Benzene carboxylates 4-aminobenzoic acid

The benzene ring has been proposed as an isosteric replacement in a dipeptide to enforce either the tram l1 1 or the cis conformation 312>31 (Scheme 1). Similarly, 2-(amino-methyl)pyrrole-l-acetic acid (8, R = H) has been proposed as a cis peptide bond mimic,141 having the same number of atoms between the amino and carboxylic acid functions as in a dipeptide. Several other amino- and carboxy-substituted aromatic structures have been used as spacers in peptides 2-, 3-, and 4-aminobenzoic acids (Abz, e.g., 7), 2-, 3-, and 4-(amino-methyl)benzoic acids (Amb, e.g., 2), 2-, 3-, and 4-(aminophenyl)acetic acids (APha, e.g., 5), 2- (4), 3-, and 4-(aminomethylphenyl)acetic acid (Ampa), (aminomethyl)pyrrole-, -thiophene-, and -furancarboxylic acids 6, (aminomethyl)pyrrole- 8 and -thienylacetic acids, and aminobiphenylcarboxylic acids. 

Direct introduction of the carboxyl group into an aromatic ring is accomplished with urea hydrochloride, phosgene, oxalyl chloride, or carbon dioxide. Carboxylation of benzene is effected in 15-58% yields by treating with liquid phosgene and aluminum chloride. No catalyst is required in the conversion of dimethylaniline and phosgene to p-dimethyl-aminobenzoic acid (50%). 9-Anthroic acid (67%) is prepared from anthracene by heating to 240° with oxalyl chloride and nitrobenzene. ... 

On this basis the lowered pA i for the aminobenzoic acids as compared with p Ta for the anilines could be rationalised as the effect of the conjugation of the carboxyl group to the benzene causing an increased likelihood for the protonated amino group to lose the proton. This would increase its strength as an acid relative to aniline. 

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