1,2,3-Triazoles, formation derivatives

Methods of this type are best considered as reactions of the fused ring-systems in question (see Chapter 4.15). The example illustrated in Scheme 91 is of potential interest in pharmacology (75T1363, cf. 74CPB1938). The conversion of the 1-aminoadenosine (192) into the imidazolyltriazole (193) amounts to triazole formation from an amidrazone intermediate and a formyl group derived from the pyrimidine moiety. 

Hexosulose hydrazones and the mixed osazones react with diazotized aniline to give formazans, and with hydrogen peroxide to give pentonic acids. Unlike the mixed osazones obtained by transhydrazonation, the derivatives obtained from the glycosulose hydrazones are pure, uncontaminated compounds, and the positions of their hydrazone residues are well established. Thus, they afford remarkable possibilities, not only in the preparation of new types of compound, but also in enabling the reaction of osazones to be followed more closely, as in the case of triazole formation," and in studying the structure of anhydro-osazones. ... 

Sitagliptin is a peptidase-4 (DPP-4) inhibitor that is used as an antidiabetic drug either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. The synthesis of sitagliptin contains triazole formation followed by coupling with a acid derivative. ... 

The Rh-catalyzed annulation of triazoles has been explored by several investigators as a novel indole synthesis. Fokin s team generated azavinyl carbenes with rhodium and parlayed this reaction into an indole synthesis (equation 3) [54], Davies and colleagues described a one-pot indole synthesis from tosyl azide and cyclohexenyl derivatives involving an in situ triazole formation (equation 4) [55], and Lin reported a synthesis of 3-indolylimines using a similar approach (equation 5) [56]. Miura and coworkers effected the Rh-cat-alyzed intramolecular synthesis of 3,4-fused indoles... 

Schematic representation of self-assemble monolayer (SAM) formation, SAM-/ -CD formation via the click reaction, the adsorption/desorption of ferrocene-modified polymers (1), and the chemical structures of HS-(CH2)n-EG6-N3 (2), HS-(CH2)n-EG4-OH (3), ferrocene-derivated PAH (4), ferro-cene-derivated CHI (5), alkyne-functionalized / -CD (6), ethynylferrocene (7), and triazole formation (8). (Reprinted with permission from Dubacheva et at. 2010. Electrochemically Controlled Adsorption of Fc-Functionalized Polymers on beta-CD-Modified Self-Assembled Monolayers. Langmuir 26 (17) 13976-13986, copyright (2010) American Chemical Society.)...

The 1,3-dipolar cycloaddition of organic azides onto dipolarophiles is a versatile method of synthesizing 1,2,3-triazole derivatives [6]. The thermal cycloaddition without metal catalysts [Scheme 16.4, Eq. (a)] of organic azides 1 to alkynes 2 was utilized for triazole formation, but frequently with low regioselectivity. Recently, this reaction has been improved in terms of the reaction rate and regioselectivity by using copper(I) catalysts, which were reported independently by Sharpless et al. [7] and Meldal et al. [8] [Scheme 16.4, Eq. (b)]. 

The most important chemistry of azidoazoles is the fragmentation of derived nitrenes of which the prototypes are (453) (454) and (455) (456). Thus 5-azido-l,4-diphenyltriazole (457) evolves nitrogen at 50 °C (70JOC2215). 4-Azido-pyrazoles and -1,2,3-triazoles (458) undergo fragmentation with formation of unsaturated nitriles (8lAHC(28)23l). 

Watanabe N, S Horikoshi, A Kawasaki, H Hidaka, N Serpone (2005) Formation of refractory ring-expanded triazine intermediates during the photocatalyzed mineralization of the endocrine disrupter amitrole and related triazole derivatives at UV-irradiated TiOj/HjO interfaces. Environ Sci Technol 39 2320-2326. 

The triazole derivative, in turn, produces an intensely colored substance, III, with a diazonium compound under the experimental conditions devised for this analysis. The reactions leading to the formation of the colored substance have not yet been fully elucidated, but it appears that opening of the triazole ring as well as coupling is involved. The chemistry of the color formation will be discussed in another publication. 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

A nucleophilic attack of morpholine on the pyrimidine ring in l,2,3-triazolo[l,5- ]pyrimidinium salts 1203 leads to unstable intermediates 1204. Spontaneous opening of the pyrimidine ring results in formation of 1,2,3-triazole derivatives 1205 that are isolated in 80-85% yield. A similar nucleophilic attack of the hydroxide anion (from aq. K2CO3) on dimethoxy derivative 1203 provides transition species 1206 that opens to intermediate 1207, and finally tautomerizes to ester 1208, isolated in 87% yield (Scheme 200) <2003T4297>. 

Cyclization of the aminomethylhydrazone derivative 167 in the presence of base gave the 1,3,5-trisubstituted 1,2,4-triazole 168 in 50% yield a mechanism for the formation of triazole 168 also accounts for the formation of accompanying di- and tricyclic by-products (Equation 53) <1997S1461>. 

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