1.2.4- Triazole structure

X-Ray crystallographic data for several basic derivatives of H-1,2,3-triazole and benzotriazole are included in CHEC(1984) and CHEC-II(1996) <1984CHEC(5)669, 1996CHEC-II(4)1>. Hundreds of new 1 //-1,2,3-triazole structures have been analyzed since some crystallographic data for representative examples (structures 5-12) are collected in Table 1. 

The perfluorinated compound (145) was treated with phenyl azide at 70 °C for a total of 27 days to yield 75% of a compound assigned the 3a, 5,6,6a-tetrahydro-37/,47/-pyrrolo[2,3-d]-1,2,3-triazole structure (146), although the regiochemistry of cycloaddition was not determined unambiguously <82JCS(P1)2105>. 

Several types of molecular orbital calculation have been carried out on IH- and 2H- 1,2,3-triazole structures, often in combination with predictions of the most reactive sites, and studies of dipole moments, H, and NMR chemical shifts, proton exchange... 

Natural products derived from 1,2,3-triazole are not known. The 1,2,3-triazole structure is contained in a number of pharmaceuticals (see p 473). It is used, for example, to modify the pharmacokinetic properties of the clinically employed y -lactam antibiotic cefatrizin 14 ... 

B. Synthesis by Annulation of the Pyrimidine Ring ONTO A 1,2,4-Triazole Structure... 

The reaction is most effective with azides bearing electron-withdrawing groups, such as nitrophenyl, toluene-p-sulfonyl, and ethoxy carbonyl. Sulfonyl azide adducts give iV-unsubstituted triazoles, the substituent being lost on aromatization. The triazole which is isolated as a minor product of the reaction of 1,1-dimethoxyethylene with ethoxycarbonyl azide has been assigned a 2/7-triazole structure it is likely that other ethoxycarbonyltriazoles formed by this route also have 2H-structures. 

Only those compounds which do not have tautomeric aromatic triazole structures will be considered here, the others having been treated as triazoles. The triazolines are unstable and have been subjected to little study. Compounds which are disubstituted at the C(3) or C(5) atom are more stable than the mono- or unsubstituted analogues. The equilibrium has been observed by NMR spectroscopy between the six-membered tetrazine (75) and the triazolinethione (76) via the open-chain form, thus mirroring monosaccharide equilibria (Scheme 12) <90TL3927>. 

Again, as with the triazolines, only those compounds which do not have tautomeric aromatic triazole structures would be treated here and these systems are unstable and have been even less studied than their dihydrocounterparts. 4-Phenyltriazolidininedione is a precursor of PTAD (see Section 4.02.6.3). 

Although 4-phenyltriazolinedione (PTAD) has a tautomeric aromatic triazole structure it has been treated separately here because of its distinct and extensive chemistry. 

Two strategies have been used to construct the pyrimidine ring onto a triazole structure in order to produce l,2,4-triazolo[l,5-c]pyrimidines ... 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

The triorganotin species have been used as industrial biocides for over 30 years [117, 118]. Examples are triphenyltin hydroxide (structure 5) for fungal diseases on celery, rice, sugar beets, and coffee tricyclohexylstannyl-1,2,4-triazole (structure 6) as an acaricide for apple, pear, and citrus fruit trees bistributyltin oxide (structure 7) as a wood preservative and tributyltin-methylacrylate monomers (structure 8) polymerized with other acrylates to yield a marine antifoulant polymer that prevents the build of up barnacles, algae, and other marine animals on ships. 

Itraconazole. Itraconazole (18) is a highly lipophilic compound with a triazole structure. Compared to ketoconazole, itraconazole has a broader spectrum (including Aspergillus spp.) (29,30) and an in vitro activity that is 10 times higher than ketoconazole for most species. 

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