3- Aryl-substituted 1,2,3-triazole 1-oxides

The 3-alkyl- or aryl-substituted 1,2,3-triazole 1-oxides 448 are usually stable, crystalline, polar, and somewhat hygroscopic compounds. 3-Sub-stituted 1,2,3-triazole 1-oxides 448 are weak bases being subject to protonation at the negatively charged oxygen atom. 3-Hydroxy-l,2,3-triazole 1-oxide 456 (R=OH) acts both as a base and as an acid. No pKa values for 3-substituted 1,2,3-triazole 1-oxide have been reported. 

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>. 

Acid hydrolysis of 3-methyl-6-phenyl-l,2,4-triazine 4-oxide (827) yields 4-phenyl-1,2,3-triazole through an acyclic intermediate (828) (Scheme 168) <89AHC(46)73>. 1,2,4-Triazine 2-oxides (829) undergo rearrangement in basic conditions (Equation (80)) to form 4-substituted 2//-1,2,3-triazoles <89AHC(46)73>. l-(2-Nitrophenyl)-5-aryltetrazoles (830) and l-aryl-5-(2-nitrophenyl)tetrazoles are converted into 2-arylbenzotriazoles (831) by refluxing in nitrobenzene (Equation (81)) <81AJC69l>. 

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. 

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... 

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],... 

Regiospecific synthesis of 2-substituted-l,2,3-triazoles are rare. 5-Carbomethoxy-2-carbomethoxymethyl-4-trinitromethyl-l,2,3-triazole (84a) was prepared by 1,3-dipolar cycloaddition/ alkylation of NCC(N02)3 with Me02CCHN2. X-ray crystallographic data shows the trinitromethyl substituent of 83a is a strained sp center which infers chemical reactivity comparable to that observed for polynitrometnanes thus, 84a with ethanolic KOH afforded potassium 4-dinitromethyl-l,2,3-triazole salt (84b) [93ZOR(29)1231]. Copper-catalyzed oxidative cyclizations of arylhydrazones, while sensitive to substituent effects, provides 2-aryl-l,2,3-triazoles (85) [94H(38)739]. 

Davies et al. disclosed a one-pot indole synthesis from cyclohexene 154 and tosylazide (155).The reaction proceeds via a click reaction to form the triazole, followed by Rh-based decomposition, pyrrole formation, and oxidation to indole 156. The indoles (and azaindoles) are formed in very good yield and may be substituted with alkyl-, aryl-, or silyl-proteaed alcohols (13JA11712). 

Oxidation of amines containing a-hydrogen atoms is of variable difficulty (equation 23). Permanganate oxidation of l-aryl-5-(tertiary)amino-v-triazoles leads to the corresponding amides. Benzyl(tri-ethyl)ammonium permanganate oxidizes a variety of simple, substituted amines. Tertiary amines give go yields of amides, but secondary and primary amines give moderate yields due to the formation of imines. 

Low yields were obtained in the absence of pivalic acid however, employing greater than 30% pivalic acid did not further improve yields or reactivity. Substrates that performed well included C3-substituted benzothiophenes, C2-substituted thiophenes, pyrroles, imidazole, triazole, imidazopyridine, thiazole, and oxazoles, which could be efficiently arylated with aryl bromides. Unfortunately, benzofuran produced low yields (29% with 2-bromotoluene), and furans encountered issues with diarylation, which could be minimized by using more sterically hindered aryl bromides. Arylation of indolizines could be achieved, albeit electron-deficient aryl bromides required longer reaction times (16-24 h). Heterocyclic aryl bromides, such as 3-bromopyridine, could also be employed with thiazole. Problematic aryl halides included cyano, nitro, acetyl, pyridyl functionalities, and N-heterocyclic V-oxides. Other coupling partners, such as aryl tri-flates and aryl chlorides, performed poorly under the reaction conditions. Unsuitable heterocycles included unprotected imidazoles, 2-aminothiazole, isoxazole, benzothiazole, and benzoxa-zole, which failed to produce arylated products. 

Notably, 2-substituted 1,2,3-triazole was inactive under both alkenylation and arylation conditions, illustrating the unique reactivity of its N-oxide analogue. 

The synthesis of imidazo[l,2- ]pyridine derivatives from simple substituted pyridines is also developed recently. Fu et al. reported an efficient Cul-catalyzed aerobic oxidative C-H functionalization of substituted pyridines with N-(alkylidene)-4//-l,2,4-triazol-4-ammes leading to imidazo[l,2- ] pyridine derivatives in moderate to good yields using O2 (1 atm) as the oxidant (Scheme 8.63). The reaction proceeds by the cleavage of the N-N bond in the N-(alkylidene)-4//-l,2,4-triazol-4-amines and activation of an aryl C(sp )-H bond in the substituted pyridines [108]. 

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