1.2.3- Triazole 1-oxide 5-nitro

Three methods for making 4,5,6,7-tetrahydrotriazoIopyridines use two fragments to form the triazole ring. The lithium derivative of A/-nitro-sopiperidine reacts with benzonitrile to give the 3-phenyl derivative 19.28 Diazonium salts react with a-amino acids to give mesoionic triazole oxides if pipecolic acid is used, the product is a tetrahydrotriazolopyridine 3-oxide... 

In aryl- or amino-substituted 1,2,4-triazols the nitro group enters the side chain [269-271], An attempt to realize the nitration of 3,5-bisphenylamino-l,2,4-triazole led to opening of the triazole ring. Picrylurea was isolated as the only reaction product [272], The nitration products of 2-methyl-l,2,3-triazole 1-oxide under mild conditions (20°C) are a mixture of 5-nitro (75%) and 4-nitro (23%) derivatives. Under more... 

Triisopropylbenzenesulfonyl)-3-nitro-1,2,4-triazole in the presence of 4-rtiorpholine pyridine-1-oxide was used with advantage as a coupling reagent for a solid-phase (p-alkoxybenzyl ester type resin) synthesis of peptides such as Leu-AIa-Gly-Val-OH or Leu-enkephalinamide (Tyr-Gly-Gly-Phe-Leu-NHs). The overall yield in the latter case was 70%, the purity of the peptide was 85-90%, and racemization was virtually zero.[38]... 

Substitution of the 4-nitro group in 3,4-dinitrofuroxan 1176 by ammonia occurs readily, even at low temperature. Subsequent treatment of the obtained amine, product 1177, with r-butylamine results in formation of 4-amino-2-(/-butyl)-5-nitro-l,2,3-triazole 1-oxide 1178. However, there must be some additional side products in the reaction mixture, as the isolated yield of compound 1178 is only 17%. Upon treatment with trifluoroperacetic acid, the r-butyl group is removed. The obtained triazole system can exist in two tautomeric forms, 1179 and 1180 however, the 1-oxide form 1179 is strongly favored (Scheme 195) <2003CHE608>. 

Thermal recyclization of the 3-diazenofuroxanyl unit to form the 4-nitro-l,2,3-triazole fragment has been found in noncondensed 1,2,5-oxadiazole 2-oxide derivatives (3,3 -azofuroxans) with acetamido substituents in the 4,4 -posi-tions <1999MC17>. 

It was shown that furoxans can be transformed to 1,2,3-triazoles. Thus, 4-acetylamino-3-arylazo-l,2,5-oxadiazole 2-oxides undergo two successive (cascade) mononuclear heterocyclic rearrangements in an aqueous basic medium with the formation of 4-acetylamino-2-aryl-5-nitro-2/7-l,2,3-triazoles (Equation 12) <2001MC230>, or 3,3 -disubsti-tuted 4,4 -azo-l,2,5-oxadiazole 2-oxides were found to undergo a rearrangement into 2-(furoxan-4-yl)-4-nitro-2//-1,2,3-triazole 1-oxides on heating in pertrifluoroacetic or peracetic acids (Equation 13) <2003MC272>. 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

Intramolecular [3+2] dipolar cycloadditions have also been employed as a post-Ugi transformation to generate heterobicyclic structures, namely fused isoxazolines [130], isoxazoles [130] and triazoles [131] (Fig. 31). Isoxazoles were obtained through intramolecular nitrile oxide cycloaddition. The precursor of the nitrile oxide (a nitro group) was introduced into the carboxylic component, while a triple bond was positioned in the starting amine. Treatment of 152 with POCl3/Et3N gave the intermediate nitrile oxide, which spontaneously cyclized to isoxazoles 153. 

The bishydrazones of the 1,2-diketones from inositols have also been converted into triazoles.222,223 The conversion of arylosazones into the corresponding osotriazoles requires the presence of an oxidant, and it is obvious that simple removal of aniline from the osazone, as suggested by the equation, is not involved. In addition to copper(II) sulfate, the reagent most commonly used, other oxidizing heavy-metal salts, such as ferric sulfate and chloride,224 and mercuric acetate,223 have been used, as well as halogens225 and nitro-sulfonates.226 The osazone acetates are converted into osotriazoles by nitrous acid,227 which decomposes the unacetylated osazones to the aldosuloses228 and the osazone formazans are cyclized with warm... 

Despite many attempts it has not been possible to oxidize 2-substituted 1,2,3-triazoles 382 to the corresponding 1-oxides 326. Peracetic acid, 3-chloroperbenzoic acid, dichloropermaleic acid, trifluoroperacetic acid, peroxydisulfuric acid, and f-pentyl hydrogen peroxide in the presence of molybdenum pentachloride all failed to oxidize 382 (1981JCS(P1)503). Alkylation of 1-hydroxytriazoles 443 invariantly produced the isomeric 3-substituted 1,2,3-triazole 1-oxides 448 (see Scheme 132). However, the 2-substituted 1,2,3-triazole 1-oxides 326 can be prepared by oxidative cyclization of 2-hydroxyiminohydrazones (1,2-hydrazonooximes, a-hydrazonooximes) 345 or by cyclization of azoxyoximes 169. Additional methods of more limited scope are reaction of nitroisoxazoles 353 with aryl-diazonium ion and base, and reaction of nitroimidazoles 355 with hydroxy-amine- or amine-induced rearrangement of nitro-substituted furoxanes 357. 

Nitro-2-phenylhydrazonooximes 347 when treated with acetic acid cyclize to give 4-hydroxy-l,2,3-triazole 1-oxides 349 presumably via a Nef type mechanism (1974S198) (Scheme 103). 

Nitro-l,2,4-triazole (45%) [451] and l-methyl-4-cyano-5-nitropyrazole (42%) [452] were isolated during the oxidation of corresponding aminoazole derivatives by a solution of hydrogen peroxide in trifluoroacetic acid. One of the amino groups in l-acyl-3,5-diamino-l,2,4-triazole is oxidized by hydrogen peroxide in the presence of sodium tungstate [453] (Scheme 59). 

Thermal recyclization of the 4,4 -bis(acetamido)-3,3 -azofuroxan leads to 4-acetamido-3-(5-acetamido-4-nitro-l,2,3-triazol-2-yl)furoxan [558], This transformation is probably initiated by the nucleophilic attack of an amide anion or amine on the nitrogen atom of the furoxan. The oxidation of the latter results in two isomers 4-nitro-3- and 3-nitro-4-(4,5-dinitro-l,2,3-triazol-2-yl)furoxan in the 8 1 ratio, which were separated by chromatography on Si02 (Scheme 102). 

Nitro-1,2,3-triazole 1-oxide derivatives may be obtained directly from furoxans [565] (Scheme 105). 

It should be noted that 3-amino-4-nitrofurazan has been isolated as a side product of 1,2,3-triazole 1-oxide in all cases of this reaction. For example, 2-ethyl-4-ethylamine-5-nitro-l,2,3-triazole 1-oxide with excess ethylamine transforms quantitatively into nitroaminofurazan [565] (Scheme 107). 

The molecule of 4-amino-2-methyl-5-nitro-l,2,3-triazole 1-oxide is nearly planar, except that the hydrogen atoms of the methyl group deviate from the ring plane by 0.505, 0.918, and 0.324 A [175], Coplanarity of the nitro group with the ring plane (1.8°) is caused by intramolecular hydrogen bond O...H...N (the O...N distance is 2.851 A). This fact also explains an elongation of N6-O8 bond (1.233 A) relative to N6-07 (1.225 A). 

H NMR spectroscopy was used for the investigation of 2-(2,4-dinitrophenyl)-4-nitro-l,2,3-triazole [600], 4-amino-3-(4-nitro-l,2,3-triazol-l-yl)furazan [601], 2-aryl(heteryl)-4-acetylamino-5-nitro-l,2,3-triazoles [141, 177, 602-604], nucleophilic substitution in the series of 4,5-dinitro-2-alkyl-l,2,3-triazoles [605] and 4,5-dinitro-2-aryl-l,2,3-triazole-l-oxides [606],... 

The EC oxidation first wave is diffusive and corresponds to one-electron transfer. An increase in the number of ring nitrogen atoms (the number of nitro group being the same) in a series of imidazole, pyrazole, triazole, tetrazole, as well as an increase in the number of nitro groups in the series nitroazole, di-, and trinitroazole essentially complicates the ability of nitroazole anions to electrochemical oxidation. [920]. In case of bicyclic C-C bound nitroazole dianions there is a dramatic decrease in E1/2 that... 

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