3- Substituted 1,2,3-triazole 1-oxides derivation

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]. 

The hydroxytriazole 1-oxides 500 and 502 when treated with methyl iodide were methylated predominantly at the N-oxygen affording mesoionic anhydro l-methoxy-3-methyl-4-hydroxy- or 5-hydroxy-l,2,3-triazolium hydroxide 501 or 503 (Scheme 146) (1987ACSA(B)724). In both cases methylation at the C-hydroxy group took place to a minor extent giving rise to methoxy-substituted triazole 1-oxides 499 or 503, respectively. Under similar conditions 3-methyl 4-hydroxy-5-chloro-l,2,3-triazole 1-oxide 505 produced a 2 1 mixture of the C-methoxy and the N-methoxy derivatives 504 and 506. The mesoionic triazoles 501, 503, and 506 were dealkylated upon heating with 1-M sodium methoxide, reforming the hydroxy-substituted N-oxides 500, 502, and 505, respectively. 

Monocyclic 2-substituted 1,2,4-triazole 1-oxides derived from 522 have been reported (Scheme 153). The structure of the /V-oxide fragment was proved by X-ray crystallography (2010LOCEC377). IR, H NMR, C NMR, and MS data have been published (1976JCS(P1)2166). 2-Substituted... 

A large series of 1,2,3-triazole-l-oxide derivatives including nitro-substituted ones was synthesized and studied by mass spectrometry (Table 3.74.) [177, 608], A more intensive peak in nitro derivatives of 1,2,4-triazole is m/z 30 (NO+) that is caused by the presence of N02-group (Scheme 3.67, Table 3.75) [1329],... 

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

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>. 

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). 

Aminotriazoles and their derivatives can be prepared from bis hydrazones and from substituted bis hydrazones of a-diketones. The bis hydrazones may in some cases be prepared more conveniently from -bromoketones than from a-diketones. Oxidation with mercuric oxide or with manganese dioxide gives the 1-aminotriazoles directly (Scheme m-ns Although two isomeric triazoles would be ex-... 

The aromatic 3-substituted 1,2,3-triazole 1-oxides 448 are derived from 1-substituted 1,2,3-triazoles 457 by appending an oxygen atom to the... 

Two 4-substituted 1,2,4-triazole 1-oxides, namely 2-(l -hydroxymethylene-2-oxo-l,2,3,4-tetrahydroquinoxaline-1-yl)-4-allyl-5-methylthio 1,2,4-triazole 1-oxide 530 (1984H695) and 4-hydroxy-l,2,4-triazole 1-oxide 531 (1995J CS(P1)243), (Scheme 157) derived from the parent species 528 (Scheme 156), have been described. The compounds were characterized by their H NMR and C NMR spectra. 

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>. 

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... 

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