Lab Report On Synthesis Of Aspirin

Synthesis of Aspirin: A Comprehensive Lab Report

Aspirin, or acetylsalicylic acid, stands as one of the most widely used medications globally, primarily recognized for its analgesic, antipyretic, and anti-inflammatory properties. This lab report details the synthesis of aspirin through the esterification of salicylic acid with acetic anhydride, catalyzed by an acid. This experiment allows for a practical understanding of organic synthesis techniques, reaction mechanisms, and purification methods crucial in pharmaceutical chemistry.

Introduction

Aspirin's history traces back to Felix Hoffmann, a chemist at Bayer, who first synthesized acetylsalicylic acid in a stable form in 1897. Its rapid adoption as a pain reliever and fever reducer cemented its place in medicine. The synthesis of aspirin is a classic example of esterification, a fundamental organic reaction. This experiment not only demonstrates the synthesis process but also emphasizes the importance of purification and yield calculation in chemical synthesis. The experiment's success hinges on understanding the reaction mechanism, careful execution of the procedure, and accurate data analysis.

Objective

The objectives of this experiment are:

• To synthesize aspirin (acetylsalicylic acid) from salicylic acid and acetic anhydride.
• To understand the esterification reaction mechanism.
• To purify the synthesized aspirin via recrystallization.
• To determine the yield and purity of the synthesized aspirin.

Background Theory

The synthesis of aspirin involves reacting salicylic acid with acetic anhydride in the presence of an acid catalyst, typically sulfuric acid or phosphoric acid. This reaction is an esterification, where the hydroxyl group (-OH) of salicylic acid reacts with acetic anhydride to form an ester (acetylsalicylic acid) and acetic acid as a byproduct.

Chemical Equation:

C₇H₆O₃ (Salicylic Acid) + (CH₃CO)₂O (Acetic Anhydride) → C₉H₈O₄ (Acetylsalicylic Acid) + CH₃COOH (Acetic Acid)

Reaction Mechanism:

1. Protonation of Acetic Anhydride: The acid catalyst protonates the carbonyl oxygen of acetic anhydride, making it more electrophilic.
2. Nucleophilic Attack: The hydroxyl group of salicylic acid acts as a nucleophile, attacking the electrophilic carbonyl carbon of the protonated acetic anhydride.
3. Tetrahedral Intermediate Formation: A tetrahedral intermediate is formed as the hydroxyl group bonds to the carbonyl carbon.
4. Proton Transfer: A proton is transferred from the hydroxyl group of salicylic acid to one of the oxygen atoms of the tetrahedral intermediate.
5. Leaving Group Departure: Acetic acid is eliminated as a leaving group, regenerating the acid catalyst and forming acetylsalicylic acid.
6. Deprotonation: The carbonyl oxygen of acetylsalicylic acid is deprotonated, yielding the final product, aspirin.

Role of Sulfuric Acid:

Sulfuric acid (H₂SO₄) acts as a catalyst in this reaction. It speeds up the reaction without being consumed. The protonation of acetic anhydride by sulfuric acid enhances the electrophilicity of the carbonyl carbon, facilitating the nucleophilic attack by salicylic acid.

Materials and Methods

Materials

• Salicylic acid (C₇H₆O₃)
• Acetic anhydride ((CH₃CO)₂O)
• Sulfuric acid (H₂SO₄) - as a catalyst
• Distilled water (H₂O)
• Ethanol (C₂H₅OH)
• Ice
• Filter paper
• Melting point capillary tubes

Equipment

• Beakers (50 mL, 100 mL)
• Erlenmeyer flask (125 mL)
• Hot plate
• Stirring rod
• Ice bath
• Filter funnel
• Filter paper
• Drying oven
• Melting point apparatus
• Analytical balance

Procedure

1. Reaction Setup:

   • Weigh approximately 2.0 grams of salicylic acid and transfer it to a clean, dry 125 mL Erlenmeyer flask. Record the exact mass of salicylic acid used.
   • Add 4.0 mL of acetic anhydride to the flask.
   • Carefully add 5 drops of concentrated sulfuric acid as a catalyst. Swirl the flask gently to mix the contents.

2. Reaction:

   • Place the flask on a hot plate in a fume hood and heat the mixture gently at around 50-60°C for 15 minutes. Swirl the flask occasionally to ensure thorough mixing and to promote the reaction. The mixture should become clear as the salicylic acid dissolves.

3. Cooling and Precipitation:

   • Remove the flask from the hot plate and allow it to cool to room temperature.
   • Add 50 mL of ice-cold distilled water to the flask to precipitate the aspirin. The water hydrolyzes any unreacted acetic anhydride, converting it to acetic acid.
   • Place the flask in an ice bath to further cool the mixture and maximize the precipitation of aspirin.

4. Filtration:

   • Set up a vacuum filtration apparatus using a Buchner funnel and filter paper.
   • Filter the mixture to collect the solid aspirin. Wash the solid with a small amount of ice-cold distilled water to remove any remaining impurities.
   • Continue to draw air through the filter cake for several minutes to help dry the solid.

5. Recrystallization (Purification):

   • Transfer the crude aspirin to a clean 100 mL beaker.
   • Add approximately 20 mL of ethanol to the beaker and heat the mixture gently on a hot plate, stirring continuously, until the aspirin dissolves. If necessary, add more ethanol in small increments until the aspirin is completely dissolved.
   • Once the aspirin is dissolved, slowly add 50 mL of warm distilled water to the solution. This will reduce the solubility of aspirin and initiate recrystallization.
   • Allow the solution to cool slowly to room temperature, undisturbed, to form crystals. Then, place the beaker in an ice bath to further cool the solution and maximize crystal formation.

6. Second Filtration:

   • Filter the recrystallized aspirin using a Buchner funnel and filter paper. Wash the crystals with a small amount of ice-cold distilled water.
   • Draw air through the filter cake for several minutes to help dry the crystals.

7. Drying:

   • Transfer the purified aspirin crystals to a pre-weighed watch glass.
   • Place the watch glass with the aspirin in a drying oven at a temperature of around 60°C until the crystals are completely dry. This may take several hours or overnight.
   • Remove the watch glass from the oven and allow it to cool to room temperature.
   • Weigh the watch glass with the dried aspirin to determine the mass of the purified aspirin.

8. Melting Point Determination:

   • Prepare a sample of the purified aspirin for melting point determination by packing a small amount of the dried crystals into a melting point capillary tube.
   • Use a melting point apparatus to determine the melting point range of the synthesized aspirin. Compare the observed melting point range with the literature value for pure acetylsalicylic acid (135-136°C).

9. Yield Calculation:

   • Calculate the theoretical yield of aspirin based on the amount of salicylic acid used.
   • Calculate the percent yield of aspirin using the following formula:

   Percent Yield = (Actual Yield / Theoretical Yield) × 100

Safety Precautions

• Always wear safety goggles to protect your eyes from chemical splashes.
• Handle concentrated sulfuric acid with extreme care, as it is corrosive. Add sulfuric acid dropwise and avoid contact with skin and clothing.
• Acetic anhydride is also corrosive and can cause burns. Handle it in a fume hood to avoid inhaling the vapors.
• Ethanol is flammable. Use it in a well-ventilated area and keep it away from open flames or heat sources.
• Dispose of chemical waste properly according to laboratory guidelines.

Results

Data Collection

• Mass of Salicylic Acid Used: 2.015 g
• Volume of Acetic Anhydride Used: 4.0 mL
• Drops of Sulfuric Acid Used: 5 drops
• Mass of Watch Glass: 25.235 g
• Mass of Watch Glass + Dried Aspirin: 27.780 g
• Mass of Dried Aspirin (Actual Yield): 2.545 g
• Observed Melting Point Range: 134-136°C

Calculations

1. Theoretical Yield Calculation:

   • Molar mass of Salicylic Acid (C₇H₆O₃): 138.12 g/mol
   • Moles of Salicylic Acid: 2.015 g / 138.12 g/mol = 0.0146 mol
   • Molar mass of Acetylsalicylic Acid (Aspirin, C₉H₈O₄): 180.16 g/mol
   • Theoretical Yield of Aspirin: 0.0146 mol × 180.16 g/mol = 2.63 g

2. Percent Yield Calculation:

   • Percent Yield = (Actual Yield / Theoretical Yield) × 100
   • Percent Yield = (2.545 g / 2.63 g) × 100 = 96.77%

Results Summary

Discussion

Yield Analysis

The percent yield of aspirin obtained in this experiment was 96.77%. This high yield indicates that the synthesis was efficient and that minimal product was lost during the purification process. Several factors contributed to the high yield:

• Efficient Reaction Conditions: The use of sulfuric acid as a catalyst and the controlled heating of the reaction mixture facilitated the esterification process, leading to a high conversion of salicylic acid to aspirin.
• Effective Purification: The recrystallization process effectively removed impurities, resulting in a relatively pure product and minimizing the loss of aspirin during filtration and washing.
• Careful Experimental Technique: Accurate measurements of reactants, proper mixing, and controlled cooling and drying contributed to the high yield.

Purity Assessment

The purity of the synthesized aspirin was assessed by determining its melting point range. The observed melting point range of 134-136°C is very close to the literature value for pure acetylsalicylic acid (135-136°C). This indicates that the synthesized aspirin is of high purity. A narrow melting point range also suggests that the sample is relatively free of impurities.

Error Analysis

Despite the high yield and purity of the synthesized aspirin, some potential sources of error could have affected the results:

• Loss During Transfer: Small amounts of product may have been lost during the transfer of materials between containers, filtration, and recrystallization.
• Incomplete Drying: If the aspirin crystals were not completely dry before weighing, the mass of the product would have been overestimated, leading to an artificially high yield.
• Impurities: Although recrystallization was performed to purify the aspirin, trace amounts of impurities may still have been present in the final product.
• Melting Point Measurement: The accuracy of the melting point determination depends on the proper calibration of the melting point apparatus and the skill of the operator. Small variations in the observed melting point may occur due to these factors.

Comparison with Literature

The synthesis of aspirin is a well-established organic chemistry experiment. The reaction mechanism, procedure, and expected results are widely documented in chemical literature. The results obtained in this experiment are consistent with those reported in the literature for the synthesis of aspirin under similar conditions. The high yield and purity of the synthesized aspirin demonstrate the effectiveness of the experimental procedure and the importance of careful technique in organic synthesis.

Improvements and Future Experiments

While this experiment was successful, there are several ways to improve the procedure and expand the investigation:

• Use of a Reflux Apparatus: Instead of heating the reaction mixture on a hot plate, a reflux apparatus could be used to maintain a constant temperature and prevent the loss of volatile reactants.
• Spectroscopic Analysis: Techniques such as infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy could be used to confirm the structure and purity of the synthesized aspirin.
• Titration: Titration with a standardized solution of sodium hydroxide (NaOH) could be used to determine the acetylsalicylic acid content of the synthesized aspirin.
• Investigating Different Catalysts: The effect of using different acid catalysts, such as phosphoric acid (H₃PO₄), on the yield and purity of aspirin could be investigated.
• Green Chemistry Modifications: Exploring alternative, more environmentally friendly methods for aspirin synthesis, such as using a solid acid catalyst or a solvent-free reaction, could be a valuable extension of this experiment.

Conclusion

In conclusion, aspirin (acetylsalicylic acid) was successfully synthesized from salicylic acid and acetic anhydride using sulfuric acid as a catalyst. The synthesized aspirin was purified by recrystallization, and its purity was assessed by determining its melting point range. The high percent yield (96.77%) and the narrow melting point range (134-136°C) indicate that the synthesized aspirin was of high quality. This experiment provided valuable experience in organic synthesis techniques, including esterification, purification, and yield calculation. The results obtained are consistent with those reported in the chemical literature for the synthesis of aspirin. Furthermore, potential sources of error were identified, and suggestions for improving the procedure and expanding the investigation were proposed. This experiment serves as a fundamental introduction to the principles and practices of pharmaceutical chemistry.

FAQ

Q: What is the purpose of sulfuric acid in the synthesis of aspirin?

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

Q: Why is acetic anhydride used instead of acetic acid?

A: Acetic anhydride is more reactive than acetic acid because it has a better leaving group. This leads to a faster and more efficient esterification reaction.

Q: What is recrystallization and why is it necessary?

A: Recrystallization is a purification technique used to remove impurities from the crude aspirin. It involves dissolving the aspirin in a hot solvent (ethanol), and then slowly cooling the solution to allow pure aspirin crystals to form, leaving the impurities dissolved in the solvent.

Q: How is the purity of the synthesized aspirin assessed?

A: The purity of the synthesized aspirin is assessed by determining its melting point range. A narrow melting point range close to the literature value for pure acetylsalicylic acid indicates high purity.

Q: What are some common uses of aspirin?

A: Aspirin is commonly used as an analgesic (pain reliever), antipyretic (fever reducer), and anti-inflammatory agent. It is also used in low doses to prevent blood clots and reduce the risk of heart attacks and strokes.

Q: Is aspirin safe for everyone?

A: No, aspirin is not safe for everyone. It can cause side effects such as stomach upset, ulcers, and bleeding. It should be avoided by people with certain medical conditions, such as bleeding disorders and aspirin sensitivity, and should not be given to children or teenagers with viral infections due to the risk of Reye's syndrome.

Q: How can the yield of aspirin be improved?

A: The yield of aspirin can be improved by using a reflux apparatus, ensuring complete drying of the product, and minimizing losses during transfer and filtration.

Q: What are some alternative methods for synthesizing aspirin?

A: Some alternative methods for synthesizing aspirin include using a solid acid catalyst, performing a solvent-free reaction, and using enzymatic catalysis. These methods may be more environmentally friendly than the traditional method.

Q: What is the chemical formula of aspirin?

A: The chemical formula of aspirin (acetylsalicylic acid) is C₉H₈O₄.

Q: How does aspirin work in the body?

A: Aspirin works by inhibiting the production of prostaglandins, which are hormone-like substances that contribute to pain, inflammation, and fever. It also inhibits the production of thromboxane, which promotes blood clotting.