O Chlorobenzoic acid

If the filtrate has a faint p>ermanganate colour, add a few drops of sodium bisulphite solution until the solution is colourless. In this case (compare o-chlorobenzoic acid) concentration of the solution before precipitation only increases the yield by about 1 g. and may cause occlusion of inorganic salts. 

In a 1 litre round-bottomed flask, equipped with an air condenser, place a mixture of 44 g. of o-chlorobenzoic acid (Section IV,157) (1), 156 g. (153 ml.) of redistilled aniline, 41 g. of anhydrous potassium carbonate and 1 g. of cupric oxide. Reflux the mixture in an oil bath for 2 hours. Allow to cool. Remove the excess of aniline by steam distillation and add 20 g. of decolourising carbon to the brown residual solution. Boil the mixture for 15 minutes, and filter at the pump. Add the filtrate with stirring to a mixture of 30 ml. of concentrated hydrochloric acid and 60 ml. of water, and allow to cool. Filter off the precipitated acid with suction, and dry to constant weight upon filter paper in the air. The yield of iV-phenylanthranilic acid, m.p. 181-182° (capillary tube placed in preheated bath at 170°), is 50 g. This acid is pure enough for most purposes. It may be recrystaUised as follows dissolve 5 g. of the acid in either 25 ml. of alcohol or in 10 ml. of acetic acid, and add 5 ml. of hot water m.p. 182-183°. 

Care must be taken to use pure o-chlorotoluene in this preparation otherwise the o-chlorobenzoic acid may be contaminated with isomeric acids which are very difhcult to remove. The o-chlorotoluene therefore should be prepared from pure o-toluidine or o-chlorotoluenesulfonic acid. 

The only practical methods of preparing o-chlorobenzoic acid consist in the oxidation of o-chlorotoluene and the replacement of the amino group in anthranilic acid by a chlorine atom. Both of these methods have been fully discussed by Graebe,1 who recommends the former for the preparation of relatively large quantities. The oxidation of o-chlorotoluene by permanganate was originally described by Emmerling.2... 

The reactivity of aromatically bound halogen is increased by nitro-groups in the ortho- and para-positions likewise the chlorine in o-chlorobenzoic acid is rather loosely held. 

C7H3C12F3 2,4-DICHLOROBENZOTRIFLUORIDE 3,4-DICHLOROPHENYL ISOCYANATE p-CHLOROBENZOTRIFLUORIDE m-CHLOROBENZOYL CHLORIDE 3-NITROBENZOTRI FLUORIDE BENZOYL CHLORIDE o-CHLOROBENZOIC ACID BENZOTRI CHLORIDE BENZOTRI FLUORIDE BENZONITRILE PHENYL ISOCYANATE 2,4,6-TRINITROTOLUENE... 

Exceptions to the general pattern in Figure 6 are nitrosalicylic acids (Table 1) and the -chlorobenzoic acids. Nitrosaiicylic acid salts are more lipophilic than expected from their aqueous pKa. The o-chlorobenzoic acids are less lipophilic than a m or p-benzoic acid would be of the same pKa. The 2,6-dichlorobenzoic acid point should perhaps be on a separate line parallel to the im and p-benzoics. From the values in Table I, the following correlations can be made for predicting the pKa, and therefore log P, for similar compounds. The 95% confidence limits are indicated. 

Ullman condensation of m-trifluoromethylaniline (13) with o-iodobenzoic acid in the presence of copper-bronze affords flu-fenamic acid (14). An analogous reaction of o-chlorobenzoic acid with 2,3-dimethylaniline (15) gives mefenamic acid (16) meclofenamic acid (18) is obtained by Ullman condensation employing 2,6-dichloro-3-methylaniline (17). 

Hot, dilute sulfuric acid hydrolysis of 10, R = alkyl, aryl initially gives anthranilic acid, which is converted into salicylic acid on prolonged reaction. When dilute hydrochloric acid is employed with the same substrates iV-alkyl- and AT-arylsalicylamides are formed, but concentrated hydrochloric acid results in the formation of o-chlorobenzoic acid. - ... 

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