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

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. 

The method has also been applied to the synthesis of alkyl-substituted quinoxalin-2-amines. Thermal rearrangement of l-(2-aminophenyl)-4,5-dihydro-5-morpholino-l,2,3-triazoles 15 affords unstable 2-alkyl-l,2,3,4-tetrahydroquinoxalin-3-amines, which undergo deamination and consequent oxidation to afford 2-alkylquinoxalines 16. ... 

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. 

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 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. 

Substituted 1,2,3-triazole 1-oxide 448 can be prepared by N-oxidation of 1-substituted 1,2,3-triazoles 457, by N-alkylation of 1-hydroxy-1,2,3-triazoles 443, by cyclization of triazene 1-oxides 460, or by rearrangement of 2-substituted 1,2,3-triazole 1-oxides 445 (R=PMB). Finally, base-mediated ring opening of pyrimidinediones 463 offers a route to 464. 

N-Alkylation of 1-hydroxy-l,2,3-triazoles 443 produces 3-substituted 1,2,3-triazole 1-oxides 448 (R=Alk). Competing O-alkylation of the 1-hydroxy-l,2,3-triazoles 443 to give 1-alkoxy-l,2,3-triazole 458 is suppressed by omitting addition of base during the alkylation (1996ACSA549, 2001S1053, 2002JOC3904) (Scheme 132). 

Substituted 1,2,3-triazole 1-oxides 448 have been reported to undergo electrophilic and nucleophilic aromatic substitution and are subject to debromination, proton-metal exchange, and halogen-metal exchange followed by electrophilic addition. Transmetallation and cross-coupling have not been described. 3-Substituted 1,2,3-triazole 1-oxides 448 can be proton-ated or alkylated at the O-atom and they can be deoxygenated and deal-kylated. The individual reactions are described in Section 4.2.7.1-4.2.7.14. 

The 3-substituted 1,2,3-triazole 1-oxides 448 were alkylated at the oxygen by trimethyloxonium tetrafluoroborate using liquid sulfur dioxide as the solvent affording hygroscopic 3-substituted l-methoxy-l,2,3-triazolium tetrafluoroborate 507 in high yield (1987ACSA(B)724).The reactivity of these salts has not been reported (Scheme 147). 

Alkyl radicals. Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus, imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position. Scheme 72 shows the substitution of a protected histidine <2001BML1133>. Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. A-Alkyl-1,2,-4-triazoles can be radical substituted at C(5) <2001TL7353>. 

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]. 

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