Esterification of Salicylic Acid
AP Chemistry
Adapted from Pavia, Introduction to Organic Laboratory Techniques
In this experiment, we will prepare methyl salicylate, a familiar-smelling organic ester, from salicylic acid.
Using thin layer chromatography, we will then analyze the product for traces of unreacted salicylic acid.
Methyl salicylate was first isolated in 1843 by extraction from the bush Gaultheria procumbens. The berries
from this bush were used medicinally by native Americans, who brewed a tea from the leaves to alleviate
rheumatic symptoms, headache, fever, sore throat and various aches and pains. It was soon found that methyl
salicylate had analgesic (pain relieving) and antipyretic (fever reducing) character almost identical to that of
salicylic acid when taken internally.
Salicylic acid is the active ingredient in willow bark, which Hippocrates (5th century BCE) knew to reduce aches
and pains and fever. This remedy was also mentioned in texts from ancient Sumer, Lebanon, and Assyria. The
medicinal character of methyl salicylate arises from its ready hydrolysis to salicylic acid in the gut. [The
medicinal properties of aspirin, acetyl salicylic acid, are also due to its ready hydrolysis to salicylic acid.]
Methyl salicylate can be taken internally or absorbed through the skin. This ester also has a pleasant odor, and it
is used to a small extent as a flavoring principle.
O
OH
O
OH
+
CH3 OH
Salicylic acid
H+
O
CH3
OH
+
H2O
Methyl salicylate
Methyl salicylate will be prepared from salicylic acid, which is esterified at the carboxyl group with methanol.
Esterification is an acid-catalyzed equilibrium reaction. The equilibrium can be driven toward the product side
by increasing the concentrations of one of the reactants. In this experiment, a large excess of methanol will shift
the equilibrium to favor more complete formation of the ester.
Materials
2-dram reaction vial
methanol
salicylic acid
H2SO4, 18 M
Boiling chips
hexanes
saturated sodium bicarbonate
Beral pipets
Procedure
1. Prepare a hot water (95-100°C) bath with ~200-mL water in a 400-mL beaker.
2. Mass 0.5 g salicylic acid on weighing paper. Add to reaction vial. Add 1.5 mL methanol; use a graduated
disposable Beral pipet as the exact volume is not critical—you are using a large excess of methanol.
3. Place the vial in a small beaker for stability. Dropwise, slowly add 0.50 mL of concentrated sulfuric acid
(18 M). A white precipitate may form, but it will redissolve during heating.
4. Seal the vial. Mix the reactants by swirling the vial. Using tongs, place the vial into the hot water. Watch
for bubbles emerging from under the cap; if bubbles are observed, remove the vial and retighten the cap.
5. Heat the vial for 20-25 min at 95-100°C.
6. Remove the vial and place on tabletop until cool to the touch. If you do not have two layers, your reaction
isn’t done yet: reheat for an additional 10 min at 95-100°C. Then place the vial in an ice water bath for 2
minutes.
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7. Slowly and carefully crack the vial seal: be sure to go slowly as the vial may be under pressure and some
product may squirt out (it shouldn’t if you cooled the mixture).
8. Pour the vial contents into a 20x150 mm test tube. Slowly add saturated (~8%) sodium bicarbonate
solution to neutralize the sulfuric acid. Mix well. Test with pH paper to make sure the aqueous solution is
basic (any unreacted salicylic acid will dissolve in the basic aqueous layer as the sodium salt). Add 2 mL of
hexanes and mix well; the hexanes will dissolve the product ester and form a layer above the aqueous layer.
9. Remove the organic (upper layer) with a pipet and transfer to a labeled test tube or vial.
10. Cap your test tube with a rubber stopper and save for tlc analysis.
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Thin Layer Chromatographic Analysis
Chromatography is a technique used to separate and identify individual components in a mixture. Its name
comes from the Greek word for color because the earliest applications of chromatography dealt with mixtures of
colored substances such as plant pigments. All chromatographic techniques make use of the fact that
components of a mixture (either gaseous or in solution) tend to move (elute) at different speeds along a coated
surface. The different rates of movement are the result of differing attractions of the components to the coating
material (the “stationary phase”) compared to the tendency of the components to remain in the “mobile phase”
(either gas or liquid). Thus the relative movement of components is affected by the polarity of the molecules.
Thin-layer chromatography (TLC) is one of the easiest chromatographic techniques. A thin layer of a highly
polar solid substance is coated on a sheet of glass or plastic. By immersing one edge of the sheet in an
appropriate liquid solvent, the solvent is drawn up the sheet by capillary action, and the compounds of interest
are carried along at differing rates. This is commonly called "developing" the plate.
Unless the compounds of interest are colored, some method is necessary to make them visible. One method is
to expose the developed plate to some compound that will react chemically with the spots to make them visible.
The tlc plates we will use contain a fluorescent dye in the stationary phase. When the plate is examined under a
UV lamp, the plate will glow (fluoresce) everywhere except where the component spots are.
Materials
Tlc sheets with fluorescent indicator
capillary tubes
bunsen burner
spotting plate
400-mL beaker
watch glass
short-wave UV lamp
hexanes
ethyl acetate
Procedure
1. Using a small flame on your Bunsen burner, draw out 4 capillary tubes for spotting your samples. Heat the
center of the tube, (while rotating to prevent sagging) until it softens, then pull your hands apart about 6-12”.
Break off the thin, drawn out capillary to yield two micro-capillary spotting tubes.
2. Obtain a large beaker (400 mL) and a Petri dish
(or watch glass) to cover it. The beaker should
be large enough so that the chromatographic
sheet can lean against one side.
3. Add enough of the solvent mixture (~5% ethyl
acetate in hexanes for methyl salicylate analysis)
to give a thin layer of solvent in the bottom of the
container. To provide an atmosphere saturated
with solvent inside the container, place a piece of
filter paper around the inside surface of the
container, extending into the solvent. Then cover
the container with the Petri dish and set it aside
while preparing the chromatographic sheet. This
chamber will ensure even elution of solvent up
the plate.
4. Obtain a piece of plastic-backed
chromatographic sheet. Handle it only on the edges, as fingerprints contain UV-active materials. The
backing is flexible, but the sheet should not be bent excessively to prevent flaking of the coating. Using a
pencil (not a pen), draw a very light line across the bottom (short dimension) about 1 cm from one end.
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Then make three light marks at even intervals along the line. These are the points at which the samples will
be spotted.
8. When the front edge of the liquid has moved about 80-90% of the
way to the top of the sheet, remove the sheet. Immediately, while
the sheet is still wet, draw a pencil line on the sheet to show the top
edge of the liquid. Then lay the sheet on a clean surface in the
hood and allow the solvent to evaporate until the sheet appears dry.



ester
7. When the spots are dry, place the sheet in the developing chamber. Be sure that the
bottom edge of the TLC plate (near the spots) is in the solvent but that the spots
are above the solvent. Also be sure that the filter paper does not touch the
chromatographic sheet. Then cover with the Petri dish ; the solvent will slowly
move up the TLC sheet by capillary action.
solvent front
salicy acid
+ ester
6. Place a period-size sample of salicylic acid in one well of your spotting plate. Add a
few drops of ethyl acetate. Using a clean micro-capillary spotter for each solution,
carefully spot the salicylic acid in the left and center positions and your ester product
in the right and center marks. Allow the solvent to evaporate. Use the UV light to
check the amount of sample you have spotted: the darker the spot, the more sample
you have. Make sure you can see three distinct dark spots under the UV.
Top
salicy acid
5. Before spotting the sheet, you should practice placing very small spots of solution on
a piece of scrap paper. To do this, dip the tip of a micro-capillary spotter into a
solution, then very gently touch the tip to the paper for a brief moment. The spots
should be as small as possible in order to minimize tailing and overlapping when the
chromatographic sheet is "developed". (If a more intense spot is desired, let the spot
dry and re-spot in the same location.)
1 cm
Filter paper
TLC sheet
9. The spots are unlikely to be visible to the naked eye, but they
should be quite visible under the UV lamp. While observing under
the UV lamp, draw a light pencil line around each spot.
Caution: UV radiation is harmful to your eyes.
Do not look directly at the UV lamp.
10. Alternatively, you may visualize the spots in an iodine chamber (small bottle containing a few I2 crystals).
Organic compounds with double bonds or polar functional groups tend to absorb I2; the spots will stay
brown long enough to mark your plate.
11. For a given solvent composition, the Rf of a substance is a measure of the distance the spot moved relative
to the solvent front. Calculate the Rf for both the salicylic acid and the methyl salicylate using the formula:
Rf =
distance moved by spot
distance moved by solvent
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