Nitroindazole

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)). 

In the case of indazoles the reaction of indazole, 5-nitroindazole or 6-nitroindazole with glycosyl halides and mercury(n) cyanide gives exclusively 2-glycosylindazoles (670), (673) and (675) (7QJHC1435). Similarly, the reaction of 1-trimethylsilyl derivatives of indazole, 3-cyanoindazole, 4-nitroindazole, 5-nitroindazole and 6-nitroindazole with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide gives only, or preferentially, the 2-ribofuranosyl derivatives (670)-(674) 7QJHC117, 70JHC1329). 

It has been said that the above procedure cannot be applied to the synthesis of the corresponding nitro derivative, 8-nitro[l,2,4]triazino[5,6-b]indole-3-thione. Thus, heating 5-nitroisatin-3-thiosemicarbazone in aqueous potassium carbonate gave after acidification a mixture of oxotria-zinethione 137 and 5-nitroindazole 3-carboxylic acid (90ZOR1327). 

The formation of 5-nitroindazole from 2-amino-5-nitrotoluene in 72-80% yield is the subject of an Organic Syntheses contribution by Porter and Peterson (1955). 

Nitroheteroarenes continue to attract research activity. A series of 5-nitro-2-furyl derivatives were evaluated for in vivo efficacy against T cruzi [64] and an improved toxicity profile. Compound 65 showed a good efficacy profile in vivo and better acute toxicity profile when compared to nifurti-mox. A series of 5-nitroindazoles, represented by 66 (IC50 = 7.4 iM), were reported as having activity similar to nifurtimox (IC50 = 3.4 iM) in a growth inhibition assay [65]. 

Naphthol, 18 /3-Naphthyl ethyl ether, 11 Nef reaction, 40 Nichrome helices, 96 Nitrobenzene, 1 5-Nitroindazole, 73 /i-Nitrophenol, 60 NON AMETHYLENE BROMIDE, 25... 

The reaction of diazotized 3-amino-5-nitroindazole (329) with the substituted pyridine (330) under suitable conditions yielded the pyrido[2,3-e]-l,2,4-triazine (331). This method has also been used to prepare several pyrido[4,3-e]-l,2,4-triazines (Equation 6) <74GEP(0)2417916>. 

Indazoles are nitrated, mainly into the position 5 by a mixture of sulfuric and nitric acids or just by nitric acid (Scheme 2.1) with formation of 5-nitroindazole derivatives that are a part of so-called universal nucleosides [9],... 

In this case the activation of the methyl group by the nitro group is a necessary reaction condition. Moreover, the nitro group has to be in the ortho- or para-position to the methyl group [294, 295], If it is in the meta-position, no indazole is formed. This is in good agreement with larger yields of 6-nitroindazole in comparison with the ones of 5-nitroindazole (Scheme 2.26) [296],... 

The pathway of the reaction of 2-chloro-5-nitrobenzophenone with excess N,N-dimethylhydrazine is rather interesting (Scheme 2.29). In this case l,3-dimethyl-5-nitroindazole is formed fast and in high yield [305],... 

To simplify the synthetic technology of 3-amino-5-nitroindazole and to improve the target product quality it is reasonable to use 2-cyano-4-nitroaniline. The latter is subjected to diazotization, and the azo compound thus formed is reduced with simultaneous closure of the indazole cycle with sulfur dioxide in 5-15% sulfuric acid [315],... 

Intermediate azomethine could not be isolated. Heating of /V-(2-azido-5-nitrobenzyliden)aniline in dimethylformamide affords to 2-phenyl-5-nitroindazole, the structure of which has been confirmed by X-ray diffraction [322],... 

The pyrolysis of 4-arylhydrazono-3-methylisoxazolone-5 forms isocyanoam-ines, which undergo rearrangement to cyanoamides and corresponding indazoles (Scheme 2.35). Among other compounds 5-nitroindazole was obtained in an analogous way [323],... 

The treatment of betaines with concentrated sulfuric acid leads to the corresponding derivatives of 5-nitroindazole (products of alkylhalogenides elimination). Heating of betaines results in other nitroindazoles a product of Steven s rearrangement or a mixture of N,0- and N,N-atkyl shift products, as shown in Scheme 2.40 [328],... 

The molecule of 2-(3,5-di-ferf-butyl-4-hydroxyphenyl)-5-nitroindazole in the crystal is almost planar dihedral angles between the plane of the nitro group, phenyl substituent, and indazole system are 4.5(8) and 2.5(8)°. The C5-N02 bond length is 1.46(1)A [182],... 

N marking of the N-2 nitrogen atom, use of II, 13C, and 15N NMR spectroscopy, and coupling constants measurements 2,37N H allowed establishing the fact that the alkylation of 5-nitroindazole occurs mainly at the N-l atom [641],... 

A detailed study of PMR spectra in various solvents made it possible to assign the product of dinitroindazole nitration the structure of 2,3,5,6-tetranitroindazole [653], The II and 13C spectra of isomeric N-l and N-2 propanamides of 5-nitroindazole have been presented (Table 3.24) [645], By means of 13C NMR spectroscopy the structure of the products of 1,5- and l,6-dinitro-3-bromoindazole thermolysis in benzene was established [644], The effect of the phenyl group on the chemical shifts of the nitrazole ring atoms has been discussed [644],... 

Studies of the reactivity of 1,1-disubstituted indazol-3-yl oxides allowed the preparation of previously unknown betaines, 5-nitroindazole derivatives (Scheme 3.10) identified by 13C NMR (Table 3.24) [643, 646, 655],... 

The electron affinity of 3-(iV-methylpiperazino)-5-nitroindazole, 3,5-dinitroindazole, and molecular complex of the last with water is discussed on the basis of their half-wave potentials and in connection with their eventual radiosensitizing properties [667], The mechanism of EC behavior of 2-substituted 5(6)-nitrobenzimidazoles in acetonitrile has been investigated by classical polarography, cyclic voltammetry, and platinum rotating disk electrode with a ring (RDER) [888,991], It is shown that... 

Comparison of the electron spectra of 3-arylazo-5-nitroindazoles and their 1- and 2-methylderivatives suggests arylazoindazoles to exist as 177-tautomers [1187], The ultraviolet spectra of 6-nitroindazoles and their 1- and 2-ethyl derivatives [1188], 1-acetonitrylnitroindazoles, and other derivatives of nitroindazole [683, 1189] have been investigated. 

The mass spectra of 4-, 5-, 6-nitroindazoles and 7-methyl-, 7-chloro-5-nitroindazoles [683], and l-tetrazolyl-4,6-dinitroindazolc [1336] are reported. 

Nitroindazole, 6-nitroindazole, 7-nitroindazole and 3-bromo-7-nitroindazole 7-Nitroindazole... 

Indazole-l- N has been prepared from 2-nitrotoluene- N (Table 37) in 51% yield. Indazole-2- N has been prepared from 2-methyl-4-nitroaniline and sodium nitrite- N, through 5-nitroindazole-2- N, in three steps (overall yield 45%) (81MI40405). 

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