Indolines isatins

Piperidinomethylisatin on lithium aluminum hydride gave the indoline 67 while sodium borohydride reduction of the same isatin derivative gave a reductive dimerization to 68 and a reduction-rearrangement to 69.255... 

Another way was used to synthesize pentathiepinoindoles <2001T7185>. Thus, the reactions of 2-lithiated indole and 1-methylindole with elemental sulfur were studied, leading, for example, to a rational approach to the corresponding pentathiepino[6,7-A]indoles 126 and 127. Treatment of the anions of the corresponding indoline-2-thiones with sulfur also gave both pentathiepinoindoles (Scheme 27). Pentathiepino[6,7-A]indole 126 can be isolated from reaction of P4S10 with isatin in pyridine (Scheme 27) <1994TL5279>. 

This method has been used for the synthesis of 1-aryl and polycyclic isatins derived from phenoxazine, phenothiazine and dibenzoazepine as well as indoline. In the case of dimethoxyanilines, spontaneous cyclization to yield dimethoxyisatins in the absence of a Lewis acid has been observed, as exemplified in the synthesis of melosatin A, albeit in very low yield (Scheme 8). 

Isatins fail to yield Knoevenagel condensation products with malonic acid419. However, malonic acid can be condensed with isatin in a mixture of ethanol and pyridine, in which the initial condensation product suffers decarboxylation, furnishing an acetic acid derivative. This can be converted to the acid chloride and submitted to a Friedel-Crafts acylation reaction, yielding acetophenone derivatives420. Alternatively the oxoindolinylidene acetic acid derivative can be treated with an arene in the presence of AICI3 to yield. sy />o[indoline-3,3 -indan]-2,l-dione derivatives. ... 

Ji and co-workers [123] have reported a simple and efficient synthesis of spiro [indoline-3,4 -qumoUnes] 84 by a one-pot reaction of an isatin, malononitrile, and... 

Isatin (indoline-2,3-dione), 2-(hydroxyimino)indolin-3-one, 2-(ethoxyimino)indolin-3-one, and 3-(ethylimino)indolin-2-one are reported to undergo ring expansion to give quinazoline-2,4(l//,3//)-dione on treatment with aqueous alkali or ammonia. No yields are reported for these transformations in the relevant, older literature. ... 

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... 

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. " ... 

N-phosphonylation proceeds when there are a few electron-acceptor groups at the carbon atom of the C=N double bond [35]. Thus, 3-(0-methoxyphenylimino)indolin-2-one, obtained in 74% yield from isatin and o-anisidine, reacted with H-phosphonates in the presence of RONa to give 39-40% indoUnones 1 and 21-26% indolinones 2. 

Although I do not cover the synthesis of indolines, oxin-doles, isatins, and azaindoles in this monograph, some excellent reviews on the synthesis of these indole analogues are available [241-243],... 

Bazgir et al. (2010) developed a simple, facile, and efficient three-component procedure for the synthesis of spiro[indoline-3,4 -pyrazolo[3,4-fc]pyridine]-2,6 (TFT)-diones (179) by the reaction of 4-hydroxycoumarins (176), isatins (177), and 5-amino-lH-pyrazoles (178) in water as an environmentally benign solvent, using p-toluenesulfonic acid as an inexpensive and readily available catalyst under ultrasonic irradiation (Scheme 8.58). 

A series of 3 -aminospiro[indoline-3,r-pyrazolo[l,2- ]phthalazine]-2,5, 10 -trione derivatives (181) have been synthesized by a one-pot three-component reaction of isatin (180), malononitrile (50) or ethyl cyanoacetate (51), and phthalhydrazide (49) catalyzed by piperidine under ultrasound irradiation (Scheme 8.59). For comparison, the reactions were carried out under both conventional and ultrasonic conditions. As a whole, improvement in rates and yields were observed when the reactions were carried out under sonication compared with classical conditions (Wang et al. 2012). 

The first catalytic asymmetric formal [3h-3] cycloaddition of isatin-3-indolyhnethanol derivatives and in situ generated azomethine ylides was recently developed to synthesize structurally diverse spiro[indoline-3,4 -pyridoindoles] 228 bearing one all-carbon quaternary stereogenic center [109]. The reaction takes place with a range of A(-substituted isatin-derived 3-indolylmethanols, aromatic aldehydes 4, and diethyl 2-aminomalonate 221 and is catalyzed with chiral phosphoric acid 227 with the bulky 9-phenanthrenyl group at the 3,3 -positions of the BINOL moiety (Scheme 2.78). 

In related work, the same researchers described a four-component domino reaction that allows the one-pot synthesis of highly complex spiro systems, i.e. spiro[indoline/acenaphthylene-3,4-pyrazolo[3,4-6]pyridine derivatives 59 and 60 from phertylhydrazine, 3-aminocrotononitrile, isatin or acenaphthylene-1,2-dione and cyclic 1,3-dicarbonyl compoimds, including cyclohexane-l,3-diones and barbituric or thiobaibituric acid, in the presence of ( )-camphor-10-sulphonic acid (CSA) as catalyst (Scheme 1.30). 

The selective oxidative aromatic C-H bond functionalisation for new carbon-carbon bond formation is versatile, and various copper-catalysed or mediated reactions have been developed under molecular mg gen or air. For intramolecular reactions, 3,3-disubstituted oxindoles are provided by the oxidative coupling of Ar-H and C-H moieties in the presence of stoichiometric amounts of copper(ii) complex and a base (Scheme 15.51). Similar reactions are carried out catalytically with copper(ii) acetate (5 mol%) under air (Scheme 15.52). Indoline-2,3-diones (isatins) are afforded by... 

Keywords Isatins, malononitrile, 2-pyrazolin-5-ones, sodium bicarbonate, grinding, room temperature, solvent-free, one-pot multicomponent reaction, heterocycles, spiropyranyl-oxindoles, spiro[indoline-3,4 (l// )-pyrano-[2,3-c]pyrazol]-2-ones... 

Keywords Hydrazines, isatins, p-keto esters, malononitrile, ethyl cyanoacetate, piperidine, ethanol, room temperature, ultrasound irradiation, one-pot multicomponent synthesis, spiro[indoline-3,4 -pyrano[2,3-c]pyrazole] derivatives... 

A 100 mL flask was charged with hydrazine (1 1 mmol), p-keto ester (2 1 mmol), isatin (3 1 mmol) and malononitrile/ethyl cyanoacetate (4 1 mmol) and piperdine (20 mol%, 0.2 mmol) in ethanol (15 mL). The mixture was sonicated in the water bath of an ultrasonic cleaner (power 250 W irradiation frequency 40 kHz) at room temperature (25 30 °C). After the completion of the reaction (monitored by TLC), the resulting precipitate was filtered and washed with ethanol to afford the pure product of spiro[indoline-3,4 -pyrano[2,3-c]pyrazole] 5 as solid in good to excellent yields. Each of the products was characterized by IR, NMR, C-NMR and HRMS studies. 

Keywords Isatins, naphthaquinone, proline, ethyl lactate-water system, bio-based green solvent, room temperature, 1,3-dipolar cycloaddition, one-pot three-component reaction, spiro-oxindoles, spiro[benzo[/]pyrrolo[2,l-fl]isomdole-5,3 -indoline]-2, 6,ll-triones... 

A mixture of isatin (1 1 mmol), proline (2 1 mmol) and 1,4-naphthoquinone (3 1 mmol) in ethyl lactate-water system (5 mL 80% ethyl lactate in water v/v) was stirred magnetically at room temperature for stipulated time (20-55 min). On completion of the reaction (as indicated by TLC), the reaction mixture was left overnight. The precipitate was isolated by filtration and washed with water to furnish pure spiro[benzo[f]pyrrolo[2,l-a]isoindole-5,3 -indoline]-2, 6,ll-trione 4. Each of the products was characterized by analytical and spectral studies. 

Isatin allowed to react with diphenylphosphinyldiazomethane in acetonitrile in the presence of diethylamine 3-hydroxy-2-oxo-3-(diphenylphosphinyldiazo-methyl)indoline (Y 94%) allowed to react with ethereal HCl -> 3-hydroxy-2-oxo-4-diphenylphosphinyl-l,2-dihydroquinoline (Y 95%). F. e. s. M. Regitz et al., Tetrah. Let. 1972, 3979. 

Surprisingly, when the aryne MCRs with isatins were carried out using pyridine as the nucleophilic trigger, the reaction furnished indolin 2-one derivatives 114 instead of the expected spirooxazino pyridine derivatives [78]. This reaction likely proceeds via a conceptually new bis-(hetero)arylation reaction of isatin involving tire C-H bond functionalization... 

Under the same reaction conditions, few novel spiro[indoline-3,5 -pyrano[2,3-d]pyrimidine]-6 -carbonitriles (27) were prepared from a three-component reaction of isatins (20), 2-methylpyrimidine-4,6-diol (26), and malononitrile (3) in aqueous media (Scheme 14) [111,112],... 

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