Experiment 1

AIM/OBJECTIVE: Preparation of Aspirin and its characterization by melting point,

mixed melting point, and thin layer Chromatography
Safety Notes
1. The acetyl chloride and pyridine should only be dispensed in a fume hood.
2. Always wear appropriate eye protection while handling the chemicals.
Apparatus/glassware required: Two test tube (20 ml), glass rod, cold water/ice
bath, beaker/conical flask 100ml, Buchner funnel and flask, filter paper, stoppers
Chemicals Required: Salicylic acid, pyridine, acetyl chloride, cold water
Introduction and Theory: In this experiment you will perform an organic
synthesis to make aspirin. Aspirin is the trade name for the molecule acetylsalicylic
acid (arent you glad we dont have to use that name when you have a
headache). The earliest known use of this molecule has been traced back to the
fifth century B.C. The Greek physician Hippocrates described an extract of willow
tree bark, a bitter powder that could be used to reduce fevers. In 1829, Salicin was
isolated from willow bark and used as a pain reliever. Unfortunately Salicin was not
very popular since it was found to be very acidic and a stomach irritant. In 1897 a
German chemist named Felix Hoffman was working for the Bayer chemical
company. Hoffman was looking for a less acidic pain reliever that his father could
take for his arthritis. His research led to the synthesis of acetylsalicylic acid (ASA)
or aspirin. Bayer patented the name and commenced to market the product in
1899. It was a huge success and sales grew rapidly. In fact, the company set up by
Friedrich Bayer & Company is generally reckoned to have been the first
pharmaceutical company, and the production of aspirin is generally accepted to
have laid the foundation of the modern pharmaceutical industry. Interestingly
enough it wasnt until the 1970s that scientists began to understand how aspirin
actually worked as a pain reliever. Today 80 billion aspirin tablets are consumed
every year across the globe to reduce fevers, relieve pain, and even help prevent
heart attacks.
In commercial aspirin products, a small amount of ASA (300 to 400 mg) is bound
together with a starch binder and sometimes caffeine and buffers to make an
aspirin tablet. The basic conditions in the small intestine break down the ASA to
yield salicylic acid, which is absorbed into the bloodstream. The addition of a buffer
reduces the irritation caused by the carboxylic acid group of the aspirin molecule.
Mechanism of acetylation of alcohol:

O
CH3CH2OH

CH3C Cl

OH
O- H+ + H+
CH3C Cl
CH3C Cl
Step
2
O
O+
CH
CH
3
2
CH3CH2 H

Step1

Step 3

O
HCl

CH3CH2OCCH3

O
Step 4

CH3C
O
CH3CH2

H
+

Cl-

Aspirin can be produced in a one step chemical process by reacting salicylic acid
with acetyl chloride, according to the reaction

Aspirin is a white solid that is almost completely insoluble in water. We will use this
physical property of our product to separate it from the final solution.
Thin layer chromatography (TLC) is used to separate and identify aspirin. Small
amounts of the synthesized product, starting material (salicylic acid) and
commercial aspirin are placed along one edge of a chromatography plate. The plate
is then placed in a container with solvent. With the plate acting like a wick, the
solvent flows up the chromatogram, carrying the samples with it. Molecules that are
more soluble in the solvent will move higher on the paper; the molecules that are
more attracted to the plate will remain closer to the original line. After removing
the plate, the samples can be detected wit UV light/iodine chamber.
Procedure:
1. Place 1.4 g (0.01 mol) of salicylic acid in a 20 mL test tube and add 1 mL of
pyridine (just sufficient to dissolve it) while the tube rests in an ice bath. Keep the
test tube in the fume hood!
2. Point the open end of the test tube away from you and your partners.
Occasionally the reaction goes quickly and shoots material out of the tube! Add 1
mL of acetyl chloride to the tube. Keep the mixture in the fume hood!
3. The mixture becomes viscous at this stage. Place tube in the ice bath for 15 min.
( it does not need to be in the hood).
4. While waiting, set up a vacuum filter flask with a Bchner funnel and a piece of
filter paper which just fits the bottom of the funnel, as shown in Figure 2 below.
Attach a thick rubber tube to an aspirator mounted on a water faucet.
5. Add 5 mL of cold water to the test tube and cap it with a rubber stopper. Shake
the mixture. Do this cautiously at first until you are sure that no violent reaction is
occurring. The mixture should turn cloudy. Shaking is continued until a white
product appears (it may take several minutes, be patient!)

6. Turn on the water faucet all the way and check to be sure you have good suction.
Break the suction by disconnecting the tube from the flask (leave the water
running). Pour the mixture into the funnel, trying to get as much of the solid
transferred as possible. Connect the hose and apply full suction for at least 30
seconds. Wash the crystals with cold water. Break the suction. Do not just turn off
the water; this may create a back-flow of the water into your filter flask. Dry them
on the filter paper for about 1 hr.
Part B- Recrystallization
1. Carefully scrape off 1/10 of your crystals into a 50 mL beaker. Add about 3 mL of
cold water and place the mixture on a hot plate in a hood. Heat until all of the
crystals dissolve. When the crystals are completely dissolved, remove the beaker
and allow it to cool. You should see nice crystals of aspirin beginning to form! When
the recrystallization is complete, filter again, and dry.
Part C- Melting Point:
1. Measure the melting point with melting point apparatus
Calculations:
Calculate the theoretical yield of aspirin in grams.
Yield =
Calculate the actual yield of aspirin in grams by weighing the product.
Use this to calculate the % yield for this experiment.

Result: Report the yield and % yield, Melting point range of your aspirin and
Chemical literature melting point
Reaction and mechanism of aspirin synthesis with acetic anhydride and
sulphuric acid