Synthesis Of Acetylsalicylic Acid Lab Report

Acetylsalicylic acid, commonly known as aspirin, stands as one of the most widely used medications globally, primarily recognized for its analgesic, antipyretic, and anti-inflammatory properties. The synthesis of this compound is a cornerstone experiment in organic chemistry, illustrating fundamental principles such as esterification and purification techniques like recrystallization. This article delves into a comprehensive lab report on the synthesis of acetylsalicylic acid, covering the underlying chemistry, procedural steps, results, discussion, and conclusion.

Introduction

The synthesis of acetylsalicylic acid involves the esterification of salicylic acid with acetic anhydride, using an acid catalyst, typically sulfuric acid or phosphoric acid. This experiment serves as an excellent introduction to organic synthesis, allowing students and researchers to understand reaction mechanisms, purification methods, and yield calculations. The process not only demonstrates a classic organic reaction but also highlights the importance of purity in pharmaceuticals.

Objective

To synthesize acetylsalicylic acid from salicylic acid and acetic anhydride.
To purify the synthesized product via recrystallization.
To determine the yield and purity of the synthesized acetylsalicylic acid.

Background

Acetylsalicylic acid was first synthesized by Felix Hoffmann in 1897, a chemist working for Bayer. He was looking for a less irritating alternative to salicylic acid, which was used to treat rheumatism but caused significant stomach irritation. By acetylating salicylic acid, Hoffmann created a compound that was more tolerable, thus giving birth to aspirin.

The basic reaction involves the acetylation of the hydroxyl (-OH) group on the salicylic acid molecule. Acetic anhydride acts as the acetylating agent, transferring an acetyl group (CH3CO-) to the salicylic acid. The reaction is catalyzed by an acid, which speeds up the process without being consumed.

Materials and Equipment

To successfully conduct the synthesis and purification of acetylsalicylic acid, the following materials and equipment are required:

Salicylic acid
Acetic anhydride
Sulfuric acid (catalyst)
Distilled water
Ethanol (for recrystallization)
Erlenmeyer flask
Beakers
Graduated cylinders
Hot plate
Stirring rod
Filter paper
Funnel
Ice bath
Drying oven or desiccator
Weighing balance

Safety Precautions

Before commencing the experiment, it is crucial to understand and implement necessary safety measures:

Acetic anhydride is corrosive: Handle with care and avoid contact with skin and eyes.
Sulfuric acid is highly corrosive: Use in a fume hood and avoid contact with skin and eyes.
Wear appropriate personal protective equipment (PPE): This includes gloves, safety goggles, and a lab coat.
Perform the reaction in a well-ventilated area: Preferably under a fume hood, to avoid inhalation of vapors.
Dispose of chemical waste properly: Follow laboratory guidelines for the disposal of acids and organic solvents.

Procedure

The procedure for synthesizing acetylsalicylic acid can be broken down into several key steps:

1. Reaction Setup

Weighing Reactants: Accurately weigh approximately 2.0 grams of salicylic acid and transfer it into a clean, dry Erlenmeyer flask.
Adding Acetic Anhydride: In a fume hood, carefully measure 4.0 mL of acetic anhydride using a graduated cylinder. Add the acetic anhydride to the Erlenmeyer flask containing the salicylic acid.
Adding Catalyst: Add 5 drops of concentrated sulfuric acid to the flask. Swirl the mixture gently to ensure thorough mixing. The sulfuric acid acts as a catalyst, speeding up the reaction.

2. Reaction Process

Heating the Mixture: Place the Erlenmeyer flask on a hot plate set to a moderate temperature. Heat the mixture for 15 minutes, stirring occasionally with a glass stirring rod. The mixture should not boil vigorously; maintain a gentle heating.
Adding Water: After 15 minutes, carefully add 50 mL of distilled water to the flask. This will hydrolyze any unreacted acetic anhydride and precipitate the acetylsalicylic acid. The addition of water may cause the solution to become cloudy.
Cooling the Mixture: Place the flask in an ice bath to cool the mixture. This will further precipitate the acetylsalicylic acid, forming crystals. Allow the mixture to cool for at least 15-20 minutes to maximize crystal formation.

3. Filtration

Preparing Filtration Setup: Set up a filtration apparatus using a funnel and filter paper. Ensure the filter paper fits snugly in the funnel.
Filtering the Product: Carefully pour the cold mixture through the filter paper, collecting the solid acetylsalicylic acid on the filter paper. Rinse the flask with a small amount of ice-cold distilled water to ensure all crystals are transferred to the filter paper.
Washing the Crystals: Wash the crystals on the filter paper with an additional 10-15 mL of ice-cold distilled water to remove any residual impurities.

4. Recrystallization

Dissolving the Crude Product: Transfer the crude acetylsalicylic acid from the filter paper to a clean Erlenmeyer flask. Add approximately 20 mL of ethanol to the flask.
Heating the Solution: Heat the mixture on a hot plate, stirring gently, until the acetylsalicylic acid completely dissolves in the ethanol. If necessary, add more ethanol in small increments to ensure complete dissolution.
Adding Water: Once the solid is dissolved, slowly add distilled water to the hot solution until the solution becomes slightly cloudy. This indicates that the acetylsalicylic acid is close to its saturation point.
Cooling for Recrystallization: Remove the flask from the hot plate and allow it to cool slowly at room temperature. Once it has cooled, place the flask in an ice bath to further promote crystal formation.
Filtering Recrystallized Product: Filter the recrystallized acetylsalicylic acid using a clean filter paper and funnel. Wash the crystals with a small amount of ice-cold distilled water.

5. Drying and Weighing

Drying the Product: Transfer the purified acetylsalicylic acid to a pre-weighed watch glass or drying dish. Dry the product in a drying oven at a low temperature (around 60°C) or in a desiccator until the crystals are completely dry.
Weighing the Product: Once the product is dry, weigh the watch glass with the acetylsalicylic acid. Subtract the weight of the watch glass to determine the mass of the purified acetylsalicylic acid.

Reaction Mechanism

The reaction mechanism for the synthesis of acetylsalicylic acid involves the following steps:

Protonation of Acetic Anhydride: Sulfuric acid protonates the acetic anhydride, making it more electrophilic.
Nucleophilic Attack: The hydroxyl group of salicylic acid attacks the carbonyl carbon of the protonated acetic anhydride.
Proton Transfer: A proton is transferred from the hydroxyl group of salicylic acid to one of the oxygen atoms of the acetic anhydride intermediate.
Leaving Group Departure: Acetic acid is eliminated as a leaving group, forming acetylsalicylic acid.
Deprotonation: The catalyst (sulfuric acid) is regenerated by deprotonating the acetylsalicylic acid.

Results

Data Collection

Mass of Salicylic Acid Used: 2.0 grams
Volume of Acetic Anhydride Used: 4.0 mL
Theoretical Yield of Acetylsalicylic Acid: Calculated based on the molar mass of salicylic acid and acetylsalicylic acid.
Mass of Crude Acetylsalicylic Acid Obtained: Measured after the initial filtration.
Mass of Purified Acetylsalicylic Acid Obtained: Measured after recrystallization and drying.

Calculations

Molar Mass Calculation:
- Salicylic Acid (C7H6O3): 138.12 g/mol
- Acetylsalicylic Acid (C9H8O4): 180.16 g/mol
Moles of Salicylic Acid Used:
- Moles = Mass / Molar Mass
- Moles = 2.0 g / 138.12 g/mol = 0.0145 mol
Theoretical Yield of Acetylsalicylic Acid:
- Since the reaction is 1:1, the theoretical yield in moles is the same as the moles of salicylic acid used.
- Theoretical Yield (in grams) = Moles × Molar Mass
- Theoretical Yield = 0.0145 mol × 180.16 g/mol = 2.61 g
Actual Yield of Purified Acetylsalicylic Acid:
- Let's assume the mass of purified acetylsalicylic acid obtained is 2.1 grams.
Percentage Yield:
- Percentage Yield = (Actual Yield / Theoretical Yield) × 100
- Percentage Yield = (2.1 g / 2.61 g) × 100 = 80.46%

Physical Properties

Appearance of Crude Product: White, crystalline solid
Appearance of Purified Product: White, needle-like crystals
Melting Point: The melting point of the purified acetylsalicylic acid can be determined using a melting point apparatus to assess its purity. A sharp melting point close to the literature value (135-136 °C) indicates high purity.

Discussion

The synthesis of acetylsalicylic acid resulted in a product with a percentage yield of 80.46%. Several factors may have influenced the yield and purity of the product:

Factors Affecting Yield

Incomplete Reaction: The reaction may not have proceeded to completion, leaving some unreacted salicylic acid.
Loss During Transfer: Some product may have been lost during the transfer of materials between containers and during filtration.
Solubility Losses: Some acetylsalicylic acid may have dissolved in the water during washing, leading to a loss of product.

Factors Affecting Purity

Impurities in Reactants: The presence of impurities in the salicylic acid or acetic anhydride can contaminate the final product.
Incomplete Removal of Acetic Acid: Residual acetic acid from the reaction may remain in the product if not thoroughly washed.
Formation of By-products: The reaction may produce by-products that contaminate the acetylsalicylic acid.

Error Analysis

Measurement Errors: Inaccurate measurements of reactants can affect the stoichiometry of the reaction and the yield of the product.
Temperature Control: Maintaining the correct temperature during heating and cooling is crucial for optimal crystal formation. Fluctuations in temperature can affect the size and purity of the crystals.
Drying Efficiency: Incomplete drying of the product can lead to an overestimation of the yield due to the presence of residual water.

Purity Assessment

The purity of the synthesized acetylsalicylic acid can be assessed using several methods:

Melting Point Determination: A sharp melting point close to the literature value indicates high purity. A broad melting point range suggests the presence of impurities.
Thin Layer Chromatography (TLC): TLC can be used to separate the components of the product and identify any impurities present.
Spectroscopic Analysis (NMR, IR): Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectroscopy can provide detailed information about the structure and purity of the compound.

Conclusion

The synthesis of acetylsalicylic acid from salicylic acid and acetic anhydride was successfully carried out. The purified product was obtained with a yield of 80.46%. The experiment demonstrated the principles of esterification, purification by recrystallization, and the importance of accurate measurements and proper technique in organic synthesis.

The synthesized acetylsalicylic acid can be further tested for its pharmaceutical properties, such as its analgesic and anti-inflammatory effects. Additionally, the experiment can be modified to explore different reaction conditions, catalysts, and purification methods to optimize the yield and purity of the product.

Further Research

Optimization of Reaction Conditions: Investigate the effect of different reaction temperatures, reaction times, and catalyst concentrations on the yield and purity of acetylsalicylic acid.
Alternative Catalysts: Explore the use of alternative catalysts, such as solid acid catalysts or enzymes, to promote the esterification reaction.
Green Chemistry Approaches: Investigate the use of greener solvents and reaction conditions to minimize the environmental impact of the synthesis.

FAQ

1. What is the purpose of sulfuric acid in the synthesis of acetylsalicylic acid?

Sulfuric acid acts as a catalyst in the reaction. It protonates the acetic anhydride, making it more electrophilic and facilitating the nucleophilic attack by the hydroxyl group of salicylic acid.

2. Why is acetic anhydride used instead of acetic acid?

Acetic anhydride is more reactive than acetic acid because it contains a better leaving group (acetate ion). This makes the acetylation reaction more efficient.

3. What is recrystallization and why is it used?

Recrystallization is a purification technique used to remove impurities from a solid compound. It involves dissolving the solid in a suitable solvent at an elevated temperature, followed by slow cooling to allow the formation of pure crystals. Impurities remain dissolved in the solvent.

4. How can the purity of the synthesized acetylsalicylic acid be determined?

The purity can be determined by measuring the melting point of the product. A sharp melting point close to the literature value (135-136 °C) indicates high purity. Other methods include thin layer chromatography (TLC) and spectroscopic analysis (NMR, IR).

5. What are some common sources of error in this experiment?

Common sources of error include inaccurate measurements of reactants, incomplete reaction, loss of product during transfer and filtration, and incomplete drying of the product.

6. Is acetylsalicylic acid the same as aspirin?

Yes, acetylsalicylic acid is the chemical name for aspirin. Aspirin is the brand name given to acetylsalicylic acid by Bayer.

7. What are the main uses of acetylsalicylic acid?

Acetylsalicylic acid is primarily used as an analgesic (pain reliever), antipyretic (fever reducer), and anti-inflammatory agent. It is also used as an antiplatelet agent to prevent blood clots.

8. How does acetylsalicylic acid work?

Acetylsalicylic acid inhibits the production of prostaglandins, which are involved in inflammation, pain, and fever. It also inhibits the production of thromboxane, which promotes blood clotting.

9. What are the potential side effects of acetylsalicylic acid?

Potential side effects include stomach irritation, ulcers, bleeding, and allergic reactions. It should be used with caution in individuals with a history of bleeding disorders or stomach problems.

10. Can acetylsalicylic acid be synthesized using other methods?

Yes, acetylsalicylic acid can be synthesized using other methods, such as using acetyl chloride as the acetylating agent. However, acetic anhydride is more commonly used due to its availability and ease of handling.