Dioxindoles isatins

The products of partial reduction of isatin, dioxindole and oxindole, have been widely... 

G. A. Russell, C. L. Myers, P. Bruni, F. A. Neugebauer, and R. Blankespoor, Semidiones. X. Semidione radical anions derived from indan-2.3-dione, coumaran-2.3-dione, thianaphthalenequi-none, isatin, and IV-hydroxy isatin. Nitroxide radicals derived from isatin, dioxindole, oxindole, and other indole derivatives, /. Am. Chem. Soc. 92, 2762-2768 (1970). 

Isatin and its derivatives have reacted with both aryl and alkyl Grignard reagents to give 3-alkyl (or aryl) dioxindoles (178).232,497-500 Use of an excess of phenylmagnesium bromide with A-benzyl501 and... 

Anthranilate, as well as isatin, isatoic anhydride, dioxindole and oxindole have been... 

In the reaction of isatins with some cyclic ketones, such as 4-hydroxy-2H-benzopyran-2-one, the initial dioxindole formed reacts with a second equivalent of the ketone yielding a 3,3-disubstituted oxindole. 

Isatin has been used in the determination of the enzymatic activity of ketopantoyl-lactone reductase587"590 and other fungal carbonyl reductases591"594, as it is a substrate of these enzymes that is reduced to a dioxindole in a reaction that can be monitored by colourimetry. Ketopantoyl-lactone reductase, also named as isatin hydrolase, can be used to remove unwanted isatin from the broth of the microbial production of indigo595 596. 

The formation of oxindol and dioxindol by reduction of isatin is, however, more in favour of the following constitution for these compounds —... 

Dioxindol—Hydrindic acid—C H,NOi—is formed by the action of Na on isatin suspended in HjO. It forms yellow prisms, soluble in HaO, and combines with both bases and acids. 

This reaction was initially reported by Martinet in 1913. It is a synthesis of dioxindole derivatives by alkali treatment of the condensation products from substituted anilines and ethyl or methyl ester of oxomalonic acid in the absence of oxygen. Thus it is known as the Martinet reaction. In the presence of oxygen, the dioxindoles are further oxidized into isatins. This reaction has been extended to the preparation of a- and -naphthisatins." ... 

Baeyer s most famous researches, on the constitution and synthesis of indigo, began in 1865. Indigo had been investigated by Laurent and by Erdmann, who obtained isatin from it by oxidation (see p. 389). Baeyer showed that isatin on reduction forms dioxindole and then oxindole, which when distilled with zinc dust (a favourite method with Baeyer) is reduced to the parent substance indole ... 

Kekule s formula for isatin has, by mistake, CO=CO). Of dioxindole and oxindole he says The first body is perhaps an aldehyde in oxindole direct linking of carbon has probably occurred. When, finally, indole is produced, the... 

Martinet reactions, though treatment of preformed iV-phenylglyoxamides such as 14 with Cu(II) catalysts have been reported to give either dioxindole 15 or isatin 16 in good yields. ... 

From 1913 to 1930, R. Stolle published several manuscripts describing the synthesis of oxindoles from anilines and a-chloroacyl chlorides. His typical substrates were chloroacetanilides or the corresponding MA -diphenylamide. The manuscripts also described the synthesis of isatines (2,3-dioxindoles) from arylamines and oxalyl chloride. The reactions require high temperatures (typically > 150 °C) to complete the cyclization step. 

The Stolle reaction is thought to occur via a typical mechanism for amide formation from an amine and acid chloride, followed by Friedel-Crafts alkylation or acylation. No definitive mechanistic work has been performed on this reaction, but incorporating the mechnistic understandings of two steps provides a firm basis for understanding the mechanism of this reaction. Formation of the mono-amide from oxalyl chloride and aniline provides intermediate 4, which in the presence of AICI3 undergoes intramolecular electrophilic aromatic substitution to the desired 2,3-dioxindole (isatin) 7 via intermediates 5 and 6. 

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