Bromination: of acetanilides

The reaction of acetanilides with tetraalkylanunonium polyhalides, such as TBA Br3, BTMA Bf3, or BTMA Br2Cl in dichloromethane-methanol at room temperature gave bromo-substituted acetanilides in good yields, respectively. These bromination of acetanilides have usually given predominantly the corresponding p-bromo derivatives (Fig. 12) (ref. 17). Furthermore, the reaction of acetanilides with BTMA Br3 in acetic acid in the presence of ZnCl2 gave polybromo-substituted acetanilides which was not obtained from the reactions in dichloromethane-methanol (ref. 18). 

Fig. 12. Bromination of acetanilides with BTMA Br3 Bromination of arenes...

Microsolvent effects in the cyclodextrin cavity have also been observed in hypochlorite chlorination of acetophenone1029. Higher para selectivity has been observed in the bromination of acetanilide and benzanilide in presence of cyclodextrins or amylose1030 and in the anodic chlorination of anisole with cyclodextrin-modified electrode1031. 

The reactivity of the aniline may be modified by acetylation. Bromination of acetanilide with bromine in acetic acid gives 4-bro-moacetanilide (4.6). Under some conditions, bromination can take place first on the amide to give the A-bromo compound. This then undergoes a rearrangement known as the Orton rearrangement to give the para substituted product. 

The 4-isomer is the major product because attack at the 2-position is sterically hindered. Nevertheless, ca. 10% of 2-bromoacetaniiide is produced during the bromination of acetanilide. 

Suppose, however, that we need o-nitroaniline. The synthesis that we just outlined would obviously not be a satisfactory method, for only a trace of o-nitroacetanilide is obtained in the nitration reaction. (The acetamido group is purely a para director in many reactions. Bromination of acetanilide, for example, gives/>-bromoacetanilide almost exclusively.)... 

In this experiment, you will study the bromination of acetanilide, aniline, and anisole ... 

Although benzene (4) is a potential starting point of our synthesis (Scheme 21.4), it is an alleged carcinogen, so the sequence of reactions begins with nitrobenzene (5). Discussion of and experimental procedures for the reduction of nitrobenzene and the conversion of aniline (6) to acetanilide (7) are found in Section 21.2, so the present description starts with the bromination of acetanilide. 

Sodium bisulfite is used to discharge the yellow color produced in the electrophilic aromatic bromination of acetanilide. 

Explain why electrophilic bromination of acetanilide produces 4- rather than 2-bromoacetanilide as the major product. 

Using curved arrows to symbolize the flow of electrons, provide a stepwise mechanism for the bromination of acetanilide with Br2/HOAc. 

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. 

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