P- Bromobenzoic acid

A mixture of 35 g. of copper sulfate, 100 g. of sodium bromide, 30 g. of copper turnings, 33 g. of concentrated sulfuric acid, and 300 ml. of water is heated to boiling. After the color is gone from the solution, 40 g. (0.29 mole) of anthranilic acid is added and the mixture cooled to below 10°. An aqueous solution containing 22 g. (0.32 mole) of sodium nitrite is added dropwise, the temperature of the reaction mixture being held below 10°, and the mixture allowed to stand at room temperature for several hours. Filtration of the mixture gives a 90 yield of crude o-bromobenzoic acid. The pure acid, m.p. 150°, is obtained in 82 Jo yield by recrystallization from hot water. 

A mixture of 1.5 1. of water, 25 g. (0.15 mole) of p-bromotoluene, and 2 g. of sodium hydroxide is heated to boiling, and 51 g. of potassium permanganate is added all at once. The resulting mixture is 

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Elemental Analysis. The acetone fractions were analyzed for C, H,- and N by an automatic analyzer. Sulfur and the halogens (i.e., Cl and Br) were analyzed by combustion and subsequent titration. The following standard compounds were used for quality assurance (QA) purposes acetanilide (C, H, N), sulfanilamide (S), p-chlorobenzoic acid (Cl), and p-bromobenzoic acid (Br). 

If the solution in the flask is acidified with hydrochloric acid, about 8 g of crude p-bromobenzoic acid may be isolated. 

Fig. 4.13. Separation of acidic compounds in columns packed with (a) 5 pm Spherisorb-ODS and (b) 5 pm Spherisorb-SAX materials. In (a) the mobile phase was composed of 60% acetonitrile in 2mM phosphate buffer (pH 2.2) and in (b) the mobile phase was composed of 50% acetonitrile in 20 mM phosphate buffer (pH 2.2). The compounds were 1, 3,5-dinitrobenzoic acid 2, p-nitrobenzoic acid 3, p-bromobenzoic acid 4, o-toluic acid 5, benzoic acid 6, o-bromobenzoic acid. Reprinted from ref. [102] with permission. Copyright Elsevier 2000.

Figure 6 Chromatogram for separation of positional isomers of bromobenzoic acid in strong anion-exchange CEC. Experimental conditions mobile phase, 50% acetonitrile in 10 mM phosphate buffer pH 2.2. Peaks (1) p-bromobenzoic acid (pKa 4.00) (2) m-bromobenzoic acid (pKa 3.81) (3) o-bromobenzoic acid (pKa 2.85). (Reprinted from Ref. 41, with permission.)...

The route shown above is one of several ways to synthesize p- bromobenzoic acid and is definitely not the simplest way. (The simplest route is Friedel-Crafts alkylation -> bromination - oxidation). The illustrated synthesis shows the use of the diazonium replacement reaction that substitutes bromine for a nitro group. Oxidation of the methyl group yields the substituted benzoic acid. 

This rctrosynthetLC anttlysis has provided two valid routes from ben zone to p bromobenzoic acid iPtgurp IB 23 K... 

A mixture of 35 g. (0.17 mole) of p-bromobenzoic acid (p. 39) and 36 g. (0.17 mole) of phosphorus pentachloride is warmed on a steam bath until there is no more visible evidence of reaction. The resulting mixture is distilled under reduced pressure. The p-bromo-benzoyl chloride is collected at 136-138°/20 mm. and is obtained in 92% yield. The product solidifies in the receiver. 

It was not until thirty-eight years later that this method of synthesis was applied to the aromatic series. Bosenmund, in 1921, prepared phenyl-arsonic acid (in low yield) and o-carboxyphenylarsonic acid (44% yield) from tripotassium arsenite and bromobenzene and o-bromobenzoic acid, respectively. Since that time only one other arsonic acid, o-phenylene-diarsonic acid, - has been obtained in good yields by Bosenmund s method. From two other aromatic bromides, p-bromobenzoic acid ahd... 

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