4-Acetamidobenzenesulfonamide preparation

The fact that Prontosil was inactive in vitro but active in vivo should have suggested that the dye was converted to an active compound by the mammalian organism, but this did not occur to the bacteriologists, who were content to have found a useful antibiotic. When scientists at the Pasteur Institute later investigated Prontosil, they noted that mice given the drug did not excrete a red compound. Urine analysis showed that the mice excreted para-acetamidobenzenesulfonamide, a colorless compound. Chemists knew that anilines are acetylated in vivo, so they prepared the nonacetylated compound (sulfanilamide). When sulfanilamide was tested in mice infected with streptococcus, all the mice were cured, whereas untreated control mice died. Sulfanilamide was the first of the sulfa dmgs. 

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. 

Setting Up Prepare 20 mL of a solution of dilute hydrochloric acid by adding 10 mL of concenfrafed hydrochloric acid to 10 mL of water swirl to mix. Equip the round-bottom flask with a stirbar and add the 4-acetamidobenzenesulfonamide and an amount of dilute hydrochloric acid that is about twice the weight of the crude 4-acetamidobenzenesulfonamide. Assemble the apparatus for heating under reflux. 

Why would you expect the yield of 4-acetamidobenzenesulfonamide (9) to be lowered if the crude sulfonyl chloride 8 were not combined with ammonia until the laboratory period following its preparation ... 

In the preparation of sulfanilamide (1) from 4-acetamidobenzenesulfonamide (9), only the acetamido group is hydrolyzed. Explain this difference in reactivity of the acetamido and sulfonamido groups toward aqueous acid. 

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