UNIVERSITY OF DAR ES SALAAM

COLLEGE OF NATURAL AND APPLIED SCIENCE

CHEMISTRY DEPARTMENT

ORGANIC CHEMISTRY SECTION

CH 244

PRACTICAL REPORT No: 3

TITLE: SYNTHESIS OF ASPIRIN FROM SALICYLIC ACID

GROUP: Tuesday

DATE OF EXPERIMENT: 07th, January 2025

DATE OF SUBMISSION: 14th, January 2025

NAME REGISTRATION DEGREE SIGNATURE

NUMBER PROGRAMME

LUSINDE, FANUEL 2023-04-05724 BSc. in Chemistry

LIVINGSTONE FlivLusinde!!
AKYOO, ROBINSON 2023-04-00210 BSc. in Chemistry

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 ABSTRACT
This experiment intended to synthesize aspirin (acetylsalicylic acid) from salicylic acid using
acetic anhydride and sulfuric acid as a catalyst. The process involved esterification, where
salicylic acid reacted with acetic anhydride in the presence of concentrated sulfuric acid to
produce crude aspirin. The crude product was purified by recrystallization using an ice-water
mixture, and the purity was assessed through its melting point, which was found to be
135.7°C, closely matching the theoretical range for pure aspirin (134-136°C). The yield of
aspirin obtained was 70.844%, indicating a moderately efficient synthesis. The experimental
results were analyzed with consideration of external factors such as temperature fluctuations,
mixing efficiency, impurities in reactants, mechanical losses during filtration, and rapid
cooling, all of which could have contributed to the reduced yield. Despite these factors, the
synthesis method demonstrated reliable esterification and crystallization processes. The
findings suggest that with improved control over external factors and reaction conditions, the
yield and purity of aspirin could be further optimized. Overall, the experiment successfully
provided practical insight into organic synthesis techniques, particularly in esterification and
product purification.

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 THEORY
Aspirin, also known as acetylsalicylic acid, is one of the most widely used drugs, known for
its analgesic, anti-inflammatory, and antipyretic properties. It is also commonly employed for
the prevention of cardiovascular diseases. First synthesized in 1897 by Felix Hoffmann at
Bayer, aspirin was designed as a less irritating alternative to salicylic acid, which had been
used for centuries in the treatment of pain and fever. Over the years, aspirin has proven to be
highly effective, and its widespread use stems from its ability to reduce pain, inflammation,
and fever, as well as to prevent heart attacks (Miller, 2016). The drug's action is mainly due
to its inhibition of cyclooxygenase (COX) enzymes, which catalyze the formation of
prostaglandins responsible for mediating pain and inflammation.

The synthesis of aspirin involves the esterification of salicylic acid (C₇H₆O₃) with acetic
anhydride ((CH₃CO)₂O) in the presence of an acid catalyst, typically sulfuric acid (H₂SO₄) or
phosphoric acid (H₃PO₄). This reaction yields acetylsalicylic acid and acetic acid
(CH₃COOH) as a by-product. The overall balanced equation for the reaction is:

O
O
O
O O H2SO4
OH
+ O +
OH
O
OH acetic acid
salicylic acid acetic anhydride O OH
acetylsalicylic acid

This esterification reaction is favored under mild heating conditions, typically between 50-
60°C, which allows the acylation of the hydroxyl group on the aromatic ring of salicylic acid.
The sulfuric acid helps by removing water formed during the reaction, driving the
equilibrium toward the formation of aspirin. Acetic acid is produced as a by-product and is
typically removed during purification.

Salicylic acid is a naturally occurring compound derived from plants, particularly willow
bark, and is used extensively for its medicinal properties. It contains a hydroxyl group
attached to a benzene ring, which allows it to react easily with acetic anhydride. In the
reaction, sulfuric acid acts as a catalyst, speeding up the process by protonating the carbonyl
oxygen of acetic anhydride, making it more electrophilic and enabling the nucleophilic attack
by the hydroxyl group of salicylic acid (Smith, 2017). Acetic anhydride is typically used in
excess to ensure complete conversion of salicylic acid into aspirin.

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After the synthesis reaction, the crude aspirin product is typically purified by
recrystallization. The crude product is dissolved in a solvent such as ethanol, and as the
solution cools, aspirin crystals form while impurities remain dissolved. This purification step
is essential for obtaining a high purity of aspirin. The purified product is then characterized
using various techniques. One common method is melting point determination, with pure
aspirin having a melting point of approximately 135°C. Deviations from this value suggest
the presence of impurities. Additionally, infrared (IR) spectroscopy can be used to confirm
the presence of characteristic functional groups, such as the ester carbonyl stretch at around
1750 cm-1, and proton nuclear magnetic resonance (NMR) spectroscopy can confirm the
structure by identifying the different proton environments (Miller, 2016).

The reagents used in the synthesis of aspirin, such as acetic anhydride and sulfuric acid, are
hazardous and require careful handling. Acetic anhydride is a corrosive compound that can
cause severe irritation to the skin, eyes, and respiratory system. Sulfuric acid is a strong acid
and should be handled with appropriate protective equipment, including gloves, goggles, and
lab coats. It is important to carry out the reaction in a fume hood to avoid inhalation of vapors
and to dispose of waste materials, such as acetic acid and sulfuric acid, according to standard
safety protocols (Smith & Jones, 2017).

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 EXPERIMENTAL PART
MATERIALS AND REAGENTS

(a) Reagents used

Salicylic acid, Acetic anhydride, concentrated sulfuric acid and distilled water

(b) Apparatus used

Conical flask, beaker, measuring cylinder, hot plate, water bath, ice bath, MelTemp
instrument filter paper, funnel, watch glass, stirring rod and weighing balance.

EXPERIMENTAL PROCEDURES

(a) Reaction Setup and Synthesis

Using a weigh boat, about 2.00 g (± 0.001 g) of salicylic acid (C₇H₆O₃) was weighed and
transferred to a 50 mL Erlenmeyer flask using a powder funnel. The mass was recorded on
the Data Sheet. Next, 5.00 mL of acetic anhydride was measured using a graduated cylinder
located under the hood and added to the flask. This step was carried out in the hood while
wearing goggles to prevent contact of acetic anhydride with the skin and avoid exposure to its
vapors. Finally, 3 to 5 drops of concentrated sulfuric acid were carefully added to the flask as
a catalyst. The flask was then set up for heating in a water bath to ensure even heating. The
reaction mixture was heated gently and maintained at a constant temperature for 10 to 15
minutes to complete the acetylation process. Once heating was complete, the heat source was
removed, and the mixture was allowed to cool to room temperature before proceeding with
precipitation of the crude aspirin.

(b) Precipitation, crystallization and purification of Crude Aspirin

The crystallization of crude aspirin was carried out by dissolving the crude product in a
minimum amount of distilled water. Once dissolved, the solution was allowed to cool to room
temperature. An ice-water mixture was then prepared in a separate container, and the distilled
water solution containing crude aspirin was slowly added to this ice-water bath while stirring
gently. The aspirin crystals began to form as the temperature decreased. The mixture was
kept in the ice-water bath for about 15-20 minutes to ensure complete crystallization. The
crystals were then collected using a Buchner funnel and filter paper, ensuring that the filter
paper was properly seated with a small amount of water. The filtrate was discarded, and the
collected aspirin crystals were washed twice with ice-cold water to remove any remaining
impurities. Finally, the purified aspirin was dried in air and weighed.

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(c) Testing and Analysis of Aspirin
The melting point of the purified aspirin was determined using a MelTemp instrument. A
small amount of the aspirin sample was placed in a capillary tube, which was then inserted
into the MelTemp apparatus. The instrument was gradually heated, and the temperature at
which the aspirin began to melt was recorded as the melting point. The process was repeated
to ensure accuracy, and the observed melting point was compared with the literature value of
pure aspirin (135°C).

RAW DATA
Mass of salicylic acid used = 2.025 g

Volume of acetic anhydride used = 5 mL

Mass of empty watch glass (M0) = 22.190 g

Mass of watch glass and purified aspirin (M1) = 24.061 g

Melting point test

Initial melting point = 135.2 ℃

Final melting point = 136.2 ℃

Average melting point of purified aspirin = 135.7 ℃

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 RESULTS AND DISCUSSIONS
EXPERIMENTAL RESULTS ANALYSIS
Table 1 summarizes the results of the experiment;

Table 1; Results from the experiment

S/No. Parameter involved Data/observation Calculated values/inferences

(a) Actual yield Actual yield = M1 – M0

M0 22.190 g
Actual yield = 24.061 g – 22.190 g

Actual yield = 1.871 g

M1 24.061 g The actual aspirin yield was 1.871

g

(b) Melting point MP1 +MP1

Melting point = 2
MP0 135.2 ℃
Melting point = 136.2 ℃2 +135.2

MP1 136.2 ℃ Melting point = 135.7 ℃

The experimental melting point of
purified aspirin was 135.7 ℃

Theoretical yield calculation

From the reaction,

1 mole of salicylic acid gives 1 mol of acetylsalicylic acid

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 Table 2; Moles of reagents in the reaction

Salicylic acid Acetic anhydride

Mass = 2.025 g Volume = 5 mL

Molar mass = 138.12 g/mol Density = 1.082 g/mL
Mass Molar mass = 102.09 g/mol
Number of moles = Molar mass
Volume × Density
2.025 g
Number of moles = 138.12 g/mol Number of moles = Molar mass

5 mL×1.082 g/mL
Number of moles = 0.0147 mol Number of moles = 102.09 g/mol

The number of moles of salicylic acid used in Number of moles = 0.0530 mol
this reaction for the acetylation process is The number of moles of acetic anhydride
0.0147 mol used in this reaction is 0.0530 mol

Since the moles of salicylic acid are less than the moles of acetic anhydride, then salicylic
acid is considered a limiting reagent.

Using stoichiometry

1 mol of salicylic acid reacts to give 1 mol of aspirin

0.0147 mol of `` reacts to give ? mol of aspirin

Number of moles of aspirin = 1 mol ×10.0147

mol
mol

Number of moles of aspirin = 0.0147 mol

Molar mass of aspirin = 180.158 g/mol

Mass of aspirin = Number of moles × Molar mass

Mass of aspirin = 0.0147 × 180.158 g/mol = 2.641 g

Theoretical yield of aspirin is 2.641 g

Percentage yield calculation

Actual yield 1.871 g

Percentage yield = Theoretical yield ×100%= 2.641 g
×100% = 70.844%

Therefore, the experiment yielded 70.844% as aspirin from salicylic acid based on the
preparation technique applied.

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DISCUSSION
Yield Analysis
The percentage yield of aspirin from salicylic acid was calculated as 70.844%, which, while
slightly below the theoretical maximum, is within an acceptable range for a laboratory-scale
synthesis. Several factors may have contributed to the less-than-ideal yield, including
incomplete reaction of salicylic acid with acetic anhydride, product loss during transfer
between vessels, and incomplete crystallization. Additionally, mechanical losses during
filtration and drying could have reduced the final mass of the recovered aspirin. Despite these
factors, a yield of over 70% reflects a relatively efficient synthesis, suggesting that the
reaction conditions and purification technique were appropriate for producing aspirin of high
purity.

Purity of the Synthesized Aspirin

The experimental melting point of the purified aspirin was recorded as 135.7°C, closely
aligning with the literature value of 135°C for pure aspirin. This minimal deviation suggests
that the product obtained was highly pure, as impurities typically lower and broaden the
melting point range. The consistency in melting point indicates that the crystallization step,
involving the use of an ice-water mixture, effectively removed most impurities from the
crude product. The precise melting point measurement using the MelTemp instrument further
supports the reliability of the analytical technique employed.

Efficiency of the Analysis Method

The analysis method used in this experiment, which included melting point determination and
yield calculation, proved efficient for assessing the quality of the synthesized aspirin. The
melting point determination was particularly reliable, as the observed value was very close to
the expected standard. Yield calculation provided a quantitative measure of the reaction
efficiency and helped evaluate the effectiveness of the preparation technique. The
combination of these methods offered a comprehensive assessment of both the purity and
quantity of the product, which is essential in laboratory-scale pharmaceutical synthesis.

Sources of Error and Recommendations

While the results were satisfactory, certain sources of error could have affected the outcome.
Losses during the transfer of reactants and product, incomplete reaction due to insufficient
mixing or inadequate reaction time, and possible product loss during crystallization and
filtration are likely contributors to the reduced yield.

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Moreover, cooling the solution too rapidly during crystallization might have led to the
formation of smaller, less recoverable crystals. To improve the yield, future experiments
could focus on optimizing reaction time, ensuring thorough mixing, and improving
crystallization conditions by allowing the solution to cool more gradually.

Step-by-Step Reaction Mechanism for Aspirin Synthesis and effects on product yield
Step 1: Activation of Acetic Anhydride
In the presence of a strong acid catalyst (concentrated sulfuric acid), the carbonyl group of
acetic anhydride becomes more electrophilic. The acid protonates the carbonyl oxygen,
increasing its positive character and making it more susceptible to nucleophilic attack.

Effect on Yield:

This step is crucial, as incomplete activation of acetic anhydride could slow down the
reaction or prevent the nucleophilic attack by salicylic acid, leading to a lower yield of
aspirin.

Step 2: Nucleophilic Attack by Salicylic Acid

The hydroxyl group (-OH) of salicylic acid acts as a nucleophile, attacking the carbonyl
carbon of the activated acetic anhydride. This results in the formation of a tetrahedral
intermediate

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Effect on Yield:

If the nucleophilic attack is incomplete due to insufficient mixing or low reactivity of acetic
anhydride, less of the desired product will be formed. Ensuring proper mixing and
maintaining optimal reaction temperature enhances this step.

Step 3: Collapse of the Tetrahedral Intermediate

The tetrahedral intermediate collapses, leading to the elimination of acetic acid as a by-
product and the formation of acetylsalicylic acid (aspirin). The sulfuric acid catalyst
regenerates, allowing it to participate in further activation of acetic anhydride.

O
O
O
OH + HO S O- OH
O OH
O H
O O
O
OH O
O O
O
HO S OH
OH
OH O
O
O O
O +
H O OH
O OH
O
OH O
HO S OH O
+ H
O O
O
O HO S O-
acetylsalicylic acid (aspirin)
O

Effect on Yield

Proper removal of acetic acid from the reaction mixture (by cooling or washing) helps drive
the reaction toward completion, as acetic acid in excess can shift the equilibrium backward,
reducing the yield.

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Step 4: Crystallization of Aspirin
Once the reaction is complete, the mixture is cooled, and water is added to precipitate the
crude aspirin. Acetylsalicylic acid is less soluble in cold water, which facilitates its
crystallization. Any unreacted salicylic acid or acetic anhydride remains in the aqueous
phase.
Effect on Yield:
Inadequate cooling or rapid addition of water can prevent complete crystallization of aspirin,
leading to product loss during filtration. A slow cooling process ensures better crystal
formation and higher recovery of aspirin.
Role of external factors
Several external factors may have influenced the efficiency and outcome of the aspirin
synthesis experiment. Temperature fluctuations during the reaction can cause incomplete
acetylation or lead to side reactions, such as hydrolysis of acetic anhydride. Impurities in the
reactants, particularly salicylic acid and acetic anhydride, may result in unwanted by-products
or lower purity of the final product. Insufficient mixing during the reaction can prevent
proper interaction between salicylic acid and acetic anhydride, leading to partial conversion.
Mechanical losses during transfer and filtration processes may reduce the mass of recovered
aspirin, as some product may remain adhered to the flask or funnel. Additionally, rapid
cooling during crystallization tends to produce fine crystals that are difficult to filter,
resulting in product loss. Finally, exposure to atmospheric moisture, especially when
handling acetic anhydride, can lead to its hydrolysis and formation of acetic acid, thereby
reducing the overall yield. Understanding these factors is crucial for improving the overall
yield and purity of aspirin in future synthesis experiments.

Recommendations
To enhance the experiment’s reliability and yield, consistent heating should be ensured by
using a controlled water bath and monitoring the temperature to avoid underheating or
overheating. High-purity reactants and proper chemical storage in sealed containers are
essential to prevent contamination. Continuous stirring, whether with a magnetic stirrer or
manual swirling, promotes uniform mixing. Minimizing product loss can be achieved by
rinsing the reaction flask and funnel with cold water during filtration. Slow cooling before
ice-water crystallization allows larger, more filterable crystals to form. Lastly, conducting the
experiment in a low-humidity environment, such as a fume hood, and limiting exposure of
reactants to air can prevent hydrolysis, ensuring higher yields and purer products.

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 CONCLUSION
The synthesis of aspirin from salicylic acid using acetic anhydride and sulfuric acid as a
catalyst was successfully completed, yielding 70.844% aspirin with an experimental melting
point of 135.7°C. The melting point obtained falls within the theoretical range of pure aspirin
(134-136°C), confirming the high purity of the product. However, the moderate yield
suggests that certain external factors may have influenced the outcome. Temperature
fluctuations during the reaction, impurities in reactants, insufficient mixing, and mechanical
losses during transfer and filtration likely contributed to the reduced yield. Additionally, rapid
cooling during crystallization may have resulted in fine crystals, making filtration less
efficient. Despite these challenges, the method applied was efficient, and with better control
of these external factors, future experiments could yield higher product amounts. This
experiment provided significant practical experience in esterification and product purification
in organic synthesis.

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 REFERENCES
Miller, D. (2016). Organic Chemistry: Principles and Mechanisms. 2nd Edition: Pearson
Education.

Smith, M. &. (2017). Advanced Organic Synthesis. Oxford University Press.

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