BP607P Medicinal Chemistry-III

1. KOTA COLLEGE OF
PHARMACY
BP607P MEDICINAL CHEMISTRY – III
(Practical)
To synthesize and submit Sulphanilamide
Mr. Pradeep Swarnkar
Associate Professor

2. TO SYNTHESIS OF SULPHANILAMIDE FROM ACETANILIDE

3. REFERENCES:
1. Vogel's Textbook of Practical Organic Chemistry by
Brian S. Furniss, Antony J. Hannaford, Peter W. G.
Smith & Austin R.Tatchell; Fifth Edition: Page No. 883.
2. Practical in organic chemistry, by Hitesh G. Raval,
Sunil L. Baldania and Dimal A. Shah, Nirav Prakashan,
Page No. 308.
3. Indian Pharmacopoeia,Ministry of Health and Family
welfare, government of India, editon 1996, vol. II, page
no. A 196

4. REQUIREMENTS
Chemicals:
Acetanilide, Chlorosulphonic acid, Conc. Ammonia, Dilute
sulphuric acid, Sodium bicarbonate, Concentrated
hydrochloric acid

5. Apparatus:
Round-bottom flask - 2000 ml, Reflux condenser,
Beaker, Buchner funnel, Measuring cylinder, Filter
paper

6. THEORY:
Principle:
Sulphanilamide can beprepared by taking acetanilide and
treating it with excess of chlorosulphonic acid,which gives p-
acetamidobenzenesulphonyl chloride which readily converted
into corresponding p-acetamidobenzenesulphonamides upon
reaction with ammonia or ammonium carbonate. The
acetamido groups can easily undergo acid catalyzed hydrolysis
reaction to form p-aminobenzene sulphonamide
(sulphanilamide).

9. PROCEDURE

10. Step 1: To prepare p-acetamidobenzenesulphonyl chloride
Equip a double necked 500 ml flask with a dropping funnel and a reflux condenser. Attach the top
of the latter to a device for the absorption of hydrogen chloride. Take 20 g (0.148 mol) of dry
acetanilide in the flask and a good grade chlorosulphonic acid, 50 ml (90 g, 0.77 mol) in the
dropping funnel and attach a calcium chloride guard tube into the latter. Add the chlorosulphonic
acid in small portions and shake the flask from time to time to ensure thorough mixing. Heat the
reaction mixture on a water bath for 1 h after mixing in order to complete the reaction. Keep some
time for cooling and then pour the oily mixture in a thin stream with stirring into 300 g of crushed
ice (or ice water) contained in a 1 litre beaker. Carry out this operation carefully in the fume
cupboard since the excess of chlorosulphonic acid reacts vigorously with the water. Rinse the
flask with a little ice water and add the contents after rinsing to the contents of the beaker. Break
up the lumps (if any) of solid material and mix the content by stirring for several min in order to
obtain an even suspension of the granular white solid. Filter off the p-acetamidobenzenesulphonyl
chloride at the pump and wash it with a little cold water; press and drain well. Use the crude
product immediately in the next stage.

11. Step 2: To prepare p-acetamidobenzenesulphonamide:
Transfer the crude p-acetamidobenzenesulphonyl chloride to the rinsed
reaction flask and add a mixture of 70 ml of concentrated ammonia solution
and 70 ml of water. Mix well the contents of the flask and heat the reaction
mixture with occasional swirling (fume cupboard) to just below the boiling
point for about 15 min the sulphonyl chloride will be converted into a pasty
suspension of the corresponding sulphonamide. Cool the product suspension
in ice, and then add dilute sulphuric acid until the mixture is just acid to congo
red paper. collect the product on a buchner funnel, wash with a little cold
water and drain as completely as possible. it is desirable, but not essential, to
dry the crude pacetamidobenzenesulphonamide at 100 °C: the yield is about
18 g. The material is sufficiently pure for the next stage.

12. Step 3: To prepare p-aminobenzenesulphonamide
Transfer the crude p-acetamidobenzenesulphonamide to a 500 ml flask, mix 10 ml of
concentrated hydrochloric acid 30 ml of water. Boil the mixture gently under reflux
for 30-45 min. Then cool the solution to room temperature, should deposit no solid
amide; if a solid separates, heat for a further short period. Treat the cooled solution
with 2 g of decolourising carbon, heat the mixture to boiling and filter with suction
through a hardened filter paper. Place the filtrate of the mixture (a solution of
sulphanilamide hydrochloride) in a one litre beaker and carefully add 16 g of solid
sodium hydrogen carbonate in some portions with constant stirring. After the
evolution of gas has subsided, test the suspension with litmus paper and if it is still
acid, add more sodium hydrogen carbonate until neutral. Cool in ice, filter off the
sulphanilamide with suction and dry. The yield is 15 g (59% overall yield), m.p. 161-
163 °C. A pure product, m.p. 163-164°C, may be obtained by recrystallisation from
water or from alcohol.

13. Calculation:
Here limiting reagent is acetanilide; hence yield should be
calculated from its amount taken.
Molecular formula of acetanilide = C8H9NO
Molecular formula of sulphanilamide = C6H8 N2O5S
Molecular weight of acetanilide = 135 g/mole
Molecular weight of sulphanilamide = 172 g/mole

15. RESULT:
Sulphanilamide was synthesized and the percentage yield
was found to be......%