1. PREPARETION OF ASPIRIN
OBJECTIVES:
Purpose of this experiment is:
 To synthesize aspirin (acetyl salicylic acid) (ASA) from salicylic acid and acetic
anhydride be introduced to the concept of organic synthesis;
 Synthesize acetylsalicylic acid from salicylic acid by nucleophile acyl substitution; and
 Differentiate acetylsalicylic acid from salicylic acid by simple chemical tests.
 To predict the mass of purified aspirin that we should have theoretically obtained from
the mass of salicylic acid that we used from the start of this experiment.
INTRODUCTION
Organic synthesis is the process where a desired organic compound is constructed or prepared
from commercially available materials. The objective of organic synthesis is to design the
simplest synthetic routes to a molecule.
Acetylsalicylic acid, also known as aspirin, is one of the most widely used medications to reduce
fever and is also used as a pain killer. It is an acetyl derivative of salicylic acid. It is a white,
crystalline, weakly acidic substance which melts at 135°C.
THEORY
Aspirin is most widely sold over-the-counter drug. It has the ability to reduce fever (an
antipyretic), to reduce pain (an analgesic), and to reduce swelling, soreness, and redness (an anti-
inflammatory agent). One of the first recorded accounts for the discovery of aspirin appeared in
England, in 1763, crediting the bark of willow trees with a beneficial effect in alleviating distress
due to fevers, aches, and pains. Later, the compound salicylic acid (named for the Latin word for
willow, Salix) was isolated from willow bark; it proved to be the active ingredient. By 1860,
organic chemists were able to synthesize salicylic acid from basic starting materials, this
furthered the therapeutic use of the substance, but there were problems. Salicylic acid proved to
be irritating to the membranes of the throat, mouth, and stomach. These problems are directly
associated with the high acidity of the compound, but a simple remedy was discovered, namely,
replacement of the acidic phenolic hydrogen atom with an acetyl group.
When interpreting the structures of the above organic compounds, note the following
characteristics of these molecules. Organic molecules are complex compounds of carbon.
Carbon always bonds to four other groups or atoms. When outline structures (condensed) are
given, such as the hexagon, each point of the hexagon represents a carbon atom. If a double
bond, =, is present and the carbons are attached in a ring, only one hydrogen is attached to give
the full complement of four bonds. If a triple bond is present then only one other atom may be

2. attached. Check the structures below to see that each carbon has four and only four bonds.
Nitrogen, on the other hand, will bond covalently to only three atoms, and then oxygen bonds
only to two.
A useful synthesis of acetylsalicylic acid was developed in 1893, patented in 1899,
marketed under the trade name of “aspirin” by the Bayer Company in Germany. The name
aspirin was invented by the chemist, Felix Hofmann, who originally synthesized acetylsalicylic
acid for Bayer. . In Part I of this experiment, you will prepare aspirin by reaction of salicylic
acid with acetic anhydride, using concentrated sulfuric acid as a catalyst. By doing so you will
learn some preparative procedures used in organic synthesis in general.
Aspirin still has its side effects, note that the carboxylic acid functional group remains intact.
This may result in hemorrhaging of the stomach walls even withnormal dosages. The acidic
irritation can be reduced through the use of buffering agents, like antacids, in the form of
magnesium hydroxide, magnesium carbonate, and aluminum glycinate when mixed with aspirin
(Buffering). While the ester can be formed from acetic acid and salicylic acid, a better
preparative method uses acetic anhydrides in the reaction instead of acetic acid. An acid
catalyst, like sulfuric acid or phosphoric acid, is used to speed up the process. In Part II of this
experiment you will measure the percent acidity of aspirin by titration with a strong base.
MATERIALS
Chemicals Equipment Facilities
 Salicylic acid(powder)
 Acetic anhydride(L)
 Concentrated sulfuric
acid
 Concentrated
phosphoric acid
 Distilled water
 Ethanol
 20-25 ml test tube
 Beaker
 Section filtration
 Filter paper
 Spatula
 Analytical balance
 Droper
 Graguated cylinder
 Hot water bath(80-
90)oC
 Ice bath

3.  Ferric chloride  Clamp
 Stering rod
PROCEDURE
PART (1): PREPARETION OF ASPRIN
 All the needed materials and apparatus was set up and placed in proper manner.
 1g of salicylic acid was measured and placed into (20-25) ml of test tube.
 2.5ml of acetic anhydride was poured into the test tube that contains 1g of (SA).
 3dropes of concentrated sulfuric acid was dropped into the test tube.
 The mixture was stirred.
 The test tube was placed in hot water path for 10min.
 It was allowed to cool slowly to room temperature.
 The mixture was poured into a beaker contained 30ml of cold distilled water.
 The beaker was kept in ice bath until crystal was developed.
 The product (crystal) was collected by section filtration.
 The filter paper was weighed and the crystal was dried upon it for half an hour.
 The product (ASA) was weighed.
PART (2): PURITY TEST OF (ASA) BY PHENOLIC HYDROXYL GROUP:
 3 Clean and dry test tubes was placed on temple.
 1ml of ethanol and 1 drop of 1% aqueous ferric chloride solution were placed in each of 3
test tubes.
 A few crystals (about 5mg) of SA were placed into the first test tube.
 The same amount (about 5mg) of the product (ASA) was placed into the second test tube.
 The third test tube was leaved as a control (blank).
 The mixture of each test tube was shacked.
DATA
FOR PART (I):
Salicylic acid Acid anhydride Aspirin
Quantities 1.0g 2.5ml or 2.7g
Molar mass 138.12g/mole 102.1g/mole 180.15g/mole
Moles .00724mole 0.0245mole
Theoretical yield
Actual yield .67g

4. CALCULATION:
Limiting reagent and % Yield
• Which is the limiting reagent, 1.0 g salicylic acid or 2.5 mL of acetic anhydride?
Moles of salicylic acid used = 1.0/138.12 = 0.00724MOLE
Weight of acetic anhydride = 2.5(1.08) = 2.7 g
Moles of acetic anhydride = 2.7/102.1 = 0.0245mole
Therefore Salicylic acid is the limiting reagent. Since it exists in small amount.
• If 0.68g of aspirin were produced what is the % yield.
Theoretical yield of aspirin = 0.00724mole *180.12g/mole = 1.304g
Actual yield = 0.68 g
Percent yield = actual yield/theoretical yield x 100
%yield= .68/1.304 x 100=52.12%
FOR PART(I):
Sample Amount of ethanol
and ferric chloride
Color Intensity
Salicylic acid(5mg) 1ml, 3drop purple deep
Aspirin (5mg) 1ml, 3drop purple slight
Control (blank) 1ml, 3drop Color less
OBSERVETION:
The addition of ferric chloride to salicylic acid produces a specific color caused by the
reactionofsalicylic acid with aqueousferric(Fe (H2O) 6)+3) ion. The oxygen atoms of the acid
group –COOH, and of the -OH group on the salicylic acid together can form a complex with Fe
(H2O) 6) +3. Thatcomplexhasanintenseviolet color.Inaspirin,the-OHgroup of salicylic acid has
been replaced by a O-COCH3 group which prevents the
secondbondfrombeingformed.Theresultingcomplexwithaspirinshowsonlyaslightlyyellowcolor,
not very different from that of Fe(H2O)6)+3itself.
Discussion and Conclusions:

5. We were successful in forming acetylsalicylic acid (aspirin). The results showed that our sample
was not quite as pure as it could have been. The tests that were conducted to determine the purity
of the acetylsalicylic acid proved that the sample was not that pure. When testing for excess
salicylic acid the test came up deep purple when compared to the pure acetylsalicylic acid’s light
purple results it showed that there was an excess amount of unreacted salicylic acid. In the
formation of the acetylsalicylic acid there was 52.12% yield. The percent yield might have been
caused by a loss of crystals in transferring the substance from the filter paper to the other filter
paper. Our product took longer to crystallize which gave us better-shaped crystals but might not
have completely crystallized causing a shortage of actual yield. In order to create purer
acetylsalicylic acid, more acetic anhydride could be added to the reaction. This would ensure that
all of the salicylic acid reacted and that it was the limiting reactant. The unreacted acetic
anhydride can be destroyed when ice cold water is added. After the acetic anhydride is destroyed
a purer solution of acetylsalicylic acid should be formed.
Using the data we obtained from this experiment, we were able to conclude that after our
filtration, there was 0.68grams of pure aspirin. We were able to conclude this by taking 1.000
grams of salicylic acid and were able to synthesize it (separating the product from the reaction
mixture) until it was pure aspirin. We were also able to test for phenolic groups in the mixtures
that we created, by doing this we can determine their (aspirin and salicylic acid) structural
formula which also determines their functionality. Given the data from the experiment, we were
also able to determine our percent yield, which tells us the success of the synthesis. Our percent
yield was 52.12%.
Purple color when FeCl3 added - impure product, salicylic acid present.Unreacted salicylic acid is
present. Salicylic acid is NOT water soluble and cannot be removed by using cold distilled water. If
you do not heat the solution long enough the reaction will not be complete.
No color change, appearance ofyellowcolor, or a faint purple tinge - pure product, no unreacted
salicylic acid present.
QUIZ QUESTIONS:
1, why is the carboxyl group not acetylated?
2, the m.pt.of SA is 157-159 oC while that of ASA has a higher molecular mass is around 135oC.
Explain why?
3, what is the rational for the observed color reaction b/n SA & ferric chloride?
4, how can one use infra-red spectra to distinguish the product of this experiment from the
starting materials.

6. ANSWER FOR QUIZ QUESTION:
1. Carboxyl groups are not as nucleophilic phenols. It is possible to form a mixed anhydride of an
carboxylic acid, but likely the conditions used were either no strong enough or it was formed and
was hydrolyzed upon work up (Mixed anhydrides are also not too stable)
2. salycilic acid is 2-hydroxy benzoic acid. In aspirin the hydroxyl group is part of an ester of acetic
acid. Salycilic acid has a higher melting point than the ester as the crystal lattice forms stronger
bonds between the molecules, and so needs more heat or energy to melt it.
3. The addition of ferric chloride to salicylic acid produces a specific color caused by the
reactionofsalicylic acid with aqueousferric(Fe (H2O) 6)+3) ion. The oxygen atoms of the
acid group –COOH, and of the -OH group on the salicylic acid together can form a
complex with Fe (H2O) 6) +3. Thatcomplexhasanintenseviolet color.
4.