3,5-Dibromo-l,2,4-triazoles

The synthesis of 3,5-dibromo-l-(thietan-3-yl)-l,2,4-triazole 135 was performed by the reaction of 2-chloro-methylthiirane 99 with 3,5-dibromo-l,2,4-triazole yielding the product in 50% <2005RJ01847> (Equation 38). 

Bromination occurs readily in alkaline solution giving 3,5-dibromo-l,2,4-triazole the 3-monochloro derivative can be obtained by thermal rearrangement of the A-chloro isomer an analogous N—>C 1,5-sigmatropic shift followed by tautomerisation converts the 1- into the 3-nitro compound. ... 

Advantage was taken of the greater reactivity of the 5-position compared to the 3-position of l-aIkyl-3,5-dibromo-l,2,4-triazoles (e.g., 139) toward nucleophilic substitution to prepare l-alkyl-3-fluoro-l,2,4 triazoles 140 by halogen exchange. The initial fluorination product was deprotected to give the bromo—fluoro derivative 141 and this was used for subsequent synthetic manipulations. Included was the preparation of a 3,5-difluoro derivative 142 (Fig. 3.84). 

An example of synthesis of N-fluoro-1,2,4-triazole was described in the patent of Strazdina and Grinstein [6, 17]. Here l-flnoro-3,5-dibromo-l,2,4-triazole 8 was obtained by treating the heterocyclic substrate with the hypohalous acid or its derivatives at -40 to -h50 C in water or an organic solvent in the presence of bases. Langlet and Oslmark in a patent [18] have described the application of isomeric fluoro-triazolones 9,10 as components of explosive compositions, but the data on the synthesis of these substances have been not reported. 

The nucleophilic exchange of one bromine atom in l-benzyl-3,5-dibromo-l,2,4-triazole 21 with fluorine under the action of CsF followed by the photoinitiated elimination of the benzyl protective group led to the formation of 3-bromo-5-fluoro-lH-1,2,4-triazole 22 in 59 % overall yield. The alkylation of this substrate gave l-alkyl-3-fluoro-l,2,4-triazoles for the first time. Both bromine atoms were substituted to provide the corresponding difluoro derivative 24 under the same reaction conditions, but using l-(3,5-dimethoxybenzyl)-3,5-dibromo-l,2,4-triazole 23 as substrate for fluorination [32]. 

Halo-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halo analogues do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative. 1-Substituted 3-chloro-and 5-chloro-1,2,4-triazoles both react with amines, and alcohols <2006T2677> but selectivity is illustrated by the reaction of 1-benzyl-3,5-dibromo-1,2,4-triazole with CsF only at C(5) <1998S1357>. 

Finally, triazoles ([15N2]-labelled 3,5-dibromo-lH-l,2,4-triazole and 3,5-di-chloro-lH-1,2,4-triazole) have also been studied by 15N CP MAS NMR [209]. These compounds form cyclic trimers in their crystal structures. 

The H-1 atom of 4,5-dibromo-l,2,3-triazole (147) (67G109) is very acidic and forms instantly the triazolide salt (148) when treated with dimethylamine (67G109). The salt is stable even when heated to 260 °C for 140 hours and reacts smoothly in a conjugate addition reaction to give (149) (54JA4933). Methylation of (148) gives both the 1-methyl-IH and 2-methyl-2H derivatives (150) and (151) (70JHC961). 

Triazole reacts with bromine to afford the 4,5-dibromo derivative and an excess of hypobromite leads to l,4,5-tribromo-l,2,3-triazole. 2-Methyl-l,2,3-triazole shows in comparison a decreased readiness towards halogenation. But in the presence of iron filings as catalyst, the bromination affords 2-methyl-4,5-dibromotriazole (144) and no monobromi-nation product could be isolated (55LA(593)207). 

Dibromo-l-methoxymethyl-l,2,3-triazole forms the 5-lithio compound with n-butyllithium at-80 °C and 4,5-dibromo-2-methoxymethyl-l,2,3-triazole undergoes a comparable exchange. l-Phenyl-1,2,3-triazoles participate in Diels-Alder cycloadditions with dimethyl acetylenedicarboxylate using aluminium chloride catalysis, producing l-phenylpyrazoles. " ... 

Both 4,5-dibromo-l-methoxymethyl- and 4,5-dibromo-2-methoxymethyl-1,2,3-triazole form 5-lithio componds by exchange with n-butyllithium at -80 °C."... 

The reaction of sodium azide with l-bromo-l-nitro-2-arylethenes takes place by a formal 1,3-cycloaddition Scheme leading to 4(5)-aryl-5(4)-nitro-l,2,3-triazoles [487-489], During the synthesis of nitrotriazoles the bromonitroarylethenes can be replaced successfully by the more readily obtainable l,2-dibromo-l-nitro-2-arylethanes [489], The intermediate product in the synthesis of 3-nitropyrazoles from 2,2-dinitroethanol and diazo ketones or diazoacetic ester is 1,1-dinitroethene [490,491] (Scheme 68). 

Dimedone was treated with two equivalents of bromine in glacial acetic acid to yield 2,2-dibromo-5,5-dimethylcyclohexane-l,3-dione. The dibromo compound was subjected to reaction with substituted 2-aminothiophenols, 2-aminophenol, thiocarbohydrazones, and triazoles to furnish spiro-(2, 6 -dioxo-4, 4 -dimethylcyclohexane)-6-substituted-l,... 

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