EXPERIMENT 4 ASPIRIN

AIMS
At the end of the experiment, students should be able to synthesise pure aspirin using chemical tests such as esterification and recrystallization independently and to also find out the melting point range of aspirin using melting point determination.

INTRODUCTION
Aspirin, which is also known as acetylsalicylic acid, is one of the commonly used and widely found in any drugstore or pharmacy. Its properties make aspirin a well-rounded drug that reduces inflammation and fever and also relieves pain.
The active ingredient in aspirin was found to be salicylic acid, which has the phenolic and carboxylic acid groups that causes irritation in the lining of the stomach, mouth and the throat. Thus, acetyl anhydride was added to salicylic acid and the reaction synthesises acetylsalicylic acid, which contains an ester group. The addition of acetyl anhydride causes the phenolic group in salicylic acid to change to an acetyl group,

R—OH  R—OCOCH3 Hydroxyl group Acetyl group

However, in order for the chemical reaction to take place, an inorganic acid must be used as a catalyst. For example, concentrated sulphuric acid, H2SO4 or concentrated phosphoric acid, H3PO4.

Salicylic acid Acetic Anhydride Acetylsalicylic acid Acetic Acid

The above reaction is called esterification. Esterification involves a carboxyl (-COOH) group and an alcohol/phenol (-OH) group reacting together to form an ester group.

PROCEDURE
(I) Synthesis of Aspirin
Firstly, weigh approximately 2 grams of salicylic acid in a dry 100 mL conical flask using a top-pan balance. Record the actual weight. In the fume hood, add 5 mL of acetic anhydride to the salicylic acid in the flask. Secondly, add 3 - 4 drops of concentrated sulphuric acid to the mixture and swirl to mix. Thirdly, heat the mixture in a water bath for 15 minutes to complete the reaction. Heating the mixture is crucial as it allows salicylic acid to melt and react with acetic anhydride. Then remove the flask from the water bath and carefully add about 20 mL of cold deionized water while the mixture is hot. The addition of cold water is extremely important as it helps in the purification and isolation of the aspirin crystals from the liquid as acetylsalicylic is insoluble in cold water. Quickly stir and rub the inner walls of the conical flask with a stirring rod for 5 minutes. Immerse the conical flask in an ice bath for another 5 minutes to induce crystallisation. Lastly, Collect the raw product by suction filtration (using 2 pieces of filter paper) and wash them with a little cold deionized water. Transfer the raw product into a new 100 mL conical flask.

(II) Purification of Aspirin
Purification is crucial as it eliminates any salicylic acid and acetic anhydride that did not react.
Firstly, dissolve the raw product completely in approximately 5 mL of ethanol to form a hot saturated solution. Warm it if necessary on a hot plate. Do not let it boil. Secondly, once the solid dissolves, add approximately 30 mL of hot deionized water into the solution. If solid reappears, add 1 mL of ethanol and warm gently until the solid dissolves completely. Allow the solution to cool to room temperature. After allowing the solution to cool, ice-bath the solution in the fume hood for approximately 10 - 15 minutes. The cooling of the solution further facilitates recrystallization and purification. Do not agitate while cooling. Thirdly, weigh a clean, dry watch glass together with two pieces of filter papers. Record the total weight. Using your weighed filter paper, obtain the recrystallised product by suction filtration. Fourthly, transfer the crystals and filter paper onto the weighed watch glass. Dry them in the oven at 100°C for 15 - 20 minutes. After drying the crystals, place the crystals, filter paper and the watch glass in a desiccator for 5 - 10 minutes. Lastly, weigh and record the dried crystals with filter paper and watch glass and calculate the weight and the percentage yield of the dried crystals.

(III) Melting Point Determination of Aspirin
Determine and record the melting point of the synthesised aspirin product using melting point equipment.

RESULTS

Salicylic acid Acetic Anhydride Acetylsalicylic acid Acetic Acid

Calculation of theoretical yield
C7H6O3 + C4H6O3 C9H8O4 + CH3COOH
Number of moles of C7H6O3 = = 0.0145 mol
Number of moles of aspirin = 1 x 0.0145 = 0.0145 mol
Theoretical mass of aspirin = 0.0145 x 180 = 2.61 g

Calculation of percentage yield
Mass of watchglass + 2 pieces of filter paper = 40.68 g
Mass of watchglass + 2 pieces of filter paper + aspirin = 42.18 g
Mass of aspirin = 1.50 g
Percentage yield = x 100% = 57.5% (to 3 s.f.)

Observations
Appearance of synthesised aspirin (colour/shape): Fine, white, needle-like crystals

Determination of melting point
Trial 1: 131.4 °C – 133.4°C
Trial 2: 130.1°C – 131.2°C

DISCUSSION
Percentage yield
As stated above in the results section, the percentage yield for the aspirin is 57.7%, a difference of 42.3% for the 100% yield. Although it is impossible to get a full yield, a 70% to 80% yield is attainable, through repeated experiments and careful calculations and precautions.
Therefore, in order to increase the yield of acetylsalicylic acid, the amount of water required to wash the crystals should be reduced so that the crystals would not be dissolved. By using excess acetic anhydride and salicylic acid, the equilibrium is pushed forward and thus, increasing the yield. Another way to increase the yield of aspirin is to leave the solid crystals in the oven and the desiccator for a longer period of time so that the crystals will be dry thoroughly. Another way to increase the yield would be using another method to prepare aspirin. Excess acetic acid could be added to salicylic acid to produce acetylsalicylic acid and water. This allows the chemical reaction to react immediately, forwarding the reversible reaction to the right. Hence, improving the yield of aspirin. The reaction below consists of removal of one water molecule from two acetic acid molecules.

Salicylic acid Acetic acid Acetylsalicylic acid Water

Percentage of purity and Melting point range
The melting point range for the first trial is 131.4 °C – 133.4°C and for the second trial, it is 130.1°C – 131.2°C. However, the melting point range of acetylsalicylic acid, or aspirin, is actually 138°C to 140°C. This shows that the recorded range is far below the actual range and thus, showing that the aspirin crystals contain impurities, giving rise to a low percentage of purity.
Hence, to increase the purity rate of aspirin, recrystallization have to be repeated many times. Also, changing the solvent can increase the purity. In this experiment, water was used as the solvent. However, using ethyl acetate as the solvent allows the aspirin to dissolve more readily as both ethyl acetate and aspirin contain ester group.

Appearance of synthesised aspirin
The recorded observation of the synthesised aspirin is fine, white, needle-like crystals and the actual appearance is exactly the same. Thus, the end product, acetylsalicylic acid is prepared the same.

CONCLUSION
The obtained results for the percentage yield of aspirin is 57.7%, with one turn in the oven and the desiccator. As for the percentage purity, it can be deduced from the melting point range. The melting point rages are recorded and both ranges were far off from the actual range, thus concluding that the percentage purity of the aspirin crystals are not high.

REFERENCES
Internet references:
1. Portland Community College Staff/Student materials, Experiment 12 Synthesis of Aspirin. Available from: <http://spot.pcc.edu/~gbackes/CH222/Labs222.W05/Exp.12.Synthesis.Aspirin.htm>
2. Snelling, CR, Volunteer State Community College Chemistry Laboratory Summer 2014, Synthesis of Aspirin. Available from: <http://www2.volstate.edu/chem/1110/Synthesis_of_Aspirin.htm> [30 September 2013]
Book references:
1. Lewis, D 2003, Aspirin, 2nd Edition, Royal Society of Chemistry, London
2. Rainsford, KD 2004, Aspirin and Related Drugs, Taylor & Francis Inc, USA
3. Whitten, KW, Davis, RE, Peck, ML, Stanley, GG, Chemistry, 8th Edition, Thomas Brooks/Cole, USA

References: Internet references: 1. Portland Community College Staff/Student materials, Experiment 12 Synthesis of Aspirin. Available from: <http://spot.pcc.edu/~gbackes/CH222/Labs222.W05/Exp.12.Synthesis.Aspirin.htm> 2. Snelling, CR, Volunteer State Community College Chemistry Laboratory Summer 2014, Synthesis of Aspirin. Available from: <http://www2.volstate.edu/chem/1110/Synthesis_of_Aspirin.htm> [30 September 2013] Book references: 1. Lewis, D 2003, Aspirin, 2nd Edition, Royal Society of Chemistry, London 2. Rainsford, KD 2004, Aspirin and Related Drugs, Taylor & Francis Inc, USA 3. Whitten, KW, Davis, RE, Peck, ML, Stanley, GG, Chemistry, 8th Edition, Thomas Brooks/Cole, USA