Aspirin or acetylsalicylic acid is one of the most commonly used drugs in the world. It can act as an analgesic, an NSAID, an antipyretic, and a platelet aggregation inhibitor. Aspirin was originally derived from the active ingredient in willow bark called salicin and was first synthesized chemically in 1897. It is prepared by the esterification of the phenolic hydroxyl group of salicylic acid using acetic anhydride. The phosphoric acid catalyzes the synthesis reaction. This experiment employs two techniques known as reflux and recrystallisation, which are both commonly used as purifying techniques. Reflux involves the condensation of vapours and the return of the condensate to the system from which it originated. Any vapours that are given off are cooled back to the liquid by the condenser and fall back into the reaction vessel.
The vessel is then heated vigorously to thermally accelerate the reaction by conducting it to an elevated temperature (solvent’s boiling point). As a result, the vapour becomes enriched in the more volatile components. In recrystallisation, the mixture and impurity are dissolved in hot solvent and as the solution cools, the solubility of compounds in solution drops allowing the desired compound to recrystallise from solution. Vacuum filtration then separates crystals from the filtrate, yielding a more pure product. The aim of this experiment is to synthesize aspirin by an esterification reaction using reflux and crystallization techniques as purification methods. Melting point determination then confirms the purity of the final aspirin product.
METHOD
In a 100 mL round-bottomed flask, 2.0254 g of salicylic acid was placed with 4 mL of acetic anhydride and 5 drops of 85% orthophosphoric acid. Swirling mixed the mixture and the solution was fit to a reflux condenser and heated on a steam bath for 5 minutes. Without cooling, 2 mL of distilled water was added down the condenser. The mixture then boiled due to the hydrolysing of acetic anhydride and once the reaction subsided, 40 mL of cold water was added. Once the mixture was cooled to room temperature, stirring induced crystallisation. The product was then collected by suction filtration and the yield and melting point range of the crude material was recorded.
The crude product was then placed in a 250 mL conical flask with 30 mL of saturated hydrogen carbonate solution and stirred until no further carbon dioxide evolution occurred. This process removed polymeric by-products. The polymeric solid was removed by vacuum filtration and the filtrate was returned to the 250mL conical flask and 15 mL of 6M hydrochloric acid was slowly added with stirring. The acidified mixture was cooled in an ice-bath to induce crystallisation. The product was then collected and dried using suction filtration while washing the crystals with cold water. Once the crystals were suck dry, the yield and melting point range were recorded.
RESULTS
Mass of Salicylic Acid (through weighing by difference)| 2.0254 g| Mass of Crude Product (through weighing by difference)| 1.3042 g| Melting Point of Crude Product| 135-138°C| Mass of Pure Product (Aspirin) (through weighing by difference)| 0.9269 g| Melting Point of Pure Product (Aspirin)| 137-144°C|
DISCUSSION
In this experiment, 2.0254g of salicylic acid underwent an esterification reaction with acetic anhydride in the presence of orthophosphoric acid catalyst via a reflux condenser. In this reaction, the acetic anhydride was protonated and the phenolic oxygen attacked the acetic anhydride forming a cation. The addition of water then removed the proton and as a result, the crude aspirin was produced. The crude product was then recrystallised and filtered to dry the sample and remove impurities such as unreacted salicylic acid and polymers.
Clearly, the product was extremely wet and not dried long enough. This could be due to the flask we used for suction filtration. There was a chip on the top of the flask, but it was advised to use a plastic wrap to seal the top, which may have resulted in not enough suction. Saturated hydrogen carbonate solution was then added to the crude product, which produced a negatively charged anion (sodium acetylsalicylate) allowing it to dissolve in the polar solution. This process removed possible impurities such as polymer by-products and other molecules that may have formed.
Possible molecules are those that resulted from esterification of the phenol and acid portion of adjacent salicylic acid molecules, which are insoluble in the sodium hydrogen carbonate. Hydrochloric acid was then added to the filtrate, which then protonated the anion and formed aspirin. It is evident that too much product was produced because the product was not dried enough and that impurities were still present. At the end of the purifying techniques, the only possible impurity that could be left is the unreacted salicylic acid. Once again, it may also be due to the inadequate suction filtration equipment mentioned previously.
The crude aspirin mass was more than the recrystallized aspirin because of the greater presence of impurities. The recrystallized product had fewer impurities within it due to the fact that it was treated with sodium hydrogen carbonate. This step removed much of the polymeric by-products from the crude, which may be the reason why the crude product weight was higher when compared to the recrystallized product. The melting point of the crude ASA was lower than that of the recrystallized product. Thus, it can be inferred that the crude melting point was lower because it had more impurities within it.
1) Why does Aspirin dissolve in sodium hydrogen carbonate solution but the polymeric by-product does not?
Aspirin dissolves in sodium hydrogen carbonate and the polymeric by-products do not. This is because aspirin is a weak acid that undergoes hydrolysis in the presence of sodium hydrogen carbonate. The sodium hydrogen carbonate acts like a base and deprotonates aspirin to form sodium acetylsalicylate, carbon dioxide, and water. This reaction produces a negatively charged anion, which is soluble in aqueous solutions. Highly charged polar species are readily soluble in polar aqueous mediums based on the “like dissolves like” principle.
Polymeric by-products form as a result of esterification occurring between the phenol and acid portion of adjacent salicylic acid molecules. Polymers result when molecules bind to the remaining free substituents on these molecules. These polymeric by-products remain insoluble and do not dissolve in the sodium hydrogen carbonate because they are not charged polar compounds. Non-polar compounds do not dissolve in aqueous polar mediums. Mechanism:
CONCLUSION
Aspirin is prepared by the esterification of the phenolic hydroxyl group of salicylic acid using acetic anhydride, catalyzed by phosphoric acid. Impurities such as unreacted salicylic acid, other molecules, and polymers can result. 1.9455 g of salicylic acid was used and 3.200g of crude ASA and 3.114g of recrystallised ASA was produced. The percent yield of crude ASA was 126% and 123% of recrystallized ASA.
The determined melting point of crude ASA was 84 – 90C and 92 – 95C for recrystallised ASA. Clearly, impurities lower the melting points of molecules and wetness affects the mass and melting points as well. However, because the crude mass and melting point ranges were greater than the recrystallized ASA, it can be inferred that reflux, recrystallisation, and suction filtration are good purifying techniques. Proper working equipment is also important in producing accurate results.