Synthesis of P-Bromoacetanilide from Acetanilide

Aim: To synthesize P-Bromoacetanilide from Acetanilide by halogenation (Bromination) reaction

Reference: G Joshi and S Adimurthy, Environment-friendly bromination of aromatic heterocycles using a bromide-bromate couple in an aqueous medium, Ind. Eng. Chem. Res., 2011, Vol.50, P. No. 12271–75,

Requirement:

Apparatus: Beaker, Stirrer, Filtration assembly, conical flask etc.

Chemicals: Acetanilide, potassium bromate and potassium bromide, Oxalic acid

Theory/Principle:

Bromination is an electrophilic substitution reaction on an aromatic ring. Substituents already present on benzene nucleus determine the position and extent of substitution of the new incoming groups. These substituents are generally classified as strongly activating (e.g. -NH₂), moderately activating (e.g.-NHCOCH₃) and deactivating (e.g. -NO₂). Bromination of acetanilide provides a good example to study orientation of the incoming electrophile on a moderately activated aromatic nucleus. The traditional experiment involves the use of Br₂-AcOH and however, liquid bromine is extremely corrosive and is hazardous to handle. To avoid risks in using liquid bromine, the methods to generate bromine in situ have been developed.

Fig. 1 Traditional method of Bromination

In acidic medium, KBrO₃-KBr is known to release bromine according to Fig. 2

Fig. 2 In-situ release of Bromine molecule

The liberated bromine reacts with the aromatic substrate as shown in fig. 3

Fig. 3 Synthesis of P-bromoacetanilide from Acetanilide

       Acetanilide undergoes bromination, with the formation of a mixture of o- and p-bromoacetanilide. The ortho compound is formed in only small amount, however, and being more soluble in ethanol than the para compound can be readily eliminated by recrystallization.

Fig. 4 Mechanism of Reaction

Procedure:

1. A mixture of acetanilide, potassium bromate and potassium bromide (1:1:1 molar ratio) is placed in a conical flask fitted with a cork.
2. The required volume of water (10 ml for 0.01 mol of acetanilide) is added and the mixture is gently stirred on a magnetic stirrer.
3. An aqueous solution of oxalic acid or citric acid (0.01 mol in 10 ml of water) is added in small portions over a period of 15 minutes.
4. The reaction mixture acquires a distinct yellow colour due to slight excess of bromine, indicating that no more bromine is required for the reaction.
5. To ensure completion of bromination, the reaction mixture is stirred for another 15 minutes and the crude product is filtered at the pump, wash well with cold water, and drain
6. The p-bromoacetanilide is obtained as colourless crystals, m.p. 167°.