Skip to main content
Chemistry LibreTexts

Synthesis and Recrystallization of Aspirin

  • Page ID
    424575
  • \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)

    \( \newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\)

    ( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\)

    \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)

    \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\)

    \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)

    \( \newcommand{\Span}{\mathrm{span}}\)

    \( \newcommand{\id}{\mathrm{id}}\)

    \( \newcommand{\Span}{\mathrm{span}}\)

    \( \newcommand{\kernel}{\mathrm{null}\,}\)

    \( \newcommand{\range}{\mathrm{range}\,}\)

    \( \newcommand{\RealPart}{\mathrm{Re}}\)

    \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)

    \( \newcommand{\Argument}{\mathrm{Arg}}\)

    \( \newcommand{\norm}[1]{\| #1 \|}\)

    \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)

    \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\AA}{\unicode[.8,0]{x212B}}\)

    \( \newcommand{\vectorA}[1]{\vec{#1}}      % arrow\)

    \( \newcommand{\vectorAt}[1]{\vec{\text{#1}}}      % arrow\)

    \( \newcommand{\vectorB}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vectorC}[1]{\textbf{#1}} \)

    \( \newcommand{\vectorD}[1]{\overrightarrow{#1}} \)

    \( \newcommand{\vectorDt}[1]{\overrightarrow{\text{#1}}} \)

    \( \newcommand{\vectE}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash{\mathbf {#1}}}} \)

    \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)

    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. 

    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)

     

    aspirin_reaction_scheme.png

    Reaction scheme 1: Salicylic acid and acetic acid anhydride react to form aspirin and acetic acid, catalyzed by sulfuric acid

     

    hydrolysis_acetic_anhydride.png

    Reaction scheme 2: Acetic anhydride reacts with water to form two molecules of acetic acid

    1. Set up a hot water bath (400 mL beaker filled to 100 mL with water) on a hotplate and adjust the water temperature to about 75 °C (see photo below - after the water reaches the desired temperature, set the heating dial to the minimal value as in the photo, or turn it off if the temperature is too high).
    2. Place 2.0 g (about 15 mmol) of salicylic acid in a 125-mL Erlenmeyer flask.
    3. Under the hood, add 5 mL (5.4 g, about 50 mmol) of acetic anhydride, followed by 5 drops of conc. H2SO4 (use the provided dropper, H2SO4 is highly corrosive) and swirl the flask gently most of the salicylic acid dissolves (the remainder will dissolve as you heat the reaction).
    4. Heat the flask gently in the hot water bath for 15 minutes to run reaction scheme 1 shown above (if you overheat, you get side products; if you don't heat, you get less of the desired product). The flask will float on the hot water at an angle, which is fine.
    5. Allow the flask to cool until you can touch the bottom. Under the hood, add 10 mL of water to react with the excess of acetic anhydride (see reaction scheme below). Bring the flask back to your bench.
    6. If acetylsalicylic acid does not begin to crystallize out, scratch the inside walls of the flask with a glass rod or add a seed crystal. Cool the mixture slightly in an ice bath until crystallization is completed. If the mixture appears milky or there is a whitish oil on the bottom, consult your instructor. The product will appear as a solid mass when crystallization is completed. Then, add 50 mL of water and cool the mixture in an ice bath. Do not add the water until crystal formation is complete.
    7. Vacuum filter the product using wetted round filter paper in a Buchner funnel (see photo below for setup). The total amount will not fit in the funnel. Swirl before you pour to get the chunks transferred, and use the glass rod with rubber policeman to transfer any remaining solids.
    8. 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 (no more liquid dripping from the funnel. Place the crude solid on a pre-weighed watch glass and record the mass of the solid. Place a small amount on a watch glass to dry. We will use a portion for the ferric chloride test, and a small amount to measure the melting point next week.

    aspirin setup.PNG

    Panel A: Water bath setup (instead of clamping the Erlenmeyer, you can also carefully place it without clamping). Panel B: filtration setup. For troubleshooting tips, see center.

    Recrystallization of aspirin

    1. Place the remaining crude product into a clean 125 mL Erlenmeyer flask. Add ethanol (about 1 mL for every gram of crude product) and warm in the water bath at about 50°C. If lots of solid remains, add more ethanol in 1-mL portions. Once most or all is dissolved, add 40 mL water. Cool down to room temperature and make sure crystals form (you can use the scratching method or add a tiny crystal of crude product if crystals don't form on their own) before you cool down further in an ice bath. If you get a milky liquid instead of solid crystals, consult your instructor.
    2. Vacuum filter the product using a Buchner funnel.
    3. 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 recrystallized product for the presence of unreacted salicylic acid using the ferric chloride test (procedure below) and keep some for measuring the melting point next week.
    4. Fill out the result sheet.
    5. Record the mass and calculate the relative yield in percent.
    6. Keep the product in your drawer to dry. We will determine the melting point next week.

    Ferric chloride test for salicylic acid

    Phenols are compounds that have a hydroxyl (-OH) group attached directly to a benzene ring. Salicylic acid is a phenol while aspirin is not. Formation of an iron-phenol complex with Fe(lll) gives a definite color ranging from red to violet, depending upon the particular phenol present. Add 10 drops of aqueous 1% ferric chloride solution to a test tube containing a few crystals of the compound to be tested dissolved in 5 mL water and note the color. Do this test with 1. salicylic acid, 2. your crude product and 3. your recrystallized product.

    Melting point determination (will be done next week)

    This is done in batches of three samples (crude product, recrystallized product, store-bought product). The idea is to start with low temperature, and watch the sample visually as you ramp up the temperature, writing down the temperature at which each sample melts:

    1. Make sure the temperature of the melting point apparatus is below 70 °C.
    2. Place your samples in the melting point apparatus. Make sure you can see the solids.
    3. Turn on the heater. Watch the samples and the temperature (two people).
    4. Once the last sample is melted, turn off the heater.
    5. Make sure the heater is turned off to allow the next group of measurements to proceed as soon as possible.

    Contributors and Attributions


    Synthesis and Recrystallization of Aspirin is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

    • Was this article helpful?