12.14: Synthesis of Aspirin (Experiment)
- Page ID
- 531845
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Over history, many compounds obtained from nature have been used to cure ills or to produce an effect in humans. These natural products have been obtained from plants, minerals, and animals. In addition, various transformations of these and other compounds have led to even more medically useful compounds. During this semester, you will have an opportunity to isolate some pharmacologically active natural products and to synthesize other active compounds from suitable starting materials.
Analgesics are compounds used to reduce pain, antipyretics are compounds used to reduce fever. One popular drug that does both is aspirin. The Merck Index, which is an encyclopedia of chemicals, drugs and biologicals, lists the following information under aspirin: acetylsalicylic acid; monoclinic tablets or needle-like crystals; mp 135 °C (rapid heating); is odorless, but in moist air it is gradually hydrolyzed into salicylic and acetic acids; one gram dissolves in 300 mL of water at 25 °C, in 100 mL of water at 37 °C, in 5 mL alcohol, in 17 mL chloroform.
SYNTHESIS OF ASPIRIN (acetylsalicylic acid)
- Place 2.0 g (0.015 mole) of salicylic acid in a 125-mL Erlenmeyer flask.
- Add 5 mL (0.05 mole) of acetic anhydride, followed by 5 drops of conc. H2SO4 (use a dropper, H2SO4 is highly corrosive) and swirl the flask gently until the salicylic acid dissolves.
- Heat the flask gently on the steam bath for at least 10 minutes. (You can start with the heat set on high. Once you see it's steamy, turn it down. Keep it hot but not boiling.)
- Allow the flask to cool to room temperature. If acetylsalicylic acid does not begin to crystallize out, scratch the walls of the flask with a glass rod. Cool the mixture slightly in an ice bath until crystallization is completed. The product will appear as a solid mass when crystallization is completed.
- Add 50 mL of water and cool the mixture in an ice bath. Do not add the water until crystal formation is complete.
- Vacuum filter the product using a Buchner funnel. You can use some of the filtrate to rinse the Erlenmeyer flask if necessary.
- Rinse the crystals several times with small portions (5 mL) of cold water and air dry the crystals on a Buchner funnel by suction until the crystals appear to be free of solvent. Test this crude product for the presence of unreacted salicylic acid using the ferric chloride test.
FeCl3 TEST FOR SALICYLIC ACID
Test your sample, commercial aspirin, and pure salicylic acid. Iron(III) chloride will turn a compound with phenol purple. Aspirin should not have phenol but salicylic acid does.
- Test tube 1: Crush a commercial aspirin table in a mortar and pestle and then add a small amount (spatula tip or a few crystals) to a test tube.
- Test tube 2: Add a small amount of salicylic acid to a test tube.
- Test tube 3: Add a small amount of your reaction product, which should be aspirin.
Add about 5 mL water and 10 drops of aqueous 0.2M FeCl3 solution to each test tube. Swirl the test tubes to mix.
Formation of an iron-phenol complex with Fe(lll) gives a definite color ranging from red to violet, depending upon the particular phenol present.
Questions
- The graphic on the left shows the structure of phenol. Draw salicylic acid (shown above) in your notebook and circle the the phenol portion of the structure.
- Looking at the structure of salicylic acid, what does the CO2H refer to?
- Does aspirin have a phenol group?
- Which of the three test tubes should give a positive result (turn color) in the ferric chloride test? Which should not?
- Was your aspirin pure? How do you know?
Citations
Phenol image: National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 996, Phenol. Retrieved July 23, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/Phenol.
Contributors and Attributions
James Chickos, David Garin, and Valerian D'Souza. University of Missouri–St. Louis; Chemistry)