Question

Show how you would use the same sulfonyl chloride as used in the sulfanilamide synthesis to make sulfathiazole and sulfapyridine.

Short answer

4-acetamidobenzenesulfonyl chloride on reaction with thiazol-2-amine undergoes nucleophilic attack of amino group onto the sulphur of sulfonyl chloride group as sulphur is electron deficient so acts as an electrophile and hydrogen chloride eliminates as leaving group. In next step, on treatment with hydrogen chloride and heat, acetanilide group gets reduced to amino group and formation of sulfathiazole occurs.

Formation of sulfathiazole

Step-by-step solution

Step-1. Formation of sulfathiazole:

4-acetamidobenzenesulfonyl chloride on reaction with thiazol-2-amine undergoes nucleophilic attack of amino group onto the sulphur of sulfonyl chloride group as sulphur is electron deficient so acts as an electrophile and hydrogen chloride eliminates as leaving group. In next step, on treatment with hydrogen chloride and heat, acetanilide group gets reduced to amino group and formation of sulfathiazole occurs.

Formation of sulfathiazole

Step-2. Formation of sulfapyridine:

4-acetamidobenzenesulfonyl chloride on reaction with pyridine-2-amine undergoes nucleophilic attack of amino group onto the sulphur of sulfonyl chloride group as sulphur is electron deficient so acts as an electrophile and hydrogen chloride eliminates as leaving group. In next step, on treatment with hydrogen chloride and heat, acetanilide group gets reduced to amino group and formation of sulfapyridine occurs.

Formation of sulfapyridine