Oxindoles indoxyls

The reactive 3-carbonyl group in compounds of type (279) undergoes aldol condensation with active methylene compounds such reactions of isatin with indoxyl, oxindole (Section 3.3.2.5.4) and with thiophenes (Section 3.3.1.5.7.ii) have already been mentioned. These compounds also react with Grignard reagents and phosphorus halides as expected, e.g. isatin (279 Z = NH) with MeMgBr and PC13 yields (285) and (286), respectively. 

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. 

The following exemplify reactions of the aldol type. 3-Hydroxythiophene with benzaldehyde forms (269). Anions derived from oxindole (270 Z = NH) and indoxyl (271) react with isatin (272) to give isoindigo (273) and indirubin (274). 

The C-2 and C-3 hydroxy derivatives of pyrrole are special in the sense that the tautomeric equilibria favor the pyrrolinone structures (see Section 3.04.6.2). Furthermore, the general synthetic methods are not usually applicable so that we will call attention in this section not only to the methods of directly introducing these substituents, which are rare, but also to those ring construction processes which specifically give the pyrrolinones and indolinones. The indole derivatives have widely used trivial names, oxindole (5) for indolin-2-one and indoxyl (6) for indolin-3-one, Carbocyclic hydroxy substituents in indole and carbazole, on the other hand, for the most part act as normal aromatic phenolic groups. These compounds are usually prepared by application of the standard ring syntheses. 

Quite early in the chemical studies of Wieland and King, evidence accumulated that the calabash curare alkaloids are indole derivatives, and with present knowledge it is possible to correlate the UV-spectra of many of them with one or another of the following related chromo-phores formally derived from the indole nucleus by oxidation, reduction, and substitution, or combinations of these processes. They are the indoline (II), 2-hydroxyindoline and the derived ethers (III), iV-hydroxy-alkylindoline and its ethers (IV), 2-methyleneindoline or 1-vinylindoline (Va or Vb, respectively), indole (VI), oxindole or 1-acylindoline (Vila or Vllb, respectively), -indoxyl (VIII), and /J-carbolinium (IX) systems it is not possible to distinguish with certainty by spectroscopic methods between the chromophores III and IV, between Va and Vb, or between Vila and Vllb. 

The literature contains many transformations of compounds of the type 184 and the 2-isatylidene analogs of 184 such compounds are frequently prepared from oxindoles and indoxyls, " rather than from isatins. 

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. 

When phenyl glycine ortho-caxhoxyMc acid is fused with potassium hydroxide it first loses water yielding an acid, indoi llic acid, and this loses carbon dioxide yielding indoxyl. In indoxyl the hydroxyl group is in the 3-position while in the isomeric oxindole it is in the 2-position. All of these comp>ounds are thus condensed hetero-cyclic compounds of a benzene ring and a pyrrole ring. Indole is the mother substance and the others are hydroxy or ketone derivatives. 

Isatin, Indole, etc.—By oxidation indigo yields isatin which by successive reductions as recently explained yields di-oxindole, oxindole and finally indole. Also indoxyl, the isomer of oxindole, yields indigo by oxidation. The composition formulas of indigo and these last compounds are as follows ... 

The word indole is derived from the word India a blue dye imported from India was known as indigo in the sixteenth century. Chemical degradation of the dye gave rise to oxygenated indoles (see 20.13), which were named indoxyl and oxindole indole itself was first prepared in 1866 by zinc-dust distiUation of oxindole. 

Hydroxyindole certainly contribntes in the tautomeric equilibrium with the carbonyl form, though it is the minor component. Indoxyl, 10.46, ° is more acidic than oxindole, the anion produced is ambident reactions with electrophiles at both oxygen and carbon are known. ... 

Mirroring oxindoles, aldol-type condensation at the 2-position in indoxyls can be accomplished either using the acetate of the enol form and base catalysis,or with indoxyl itself, in either acid or basic condi-tions. Borohydride redaction and dehydration allows these aUcylidene condensation prodncts to be converted into 2-substituted indoles. 

Indoxyl reacts further by radical coupling followed by oxidation to give indigo. Other oxidizing agents, as well as air, cause such reactions. On oxidation, indoles with substituents in the 3-position are converted into indol-2(3//)-ones (oxindoles) ... 

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