Names: Shanygne Swann and Destiny Stuart Date: 22nd September 2011 Organic Chemistry II Lab 3

Topic: Synthesis of aspirin (acetylsalicyclic acid)

Introduction Aspirin is a non-steroidal anti-inflammatory drug (NSAID) and is used to treat mild to moderate pain, and also to reduce fever or inflammation. It is sometimes used to treat or prevent heart attacks, strokes, and angina. Aspirin can be synthesised by the esterification reaction between salicylic acid and ethanoic anhydride in the presence of sulfuric acid as a catalyst. Salicylic acid is a compound found in willow bark and is known to have medicinal values for alleviating pain, fever, and swellingi . Unfortunately, salicylic acid can have potentially serious side effects in certain peoplei, and this is because the salicylic acid molecule contains two acidic functional groups, the phenol group (PhOH) and the carboxylic acid group (- CO2H). These groups make salicylic acid an irritating substance that scalds the sensitive linings of the mouth, throat, esophagus, and stomach. Some of these side effects include stomach ulcers and salicylism, which is aspirin poisoningii. Fortunately, a safer derivative of aspirin was discovered by a German chemist named Felix Hoffmani. He synthesized acetylsalicylic acid, which is the acetyl derivative of salicylic acid1. This aspirin derivative greatly reduced the harsh side effects of salicylic acid but it did not reduce it by much as aspirin can cause stomach bleeding, gastrointestinal ulcers and tinnitus. It is also a blood thinner which reduces the formation of blood clots but it prevents the blood from making the necessary clots to heal wounds, which causes profuse bleeding from cuts.

Aim: To synthesize aspirin by the reaction of salicylic acid with ethanoic anhydride in the presence of concentrated sulfuric acid as a catalyst.

Outline of Procedure: Refer to flowchart attached.

Procedure: 1. 2.0 g of salicylic acid was measured on an electronic balance and then placed in to 125 ml Erlenmeyer flask. 3 ml of ethanoic/acetic anhydride and 3 drops of concentrated sulphuric acid was added to the salicylic acid swirled and properly. 2. The flask was heated for fifteen minutes in a boiling water bath occasionally being stirred so that the solid could completely dissolve. 3. After heating, the flask was allowed to cool down to room temperature and poured into a 150 ml beaker that contained 20 ml of ice water. The mixture was mixed thoroughly and placed in an ice bath. 4. The crystals that were formed while in the ice bath was removed by vacuum filtration. 5. The crystals were then washed with 5 ml portions of water. 6. The crystals were further dried still using vacuum filtration. 7. The crystals were scraped onto a paper towel and dried using the paper towel. 8. The crystals were then placed in a pre-weighed beaker so that the mass of the aspirin could be measured. After this was done, the percentage yield was calculated. 9. The melting point of the crystals was determined. 10. A test was then performed to test for any unreacted salicylic acid in the sample of aspirin obtained and commercial aspirin. Ferric chloride was used to test what color pure salicylic acid would turn to before ferric chloride was added to the sample and commercial aspirin.

Reaction Equation:
HO O HO OH O O O
H2SO4

O O O CH3

+
H3C 2-hydroxybenzoic acid CH3 acetic anhydride

HO

CH3 acetic acid

2-(acetyloxy)benzoic acid

C7H6O3

C4H6O3

C9H8O4 +

C2H4O2

Salicylic Acid + Ethanoic Anhydride Aspirin + Acetic Acid

Reagent and Product Data Table: Refer to attached table

Observations: Mass of Beaker: 103.9 g Mass of Beaker and Aspirin: 106.91g Mass of Aspirin: 3.01g # moles of C7H6O3 = 2.00 g / 138 g/mol = 0.01449 mol 1 mol C7H6O3 : 1 mol C4H6O3 : 1 mol C9H8O4 : 1 mol C2H4O2 Therefore, 0.01449 mol C7H6O3 : 0.01449 mol C9H8O4 Theoretical Mass = mol * RFM = 0.01449 mol * 180 g/mol = 2.6087 g Percentage Yield = (Actual Yield / Theoretical Yield) * 100 % Percentage Yield = (3.01 g / 2.61 g) * 100 % Percentage Yield = 115.38 % = 115 % Substance Salicylic Acid Aspirin synthesized during experiment Commercial Aspirin Color of Solution Deep purple Dark purple with traces of light brown Tan-brown with a hint of purple

Melting Point of Aspirin synthesized: 133 C Table 1 Test for Salicylic Acid Using Ferric Chloride

Discussion: During this lab, the flask that contained the reactants was placed in hot water bath so that the solid salicylic acid could dissolve completely and would be able to react with the ethanoic anhydride. Cold water was added to the reactants in order to convert any unreacted ethanoic anhydride into acetic acid which has no effect on aspirin. Cold water was also used because aspirin is insoluble in cold water so it was able to precipitate out of solution. When the theoretical yield was calculated, it was found that the actual yield, which is normally less than

the theoretical yield, was found to be more than the theoretical yield. This may suggest that mass of the salicylic acid or the volume of ethanoic anhydride, or both reactants were not measured accurately, therefore, more of one or both of the reactants were added. The melting point of the aspirin synthesized was found to be less than expected (which is 135C). This could have been the result of the fact that the sample was not dried properly so the melting point could have been altered because of the presence of water in the sample. Looking at Table 1, it is clearly shown that salicylic acid turns purple in the presence of ferric chloride. It can be seen that the aspirin synthesized was impure because there was still some unreacted salicylic acid which is represented by the hint of purple seen after ferric chloride was added to the aspirin. However, compared to the commercial aspirin, the synthesized aspirin had less salicylic acid meaning that the aspirin synthesized in the lab was found to be purer than the commercial aspirin.

Rowland, A.T.; Allen K. Clark; Carl T. Wigal; Charles E. Bell, Jr.; Douglass F. Taber; Frederick A. Bettelheim; Jan William Simek; Jerry Manion; Joe Jeffers; Joseph M. Landesberg; Joseph W. LeFevre; L.G. Wade, Jr.; Louis J. Liotta; Moses Lee; Ronald J. Wikholm; and William M. Loffredo. Organic Chemistry Laboratory Manual: Susquehanna University. Thomson Learning: Ohio, 2003.
ii

. Benzaia, Diana. 2003. Hospital for Special Surgery. http://www.hss.edu/Conditions/Arthritis/Aspirin---Caution-Required. Accessed 15, Sept. 2004.