LAB 6 - SYNTHESIS AND ANALYSIS OF ASPRIN
- Page ID
- 506283
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)The purpose of this experiment is to:
- Synthesize aspirin by the reaction of salicylic acid with acetic anhydride.
- Test the purity of the prepared sample and compare it to the commercial Aspirin.
- Analyze the product by determining its melting point, conducting thin-layer chromatography (TLC), and performing infrared spectroscopy.
INTRODUCTION
Acetylsalicylic acid, commonly known as Aspirin, reduces pain, fever, and inflammation while also lowering the risk of heart attacks and strokes. It is among the most widely used medications. Its effectiveness arises from its analgesic, antipyretic, and anti-inflammatory properties. In the small intestine, acetylsalicylic acid breaks down into salicylic acid, which is then absorbed into the bloodstream. Salicylic acid can irritate the lining of the mouth, esophagus, and stomach, potentially leading to hemorrhaging due to its phenolic and carboxylic acid groups. The Bayer company discovered that the ester of salicylic acid (acetylsalicylic acid) is less irritating than the original salicylic acid. However, it still presents side effects, such as stomach lining irritation and hemorrhaging; to reduce these effects, commercial Aspirin often includes coatings and buffering agents.
SYNTHESIS OF ASPIRIN (Acetylsalicylic Acid)
Aspirin is produced by combining salicylic acid with excess acetic anhydride (the o-acetylation of salicylic acid) and a small amount of a strong acid catalyst, which accelerates the reaction. A strong acid catalyst, such as 85% phosphoric acid or concentrated sulfuric acid, promotes the esterification reaction, resulting in the formation of white crystals. Water is then added to remove the surplus acetic anhydride. In summary, the reaction involves a carboxylic acid and an acid anhydride, which together form an ester.
Aspirin has very low solubility in cold water and is utilized for precipitation. Any unreacted salicylic acid is considered an impurity due to its similarly low solubility in cold water. Dissolved unreacted substances, such as acetic anhydride and acetic acid, remain in the water. Vacuum filtration effectively separates the crystalline aspirin from the reaction mixture, excluding unreacted salicylic acid. The synthesized aspirin should be evaluated for the presence of contaminating salicylic acid.
The purity of crude and recrystallized aspirin can be determined using iron (III) chloride (FeCl3). FeCl3 interacts with phenols (alcohol groups attached to aromatic rings) to produce violet-colored complexes. While salicylic acid contains the phenol functional group, aspirin does not; therefore, the greater the contamination of salicylic acid in your aspirin, the darker the color that will appear with FeCl3. Pure or recrystallized aspirin should not form violet-colored complexes with iron (III) chloride (FeCl3). Any contaminating salicylic acid in the product will react with FeCl3. Additionally, you will measure the melting point of your product sample, perform Thin-Layer Chromatography (TLC), conduct melting point analysis, and take an infrared spectrum to analyze and test the relative purity of your sample.
- Always wear your safety goggles during the experiment.
- Wear gloves, particularly when working with concentrated acid or phosphoric acid.
- Exercise caution when handling phosphoric acid and acetic anhydride.
- Keep this compound concealed and avoid inhaling the vapors.
- Acetic anhydride irritates the nose and sinuses. Keep the acetic anhydride bottle capped after use.
- The aspirin synthesized in this lab is not pure enough for internal use! Please do not ingest the aspirin!
- Be especially careful when handling phosphoric acid and acetic anhydride.
- All waste must be placed in the designated organic waste containers located in the fume hood.
- Thoroughly clean your work area when finished and return all equipment and chemicals to their designated places.
- Please ensure you wash your hands before leaving.
CHEMICALS AND EQUIPMENT NEEDED
| Chemicals | Equipment | Equipment |
|---|---|---|
| Ethanol | Spatula | Stirring rod |
| Salicylic acid | Ring Stand and Ring Clamp | Thermometer |
| Acetic anhydride | 10-mL graduated cylinder | Watch glass |
| Iron (III) chloride solution 3% | 600-mL beaker hot plate | Filter paper |
| 85% phosphoric acid (H3PO4) or Concentrated Sulfuric Acid (Instructor’s choice) | 400-mL beaker | Capillary tube |
| -- | Büchner filtration apparatus | Dropper |
| Ice | 125-mL Erlenmeyer flask | Latex tubing/rubber band |
EXPERIMENTAL PROCEDURE
Part A: Synthesis of Aspirin
1. Measure 2.0 g of salicylic acid and place it in a 125.0 mL Erlenmeyer flask.
2. This reaction must be conducted in the fume hood. Move the flask to the fume hood and add acetic anhydride and concentrated acid inside the hood.
a) In the fume hood, measure 5.0 mL of acetic anhydride using a 10.0 mL graduated cylinder. Pour the contents of the cylinder into the flask and swirl the mixture (keep it under the hood, as it now contains acetic anhydride, which has very irritating vapors).
b) Add five drops of concentrated sulfuric acid or 85% phosphoric acid as a catalyst (your instructor will inform you which one; choose only one).
c) Utilize the provided dropper. Concentrated sulfuric acid and phosphoric acid are extremely corrosive. Add only one type of acid, as indicated by your instructor, which may differ.
3. Swirl the reactants to mix them, add a stir bar, and while stirring, gently bring the mixture to a boil on a hot plate inside a fume hood. Heat the reactant mixture for 8 to 10 minutes, stirring until all the solids have dissolved.
4. Avoid vigorous boiling or temperatures that are too high or too low. Alternatively, heat the mixture for 15.0 minutes by placing the flask in a boiling water bath. When using a boiling water bath, securely clamp the flask to keep its opening above the water line. Ensure your instructor approves your setup.
5. While the reaction heats up, take a 100.0 mL beaker, fill it with approximately 75.0 to 80.0 mL of distilled water, and place it in an ice bath.
6. Remove the flask from the hot plate or water bath, and swirl in 20.0 mL of deionized ice water. This water will react with any excess acetic anhydride, turning it into acetic acid.
7. As the flask cools, aspirin crystals will start to form. When you notice the formation of crystals, place the flask in an ice bath for 10-15 minutes. If acetylsalicylic acid does not begin to crystallize, gently scratch the walls of the flask with a glass rod.
8. Collect the crude solid aspirin product by vacuum filtration using a Buchner funnel. Rinse the product with three to four 10.0 mL portions of cold distilled water to remove any acetic acid from the crystals. Allow the crystals to air dry, and then weigh the dry crude aspirin.
9. Reserve a small quantity of crude aspirin for melting point, IR, and TLC analysis, then recrystallize the crude aspirin using ethanol. Dry the purified crystals.
10. Store the dried, purified crystals according to the instructor's guidelines for subsequent analysis and testing of the synthesized Aspirin sample's purity in part B of the experiment.
Part B: Tests
- To evaluate the purity of the prepared sample, assess the product using the tests listed below, and compare the results.
- Your instructor may require you to evaluate your product using all the available tests, or they may select a few from those options.
- i) Melting point range of the aspirin sample (crude and recrystallized); ii) pH test; iii) iron (III) chloride (FeCl3) test; iv) thin-layer chromatography (TLC); v) IR spectrum of the product (crude and recrystallized) to confirm its structure. (Follow your instructor's directions; they may ask you to perform all or some of these tests.)
i) Melting point of the Aspirin sample
a) Use a spatula to transfer a small amount of recrystallized aspirin to a weighing boat or watch glass. If the aspirin is not finely powdered, grind it with a mortar and pestle until it becomes a fine powder.
b) Place the recrystallized aspirin in a capillary tube approximately 3 mm in diameter, ensuring it settles at the bottom of the tube.
c) Insert the capillary tube into the melting point apparatus and record the melting range of the recrystallized aspirin.
d) Note: Your instructor may offer extra guidance or show how to fill the capillary tube and use the melting point apparatus.
e) The melting point range is the temperature at which the liquid first appears until the solid has fully disappeared. Document your melting point range.
f) As your instructor indicated, dispose of the capillary tube and place the excess acid into the container designated for nonhalogenated organic waste.
g) Repeat steps 1 to 5 using the crude aspirin (synthesized aspirin).
pH Test and Iron (III) chloride (FeCl3) Test
a) Label five small test tubes A through E.
b) In test tube A, add a few crystals of salicylic acid.
c) In test tube B, add a few crystals of crude aspirin; in test tube C, add a few crystals of recrystallized aspirin, and in test tube D, add commercial aspirin (non-enteric coated). Please do not add any crystals to the fifth tube, as it will serve as your blank.
d) Add 1 mL of ethanol and 4.0 mL of distilled water to test tubes A-E, then mix the solution with a stirring rod. Be sure to clean the stir rod before mixing the next test tube.
ii) pH Test
(a) Touch the pH paper to the stir rod after dipping it into each solution. Ensure that you clean the stir rod before dipping it into the next test tube.
(b) Compare the color of the pH paper to the chart, then record the pH values of the solutions in the data table.
(c) Do not discard the solutions; we will use them to test with iron (III) chloride (FeCl3).
iii) Iron (III) chloride (FeCl3) Test
a) Add five drops of 1% FeCl3 solution to test tubes A through E.
b) Mix the solution with a stirring rod. Ensure that you clean the stir rod before mixing the next test tube.
c) Document your observations in the data table and respond to the questions.
iv) Thin Layer Chromatography (TLC)
Procedure to Analyze Aspirin Using TLC
Preparation of TLC Plate:
-Obtain a TLC plate coated with a thin layer of silica gel.
-Draw a light pencil line about 1 cm from the bottom of the plate. This will be the baseline where you will spot your samples.
Preparation of Samples:
-To create a concentrated solution, dissolve a small amount of aspirin in an appropriate solvent, such as ethanol.
-Prepare a reference solution of pure salicylic acid and acetylsalicylic acid (aspirin) in the same solvent.
Spotting the TLC Plate:
Using a capillary tube or a TLC spotter, apply small, well-separated spots of the aspirin salicylic acid solution and pure aspirin solution along the baseline of the TLC solution plate.
Developing the TLC Plate:
-Place the TLC plate in a developing chamber containing a small amount of solvent, such as a mixture of ethyl acetate and hexane. Keep the solvent level below the baseline.
-Cover the chamber and allow the solvent to rise on the plate through capillary action. This process is referred to as developing the plate.
-Once the solvent front is approximately 1 cm from the top of the plate, remove the plate and mark the solvent front with a pencil.
Visualization:
-Let the plate dry.
-Visualize the spots with UV light or in an iodine chamber. The spots will appear as dark marks against a fluorescent background when seen under UV light.
Analysis of TLC Results
Calculate Rf Values:
-Determine the distance each spot moves from the baseline. Also, determine the distance the solvent front moves from the baseline.
-Take the image/picture of your chromatograph paper once you have developed it to include with your report.
-Calculate the Rf value for each spot using the formula:
Rf = Distance traveled by the compound/Distance traveled by the solvent front
Compare Rf Values:
Compare the Rf values of the spots from the aspirin sample with those of the reference compounds (salicylic acid and pure aspirin). Pure aspirin should display a specific Rf value, and any additional spots with different Rf values may indicate impurities or unreacted starting materials.
Interpretation:
If the aspirin sample shows a single spot with the same Rf value as the pure aspirin reference, it indicates high purity. Multiple spots or spots with different Rf values suggest the presence of impurities or incomplete reactions. By following this procedure, you can effectively analyze the purity and composition of aspirin using thin-layer chromatography (TLC).
v) IR Spectrum
Procedure for obtaining an IR spectrum of aspirin to confirm its structure.
a) Turn on the FT-IR spectrometer and allow it to warm up.
b) Ensure the instrument is calibrated using standard reference material.
c) Grind a small amount of recrystallized aspirin into a fine powder. Mix it with potassium bromide (KBr) in a 1:100 ratio (aspirin: KBr). Press the mixture into a thin, transparent pellet using a pellet press.
d) Place the prepared sample pellet in the sample holder of the IR spectrometer.
e) Set the spectrometer to scan the sample over the desired wavelength range (typically 4000-400 cm-¹).
f) Start the scan and record the spectrum. The instrument will measure the sample's transmittance at each wavelength.
g) Analyze the obtained IR spectrum. Identify the characteristic peaks corresponding to different functional groups in the aspirin molecule.
h) Confirming the Structure of Aspirin
i) To confirm the structure of aspirin using its IR spectrum, look for the characteristic peaks and record them in the data table.
PRE-LAB QUESTIONS
Name ____________________________________
1. Write the balanced equation for the reaction.
2. Why is an acid catalyst used in this reaction?
3. What is the theoretical yield of aspirin for this reaction?
DATA AND OBSERVATIONS
Part A: Synthesis of Aspirin
Mass of Salicylic Acid:
Volume of Acetic Anhydride:
Theoretical yield of aspirin (show your calculations):
Mass of Crude Aspirin:
Mass of Recrystallized Aspirin:
Percent Yield (show your work):
Part B: Tests
i) Melting Point of Samples (Crude and recrystallized):
Melting Point of a Crude Aspirin Sample:
Melting Point of the Recrystallized Aspirin Sample:
ii) pH Test:
Test Tube No. |
Sample |
pH Test |
|---|---|---|
|
Test Tube A |
Containing Salicylic Acid Crystals |
|
|
Test Tube B |
Containing Crude Aspirin |
|
|
Test Tube C |
Containing Recrystallized Aspirin Crystals |
|
|
Test Tube D |
Containing Commercial Aspirin |
|
|
Test Tube E |
Blank |
iii) Test with Iron (III) chloride (FeCl3):
Test Tube No. |
Sample |
Observations with FeCl3 |
|---|---|---|
|
Test Tube A |
Containing Salicylic Acid Crystals |
|
|
Test Tube B |
Containing Crude Aspirin |
|
|
Test Tube C |
Containing Recrystallized Aspirin Crystals |
|
|
Test Tube D |
Containing Commercial Aspirin |
|
|
Test Tube E |
Blank |
iv) Thin Layer Chromatography (TLC):
Test Tube No. |
Sample |
Observation and Rf Value (show your Calculation) |
|---|---|---|
|
Test Tube A |
Containing Salicylic Acid Crystals |
|
|
Test Tube B |
Containing Crude Aspirin |
|
|
Test Tube C |
Containing Recrystallized Aspirin Crystals |
|
|
Test Tube D |
Containing Commercial Aspirin |
|
|
Test Tube E |
Blank |
Calculations:
v) IR Spectrum:
Obtain an IR spectrum of the product. Attach an image of your IR spectrum along with your remote and identify the distinguishing peaks (both crude and recrystallized) to confirm its structure. Analyze the IR spectrum: what are the key absorption bands that confirm aspirin's structure?
POST-LAB QUESTIONS
1) Discuss any possible sources of experimental error in the synthesis and suggest potential ways to increase the percent yield.
2) Explain the melting point data. Does it align with the expected range for pure aspirin?
3) Why is the aspirin washed with cold water?
4) According to your results from the ferric chloride test, what can you say about the purity of your aspirin? Be as specific as possible.
Please click here to access the Pre-Lab, Data Tables, and Post-Lab in Word or PDF format. Complete them and upload the lab report according to your instructor's instructions.