Balqees darabee

201905548
Date: 9/3/2023

Exp.1: Synthesis of Sulfanilamide

Aim of the experiment : determine Synthesis of Sulfanilamide and calculate

the percentage yield of the this drug.

Introduction:
Sulfonamides (sulfa drugs) Sulfonamides( sulfa drugs) were the first medicines largely employed and
totally used as preventative and chemotherapeutic agents against various diseasesOver 30 drugs
containing this functionality are in clinical use.
Sulfonamides are frequently given at bacteriostatic doses, which means they block or restrict bacterial
growth . By preventing bacteria from synthesizing folic acid, sulfonamides have the bacteriostatic
effect (i.e., the mechanism of action). Bacteria use endogenous substances and enzymes to create their
own folic acid. The term "endogenous chemicals" refers to substances that naturally occur in
biological systems, Sulfonamides specifically block the enzyme dihydropteroate synthase, which is
responsible for converting PABA and dihydropteroate diphosphate to dihydropteroic acid, a precursor
to folic acid and DNA. As "competitive inhibitors" of the dihydropteroate synthase enzyme,
sulfonamides fight PABA for the "active site" in this enzyme. The PABA-like structure of the
sulfonamides "tricks" the enzyme into.

Mechanism of reaction:
Preparation of 4-Acetamidobenzenesulfonyl Chloride:
The chlorosulfonyl group can be introduced para to the acetamide group in one step using the electrophilic
aromatic substitution reaction known as chlorosulfonation:This reaction is more intricate than it initially
 appears to be. Perhaps SO3 is the electrophile that first adds to the ring to create the sulfonic acid. The sulfonic
acid is the first substitution product to generate. Due to the combined electrical and steric effects, substitution is
virtually all para. By reacting with extra chlorosulfonic acid, the sulfonic acid is subsequently transformed into
4-acetamidobenzenesulfonyl chloride, with sulfuric acid as a byproduct.
Preparation of 4-Acetamidobenzenesulfonamide
The reaction between 4-acetamidobenzenesulfonyl chloride and aqueous ammonia produces the appropriate
sulfonamide. On the following page's top, the reaction equation is displayed. This step is done right after after
isolating the 4-acetamidosulfonyl chloride in order to avoid losses brought on by the sulfonyl chloride's
hydrolysis.

Preparation of Sulfanilamide
Without influencing the sulfonamide group, which hydrolyzes much more slowly, the acetamide group of 4-
acetamidobenzenesulfonamide can be hydrolyzed in an acidic environment. To isolate sulfanilamide, the acidic
hydrolysis solution is finally neutralized with sodium carbonate.

Equation:

Equipment:
Beaker , Flask, dropper, funnel, filter paper, PH paper, hot plate, balance

Reagents and chemicals:

  5ml 6M Hydrochloric acid (HCL)
 6.5ml Chlorosulfuric acid (ClSO H)
3

 2.5g Acetanilide (NO H C)

9 8

 20ml concentrated Ammonium Hydroxide (NH OH) 4

Data and Results:

Weight of acetanilide = 2.50g
Weight of empty filter paper=1.04g
Weight of filter with sample= 2.09g

Calculation
Weight of sulfanilamide= 2.09 -1.04 =1.05g
Mole acetanilide= 2.50g/135.17 (g/mole) = 0.018mole
1mole acetanilide  1mole sulfanilamide
0.0185mole sulfanilamide= g/172
Mass= 3.182g

%yield= (Actual/ Theoretical)*100%

= (1.50/3.128)*100% = 33.6%

Discussion:
There are many way to to synthesis Sulfanilamide In this experiment
we have made Sulfanilamide Since sufficient chlorosulphonic acid
was added to acetanilide, the result is p-acetamidobenzenesulphonyl
chloride, which easily was transformed into the equivalent p-
acetamidobenzenesulphonamides when it reacted with ammonia. The
acetamido groups are readily hydrolyzed by an acid to produced p-
aminobenzene sulphonamide (sulphanilamide.)

the percentage yield was 33.6%

% Error= ((|Estimated value – True value|)/ True value) * 100%

 = |33.6-59|/59 *100%
 = 43%

Error and recommendations:
  the temperature was not monitored during
heatingchlorosulfonic acid carried out sulfonation rapidly at a
very high efficiency but chlorination was slow and had a low
efficiency. An additional reagent such as phosphorus
pentachloride (PCI5) might have been required for effective
chlorination.
 The yield would have increased appreciably if a minute amount
of NH,CI was combined with chlorosulfonic acid in
chlorosulfonation.
 complete chlorosulfonation takes about 1h-3h hours. In this
experiment, and the duration of the heating was only 10
minutes. a low yield of the acetaminobenzenesulfonyl chloride
intermediate was obtained.

Conclusion:
Sulfanilamide was synthesized and the percentage yield was found to
be 33.6% This procedure does not produce a lot product due to some
of the reaction conditions used. The chlorosulfonation procedure
would be more efficient if chlorosulfonic acid was used as the
sulfonation agent and a new reagent such as PCI, was used as the
chlorination agent. A higher yield could have been possible for
sulfanilamide if the duration of the hydrolysis was longer than an
hour.

 Questions:

1. What product would be expected if aniline rather than acetanilide were

treated with chlorosulfonic acid?aniline cannot be used as the starting material in
the synthesis. The amino group of aniline is a strong electrophile. This would cause
undesirable side reactions in the first and second steps because the molecule would
tend to react as a base or as a nucleophile to form undesirable products.

Aniline is a strong base. It can react with chlorosulfonic acid in a proton exchange in
the first step.
Even if this product could be prepared in the first step, it would react with itself in
the second one as a nucleophile.

2. e compound in solution after boiling the acetamidosulfonamide in

hydrochloric acid? What would be the result if excess sodium hydroxide
solution were used for the final neutralization after acid hydrolysis?
Add HCl to for acidic media.
3. Write a balanced equation for the overall reaction of acetanilide and
chlorosulfonic acid and indicate the mechanism of the reaction(s).

4. Why was ammonium hydroxide added to the experiment?

4-acetamidobenzenesulfonyl chloride is converted to the corresponding
sulfonamide
5. Why should we work with chloroisulfonic acid in dry and cold equipment?
It’s very sensitive to water it may cause a harm during lab .( Reacts
exothermically and violently with water producing sulfuric acid, hydrochloric
acid, and large quantities of dense white acid fumes).

Reference:
 https://chem.libretexts.org/Courses/Nassau_Community_College/
Organic_Chemistry_I_and_II/22%3A_Amines/22.10%3A_Sulfa_Drugs_-
_a_closer_look
https://labmonk.com/synthesis-of-sulphanilamide-from-acetanilide

https://chem.libretexts.org/Ancillary_Materials/Laboratory_Experiments/Wet_Lab_Experiments/
Organic_Chemistry_Labs/Lab_II/17%3A_Exp._48-_Sulfa_Drugs/
17.03%3A_The_Sulfonic_Acid_Group_and_its_Derivative
https://cameochemicals.noaa.gov/chemical/5911
https://www2.chem.wisc.edu/deptfiles/genchem/Chm346/pdfs/A00.Sulfanilamideexptpdf.pdf

Signature:
Darabee Balqees