Indole N-oxides

Pheny 1-3-pheny 1 imino-3-// -indole N -oxide (an indolic nitrone) reacts with triethyl and triisopropyl phosphite in refluxing xylene and fert-butylbenzene to give 2-phenylimino-3// -indole (indolenine) in very good yield (505). 

Fig. 23 Chemical structure of 5,7-di-ferf-bulyl-3,3-dimcthyl-3H-indolc N-oxide (1) and 6-tert-butyl-3,3-dimethyl-3N-indole N-oxide (2) [150]...

Kurihara, T., Doi, M., Hamaura, K., Ohishi, H., Harusawa, S., Yoneda, R. Meisenheimer rearrangement of 2-ethenyl-1,4,5,10b-tetrahydro-2H-azetopyrido[3,4-b]indole N-oxides new route to the 12(S)carba-eudistomin skeleton. Chem. Pharm. Bull. 1991, 39, 811-813. 

Another example of the reaction proceeding in a similar manner is the conversion of 2-(5-chloro-2-nitrophenyl)-3-phenylpropionitrile into A-hydroxyindole derivative (Scheme 71) [189]. The intermediate vinyl nitroso compound undergoes electrocyclization, resulting in the formation of nitrone (2//-indole N-oxide), which is tautomerized into A-hydroxyindole. 

The pyridine-N-oxide 245 was converted into the cyanopyridine 246 and its isomer (Scheme 80). Grignard reaction, Fischer s indole synthesis, and N-protection gave a pyridinyl indole 247. Selenium dioxide selectively oxidized the methyl group to give the isonicotinic acid. The synthesis of Flavocarpine (244) was finally accomplished by a set of standard reactions as outlined in Scheme 80 (87TL5259). 

Ebenfalls mit guten Ausbeuten wird 3-Phenylimino-2-phenyl-3H-indol-l-oxid unter Reduktion einer N-Oxid-Funktion aus dem Bis-oxid I erhalten2 ... 

Other quinoline A-oxide derivatives have been examined. A 1,3-oxazepine is the major product of irradiation of 2-cyanoquinoline A-oxide whereas lactam formation predominates on irradiation of 4-methylquinoline N-oxide in aqueous ethanol.60 Lactam formation has been shown to be influenced by an external magnetic field and on this basis it has been proposed that the first step in this transformation is the formation of an excited radical-ion pair.61 1,3-Oxazepines undergo further reaction on prolonged irradiation. The synthesis of 4-substituted indoles, for example, has been accomplished in this way by irradiation of 5-substituted quinoline A-oxides.62... 

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

The preparation and stereochemistry of some indole alkaloid N-oxides was studied by Sakai and co-workers (276). The N-oxidation of yohimbine (74) with m-chloroperbenzoic acid under mild reaction conditions led to two isomeric N-oxides (556 and 557) in a ratio of 10 1. MCPBA oxidation of pseudoyohimbine (88) afforded a single product (558). 

Epoxyhexahydroazocino[5,4- 7]indole 56 (in the original paper mistakenly related to azocino[5,6- 7]indoles) has been obtained in 60% yield by a Meisenheimer rearrangement of the N-oxide of azetopyrido[3,4-fc] indole 55 (91CL1781 Scheme 17). 

Another example is the reaction of indoles with nitrosoarenes in the presence of acids. The redox potentials of the reactants cannot justify an outer-sphere ET process, thus the formation of the phenylaminoxyl detected for the reaction carried out in the ESR cavity, could be more likely justified by an inner-sphere ET mechanism95. In fact the reaction of quinoline N-oxide with primary alkyl Grignards for which an outer-sphere mechanism was earlier proposed, takes place through classical nucleophilic addition96. 

The principal reason that DMT must be administer parenterally is its rapid and efficient metabolism. It can be oxidized to the N-oxide. It can be cyclized to b-carbolines, both with and without an N-methyl group. It can be N-dealkylated to form NMT and simple tryptamine itself. Best known is its oxidative destruction, by the monoamine oxidase system, to the inactive indoleacetic acid. There is a wild biochemical conversion process known for tryptophan that involves an enzymatic conversion to kynurenine by the removal of the indole-2-carbon. A similar product, N,N-dimethylkynuramine or DMK, has been seen with DMT, when it was added to whole human blood in vitro. 

Table 6 Indoles by Photochemical Ring Contraction of Quinoline N-Oxides...

Lithium diisopropylamide, 163 Phenyliodine(III) diacetate, 242 Tetrakis(triphenylphosphine)-palladium(O), 289 Trimethylamine N-oxide, 325 Containing one nitrogen—indoles Hexamethyldisilazane-Chlorotri-methylsilane, 141 Iron carbonyl, 152... 

A series of tricyclic indole alkaloids (physostigmine alkaloids) has been obtained from the cheilostome bryozoan Flustrafoliacea (90). In addition, flustramide B (83) and flustrarine B (84) were isolated from this bryozoan (91). Flustrarine B (84) was prepared from previously known fiustramine B (85) (92) via oxidation with hydrogen peroxide. Five fiustramine derivatives, dihydroflustramine C (86) and its N-oxide (87), fiustramine D (88) and its N-oxide (89), and isoflustramine D (90), were isolated from the methylene chloride fraction of the aqueous methanol extract of a Canadian F. foliacea, and these alkaloids were found to be responsible for the antimicrobial activity of the extract (93). Oxidation of dihydroflustramine C (86) and fiustramine D (88) with m-chloroperbenzoic acid afforded the corresponding A-oxides (87 and 88, respectively). 

Kaneko, C., Fujii, H., Kawai, S., Yamamoto, A., Hashiba, K., Kimata, T., Hayashi, R. and Somei, M. (1980) Studies on the N-oxides of Jt-deficient N-heteroaromatics. XXXIV. A novel synthesis of substituted indoles by photochemical ring contraction of 3,1-benzoxazepines. Chemical e[ Pharmaceutical Bulletin, 28 (4), 1157-1171. 

Dicarbonylimidazole reacted with the anthranilic acid derivative (498) to produce the fused isoxazolone IV-oxide (499) (77ZOR462). Methyl nitroacetate reacted with indole-3-carbaldehyde to produce (500) (70KGS1505). Treatment of (501) with base gave 3,4,5-triphenyl-2-isoxazoline N-oxide (Scheme 142) (69JOC984). The reaction was reported to be a direct displacement as (502) did not give a product and no incorporation of deuterium was found using DOMe. 

Whereas cyclic secondary enaminones and nitroolefins mainly yield indoles in which the enamine nitrogen is incorporated into the heterocyclus (equation 242), linear tertiary a-ketoenamines are shown to react with nitroolefines at low temperature under kinetic control to give 1,2-oxazine N-oxides as [4 + 2]-cycloadducts, followed by retro-Diels-Alder reaction or rearrangement under thermodynamic control which leads diastereo-selectively to aminocyclopentenes. The reaction is called [3 + 2]-carbocyclization, apparently because the ketoenamine is reacting as a 1,3-dipole. The products are hydrolysable to polysubstituted nitrocyclopentanones with retained configuration325 (equation 243). 

A catalytic method which promises to find wide application in view of its mildness and ease of execution uses a catalytic amount of tetra-n-propylanunonium perruthenate (TPAP) with A(-methylmoipholine N-oxide (NMO) as the cooxidant. Wmary (and secondary) alcohols which contain a range of functional groups (alkenes, tetrahydropyran ethers, epoxides, lactones, silyl ethers and indoles inter alia) can be oxidized without interference by the other functional group (equations 21-23). The performance of the reagent is improved further by including molecular sieves in the reaction mixture. ... 

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