Acetamidobenzenesulfonyl chlorides Acetanilide

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. 

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

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.)... 

One of the most important examples is the chlorosulfonation of acetanilide 13 to /7-acetamidobenzenesulfonyl chloride 14 (Equation 38), since the latter is used as an intermediate in the manufacture of sulfonamide antibacterial drugs. The optimum reaction conditions were found to be the use of a relatively large excess of the reagent (five equivalents) at 60 °C (2 hours). In acetanilide (A -phenylacetamide) 13, the bulky acetamido (MeCONH) group is electron-donating (+M effect) and its large size virtually excludes o-sulfonation, so the / -sulfonyl chloride 14 is isolated as almost the sole product. 

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