Sulfa Drugs Preparation of Sulfanilamide

Testing the action of drugs on bacteria Preparation of a sulfonamide Aromatic substitution 

In this experiment, you will prepare the sulfa drug sulfanilamide by the following synthetic scheme. The synthesis involves converting acetanilide to the intermediate p-acetamidobenzenesulfonyl chloride in Step 1. This intermediate is converted to sulfanilamide by way of p-acetamidobenzenesulfonamide in Step 2. 

The intermediate sulfonyl chloride is converted to p-acetamidobenzene-sulfon-amide by a reaction with aqueous ammonia (Step 2). Excess ammonia neutralizes the hydrogen chloride produced. The only side reaction is the hydrolysis of the sulfonyl chloride to p-acetamidobenzenesulfonic acid. 

The protecting acetyl group is removed by acid-catalyzed hydrolysis to generate the hydrochloride salt of the product, sulfanilamide. Note that of the two amide linkages present, only the carboxylic acid amide (acetamido group) was cleaved, not the sulfonic acid amide (sulfonamide). The salt of the sulfa drug is converted to sulfanilamide when the base, sodium bicarbonate, is added. 

Reaction Methods Filtration, Sections 8.3 and 8.7 Crystallization, Section 11.4 Infrared Spectroscopy, Sections 25.4 and 25.5 Sulfa Drugs 

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