Indoline-2,3-diones

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. ... 

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. " ... 

A set of new two-carbon-tethered fused acridine/indoles 62 were synthesized via a AcOH-promoted domino reaction of indoline-2,3-dione 61 and C2-tethered indol-3-yl enaminones 57a (Scheme 12.22) [43]. The reaction was further expanded to prepare C-tethered fused acridine/pyridines pairs, N-substituted amino acids, N-cyclopropyl, and N-aryl-substituted fused acridine derivatives. In these domino processes, a fused acridine skeleton with concomitant formation of two new rings was readily achieved in good yields. 

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... 

A novel CuClj-catalyzed intramolecular C-H oxidation/acylation protocol using two C—H bonds as the reaction partners and Oj as the terminal oxidant was reported by Li and coworkers (Scheme 8.36). Various substituted indoline-2,3-diones could be prepared in moderate to good yields with high tolerance of functional groups. The kinetic isotope effect = 2 4) was observed by FTIR... 

Scheme 8.37 Cu(OAc)2-catalyzed synthesis of indoline-2,3-dione derivatives from secondary anilines and ethyl glyoxalate.

Very recently, the combination of a cinchona-based chiral primary amine and a chiral phosphoric acid has been demonstrated by Wang and coworkers [36] as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with a,P-unsaturated ketones (Scheme 43.23). Various novel chiral spiro[cyclohexane-l,3 -indoline]-2, 3-diones were obtained in high... 

The second dimeric alkaloid conophyllidine (304) is identical in all respects with conophylline except for replacement of the epoxide function at positions 14 and IS of the tabersonine epoxide unit by a double bond. Conophylline has also been subsequently isolated from the South American species, Tabernaemontana glandulosa [182], and from the Thai species, Ervatamia microphylla [183]. It has also been reported from another Malaysian species, Ervatamia polyneura, under the name polyetvine [184]. The leaf extract of Ervatamia polyneura also yielded the related dimer, polyervininc (306), which is similar to conophylline except for the aromatic portion of the vincadifformine unit which now possesses an indoline dione chromophore, existing predominantly in its zwitterionic quinoniminium form. 

Adrenochrome (3-hydroxy-l-methyl-5,6-indoline-dione) [54-06-8] M 179.2, m 125-130 (dec). It was crystallised from MeOH/formic acid, as red crystals of the hemihydrate, and stored in a vacuum desiccator. The mono-semicarbazone (Carbazochrome) [69-81-8] M 236.2, crystallises as orange-red crystals from dilute EtOH with m 203° (dec) and is haemostatic. [Heacock Chem Rev 59 181 1959, Beilstein 21 IIEIV 6434.]... 

Indenopyrene, see Indeno[l,2,3-crf pyrene l//-Indole, see Indole Indolene, see Indoline Inexit, see Lindane Inhibisol, see 1,1,1-Trichloroethane Insecticide 497, see Dieldrin Insecticide 4049, see Malathion Insectophene, see a-Endosulfan, p-Endosulfan Intox 8, see Chlordane Inverton 245, see 2,4,5-T lodomethane, see Methyl iodide IP, see Indeno[l,2,3-crf pyrene IP3, see Isoamyl alcohol Ipaner, see 2,4-D IPE, see Isopropyl ether IPH, see Phenol Ipersan, see Trifluralin Iphanon, see Camphor Isceon 11, see Trichlorofluoromethane Isceon 122, see Dichlorodifluoromethane Iscobrome, see Methyl bromide Iscobrome D, see Ethylene dibromide Isoacetophorone, see Isophorone a-Isoamylene, see 3-Methyl-l-butene Isoamyl ethanoate, see Isoamyl acetate Isoamylhydride, see 2-Methylbutane Isoamylol, see Isoamyl alcohol Isobac, see 2,4-Dichlorophenol Isobenzofuran-l,3-dione, see Phthalic anhydride 1,3-Isobenzofurandione, see Phthalic anhydride IsoBuAc, see Isobutyl acetate IsoBuBz, see Isobutylbenzene Isobutane, see 2-Methylpropane Isobutanol, see Isobutyl alcohol Isobutene, see 2-Methylpropene Isobutenyl methyl ketone, see Mesityl oxide Isobutyl carbinol, see Isoamyl alcohol Isobutylene, see 2-Methylpropene Isobutylethylene, see 4-Methyl-l-pentene Isobutyl ketone, see Diisobutyl ketone Isobutyl methyl ketone, see 4-Methyl-2-pentanone Isobutyltrimethylmethane, see 2,2,4-Trimethylpentane Isocumene, see Propylbenzene Isocyanatomethane, see Methyl isocyanate Isocyanic acid, methyl ester, see Methyl isocyanate Isocyanic acid, methylphenylene ester, see 2,4-Toluene-diisocyanate... 

Rings with one heteroatom are [6]-fused unless otherwise stated. h The numbering used is that of bicyclic systems (295, 296). Tropolones. d- / Also antistrychnine, antiallergic, or cardiovascular agents, respectively. 8 See 90H(31)677 94JHC1557. h 67/-Benzo[5,6]cyclohept[ 1,2,3-cd]indoline-1,6-diones. 1 See 91MI1. 

The formation of by-products appears to predominate with annelated derivatives, and the desired phenanthridone is, at best, only a minor product of the copper-catalyzed decomposition of the appropriate diazonium salt. Typically (and contrary to an earlier report123), the decomposition of iV-methyl-2-naphthanilide-l -diazonium fluoro-borate (96) gives poor yields of four products 2-naphthanilide (2%), jN7-methyl-9,10-benzophenanthridone (97) (3%), 2-methyl-6,7-benziso-indoline-l-spirocyclohexa-2, 5 -diene-3,4,-dione (98) (5%), and bi-(2 - methyl - 3 - oxo - 6,7 - benzisoindoline -1 - spirocyclohexa - 2, 5 - dien-4 -yl) (99) (15%).132 133... 

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. ... 

The intramolecular Diels-Alder reaction of 5-(3-butynyl)-3//-pyran[2,3-c]isoquinoline-3,6-dione (132) in boiling benzene afforded a pyrrolophe-nanthridone, which yielded 2-methoxy-anhydrolycorin-7-one (136). Hippadine (44) was synthesized by means of l-aza-T-oxa[3.3]sigmatropic rearrangement of A-(2-methoxycarbonylvinyloxy)-8,9-methylenedioxy-phenanthridin-6-one (133) (137) or by palladium-mediated intramolecular cyclization of 7-bromo-A-[(6-bromo-3,4-methylenedioxy)benzoyl]indoline (134) (138) (Fig. 10). 

Radical addition reactions were also recently added to the repertoire of 2-nitroin-dole (21), previously dominated by nucleophilic reactions [17]. Treatment of the indole with activated methylene compounds such as dimethyl malonate, malonitrile and pentane-2,4-dione in a refluxing solution of Mn(0Ac)3-2H20 in acetic acid gave mainly 2-oxo-indolin-ylidenes 22 after an in situ Nef reaction. The expected 3-subsitiuted 2-nitroinole 23, however, was only observed with the methine compounds 3-methylpentane-2,4-dione and 5-oxo-4-propionyUieptane-nitrile. 

Upon treatment with an amine at room temperature, cyclohexane-1,3-dione-2-spirocyclopropane 145 underwent ring opening followed by condensation of the amine with ketone loss of water delivered indoline scafrbld 146, which could be further elaborated to indole 147 over four steps (14OL4012). 

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). 

Bazgir, A., Ahadi, S., Ghahremanzadeh, R., Khavasi, H. R. and Mirzaei, R 2010. Ultrasound-assisted one-pot, three-component synthesis of spiro[indoline-3,4-pyrazolo[3,4-<>] pyridine]-2,6 (l7/)-diones in water. Ultrason. Sonochem. 17 447—152. 

An efficient method to prepare l /f-spiro-[indoline-3,3 -quinoline]-2, 4 -diones and their trifluoromethylated products was developed hy Wang and co-workers in 2014. The reaction proceeds via a palladium-catalyzed Sono-gashira coupling-Wacker-type ojqqjalladation-cyclization cascade reaction sequence. The amount of water in the reaction system played an important role in the in situ trifluoromethylation reaction, and the trifluoromethylation exhibited excellent molecular self-induced stereoselectivity. 

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). 

Ramin et al. performed the combination of isatin, barbituric acid, and cyclohexane-l,3-dione derivatives in the presence of alum (KAl(S04)2 l2H20) as a catalyst in [BMIM][PF6] to afford spiro[chromeno[2,3-d]pyrimidine-5,3 -indoline]-tetraones 183 after 15 min at 100 °C (Scheme 107). A total of eight types of substituted isatins, two types of 1,3-cyclohexanediones, and three types of barbituric acids were used in this tactic for the library validation. The authors investigated tiie catalytic effect of other Lewis and Bronsted acids such as SSA (silica sulfuric acid), SnCb, p-TSA (para-toluenesulfonic acid), and CAN (ceric ammonium nitrate) under this methodology and foxmd that alum at 10mol% demonstrated significant capability and promotion of reaction rate in [BMIM][PF6] as reaction medium [287]. 

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