A. 3,5-Dichloro-2-aminobenzoic acid. A solution of 45 g. (0.33 mole) of anthranilic acid, 150 ml. of concentrated hydrochloric acid, and 850 ml. of water is placed in a 2-l. three-necked flask in a hood and weighed. While the solution is stirred rapidly, chlorine is introduced until the reaction mixture gains 45 g. (0.63 mole) in weight (Note 1). The flask is surrounded by a water bath to maintain the temperature of the reaction mixture below 30° during the chlorination procedure. The reaction mixture is filtered by suction, using a large (10–12 in.) Büchner funnel; the crude product is washed with water and then dried at room temperature (Note 2). There is obtained 55–65 g. of crude product melting at about 205°. The crude product is leached with 4 ml. of boiling benzene per gram, filtered by suction, and washed on the filter with 1 ml. of cold benzene per gram. After drying at room temperature, there is obtained 46.5–53 g. (69–78%) of crude 3,5-dichloro-2-aminobenzoic acid. The melting point of this material should not be lower than 211° (Note 3) and (Note 4).

B. Diazotization of 3,5-dichloro-2-aminobenzoic acid. Fifty grams (0.24 mole) of 3,5-dichloro-2-aminobenzoic acid is dissolved in a solution of 12 g. (0.3 mole) of sodium hydroxide in 700 ml. of water. To this solution is added 20 g. (0.29 mole) of sodium nitrite, and the solution is cooled to 10° (Note 5). One hundred milliliters of concentrated hydrochloric acid (sp. gr. 1.191) and 200 ml. of water are placed in a 2-l three-necked flask and cooled to 10°. The cold solution of sodium 3,5-dichloro-2-aminobenzoate and sodium nitrite is then added to the hydrochloric acid solution with cooling (10°) and efficient stirring at such a rate that no appreciable accumulation of undiazotized amine results (Note 6). At the conclusion of the diazotization, the resulting solution is stirred a few minutes with 2 g. of diatomaceous earth and filtered by suction (Note 7).

C. Preparation of the reducing agent. One hundred and twenty-five grams (0.5 mole) of cupric sulfate pentahydrate is dissolved in 500 ml. of water contained in a 3-l. three-necked flask equipped with a mechanical stirrer, and then 210 ml. of concentrated ammonium hydroxide (sp. gr. 0.90) is added with stirring. The solution is cooled to 10°. A solution of 40 g. (0.57 mole) of hydroxylamine hydrochloride in 140 ml. of water is prepared and also cooled to 10°. To the hydroxylamine hydrochloride solution there is added 95 ml. of 6N sodium hydroxide solution, and if not entirely clear, it is filtered by suction. This hydroxylamine solution is immediately added to the ammoniacal cupric sulfate solution with stirring. Reduction occurs at once with the evolution of nitrogen, and the solution becomes pale blue. If this solution is not used at once, it should be protected from the air.

D. dl-4,4',6,6'-Tetrachlorodiphenic acid. The reducing solution prepared above is cooled to 10° and maintained at 10–15° during the addition of the diazo solution from Part B, which is added from dropping funnel. A feed tube having a 2-mm. opening and dipping well below the surface of the reducing solution should be attached to the stem of the dropping funnel. The feed tube should be bent upward at the end and so placed that mixing of the reducing solution occurs rapidly (Note 8). The diazo solution is added at approximately 25 ml. per minute, and excessive foaming is suppressed by the addition of small amounts of ether (Note 9). At the conclusion of the reaction (Note 10), the ammoniacal solution is transferred to two 4-l. beakers, heated to 80–90°, and rapidly acidified to litmus with concentrated hydrochloric acid with vigorous stirring (Note 11). At this point acidification is continued more carefully until the solution is acid to Congo red (Note 12). A total excess of 100 ml. of acid is then added, and the solution is allowed to stand overnight. The product is filtered by suction and washed on the filter with four 250-ml. portions of water. After drying, the yield of crude product, melting at 180–215°, is 29–38.5 g. (63–84%).

The crude product is dissolved in 3.5 ml. of concentrated sulfuric acid per gram, heated with stirring to 150° for 5 minutes, and allowed to cool overnight. The resulting product is filtered by suction through a sintered-glass funnel and washed on the filter with three 15-ml. portions of concentrated sulfuric acid at room temperature. The filter cake is removed from the funnel and boiled with 50 ml. of water to remove adherent sulfuric acid. The product is then filtered and dried. The above procedure yields 19–22 g. (41–48%) of almost colorless dl-4,4'6,6'-tetrachlorodiphenic acid melting at 243–250° (uncor.) (Note 13). Pure acid may be obtained by a second recrystallization from concentrated sulfuric acid. Twenty grams of crude dl-4,4',6,6'-tetrachlorodiphenic acid, m.p. 243°, recrystallized from 70 ml. of concentrated sulfuric acid yields 6.54 g. (33% recovery) of colorless product melting at 258–259°.