Preparation from Isatin

Anthranilates can be prepared from isatins by reaction of hydrogen peroxide in an... 

Wierenga discovered that borane-dimethyl sulfide reduced 3-(alkylthio)oxindole 5 to the desired indole (Scheme 3, equation 1), because LAH was sluggish or completely ineffective [15]. Subsequently, Wierenga generalized this smooth reduction of 3-(alkylthio)oxindoles (equation 2) [16]. Also reduced to 3-alkylindoles with BH -SMe were 3-hydroxyoxindoles (88-93%), which were prepared from isatins by selective C-3 addition of Grignards. Sano and coworkers used aluminum hydride to reduce 3-(phenylthio)oxindole 6 to the desired indole (equation 3)... 

An array of 25 600 analogues of 49a was prepared from 80 chalcones, 20 amino acids, and 16 isatins <1998T4085>. 

Imperial Chemical Industries (ICI) chemists " prepared a novel series of spirocyclic 2,4-oxazolidinediones 243 derived from 7-substituted isatins (Scheme 6.54). The key intermediate a-acyloxy amides 242 were readily prepared from 241 in three steps. Base-catalyzed cyclization of 242 then afforded the target compounds that were reported to be potent inhibitors of aldose reductase. Pfizer chemists approached 5-substituted isatin spirocyclic analogues 243 via a-hydroxy esters 244 that were converted to the corresponding a-carbamyloxy esters 245 in good yield using chlorosulfonyl isocyanate. Cyclization of 245 with potassium ferf-butoxide then produced 243 in acceptable yield (Scheme 6.54 Table 6.10, Fig. 6.20). 

Isatin cr-chloride (2-chloroindolone, 160a) has been known for a long time.105 It is usually considered as a derivative of isatin,106 from which it is prepared by treatment with phosphorus pentachloride in boiling benzene. The methyl ether (160b) is readily prepared from the silver salt of isatin.107... 

Isatin, JV-methylisatin, and JV-hydroxyisatin can be reduced to semidiones by treatment with the enolate anion of propiophenone in dimethylsulfoxide.258 Nitroxides are prepared from iV-hydroxyisatin by treatment with lead dioxide in dioxan, while another nitroxide was formed spontaneously from iV-hydroxyisatin in basic dimethyl sulfoxide solution in the presence of oxygen.256... 

The literature contains many transformations of compounds of the type 184 and the 2-isatylidene analogs of 184 such compounds are frequently prepared from oxindoles533-538 and indoxyls,539,540 rather than from isatins. 

Adolf von Baeyer reported the chemical structure of indigo in 1883, having already prepared the first synthetic indigo from isatin (2) in 1870. Until then, isa-tin had only been obtainable by oxidation of indigo. It was not until 1878 that von Baeyer first synthesized it from phenylacetic acid, making a complete synthesis of indigo possible [1],... 

Meth-Cohn and co-workers have observed that the treatment of 1,2-bis (N-methylanilino)-l,2-dichloroethanes, obtained by the dimerisation of the Vilsmeier reagents prepared from iV-methylformanilides in POCI3 using a tertiary amine, with an eletrophilic species yielded isatins in 11 to 79% after hydrolysis. The best yields were observed when bromine was used as the electrophilic species60 (Scheme 18). 

Isatinates, obtained from the alkaline hydrolysis of isatin derivatives, are the precursors of the quinoline-4-carboxylic acids. These compounds are prepared by the Pfitzinger reaction from isatins in the presence of enolizable keto compounds in strongly alkaline medium, such as 8N KOH. In these solutions, isatinates condense with the keto compound and subsequently cyclize to the quinoline products. Recently, a modified procedure has been described, using acidic conditions. This methodology was subsequently applied to a concise manner for the preparation of derivatives of camptothecin, a topoisomerase I inhibitor23 (Scheme 115). 

Isatin.—Furthermore, a di-ketone derivative of di-hydro indole-known as isatin is prepared from ortho-amino benzoyl formic acid as a lactam anhydride. 

Halogen derivatives [33] of indigotin have been prepared from the corresponding derivatives of isatin and of orthonitrobenz-aldehyde [37]. r... 

Dinitro- and diamido-indigotin have been prepared from dinitro-isatin [33]. (Compare the Synthesis of Indigo Blue, p. 231.)i... 

This compound is isomeric with indigotinj and is formed as a bye-product in the preparation of the latter from isatin chloride [22, 38]. 

A mixture of Meldrum s acid or barbituric acid derivatives, urea and aldehyde gave 99, stereoselectively. Reaction of 2-methylene indoline derivatives with l-nitroso-2-naphthol gave 100. Spiroheterocycles 101 were prepared from a mixture of isatin and aromatic or heterocyclic... 

Enantiomerically pure spiro oxindoles (Scheme 35) were prepared by using solid-supported N-cinnamoyl Evans oxazolidinone (164) [265]. Thus, chiral oxazolidi-none prepared from L-tyrosine was attached to a Merrifield resin and then N-acylated with the required unsaturated acyl chloride such as cinnamoyl chloride (not shown). The resin (165) was then suspended in aqueous dioxane and treated with proline and N-phenyl isatin at 80-90 °C overnight to give a highly substituted spiro compound (167). 

Stable phosphorus ylides (50) and (51) have been prepared from the reaction of electron-deficient acetylenic esters, such as dialkyl acetylenedicarboxylates or alkyl propiolates and triphenylphosphine in the presence of 3-chlorotetrahyd-rofuran-2,4-dione (Scheme 10). These reactions are thought to proceed via vinylphosphonium salt intermediates which undergo Michael addition with the conjugate base of the CH-acid. Similar methodology has been used to prepare phosphonium ylide (52) from triphenylphosphine, isatin (indoline-2,3-dione) and dimethyl acetylenedicarboxylate. " ... 

When thiophene is treated with isatin (667) and sulphuric acid a blue coloration is formed. The production of color in this way, the so-called indophenin reaction, led to the discovery of thiophene by Victor Meyer. Before thiophene was discovered it was thought that the reaction was characteristic of benzene. A certain sample of the hydrocarbon failed to give the test. On investigation it was found that the benzene used had been prepared from benzoic acid. As benzene obtained from coal-tar gave the test, it was evident that the color-reaction was produced by a substance mixed with the hydrocarbon. When benzene containing thiophene is shaken with concentrated sulphuric acid, the thiophene is more rapidly converted into a sulphonic acid than is the benzene. Thiophene is obtained from the sulphonic acid prepared in this way by heating the latter with water under pressure. 

Cyclocondensation of mercaptoacetic acid with diimines 828, prepared from two equivalents of isatin or iV-methylisatin with one equivalent p-phenylenediamine, was carried out under MWI to yield 829 in 74-78% yields (Scheme 156) (00SC537). 

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