Isatin oximes

The antitumor activities of indole and isatin oximes and of furan oximes were studied by several investigators. Furan oximes were found to inhibit DNA, RNA and protein synthesis in lipoid leukemia cells. Derivatives of quinoline oximes were also shown to possess antitumor activity , and glucosinolates, 15, were suggested as cancer-preventive agents . ... 

Isatin and 1-alkylisatins react with hydroxylamine or O-methyl hydroxylamine hydrochloride under aqueous alkaline conditions to furnish the corresponding 3-oximes, which have been studied as monoamine oxidase inhibitors . Isatin oximes can be acylated... 

The lithium and thallium (I) salts of i satin-3-oxime (isatin oximates) were employed in the development of ion-selective electrodes for these cations. Transition metal complexes of isatin derivatives can also be employed as catalysts for the oxidative self-coupling of alkylphenol s639,640. 

Sin N, Venables BL, Combrink KD et al (2009) Respiratory syncytial virus fusion inhibitors. Part 7 structure-activity relationships associated with a series of isatin oximes that demonstrate antiviral activity in vivo. Bioorg Med Chem Lett 19 4857 -862... 

Several novel compounds have been discovered to have potential utility in the treatment of the effects of ischemia following stroke. For example, indoramin (159) increases the rate of ATP synthesis in the brain and may be useful in treating ischemia AMPA receptor antagonist, is a candidate for the treatment of stroke <94BMC371 ). The generation of superoxide anion, which is associated with injury to the central nervous system. 

Baeyer confirmed his results by the total synthesis of oxindole, isatin and indole. Nitration ofphenylacetic acid, isolation of the o-nitro isomer, and reduction of the latter followed by ring closure gave oxindole. Reaction with nitrous acid ( .e. potassium nitrate and sulfuric acid) gave isatin oxime, from which by reduction, dehydrogenation with iron(lll) chloride and final hydrolysis, isatin itself was obtained. 

Pinto and Neto demonstrated that if the isatin formation was run using an imidazolium based ionic liquid 27 as the solvent, the reaction could be sloped at isatin oxime 26. The choice of acid and ionic liquid counter anion had a substantial influence on this reaction efficiency. ... 

N-Pheaylnitn amino-snccinimid 21, 381. N-Acetybisatin-dioxim 21, 448, II339. N-Acetamino-isatin- -oxim 21II341. 

E. Abele, R. Abele, O. Dzenitis, E. Lukevics, Indole and isatin oximes synthesis, reactions, and biological activity, Chem. Heterocycl. Compd. 39 (2003) 3-35. 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

Synthesis of isatin 109 derivatives readily proceeds from anilide-derived oximes 108 by interaction with sulfuric acid (equation 46) ... 

Reaction of isatin 3-monooxime sulfonate 159 with hydrazides leads to 1-aryltriazoli-nones 160 with 41-46% yields (equation 70) . Interaction of oxime PhC(=NHPh)CCl=... 

The presence of ethyl acetate is essential as otherwise the yellow oxime 5 (mp 233-235°C) is formed in yields of 20-30%. Ethyl acetate is added in order to extract the isatin 3 from the aqueous phase immediately upon formation. Oxime 5 is probably formed... 

Very few complexes with oximes have been recorded. A pyridine-2-aldoxime (C5H4N)CH=NOH) complex, possibly Th(C6H5N20)4, is obtained as a green solid by evaporating an absolute ethanol solution containing Th(NQ3)4 and the ligand. Isatin /5-oxime... 

Z = 0, NH), then the carbonyl group not adjacent to the heteroatom is preferentially attacked. Thus, isatin and indoxyl and their O- and 5-analogues (279, 282) react with hydroxylamine, hydrazine, phenylhydrazine, semicarbazide, etc., to give oximes, hydrazones, phenylhydrazones, semicarbazones, etc. (282 — 283 279 — 284). 

A number of ring closures have been reported that lead to 2- or 3-substituted isatins. Thus, treatment of nitromalonbis-A-methylanilide with acid gives N-methylisatin-3-oxime.103 Reaction of 25 with cyclohexyl or Mnitylisocyanide gives 26, which was hydrolyzed by acid to 27.104 Heating of 28 gives, with oxidation, the isatin-2,3-dianil 29.105... 

Dihalogenation of oxindole followed by alkaline hydrolysis of the 3,3-dihalooxindole has been applied to the synthesis of some isa-tins.66,126,136 137b A number of oxindoles have been treated with nitrous acid to give isatin-3-oximes.100,138 Reduction of the oximes to 3-aminooxindoles followed by ferric chloride oxidation gave isatins.100,138 When this sequence was applied to 7-azaoxindole, the azaisatin 33 was... 

A wide variety of substituted isatins have reacted with hydroxyl-amine to give isatin-3-oximes (72).6,26,42,51,92,107,126,169 274 O-Substi-tuted hydroxylamines also give this reaction.275 5-Bromoisatin-3-oxime... 

Isatin-3-oximes readily form complexes with a variety of metal ions.278,279 In a number of cases, these have seen analytical applications.6,42,280-283 Isatin-2-oximes1 also form metal complexes.279,284-287... 

Reduction of isatin-3-oximes to the corresponding 3-aminooxindole has been carried out using stannous chloride in acetic acid51 or in hydrochloric acid.92 3-Aminooxindole has also been obtained by electrochemical reduction288 and catalytic hydrogenation.169 Reduction... 

Isatin-3-oxime reacts with isocyanates to give carbamoyloximino-isatins (75).290 Irradiation of AT-inethylisatin-3-oxime causes syn-anti isomerization,291 while A -acetylindazolone is obtained from irradiation of AT-acetylisatindioxime.291 Treatment of this dioxime with acetic... 

Treatment of a number of isatin-3-oximes with sodium methoxide at 140°293 or simply thermally274,294 leads to o-aminobenzonitriles. Thermal treatment of isatin-2-oxime gave isatin and 79.294 Beckman rearrangement of isatin-3-oximes resulted in the formation of o-cyano-phenylisocyanates.26,295 With the Vilsmeier reagent, phosphorus... 

Since the Pfitzinger reaction requires a large excess of alkali, aliphatic aldehydes, which readily polymerize under these conditions, cannot be used in the reaction. However, it was possible to overcome these difficulties by using the aldoximes. Thus, Pfitzinger heated the isatin 7 with acetaldehyde oxime in the presence of potassium hydroxide in water and obtained 4-quinolinecarboxylic acid together with the oxime of isatinic acid 196 [175],... 

Ketoximes containing a CH2 group adjacent to the oxime group are also capable of entering into the Pfitzinger reaction. Thus in the reaction of the isatin 7 with the ketoxime 199 3-cyano-2-methylquinoline-4-carboxylic acid 200 is formed with a 50% yield [177],... 

The condensation of isatin 7 with the oximes of cyclic diketones 201 led to the dicarboxylic acids 202 (yields 22-23%) [178],... 

The action of 50% aqueous potassium hydroxide on equimolar amounts of isatin and nitromethane leads to the formation of the acid 218 and the oxime 219. With a twofold excess of nitromethane only 219 is obtained [184],... 

It has long been known16 that primary aromatic amines react with chloral hydrate and hydroxylamine hydrochloride (or preformed chloral oxime) in aqueous solution to give isonitrosoacetanilides (e.g, 40). The reaction is improved by addition of certain inorganic ions (e.g., sulfate16) and is of value as a route to isatins obtained by... 

Nitroacetanilides, obtained by alkaline hydrolysis of l-arylamino-l-methylthio-2-nitroethenes, are readily cyclised to isatin-3-oximes by the use of concentrated sulfuric acid or trifluoromethanesulfonic acid at room temperature the latter giving somewhat higher yields. Although this methodology is related to the Sandmeyer methodology, it has no obvious benefit over the latter (Scheme 7). 

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