Acetanilide, electrophilic aromatic substitution

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Acetanilide is quite similar to anisole in its behavior toward electrophilic aromatic substitution. 

Acetanilide, having a much less basic N atom compared to aniline, undergoes electrophilic aromatic substitution under Friedel-Crafts conditions, forming a mixture of ortho and para products. 

Acetanilide reacts with chlorosulfonic acid in an electrophilic aromatic substitution ... 

Qi) Acetanilide is a reactive substrate toward electrophilic aromatic substitution. On reaction with chloroacetyl chloride, it undergoes Friedel-Crafts acylation, primarily at its para position. 

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/>-acetamidobenzene-sulfonyl 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.)... 

Bromine is a good electrophile, and acetanilide a good nucleophile, due to the presence of the donating amide nitrogen. Electrophilic aromatic substitution (SfAr) by the bromine gives the aryl bromide product, in which substitution of Br" occurs at the o-position. 

Purpose. This experiment extends our understanding of the experimental conditions under which electrophilic aromatic substitution reactions are carried out (also see Experiments [27] and [29A]-[29D]). It deals with electrophilic aromatic halogenation. The directive influence of the acetamido, —NHCOCH3, group on the bromination of acetanilide is explored. 

How do you account for the fact that N-phenylacetamide (acetanilide) is less reactive toward electrophilic aromatic substitution than is aniline ... 

Udenfriend et al. observed that aromatic compounds are hydroxyl-ated by a system consisting of ferrous ion, EDTA, ascorbic acid, and oxygend Aromatic and heteroaroinatic compounds are hydroxylated at the positions which are normally most reactive in electrophilic substitutions. For example, acetanilide gives rise exclusively to the o-and p-hydroxy isomers whereas quinoline gives the 3-hydroxy prod-uct. - The products of the reaction of this system w ith heterocyclic compounds are shown in Table XIII. 

The question of the identity of the nitrating species can be approached by comparing selectivity with that of nitrations known to involve the nitronium ion. Examination of Part B of Table 9.8 shows that the position selectivity exhibited by acetyl nitrate toward toluene and ethylbenzene is not dramatically different from that observed with nitronium ion. The data for 2-propylbenzene suggest a higher o p ratio for nitronium ion nitrations, however. Several substituted aromatic compounds— for example, anisole and acetanilide — give much higher 0 p ratios when nitrated by acetyl nitrate than when nitronium ion conditions are used, suggesting the involvement of a different electrophile. ... 

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