4-Bromoacetanilide preparation

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

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. 

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). 

Setting Up Suspend 500 mg of 4-bromoacetanilide in a stirred solution of 1 ml of concentrated hydrochloric acid and 1.3 ml of glacial acetic acid contained in the conical vial. If necessary, heat the mixture gently with stirring until it becomes homogeneous and then cool the solution to 0 C. Prepare a solution of 150 mg of sodium chlorate in about 0.5 ml of water. 

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