Carboxylic acids benzoic acid, synthesis from

Initial efforts to prepare benzoic acid 28 from methyl or ethyl 4-aminobenzoate and biphenyl-2-carboxylic acid (27) afforded poor yields of 28 (48% and 7%, respectively). However, acylation of 4-aminobenzoic acid with biphenyl-2-carbonyl chloride was found to provide 28 in excellent yield (95%) when DMAP was employed as a base. Selective acylation of the anilinic nitrogen of 26 with benzoic acid 28 was accomplished in analogy with the first-generation process synthesis by conversion of 28 to the corresponding acid chloride (SOCl2, CH3CN) followed by acylation of 26 in acetonitrile. Subsequent addition of ethanolic hydrogen chloride to the reaction mixture resulted in the precipitation of conivaptan HCl (1), which was isolated in 90% yield. 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

Only para coupling was observed during the alkaline ferricyanide oxidation of 4-hydroxy-3-(3-hydroxybenzoyl)benzoic acid. 7-Hydroxy-9-oxoxanthene-2-carboxylic acid (515) was obtained in 21% overall yield from methyl 4-hydroxybenzoate (78JCS(P1)876). The synthesis utilizes a photochemical Fries rearrangement of methyl 4-(3-methoxybenzoyloxy)benzoate to prepare the benzophenone (514 Scheme 189). A similar route was used to prepare 2-hydroxy-2 -methoxybenzophenones, which undergo intramolecular cyclization with loss of methanol on treatment with base. 

An acyl transfer agent which can be used for the synthesis of acid anhydrides is obtained from the reaction of an acid chloride with 4-benzylpyridine (equation 24). In this way benzoic acid anhydride and cinnamic acid anhydride were obtained in 72% and 57% yields, respectively. As the intermediate, 1-acyl-4-benzylidene-l,4-dihydropyridines, can be isolated, Ais procedure should be well suited for the preparation of mixed anhydrides. Mixed aromatic and aliphatic anhydrides can be prepared with 2-ben-zoylthio-l-methylpyridinium chloride and salts of carboxylic acids. These reactions are carried out in aqueous solution. Iliey make use of the high reactivity of esters of thiocarboxylic esters towards nucleophiles. The mixed anhydrides of benzoic acid with 3-phenylpropanoic acid, phenoxyacetic acid, isobu-tyric acid, p-toluic acid and cinnamic acid were formed in 82, 79,61,91 and 66% yields, respectively. 

A further solution to the problem of isomer formation in the synthesis of oxoacridine carboaylic acids is to mask one of the two carboxyl groups. The requisite 2-(2-metho carbonylphet lamino)benzoic acids are available from methyl anthranilates reaction with diphenyliodonium carboxylates. The esters which result after cyclisation with polyphosphoric ethyl ester undergo ready alkaline l drolysis to the acid (G.W. Rewcastle and W.A. Denny. Synthesis. 1985. 220). 

The reagents used and the products liberated are depicted in Table 5.1. From a single anchor structure and synthesis, different products can be generated with the use of different cleavage reagents providing a further source of diversity (e.g., with hydroxymethyl-benzoic acid as linker — five carboxylic acid derivatives). 

Enantiopure l,2-cis-dihydroxycyclohexa-3,5-diene carboxylic acids have considerable synthetic potential as building blocks in chiral synthesis. Such cis-diols can be produced from benzoic acid derivatives by the action of toluate- 1,2-dioxygenase of Pseudomonas putida mt-2125 or homologous enzymes of a different origin (Fig. 16.6-... 

Protection of —COOH (3, 14-15). Full experimental details have been published for the protection of carboxyl groups as the 4,4-dimethyl-A -oxazoline derivatives. The derivatives are stable to Grignard and hydride reagents. This mode of protection was used in the synthesis of various substituted benzoic acids from the corresponding bromo acids. ... 

Anthranilic acid (o-amino benzoic acid) is an important monomer for the synthesis of carboxylic acid group-substituted PANI (Fig. 6.15). Studies on the synthesis of poly(anthranilic acid) (PANA) from an aqueous acidic solution are scarcely reported in the literature, probably because of difficulty in synthesis, poor yield, and brittle nature of the film due to presence of an electron-withdrawing carboxylic group. PANA reveals high solubility in an aqueous solution of NaOH or NMP. Similar to poly(metanilic acid), PANA exhibits electrochemical activity over a wide pH range in aqueous solutions owing to the substitution of the carboxylic acid group. 

A new, eco-friendly o-iodoxy benzoic acid-mediated synthesis of 3,5-dia-rylisoxazoles and 5-arylisoxazole-3-carboxylic acids from a,p-unsaturated ketoximes has been reported (14SC1453). 

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