Synthesis of Acetylsalicylic Acid through Esterification Helen Rowi M. Tolentino, Jose Angelo S. Trinidad, Maria Cherisse P. Tuazon. Maria Christine P. Tuazon** College of Science, Department of Biological Sciences, University of Santo Tomas, España Blvd., Manila
Abstract The experiment seeks to synthesize and purify acetylsalicylic acid from a reaction of salicylic acid and acetic anhydride. Recrystallization was the technique used in purifying and a Hydoxamic test was used to characterize Aspirin. The researchers were able to obtain a 70.3313 percentage yield after the experiment. Keywords: Acetylsalicylic Acid, Aspirin, Salicylic acid, Acetic anhydride, Recrystallization
Introduction Acetylsalicylic acid or aspirin is one of the oldest drugs known to Medicine. It is commonly used as an analgesic. Its history dating back since ancient Greek times. Salicylic acid was first used as an analgesic for centuries. However, using Salicylic acid alone caused various negative results such as gastric pains that would cause more problems rather solving the original problem. Salicylic acid was corrosive, therefore, adding an acetyl group would help solve this problem. The term Aspirin then was used to reflect its acetic nature and its natural occurrence in the spirea plant. Salicylic acid, also known as 2-Hydroxybenzoic acid, is a phenolic phytohormone. Its chemical structure is composed of a carboxylic group with a phenol whose hydroxyl group attached to the second carbon. Acetic, also known as ethanoic anhydride, is commonly used for acetylations in the production of commercial products. The synthesis of Aspirin is made possible by Esterification. Esterification is simply the reaction between a carboxylic acid and an alcohol with the presence of an acid catalyst. Recrystallisation is a technique used to purify an organic compound. The goal is to find a solvent 1
that dissolves the product more readily at a high temperature than at a low temperature. This would help remove impurities obtained during the synthesis proper. A Hydroxamic test is used to test for amides and esters by the production of hydroxamic acids. The experiment’s objective is to synthesize, isolate and purify aspirin from a one-step reaction of salicylic acid and acetic anhydride. It also aims to characterize aspirin to confirm its molecular structure.
Methodology In choosing the crystallizing agent, a micro-spatula of pure aspirin was placed in 3 separate test tubes. 1 ml of water, hexane, and methanol was added to the first, second and third tube respectively. The mixtures were heated in boiling water and their solubility were recorded. The mixtures were then placed in a beaker of ice water to cool. Their solubility was recorded as well. Based on the observations, the best solvent was chosen. For the synthesis of Aspirin, 2 grams salicylic acid, 4 acetic anhydride and 5 drops of concentrated
H 2 SO 4
were mixed in an Erlenmeyer flask. The mixture was heated in a
0
80
C water bath. The heated flask was then cooled through a running tap. 20 ml ice water was added to the flask and was then placed in an ice bath. A vacuum filter was then used for the aspirin crystals. Purification was done by transferring all the solids in a beaker and adding just enough of the recrystallizing solvent. The solids were then boiled and let cool in an ice bath. The mixture was then subjected to a vacuum filter again. After vacuum filtration, grain-sized aspirin crystals 2
were separated from the filtrate. The grain-sized aspirin was dissolved with ethanol and subjected to the Hydroxamic Test. The aspirin crystals left were then transferred to a filter paper and let dry in the locker. After several days, the filtered aspirin crystals on the pre-weighed filter paper. And the percentage yield was calculated.
Results and Discussion Salicylic acid Round filter paper Pre-weighed square filter paper Post-weighed square filter paper Actual yield Theoretical yield Percentage yield
2.0080g 0.1681g 0.9821g 2.4151g 1.4330g 2.0294g 70.61%
Table 1
2.008 g Salicylic acid .
1mol SA 1 mol Aspirin 140.146 g Aspirin . . =2.0375 g Aspirin 138.118 g SA 1 mol SA 1mol Aspirin
1.4330 g .100=70.3313 2.0375 g Hydroxamic Test: Sample Standard Aspirin Experimental Aspirin
Result Dark Purple Dark Purple with colorless bottom
Table 2
Salicylic acid, acetic anhydride, and an acid catalyst
H ¿ 2 (¿ SO 4 ) ¿
are mixed and
heated briefly. This process is commonly known as Esterification. In the process, the hydroxyl
3
group from salicylic acid is cleaved from the carboxylic acid by replacing it with the ester group from the acetic anhydride, forming acetylsalicylic acid. The hydroxyl group attached to the other ester from acetic anhydride and forms the other product; Acetic acid. The reaction is optimized when done at a temperature of
800 C, using a temperature higher than this could decompose
the reactants. Adding ice water aids in the solidification of the product. The solid produced after this is the acetylsalicylic acid. The other contents that are left should be separated from the solid that is why a vacuum filter was used. However, the solid product is not pure since there may be some of the reactants left.
Figure 1
Adding the crystallizing solvent (water) dissolves the salicylic acid and converts the excess anhydride to acetic acid. This purifies the product. Vacuum filtering it finally separates the aspirin from the impurities. Esters react with hydroxylamine with the aid of sodium hydroxide to form the sodium salt of the corresponding hydroxamic acid. On acidification (addition of HCl) and addition of ferric chloride, the purple-colored iron (III) complex of the hydroxamic acid is formed. That is
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why the hydroxamic acid test gave a positive result. The standard aspirin and the experimental aspirin showed similar results, confirming to have the same product present. The actual yield was calculated by subtracting the weight of the pre-weighed square filter paper from the weight of the post-weighed square filter paper. The theoretical yield was calculated by dividing 2.008g of salicylic acid by the molecular weight of salicylic acid. Next step was to multiply it with the molecular weight of acetylsalicylic acid, resulting to the theoretical yield. The percentage yield was computed by dividing the actual yield by the theoretical yield and multiplying it to 100.
Conclusion Acetylsalicylic acid was successfully synthesized by reacting salicylic acid and acetic anhydride. The researchers were able to compute a 70.3313 percentage yield. Both the standard aspirin and experimental aspirin tested positive in the Hydroxamic acid test, confirming the presence of esters, thus the presence of Acetylsalicylic acid.
References Ebbing, D. & Gammon, S. (2016). General Chemistry (11th ed.). New York, NY: Cengage Learning Lewis, D. (2003). Aspirin. London: Royal Society of Chemistry Mwaniki, J. (2015). Chemistry 2. University of Nairobi: Department of Chemistry
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Pavia et al. (1998). Introduction to Laboratory Techniques. USA: Harcourt Brace & Company
Williamson K. et al. (2011) Macroscale and Microscale Organic Experiments. Cengage Learning Basic Organic Chemistry Laboratory Course. (2013). University of Helsinki: Laboratory of Organic Chemisrty
Esterification: Preparation of Aspirin (Acetylsalicylic acid). http://fog.ccsf.cc.ca.us/pherrman/documents/aspirin.pdf (May 12, 2016) Esterification: The Synthesis of Aspirin (ASA) http://www.drcarman.info/kem220lb/01lab220.pdf (May 12, 2016)
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