 O 4 formed)
may cause respiratory irritation.

Methanol May be fatal or cause blindness if

32.04 2 ml
CH3OH swallowed, vapor harmful, flammable
liquid and vapor, harmful if swallowed,
inhaled, or absorbed through the skin.
Causes eye, skin, and respiratory tract
irritation, may cause central nervous
system depression, cannot be made non-
poisonous.
Target Organs: Eyes, nervous system,
optic nerve.
Water H2O 18.0153 - -

Methods: (2)

First Experiment: Synthesis of Aspirin

3g of salicylic acid were weighed and added to a 125 mL Erlenmeyer flask then 6mL of acetic
anhydride were added to the same flask while being stirred in the fume hood.10 drops of
concentrated acid (hydrochloric acid) were also added to the Erlenmeyer that was then closed
with a one-hole cork fitted with an inverted Pasteur pipet after mixing the reactants thoroughly.
The Erlenmeyer was heated for 15 minutes in a steam bath. After that the flask was removed 5
mL of ice-cold water were immediately added. Then, 35mL of distilled water were added and the
mixture was left to cool down in an ice-bath while thewalls of the flask were scratched with a
glass rod. After that, vacuum filtration for the solution using a Buchner funnel was done to
collect the product, that was then rinsed with 15 ml of ice-cold water and air vacuumed for
several minutes. Once dried, it was weighed on the balance and the weight of the filter paper and
the watch glass were subtracted.
Second Experiment: Purity Test:

After drying, few crystals of synthesized aspirin were introduced in a test tube and 1 mL of
methanol were added. In another test tube, salicylic acid crystals were added along with 1 ml of
methanol. Then, few drops (1-2 drop) of FeCl3 were added over both solutions in the 2 test-tubes
and they were swirled. The color of the solutions was observed.

Results: (2)

First Experiment:
Reaction:

Mechanism:
Calculations:

𝑚salicylic acid 3
n salicylic acid = = = 0.0217 mol
𝑀salicylic acid 138.121

m acetic anhydride = d acetic anhydride × V acetic anhydride = 1.09 × 6 = 6.54 g

𝑚acetic anhydride 6.54
n acetic anhydride = = = 0.065 mol
𝑀acetic anhydride 102.09

Since the reaction occurs in a 1:1 ratio and n salicylic acid < n acetic anhydride
Acetic anhydride is added in excess and salicylic acid is the limiting reagent.
Theoretically:
n acetyl phenylalanine theo= 0.0217 mol (also based on the stoichiometry)
m acetyl phenylalanine theo = n aspirin theo× M aspirin
= 0.0217 × 180.157
= 3.9 g

However, experimentally, we obtained:

m aspirin exp = m total – m filter paper
= 5.43 – 0.35
= 5.08 g

m aspirin exp 5.08

% yield = = = 130 %
m aspirin theo 3.9

Second experiment:

Both test tubes turn the brown (was it brown?) color of ferric chloride into purple: both had

a dark purple indicating a significant amount of salicylic acid.

Discussion:

Since the esterification reaction with acetic anhydride is reversible and hydrolyses of acetic

anhydride and aspirin occur with water at high temperatures, shifting the reaction backward

and reducing the yield, an inverted Pasteur pipet was used to avoid water condensation in

the Erlenmeyer, and thus shifting the reaction forward.

The acetic anhydride, not salicylic acid, was added in excess because it can be easily

separated from the product by adding water to hydrolyze it into its corresponding

carboxylic acid. HCl was added as a catalyst that induces the reaction. HCl was added

slowly and under the hood to avoid splashing due to the reaction with the solution as it is a
strong, irritant, and corrosive acid. The solution was heated in a steam bath to accelerate the

reaction.

5ml of ice water were directly added to the hot solution to hydrolyze the excess acetic

anhydride, since the hydrolysis in a cold solution would have been slow.

The 35 ml of water were added to precipitate aspirin since it is insoluble in water. Putting

the flask in an ice bath assists the precipitation. Scratching the Erlenmeyer wall induces

aspirin precipitation and crystallization.

Aspirin has a low solubility in water so it can be filtered out of the reaction mixture by

vacuum filtration which was performed to isolate aspirin and dry it (after washing the

crystals with 15 ml ice-cold water) from any remaining solvent.

The FeCl3 test was used to determine if the reaction was complete and if the aspirin is pure.

Since salicylic acid is a phenol, it forms coordination complexes with the iron changing the

brown color of FeCl3 into purple. Since it is the limiting reagent, its presence indicates the

reaction did not go to completion. The color obtained upon adding FeCl3 to aspirin and

water was dark purple indicating that the test is positive due to the formation of a phenol-

iron complex. The reaction was not complete since some salicylic acid remains thus the

product is impure. The incomplete reaction and the presence of salicylic acid in the sample

are probably due to insufficient heating (short time) or insufficient amount of the added

acetic anhydride (not in excess). So, by this we can explain the high yield (130%) that

exceeded 100% and which is completely impossible: not all the mass collected was aspirin

however we had some salicylic acid that increased that mass. And that was verified by the

positive FeCl3 test. The sample was most likely wet as well

Sources of error encountered during the experiment include loss of salicylic acid on the
walls of the vial while emptying it into the E. flask, insufficient heating time, loss of the

reaction mixture on the walls of the E. flask while filtering, insufficient air drying time, and

possibly a mis calibrated balance while weighing the 3g of salicylic acid or the aspirin

formed which has probably led to a decrease in the yield (of pure aspirin)

Conclusion: (1)

Aspirin is produced by reacting salicylic acid with excess acetic anhydride in the presence

of phosphoric acid as a catalyst and heat. The purity of the produced aspirin can be

determined by performing the FeCl3 test. In this case ferric chloride turns to purple, so the

aspirin is impure. The yield is high since the product is crude and contains impurities

(mainly the salicylic acid).

Questions:

1- What is the purpose of sulfuric acid or phosphoric acid used in the

acetylation reaction? Useequations to explain this purpose. (1)

H3PO4 and H2SO4 are used as catalysts to make the reaction faster and that through the first
step of the mechanism:

2- The procedure calls for cautious addition of water to the reaction mixture while it is
still hot. What purpose does the addition of water serve and why should the addition
be done while the reaction mixture is hot? Provide an equation for the reaction
involved. (1)
The water decomposes the excess of acetic anhydride to form the acetic acid. The reaction
in this process should be hot because to get a faster result.

3- Using the quantities of salicylic acid and acetic anhydride noted in the
procedure and any othernecessary data, calculate the theoretical yield in
moles and grams of aspirin.

Theoretically:
n aspirin theo= 0.0217 mol (based on the stoichiometry)
m aspirin theo = n aspirin theo× M aspirin
= 0.0217 × 180.157
= 3.9 g

4- Describe how and why the ferric chloride test can be used to detect whether
your reaction has gone to completion. (1)

Ferric chloride forms a complex with salicylic acid (since it contains a phenol
group). The complex is purple. If the solution has a purple color: There is some
non-reacted salicylic acid that formed a complex with FeCl3.If the solution stays
colorless: there is no non reacted salicylic acid, the product is only aspirin, and
the reaction went to completion.

5- What impurity is most likely to be present in the sample of aspirin you

prepared? What effect would this impurity have if the product were
intended for human consumption? (1)

Salicylic acid could be present. When ingested, salicylic acid has

irritating effects on the stomach lining. In big amounts, it could be
toxic
 6- Write an equation for the reaction that occurs when aspirin is hydrolyzed in the
body. (1)

References: (1)

The lecture power point presentation (Synthesis of Aspirin)

For the MSDS:

Fisher Scientific. Lab Equipment and Lab Supplies. https://www.fishersci.com/us/en/home.html.

For the questions:

U.S. National Library of Medicine. PubChem. National Center for Biotechnology Information.
PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/.