Materials Included In Kit

Additional Materials Required

Safety Precautions

Concentrated sulfuric acid is severely corrosive to eyes, skin and body tissue. Keep sodium carbonate or other acid neutralizer on hand to clean up acid spills. Acetic anhydride is a corrosive liquid and the vapors are highly irritating. The liquid is flammable and a strong lachrymator—contact with the liquid will cause severe eye irritation. Work with acetic anhydride in the hood or in a well-ventilated lab only. Do not inhale the vapors. Salicylic acid is moderately toxic by ingestion. Avoid contact of all chemicals with eyes and skin. Wear chemical-splash goggles, chemical-resistant gloves and a chemical-resistant apron. Remind students that all chemicals prepared in the lab are for laboratory use only and should never be removed from the lab. The aspirin prepared in this lab may be impure and contaminated with chemicals that could be dangerous if ingested. Please review current Safety Data Sheets for additional safety, handling and disposal information. Remind students to wash their hands thoroughly with soap and water before leaving the lab.

Disposal

Please consult your current Flinn Scientific Catalog/Reference Manual for general guidelines and specific procedures, and review all federal, state and local regulations that may apply, before proceeding. The products may be disposed of in the solid waste according to Flinn Suggested Disposal Method #26a.

Lab Hints

• For best results, schedule at least two 50-minute lab periods for this experiment. In addition, at least two hours (overnight is best) are needed to dry the aspirin. The mass of the aspirin and its melting point can be determined after school or during a free period the next day. The products may be stored covered in a lab drawer until the next regularly scheduled lab (i.e., the following week).
• Concentrated sulfuric acid and acetic anhydride are corrosive liquids. We recommend setting out and dispensing these chemicals in a central and supervised location. This is best done in the fume hood. Place the reagent bottles on a demonstration tray or a laboratory spill mat (LabMat™) to contain any chemical spills. To further reduce spillage, tape a small test tube to the side of each reagent bottle. Store a pipet in the test tube for students to use.
• The procedure calls for scraping the product from the filter paper onto a watch glass prior to drying the crystals. The filter paper tends to retain some acetic acid from the reaction mixture and does not dry out well, even overnight.
• Crush the aspirin tablets and place in a labeled vial for students to use in step 19.
• Thiele-Dennis tubes are designed to give excellent convection and heat transfer for melting point and boiling point determinations. The unique design creates convection currents when the oil inside the tube is heated, allowing the oil to flow continuously through the tube without stirring or shaking. The recommended heating fluid is silicone oil or vegetable oil. Fill the tube to the level shown—the oil will expand when heated.
  {12549_Hints_Figure_4_Design and use of a Thiele-Dennis tube}
• Melting points and boiling points of organic compounds may be found in The Merck Index, CRC Handbook of Chemistry and Physics and Lange’s Handbook of Chemistry among others. Melting points may also be found online by looking up Safety Data Sheets. Section 9 of the SDS lists common physical and chemical properties, including melting point, boiling point, and density. Visit the Flinn website at www.flinnsci.com to download current SDSs for all Flinn chemicals.
• Compare the acidity of salicylic acid and acetylsalicylic acid (aspirin) by testing the pH of solutions (see step 20 in the Procedure) with narrow range (3.0–5.5) pH paper. Salicylic acid is more acidic than aspirin (pH 3.0 versus 3.5).

Answers to Prelab Questions

1. Acetic anhydride is a lachrymator. What is a lachrymator and what safety precautions should be followed when working with acetic anhydride?

   A lachrymator is a substance that causes tearing and severe eye irritation. Avoid breathing the vapor and use the substance in the fume hood or in a well-ventilated lab only. Wear chemical splash goggles and chemical-resistant gloves and apron.

2. What is concentrated sulfuric acid used for in this experiment? What are the hazards of working with concentrated sulfuric acid?

   Concentrated sulfuric acid is used as an acid catalyst for the esterification reaction of salicylic acid with acetic anhydride. It is extremely corrosive and will cause severe burns. Be very careful when working with concentrated acids and avoid contact with eyes and skin. Notify the teacher immediately if any acid, even a few drops, is spilled. Wear chemical splash goggles and chemical-resistant gloves and apron.

3. Calculate (a) the molar mass of salicylic acid and acetic anhydride and (b) the number of moles of each that will be used in this experiment. Note: The density of acetic anhydride is 1.08 g/mL.
   {12549_Answers_Equation_2}
4. Define the term limiting reactant. Complete the following statement: The maximum number of moles of aspirin that can be obtained in this experiment is equal to the number of moles of salicylic acid used.

   The limiting reactant in a chemical reaction is the reactant that is present in the smallest number of moles based on the stoichiometric mole ratios for the reactants. The number of moles of the limiting reactant determines (i.e., limits) the maximum amount of product that can be obtained.

5. Determine the chemical formula of acetylsalicylic acid and calculate its molar mass.

   Acetylsalicylic acid, C₉H₈O₄, 180 g/mole

Sample Data

Answers to Questions

1. Calculate the number of moles of salicylic acid used in this experiment.
   {12549_Answers_Equation_3}
2. Calculate the maximum amount of aspirin in grams that could be obtained from this amount of salicylic acid. This is the theoretical yield. Hint: See Prelab Questions 4 and 5.

   0.0037 moles x 180 g/mole = 0.67 g aspirin

3. Determine the mass of aspirin obtained in this experiment and calculate the percent yield.
   {12549_Answers_Equation_4}

   (0.40 g/0.67 g) x 100 = 58%

4. Iron(III) ions are used as a qualitative test for phenols (aromatic compounds containing an –OH functional group). (a) What compound was used as a positive control for the Fe³⁺ test in this experiment? (b) Did the reaction product give a positive or negative test with Fe³⁺ ions? Explain.
   1. Salicylic acid, which contains a phenolic –OH group in its structure, served as a control sample that would give a positive test. Salicylic acid gave a dark purple product when iron(III) chloride solution was added.
   2. The aspirin product gave a negative test with Fe³⁺ ions—no color change was observed. Aspirin does not contain an –OH functional group attached to the aromatic ring. The –OH group in salicylic acid was converted to an acetyl (–OCOCH₃) group.
5. Old aspirin tablets often have a faint vinegar smell and give a positive test with iron(III) ions. Write a balanced chemical equation for the hydrolysis of aspirin (reaction of aspirin with water) to explain these observations.

   Hydrolysis of aspirin gives salicylic acid (positive Fe³⁺ test) and acetic acid (vinegar smell).

   {12549_Answers_Figure_5}
6. Acetic anhydride was used in excess in this experiment. What does this mean, and how was the excess acetic anhydride decomposed at the end of the reaction?

   The number of moles of acetic anhydride was greater than the number of moles that would react completely with the amount of salicylic acid in the reaction mixture. Excess acetic anhydride was therefore left over in the reaction mixture after all the salicylic acid had been converted to product. The acetic anhydride remaining at the end of the reaction was decomposed to acetic acid by adding water to the reaction mixture prior to crystallization.

7. Look up the melting points of salicylic acid and aspirin (acetylsalicylic acid) in a reference book or online and compare with the melting point of the reaction product.

   Literature melting points
   Salicylic acid, mp 157–159 °C
   Acetylsalicylic acid, mp 135 °C (dec)
   Melting point of product, 120–122 °C
   The product does not appear to be pure. The most likely contaminant is unreacted salicylic acid—the melting point of a mixture is lower than that of the pure substance.

References

This activity was adapted from Flinn ChemTopic™ Labs, Vol. 19, Chemistry of Organic Compounds; Cesa, I., Editor; Flinn Scientific: Batavia IL (2006).

Introduction

Aspirin, first synthesized in 1897, is one of the oldest, yet most common, drugs in use today. Like many modern drugs, aspirin has its roots in an ancient folk remedy—the use of willow extracts to treat fever and pain. Aspirin is prepared the same way today that it was more than 100 years ago. Let’s look at the structure, synthesis and properties of aspirin.

Concepts

• History of aspirin
• Salicylic acid derivatives
• Esters and esterification
• Excess and limiting reagents

Background

Native Americans, as well as the ancient Chinese, Egyptians and Greeks, used willow extracts to treat fever, pain and inflammation. The Ebers papyrus, dating to at least 1500 B.C. in Egypt, contains the earliest written reference to the use of willow extracts, “to draw the heat out” from inflammation. Willow extracts remained a popular folk medicine remedy throughout the middle ages. The first scientific study of the effectiveness of willow extracts was carried out in 1763 by the Rev. Edward Stone in England. In one of the first ever “clinical trials” of a drug, Stone reported using willow extracts to treat fever and pain in more than 50 patients suffering from malaria.

In the early 19th century, organic chemistry was only a fledgling science, with roots in the study of natural products. In 1828, Johann Büchner at the University of Munich in Germany isolated a crystalline compound from willow bark and named it salicin, after the Latin name for the white willow, Salix alba. Ten years later, the Italian chemist Raffaele Piria converted salicin to salicylic acid, which had also recently been isolated from meadowsweet flowers (Spiraea). Salicylic acid (see Figure 1) was found to be the active ingredient responsible for the medicinal properties of many plants, including willow, poplar, aspen and myrtle. In 1859, Hermann Kolbe at Marburg University in Germany determined the chemical structure of salicylic acid and synthesized it from phenol, a derivative of coal tar. By 1870, salicylic acid was widely used in Europe for the treatment of arthritis, pain, and fever. Unfortunately, the compound was “tough to swallow” and very irritating to the stomach. Many people could not tolerate the drug because of its severe and unpleasant side effects.

Felix Hoffmann, an organic chemist working at Friedrich Bayer and Company in Germany, attempted to chemically modify salicylic acid and thus reduce its side effects. In 1897, Hoffmann prepared acetylsalicylic acid by reacting salicylic acid with acetic anhydride (Equation 1). The synthesis of acetylsalicylic acid is an example of an esterification reaction in which the phenolic –OH group in salicylic acid is replaced with an acetyl or ester functional group (–OCOCH₃). Masking the –OH functional group in this way makes the compound less acidic. Acetylsalicylic acid is an effective analgesic (pain reliever) and antipyretic (fever reducer) but is less acidic or harsh than salicylic acid. In 1899, the Bayer Company marketed acetylsalicylic acid under the trade name aspirin, with a– denoting the acetyl group and –spirin referring to Spiraea, the plant from which salicylic acid was first isolated. It is estimated that approximately 50 billion aspirin tablets are consumed per year all over the world, and that as many as one trillion (1 x 10¹²) aspirin tablets have been produced in the 100 years since its discovery!

Acetylsalicylic remains a versatile drug in the 21st century. The two most common uses of aspirin today are for the prevention of heart attack and stroke and to relieve the pain and reduce the inflammation of arthritis. The American Heart Association recommends “an aspirin a day” to prevent a second heart attack in individuals who have had a previous heart attack or stroke. The myriad physiological effects of aspirin were explained in 1972 by Sir John Vane (Nobel Prize in Medicine, 1982) and coworkers at the Wellcome Research Laboratories in Great Britain. Vane found that aspirin inhibited an enzyme involved in the synthesis of prostaglandins and thus interfered with their production in the body. Prostaglandins are hormone-like “chemical messengers” that play a key role in a variety of physiological processes, including inflammation, blood clotting, labor and childbirth, and blood pressure. Aspirin prevents the formation of blood clots that are a major cause of heart attacks and strokes.

Experiment Overview

The purpose of this experiment is to prepare acetylsalicylic acid (aspirin), determine its purity and investigate its chemical properties.

Materials

Prelab Questions

Read the entire Procedure and the Safety Precautions.

1. Acetic anhydride is a lachrymator. What is a lachrymator and what safety precautions should be followed when working with acetic anhydride?
2. What is concentrated sulfuric acid used for in this experiment? What are the hazards of working with concentrated sulfuric acid?
3. Calculate (a) the molar mass of salicylic acid and acetic anhydride and (b) the number of moles of each that will be used in this experiment. Note: The density of acetic anhydride is 1.08 g/mL.
4. Define the term limiting reactant. Complete the following statement: The maximum number of moles of aspirin that can be obtained in this experiment is equal to the number of moles of _____________________ used.
5. Determine the chemical formula of acetylsalicylic acid and calculate its molar mass.

Safety Precautions

Concentrated sulfuric acid is severely corrosive to eyes, skin and body tissue. Notify the teacher immediately in the event of a spill. Acetic anhydride is a corrosive liquid and the vapors are highly irritating. The liquid is flammable and a strong lachrymator—contact with the liquid will cause severe eye irritation. Work with acetic anhydride in the hood or in a well-ventilated lab only. Do not inhale the vapors. Salicylic acid is moderately toxic by ingestion. Avoid contact of all chemicals with eyes and skin. Wear chemical-splash goggles, chemical-resistant gloves and a chemical-resistant apron. Wash hands thoroughly with soap and water before leaving the laboratory.

Procedure

1. Fill a 250-mL beaker about two-thirds full with hot tap water and add a boiling stone.
2. Place a hot plate on the base of a ring (support) stand and place the beaker on the hot plate. Heat the water to about 80 °C using a medium-high setting of the hot plate.
3. Tare (zero) a clean 50-mL Erlenmeyer flask. Place about 0.5 g of salicylic acid in the flask and measure the precise mass to 0.01 g. Record the mass of salicylic acid in the data table.
4. Take the Erlenmeyer flask to the hood where the acetic anhydride is being dispensed. Carefully add 1 mL of acetic anhydride to the flask using a graduated Beral-type pipet.
5. Using a glass eyedropper or Pasteur pipet, carefully add 2 drops of concentrated sulfuric acid to the Erlenmeyer flask.
6. Place the Erlenmeyer flask in a clamp and attach the clamp to the ring stand. Carefully lower the Erlenmeyer flask into the 80 °C water bath (see Figure 2).
   {12549_Procedure_Figure_2}
7. Heat the reaction mixture in the hot water bath for 10 minutes.
8. Half-fill a second 250-mL beaker with crushed ice and water to use as an ice bath. Obtain about 15 mL of distilled water in a small beaker or test tube and place the beaker in the ice bath to chill the water.
9. After 10 minutes, raise the clamp and carefully lift the Erlenmeyer flask out of the 80 °C water bath.
10. Allow the Erlenmeyer flask to cool, then add 3 mL of ice-cold water (from step 8) dropwise to the reaction mixture. Note: Water will react vigorously with acetic anhydride to form acetic acid. A vinegar smell may be noticed.
11. Add an additional 5–6 mL of ice-cold water to the Erlenmeyer flask and place the flask in the ice bath (step 8) to allow the aspirin to crystallize. If no crystals have formed after 5 minutes, remove the flask from the ice and scratch the sides of the flask with a stirring rod.
12. Keep the flask in the ice-water bath for 10 minutes to complete crystal formation.
13. Set up a funnel for gravity filtration as shown in Figure 3. Place a clean beaker or flask under the funnel to collect the filtrate. Wet the filter paper with a few drops of distilled water.
    {12549_Procedure_Figure_3}
14. Using a stirring rod to direct the stream of liquid, slowly pour the reaction mixture from the Erlenmeyer flask into the funnel. Gently swirl the flask to get as much of the solid as possible into the funnel with just one pour.
15. When most of the liquid has passed through the funnel, rinse any remaining crystals from the flask into the funnel with a small amount (no more than 4 mL) of ice-cold water.
16. Measure and record the mass of a clean and dry watch glass to the nearest 0.01 g. When there is no more liquid in the funnel, carefully remove the filter paper and scrape the crystals onto the preweighed watch glass. Note: If the product will be recrystallized (step 17), transfer the crystals to a clean 50-mL Erlenmeyer flask.
17. (Optional) To recrystallize the product, dissolve in 3 mL of 95% ethyl alcohol and gently heat (do not boil) the mixture on a hot plate. Add about 6 mL of distilled water to the hot solution until the solution is slightly cloudy. Cool the flask in an ice bath to obtain crystals and then repeat steps 13–16 to filter and wash the crystals.
18. Label the watch glass with your initials and allow the crystals to air dry for at least 2 hours. Measure and record the combined mass of the watch glass and aspirin in the data table.
19. Label three small test tubes A–C and add a small amount (about 20 mg) of (a) salicylic acid, (b) the reaction product and (c) crushed aspirin to the appropriate test tube.
20. Add about 2 mL of 50% ethyl alcohol to each test tube to dissolve the solids.
21. Add 3 drops of 0.1 M iron(III) chloride solution to each test tube. Record observations in the data table.
22. Follow the instructor’s directions to measure the melting point of the reaction product.
23. Dispose of the reaction product as directed by the instructor.

Student Worksheet PDF

12549_Student1.pdf