CHM 1330, Winter 2023 Ingalls, January 2023

Synthesis of Aspirin
Adapted from John Mouser, PhD.
Objectives:
- Synthesize and isolate Aspirin from salicylic acid
- Use laboratory techniques such as hot water baths and vacuum filtration
- Calculate theoretical verses actual percent yield.

Introduction:

In this experiment we will synthesize a well-known over-the-counter drug, Aspirin, from salicylic acid. Salicylic
acid is a natural product, meaning it can be obtained from a plant or animal source. Salicylic acid historically was
extracted from plants. Not only is it a precursor to Aspirin, but it is also used in the cosmetic industry as a
chemical exfoliant.

In this reaction, salicylic acid is combined with acetic anhydride in the presence of a strong inorganic acid (1).

O CH3

OH

O O O O
85% H3PO4
OH + + (1)
H 3C O CH3 OH HO CH3

Salicylic Acid Acetic Anhydride Aspirin O Acetic Acid

The reaction is catalyzed by the presence of a concentrated strong acid, Phosphoric Acid. Additionally, the
byproduct of the reaction is a carboxylic acid known as acetic acid or vinegar.

Acetic anhydride is added in excess in this reaction. To remove the excess acetic anhydride, water is added to
the reaction flask in step 3. The addition of the water rapidly hydrolyzes the remaining acetic anhydride to
create 2 molecules of acetic acid (2).

O O O
H 2O
2 (2)
H 3C O CH3 HO CH3

Acetic Anhydride Acetic Acid

After all the acetic anhydride reacts, the newly formed Aspirin can precipitate from the acidic water solution. If
no crystals participate, the technique of “scratching” can be used. Scratching is gently rubbing the end of a glass
stirring rod against the bottom or side of the glass container. Finally, the formed crystals can be isolated by
vacuum filtration (see technique below) and dried under a heat lamp.

1
CHM 1330, Winter 2023 Ingalls, January 2023

Technical Skill: Vacuum Filtration with a Buchner Funnel

Vacuum filtration is a technique that will allow you to isolate

solid precipitate from a solution. Setup a side-arm filter
flask, rubber adapter, and Buchner funnel with a clamp as
shown at right. It is important to clamp the flask in place as
the setup can become rather top heavy and prone to tipping
over, particularly if the vacuum hose is twisted.

The correct size of filter paper will set flat over the holes in
the Buchner funnel and will cover all the holes. Often, it is
beneficial to weigh the filter paper prior to vacuum filtration
so that you do not need to remove your product from the
filter paper to measure the final mass of the product.

Step 1: Place the filter paper in the Buchner funnel and turn
on the vacuum. Wet the filter paper with the solvent that
your reaction mixture is in. It should suction down tightly to
the Buchner funnel. This will prevent your solid from
“escaping” around the side of the filter paper.

Step 2: Slowly pour your solution and precipitate into the Buchner funnel. Ideally, you will make a small
pile of solid product in the middle of the piece of filter paper and the solvent will suction through the
filter paper into the filter flask.

Step 3: Gently move the solid around the filter paper to maximize the surface area and allow air to suck
through the solid product. Rinse the product with small amounts (~1-2 mL) of cold solvent (do not use
warm solvent, or there will be product that dissolves and is sucked through the filter paper). Once the
product has dried sufficiently, the filter paper will easily lift from the Buchner funnel.

A note about a “trap” for the vacuum filtration setup:

If you are filtering a large volume of solvent or your solvent is a volatile organic solvent (such as toluene and acetic
acid/acetic anhydride in this experiment), you should include a trap in your vacuum filtration setup to prevent
organic waste from entering the environment. See the diagram below.

2
CHM 1330, Winter 2023 Ingalls, January 2023

The trap piece prevents solvent from being sucked out

of the apparatus and into the waste stream.
Additionally, the stopcock lets you bleed air back into
the system to disconnect everything. Alternatively, the
second flask may only have one tube at the top and no
stopcock. Since our Buchner funnels easily pop apart, it
is straightforward to dismantle without the stopcock.

3
CHM 1330, Winter 2023 Ingalls, January 2023

Pre-Lab Questions. Due at the beginning of lab (on paper).

1) What is a limiting reagent or reactant? Which starting material is the limiting reactant?

2) Only 6 drops of phosphoric acid necessary for the reaction. Why do you think such little is needed? Do you
think that adding or forgetting 1 drop will change the reaction?

3) What are the functional groups found is salicylic acid? Aspirin? And, classify the general reaction type for
equation (1).

4) Create two copies of a table with the following on a separate piece of paper. Include a copy with your pre-
lab and keep a copy to use during the lab. The pre-lab copy can be a photocopy.
a) Column with each reagent and product (salicylic acid, acetic anhydride, phosphoric acid, water, aspirin
and acetic acid).
b) Filled in column with the MW of each in a).
c) Empty column for mass/volume/approximate addition of each in a).
d) Empty column for moles of each in a).
e) Filled in column for density for liquids found in a).
f) Filled in column for bp (liquids) or mp (solids).

5) Underneath your table summarize experimental steps 1-5 in your own words. Each step can be brief and you
may sketch out any equipment needed instead of using words.

4
CHM 1330, Winter 2023 Ingalls, January 2023

EXPERIMENTAL PROCEDURE:

This lab will be completed with your lab partner. Using your created table (pre-lab), please write
down any observations and data.

Synthesis and Isolation:

1. Charge a 125 mL Erlenmeyer flask with ~2 grams (weigh and record to ±0.01 g) of salicylic acid. In a
hood carefully add 4 mL of acetic anhydride to the flask. To the mixture add 6 drops of 85%
phosphoric acid and swirl to allow sufficient mixing.

2. Place the flask in a boiling water bath and stir until all the salicylic acid has dissolved. Heat the
mixture for an additional 2 minutes. Remove the flask from the water bath and allow to it to cool to
room temperature.

3. Slowly add 2 mL of water to the cooled mixture. When the vigorous reactions have finished, add 50
mL of ice-cold water. If crystals do not form then use “scratching” or carefully rub the bottom of the
flask with a stirring rod to induce crystallization. Place your flask on an ice bath for 5 minutes to
complete crystallization.

4. Collect the product by vacuum filtration and rinse it with two 10 mL portions of ice-cold water.

5. Allow your crystals to dry under a heat lamp for approximately 10-15 minutes and then weigh.
Monitor for potential melting!

Analysis:

6. Place a few crystals of your aspirin (~10 mg) in a small test tube. Add 1 mL of water and allow for
mixing. Possibly, not all of the aspirin will dissolve. This is okay since the ferric chloride test is very
sensitive. Add 3 drops of a 1% ferric chloride solution. If starting material, salicylic acid, is present a
purple color will be observed. Trace amounts of salicylic acid is indicated by a faint purple (or pink)
color (include this in your observations and conclusion).

Hazardous Waste:

Dispose of filtrate (liquid from vacuum filtration) in the appropriate liquid waste container.
Dispose of aspirin in appropriate solid organic waste container.

Post lab report.

1. Copy of data table and observations.

2. Calculations

5
CHM 1330, Winter 2023 Ingalls, January 2023

1. Determine the moles of the starting materials, salicylic acid and acetic anhydride (see
step one of the procedure).
2. Calculate the theoretical yield* of acetylsalicylic (aspirin) acid in grams.
3. Determine the mass and moles of acetylsalicylic acid (aspirin) isolated.
4. Calculate the percent yield of acetylsalicylic acid (aspirin).

𝑚𝑜𝑙𝑎𝑟 𝑟𝑎𝑡𝑖𝑜 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡(𝑎𝑠𝑝𝑖𝑟𝑖𝑛)

Theoretical yield = moles of limiting reagent ∗ ∗ 𝑚𝑜𝑙𝑎𝑟 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡(𝑎𝑠𝑝𝑖𝑟𝑖𝑛)
𝑚𝑜𝑙𝑎𝑟 𝑟𝑎𝑡𝑖𝑜 𝑜𝑓 𝑙𝑖𝑚𝑖𝑡𝑖𝑛𝑔 𝑟𝑒𝑎𝑔𝑒𝑛𝑡

!"#$!% '()%*
𝑃𝑒𝑟𝑐𝑒𝑛𝑡 𝑦𝑖𝑒𝑙𝑑 = #+),-)#("!% '()%* ∗ 100