1.2.3- Triazole 3-oxides, bromination

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]. 

In [l,2,4]triazolo[4,3-a]pyrazine (174) bromination took place at the 5-position rather than in the triazole ring (77JOC4197). It was not possible to convert the 3-hydroxy derivative into the 3-chloro analogue (68JHC485). The isomeric [1,5-a] compound (175) was also brominated at C-5 (74TL4539), whereas its 7-oxide gave the 8-chloro derivative under Meisenheimer conditions [80JCS(P1)506]. 

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... 

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>. 

Strongly activating substituents assist halogenation at the adjacent ring site. When 4-hydroxy-2-phenyl-1,2,3-triazole was treated with bromine, the product was mainly 5-bromo, but a small amount of 2-p-bromophenyl product was also observed. The corresponding 1-oxide gave only resins when similarly treated (88JOU599). 

Bromine at C5 of 2-substituted 1,2,3-triazole 1-oxides 361 is readily removed without touching the N-oxygen by treatment with aqueous-methanolic Na2S03 (2010UP2). Debromination has also been achieved by metallation followed by protonation as described in Section 4.1.6.4 (Scheme 109). 

Bromine and iodine at the 5-position of 2-phenyl-l,2,3-triazole 1-oxides 361 and 370 could be replaced with lithium or magnesium using BuLi or z -PrMgCl (2010UP2) (Scheme 111). 

The 4-chloro-substituted triazole 1-oxide 470 could be chlorinated and brominated at the 5-position affording 471 or 472 in excellent yield (1987ACSA(B)724). Even the 3-phenyl compound 470 (R=Ph) reacted regioselectively in the triazole ring confirming the activation conveyed by the N-oxide functionality (Scheme 137). 

While 5-chloro-l,2,3-triazole 1-oxide 467 reacted with sodium methox-ide with replacement of the chlorine (see Section 4.1.6.8), the corresponding bromo compound 468 under similar conditions afforded the cme-substitution product 483 as the main product (1987ACSA(B)724). A mechanism involving halogen dance and supported by control experiments is sketched in Scheme 142. The bromine in 468 is located at the less activated position with respect to nucleophilic displacement. On the other... 

Rearrangement of acyl and halo groups are the most common reactions of triazoles with functions on nitrogen. The chemistry of 4-hydroxytriazoles , in effect Af-oxides, has been less extensively studied than that of triazolinones. The N—O bond is cleaved by phosphorus halides and acidic anhydride but not by oxidation with permanganate or by alkaline bromination (70jpr610). 

The reaction between heteroaromatic iV-oxides and 2-chloro, 5-dihydroimidazole 955 results in a formal ureida-tion of the heteroaryls. This reaction was extended to 2- and 4-picoline iV-oxides for the synthesis of 956 and 957, respectively (Scheme 232) <2002JHC911>. The 2-bromine of nitronyl nitroxide 958 is easily displaced with sodium azolides to give spin-labeled azoles (imidazole, pyrazole, triazole) 959 which are prone to hydrolysis to hydroxamide acid anion 960 <2004T99>. 

A general method for synthesizing triazoles 101 from bis(arylhydra-zones) 100 was achieved by various oxidizing agents, such as metal salts in their higher valency state, nitrous acid, and halogens such as bromine (Scheme 25). The latter bromination affords the corresponding p-bromo-phenyl derivative of 101. These reactions are applicable with various... 

Scott and others have shown that the hydrazones of many azoles undergo ring closure to fused triazoles [Eq. 20)] either by oxidation (R = H) or by displacement of halogen (R = Br). Thus triazolotriazoles (180) were obtained by lead tetraacetate oxidation of the corresponding s-triazolehydrazone, " or by displacement of bromine from the appropriate bromo derivative. s-Triazolo[4,3-rf]tetrazoles (181) were prepared by oxidation or displacement of bromine " from the appropriate derivative, and similar methods were used to prepare s-triazolobenzothiazoles (182) s-triazolooxadiazoles (183), and pyrazolo[3,2-c]-s-triazoles. ... 

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