Experiment # 5
Esterification. Synthesis of Aspirin
Background
Esterification reactions are those involving the preparation of the ester functional group.
From lecture we know that the reaction between a carboxylic acid and an alcohol, under
the proper conditions, produces an ester and water as depicted below:
carboxylic acid
+
H+
alcohol
---->
heat
ester
+
water
An improved esterification procedure is one that uses an acid anhydride rather than a
carboxylic acid. An acid anhydride is yet another functional group in organic chemistry;
one we won’t study except for purposes of this experiment. Using an acid anhydride
rather than a carboxylic acid simply is better way to esterify; the reaction time is much
shorter and the amount of heat required is less. Note, however, that when using an acid
anhydride instead of a carboxylic acid, an ester and a carboxylic acid are formed as
depicted below:
acid anhydride
+
H+
alcohol ----->
heat
ester
+
carboxylic acid
Think of the acid anhydride functional group as a more potent form of a carboxylic acid
functional group. In today’s experiment salicyclic acid is reacted with acetic anhydride
to give acetylsalicyclic acid (aspirin) and acetic acid:
Note that salicyclic acid has three different functional groups in its structure; namely,
aromatic, carboxylic acid, and alcohol functional groups. In reacting with the acetic
anhydride, the salicyclic acid reacts ONLY as if it were an alcohol; the carboxylic acid
and aromatic functional groups are not involved in the reaction!
Once isolated from the reaction mixture, the crude aspirin will be analyzed by thin layer
chromatography to see how impure it is and will subsequently be purified by a
technique called recrystallization. The purified aspirin will then be checked for purity
by tlc to see if the recrystallization removed any impurities.
Objectives
To prepare aspirin via an esterification reaction
To purify the crude aspirin by recrystallization
To analyze the aspirin (crude and purified) by tlc
Directions
Part 1
At your station prepare a hot water bath by warming a 400 ml beaker half full with tap
water; set the heating dial on the hot plate to about 4-5. While the water is warming,
weigh out exactly 1.0 gram of salicylic acid onto a piece of tared weighing paper and
then transfer all of the material into a 125 ml Erlenmeyer flask. Carefully add a tefloncoated magnetic stirring bar to the flask (don’t drop it into the flask as it might break the
bottom of the flask). Take the flask to your instructor who will dispense the acetic
anhydride (5 ml) and 85 % phosphoric acid (10 drops) into your flask.
Part 2
Lower the Erlenmeyer flask into the warm water bath and swirl the contents of the flask
occasionally. As the reaction mixture becomes warm, the acetic anhydride will dissolve
the salicylic acid. The acetic anhydride acts both as a starting material and as the
solvent. Once all of the salicylic acid has dissolved, continue to heat the reaction mixture
in the warm water bath for at least 15 minutes. Remove the flask from the hot water and
allow cooling to room temperature on the bench top.
Part 3
Once the flask has cooled to room temperature, chill the flask in an ice/water bath for at
least five minutes. Then CAREFULLY add 3 ml of distilled water DROPWISE to the
reaction mixture. The water will decompose the excess acetic anhydride to give acetic
acid and heat; hence the reason for the ice/water bath. Over a period of a few minutes
add 30 ml of distilled water; add it at a rate you feel comfortable with as the acetic
anhydride continues to decompose. Allow the reaction mixture to continue to chill in
the ice/water bath; solid aspirin will (should) precipitate out of the reaction mixture.
Save the ice/water bath for use later.
Part 4
As demonstrated by the instructor, vacuum filter (need to get rubber tubing) the aspirin
slurry. Wash the precipitate (aspirin) twice with a small amount of cold distilled water.
Continue to vacuum dry the crystals until they are somewhat dry. Transfer the crystals
onto a piece of tared weighing paper and record the weight of the “crude” aspirin on
the data sheet. Be sure to save a small amount of the crude aspirin for analysis by tlc
later. Transfer the crystals to a 50 ml beaker and add 5 ml of distilled water. The aspirin
will not dissolve in room temperature water but will dissolve in hot water. As
demonstrated by the instructor, warm the beaker near boiling using a bunsen burner.
Be sure all of the aspirin dissolves in the hot water; if not, add a bit more water and
reheat. Allow the hot solution to cool to room temperature; this may take 10-15 minutes.
As it cools, the aspirin may precipitate out. Once cooled to room temperature, chill the
beaker in an ice/water bath for at least five minutes. Crystals should begin to precipitate
out during this period; if not, ask your instructor for help as there as some “tricks of the
trade” to get the aspirin to come out of solution. Vacuum filter the purified aspirin
crystals as before, using a new filter paper. Wash the crystals twice with a small amount
of cold distilled water. Continue to vacuum filter to dry the crystals as much as possible.
Transfer the crystals to a new piece of filter paper for air drying.
Part 5
Determine the weight of your purified aspirin crystals (your actual yield) and record on
the data sheet. Using the following formula, determine the percent yield for this
reaction and record on the data sheet.
actual yield (g)
Percent Yield = -------------------- x 100
1.00 g
Determine the purity of both the crude and purified aspirin by tlc. Obtain three glass
vials and label one as “crude” and the other as “pure” with a felt marker. Transfer a
small amount of solid material to the appropriate vial. Add a small amount of acetone
to each vial in order to dissolve the solid material. Use approximately the same amount
of manufactured aspirin (provided) and also dissolve in acetone in the third vial.
As demonstrated by your instructor, spot the acetone solution of all three i. e. crude
aspirin aspirin onto the left lane of the tlc plate, and the acetone solution of the purified
aspirin onto the right lane of the tlc plate and the manufactured asprin in the middle
lane. Be sure to save the vial marked “pure” for use later. Elute the plate in Solvent A
(15% acetone in dichloromethane plus 10 drops of glacial acetic acid). Remove the plate
from the chromatography jar and mark the solvent front either with a fingernail or a
pencil. What do you see under uv light? Circle all spots with a pencil and develop the
plate in a silica gel/iodine chamber to visualize the spots.
Crush up one Excedrin Migrane caplet using a mortar and pestle. Add some acetone to
the powder and stir briefly; the acetone will dissolve the three drugs present in Excedrin
Migrane. To a second tlc plate, spot your acetone solution of the purified aspirin in the
left and middle lanes; spot the acetone solution of Excedrin Migrane in the middle and
right lanes. Elute as before and observe the spots under uv light; circle all spots with a
pencil. Visualize the spots as before. Which spot from the Excedrin Migrane extract is
the aspirin? How could you tell which other spots are the caffeine and acetaminophen?
Part 6
Take a very tiny amount of your crude, purified aspirin and Excedrin in a test tube.
(Use a mortar pistil to crush your Excedrin tablet). Then add 2 ml. of FeCl3 1% solution
to each test tube. Look for color violet to brown, where violet represents pure aspirin.
Experiment #5
Data Sheet
Name ________________________
Part 1
Weight of salicyclic acid used:
______________
Part 4
Weight of “crude” aspirin:
______________
Part 5
Actual yield of purified aspirin:
______________
Percent Yield of Aspirin:
(show calculations)
______________
Rf of purified aspirin:
____________
__
(show calculations)
Was there any difference in the tlc of the crude and purified aspirin?
If yes, what was the difference?
How many spots could you see from the tlc plate of the Excedrin Migrane extract
besides the aspirin spot?
Scotch tape photocopies of both tlc plates to a plane piece paper and staple to the back
of this page, identifying all spots on both plates.
Part 6
How pure was your aspirin? (hint: compare Rf values) ____________________