4-Acetamidobenzenesulfonamide

Brown, Mueller, and Morehouse reported studies with 2-chloro-4-nitrobenzamide (XIV) and combinations of XIV with N-(p-nitro-phenyl)-4-acetamidobenzenesulfonamide (XV) against coccidiosis. These authors noted that tolerated levels of XIV were able to protect chickens from mortality due to exposure to E. necatrix or E. tenella, but that protection against E. acervulina could be achTeved only at toxic levels with XIV alone. A combination equivalent to a final dietary concentration of 0.025% of XIV and 0.020% of XV, designated Novastat prevented development of coccidiosis when tested against all three Eimeria species E. tenella,... 

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 ... 

Concentrated ammonia contains 72% water, yet its reaction with 4-acetamidobenzenesulfonyl chloride (8) produces 4-acetamidobenzenesulfonamide (9) rather than 4-acetamidobenzenesulfonic acid (17). Why is ammonia more reactive than water toward 9 ... 

Using curved arrows to symbolize the flow of electrons, write a stepwise mechanism for the aminolysis of 4-acetamidobenzenesulfonyl chloride (8) to give 4-acetamidobenzenesulfonamide (9). 

Discuss the differences observed in the IR and NMR spectra of 4-acetamido-benzenesulfonyl chloride and 4-acetamidobenzenesulfonamide that are consistent with the formation of the latter in this procedure. 

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. 

Following hydrolysis of 4-acetamidobenzenesulfonamide (9) with aqueous acid, the reaction mixture is homogeneous, whereas 4-acetamidobenzenesulfonamide is insoluble in aqueous acid. Explain the change in solubility that occurs as a result of the hydrolysis. 

What would be observed if 4-acetamidobenzenesulfonamide were subjected to vigorous hydrolysis conditions, such as concentrated hydrochloric acid and heat, for a long period of time Write an equation for the reaction that might occur. 

The replacement of the reactive 5-chloro by a sulfonamido group in 1,2,4-thiadiazoles affords a convenient synthesis of the 5-sulfonamido heterocycles.92- 3,168-172 173 Thus, 5-halogeno compounds (171), on treatment with p-acetamidobenzenesulfonamide and potassium carbonate in diphenyl ether at 200°, afford the sulfonamido derivatives (170) in 70 % yields. Nitrobenzenesulfonamides do not react. This route is valuable, because the products are obtainable with difficulty by sulfonylation of the parent amine (see Section III,D, 1,A).8-8S-86-87 The superiority of route 171 -> 170 over route 169-y 170, though unusual in the heterocyclic field, recalls similar observations made in the synthesis of sulfonamidotriazines.174... 

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. 

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