EXERCISE 11

SYNTHESIS OF ASPIRIN

(Acetylsalicylic Acid from Salicylic Acid)

Palis, Maria Camille D.

Group 2

CHEM 40.1 4L
I. Introduction

The word synthesis, in Greek, means put together. Synthesis organic

chemistry is the art of building-up complex molecular structures of organic
compounds by putting together smaller, easily accessible and commercially
available compounds (Nicotra, 2006).
There are still some organic compounds that require more research
about its properties. However, these compounds may not be available or are too
expensive, and this is where organic synthesis is utilized in order to obtain the
desired organic compound.
Synthesis of organic compounds must be target oriented, or must be as
efficient as possible in terms of yield, cost and time (Nicotra, 2006). The
synthesis must be planned in such a way that the steps are as few as possible,
and the major product must be the desired compound, not a mixture of
products.
Acetylsalicylic acid, commonly known as aspirin, is one of the many
organic compounds that can be synthesized in the laboratory. Aspirin is an
analgesic, antipyretic and anti-inflammatory drug, and is used to reduce fever
and relieve pain. It works by inhibiting a certain enzyme necessary for the
synthesis of prostaglandins (McMurry, et al, 2000). Prostaglandins are known to
be the cause of headaches, platelet aggregation and vasoconstriction. Also,
aspirin may also be used to lower possible incidents of heart attacks and stroke,
by preventing blood clots (intake of small doses of aspirin).
German industrial chemist, named Felix Hoffman, was the one who found
out about the practical synthesis of aspirin back in 1897. Via nucleohpilic acyl
substitution, acetylsalicylic acid may be synthesized from salicylic acid. The
mechanism of the reaction is given as:

In the experiment, some of the salicylic acid will not react to form
acetylsalicylic acid thus, an addition of Iron (III) Chloride or FeCl3 can be done to
test the presence of salicylic acid or differentiate salicylic acid from acetylsalicylic
acid.

3 C7H6O3 (aq) + FeCl3 (aq) Fe(C7H5O3)3 (aq) + 3 HCl (aq)

II. Objectives

The objectives of this laboratory exercise is to explain the concept of

organic synthesis, to synthesize acetylsalicylic acid from salicylic acid by
nucleophilic acyl substitution, and to describe and explain differences in the
properties of acetylsalicylic acid and salicylic acid by simple chemical tests.

III. Materials and Methods

 A. Schematic Diagram of the Procedure

1 gram salicylic acid in 125-mL Erlenmeyer flask

+ 3-mL acetic anhydride
+ 1 drop 85% phosphoric acid
-swirl
- heat in steam bath for 15 mins
+ 2-mL dH2O
+ 20-mL ice cold H2O
-cool to RT
-place in an ice bath
-perform suction filtration

residue filtrate
-- wash several times
-- transfer crystals to pre-weight watch glass
air dry
weight dry aspirin
calculate % yield
crude aspirin
set aside small quantity for MP determination
transfer the rest to 125-mL Eflask
+ 95% ethanol dropwise
swirl until almost all dissolves
+ cold dH2O dropwise until almost all crystals appear
cool flask in a cool bath
suction filtration
- calculate % recovery

(continuation)

residue filtrate
wash crystals with small portions of cold H2O
- transfer crystals to pre-weight watch glass
air dry
weight dry aspirin
calculate % recovery
transfer aspirin to vial
label
determine the MP of crude and
recrystallized aspirin
Compare
Characterization of Aspirin:

Reaction with KMnO4 :

5 drops dilute, slightly acidic KMnO4 in test tube
+ pinch of the sample
- warm the tube in water bath for 5 mins.
- examine mixture

Reaction with FeCl3 :

pinch of the sample in test tube
+ 3 drops 2.5% aqueous FeCl3
+ 1-mL dH2O
- examine mixture

Differentiation of the synthesized acetylsalycylic acid from commercially available aspirin:

pinch of the sample test tube

+ 5 drops H2O and iodine - examine
B. Setup(s)

Figure 1. Suction filtration setup.

Figure 2. Steam bath setup???

C. List of Necessary Chemicals

Name and Function in Physical Hazards Precautions
Structure of the Exercise Properties
the
Compound
++aspirin

IV. Data
V. Sample Calculations