Tri-substituted 1,2,3-triazoles

Compounds of this type are the most common products obtained from thermal 1,3-dipolar cycloaddition of disub-stituted alkynes to azides. Many examples of such reactions can be found in Section 5.01.9. 

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Sol 2. Reaction involves the cycloaddition of the azide to the most electron-deficient double bond (path A), which initially resulted in the formation of the triazoline intermediate (I). Subsequent loss of furan in a fast retro Diels—Alder reaction led to the formation of the stable 1,4,5-tri-substituted-1,2,3-triazole. Azide cycloaddition onto the unsubstituted double bond (path B), via intermediate II, resulted in the monosubstituted 1,2,3-triazole and a 3,4-substituted furan derivative. 

Although both double bonds can react in the [3 + 2] cycloaddition, the retro Diels—Alder reaction of the intermediates occurs rapidly to give 1,4,5-tri-substituted-1,2,3-triazole predominantly. 

The 1,2,3-triazole 1-oxides 326 are usually stable, crystalline, semipo-lar, and colorless compounds. The lower 2-alkyl-substituted 1,2,3-triazole 1-oxides tend to be slightly hygroscopic. They act as very weak bases, protonation requiring acids like triflic acid and O-alkylation requiring tri-methyloxonium salts. No pKa values have been reported. 

The resonance structures of the 3-substituted 1,2,3-triazole 1-oxides 456 are discussed in Section 1.1.1. 3-Substituted 1,2,3-triazole 1-oxides 456 are strictly according to IUPAC nomenclature 1-substituted 1H-1,2,3-triazole 3-oxides since when R=H the hydrogen position takes numbering precedence. The alternative, correct name 1-subshtuted 3-oxo-lH-l,2,3-tri-azoles has not been adopted in the literature. In the present review the most commonly used naming is adopted calling structure 456 a 3-sub-stituted 1,2,3-triazole 1-oxide. This naming is accepted by IUPAC, Chem. Abstr. Autonom. 

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

The vapor-phase pyrolysis of 4-hydroxy-1,2,3-triazole and its iV-methyl derivative affords methan-imine and its A-methyl analog. Analysis of the reaction path by the MNDO method shows the presence of two stable or metastable isomers, (liif)-4-hydroxy-l,2,3-triazole and its ketone protomer <89NJC551>. 4-Diazo-1,2,3-triazoles (122) thermolyze or photolyze in benzene to 4//-l,2,3-tri-azolylidenes (123) which convert benzene to 4-phenyl-1,2,3-triazoles and/or isomerize to a-diazo-nitriles (124). Intermediates (124) react with benzene via a carbene to give addition, ring expansion or substitution products (Scheme 17) <82TL5115>. The similar thermolysis of diazotriazoles in substituted benzene gives complex mixtures in which all of the components are sometimes impossible to isolate and identify <90AHC(48)65>. 

The difficulty in trying to forecast which way round a 1,3-dipolar cycloaddition will go is well illustrated when a substituted azide adds to an aUcyne in the synthesis of 1,2,3-triazoles. Reaction of an alkyl azide with an unsymmetrical alkyne, having an electron-withdrawing group at one end and an alkyl group at the other, gives mostly a single triazole. 

Aminotriazole, and some of its 5-substituted derivatives, when fused with 1,2,3,5-tetra-O-acetyl- or -benzoyl-/ -D-ribofuranose, gave a 1 1-mixture of 2- and 3-ribofuranosyltriazoles (76USP3968103). 4-Acetamidotriazole-5-carboxamide, mercuric cyanide, and tri-0-benzoyl-/ -D-ribofuranosyl chloride, when refluxed in nitromethane, furnished 4-acetamido-l- 2, 3, 5-tri-O-benzoyl-/S-D-ribofuranosyl)triazole-5-carboxamide (3 hr, 48%), from which the benzoyl groups were removed in methanolic ammonia (0°C, 3 days, 54%) (72BCJ2577). Occupation of the 1 position in this and other ribosylations was unexpected but was carefully verified. 

Reactions of 2-formyl-galactal, presented as an unsaturated sugar derivative with push-pull functionalization, with guanidinium and amidinium salts, respectively were carried out imder basic conditions to furnish the substituted 5-( 1,2,4-tri-O-benzyl-D-lyxo- l,2,3,4-tetrahydroxy-butyl)pyrimidines 92 (Fig. 16). Treatment of the 2-formyl pentose glycals with 2-aminobenzimid-azole and 3-amino-1,2,4-triazole, respectively afforded 3-(l,2,4-tri-0-benz-yl-D-lyxo-l,2,3,4-tetrahydroxy-butyl)benzo[4,5]imidazo[l,2-a]pyrimidine 94... 

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