The aim of this experiment was to synthesize aspirin from acetic anhydride and salicylic acid and also to purify the product (aspirin) using recrystallization process. Aspirin is widely used to decrease fever, relieve pain, and as an anti-inflammation purposes.  Aspirin’s use started in the 18th century, after the discovery that extracts from willow tree's bark could reduce fever and pain.  Researchers discovered that salicylic acid was the main agent found in the bark (Desborough et al., 2017). However, salicylic acid had some side effects, including irritation to the mouth lining, stomach, and esophagus. Salicylic acid also caused stomach lining hemorrhaging. Bayer Company, based in Germany, later modified Salicylic acid and named the drug aspirin in 1899. 

Figure 1: Structure of Salicylic Acid

Salicylic acid belongs to the phenol group, with a chemical equation of. Esterification is used to obtain acetylsalicylic acid which causes minimal irritations (Desborough et al., 2017).  The reaction between acetic acid with salicylic acid combined with a catalyst forms aspirin. Esters are formed after the reaction between salicylic acid’s phenol group and acetic acid’s carboxyl group. The esterification process using acetic acid is slow with a quite small yield. Therefore, acetic anhydride is used in place of acetic acid to speed up the reaction and obtain greater yield.

IR and NMR analyses are conducted on synthesized aspirin for determining the organic functional groups and hydrogen atoms present. Furthermore, the analyses are used to determine aspirin’s overall identity.

Figure 2: The Structure of Aspirin

Safety precautions should be observed during the experiment. The compound should be covered every time to avoid inhaling the gases. Aspirin made in the lab is impure and should, therefore, not be ingested. Furthermore, the chemicals used in the experiment should not be touched as they could irritate. Goggles should be used to avoid eye damage and organic waste containers should be used in correct waste disposal.

1. Method
2. Synthesis of Aspirin (Crystallization)

5.48g of salicylic acid was added to 10ml of acetic anhydride in a 100ml round bottom flask.  The mixture of salicylic acid and acetic anhydride initiates the esterification process. The contents of the flask were stirred to make a homogenous mixture. Eight phosphoric acid drops were then added to the mixture (Onyia, 2018). Phosphoric acid acted as a catalyst to speed up the reaction between salicylic acid and acetic anhydride. Afterward, heat was applied to the flask contents for twenty minutes in the fume cupboard. The bottle contents were then allowed to cool and mixed with 75cm3 of deionized water to form crystals.  The deionized water reacts with excess acetic anhydride to form acetic acid. A vacuum filter was used to separate the crystals formed. Afterward, cold water was used to wash the filtered crystals to enhance crystal formation. The evaporating dish’s mass was recorded. The mass of the crystals and the evaporating bowl was also recorded. The difference between of the masses gives the quantity of aspirin crystals obtained from the reaction.

1. Recrystallization of Aspirin

Some aspirin was added to an empty conical flask.  Hot water (40cm3) was slowly added to the flask contents placed.  Heating of the container was done to dissolve the crystals. The flask contents were covered and left to cool for crystallization to take place. A vacuum filter was then used to rinse the crystals using cold deionized water (Lim et al., 2018).  The product was dried for thirty minutes. Drying the product enables one to obtain a meaningful melting point test.  A melting point test and IR analysis was conducted on the product. The melting point and IR determination enables one to know if the aspirin acquired is pure or impure. 

1. Results 

IR spectroscopy:

The carboxylic acid displayed a peak of 1681 while the ester had a peak of 1749

The melting point test revealed that Aspirin has a M.P. of 134oC

1. Sample Calculations
2. Mass of acetic anhydride

1. Mass of synthesized aspirin

1. Limiting Agent

* Salicylic Acid is the limiting reagent *

1. Theoretical Yield

1. Percent yield:

76%

1. Percent error:

24%

1. Discussion and Conclusion

Esterification occurs after a reaction between a carboxyl with a hydroxyl or phenol group. Aspirin and acetic acid are the main products formed in the reaction between acetic anhydride and salicylic acid (Ashraf et al., 2017).

Figure 3: Chemical Reaction for Aspirin Synthesis

Phosphoric acid attacks the carbon-oxygen bond resulting in a positive charge in acetic anhydride (Silverman et al., 2019). The reaction for aspirin synthesis is slow; hence phosphoric acid is used as a catalyst. Aspirin synthesis is an endothermic process; hence heating is required to enhance product formation by increasing solubility and particle collision. Aspirin’s actual yield was 5.77g.  The amount of acetylsalicylic acid used was 5.84g. The aspirin’s theoretical yield was found to be 7.6g. The sample’s percentage yield was found to be 76%.The error percentage was found to be 24%. 

Sources of errors in the experiment caused low yield percentage. The first error could have been due to exposing the product to the atmospheric air causing losses. Secondly, insufficient heating could have also caused product loss leading to a lower yield. The IR value for the salicylic acid was found to be 1681cm-1 and 1749cm-1 for Aspirin. Aspirin traveled further because it has less polarity than salicylic acid. The theoretical IR for salicylic acid was 1652.36, while that of ester formed is between 1736 and 1761 (Silverman et al., 2019). According to the melting point test, the MP of aspirin was found to be 134oC. The theoretical melting point is between 138-140oC. Lower melting points indicate impurities’ presence hence the aspirin obtained was impure.

References

Ashraf, A., Hanif, M., Kubanik, M., Söhnel, T., Jamieson, S.M., Bhattacharyya, A. and Hartinger, C.G., 2017. Aspirin-inspired organometallic compounds: Structural characterization and cytotoxicity. Journal of Organometallic Chemistry, 839, pp.31-37.

Desborough, M. J., & Keeling, D. M. (2017). The aspirin story–from willow to wonder drug. British journal of hematology, 177(5), 674-683.

Lim, J., Song, Y., Jang, J.H., Jeong, C.H., Lee, S., Park, B. and Seo, Y.H., 2018. Aspirin-inspired acetyl-donating HDACs inhibitors. Archives of pharmacal research, 41(10), pp.967-976.

Onyia, N. (2018). CHEM 244A-Organic Chemistry II Lab.

Silverman, J. R., Bode, C., & Subramaniam, B. (2019). Open-Access Chemical Assessments for Students and Educators: A Case Study for Evaluating Aspirin Synthesis. In Technology Integration in Chemistry Education and Research (TICER) (pp. 119-127). American Chemical Society.

Xiong, L., Zhou, L., Zhang, X., Zhang, M., Hou, B., Bao, Y., Du, W., Su, W., Zhang, S. and Yin, Q., 2018. Determination of metastable zone widths and nucleation behavior of aspirin in acetic acid and acetic anhydride binary solvent mixture. Journal of Molecular Liquids, 269, pp.805-815.