Dipolar cycloadditions 1,2,3-triazoles from

Under a variety of reaction conditions we found values for the ratio of tri-azole-to-cucurbituril of 2 or more. In one instance the value was as high as 6.8, although it is believed that in this specific case the higher reaction temperature led to a significant proportion of thermally activated dipolar cycloaddition. Triazole oligomers were identified by MS after they had been separated from the catalyst... 

The Cu(I)-catalyzed Huisgen [3 + 2] dipolar cycloaddition was also utilized by Van der Eycken and co-workers to obtain a new class of glycopep-tidomimetics based on the 1,2,3-triazole ring system 78 starting from glu-copyranosyl azide 75 and the pyrazinone compound 76 (Scheme 26) [58]. 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

Azide 367 is prepared from 4-r -butyl-2-nitroaniline in 76% yield by its diazotization followed by treatment with sodium azide. In a 1,3-dipolar cycloaddition with cyanoacetamide, azide 367 is converted to triazole 368 that without separation is directly subjected to Dimroth rearrangement to give derivative 369 in 46% yield. Reduction of the nitro group provides ortfc-phenylenediamine 371 in 91% yield <2000EJM715>. Cyclocondensation of diamine 371 with phosgene furnishes benzimidazol-2-one 370 in 39% yield, whereas its reaction with sodium nitrite in 18% HC1 leads to benzotriazole derivative 372, which is isolated in 66% yield (Scheme 59). Products 370 and 372 exhibit potassium channel activating ability <2001FA841>. 

A mild and greener approach to the synthesis of 1,2,4-triazoles by the dipolar cycloaddition of nitrilimines with nitriles has been reported. The nitrilium intermediates were generated in situ from hydrazonyl chlorides 120 and reacted with the nitriles in a one-pot process. Yields of the 1,3,5-trisubstituted products 121a-o were good in the majority of cases (Equation 37 and Table 20) <2005H(65)1183>. 

The thermal cycloaddition of azides to acetylenes is the most versatile route to 1,2,3-triazoles, because of the wide range of substituents that can be incorporated into the acetylene and azide components. The accepted mechanism for the reaction is a concerted 1,3-dipolar cycloaddition. The rates of addition of phenyl azide to several acetylenes have been measured the rates of formation of the aromatic triazoles are not appreciably different from the rates of cycloaddition to the corresponding olefins, indicating that the transition-state energy is not lowered significantly by the incipient generation of an aromatic system. 

D-Triazoles have been isolated from the reaction of several activated nitriles, such as cyanogen, cyanogen halides, methyl cyanoformate, and cyanic acid esters, with diazoalkanes. The reaction can formally be regarded as a 1,3-dipolar cycloaddition. The v-triazoles may be... 

Some related cyclic scaffolds, such as the azepines, were obtained by Ugi-4CR/ RCM combinations (Fig. 5a) [61], and fused benzodiazepine/triazole frameworks were derived from sequential Ugi-4CR/alkyne-azide dipolar cycloaddition (Fig. 5b) [62]. Both are considered as interesting (3-tum mimics. Similarly, bicyclic systems featuring fused DKP rings (Fig. 5c) have been reported to mimic the ten-membered pseudo-cycle of type 1 (3-tums [63, 64]. 

Various 1-(1-naphthyl)-1,2,3-triazoles with electron-withdrawing groups at the 4- and/or 5-pos-itions (e.g. (135)) are synthesized from 1-azidonaphthalene and alkynes <87JCS(P1)413>. l-(Naphthyl)-benzotriazoles (127) are prepared by cycloaddition of the appropriate 1-azidonaphthalenes to benzyne or substituted benzynes, generated from 3-methylanthranilic acid. l-(l-Naphthyl)-naphthotriazole is similarly prepared by cycloaddition to 2,3-dihydronaphthalene. 1,3-Dipolar cycloadditions of 8-azidoquinolinone with benzyne and DMAD give benzotriazoles and triazoles (e.g., (130)), respectively <87JCS(Pi)403>. 

The 1,3-dipolar cycloaddition of equimolar amounts of enamide and aryl azide at room temperature, over a period of time (3 days to 10 months), affords the A -1,2,3-triazolines (733) as stable crystalline products (Equation (63)). In refluxing ethanol, however, the reaction yields the corresponding triazoles as the major product with loss of the amides <92JOC3075>. 5-Amino-1-aryl-1,2,3-triazolines (e.g., (734)-(735)) are readily prepared from the [3 -I- 2] cycloaddition of azides to... 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

Erba et al. (102) observed a novel formation of pyrrole imines 181 from the 1,3-dipolar cycloaddition of mtinchnones 179 and 5-amino-l-aryl-4,5-dihydro-4-methylene-1,2,3-triazoles 180 (Table 10.4). Treatment with benzaldehyde yielded 3-formylpyrroles (182). The reaction presumably involves loss of carbon dioxide, nitrogen, and morpholine from the initial cycloadduct. Unsymmetrical mtinchnones behave regioselectively and furnish products derived from bonding between C(2) of... 

Complexes of the heteroaromatic compounds may be prepared by building up the heterocyclic ligand. The most effective method for the N (10, E = N) and C (11) derivatives is 1,3-dipolar cycloaddition from the metal azides. The N and C derivatives of triazole (67) and (68), tetrazole (69-72) and other azoles, e.g., 73, were prepared.The transformations leading to the complexes are summarized later. 

Scheel, A.J., Komber, H. and Voit, B.I. (2004) Novel hyperbranched poly([l,2,3]-triazole) s derived from AB2 monomers by a 1,3-dipolar cycloaddition. Macromol. Rapid Commun., 25, 1175. 

The 1,3-dipolar cycloaddition of azidoalkylphosphonates to enamines afforded A2-1,2,3-triazoles which are further converted to the 1,2,3-triazoles [95H(40)543] fused triazoles are similarly obtained when a cyclic enamine was employed. Fused 1,2,3-triazole (88), a xanthine oxidase inhibitor, was prepared by the reaction of an alkyl azide with cyanoacetamide with further elaboration of intermediate (87) by treatment with HMDS in xylene [95FES257]. The fused 4H-l,2,3-triazolo[l,5- ][l,4]benzodiazepin-6(5H)-one (90) was obtained from propargylamide (89) via an intermediate azide [95S647]. 

The structure of 6-exo-ethoxycarbonyl-2,3a,4,6a-tetraphenyl-3,3a,4,5,6,6a-hexahydropyrrolo [2,3-cf]-1,2,3-triazol-2-ium-3-ide (6) has been determined compound (6) arises from an initial 1,3-dipolar cycloaddition between ethyl acrylate and the dipole (7), followed by sigmatropic rearrangements <90JCS(P1)2537>. 

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