Methylene oxindole

Oxidation of IAA (2.49) results in cation 2.50, which undergoes decarboxylation and results in the skatolyl radical (2.51). This compound reacts with molecular oxygen to form peroxyl radical 2.52. With IAA or another cellular reductor, the hydroperoxide 2.53 is formed. It is this compound that activates the peroxidase, and thus allows the oxidation of other substrates, such as coniferyl alcohol. Among the degradation products of 2.53, 3-methylene 2-oxindole (2.54) is the most abundant. 

Folkes, L. K., Rossiter, S., and Wardman, P., 2002, Reactivity toward thiols and cytotoxicity of 3-methylene-2-oxindoles, cytotoxins from indole-3-acetic acids, on activation by peroxidases, Chem. Res. Toxicol. 15 877-882. 

LXXXIV) or undergo further oxidation and base-catalyzed decarboxylation (LXXXVI) to the labile nonisolable 3-methyleneoxindole (LXXXVIIa), characterizable as the sodium bisulfate addition product (LXXXVIIb). 8-Methylene oxindole (LXXXVIIa) bears a spectral resemblance to the oxidation product of auxin produced by peroxidase or indoleacetic acid oxidase from the fungus Omphalia ftavida (Ray and Thimann, 1956). 

Several examples are known of the ring-expansion reactions that transform isatins into quinazolines. iV-Carbamoyl isatins rearrange in the presence of amines into derivatives of 4-carboxy-4-hydroxy-3,4-dihydroquinazolin-2(lH)-ones, and iV-carbamoyl-3-(dicyano)methylene oxindoles provided 4-(dicyano)methylene-3,4-dihydroquinazolin-2(l//)-ones. The two isomeric A-oxides 102 and 103 underwent ring expansion on photolysis and produced the same 1,3-disubstituted quinazoline-2,4-diones (104) among other products, which include isatins. The ratio of products was sensitive... 

A 1,3-dipolar cycloaddition using a nitrile oxide dipole was described by Roth and Singh as an approach to the 3-hydroxy-3-alkyl oxindole scaffold (2011OL2118). Spirocychc isoxazoline 307 was obtained by cycloaddition of nitrile oxide 305 with 3-methylene oxindole 306 and was further elaborated to 3-hydroxy-3-cyanomethyl oxindole 308. This novel protocol was then used to synthesize the tricyclic pyrrolidinoindohne natural product ( )-alline 310 via the tricycHc intermediate 307 (Scheme 55). Thus... 

The same research group developed a similar cascade leading to the synthesis of spirooxindoles bearing four stereogenic centers. The starting material this time was a-methylene oxindoles (90) instead of 2-cyanoacrylate derivative. The reaction renders the spirooxindole derivatives 110 in excellent yields and enantioselectivities [59]. In 2011, Rios and co-workers [70] expanded the scope of the reaction using a-methylene pyrazolones 111, leading to spiropyrazolones 112 with excellent results (Scheme 10.29). 

Acetylderivat dee 7-MethyI-3.3 pentaf methylen-oxindols 21II271. 

Aziridine-2-phosphonates spiro-fused with 2-oxindole (790) have been prepared by a straightforward Horner-Wadsworth-Emmons reaction of ethyl 7V- [(4-nitrophenyl)sulfonyl]oxy -carbamate (791) and 3-(phosphoryl-methylene)oxindoles (792) in the presence of calcium oxide. Oxindoles (792) were also transformed into novel oxirane-2-phosphonates (793), as oxygen analogues of (790), by reaction with H202/Na0H (Scheme 201). " Cinchonine-based thiourea (797) catalysed asymmetric Michael addition of simple p-oxo-alkyl phosphonates (794) to nitro olefins (795), which afforded valuable a-substituted p-oxo phosphonates (796) in satisfactory yields with good to excellent enantioselectivities (up to 98% ee) (Scheme 202). ... 

Irradiation of 4-hydroxy- and 4-alkoxy-3-pyrazolin-5-one derivatives (163 R = OH, OR) leads to ring cleavage with the formation of /3-diamides (165) 69TL271). The methylene blue sensitized rearrangement of the same pyrazolinone (R = H) to the oxindole (166) also... 

Other important compounds include oxindole, which is the lactam of 2-aminophenylacetic acid. This compound has an active methylene group, which can be deprotonated with a base such as sodium ethoxide, and the anion that is formed can be alkylated with- a variety of electrophiles (Scheme 7.20). In the case of benzaldehydes, the initially formed aldols are unstable and these dehydrate readily to the corresponding (E)- and (Z)-(benzy lidene)oxindoles. 

The reactive 3-carbonyl group in compounds of type (279) undergoes aldol condensation with active methylene compounds such reactions of isatin with indoxyl, oxindole (Section 3.3.2.5.4) and with thiophenes (Section 3.3.1.5.7.ii) have already been mentioned. These compounds also react with Grignard reagents and phosphorus halides as expected, e.g. isatin (279 Z = NH) with MeMgBr and PC13 yields (285) and (286), respectively. 

The 3-methylene group of l-methoxy-2-oxindole (163) is easily ionized to give a carbanion that undergoes well-known types of reactions with alkyl halides or activated olefins without loss of the methoxyl group (e.g. 

The base facilitated Knoevenagel reaction has been used on an oxindole scaffold as indicated in Fig. 17 49 Position 3 of this heterocycle consists of an activated methylene function, which lends itself to classic... 

An important issue with respect to the Knovenagel condensation is that a mixture of isomeric disubstituted 3-methyleneoxindoles can be obtained. NMR measurements, including nOe experiments, and quantum chemical calculations have also shown that 3-[cyano(ethoxycarbonyl)methylene]-2-oxindoles, which are obtained from the reaction of isatin or from 1-methylisatin with ethyl cyanoacetate, exist as a mixture of the E and Z isomers, and that the E isomer exists in an equilibrium between two conformers, trans-s-cis and (rans-s-/ram431 (Scheme 100). 

A new carbon-carbon bond is formed during the reaction of lactim ethers with compounds containing active methylene groups, such as malonic ester and its derivatives, acetylacetone, barbituric acid, rhodanine, nitromethane, and oxindole.8 9 33 100-102 Examples are the condensation of the lactim ether of tetrahydro-/S-carbolinone with acetoacetic ester103 [Eq. (5)] and the condensation of the bislactim ether of 2,2 -dipyrrolidine-5,5 -dione (48) with butyl cyanoacetate20 [Eq. (6)]. Another instance is the reaction of 2 (R = Me) with 2-phenyloxazolin-5-one, to give 3,4-pentamethyleneimidazoles (49) via the intermediate 4-(homopiperid-2-ylene)oxazolin-5-one (50)104 (Scheme 16). 

Mercaptoacetic Add 2-Mercaptobenzoic Acid Methane Methanol Methionine Methotrexate Methylene Blue A-Methyl Glycine 5-Methylindole Methyl Isocyanate Methylmalonic Add Methyl Methacrylate Methylmethane Sulfonate Methyl Thiocyanate A-Methyl Thiourea Methyl Urea Naphthalene Nicotinic Acid Ornithine Orotic Acid Oxalic Acid Oxindole Palmitic Acid Paraldehyde Pentobarbital Phenol... 

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