1.2.4- Triazoles reactions with acetylenic esters

As l,2,4-triazole-3,5-dione (PTAD) is a stronger dienophile than acetylenic esters, more facile formation of the Diels-Alder cycloadducts was expected. But because it cannot behave as a diene in a reaction with alkynes such as diethyl azodicarboxylate, the formation of dihydrooxadia-zines is excluded. In spite of these characteristics, no Diels-Alder adducts were obtained in the reaction of l-phenyl-4-vinylpyrazole with PTAD in acetone at -80°C and 2,2-dimethyl-4(l-phenylpyrazol-4-yl)-8-phenyl-l,6,8-triaza-3-oxabicyclo[4.3.0]nona-7,9-dione 277 was obtained as a major product. The isolation of the tetrahydrooxadiazine 277 indicates that the 1,4-dipole 278 was formed and trapped with acetone. 

The converse addition of a phosphorus-containing dipolar reactant to a dipolarophile which lacks phosphorus is exemplified by the addition reactions of diethyl (1-azidoalkyl)-phosphonates (503) to acetylenic compounds to give the 1,2,3-triazoles 504 [X = H, Me, Ph, COPh, or COOMe Y = COOMe, COOEt, P(0)(OEt)2, or P(0)PhJ related reactions have also been carried out with the ester 503 (R = NHR ) The (l-diazoalk-2-enyl)phosphonates 505 readily cyclize to 506 and the diazoamide 507 (Z = NH2) also behaves analogously to give 508 , but may (for Z = OMe or OEt) react in an intermolec-ular fashion. ... 

An interesting report from Loupy et al. described the use of solvent-free conditions and microwaves for the synthesis of regioisomeric 1,2,3-triazoles 188 and 189 with substantial reduction for reaction times - down to 5-30 min compared with 30-40 h under reflux in toluene under thermal conditions for the 1,3-dipolar cycloaddition between phosphonate azides 186 and acetylenic esters 187 (Scheme 11.48) [31c]. 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

Only the 1-benzyl-vic-triazole, crysts(from eth at 20°), mp 61°, appears to have been prepd and reported in the literature. Curtius Raschig(Ref 2) prepd 1-benzyl-vic-triazole by the reaction of benzyl azide with the methyl ester of acetylene-dicarboxylic acid, followed by sapon and decarboxylation. Wiley et al(Ref 3) prepd the compd directly and in better yield from acetylenedicar-boxylic acid, followed by decarboxylation to 1 -benzyl-vic-triaZole(77% yield)... 

On heating the 2-yS-azidomethyl penam sulphone (85) with suitable acetylenes, a series of 2-/S-(l,2,3-triazolyl)methyl penam sulphone esters was obtained, which upon deprotection gave the free acids (86) [48, 49]. In particular, reaction of (85) with either vinyl acetate or (trimethylsi-lyl)acetylene provided the parent triazole, tazobactam (30), after hydrogenation (and prior potassium fluoride-18-crown-6 treatment in the case of the TMS acetylene) [50]. 

Acetylenic sulfones are reactive dipolarophiles. 1,3-Dipolar cycloaddition with nitrile oxide gave ester-linked isoxazoles (Scheme 11.47). However, the cycloadducts were cleaved from the resin with the sulfone moiety under alkaline hydrolysis. The method was applied later to the 1,3-dipolar cycloaddition reaction to prepare a wide selection of heterocycles, such as pyrroles, pyrazoles, 1,2,3-triazoles, and isoxazoles. " ... 

Lermontov et al. reported some successful reactions of two a,a-difluoroazides, namely, 2-hydroperfluoropropyl azide and the methyl ester of 3-azido-perfluoropropanoic acid, with various acetylene compounds, and described some properties of the resulting products [45], Thus, phenylacetylene reacts with 2-hydroperfluoropropyl azide to give the corresponding 4-phenyl-l-(2H-perfluoropropyl)- ,2,3-triazole 41 and 5-phenyl-l-(2H-perfluoropropyl)-l,2,3-triazole 42 in 1/2 ratio. Disubstituted acetylenes also react with these azides to give the corresponding lH-1,2,3-triazoles [45]. Thus in the case of triazole 43 the yield is close to the quantitative. 

---