Indoxyl-2-carboxylic acid

The quindoline 224 may be prepared by the condensation of indoxyl-2-carboxylic acid with 6-aminopiperonaldehyde in the presence of hydrochloric acid, when decarboxylation and cyclization take place. Nitric acid oxidation of 224 gave an unstable nitrodicarboxylic acid which decarboxylated readily to a nitromonocarboxylic acid formulated as 8-nitro-8-carboline-3-carboxylic acid (225). ... 

S-Arylthioglycolic acids possessing an ortho carboxyl group (77 R = R = H) are cyclized by acetic anhydride or base to the corresponding thioindoxyl-2-carboxylic acids (78 R = H) (method c), which often lose carbon dioxide spontaneously to give the thio-indoxyls (Table V).315 S>-(o-Cyanophenyl)thioglycolic acids give similar products on treatment with alkali (method d) (Table V).315... 

Reaction of enaminones and carboxylic acids is mainly interesting as a route for cyclization of suitable substituted enaminoketones to N-heterocycles45. In this way iV-cyclohexenylglycines can cyclize to indoxyl derivatives (equation 30). By a similar intramolecular acylation at the / -carbon of enaminones, fused indoles or pyrrole derivatives are obtained46-48. 

According to Chemical Abstracts 3-Hydroxy-lfl -pyrrolo[2,3-b]pyridine-2-carboxylic acid. The common names indoxyl, oxindole, and isatin will be used as they do not imply which tautomer is predominant. It is noted that the tautomers shown are in accord with current theory for indoles and have not been established as such. 

Indoxyl.—One more derivative of indole must be mentioned connected with the synthetic production of indigo. Isomeric with oxindole is another mono-hydroxy indole known as indoxyl. It is prepared from phenyl glycine or//fo-carboxylic acid, anthranil acetic acid. 

Heumann s Synthesis, Phenyl Glycine Ortho-carboxylic Acid.—The synthesis that has resulted in placing synthetic indigo on the market is that of Heumann by the fusion of phenyl glycine ortho-carboxylic acid with caustic potash. The product of this fusion is indoxyl which by atmospheric oxygen is oxidized to indigo. The industrial success of this synthesis was achieved only when the preparation of the-phenyl glycine ortho-carboxylic acid from a cheap source was accomplished. 

Finally the phenyl glycine ortho-carboxylic acid is fused with sodium hydroxide and converted into indoxyl which by atmospheric oxidation... 

Among later syntheses of indigo was that from phenylglycine carboxylic acid by Heumann. This was first made from aniline, but its preparation from naphthalene made the process technically workable. The research was carried out for the Badische Co. by their chemist E. Sapper (1891-7) and depended on the oxidation of naphthalene to phthalic acid by heating with concentrated sulphuric acid in presence of mercury as a catalyst (said to have been discovered accidentally by the breaking of a thermometer bulb). Phthalic acid was converted into phthalic anhydride, phthalimide, and anthranilic acid, and phenylglycine carboxylic acid by condensation of this with chloracetic acid. On fusion with caustic potash, or better sodamide, this formed indoxylic acid, and indoxyl, which was easily oxidised to indigo. 

Indoxylic Acid (i-Hydroxyindole-2-carboxylic acid, indogenic acid)... 

Indoxyls (140) have been reported to be oxidized under a variety of conditions to indolones (158). However, the literature claims are conflicting. Ruggli claimed to oxidize 2-phenyl-6-nitroindoxyI to the corresponding indolone with nitrous acid, but attempts to repeat this reaction failed.Benzoyl peroxide oxidized 2-(4-aminophenyl)-4,6-dinitroindoxyl to the corresponding indolone, but methyl indoxyl-2-carboxylate to the diindoxyl (141 R = COjMe). Isatogens are reduced under a variety of conditions to a number of different products which include some indolones (158 R = Ph, 4-methoxyphenyl) and indolone hydrates (139 R = COjMe, 2-pyridyl R = H) for a detailed discussion see Section II1,B and Table I. 

Nakaura and Ukita devised a simple indole synthesis from the Rh-catalyzed condensation of a-diazophospho-nates and o-acylanilines (Scheme 6, equation 1) [58]. Moody and colleagues combined diethyl diazomalonate and Af-alkylanilines in a Rh-catalyzed synthesis of indox-ylic acid esters (equation 2) [59], This chemistry represents a simple synthesis of these rare indoxyl-2-carboxylates. 

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