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Title: Synthesis and Characterization of Aspirin (Acetylsalicylic Acid)

Name:

Instution:
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Abstract:
This experiment focuses on the synthesis of acetylsalicylic acid (aspirin) through the
esterification of salicylic acid with acetic anhydride in the presence of sulfuric acid as a
catalyst. The reaction mechanism involves nucleophilic acyl substitution, a key concept in
organic chemistry. After synthesis, the crude product was purified using recrystallization.
The final aspirin product was analyzed using melting point determination and Thin Layer
Chromatography (TLC) to assess purity. The percentage yield of the reaction was calculated
and compared to theoretical values. Results showed a moderate yield, and the melting point
was close to literature values, suggesting successful synthesis with minor impurities.
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Introduction

Organic chemistry involves understanding reactions and mechanisms that drive the

transformation of molecules. Aspirin synthesis is a classic organic lab experiment because it

illustrates several fundamental concepts such as esterification, purification, recrystallization,

and yield determination.

Aspirin (acetylsalicylic acid) is a widely used analgesic and anti-inflammatory drug.

It is synthesized from salicylic acid, which contains both a phenol group (-OH) and a

carboxylic acid group (-COOH). When reacted with acetic anhydride, the hydroxyl group of

salicylic acid forms an ester, producing aspirin and acetic acid as a byproduct.

The reaction can be summarized as:

Salicylic acid + Acetic anhydride → Acetylsalicylic acid + Acetic acid

Sulfuric acid (H₂SO₄) or phosphoric acid (H₃PO₄) is commonly used as a catalyst to

speed up the reaction. After the reaction, the crude product is purified by recrystallization using

ethanol and water.

This lab report presents a complete synthesis process, followed by characterization and

analysis of the synthesized aspirin.

Materials and Methods

Materials:

• Salicylic acid (C₇H₆O₃)

• Acetic anhydride (C₄H₆O₃)

• Concentrated sulfuric acid (H₂SO₄)

• Distilled water

• Ice

• Ethanol (95%)
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• Watch glass

• Hot plate

• Beaker (250 mL)

• Flask (Erlenmeyer, 125 mL)

• Graduated cylinder

• Spatula

• Stirring rod

• Filter paper

• Buchner funnel and vacuum filtration setup

• Melting point apparatus

• Thin Layer Chromatography plates

• Capillary tubes

Procedure:

1. Synthesis:

o In a 125 mL Erlenmeyer flask, 2.0 g of salicylic acid was added.

o 5 mL of acetic anhydride was added to the flask.

o 5 drops of concentrated sulfuric acid were added carefully using a dropper.

o The mixture was swirled gently and then heated in a water bath at 60–70°C for

15 minutes.

2. Crystallization:

o After heating, the reaction mixture was removed from the bath and allowed to

cool slightly.

o 50 mL of cold distilled water was added to decompose excess acetic anhydride

and initiate crystallization.

o The flask was placed in an ice bath for 10–15 minutes to complete

crystallization.

3. Filtration and Drying:

o Crystals were collected by vacuum filtration using a Buchner funnel.

o The product was washed with cold water to remove impurities.

o The crude aspirin was dried on a watch glass.

4. Recrystallization:

o The crude product was dissolved in a minimum amount of ethanol.

o Hot water was added dropwise until the solution became clear.

o The solution was cooled to room temperature, then placed in an ice bath.

o Pure aspirin crystals were collected by vacuum filtration and dried.

5. Melting Point Determination:

o A small amount of dried product was placed in a capillary tube.

o Melting point was determined using a melting point apparatus.

6. TLC Analysis:

o Aspirin product and salicylic acid were spotted on a TLC plate.

o The solvent system used was ethyl acetate:hexane (3:1).

o The TLC plate was developed, dried, and observed under UV light.

Results

Observations:

• Upon adding acetic anhydride to salicylic acid, the mixture turned cloudy.

• Heating caused the solution to become clear.

• Addition of cold water caused the formation of white, needle-like crystals.

• Recrystallized product appeared purer and finer than crude product.

• TLC showed a single major spot for the product, indicating good purity.

Data:

Measurement Value

Mass of salicylic acid used 2.00 g

Molar mass of salicylic acid 138.12 g/mol

Moles of salicylic acid 0.0145 mol

Molar mass of aspirin 180.16 g/mol

Theoretical yield of aspirin 2.61 g

Actual yield after recrystallization 1.92 g

Percentage yield 73.6%

Melting point of product 134–136°C

Literature melting point of aspirin 135–136°C

TLC Results:

• Rf value of product = 0.72

• Rf value of salicylic acid = 0.50

Discussion

Reaction Mechanism:

The synthesis of aspirin involves nucleophilic acyl substitution. The hydroxyl group

(-OH) of salicylic acid acts as a nucleophile and attacks the carbonyl carbon of acetic

anhydride. This leads to the formation of an ester linkage and acetic acid as a by-product.

Sulfuric acid catalyzes the reaction by protonating the carbonyl oxygen of acetic

anhydride, increasing the electrophilicity of the carbonyl carbon, and facilitating the

nucleophilic attack.

Yield and Purity:

The percentage yield of 73.6% indicates a fairly efficient reaction, though not complete.

Losses may have occurred during transfer, recrystallization, or filtration. The observed melting

point (134–136°C) is very close to the literature value, confirming the identity and purity of

the product. Minor impurities or moisture may explain the slight deviation.

TLC Analysis:

The TLC analysis revealed one major spot for the aspirin product and no visible spot

corresponding to unreacted salicylic acid, suggesting successful conversion. The Rf value for

aspirin (0.72) was higher than salicylic acid (0.50) due to decreased polarity after esterification,

which aligns with theoretical expectations.

Sources of Error:

• Incomplete drying could lower the melting point.

• Excess water in recrystallization could reduce crystal formation.

• Product loss during transfer or filtration.

• Inaccurate temperature control during synthesis might affect reaction

completion.

Conclusion

The synthesis of acetylsalicylic acid from salicylic acid and acetic anhydride was

successful. A good percentage yield and high purity were achieved, as indicated by melting

point and TLC analysis. This experiment demonstrates essential techniques in organic

chemistry, including esterification, recrystallization, yield calculation, and qualitative analysis

through TLC.

The close agreement between the observed and literature melting points, and the

successful purification steps, confirm that acetylsalicylic acid was synthesized with high

efficiency and purity.

References

Pavia, D. L., Lampman, G. M., Kriz, G. S., & Engel, R. G. (2014). Introduction to Organic

Laboratory Techniques: A Microscale Approach. Cengage Learning.

Williamson, K. L., & Masters, K. M. (2010). Macroscale and Microscale Organic

Experiments (6th ed.). Cengage Learning.

Mayo, D. W., Pike, R. M., & Forbes, D. C. (2010). Microscale Organic Laboratory: With

Multistep and Multiscale Syntheses (5th ed.). Wiley.