P-Bromoacetanilide

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 ... 

Bromo-4-acetaminotoluene, 593, 605 p-Bromoacetanilide, 577, 580 p - Bromoace tophenone. 726, 732 m-Bromo-p-acetotoluidido, 593, 605 3-Bromo-4-aminotoluene, 593, 605 hydrochloride, 605 p-Bromoanilides, 361 p-Bromoaniline, 577, 580 o-Bromoanisole, 404 p-Bromobenzaldehyde, 689, 694, 696 diacetate, 696... 

Protection of the amino group by acetylation, as in acetanilide, therefore usually permits monosubstitution reactions with appropriate electrophilic reagents to proceed smoothly. Thus with bromine, p-bromoacetanilide is the main product the small quantity of the ortho isomer simultaneously formed can be easily eliminated by recrystallisation (Expt 6.67) hydrolysis of p-bromoacetanilide gives p-bromoaniline. Nitration leads similarly to p-nitroacetanilide which can be hydrolysed to p-nitroaniline (Expt 6.68). 

Hydrolysis of p-bromoacetanilide. Dissolve 18 g (0.084 mol) of p-bromoacetanilide in 35 ml of boiling ethanol contained in a 500-ml round-bottomed flask equipped with a reflux condenser. With the aid of a pressure-equalising dropping funnel add 22 ml of concentrated hydrochloric acid down the condenser in small portions to the boiling solution. Reflux for 30-... 

Caira, M. R. and Dodds, D. R. 1999. Inclusion of nonopiate analgesic drugs in cyclodextrins. I. X-ray structure of a 1 1 beta-cyclodextrin-p-bromoacetanilide completed. Phenom. Macrocycl. Chem. 

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. 

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