O-Bromobenzoic acids

A limited number of pure substances are available from NIST, primarily clini-cally-relevant compounds such as cholesterol, urea, uric acid, creatinine, glucose, cortisol, tripalmitin, and bilirubin (NIST SRM website). These compounds are certified for purity (greater than 99 %) and are used as primary calibrants in definitive methods for these clinical analytes (see below). Several additional pure substances are available for specific applications such as microchemistry, i.e. elemental composition (acetanilide, anisic acid, cystine nicotinic acid, o-bromobenzoic acid, p-fluoro-benzoic acid, m-chlorobenzoic acid), polarimetric standards (sucrose and dextrose), acidimetric standard (benzoic acid and boric acid). Only three pure substance NIST RMs are available for environmental contaminants, namely the chlorinated pesticides, lindane, 4,4 -DDT, and 4,4 -DDE. 

The coupling of o-bromobenzoic acid and phenols leads directly to annelated coumarins (75CJC343). The formation of a similar quantity of salicylic acid, formed through a competitive... 

The conversion of the substituted 1,3-dicarbonyl compound into homophthalic acid is remarkably facile loss of the acetyl group by a retro-Claisen condensation and hydrolysis of the ester group are complete in a few minutes in aqueous sodium hydroxide. The overall synthesis of homophthalic acids from o-bromobenzoic acids occurs in high yield and provides an attractive route. 

In addition to out-of-plane bending, significant in-plane splaying-out of the exocyclic valency bonds was found in the above acids. Thus, the angle between exocyclic carbon-carbon and carbon-halogen vectors is increased beyond the value of 60° appropriate to a regular planar model to 67 4° in o-chlorobenzoic acid, to 68 3° in o-bromobenzoic acid, and to 67 2° in 2-chloro-5-nitrobenzoic acid. 

It was not until thirty-eight years later that this method of synthesis was applied to the aromatic series. Rosenmund,8 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,29 82 has been obtained in good yields by Rosenmund s method. From two other aromatic bromides, p-bromobenzoic add and... 

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.)...

This compound can also be synthesized by Fischer esterification of o-bromobenzoic acid with 2-propanol and an acid catalyst. 

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% yield by recrystallization from hot water. 

The acid has also been obtained by heating o-bromobenzoic acid in 10 per cent, potassium hydroxide with a 50 per cent, aqueous solution of potassium axsenite, 20 c.c. of alcohol and a little copper powder, in a reflux apparatus for ten to twelve hours at about 90° C. 20 grams of o-bromobenzoic acid yield about 12 grams of carboxylated acid. ... 

Carboxydiphenylamine-6 -arsinic acid.— This may be prepared from n-aminobenzoic acid as detailed on p. 463, or by replacing the o-bromobenzoic acid in the preceding preparation by the corresponding m-aeid. This acid crystallises from dilute acetic acid in small, yello-wish needles, decomposing at 235° to 288° C. Its solubility and colour reactions are similar to those given above. 

---