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Addition of substituted isatins to 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone, generated in situ from 3,5-di-tert-butyl-4-hydroxybenzyl acetate, to form 1-substituted hydroxybenzylisatins, is reported. On the basis of these isatins novel isatin-3-thiosemicarbazones as well as isoindigo derivatives bearing a 2,6-di-tert-butylphenol moiety were obtained. The structures of all novel compounds are confirmed by IR, H NMR and C NMR.

An easy and convenient step-by-step synthetic procedure towards the design of a novel spiroindolomethanofullerene bearing an isoindigo fragment is reported.

Synthetic approaches towards isoindigo derivatives and their application in medicinal chemistry as well as in the chemistry of materials are reviewed. The literature data up to 2014 are covered.

A Pfitzinger reaction of isatin with 2-methyl-(4-oxopent-2-yl)dialkyl(diphenyl)phosphine oxides was used to synthesize new derivatives of 4-quinolinecarboxylic acids, containing a phosphine oxide fragment, and screening for antimicrobial activity was performed.

The reaction of 3,4,6-triisopropyl-1,2-benzoquinone with phenylacetylene and phosphorus trichloride gave 2,6-dichloro-5,7,8-triisopropyl-4-phenyl-1,2λ5-benzoxaphosphinine 2-oxide whose structure was determined by X-ray analysis.

The reaction of substituted benzyl-, aroylmethyl-, or 1-phenetylisatins with hexaethyltriaminophosphine has been shown to lead to the formation of a library of 3,3′-biindolinylidene-2,2′-diones with functionalized benzyl-, aroylmethyl-, and 1-phenetyl fragments at the nitrogen atom.

The crystal and molecular structure of 1,1′-dimethyl-isoindigo is studied by single crystal X-ray diffraction analysis. It is shown that the molecules of 1,1′-dimethyl-isoindigo are nonplanar due to the rotation of two oxindole rings relative to the double bond.

New 1-(ω-chloroalkyl)isatins were synthesized by alkylation of isatin with α-bromo-ω-chloroalkanes. The reaction of 1-(3-chloropropyl)isatin with tris(diethylamino)phosphine followed the deoxygenation path with selective formation of isoindigo derivative.

A series of novel 2′-oxospiro[cyclopropafullerene-3,3′-indolines] was synthesized. Compounds of this type have a significant potential for use as electron-withdrawing components of light-absorbing layers of solar cells.

Isatin is a widely known natural compound occurring in various plant species, e.g., Isatis tinctoria L. and Couropita guianancis aubl. [1, 2]. Isatin was also isolated as a human adrenaline metabolite [3]. Extensive studies on the synthesis and reactivity of isatins have led to the discovery of new diverse aspects of organic reactions. Numerous methods for the preparation of various heterocyclic systems have been developed starting from isatin; in particular, spiro pyrrolidines, quinolines, indoles, β-lactams, oxindoles, and other heterocycles possessing a considerable potential of biological activity have been obtained [4, 5]. Isatin derivatives containing a reactive bromoalkyl fragment have recently attracted strong interest. These compounds were used to synthesize various conjugates with known biologically active compounds (including medicinal agents) which also showed high antibacterial [6–8], antiviral [9], and antitumor activity [10, 11]. The existing methods for the preparation of N-bromoalkylisatins are few in number and are not free from disadvantages related to side formation of alkylenediisatins. In the present communication we describe a new synthetic approach to 1-(ω-bromoacyl)isatins, which is based on acylation of isatin sodium salt (I) with ω-bromoalkanoyl chlorides II and III. The reactions were carried out in anhydrous benzene at 15°C, and the corresponding 1-(ω-bromoacyl)isatins IV and V were obtained in high yields (88–89%). Compound IV was converted into isoindigo derivative VI according to the procedure described by us previously [12]. Almost quantitative formation of hexaethylphosphoric triamide (according to the P NMR data) and high yield of VI indicated that the reaction is not accompanied by side quaternization of initial phosphorous triamide.

New phosphorus-containing derivatives of quinoline-4-carboxylic acid were synthesized by the Pfitzinger reaction from isatin and dialkyl(aryl)(2-methyl-4-oxopent-2-yl)phosphine oxides.

The reaction of aminomethylisatins (isatin N-Mannich bases) with hexaethylphosphorous triamide leads to the formation of 1,1′-bis(dialkylaminomethyl)-3,3′-bis(indolin-3-ylidene)-2,2′-diones and 1,1′-bis(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1H,1′H-[3,3′]bisindolylidene-2,2′-dione.

A high-yield synthesis of some novel isatin-3-acylhydrazones on the base of 5-ethylisatin derivatives and Girard's reagent T is described. Antimicrobial activity preliminary SAR study of both 1-benzylated isatins and water-soluble hydrazones was established. The most active against Staphylococcus aureus and Bacillus cereus are ammonium salts bearing 3,4-dichloro- or 4-CF3 substituents in benzyl fragment.

A reaction of 3,6-di(tert-butyl)-1,2-benzoquinone with alkynes in the presence of phosphorus trichloride leads to a predominant formation of 4-alkyl- and 4-haloalkyl-5,8-di(tert-butyl)-2,6-dichloro-2 H- benzo[e][1,2]oxaphosphinine 2-oxide. An ipso-substitution of the tert-butyl group at ortho-position to the oxygen atom of the benzophosphinine system with the formation of 4-alkyl-5- tert-butyl-2,8-dichloro-2 H-benzo[e][1,2]oxaphosphinine 2-oxide was the minor route of the reaction with alkylacetylenes. Molecular structures of 4-butyl-5,8-di( tert-butyl)-2,6-dichloro-2 H- benzo[e][1,2]oxaphosphinine 2-oxide and 5,8-di( tert-butyl)-2,6-dichloro-4-hexyl-2 H-benzo[e][1,2]oxaphosphinine 2-oxide were studied by X-ray analysis.

The reactions of 1,2-naphthoquinones with hexaethyltriaminophosphine or tri(n-butyl)-phosphine followed by bromine or hydrogen bromide treatment has been shown to lead to the quantitative formation of the new 1,2-naphthoquinones and 1,2-dihydroxynaphthalenes containing phosphorus-carbon bond. Its structure established by NMR and single crystal X-ray diffraction.

The reactions of 3,5-di(tert-butyl)-1,2-benzoquinone with aryl-and alkylacetylenes in the presence of phosphorus trichloride afford 4-aryl(alkyl)-8-tert-butyl-2,6-dichloro-2-oxo-2H-benzo[e][1,2]oxaphosphinines as the major ipso-substitution products of the tert-butyl group by the chlorine atom. 4-Aryl(alkyl)-6,8-di(tert-butyl)-2,5-dichloro-2-oxo-and 4-aryl(alkyl)-6-tert-butyl-2,8-dichloro-2-oxo-2H-benzo[e][1,2]oxaphosphinines were obtained as the minor products. The structures of the stable representatives of this series were confirmed by X-ray diffraction.

Stable reaction products of mucochloric acid with aromatic and heterocyclic thiols were synthesized and characterized. Under basic conditions the reactions proceeded with the substitution of the chlorine atom(s) by arylthiogroup(s), while in an acidic medium the hydroxy group at C 5 was substituted. Different types of new sulfur-containing products of di- and trisubstitution on the basis of mucochloric acid were obtained. In one case a new acyclic product—di-p-tolyl-2,3-bis-(p-tolylthio)butanedithioate—was isolated. The structure of all synthesized compounds was confirmed by IR, 1 H, and 13 C NMR spectroscopy; three compounds were characterized by single crystal X-ray diffraction.

In this review we generalize and analyze information about reactions between isatin and three-, four-, and five-coordinate phosphorus compounds, published between 1966 and 2014.

Maleic anhydride undergoes C-phosphorylation under the action of tris(diethylamino)phosphine to afford 3-dihydrofuranylidene-4-phosphorylidene-oxolane-2,5,5′-trione whereas 2,3-diphenylmaleic anhydride under the same conditions turns into N,N,N′,N′-tetraethyl-2,3-diphenylbut-2-enediamide. The latter reaction can serve as a novel approach for the synthesis of dicarboxylic acids diamides from corresponding cyclic anhydrides. Their structures were established by NMR and X-ray diffraction.

2,2,2-Trichloro-5-chlorocarbonylbenzo[d]-1,3,2-dioxaphosphole was prepared for the first time by the reaction of protocatechuic acid with phosphorus pentachloride or trichloride followed by chlorination. According to the results of NMR spectroscopy, the reaction of this phosphole with phenylacetylene gave rise to 2,5-dichloro- and 2,8-dichloro-6-chlorocarbonyl-2-oxo-4-phenylbenzo[e]-1,2-oxaphosphorinines as the major products. The molecular and supramolecular structures of their stable derivatives, viz., 2-tert-butylamino-6-tert-butylaminocarbonyl-5-chloro-2-oxo-4-phenylbenzo[e]-1,2-oxaphosphorinine and isopropylammonium 8-chloro-6-isopropylaminocarbonyl-2-oxo-4-phenylbenzo[e]-1,2-oxaphosphorinin-2-oate, respectively, were established by X-ray diffraction analysis.

ortho-Quinones are widely spread in the nature and they attract rapt attention of researchers due to the versatile biological action (antitumor agents [1] and key intermediates in the processes of development of carcinomas [2], tuberculocidal drugs [3], pharmaceuticals for treating Shagas disease [4]). On the other hand, the ready formation of semiquinolate radicals makes these compounds promising for designing polymeric photosensitive materials [5]. ortho-Quinones as a rule are prepared by oxidation of the corresponding catechols with various oxidants like silver oxide [6], sodium periodate [7], lead dioxide [8], hydrogen peroxide [9]. In many cases for the synthesis of quinines containing other functional substituents milder oxidants should be applied. In this study we for the fi rst time have developed an effi cient procedure of the oxidation of bis-catechols linked through phosphonium groups by a polyalkylene chain into the corresponding ortho-quinones by treating with bromine. The oxidation of bis-phosphonium derivatives I, II proceeds under mild conditions at room temperature affording phosphorus-containing diquinones III, IV in nearly quantitative yelds. The completion of reaction was monitored by the IR spectroscopy following the disappearance of broad absorption bands of hydroxy groups in the region 3100–3300 cm–1 and the appearance of strong narrow absorption bands in the region 1682–1692 cm–1 corresponding to the ortho-quinone fragment. The formation of the ortho-quinone fragment is

1,4-Bis(diphenylphosphino)butane and 1,5-bis(diphenylphosphino)pentane add two molecules of 6-bromo-1,2-naphthoquinone to afford bis-ylides which on treatment with protic acids are converted into the corresponding P,P’-bis(7-bromo-3,4-dihydroxy-1-naphthyl)-substituted bis-phosphonium salts.

Regioselective bromination of 4-phenyl-2,7-dichloro-2H-chryseno[6,5-e][1,2]phosphinine 2-oxide proceeded in the position 3 with the formation of 3-bromo-4-phenyl-2,7-dichloro-2H-chryseno[6,5-e][1,2] phosphinine 2-oxide; the structure of its 2-tert-butylamino derivative was established by XRD analysis and correlation spectroscopy.

A convenient one-step synthesis of symmetrical 1,1’-dialkyl derivatives of isoindigo is described. Key words carbenes, deoxygenation, heterocycles, regioselectivity, phosphorus. In the last years, isoindigo [1H,1’H-bis(indolin-3-yliden)-2,2’-dione] and especially it’s N- and N,N’-derivatives attract great attention not only as dyes, but as substances which possess a specific biological activity (anti-leukemia, antiproliferative, anti-inflammatory etc.). 1-4 Thus, 1-(β-D-glucopyranosyl)-isoindigo was found to be an anti-leukemia drug. 2-4 It has to be noted that the synthesis of 1-substituted isoindigo often is a multistep procedure. The best approach to the synthesis of isoindigo derivatives seems to be the dimerization of ketocarbenes generated from isatin derivatives. It has been assumed 5,6 that mixture of 3-(triphenylphosphoranyliden)-2,3-dihydro-1H-indol-2-one and isoindigo is formed with moderate yield by the reaction of triphenylphosphine with isatin and 1-methylisatin through intermediate carbene formation. However, generation of carbenes from heterocyclic -diketones under the action of trivalent phosphorus deriv-atives has been insufficiently studied.

A series of phosphorus-containing 1,2-dihydroxynaphthalenes have been obtained via the reaction of 1,2-naphthoquinone derivatives with tri(n-butyl)- or triphenylphosphine followed by treatment of the intermediate phosphobetaines with various acids. The antimicrobial activity of the synthesized compounds has been studied and the structure—activity relationship established, which gives grounds for the search for new biologically active compounds in this direction.

The three-component reaction of acenaphthenequinone, fullerene C 60 and hexaethyltriaminophosphine leads to the formation of the new methanofullerene – 2-{3’-cyclopropa[1,9](C 60 -I h )[5,6]fulleren-3’-yl}-1-acenaphthenone.

The reaction of 6-bromo-1,2-naphthoquinone with tri(2-cyanoethyl)phosphine or tricyclohexylphosphine leads to the unusual formation of 6,6’-dibromo-1,1’,2,2’-tetrahydroxy-4,4’-binaphthyl; its structure was confirmed by NMR spectroscopy and single crystal X-ray diffraction analysis.

Isoindigo [1H,1'H-bis(indolyl-3-indeno)-2,2'-dione] and its 1and 1,1'-substituted derivatives in the recent years attract attention of researchers not only as dyes, but also as the substances with specific biological activity (antileukemic, enterohemorragic, proliferative, antiinflammation and others), inhibiting orthomonooxygenases or kinases and possessing other related properties [1–4]. 1-(β-D-glucopyranosyl) isoindigo and isoindigo glycoside have been proposed as antileilkemia means [2, 3].

A reaction of 6-bromo-1,2-naphthoquinone with tri(n-butyl)phosphine gave 2-hydroxy-4-tri(n-butyl)phosphonionaphth-1-olate (betaine with the P—C bond). When treated with bromine, this betaine changed into (6-bromo-1,2-dihydroxy-4-naphthyl)tri(n-butyl)phosphonium bromide and (6-bromo-1,2-dioxo-1,2-dihydro-4-naphthyl)tri(n-butyl)phosphonium bromide in the ratio ∼1: 1.

Reactions of substituted isatins with tervalent phosphorus compounds provide a convenient synthetic route to isoindigo derivatives. 1-Methylisatin is converted into 1,1′-dimethylisoindigo in ~40% yield by the action of sodium diethyl phosphite [1] or triphenylphosphine [2] in boiling benzene. It is presumed that the reaction involves intermediate generation of carbenes. If more nucleophilic tris(diethylamino)phosphine was used instead of triphenylphosphine under mild conditions (in methylene chloride), symmetrically substituted isoindigo derivatives were obtained in high or nearly quantitative yield [3–6]. Intermediate formation of carbene species was proved experimentally by trapping them with fullerene C60 [7]. In order to reveal how the solvent nature affects the result of the above reaction, weakly polar aprotic methylene chloride was replaced by more polar ethanol. In the reactions of 1-methyland 1-ethylisatins 1 and 2 with tris(diethylamino)phosphine in ethanol at 20°C we isolated red solids. Analysis of the H and C NMR spectra of the products unambiguously showed that they are mixtures of isoindigo derivatives 3 and 4 with epoxy compounds 5 and 6. The latter are likely to result from dimerization of intermediate carbenes or their insertion into the C=O bond of initial isatin. In all cases, the P NMR spectra of the reaction mixtures contained one major signal belonging to tris(diethylamino)phosphine oxide (δP 25.1 ppm) and two minor signals due to its alcoholysis [8] and hydrolysis products (Et2N)2P(O)H (δP 21.9 ppm) and EtO(O)P(H)OH (δP 8.9 ppm). The formation of some amount of oxirane derivatives was observed by us previously in reactions of some alkylisatins with tris(dimethylamino)phosphine [9]; the same process in the examined reaction is related to the effect of ethanol. Presumably, in our case epoxides could be formed via reaction of isatins 1 and 2 with the alcoholysis products of tris(diethylamino)phosphine, ethyl N,N,N′,N′-tetraethylphosphorodiamidite (EtO)P(NEt2)2 and diethyl N,N-diethylphosphoramidite (EtO)2PNEt2 [8, 10]. Reaction of 1-methylisatin (1) with tris(diethylamino)phosphine in ethanol. Tris(diethylamino)phosphine, 1.26 mL (4.78 mmol), was added dropwise over a period of 10 min at room temperature to a solution of 0.77 g (4.78 mmol) of isatin 1 in 7 mL of anhydrous ethanol, and the mixture turned dark brown. Evaporation of the solvent left a red powder which was a mixture of 1,1′-dimethylisoindigo (3) and

The reaction of 2,2,2-trichlorobenzo[d]-1,3,2-dioxaphosphole-5-carbonylchloride with phenylacetylene in benzene (80 °C) afforded 2-(2-chloro-2-phenylethenyl)-2,2-dichlorobenzo[d]-1,3,2-dioxaphosphole-5-carbonylchloride (yield >95%) as a result of the electrophilic cis-addition of the phosphorus(v) derivative at the triple bond of acetylene with retention of coordination of the P atom. Hydrolysis of this compound affords predominantly 2-hydroxy-5-(hydroxycarbonyl)phenyl (2-chloro-2-phenylethenyl)phosphonate.

The reaction of 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione with hexaethyltriamido-phosphite in the presence of diethylammonium chloride afforded a stable quasiphosphonium salt, viz., (1,7,7-trimethyl-2-oxobicyclo[2.2.1]hept-3-yloxy)tris(diethylamino)phosphonium chloride, as one diastereomer (racemate, 1R*,3S*,4S*).

The reaction of 3,4,6-triisopropyl-1,2-benzoquinone with phenylacetylene and phosphorus trichloride gave 2,6-dichloro-5,7,8-triisopropyl-4-phenyl-1,2λ5-benzoxaphosphinine 2-oxide whose structure was determined by X-ray analysis.

The reaction of N-benzyl/aroylmethyl substituted isatins with hexaethyltriaminophosphine gives access to a small library of bis-indolinylidene derivatives (II).

This simple procedure involves a novel deoxygenation reaction of isatins (I) with hexaethylphosphorous triamide furnishing the bis(aminomethyl)isoindigos (II) under mild conditions in a short reaction time.

Heterocyclic α-diketones are used as starting materials for the synthesis of new heterocyclic compounds possessing useful properties, from those exhibiting specific biological activity to new functional materials [1–3]. A particular place is occupied by pyrrole-2,3dione and 3,3′-bipyrrolylidene derivatives which have recently found increasing application in the preparation of synthetic analogs of natural chromophore systems [4], as well as in organic semiconducting and photovoltaic devices [5].

Multi-component reactions of building blocks with more than one MCR-reactive group will give rise to oligomeric MCR products. The proper choice of at least two bifunctional building blocks will give either a polymeric or a cyclic product. Apart from polymerization, repetitive or consecutive Ugi reactions have been used to produce linear MCR-heterooligomers with such building blocks.

Benzo[e][1,2]oxaphosphinine 2-oxide derivatives are obtained in the reaction of alkyl- and haloalkylacetylenes with sterically hindered benzoquinone (I) in the presence of phosphorous trichloride.

The reaction of 6-bromo-1,2-naphthoquinone with tri(2-cyanoethyl)phosphine or tricyclohexylphosphine leads to the unusual formation of 6,6’-dibromo-1,1’,2,2’-tetrahydroxy-4,4’-binaphthyl; its structure was confirmed by NMR spectroscopy and single crystal X-ray diffraction analysis.

A reaction of 6-bromo-1,2-naphthoquinone with tri(n-butyl)phosphine gave 2-hydroxy-4-tri(n-butyl)phosphonionaphth-1-olate (betaine with the P—C bond). When treated with bromine, this betaine changed into (6-bromo-1,2-dihydroxy-4-naphthyl)tri(n-butyl)phosphonium bromide and (6-bromo-1,2-dioxo-1,2-dihydro-4-naphthyl)tri(n-butyl)phosphonium bromide in the ratio ∼1: 1.

Deoxygenation under the action of the P(III) derivatives is widely used in organic chemistry [1, 2]. Among the variety of reactions a separate group includes the deoxygenation of nitro compounds with the P(III) derivatives resulting in the nitrogencontaining heterocycles of different structures [3]. The tertiary phosphines and phosphites are most commonly used as the P(III) derivatives. One of the most studied reactions of this type is the cyclization of nitroarenes to form the corresponding nitrogen-containing heterocycles (indoles, pyrrolopyrimidines, carbazoles, quinolines) under the action of the phosphorous acid esters. Presumably, the reaction proceeds through the intermediate formation of nitrenes. If 2-nitrobiaryls were used, the nitrene inserts on the C–H bond adjacent to the aryl moiety, to give the corresponding carbazoles [4, 5] or δ-carbolines [6]. The reaction of 2nitrophenylsulfide with an excess of triethyl phosphite, resulting in phenothiazine, can be attributed to the same type of the reactions [7, 8]. If the aryl contains a double bond ortho-positioned relative to the nitro group (o-nitrostyrene), the nitrene inserts on the β-C– H bond of the vinyl moiety to give the substituted indoles [9–11]. The reactions of o-dinitrobenzene with the P(III) derivatives should be specially noted. For example, under the action of triethyl phosphite, diphenylethylphosphinite, or methyldiethylphosphonite one of the nitro groups is substituted by the phosphorus moiety and ethyl nitrite is eliminated [12]. At the same time, the reduction of 2,2'-dinitrobiphenyl with the gaseous PH3 stops when benzocinnoline-2,2'dioxide forms [13].

Deoxygenation and desulfonation of organic compounds by the action of trivalent phosphorus derivatives are widely used in organic chemistry [1, 2]. Among the various transformations occurring in this case a group of processes can be separated that are realized in the reactions of carbonyl compounds with P(III) derivatives. For example, the reaction of trialkylphosphites or sodium diethylphosphite with various benzaldehyde derivatives gives rise to the corresponding ethylenes including stilbenes [3, 4] in moderate yields. 2,2'-Diformylbiphenyl and its derivatives undergo the intramolecular cyclization to the corresponding 1,2-diphenyloxiranes under the action of tris(dimethylamino)phosphine [5]. It is assumed that the deoxygenation of 1,3-dicarbonyl compounds (the cyclic anhydrides or thioanhydrides) proceeds through the stage of the carbene formation [6, 7]. In the reactions of aroyland hetaroylphosphonates with trialkylphosphites the formed intermediate of carbene nature is added intramolecularly to the multiple bond [8–14]. Nevertheless, in a considerable number of the studies the intermediate formation of carbenes is only postulated, and other versions of explanation of these synthetic results may be offered. Unlike the deoxygenation of ketones and carboxylic acid anhydrides, similar processes with α-dicarbonyl compounds are described in only few works [4, 15, 16].