Para-Bromoacetanilide

Following are a few typical examples of medicinal compounds that are prepared by the help of bromination method, namely para-Bromoacetanilide para-Bromophenol Tetrabromofluorescein (or Eosin). 

Recrystallization. The crude product (3.0 g) may be recrystallized from rectified spirit (25 ml) either at room temperature or slightly warming it in an electric-water bath. The yield of pure colourless para-bromoacetanilide is 2.8 g (mp 166.5-167°C). 

Somewhat similar methods are used in the preparation of bromo-anilines. Consider, for example, the preparation of p-bromoaniline. The action of bromine on aniline gives quantitatively 2, 4, 6-tribro-moaniline. If aniline is first acetylated and then brominated, ortho-and poro-bromoacetanilides are formed with the para isomer predominating. The ortho compound is more soluble in alcohol than the para isomer, and thus can be removed by crystallization. The p-bromoacetanilide is then hydrolyzed. A variation of this method is to add bromine very slowly to aniline dissolved in a large excess of glacial acetic acid, when p-bromoaniline is directly formed, thereby eliminating acylation and hydrolysis. 

Acetanilide (i.e., the acetyl derivative of aniline) on being subjected to bromination (with Bvg) in a medium of glacial acetic acid gives rise to the /jura-bromoacetanilide with the liberation of a mole of HBr. The acetamide (—NHCOCHg) is an ortho, para director function hence, the incoming bromo moiety shall yield both ortho- and para-isomers. The latter is produced predominantly (upto 90%) as a white solid. 

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.)... 

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