BACHELOR IN IN PHARMACEUTICAL, MEDICAL AND

AGRONOMICAL BIOTECHNOLOGY

Practical Organic chemistry 2.1

Part I: Synthesis of Paracetamol (Acetamonophen).

1.Introduction: Preparation of acetaminophen involves treating an amine with an acid anhydride

to form an amide. In this case, p-aminophenol,
p thee amine, is treated with acetic anhydride to
form acetaminophen (p-acetamidophenol),
acetamidophenol), the amide.

Acetaminophen (paracetamol) an analgesic and fever-reducing

fever reducing medicine similar in effect to
aspirin. It is an active ingredient in many
m over-the-counter medicines, including Tylenol and
Midol. Introduced in the early 1900s,
190 acetaminophen is a coal tar derivative that acts by
interfering with the synthesissis of prostaglandins and other substances necessary for the
transmission of pain impulses.

Although its action is similar to that of aspirin, it lacks

la aspirin’s anti-inflammatory
inflammatory and blood-
thinning effects, is less irritating to the stomach,
sto and can be used by people who are allergic to
aspirin. Heavy use, however, has as been
b linked to an increased incidence of liver failure, especially
in heavy drinkerss of alcoholic beverages and in those who are not eating enough, and overdose,
especially in children, can be fatal.
fatal

2. Reaction:
Paracetamol can be made in three steps from phenol. 1st step is the nitration of phenol, 2nd step
is the reduction of a nitro group to an amine and the last step is the formation of an amide.

For this practical course, you realize the last step: the acetylation from 4-aminophenol to
paracetamol by using acetic anhydride at the ambient temperature.

3. Caution:

– Acetic anhydride can cause irritation of tissue, especially in nasal passages. Avoid
breathing the vapor and avoid contact with skin and eyes.

– p-Aminophenol is a skin irritant and is toxic.

– Aqueous solutions obtained from filtration operations may be diluted with water and
flushed down the drain.

4. Protocol:

– Place 5 g of 4-aminophenol in 25 ml of distilled water in a 100 ml conical flask with a

stir bar then heat the reaction mixture at about 115°C and stir gently.

– In a fume cupboard, add 5.6 g of acetic anhydride to the stirred suspension and gently
shake to mix, continue heat until the solution completely soluble.

– Keep heating for 30 min.

– After 30 min, Remove the flask from the heat and allow it to cool, remove the stir bar and
wash it with a litter hot water.

– Let the flask cool to room temperature. If crystallization has not occurred, scratch the
inside of the vial with a glass stirring rod to initiate crystallization. Cool the mixture thoroughly
in an ice bath for 15-20 minutes and collect the crystals by filtration, washed with a little cold
water and dried (3x5 ml maximum).

– The product will be purified by crystallization from distilled water. Dissolve the crude
product in the minimum of distilled water at about 80°C.

– Allow the clear solution to cool slowly to room temperature and collect the recrystallized
product by suction filtration, washing with 10 ml of ice-cold distilled water.

– Dry the recrystallized product either between filter papers or by gently warming in an
oven (55°C) (about 2h), determine the yield and the melting point.

Question:

1. Draw the mechanism of 3 reactions in the synthesis of paracetamol from phenol?

2. During the crystallization of acetaminophen, why was the mixture cooled in an ice bath?

3. Give two reasons why the crude product in most reactions is not pure.

4. Phenacetin has the structure shown below. Write an equation for its preparation starting from
4-ethoxyaniline.
Part II: Extract Curcumin form Curcuma Longa powder by crystallization.

1.Introduction:

Curcumin, C21H20O6, diferuloylmethane, or (1E,6E)-1,7-bis (4-hydroxy- 3-methoxyphenyl) -1,6-

heptadiene-3,5-dione, is a polyunsaturated polyphenolic compound which can be found in
several plant species, but mostly found with significant concentration in the rhizomes of turmeric
(Curcuma longa L.) along with its two derivatives, demethoxycurcumin and
bisdemethoxycurcumin.

For a long time before curcumin was isolated from turmeric, the spice itself had been appeared
and popularly used as spice and in mixture with other spices to form the curry powder, which is
described in ancient medicinal literature (in Vietnamese: khương hoàng) as one of the good spice
that helps the digestive system and cure either hepatic, gastric-intestinal diseases or
inflammation. Right after curcumin was separated from turmeric, its clinical approach became
favourite subject of scientists around the activity of its antioxidant-supported structure and the
mechanism of how it attacks to treat such diseases and until nowadays, finally almost all of
curcumin fuctions was found and detailed and this knowledge lets us understand one of the most
enthralling yet wonderful and multifunction compounds.

2. Chemicals, Reagents and Equipments

 Curcuma Longa powder

 Ethanol
 Distillated water
 Erlenmeyer 125-250 ml
 Glass beaker 100 ml
 Funnel
 Water bath
3. Procedure:
Step 1: In Erlenmeyer, add the mixture of 2g of Curcuma Longa powder and 50ml of Ethanol are
placed and heated to boil for 20 minutes.

Step 2: The unsoluble is removed through the funnel containing filter paper.

Step 3: The filtrate is added some dropwise of distilled water until the solution become opaque
then add a few drop of hot ethanol until the solution become limpid again. Let the solution be
cooled for about 4h at 0C and the crystal of curcumin is formed.

Step 4: The crystal of curcumin is collected by filtration through a Buchner funnel. and is
warmed in an oven (55°C) (about 2h).

Step 5: Check the purity of Curcumin by TLC (The solvent system: mixture of ethyl acetate/n-
hexane (40/60) and melting point is verified also.

A TLC plate

4. TLC analysis

Step 1: Prepare a TCL plate with 6 cm long and 2 cm wide (silica gel 60 F254 coated on
aluminium 0,25 mm plate from Merck).

Step 2: Dissolve small amount of product of Curcumin in n-hexane in a eppendorf. Dissolve

small amount of the Curcuma Longa powder in ethyl acetate in n-hexane also.

Step 3: Put solution of Curcuma Longa powder sample and the solution of product on the TLC
plate by capillary tube.

Step 4: Prepare the TLC developing chamber, the solvent system is a mixture of ethyl acetate/n-
hexane (40/60).
 Organic Chemistry Lab Report
I. PRELAB WORK

EXP. NUMBER SUBJECT DATE

NAME COURSE

I.1 Introduction (In a sentence or two, explain the brief theoretical background and value of
the experimental procedure. State the exact reaction that will be carried out and state how the product
will be analyzed)

I.2 Chemical Reactions (Write a balanced chemical equation representing the reactions
which occur during the experiment)
 I.3 Physical Data (List the molecular weight, melting point, boiling point, density,
solubility, and hazards of all pertinent chemicals used in the experiment. Chemfinder.com is an excellent
site to find this data.)

Chemicals used MW mp bp Density Solubility Hazards

II. DURING AND AFTER LAB WORK

II.1 Procedure (Briefly summarize the procedure to be followed. You do not need to write
out the procedure in complete sentences and do not copy directly from the Lab Manual. All you need
is a brief but complete listing of what you plan to do in the lab.)
 II.2 Data and Observations (Your observations of the experiment as it progresses are
important, new information. Write these observations like color changes, appearance of crystals,
formation of an emulsion, boiling temperatures, test results, etc. in your notebook as you do the
experiment. Also record the weights of reagents and products and tare weights in this section.)

II.3 Discussion and Conclusions (This is the section you should explain what you did, what
you observed (your results), what this indicates, and what this indicates. Discuss the results you obtained,
explain where sources of error could have originated. Be sure to state if the objectives of the experiment
were successfully met or not.)
II.4 Questions and mentions (In this section you should answer the questions given by the
lecture and maybe give some mention about the experiment that you did.)