P-Acetamidobenzenesulfonyl chloride

The first pyrimidine analogues of sulfanilamide were introduced in 1942, some five years after the start of the bacterial chemotherapy revolution. Sulfadiazine (1018 R = R = H) and sulfamerazine (1018 R = Me, R = H) may be made by treatment of pyrimidin-2-amine or its 4-methyl derivative, either with p-acetamidobenzenesulfonyl chloride followed by... 

Benzenesulfonyl azide, 4-(acetylamino)- (9) (2158-14-7) p-Acetamidobenzenesulfonyl chloride Sulfanilyl chloride, N-acetyl- (8) Benzenesulfonyl chloride, 4-(acetylamino)- (9) (121-60-8)... 

The following chemicals were obtained from the Aldrich Chemical Company, Inc., and were used without further purification p-acetamidobenzenesulfonyl chloride, 97% acetone, 99.9+%, HPLC grade sodium azide, 99% ethyl acetoacetate, 99% triethylamine, 99% rhodium(ll) acetate dimer phenylacetylene, 98%. The following solvents were obtained from Fisher Scientific and were used without further purification toluene, certified A. C. S. ethyl ether (Solvent grade, Concentrated) petroleum ether, certified A. C. S. Dichloromethane was distilled from calcium hydride. 

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. 

Chlorosulfonic acid must be handled with care because it is a corrosive liquid and reacts violently with water. The p-acetamidobenzenesulfonyl chloride should be used during the same laboratory period in which it is prepared. It is unstable and will not survive long storage. The sulfa drug may be tested on several kinds of bacteria (Instructor s Manual). 

Prepare a hot water bath at 70°C. Place the crude p-acetamidobenzenesulfonyl chloride into the original 5-mL conical vial and add 1.1 mL of dilute ammonium hydroxide solution. Stir the mixture well with a spatula and reattach the air condenser and drying tube (gas trap) using fresh, moistened glass wool. Heat the mixture in the hot water bath for 10 minutes. Allow the conical vial to cool to the touch and place it in an ice-water bath for several minutes. Collect the p-acetamidoben-zenesulfonamide on a Hirsch funnel and rinse the vial and product with a small amount of ice water. You may stop here. 

When the reaction is conducted in this way, however, a polymeric product is produced after Step 1. What is the structure of the polymer Why does p-acetamidobenzenesulfonyl chloride not produce a polymer ... 

Acetylation of aniline produces acetanilide (2) and protects the amino group from the reagent to be used next. Treatment of 2 with chlorosulfonic acid brings about an electrophilic aromatic substitution reaction and yields p-acetamidobenzenesulfonyl chloride (3). Addition of ammonia or a primary amine gives the diamide, 4 (an amide of both a carboxylic acid and a sulfonic acid). Finally, refluxing 4 with dilute hydrochloric acid selectively hydrolyzes the carboxamide linkage and produces a sulfanilamide. (Hydrolysis of carboxamides is much more rapid than that of sulfonamides.)... 

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