Sulfa drugs sulfanilamide preparation

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. 

Purpose. The sequential synthesis is completed and the sulfa drug, sulfanilamide, is obtained by treatment of the sulfonyl chloride intermediate prepared in Experiment [C2], with an aqueous ammonia solution. This interesting product is fully characterized. 

The sulfonamides, or sulfa drugs, date back to the early 1900s but were not systematically studied until the 1930s. Sulfanilamide (A.17), a key reagent in the synthesis of certain dyes, was the first widely marketed sulfonamide (Figure A.5). Sulfonamides are antimetabolites and competitively inhibit a bacterial enzyme, dihydropteroate synthetase (DHPS) (see Chapter 1 and Chapter 6). DHPS plays a role in the synthesis of tetrahydrofolic acid (THF), an important compound in the preparation of thymidine. Because they limit the... 

As expected, the reaction of a sulfonyl chloride with ammonia produces a sulfonamide. This reaction is used in the preparation of sulfanilamide, a sulfa drug that was one of the first antibacterial agents ... 

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. 

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