Table of Contents

No Date Title of the Experiment Page Signature

01 Synthesis of Paracetamol 01-02

02 Synthesis of Aspirin 03-04

Synthesis of P-Amino Benzoic Acid

03 05-06
(PABA)

04 Synthesis of Para Amino Phenol 07-08

05 Synthesis of Benzocaine 09-10

Total No of Experiments:

No of Experiments signed:
Overall Remarks:

Signature of the Instructor

Department of Pharmacy International

Islamic University Chittagong
Pharm-3508 Medicinal Chemistry-I Lab

Experiment No: 01 Date:

Experiment Name: Synthesis of Paracetamol.
Principle:
Paracetamol is a black colored powder. It is less acidic than parent compound
Phenol. It possesses strong antipyretic and analgesic action. It is not toxic like
as P-amino phenol and safe. There are many pathways to synthesize
Paracetamol. Among them synthesis of Paracetamol from P-aminophenol is
most widely followed. In this process first of all P-amino phenol is prepared
from P-nitro phenol by reducing with tin powder and HCL in the presence of
SnCl2 and heat. When P-amino phenol is treated with acetic anhydride in
presence of conc.H2SO4 then Paracetamol is produced.

Apparatus:
1. Beaker 2. Glass rod 3. Cold water 4. Beaker [Link]
6. Filter paper 7. Pipette 8. Pipette pump 9. Water bath

Reagent:
1. 6gm P-aminophenol. 2. Acetic anhydride. 3. Conc. H2SO4.
4. Tin Powder

Procedure:
1. 6gm of P-amino phenol was weighed and transferred to 100ml of beaker.
2. 6.5ml of acetic anhydride and 3-4 drops of conc. H2SO4 was added
cautiously.
3. The mixture was mixed continuously on a water bath of 60 0C for about
20-25 min with constant stirring.
4. The mixture was allowed to attain room temperature and add 100ml of
cold water & stirred vigorously.
5. The crude product from previous step was filtered onto a Buchner funnel
using suction pump and washed with plenty of cold water.
6. The product was dried at oven (1600c). Then the amount of crude
Paracetamol drug was produced (at temp. 1690C -1700C).
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Pharm-3508 Medicinal Chemistry-I Lab

Calculation:

Theoretical yield value:

109gm of P-amino phenol produce = 151gm of Paracetamol.
6gm of P-amino phenol produce = 151*6/109gm of Paracetamol.
= 8.31 gm
Practical yield value:
Initial weight of filter paper = 0.74 gm
Weight of filter paper with crude drug = gm
Therefore, weight of crude drug = gm.
= gm.

Percentage of yield value:

practical yield value/
% of yield value = Theoretical yield value *100

% of yield value = *100

= %

Result: Thus, the % of yield value of Paracetamol was found to be= %

Precaution:
1. Apparatus must be clean and dry.
2. Conc. H2SO4 should be used with great caution.
3. The temperature should be maintained properly.
4. The mixture should be stirred constantly.

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Pharm-3508 Medicinal Chemistry-I Lab

Experiment No: 02 Date:

Experiment Name: Synthesis of Aspirin.
Principle:
Aspirin is one of the most widely compounds in therapy and used for many
years and is not associated with unwanted effects. The hydrogen atoms of the
hydroxyl group are salicylic acid which has been replaced by the acetyl group
and aspirin is found. The reaction for the synthesis of aspirin and the
mechanism for the synthesis of aspirin are given below.

Aspirin occurs as white crystals or as white crystalline powder. It is

slightly soluble in water and soluble in alcohol and chloroform. Aqueous
solubility may be increased by using acetated or citrated of alkali metals.
In the presence of moisture, it is slowly hydrolyzed into acetic acid and
salicylic acid. Aspirin is hydrolyzed in presence of weak acids and
digestive fluids of stomach. The gastric mucosal irritation of aspirin has
been observed due to salicylic acid formation.

Chemicals: 1. Salicylic Acid (3.5gm) 2. Acetic Anhydride 3. H2SO4

4. Acetic Acid (7.5ml)

Apparatus: 1. Beaker, [Link] rod, 3. Water bath, 4. Pipette, 5.

Pipette pump. 6. Hot air oven, 7. Buchner funnel, 8. Filter paper, 9.
Suction pump.

Procedure and Results:

1. Placed 3.5 g of salicylic acid in a 250 ml beaker.
2. Added 5 ml of acetic anhydride, and 3-5 drops of conc. H2SO4.
3. Added 7.5 ml acetic acid
4. Heated the flask gently on the water bath at 500c-600 for 25-30 minutes.
5. Allowed the flask to cool to room temperature. If acetylsalicylic acid does
not begin to crystallize out, scratch the walls of the flask with a glass rod.
Cool the mixture slightly in an ice bath until crystallization is completed.
The product will appear as a solid mass when crystallization is
completed.
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Pharm-3508 Medicinal Chemistry-I Lab

6. Added 50 mL of water and cool the mixture in an ice bath. Do not add the
water until crystal formation is complete.
7. Vacuum filtered the product using a Buchner funnel.
8. The product is then placed into hot air oven at 60 0c for (1-2hr).
9. Then the yield value was measured by calculation.

Calculation:

Theoretical yield value:

138 gm of Salicylic acid on reacting with 102gm acetic anhydride yields
Aspirin = 180gm of aspirin.
3.5gm of Salicylic acid is used for = 180*3.5/138.12 gm of aspirin.
= 4.5 gm
Practical yield value:
Initial weight of filter paper = gm
Weight of filter paper with crude drug = gm
Therefore, weight of crude drug = gm.
= gm.
Percentage of yield value:
practical yield value/
% of yield value = Theoretical yield value *100

% of yield value = *100

= %

Result:
Thus, the % of yield value of Aspirin was found to be %

Precaution:
1. Apparatus must be clean and dry.
2. Conc...H2SO4 should be used with great caution.
3. The temperature should be maintained properly.
4. The mixture should be stirred constantly.

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Pharm-3508 Medicinal Chemistry-I Lab

Experiment No: 03 Date:

Experiment Name: Synthesis of P-amino benzoic acid
(PABA)
Principle:
P-amino benzoic acid has been mentioned as a bio-synthetic compound of folic
in bacteria, higher mammalian can`t synthesize folic acid from its precursors. It
seems to perform some metabolic function in some animals. PABA is a white
crystalline substance that occurs widely over the plant animal kingdoms. It is
soluble in water slightly, freely soluble in alkali and alcohol. PABA is prepared
by reduction of P-nitro benzoic acid in the presence of tin and conc. HCl. PABA
is the ingredient of Vit. B complex. It is used for the preparation of certain local
anesthetic as “Novocain”. Novocain is used in dentistry. PABA will protect
some animals from total infections of epidemic typhoid, Rocky Mountain
spotted fever. PABA appears to function as a co-enzyme. It has been suggested
as an effective sunscreen as a 5% solution in 55% to ethyl alcohol.

P-nitro benzoic acid P-amino benzoic acid

Chemicals: 1. P-Nitro Benzoic Acid. 2. Tin Powder. 3. Conc. HCl

4. Acetic Acid 5. Ammonium Solution 6. Cold
water

Apparatus : 1. Round bottom flask 2. Glass rod 3. Condenser

4. Spirit lamp 5. Litmus paper 6. Filter paper 7. Pipette

8. Pipette pump 9. Hot air oven, 10. Buchner funnel

Procedure:
1. 5 gm. of P-nitro benzoic acid was taken in 250 ml round bottom flask.

2. Then 12 gm. of tin powder and 25 ml conc. HCl was added.

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Pharm-3508 Medicinal Chemistry-I Lab

3. The flask was fitted with a condenser and the mixture was heated in
low flame until the tin undergoes reaction for 1-2 hrs. / (40 minutes).

4. The mixture was collected at a room temperature and excess was

removed by suction.

5. Add conc. Ammonia solution to the mixture.

6. Then it was acidified with glacial acetic acid and replaced in a

container of ice water until crystals to be separate.

7. The crystal was then collected and dried in oven weighted. Finally yield
value is measured.

Calculation:

Theoretical yield value:

167 gm of P-nitro benzoic acid produce = 137 gm of PABA
5 gm of P-nitro benzoic acid produce = 137*5/167 gm of PABA.
= 4.10 gm
Practical yield value:
Initial weight of filter paper = 0.74 gm
Weight of filter paper with crude drug = gm
Therefore, weight of crude drug = gm.
= gm.

Percentage of yield value:

practical yield value/
% of yield value = Theoretical yield value *100

% of yield value *100

= %

Result: Thus, the % of yield value of PABA was found to be %

Precaution: 1. Apparatus must be clean and dry.

2. Conc. HCl should be used with great caution.
3. The temperature should be maintained properly.
4. Weight of chemical should be taken carefully.

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Pharm-3508 Medicinal Chemistry-I Lab

Experiment No: 04 Date:

Experiment Name: Synthesis of P-amino phenol.

Principle:
4-Aminophenol is the organic compound with the formula H2NC6H4OH.
Typically available as a white powder, reflecting its slightly hydrophilic
character, the white powder is moderately soluble in alcohols and can be
recrystallized from hot water. In the presence of a base, it oxidizes readily. It is
used as developer in black and white film. Para amino phenol is a building
block compound. Prominently it is the final intermediate in the industrial
synthesis paracetamol. Para amino phenol is prepared from para-nitro phenol by
reduction with tin (Sn) and HCl in presence of SnCl2 and heat.

Chemicals :
1. P- nitro phenol 2. Tin powder.
3. Conc HCl. 4. Acetic acid
5. Ammonium solution 6. Cold water

Apparatus:
1. Pound bottom flask 2. Glass rod 3. Condenser
4. Spirit lamp 5. Litmus paper 6. Filter paper 7.
Pipette
8. Pipette pump 9. Hot air oven, 10. Buchner funnel
11. Suction pump.

Procedure:
1. 3.5 gm of P-nitro phenol was taken in 250 ml round bottom flask.

2. Then 3.5gm of tin powder and 7 ml conc. HCl was added.

3. The flask was fitted with a condenser and the mixture was heated in low
flame until the most of the Tin undergoes for 1-2 hrs. / (40 minutes).

4. The mixture was collected at a room temperature and excess Tin

separates by suction.

5. Add conc. Ammonia solution to the mixture just alkaline.

6. Then it was acidified to glacial acetic acid and replace in a container of

ice water until crystals to be separate.

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Pharm-3508 Medicinal Chemistry-I Lab

7. The crystal was then collected and dried in oven weighted. Finally yield
value is measured.

Calculation:

Theoretical yield value:

139 gm of P-nitro phenol produce = 109.13 gm of P amino phenol.
3.5 gm of P-nitro phenol produce = 109.13*3.5/139 gm of P amino
phenol.
= 2.74 gm

Practical yield value:

Initial weight of filter paper = 0.74 gm
Weight of filter paper with crude drug = gm
Therefore, weight of crude drug = gm.
= gm.
Percentage of yield value:

% of yield value = practical yield value/Theoretical yield value *100

% of yield value = *100
= %

Result:
Thus, the % of yield value of P-Amino phenol was found to be %

Precaution:
1. Apparatus must be clean and dry.
2. Conc. HCl should be used with great caution.
3. The temperature should be maintained properly.
4. Weight of chemical should be taken carefully.

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Pharm-3508 Medicinal Chemistry-I Lab

Experiment No: 05 Date:

Experiment Name: Synthesis of Benzocaine.

Principle:
Benzocaine is an ester and a local anesthetic. It is commonly used as a topical
pain reliever or in cough drops. It is the active ingredient in many over-the-
counter anesthetic ointments such as products for oral ulcers. It is also
combined with antipyrine to form A/B otic drops to relieve ear pain and remove
earwax. It is not recommended in children younger than two years old.
Benzocaine is sparingly soluble in water, it is soluble in dilute acids and very
soluble in ethanol. Chloroform and ethyl ether. Benzocaine is the ethyl ester of
P-amino benzoic acid (PABA). It can be prepared from PABA and ethanol.

Benzocaine

Chemicals:
1. PABA 2. Conc. HCl. 3. Ethyl alcohol 4. NaHCO3.

Apparatus:
1. Round bottom flask 2. Glass rod 3. Condenser
4. Spirit lamp 5. Filter paper 6. Pipette
7. Pipette pump 8. Hot air oven, 9. Buchner funnel
10. Suction pump.

Procedure:
1. 20 ml ethyl alcohol was taken to round bottom flask
2. 2.5 ml conc. HCl was added and 3 gm PABA was introduced to the
mixture.
3. After that a condenser is fitted to the flask and refluxes the mixture
for 40 min.
4. Then cooled the residue and water is added to the residue.
5. After that the mixture was heated with NaHCO 3 solution.

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Pharm-3508 Medicinal Chemistry-I Lab

6. The mixture was collected at a room temperature and then removed

by suction.
7. The crystal was then collected and dried in oven and weighed.
Finally yield value is measured.

Calculation:

Theoretical yield value:

137.14 gm of PABA produce = 165.2 gm of benzocaine
3 gm of PABA produce = 165.2*3/137.14 gm of benzocaine
= 3.61 gm

Practical yield value:

Initial weight of filter paper = 0.74 gm
Weight of filter paper with crude drug = gm
Therefore, weight of crude drug = gm.
= gm.
Percentage of yield value:

% of yield value = practical yield value/Theoretical yield value *100

% of yield value = *100
= %

Result:
Thus, the % of yield value of P-Amino phenol was found to be %

Precaution:
1. Apparatus must be clean and dry.
2. Conc. HCl should be used with great caution.
3. The temperature should be maintained properly.
4. Weight of chemical should be taken carefully.

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