Synthesis of Methyl Salicylate from Aspirin

Esters are a class of organic compounds. An ester compromises an organic or inorganic acid in which one or more hydroxy
(OH) groups have been replaced by and alkoxy (O-alkyl) group. For example, the simplest ester, methyl formate (CHO-
OCH3), is made up of formic acid (CHO-OH) in which the hydroxyl group has been replaced by a methoxy group (-OCH3).
Similarly, ethyl acetate (CH3CO-OCH2CH3) is made up of acetic acid (CH3CO-OH) in which the hydroxy group has been
replaced by an ethoxy group (-OCH2CH3)

Although esters can be produced by many mechanisms, the most commonly used method is called esterification, which is a
condensation reaction between an alcohol and an acid, typically in the presence of a strong acid catalyst, such as sulfuric
acid. For example, ethyl acetate can be produced by reacting ethanol (ethyl alcohol) with acetic acid and isopropyl butyrate
by reacting isopropanol (isopropyl alcohol) with butyric acid.

Esters were traditionally named by combining the name of the alcohol with the root name of the acid and adding “ate” as a
suffix. Traditional names are still widely used by most chemists, particularly for the simple esters. The IUPAC naming
system uses the systematic names for the alcohol and root name of the acid, followed by “oate.” For example, the
traditional name n-amyl acetate (n-amyl alcohol with acetic acid) is represented in IUPAC nomenclature as 1-pentyl
ethanoate (1-pentyl alcohol, the systematic name for n-amyl alcohol, with ethanoic acid, the systematic name for acetic
acid).

Esters typically have strong, often pleasant, scents and tastes, so many esters are used as flavorings and perfume agents,
either individually or in combination. For example, the scent and taste of strawberries is due to the presence of (among
others) methyl cinnamate, ethyl butyrate, ethyl caproate, isobutyl acetate, and benzyl acetate.

In this lab, we’ll synthesize methyl salicylate, whose common name is oil of wintergreen. You might expect that we’d
synthesize this compound by reacting methyl alcohol (methanol) with salicylic acid, and that is indeed one possible method.
Instead, however, we’ll synthesize methyl salicylate by reacting methanol with aspirin, which is much easier to come by
than salicylic acid. Aspirin is actually a substituted salicylic acid, called acetylsalicylic acid, which is itself both an acid and an
ester.

Figure 1: Conversion of aspirin to salicylic acid to methyl salicylate

Materials:
 balance  Erlenmeyer flask, 125 mL  eye dropper or Beral pipette
 hot water bath (60°C)  graduated cylinder, 10 mL  thermometer
 test tube  graduated cylinder, 100 mL  aspirin (13.0 g)
 beaker, 50 mL  pipette, 10.00 mL  methanol (~100 mL)
 beaker, 250 mL  ring stand  sulfuric acid, concentrated (~10mL)
 beaker, 600 mL  utility clamp (for flask)  saturated sodium bicarbonate
 separatory funnel  stirring rod solution (50 mL; 3.9 g/50 mL)

Modified from:
Thompson, R.B. (2008). Illustrated guide to home chemistry experiments. Beijing: O'Reilly.
Procedure:

This lab is broken down into three parts. In Part I, we’ll synthesize methyl salicylate. In Part II, we’ll isolate and purify the
product. In Part III, we’ll determine the density and freezing point of our product.

Before you begin this lab (or, indeed, any organic synthesis), you should calculate the theoretical yield for the reaction.
We’ll react 13.0 g of aspirin with excess methanol to form methyl salicylate. The density of methyl salicylate is 1.1825 g/mL.

Part I: Synthesize Methyl Salicylate

Perform this part of the lab in a well ventilated area. The reaction produces a strong odor or methyl salicylate and
methanol vapor. Make certain there are no open flames or other ignition sources nearby.

1. Transfer about 60 mL of methanol to the 125 mL Erlenmeyer flask. Add 13.00 g of aspirin to the flask and swirl
until the tablets dissolve. (Aspirin tablets may contain binders that do not dissolve in methanol, which is no cause
for concern.)
2. Add about 10.0 mL of concentrated sulfuric acid to the reaction vessel and swirl to mix the solutions. Be careful to
add the acid slowly to avoid boiling the solution and causing some of the acidic solution to sputter out of the flask.
3. Clamp the flask to a ring stand and partially immerse it in a hot water bath at about 60°C.
4. Allow the reaction to proceed, stirring the reaction mixture occasionally, for 60 minutes. As the methyl salicylate
forms, you’ll notice a distinct wintergreen odor. Keep the reaction mixture at about 60°C, adding water to the bath
if necessary to keep its level up. The level of the liquid in the reaction vessel will decrease as methanol evaporates
from the flask. Add more methanol as needed to keep the reaction vessel near its original volume.
5. After 60 minutes, stop adding methanol to the flask. Increase the heat slightly to being the liquid in the reaction
flask to a gentle boil. Boil the solution long enough to vaporize most of the remaining methanol.
6. When enough methanol has boiled off to reduce the volume in the reaction vessel to about half its original
volume, remove the flask from the water bath and set aside to cool.

Part II: Isolate and Purify the Product

The brown liquid in the reaction vessel is a complex solution that contains methanol, crude methyl salicylate, sulfuric acid,
unreacted aspirin, and other impurities. Methyl salicylate is freely soluble in methanol, but only very slightly soluble in
water. We’ll take advantage of that differential solubility to extract most of the water-soluble impurities from the crude
product.

1. Pour the contents of the reaction flask into the sep funnel.
2. Add about 50 mL of ice cold tap water to the sep funnel, cap the funnel, and agitate the contents vigorously for 30
seconds.

Lab Technique Note: Generally, sep funnels need to be vented after vigorous shaking. Even if a gas isn’t
generated, it’s good practice. The sodium bicarbonate wash in step 5 will definitely have to be vented
during and after shaking. Enough gas is generated to blow the stopper off the back of the sep funnel.

3. Allow the contents of the sep funnel to separate into two layers. The aqueous layer contains nearly all of the
sulfuric acid and most of any other water-soluble impurities. (Make sure you know which layer is which.) Separate
the two layers, and transfer the aqueous layer to the 250 mL beaker.
4. Do a second washing by repeating steps 3 and 4.
 5. Add about 50 mL of sodium bicarbonate solution to the sep funnel, cap the funnel, and agitate the contents
vigorously for 30 seconds. (See previous note on venting)
6. Allow the contents of the sep funnel to separate into two layers. The aqueous layer contains an excess of sodium
bicarbonate and a small amount of sodium sulfate produced by the neutralization of any sulfuric acid that
remained in the organic layer. Separate the two layers, and transfer the aqueous layer to the 250 mL beaker.
7. Neutralize the sulfuric acid in the 250 mL beaker with sodium carbonate (soda ash) and flush the neutralized
solution down the drain with plenty of water. Retain the organic layer in the sep funnel, which contains the crude
methyl salicylate.

Part III: Determine Density and Freezing Point of the Product

Our product is a few mL of semi-pure methyl salicylate. If we had the equipment needed to micro-scale distillations, we
could purify our raw product by distillation. We don’t have that equipment, so we’ll test our product as-is to determine its
density and freezing point.

We know that the density of pure methyl salicylate is 1.1825 g/mL, so the density of our product will give us some idea of
its purity. That’s not sufficient, however. Even if the density of our product is very close to 1.1825 g/mL, for all we know
our product might be a small amount of methyl salicylate mixed with a large amount of some impurity that has the same
density. Pure methyl salicylate freezes (or melts) at -8.3°C. Furthermore, the sharpness of the freezing/melting point gives
a good indication or a product’s purity. Pure substances tend to freeze/melt very sharply, at one particular temperature.
Impure substances freeze/melt more gradually, over a range of a few degrees.

For this lab, you can earn extra credit by coming up with a method for determining the density and freezing point of your
product from this lab. You have one week from today to determine your method, conduct your investigation, and write up
your findings. Your methods should have background sources for support and your experimentation should be conducted
and cleaned up to scientific laboratory standards. If you decide to do this, you need to add this to the general write up
requirements below:

General write ups for this lab should include:

 A brief introduction to the problem.

 Data collected during the lab.
 A calculation of theoretical yield for the amount of aspirin actually used.
 Actual and percent yields
 Error Analysis
 Answers to the following questions:
1. Why is an esterification reaction called a condensation reaction?
2. Why is freezing/melting point useful for determining product purity.
3. If we had used pure salicylic acid instead of aspirin how would you expect the percent yield to change?
Explain.
4. Aspirin that is very old or stored improperly often has a strong odor of vinegar. On that basis, what ester
other than methyl salicylate would you expect to be present in your crude product?