1- Substituted 1,2,3-triazoles, metallation

The direct lithiation of a 2-substituted 1,2,3-triazole has not been reported. Halogen-metal exchange of 4,5-dibromotriazole with n-butyllithium at — 80 °C occurs smoothly and the subsequent reaction of the lithium intermediate (244) with various electrophiles except aldehydes gives the 4-bromo-5-substituted triazoles (245) (Scheme 46). The corresponding 1-substituted 4,5-dibromo-1,2,3-triazole undergoes a similar reaction at the 5-position . 

Substituents at carbon atoms of 1,2,4-triazoles was efficiently achieved by designing triazoles with the required substituents in place [38,39]. Through this process various fluoroalkyl-substituted 1,2,4-triazolium salts were obtained [40], first via reaction of 1,3,5-substituted triazoles (21a-c) with iodomethane to form quaternary salts (22a-c), which when metathesized with various metal salts resulted in ionic hquids and energetic salts (23a-h) (Scheme 6). The yields of products are usually excellent. 

Although most of the catalytic activations of Huisgen reaction involve metal salts, a very interesting activation by boronic acids has been recently published [151]. This remarkable mild transformation enables the access to 4-carboxy-substituted triazoles without decarboxylation (Scheme 62). 

Condensation of benzaldehydes with benzotriazole in the presence of thionyl chloride readily gives a,a-/fe(benzo-triazol-l-yl)toluenes 727 that can be considered as l,l -gm-dicarbanion equivalents. Thus, treatment of derivatives 727 with ketones and lithium metal suspended in THF at — 78 °C generates substituted propylene glycols 728 (Equation 18) <1998TL2289>. 

Azoles can form stable compounds in which metallic and metalloid atoms are linked to nitrogen. For example, pyrazoles and imidazoles TV-substituted by B, Si, P, Ga, Ge, Sn and Hg groups are made in this way. Imidazoles and 1,2,3-triazoles with a free NH group can be TV-trimethylsilylated and N-cyanated (with cyanogen bromide or l-cyano-4-dimethylaminopyridinium bromide (88S470 9IRRC573) (see also Section 3.4.3.12.4)). Imidazoles of low basicity can be TV-nitrated. 

Substituted 1,2,3-triazoles, 1,2,4-triazoles and tetrazoles are metallated by n-butyllithium at low temperature at the 5-position. At room temperature 5-lithium derivatives tend to undergo ring opening. No direct lithiation of a 2-substituted 1,2,3-triazole has been reported. 

Reedijk and co-workers have prepared and studied a variety of Ru(ll) complexes of pyridyl- and pyrazinyl-substituted 1,2,4-triazoles of which 26 is an example. In ail cases the heterocyclic ligands were chelated to the metal center via one azole and one azine nitrogen atom and, in addition to various electrochemical and spectroscopic studies, pKa values for the pyrrole proton of the triazole ring were obtained. The Ru(bpy)2 + com-... 

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). 

The anions generated by proton-metal or halogen-metal exchange (Section 4.1.6.3-4) reacted readily with electrophiles like MeOD, Mel, I2, and A/-formyI morphol i ne (NFM) to give the 5-substituted 1,2,3-triazole 1-oxides 372 (2010UP2) (Scheme 112). 

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. 

Quantitative estimation of the stability constants for metal ion complexation with 1-substituted tetrazoles has been performed <2005CEJ6246>. It was demonstrated that tetrazole nucleoside 277 shows a low tendency to form stable complexes with ions Ag(l) and Hg(ll) comparing with imidazoles and 1,2,4-triazoles. Only Ag+ is able to form a 1 1 complex with compound 277 (log0.86), and no coordination of Hg2+ to 277 can be detected. 

Nucleophilic substitution of the diazo group is practically the only method for the production of nitro derivatives of tetrazole [392, 436 143], 5-Nitrotetrazole itself was isolated and identified in the form of metallic salts [436-440, 442, 443], The mechanism of substitution of the diazo group by a nitro group in heterocyclic compounds has not been studied specially. As already mentioned, in many cases the reaction takes place as catalytic nucleophilic substitution and does not require the use of a catalyst (copper salts) [392,444], The results from investigation of the kinetics of the substitution of the diazonium group by the nitro group in compounds of the benzene series make it possible to suppose that the diazonitrite is formed intermediately and quickly reacts with a second nitrite anion [392,444], Some difference between the kinetics of the reaction of 3-diazonium-5-carboxy-l,2,4-triazole and 3-diazonium-5-methoxycarbonyl-l,2,4-triazole with sodium nitrite in hydrochloric acid and the analogous process in the benzene series is probably due to prototropic... 

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