Indazoles reduction

Hydriodic acid reduction of the azo-con )ound PhN N-CFj has been found to yield indazole. Reduction of perfluoroazomethane with hydriodic acid or hydrogen sulphide yields perlluorohydrazomethane, isolable as the etherate (CF3-NH NH CF3)OEt2 this can be distilled without appreciable... 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

Only two topics are of importance for this section the reduction of pyrazolium salts and 3-pyrazolin-5-ones by complex hydrides, and the nucleophilic photosubstitution of pyrazoles and indazoles. 

The photochemical cyclization of anthranilonitriles (190 Section 4.04.2.1.2) yields indazoles (72CC126). Reduction of o-benzonitrile with lithium aluminum hydride yields indazole (75ACS(B)1089). 2-Aminoindazole (576) has been prepared in 94% yield from (574) via the o-phthaloyl derivative (575 = o-phthaloyl) (72JOC2351). Similarly, treatment... 

Indazole, 5,5-dimethyl-3-trifluoromethyl-4,5-dihydro-trichomonacidal activity, 5, 291 Indazole, 2-ethoxycarbonyl-reactions, 5, 269 Indazole, 3-fluoro-synthesis, S, 263 Indazole, 1-germyl-synthesis, 5, 236 Indazole, 1-glycosyl-synthesis, 5, 289 Indazole, 2-glycosyl-synthesis, 5, 289 Indazole, halo-reactions, S, 266 Indazole, 2-hydroxy-methylation, 5, 269 Indazole, 3-hydroxy-reactions, S, 264 Indazole, 6-hydroxy-diazo coupling, 5, 86 Indazole, hydroxyphenyl-synthesis, S, 288 Indazole, 3-iodo-synthesis, S, 241 Indazole, l-isopropyl-3-phenyl-reduction, 5, 243 Indazole, 3-mercapto-1 -substituted tautomerism, 5, 265 Indazole, methoxy-... 

Support for this suggestion comes from many quarters. Reduction of the jS-carboline anhydro-bases with sodium and alcohol or with tin and hydrochloric acid gives the 1,2,3,4-tetrahydro derivatives, as does catalytic reduction over platinum oxide in an alkaline medium. On the other hand, catalytic reduction with platinum oxide in acetic acid results in the formation of the 5,6,7,8-tetrahydro-j3-carbolinium derivatives (see Section III,A,2,a). It should be noted, however, that reduction of pyrido[l,2-6]indazole, in which the dipolar structure 211 is the main contributor to the resonance hybrid, could not be effected with hydrogen in the presence of Adams catalyst. 

The procedure given here is essentially that described previously by the submitters2 and is based on the early work of Knoevenagel.8 2-Phenylindazole has been prepared by reduction of N-(o-nitrobenzyl)aniline with tin and hydrochloric acid,4 by reduction of N-(o-nitrobenzyl) -N-nitrosoaniline with tin and hydrochloric acid,5 by dehydration of 2-(phenylazo)benzyl alcohol,6 by elimination of acetic acid from 2-(phenylazo)benzyl acetate,7 by dehydrogenation of 3,3a,4,5,6,7-hexahydro-2-phenyl-indazole with sulfur,8 and by thermal decomposition of o-azido-benzalaniline.9... 

Interposing an additional carbon atom between the indazole nucleus and the acetic acid side chain provides another compound that shows anti-inflammatory activity in model systems. Reduction of the carboxylic acid in the indazole (38-1) by means of hthium aluminum hydride leads to the carbinol (38-2). Alkylation of the enolate from the alcohol with methyl 2-bromo-2-methylpropionate leads to the corresponding ether. Saponification gives the free acid and thus bindarit (38-3) [40]. 

Indazole has been prepared according to the method reported in Organic Syntheses.6 The present method employs milder reaction conditions. Recently, indazole has been prepared by the hydrolysis or reduction of 3-cyanoindazole,6 by heating l-o-tolyl-3,3-dimethyltriazine,7 by the coupling of N-nitroso-o-benzo-(or aceto)-toluidide,8 9 and by the decomposition of cis-2-stil-benediazonium fluoroborate.10... 

Pyrazole also causes, both in vitro and in vivo, a reduction in the activity of the mixed function oxidase enzyme system (B-79MI10504), and has also been used to inhibit the copper-containing enzyme monoamine oxidase in vitro, as have several related heterocyclic compounds (80MI10507) such as indazole (78), isoxazole (75) and benzothiazole (79). 

Similar redox-combined processes have been reported. For example, it has been clarified by control experiments using a photoirradiated semiconductor electrode that the photocatalytic production of indazoles from substituted azobenzenes is based on the condensation of two intermediates formed through oxidation and reduction.38 40) In the case of oxidation of substituted olefins a similar redox combined mechanism is assumed cation and anion radicals are formed by the reaction of olefin with positive hole and of 02 with excited electron, respectively, and they react to produce a 4-membered ring intermediate, a dioxethane, to undergo bond cleavages into the desired products.4l) In the photocatalytic reactions, a positive hole and excited electron must react at the neighboring surface sites of a small semiconductor particle, enabling the combination of reduction and oxidation without the addition of an electrolyte, which is an indispensable component in electrolysis. However, in the particulate system the recombination of positive hole and electron is also likely, as well as... 

The first information (37JGU739 67CB2164) about the synthesis of 1,2-dihydrobenzo[crf]indazole by reduction of 1,8-dinitronaphthalene or naphtho[equilibrium with 1,3- and l,5-dihydrobenzo[c[Pg.43]

Jakupec MA, Reisner E, Eichinger A, Pongratz M, Arion VB, Galanski M, Hartinger CG, Keppler BK (2005) Redox-active antineoplastic ruthenium complexes with indazole correlation of in vitro potency and reduction potential. J Med Chem 48 2831-2837... 

Carbethoxypyrazol-5-yl-, indazol-3-yl- and indazol-5-yl-2-iodobenzamides have been synthesized from the corresponding 1,2,3-benzotriazinones <02FES183>. The reduction of benzo-l,2,3,4-tetrazine 1,3 dioxides 72 afforded benzotriazoles 74 via intermediates 73 <02OL3227>. 

The nucleus of indazole, like that of pyrazole, is stable to reduction, so that treatment of the amido derivative (23) with LAH leads only to the amine (24).Indazolium salts (25) are more reactive and undergo reduction with potassium borohydride to give indazolines (26). ... 

Reaction of 2-nitrobenzyl triphenylphosphonium ylide 745 with aryl isocyanates afforded 2-aryl-2//-indazoles 746 (Equation 159) <2000TL9893>. Reductive cyclization of o-nitroketoximes 747 in the presence of catalytic iron dimer in dioxane under a carbon monoxide atmosphere furnished l//-indazoles 748 (Equation 160) <2004H(63)373>. 

Indazoles may be obtained by reduction of o-nitrobenzylamines followed by reoxidation of the hydroxylamine to a nitroso group ring closure occurs by addition of the amino group to the nitroso group followed by elimination of water [114]. 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

The azlactone of a-benzoylaminocinnamic acid is reduced to DL-phenylalanine ° by stirring a mixture of the azlactone, a large excess of red phosphorus, and acetic anhydride (125 ml.), adding 50% hydrogen iodide in the course of 1 hr., and refluxing the mixture for 3-4 hrs. Reduction of 3-chloroindazole to indazole is accomplished... 

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