Abstract
The various methods available to synthesize aspirin lead to the need to examine and evaluate production efficiency and purity. The purpose of our experiment was to synthesize acetyl salicylic acid (aspirin) and then determine the relative purity of the synthesized sample by observing the melting point temperature range. The procedure performed in our experiment involved chemically reacting salicylic acid and acetic anhydride in order to form acetyl salicylic acid. The limiting reactant in this chemical reaction was salicylic acid, with acetic anhydride present in excess in order to react with any water produced during the reaction of the reactants, and thus improve the yield of aspirin. The addition of a catalyst, 85% phosphoric acid, facilitated an increase in the reaction rate during the initial synthesis process. Once synthesized, the crude aspirin was recrystallized in order to attain a sample with a higher level of purity.
The percent yield of our crude and recrystallized aspirin samples was 77.81% and 53.81%, respectively. By obtaining the percent yield of our synthesis process we were able to infer some conclusions regarding the efficiency of the techniques performed. The melting point temperature ranges were 126oC-132oC and 129oC-134oC for the crude and recrystallized aspirin samples, respectively. Determining the relative percent yield and attained purities of different synthesis processes is vital to the viability of an affordable commercial product for the aspirin market.
Introduction
The objective of this experiment was to synthesize acetyl salicylic acid (aspirin) from salicylic acid and acetic anhydride and then determine the purity of the samples from the observed melting point temperature ranges and the efficiency of the techniques performed from the percent yield of our samples compared to the theoretical yield of 2.6 grams of aspirin. Aspirin, an acetyl derivative of salicylic acid, is a white, crystallize, weakly acidic substance, with a melting point of 136oC and a boiling point of 140oC (Meyers, 2007). The synthesis of aspirin is classified as an esterification reaction. An esterification reaction is the general name for a chemical reaction in which two reactants, typically an alcohol and an acid, form an ester as the reaction product (Palleros, 2000). Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid’s hydroxyl group in an ester group (Palleros, 2000). This process yields aspirin and acetic acid (normally thought of as a byproduct).
For millennia humans have looked to the natural world for substances with medicinal properties (Trost, 2008). For centuries it has been known that willow-bark was useful for treating inflammation, pain, and fever (Experiment 3, 2013). In 1840, the active compound responsible for willow-barks favorable properties was isolated and identified as Salicin (Sneader, 2000). Soon after its isolation salicin was oxidized into salicylic acid which was distributed in its sodium salt form: sodium salicylate (Sneader, 2000). However, this medicine produced undesirable effects in tandem with its medicinal properties, such as: a very sour taste, irritation of the stomach lining, itching, and rash (Experiment 3, 2013).
In the late 19th century Felix Hoffmann, at the behest of his rheumatic father, endeavored to produce a medicine devoid of the unpleasant effects of sodium salicylate (Sneader, 2000). This led him to synthesize the first pure sample of acetylsalicylic acid. The new compound was marketed by the Bayer Company under the registered trademark of Aspirin (Sneader, 2000). This new derivative of salicylic acid contained the same analgesic, antipyretic, and anti-inflammatory properties of salicylic acid without the same undesired side effects (Sneader, 2000).
Since its isolation in 1897 aspirin has been used widely to treat a variety of ailments and diseases. Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 tons of it being consumed each year (Warner & Mitchell, 2002). Due to its large annual demand, cost effective techniques are vital to the commercial production of aspirin. Since aspirins inception as a commercial product the various methods of production have been studied exhaustively to achieve the highest synthesis efficiency while also yielding the highest purity aspirin possible from the least amount of reactants, and thus reducing the final cost of the product. The scope of this experiment is to examine one of the most common methods of aspirin synthesis and then examine the efficiency of the process and the purity of the samples produced.
Experimental Data/Methods
2.0g of salicylic acid was combined with 5.0mL of acetic anhydride in an Erlenmeyer flask. 5 drops of 85% phosphoric acid, a catalyst, was added to the solution. The beaker was swirled continuously for five minutes and then submerged in a warm water bath in the temperature range of 670C-78oC for 15 minutes, where it was swirled occasionally. After 15 minutes in the warm water bath 2mL of deionized water was added to the solution, to decompose any excess acetic anhydride. The flask was removed from the hot water bath and 20mL of DI water was added. This solution was mixed thoroughly and then allowed to cool. Once cool, the flask was put in an ice bath and left for 12 minutes. The aspirin crystals began to form during this period. The aspirin crystals were vacuum filtered through a Buchner funnel. Precipitate remaining in the Erlenmeyer flask was removed by the addition of 33mL of cold water and the use of a rubber policeman. The precipitate was dried in an oven for five minutes. Once dry, the crude aspirin crystals were weighed and a small sample was put in a capillary tube.
The crude aspirin crystals were recrystallized. The crude aspirin crystals were put in a beaker and 10mL of 95% ethanol was added, to aid in dissolution. Once the aspirin crystals were dissolved 25mL of deionized water was added to the beaker. This solution was submerged in an ice bath for 6 minutes to allow for crystallization. The solution was vacuum filtered through a Buchner funnel. Remaining precipitate in the Erlenmeyer flask was removed by the use of DI water and a rubber policeman. The recrystallized aspirin was dried in an oven and then massed. Next, a small sample of the recrystallized aspirin was taken and put in a capillary tube. Both capillary tubes, crude and recrystallized, were melted in the Mel-Temp apparatus, in order to determine the melting point temperature range. All relevant data and observations were recorded.
Results and Discussion
Table 1. Experimental Measurements
I. Preparation of Crude Aspirin
Mass of Salicylic Acid
2.000g
Amount of Acetic anhydride(5.0mL)
5.0mL
Drops of 85% Phosphoric Acid added
5 drops
Temperature on Hotplate(70-80oC)
67oC-78oC
Tim of Mixture on Hotplate
15 minutes
DI water added to solution while on hotplate
2mL
Amount of water added to solution while on hotplate
20mL
Time solution was in ice-bath
12 minutes
After vacuum filtration, amount of water added to flask to remove an remaining precipitate 33mL
Amount of water used to wash the crystals
3mL
Weight of dry crude aspirin crystals
2.023g
Percentage Yield of crude aspirin
(2.023g/2.6)X 100 = 77.81%
II. Recrystallization(Preparation of Recrystallized Aspirin) Amount of 95% ethanol added to crystals
10mL
Amount of water added to solution
25mL
Amount of time beaker was in ice bath
6 minutes
Mass of dry purified aspirin
1.399g
Percentage Yield of recrystallized aspirin
(1.399g/2.6g) X 100 = 53.81%
III. Identification of Melting Point
Temperature range of crude sample
126oC-132oC(Median Temp: 129oC)
Temperature range of purified(recrystallized) sample
129oC-134oC(Median Temp: 131.5oC)
Known(Theoretical) Melting Point of Aspirin
136oC (Haynes & Lide, 2010)
Experimental Percent Error
[(136oC – 131.5oC)/ 136oC)] X 100 = 3.31%
The aim of this laboratory experiment was to synthesize aspirin, also known as acetyl salicylic acid or 2-(Acetyloxy)-benzoic acid, from 2.0g of salicylic acid and 5.0mL of acetic anhydride. The limiting reactant in this chemical reaction was salicylic acid, with acetic anhydride present in excess in order to react with any water produced during the reaction of the reactants improving the yield of aspirin. A catalyst, 85% phosphoric acid, was added to this reaction in order to increase the reaction rate. Once synthesized the melting point temperature ranges of the prepared samples, crude and recrystallized aspirin, were analyzed and recorded in order to gauge the relative purity of the substances.
The measurement and calculations obtained from this experiment are present in Table 1, above. The actual yield of the crude aspirin was 2.023g with a percent yield of 77.81%. This sample had a median melting point temperature of 129oC. The recrystallized aspirin yielded 1.399g and had a percent yield of 53.81%. The median melting point temperature of this sample was 131.5oC. The experimental percent error for our recrystallized aspirin sample when compared to the known melting point of aspirin, 136oC, was 3.31%. The percentage error for our experimentation when considered in conjunction with the wide melting point temperature range implies much about the actual purity of our recrystallized aspirin sample. From the data it is safe to conclude that the recrystallized aspirin sample is not completely pure. This is apparent from the fact that the higher end of the melting point temperature range is below the actual melting point of aspirin. The impurities in our recrystallized sample actually lowered the melting point of the overall sample and widened the melting point range. When compared to the crude aspirin’s melting point range and mass we can conclude that the recrystallized aspirin sample did have increased purity but also had a reduced yield of aspirin.
The purity of both the crude and recrystallized aspirin samples may have been affected by contamination of some combination of water, reactants, or other substances added during this experiment. This contamination may have inflated the actual yield of aspirin above the mass of aspirin actually present in the samples. This contamination of substances other than aspirin in the prepared samples had a direct effect on the melting point temperature of the synthesized aspirin samples. However, our samples were most likely mainly compromised by the presence of water due to incomplete drying of our samples.
Water present in our samples would have inflated the mass of their respective samples leading to an increase in the actual yield, and thus increasing the percentage yield. If not taken into account this may appear to offset the multiple physical losses at every step in the separation. However, the presence of water in the samples leads to not only inaccurate data but also inaccurate conclusions regarding percent yield, purity of our aspirin samples, and the effectiveness of our synthesis techniques and chosen reactants and catalysts. Analysis on the actual impurities in the sample and their % mass composition was not performed, but their presence in the sample is clearly evident by their effects on melting point temperature.
The most obvious reason for our less than perfect theoretical yield was the constant physical loss of reactants and products at each step in our synthesis scheme. Minute losses of material are to be expected in any experiment. However, imprecise techniques, on account of the unskilled experimenters, led to an increase in the amount of materials lost beyond what was practically preventable. This culminated in an overall effect where each additional step performed to purify the aspirin contributed to a larger loss in final yield.
The reactants in this chemical reaction most likely proceeded through undesired side reactions, despite the addition of a catalyst and DI water to react with excess acetic anhydride. Also, some of the reactants may have not completely reacted with each other despite being present, leaving some of the limiting reactant unused. This could be due to environmental conditions which the sample experienced, such as: inadequate stirring, insufficient application of heat and cold or just pure chance. When attempting to recrystallize the aspirin, some may have stayed in solution and not crystallized during each of the cooling procedures. Each of the above reasons could have played a part in reducing the actual yield of the final product.
A 100% actual yield is not practically possible; but the actual yield of this synthesis was reduced by multiple factors, including: imprecise synthesis techniques and continual loss of materials at each step. This problem was magnified by the novice level of skill of the experimenters which increased loss beyond what could have been attainable.
Despite the less than percent success of our experimentation we were able to draw some very sound conclusions from our data. It is safe to conclude that the presence of impurities will reduce the melting point of synthesized aspirin samples. This method of analysis can be used to determine the relative purity of aspirin samples. Another important observation is that synthesis techniques that increase the purity of a sample also lead to a decrease in percent yield. This makes the efficiency of reactant use decrease as a tradeoff for increased purity. This has very important practical applications. One could conclude that to perform the most efficient synthesis of aspirin one must conduct a process that contains the least amount of steps from reactants to product, to reduce loss and increase percent yield. It should also be noted that recrystallization of aspirin samples significantly increases their purity. For a commercial enterprise manufacturing aspirin studies such as this one are vital to determine the most efficient processes to synthesize aspirin.
Conclusion
The purity of our crude and recrystallized aspirin samples were quantitatively measured by determining their respective melting point temperature ranges. The mass of the recrystallized aspirin was 1.399g, with a percent yield of 53.81%. This low percent yield leads me to conclude that the relative efficiency of our synthesis techniques could be improved. The median melting point temperature of the recrystallized aspirin was 131.5oC. The experimental percent error for our recrystallized aspirin when compared to the known melting point of aspirin, 136oC, was 3.31%. The wide melting point range of our recrystallized aspirin indicates that our sample was not entirely pure and contained impurities within. When comparing the data obtained for the crude and recrystallized aspirin samples one can conclude that steps that increase purity lead to a reduction in actual yield. Repeated experimentation is recommended to obtain higher purities and percent yields to more effectively demonstrate the practical efficiency of this synthesis method.
References
“Experiment 3. Synthesis of Aspirin.” {2013}. In: [Lab] Haynes, W. M., & Lide, D. R. (Eds.). (2010). CRC: Handbook of chemistry and physics (91st ed.). Boca Raton, Fl: CRC Press, Taylor & Francis Group. Meyer, R. L. (2007). The 100 Most Important Chemical Compounds. Westport, CT: Greenwood Press. Palleros, Daniel R. (2000). Experimental Organic Chemistry. New York: John Wiley & Sons. p. 494. ISBN 0-471-28250-2. Trost, B. (2008). Making the paper: technique cuts time and resources to make complex potential drug. Nature, 456(7221), xii. Silberberg, M. S. (2012). Chemistry: The molecular nature of matter and change. New York, NY: McGraw Hill Sneader, W. (2000). The discovery of Aspirin: a reappraisal. British Medical Journal, 321.7276: 1591. Warner, T. D. & Mitchell, J. A. (2002). Cyclooxygenase-3 (COX-3): Filling in the gaps toward a COX continuum? PNAS: Proceedings of the National Academy of Sciences of the United States of America, 99(21), 13371-13373. doi: 10.1073/pnas.222543099
