1.2.3- Triazole 1-oxide

Other examples of nucleophilic attack on a furoxan ring leading to ring opening/recyclization are the formation of 1,2,3-triazole 1-oxides 198 from 4-alkylamino-3-nitrofuroxans 197 and alkylamines (Scheme 129). 3-Amino-4-nitrofurazan was observed as by-product (95MC194, 96CHE580, 96KGS675). 

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>. 

Other heterocyclic N-oxides have been found to display biological activities that may depend on their proven or hypothesised ability to release NO these include 4/ /-pyrazol-4-oTie 1,2-dioxides 71, 2H-1,2,3-triazole 1-oxides 72, benzotetrazine 1,3-dioxides 73 and 1,2,3-benzotriazine 3-oxides 74. These systems have been less extensively studied than the furoxan and 1,2-diazetine dioxide systems discussed above. 

A number of 2H-1,2,3-triazole 1-oxides 72 were prepared by chemists at the Cassella Company as potential NO-donors in view of their formal structural similarity with furoxan derivatives [18]. Derivative 72a was studied in depth. It was obtained by cupric sulfate oxidation of intermediate 79, derived from the action of the substituted phenylhydrazine 78 on the oximino acetoacetic acid amide 77 (Scheme 6.13). 

Anodic oxidation of the monooxime phenylhydrazone of a 1,2-dicarbonyl compound 93 in CH3CN-O.I mol/I Et4NC104 solution gave 2-phenyl-1,2,3-triazol-1-oxide 94 in very good yield [125,126] (Scheme 51). 

Disubstituted 2-phenyl-277-1,2,3-triazole-1-oxides (150) can be easily obtained from the corresponding bis(hydroxyimino)butanes 148 in three steps. Thus, treatment of dioximes 148 with diluted HCl in dioxane with subsequent interaction with PhNHNH2/EtOH/AcOH afforded a-hydrazinooximes 149 in excellent yields. Reaction of 149 with A-iodosuccinimide (NIS) in CCI4 or with CUSO4 in aqueous pyridine afforded triazoles 150 (equation 65) . Similar cyclization in the presence of SOCI2 also leads to... 

Substituted 1,2,3-triazoles are oxidized by w-chloroperoxybenzoic acid at the more basic N(3) to give the corresponding triazole A -oxides. The yield is lower if an electron-withdrawing substituent is present at the C(4) or C(5) position <87ACS(B)724>. 2-Alkyl-1,2,3-triazole-1-oxides are produced from the oxidative cyclization of alkyl hydrazono oximes <86ACS(B)262> see Section 4.01.8.1. 

Triazoles can be activated towards electrophiles by the introduction of an A-oxide group. N-Oxidation gives rise to better activation of the 5-position than the 4-position. Thus, bromination of 3-benzyl-1,2,3-triazole 1-oxide (192, R = PhCH2) requires only 120 h at 20 °C and affords the 5-bromo compound (193) in quantitative yield <87ACS(B)724>. 3-Phenyl-1,2,3-triazole 1-oxide is... 

Phenyl-1,2,3-triazole 1-oxide (209) is selectively silylated at C(5) to afford (210) by treatment with trimethylsilyl triflate and diisopropylethylamine. If the C(5) position is blocked, electrophilic attack occurs at the C(4) position <93JCS(PI)625>. 

The nucleophilic substitution of 1,2,3-triazole is also activated by A-oxidation. In 3-substituted 1,2,3-triazole 1-oxides, a halogen substituent at C(4) is more reactive than one at C(5) <87ACS(B)724>. Therefore, the C(4) chlorine of compound (221) (Equation (19)) is displaced by methoxide under much milder conditions than the corresponding C(5) chlorine of (222) (Scheme 39), and the only C(5) bromine is displaced in the case of 4,5-dibromotriazole 1-oxide <88BSB573>. 

Protons of 1,2,3-triazole rings can also be activated by A -oxides. The H(4) and H(5) protons in 3-substituted 1,2,3-triazole-1 -oxides (254) are more reactive but exchange with deuterium at a similar... 

The synthetic applications of substituted 1,2,3-triazole 1-oxides and 1,2,3-triazolium-l-imides in the preparations of 1,2,3-triazines, 1,3,4,5-oxo- and -thia-triazines, and 1,2,3,5-tetrazines have been discussed in Section 4.01.4.12. Conversions of 1,2,3-triazolines into aziridines either thermally or photochemically were described in detail in CHEC-I <84CHEC-1(5)691 > and in a review <84AHC(37)217>. Some recent developments are discussed in Section 4.01.5. 

The oxide group mildly activates 3-substituted 1,2,3-triazole 1-oxides to electrophilic attack. Thus, 3-benzyl-1,2,3-triazole 1-oxide reacted much more rapidly than the unoxidized compound in giving the 5-bromo derivative, and there have been a number of other examples of 5-bromination and 5-chlorination of triazole oxides, including that of the 3-phenyl-l-oxide, which was not para-halogenated [87ACS(B)724]. 

A similar anodic cyclization167,168 is the oxidation of benzilmonoxime phenylhydrazone to 2,4,5-triphenyl-1,2,3-triazole 1-oxide (83% yield) and of 3-hydroxyiminomethylenamino-6-chloropyridazine to 6-chloro-s-triazole-[l,5-b]pyridazine 3-oxide (28% yield).167... 

Two alternative routes lead to 2-alkyltriazole 1-oxides from a-dicarbonyl compounds (Scheme 50, routes A and B). Unsymmetrical dicarbonyl compounds frequently, but not invariably, give rise to two isomeric hydrazones and two isomeric oximes and hence two isomeric 1,2,3-triazole 1-oxides (81JCS(P1)503). 2-Phenyltriazole 1-oxide is obtained from glyoxal via route A. However, 2-methyl-triazole 1-oxide is prepared from glyoxal by route B in a one-pot process under neutral conditions. 2-Benzyltriazole 1-oxide is obtained similarly. 2,5-Dimethyltriazole 1-oxides are accessible through both routes (86ACS(B)262). 

Photolysis of , 4,5-triphenyl-1,2,3-triazole 1-oxide gives the 1,3,4,5-oxatriazine (13) (80AJC2447). This is the only reported example of this monocyclic ring system, and the mechanism of its formation (Scheme 35) probably involves the intermediacy of an oxaziridine and an oxygen walk process not uncommon in the photochemistry of heterocyclic iV-oxides. 

The formula for the parent 2-substituted 1,2,3-triazole 1-oxide 341 is shown in Scheme 100. 

The aromatic 2-substituted 1,2,3-triazole 1-oxides are represented by the structure 341. The parent compound 342 is one of the three possible tautomeric forms of 1-hydroxy-l,2,3-triazole 343. 1-Hydroxy-l,2,3-triazoles 343 constitute a separate group of compounds, which are not included in the present review (Scheme 101). 

The resonance structures of the 2-substituted 1,2,3-triazole 1-oxides 341 are discussed in Section 1.1.1. According to IUPAC nomenclature, structure 341 is a 2-substituted 2H-l,2,3-triazole 1-oxide. Other names found in the literature are 2-substituted 1,2,3-triazole 1-oxides. In the present review the most commonly used naming, which is accepted by IUPAC, Chem. Abstr. Autonom., has been adopted calling structure 341 a 2-substituted 1,2,3-triazole 1-oxide. 

The first 1,2,3-triazole 1-oxide 326 was reported in 1898 (1898JPC160, 1898G173). It was obtained in low yield by oxidative cyclization of 2-hydroxyiminophenylhydrazones (2-oxime phenylhydrazones) using HgO as the oxidant. About 285 2-substituted 1,2,3-triazole 1-oxides 326 with a variety of substituents at C3, C4, and C5 have been reported. A review appeared in 1989 (1989CHE113). Examples of the use of 1,2,3-triazole 1-oxides in the synthesis of substituted 1,2,3-triazoles have been discussed (1988BSB573). 

The 1,2,3-triazole 1-oxides 326 are usually stable, crystalline, semipo-lar, and colorless compounds. The lower 2-alkyl-substituted 1,2,3-triazole 1-oxides tend to be slightly hygroscopic. They act as very weak bases, protonation requiring acids like triflic acid and O-alkylation requiring tri-methyloxonium salts. No pKa values have been reported. 

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. 

The cyclization mechanism is unknown but a one-electron transfer mechanism has been suggested (1997JOC9177). Anodic oxidation of 2-hydroxyiminohydrazones 345 gives respectable yields of 1,2,3-triazole 1-oxides 346 (1982ZC25). 

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