P-Chlorobenzoic acid

Chlorobenzene, electrostatic potential map of, 565 13C NMR absorptions of, 536 phenol from, 575 p-Chlorobenzoic acid, pKa of, 760... 

It is often possible in these cases to predict the correct isomer. In many cases, the groups already on the ring reinforce each other. Thus, 1,3-dimethylbenzene is substituted at the 4 position (ortho to one group and para to the other), but not at the 5 position (meta to both). Likewise the incoming group in p-chlorobenzoic acid goes to the position ortho to the chloro and meta to the carboxyl group. 

Many benzenesulfonamides have diuretic properties, particularly those having two such functions situated meta to one another. To some extent a carboxyl group can serve in place of one of the sulfonamido groups. Bumetanide (8) is such a substance. Chlorosulfonation of p-chlorobenzoic acid leads to 5, which is nitrated, and then converted to sulfonamide 6 with ammonia. 

The diuretic clopamide (35) is synthesized from p-chlorobenzoic acid (33) by chlorosulfonation and subsequent ammonia treatment to give 34. This is converted to its acid chloride with thionyl chloride and reacted with the desired hydrazine derivative... 

A. T. Hu, G. C. Sinke, M. Mansson, B. Ringner. Test Substancesfor Bomb Combustion Calorimetry. p-Chlorobenzoic Acid. J. Chem. Thermodynamics 1972, 4, 283-299. 

According to the other scheme, phenylhydrazone (3.2.46) undergoes cyclization in the presence of the same p-chlorobenzoic acid chloride, during which acylation of hydrazone and its cyclization into methyl ester of 5-methoxy-2-methyl-2-(p-chlorobenzoyl)-3-indoly-lacetic acid (3.2.52) simultaneously take place. The resultiug product is further hydrolyzed by au alkali to give indomethaciu (3.2.51) [113,114]. 

Addition of a suspected intermediate. If a certain intermediate is suspected, and if it can be obtained by other means, then under the same reaction conditions it should give the same products. This kind of experiment can provide conclusive negative evidence if the correct products are not obtained, the suspected compound is not an intermediate. However, if the correct products are obtained, this is not conclusive since they may arise by coincidence. The von Richter reaction (3-25) provides us with a good example here too. For many years it had been assumed that an aryl cyanide was an intermediate, since cyanides are easily hydrolyzed to carboxylic acids (6-5). In fact, in 1954, p-chlorobenzonitrile was shown to give p-chlorobenzoic acid under normal von Richter conditions.29 However, when the experiment was repeated with 1-cyanonaphthalene, no 1-naphthoic acid was obtained, although... 

Figure 5. Standards recovered from 10 mL of distilled-deionized water on a strong-anion-exchanger packed precolumn. Peak identities 1, 0.87 pg of phenoxyacetic acid 2, 1.2 pg of p-chlorobenzoic acid 3, 0.33 pg of 2-naphthalenesulfonic acid and 12, 0.055 pg of pyrene. Conditions for concentration, analytical separation, mobile-phase gradient, and detection were the same as in Figure 3. (Reproduced with permission from...

---