Materials Included In Kit

Additional Materials Required

Prelab Preparation

Prepare two or more synthetic pain relief mixtures, total mass of 6 g, for a class of 24 students working in pairs.

Sample A: To make a 3 g batch, measure and mix 0.3 g acetaminophen, 2.25 g acetylsalicylic acid, and 0.45 g binder (silica gel) in a 50-mL beaker. It is important to thoroughly mix the sample with a stirring rod to ensure a homogenous mixture. Provide this sample for half of the groups in the class.

Sample B: To make a 3 g batch, measure and mix 0.3 g binder (silica gel) and 2.7 g acetaminophen in a 50-mL beaker. It is important to thoroughly mix the sample with a stirring rod to ensure a homogenous mixture. Provide this sample for half of the groups in the class.

Safety Precautions

The 6 M hydrochloric acid is toxic by inhalation and ingestion. It is severely corrosive to all body tissues, especially skin and eyes. Ethyl acetate is a colorless, fragrant and flammable liquid. Handle ethyl acetate in a properly ventilated area, such as a fume hood and keep away from flames, sparks and other sources of ignition. Ethyl acetate is also slightly toxic by inhalation, ingestion, and skin absorption. Acetaminophen is harmful by ingestion and irritating to skin and eyes and mucous membranes. It is a possible sensitizer. Aspirin (acetylsalicylic acid) is toxic by ingestion. It is an allergen and irritant and may cause internal bleeding. The acetaminophen and aspirin are not sold for human consumption. Avoid contact of all chemicals with eyes and skin. Wear chemical splash goggles, chemical-resistant gloves and a chemical-resistant apron. Remind students to wash their hands thoroughly with soap and water before leaving the lab. Please follow all normal laboratory safety guidelines. Review current Safety Data Sheets for additional storage, handling and disposal information.

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 leftover pain relief mixture containing acetylsalicylic acid (aspirin), silica gel (binder), and acetaminophen may be placed in a small bag with coffee grounds and placed in the trash according to Flinn Suggested Disposal Method #26a. Solutions containing 6 M hydrochloric acid or the aspirin filtrate may be neutralized according to Flinn Suggested Disposal Method #24b. The ethyl acetate may be handled according to Flinn Suggested Disposal Method #18a. Leftover sodium bicarbonate solution may be flushed down the drain with excess water according to Flinn Suggested Disposal Method #26b.

Lab Hints

• This laboratory activity can be completed in three 50-minute class periods. It is important to allow time between the Introductory Activity and the Guided-Inquiry Activity for students to discuss and design the guided-inquiry procedures. Also, all student-designed procedures must be approved for safety before students are allowed to implement them in the lab. Prelab Questions may be completed before lab begins the first day.
• Acetaminophen is slightly soluble in ethyl acetate. Thoroughly mix the acetaminophen sample in the Introductory Activity. Using a test tube stirrer may help.
• About 6 g of synthetic pain relief mixture are needed for 24 students working in pairs. Each pair will need about 450 mg. The class test any combination of pain relief mixtures. The Prelab Preparation describes two mixtures that may be split among the groups for cooperative class studies. In order to successfully isolate aspirin, the majority of the sample should be aspirin. See Prelab Preparation for Sample A.
• Proper ventilation is required to perform this lab. The ethyl acetate has a strong, sweet odor and is volatile. See the Teacher Tips for methods to remove ethyl acetate to isolate acetaminophen.
• The recommended amount of solvent to dissolve the soluble components is 50 mL of ethyl acetate per 450 mg of pain relief mixture. After adding 50 mL of ethyl acetate to the mixture, the sample should be stirred for 5–7 minutes to ensure most or all of the aspirin and acetaminophen dissolve. It is best to use a magnetic stirrer and stir bar. The Flinn Mini Magnetic Stirrer is an excellent choice (Catalog No. AP6067).
• Students may use an extra 10 mL of ethyl acetate to rinse glassware and products during filtration to promote quantitative transfer.
• For sample pain relief mixtures containing acetylsalicylic acid, about 25–30 mL 6 M hydrochloric acid should be sufficient to precipitate and recover the solid. Place the beaker or flask in an ice bath on a stirrer for the precipitation of aspirin. Leave stirring for approximately 10 minutes. Caution: Remind students to add hydrochloric acid slowly, in small amounts, with a pipette.

Teacher Tips

• Depending on available equipment, ethyl acetate may be removed by distillation or rotary evaporation to isolate acetaminophen.

• Acetaminophen may be recrystallized and isolated by gently heating the ethyl acetate on a hot plate and adding 20–30 mL of hexanes or petroleum ether. Removing the ethyl acetate from the hot plate and placing in an ice bath may result in the acetaminophen falling out of solution. The crystals may be isolated by filtration and the remaining ethyl acetate may be handled according to Flinn Suggested Disposal Method #18a. The solvent may also be recycled for future use by distillation.

Further Extensions

Alignment to the Curriculum Framework for AP^® Chemistry

Enduring Understandings and Essential Knowledge
Chemical and physical transformations may be observed in several ways and typically involve a change in energy. (3C)
3C1: Production of heat or light, formation of a gas, and formation of a precipitate and/or a color change are possible evidences that a chemical change has occurred.

Electrostatic forces exist between molecules as well as between atoms or ions, and breaking the resultant intermolecular interactions requires energy. (5D)
5D2: At the particulate scale, chemical processes can be distinguished from physical processes because chemical bonds can be distinguished from intermolecular interactions.

Learning Objectives
3.10 The student is able to evaluate the classification of a process as a physical change, chemical change, or ambiguous change based on both macroscopic observations and the distinction between rearrangement of covalent interactions and noncovalent interactions.
5.10 The student can support the claim about whether a process is a chemical or physical change (or may be classified as both) based on whether the process involves changes in intramolecular versus intermolecular interactions.

Science Practices
1.4 The student can use representations and models to analyze situations or solve problems quantitatively and qualitatively.
4.4 The student can evaluate sources of data to answer a particular scientific question.
5.1 The student can analyze data to identify patterns or relationships.
6.1 The student can justify claims with evidence.

Answers to Prelab Questions

1. The Department of Transportation uses a mixture of sand and salt to de-ice roadways in the winter. The mixture contains 8.35 tons of salt and 6.28 tons of sand. What is the mass percent of each component in the mixture?

   mass % component = (mass of component/mass of mixture) x 100%

   {13769_PreLabAnswers_Equation_2}
   {13769_PreLabAnswers_Equation_3}
2. A bakery needs a mixture of flour and sugar to make cookies. The mixture should contain 62.5% flour and 37.5% sugar. You are in charge of ordering the components to make 275 pounds of the mixture. How many pounds of flour and sugar should be ordered?

   mass % sugar = 37.5 = (mass of sugar/275 pounds) x 100%
   mass % flour = 62.5 = (mass of flour/275 pounds) x 100%
   Solve for the mass of flour and mass of sugar needed to prepare 275 pounds of baking mixture.
   mass of flour = (62.5/100) x 275 pounds = 172 pounds
   mass of sugar = (37.5/100) x 275 pounds = 103 pounds

3. In the Introductory Activity, the solubility of the possible components in the synthetic pain relief mixture will be tested using a 10% sodium bicarbonate solution. Is this solution acidic or basic? What is the likely pH of the sodium bicarbonate solution?

   Sodium bicarbonate solution is basic, with a likely pH of 8−10.

4. Predict which component in the synthetic pain relief mixture is likely to dissolve in sodium bicarbonate solution. Explain.

   Acetylsalicylic acid will dissolve in sodium bicarbonate solution. The acidic —CO₂H side chain will be neutralized by reaction with hydroxide ions in the basic solution to form its soluble, conjugate base salt.

Sample Data

Observations for Introductory Activity

• Acetaminophen and acetylsalicylic acid dissolve in ethyl acetate with vigorous mixing. Binder does not go into solution.
• Water is not miscible with ethyl acetate. Water layer is more dense than ethyl acetate so it is at the bottom of the test tubes containing acetaminophen and acetylsalicylic acid solutions.
• Acetaminophen does not dissolve in sodium bicarbonate. Acetylsalicylic acid goes into solution with vigorous mixing.
• When acid is added to the sodium bicarbonate solution containing acetylsalicylic acid, there is a lot of bubbling and a precipitate may fall out of solution.

Guided-Inquiry Activity

Sample A: Binder (silica gel), aspirin and acetaminophen

Mass of pain relief mixture sample 0.510 g
Mass of binder 0.077 g
Mass of acetaminophen 0.0880 g
Mass of aspirin 0.154 g
Percent yield = (0.077 g + 0.0880 g + 0.154 g)/0.510 g c 100 = 62.5%

Sample B: Binder (silica gel) and acetaminophen

Mass of pain relief mixture sample 0.410 g
Mass of binder 0.0480 g
Mass of acetaminophen 0.221 g
Percent yield = [(0.0480 g + 0.221 g)/0.410 g] x 100 = 65.6%

Answers to Questions

Answers to Guided-Inquiry Discussion Questions

1. Which potential component in the synthetic pain relief mixture can be separated from the others based on the results of the solubility test with ethyl acetate? Explain.

   Both acetaminophen and acetylsalicylic acid dissolve in ethyl acetate. Silica gel does not. Therefore, the binder can be separated from the mixture using this solvent.

2. Which potential component in the synthetic pain relief mixture could be separated from the mixture using liquid–liquid extraction with sodium bicarbonate solution? Explain.

   Acetylsalicylic acid dissolves in 10% sodium bicarbonate solution while acetaminophen does not. These two components can be separated from one another after the insoluble binder was removed in the first step.

3. Explain how this component could be recovered from the resulting aqueous extract.

   Acetylsalicylic acid can be recovered from the aqueous sodium bicarbonate extract by acidifying the latter with 6 M HCl. This will convert the soluble conjugate base salt back to the parent acetylsalicylic acid, which is insoluble in water and will precipitate out as a solid.

4. Write balanced chemical equations for the extraction of the component with a base (Question 2) and the subsequent recovery of the component (Question 3).

   C₉H₈O₄ + NaHCO₃ → C₉H₇O₄Na(aq) + H₂CO₃(aq)
   C₉H₇O₄Na + HCl → C₉H₈O₄ + NaCl

5. Review the design of a separatory funnel and the following procedure for using a separatory funnel with volatile organic solvents. Explain the reasoning for each step and the precaution.

   Close the stopcock to ensure the liquid will not spill! Hold the stopper when inverting the funnel to avoid having the stopper fall out when the funnel is upside down. Open the stopcock to vent any excess pressure that might build up due to the use of a volatile organic solvent. Repeat the shaking/venting process to ensure equilibrium distribution of the organic solute(s) between or into the desired layers.

6. Which liquid will be the bottom layer in the separatory funnel? Explain.

   The aqueous sodium bicarbonate solution is more dense than ethyl acetate and will be the lower or bottom layer in the separatory funnel.

7. Which component will remain in the ethyl acetate solution after the extraction step? How can this component be recovered to determine its amount?

   Acetaminophen will remain in the ethyl acetate solution. It can be recovered by evaporating the solvent.

8. What precautions are needed when carrying out the recovery step in Question 7? Explain.

   Ethyl acetate has a volatile odor and is flammable. Evaporate or distill the solvent in a fume hood and avoid contact of the solvent with flames, sparks or other sources of ignition.

9. Draw a flow chart and outline a process for separating and recovering the components in a synthetic pain relief mixture.
   {13769_Answers_Figure_4}

Opportunities for Inquiry—Analysis of a Commercial Pain Relief Tablet

When students test a commercial pain relief tablet, the tablet should be crushed using a mortar and pestle. Upon dissolving in ethyl acetate, students will find that the pain reliever does not readily dissolve in the organic solvent. The insoluble portion may be filtered out so that students may finish the experiment. The collected yield of pain reliever may be lower due to the solubility issues of the commercial tablet.

Review Questions for AP^® Chemistry

Acetylsalicylic acid (aspirin) is prepared commercially from its parent acid, salicylic acid (structure shown in Figure 3). A solid mixture of charcoal and salicylic acid was separated by dissolving the solid in aqueous sodium hydroxide solution, filtering the mixture, and acidifying the solution to recover the salicylic acid. The following results were obtained:

1. Write a balanced chemical equation for the neutralization reaction of salicylic acid with sodium hydroxide.
   {13769_Answers_Reaction_1}
2. Calculate the percent recovery of the charcoal–salicylic acid mixture.
   {13769_Answers_Equation_3}

   Percent recovery = (0.51 g/0.52 g) x 100% = 98%

3. Determine the mass percent of (a) charcoal and (b) salicylic acid in the mixture.

   Mass percent of charcoal = (0.24 g/0.51 g) x 100% = 47%
   Mass percent of salicylic acid = (0.27 g/0.51 g) x 100% = 53%
   Note: The actual percent composition of the prepared charcoal-salicylic acid mixture was 30% charcoal, 70% salicylic acid. The percent recovery results are generally excellent, but the percent composition results consistently give higher than expected values for charcoal. This is probably due to salicylic acid trapped (adsorbed) on the charcoal, since salicylic acid by itself dissolves completely in control tests under the process conditions.

4. Label each of the following as a physical or chemical change. (a) Salicylic acid dissolves in the sodium hydroxide solution. (b) The mixture is filtered to separate the charcoal. (c) The filtrate is acidified to precipitate the salicylic acid.
   1. Salicylic acid dissolves in the sodium hydroxide solution.

      Chemical change

   2. The mixture is filtered to separate the charcoal.

      Physical change

   3. The filtrate is acidified to precipitate the salicylic acid.

      Chemical change

5. Salicylic acid may be crystallized from hot water by dissolving the solid in a minimum amount of boiling water and then cooling the mixture to room temperature. Is this a physical or a chemical change?

   Physical change—the composition of salicylic acid is not altered when it dissolves in hot water and then crystallizes at room temperature.

References

AP^® Chemistry Guided-Inquiry Experiments: Applying the Science Practices; The College Board: New York, NY, 2013.

Introduction

Most over-the-counter drugs consist of mixtures, or physical blends, of active drug ingredient(s) and binders. The main characteristic of a mixture is that it has a variable composition—the components of the mixture may be present or mixed in varying proportions. The substances in a mixture retain their distinctive chemical identities, as well as some of their unique physical properties. The purpose of this investigation is to study the physical properties of ingredients in a synthetic pain relief mixture and determine its percent composition.

Concepts

• Mixture vs. pure substance
• Physical and chemical changes
• Homogenous vs. heterogeneous
• Over-the-counter drugs
• Separation of a mixture
• Mass percent composition

Background

A mixture is a combination of two or more pure substances that retain their separate chemical identities and properties. Since the amount of each substance making up a mixture can be changed, the physical properties of a mixture will depend on its composition. Pharmaceutical companies manufacture different over-the-counter drug formulations with varying amounts of active drug ingredients, binders and other inert materials. Binders are added to drug mixtures to form the pill, hold it together, and control release of the drug in the body at varying rates. Pain relievers usually contain starch or silica gel as the binder. Two common active drug ingredients in pain relievers are aspirin and acetaminophen. When not combined into pill form, aspirin and acetominophen, like all pure substances, have characteristic physical properties. Examples of physical properties that can be used to separate pure substances from a mixture and identify them include solubility, conductivity, magnetism, density, boiling point and melting point.

By taking advantage of the unique physical properties of individual components within a mixture, it is possible to separate a mixture into its components. For example, if one component in a mixture of two solids dissolves in water while the second component does not, the substances can be separated by adding water to the mixture and then filtering the residue. Subjecting the mixture to a physical change in this way would change the ratio of components in the mixture. This leads to one of the definitions of a mixture—a substance whose composition can be altered by a physical change. Physical changes that can be used to separate the components of a mixture include filtration, evaporation, crystallization, distillation and extraction.

Extraction is a convenient method for isolating and separating organic substances. Solid−liquid extraction is a familiar technique used to prepare beverages such as coffee or tea—organic compounds, including caffeine and various flavor ingredients, are extracted using hot water. In liquid−liquid extraction, a substance that is at least partially soluble in two immiscible liquids can be transferred from one liquid to the other. This is usually done in a separatory funnel by shaking a solution containing two or more solutes with a second, immiscible solvent that will dissolve only one of the solutes. The liquids separate into two layers in the separatory funnel, with the more dense liquid in the bottom layer and the less dense liquid in the top layer.

The structures of acetylsalicylic acid (aspirin) and acetaminophen are shown in Figure 1. Acetylsalicylic acid is an organic carboxylic acid (—CO₂H group) that also contains an ester functional group (CH₃CO₂—) as a side chain on the benzene ring. Acetaminophen has two primary functional groups, a hydroxyl group on the benzene ring, as well as an amide side chain (CH₃CON—).

Carboxylic acids that do not dissolve in water can be extracted from an organic solvent with an aqueous solution containing an inorganic base, such as dilute sodium hydroxide. The base converts the carboxylic acid to its conjugate base, a sodium salt that is soluble in water. An example of this process is shown in Equation 1 as the neutralization reaction of benzoic acid with sodium hydroxide. Mass percent composition is a convenient way to express the actual composition of a mixture in terms of the amount of each component. The mass percentage of each component in a mixture is calculated as follows:

mass % of component = (mass of component/total mass of mixture) x 100%

In order to determine the percent composition of a mixture, it is necessary to separate the components quantitatively—ideally, without loss of material—and then measure the mass of each recovered component. The sum of the mass percentage of all components in a mixture equals 100%.

A flow chart is often used to illustrate the steps involved in separating a mixture. In a flow chart, the substances in the mixture are listed inside boxes that are connected by arrows. The actual physical steps that must be carried out to separate the components are listed next to the arrows. Imagine a sample of seawater that has been collected at the beach. There is a liquid layer, consisting of dissolved salt in water, and solid sand particles suspended in the liquid. Figure 2 shows a simple method for separating and determining the amount of each component in a sample of seawater.

Experiment Overview

The purpose of this advanced inquiry investigation is to separate a mixture that represents a pain reliever. The mixture may contain binder, acetaminophen and acetylsalicylic acid in varying amounts. The lab begins with an introductory activity to test the solubility of each possible component in an organic solvent, ethyl acetate, and in a basic aqueous solution of sodium bicarbonate. The results provide a model for the guided-inquiry design of a flow chart that will map the procedure used to separate components in a mixture and determine percent composition. Optional extension activities include varying the amounts of individual components in the synthetic mixtures and analyzing consumer samples. Students may also measure the melting points of the isolated components, acetylsalicylic acid and acetaminophen, to confirm their identity.

Materials

Prelab Questions

1. The Department of Transportation uses a mixture of sand and salt to de-ice roadways in the winter. The mixture contains 8.35 tons of salt and 6.28 tons of sand. What is the mass percent of each component in the mixture?
2. A bakery needs a mixture of flour and sugar to make cookies. The mixture should contain 62.5% flour and 37.5% sugar. How many pounds of flour and sugar should be ordered to make 275 pounds of the mixture?
3. In the Introductory Activity, the solubility of the possible components in the synthetic pain relief mixture will be tested using a 10% sodium bicarbonate solution. Is this solution acidic or basic? What is the likely pH of the sodium bicarbonate solution?
4. Predict which component in the synthetic pain relief mixture is likely to dissolve in sodium bicarbonate solution. Explain.

Safety Precautions

The 6 M hydrochloric acid is toxic by inhalation and ingestion. It is severely corrosive to all body tissues, especially skin and eyes. Ethyl acetate is a colorless, fragrant and flammable liquid. Handle ethyl acetate in a properly ventilated area such as a fume hood and keep away from flames, sparks and other sources of ignition. Ethyl acetate is also slightly toxic by inhalation, ingestion, and skin absorption. Acetaminophen is harmful by ingestion and irritating to skin and eyes and mucous membranes. It is a possible sensitizer. Aspirin (acetylsalicylic acid) is toxic by ingestion. It is an allergen and irritant and may cause internal bleeding. The acetaminophen and aspirin are not sold for human consumption. 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 lab. Please follow all normal laboratory safety guidelines.

Procedure

Introductory Activity

1. Obtain small, pea-size amounts (1–2 mg each) of acetylsalicylic acid, acetaminophen, and silica gel in separate labeled test tubes.
2. Add 1 mL of ethyl acetate to each test tube and record observations.
3. Add 1 mL of deionized or distilled water to each test tube. Record all observations.
4. Obtain additional 1–2 mg samples of acetylsalicylic acid and acetaminophen in separate clean and labeled test tubes. Add 1 mL of 10% sodium bicarbonate to each test tube and record observations.
5. Slowly and carefully add about 1–2 mL of 6 M hydrochloric acid drop-wise to the test tube mixtures from step 4. Record observations. Place test tubes in an ice bath for 5 minutes and record any additional observations.

Guided-Inquiry Design and Procedure

Form a working group with other students and discuss the following questions.

1. Which potential component in the synthetic pain relief mixture can be separated from the others based on the results of the solubility test with ethyl acetate? Explain.
2. Which potential component in the synthetic pain relief mixture could be separated from the mixture using liquid–liquid extraction with sodium bicarbonate solution? Explain.
3. Explain how this component could be recovered from the resulting aqueous extract.
4. Write balanced chemical equations for the extraction of the component with a base (Question 2) and the subsequent recovery of the component (Question 3).
5. Review the design of a separatory funnel and the following procedure for using a separatory funnel with volatile organic solvents. Explain the reasoning for each step and the precaution, which is shown in italics.
   • Place the separatory funnel in a ring clamp that is attached to a support stand. Make sure the stopcock is closed and pour the organic solvent (or solution) into the funnel.
   • Add water or another aqueous solution to the solvent in the funnel and place the stopper in the top of the funnel.
   • Remove the funnel from the ring clamp and carefully invert it, making sure to hold the stopper with one hand. Immediately after inverting the separatory funnel, open the stopcock
   • Close the stopcock and gently shake the funnel once to mix the aqueous and organic layers. Keep the separatory funnel inverted, and make sure to hold on to the stopper!
   • Open and close the stopcock. Repeat the shaking/venting process a few times.
6. Which liquid will be the bottom layer in the separatory funnel? Explain.
7. Which component will remain in the ethyl acetate solution after the extraction step? How can this component be recovered to determine its amount?
8. What precautions are needed when carrying out the recovery step in Question 7? Explain.
9. Draw a flow chart and outline a process for separating and recovering the components in a synthetic pain relief mixture.
10. Write a detailed, step-by-step procedure for separating the components and determining the percent composition of the mixture. Include the safety precautions, (i.e., Add the hydrochloric acid slowly and carefully with a pipet) and specify the glassware and equipment you will need, the amounts of any solvents and additional chemicals, and any observations or measurements you will need to make. Note: Use about 450 mg of the synthetic pain relief mixture.
11. Review additional variables that may affect the reproducibility or accuracy of the experiment and how these variables will be controlled.
12. Carry out the experiment and record results in an appropriate data table.

Analyze the Results
Calculate the mass percent composition of all the components in the synthetic pain relief mixture.

Opportunities for Inquiry

Analysis of a Commercial Pain Relief Tablet
The identities of the active ingredients recovered from the synthetic pain relief mixture may be verified by measuring their melting points. The solids may also be recrystallized by dissolving in a minimum amount of hot ethyl acetate and cooling the resulting solutions in an ice bath. The melting points of the pure solids are available in their respective Safety Data Sheets (SDSs) and also in literature references, such as The Merck Index or the Handbook of Chemistry and Physics. As an extension to this advanced inquiry lab, any combination of synthetic pain relief mixture may be provided. Students may also separate the components and analyze commercial pain relief medications, such as Tylenol^® and Excedrin^®. Observations, conclusions and cooperative class discussions are encouraged.

Student Worksheet PDF

13769_Student1.pdf