Indazole oxides, oxidation

The oxidation of indazole oxides constitutes a method for the preparation of unsymmetrical aromatic azoxy compounds with the position of the oxygen atom unequivocally established. 

The assignment of the structures of unsymmetrical azoxy compounds was traditionally based on the results obtained from substitution reactions. This required assumptions about directing influences which were difficult to substantiate. The technique of oxidizing indazole oxides followed by decarboxylation represents an unequivocal synthetic procedure for the establishment of the position of the azoxy oxygen in the trans azoxy isomers. The reaction sequence used is given in Eq. (29) [34]. 

Irradiation of l//-indazoles under nonacidic conditions resulted in isomerization to benzimidazoles and also ring opening to isomeric benzonitriles. With 1-substituted benzimidazoles and sensitized irradiation, nitriles were formed, but these are only minor products with other substitution patterns 67HCA2244, 64TL2999). Irradiation of benzimidazoles leads to oxidative dimerization. 

With mixed acid 1-methylpyrazole 2-oxide (268) gives high yields of l-methyl-5-nitropyrazole 2-oxide (269) (B-76MI40402). The form undergoing the reaction is the base, for which first-order kinetics are observed in the Hq range from -5 to -6.5 a dinitro derivative is also formed under slightly different conditions. The reaction of indazole with fuming nitric acid affords a nearly quantitative yield of 5-nitroindazole (Section 4.04.2.3.2(i)). 

The creation of the N—N bond as the last step of the ring synthesis is common in indazoles and very rare in pyrazoles. In indazoles this method is well known (type B synthesis (67HC(22)l), for example, the dehydration of oximes (570) with acetic anhydride yields 1-acetylindazoles (571), and in basic medium the indazole 1-oxides (573) are formed from the nitro derivatives (572). 

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. 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

Dinitro-naphthalin liefert nach der Elektrolyse bei -0,7 V an Quecksilber letztlich (Benzo-[c,d]-indazol)-N-oxid (32% d.Th.)2 ... 

Dzoljic, M. R., de Vries, R. van Leeuwen, R. (1996). Sleep and nitric oxide effects of 7-nitro indazole, inhibitor of brain nitric oxide synthase. Brain Res. 718, 145-50. 

Z., Hart, S. L., Babbedge, R. C., Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles antinociceptive and cardiovascular effects, Br. J. Pharmacol. 110 (1993), p. 219-224... 

S. L., 7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse... 

So erhalt man aus 4-Formyl-benzofurazan-l-oxid mit primaren Aminen die entsprechenden 2-Alkyl-7-nitro- und 2-Aryl-7-nitro-2H-indazole (s.Bd.E8b)270 ... 

AzoindoIe und -indazole sind ebenfalls in guten Ausbeuten ( 75%) durch Oxidation der Amine mit Kalium-hexacyanoferrat(III) zuganglich4. 

The E conformation has been assigned (73CR(C)(277)1163) to 2-acetyl-indazole (84). Whereas no definite conformational results have been found for 1-acylbenzotriazoles (82MI2), the solid-state structure of 3-acylbenzotriazole 1-oxide (85) is (85JOC2174) of E conformation. 

A ring closure may occur by reaction between a nitroso group and an amino group thus o-nitrobenzylamines (98) may be reduced to the hydrox-ylamine in an ammonia buffer and the hydroxylamino group oxidized to a nitroso group. If the amino group is primary or secondary, indazoles (99) are formed159 [Eq. (77)]. 

Diphenylhydrazine (Ph2NNH2) is converted into indazole (215) by Cl2C = NMe2. Oxidative cyclizations are also known thus, fully methylated 6-(benzylidenehydrazino)uracils (216) on photolysis or in hot AcOH give the pyrazolo[3,4-d]pyrimidines (217) (75BCJ1484,92KGS219). 

Amino- (459) and 3-amino-quinazolin-2-ones (460) (75JCS(Pl)3l), as well as 1-amino- and 2-amino-indazoles (92AHC(53)85) can be oxidized to 1,2,3-benzotriazines. C-Amino compounds can also give triazines oxidation of 3-aminoindazole (461) with hydrogen peroxide forms 1,2,3-benzo-triazin-4-one (462) <1899LA(305)289). 

Methylpyridazin-3 (2H)-one 1-oxides unsubstituted at position 6 afford photochemi-cally a mixture of the corresponding 6-hydroxypyridazin-3(2H)-one, lactone (46) and isomaleimide (47). 4-Methylcinnoline 1-oxide gives a mixture of the methyl substituted benzofuran (48), the indazole (49) and the indole (50), while 4-methylcinnoline 2-oxide gives a mixture of the deoxygenated starting compound, benzisoxazole (51) and o-aminoacetophenone (Scheme 16). 

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... 

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