Isomeric Triazoles Research Articles

Synthesis of TRIPCO: A New Cyclooctyne for iSPAAC

Strain-promoted azide–alkyne cycloadditions (SPAAC) are widely used for labeling azide-functionalized biomolecules in living cells but create mixtures of isomeric triazoles. We recently expanded the scope of SPAAC to the isomer-free generation of large functional molecules in living cells by designing the symmetrical pyrrolocyclooctynes PYRROC and SYPCO, which do not form isomers in SPAAC. Here, we present the synthesis and kinetic characterization of the cyclooctyne TRIPCO as a new reagent for isomer-free SPAAC (iSPAAC). TRIPCO was found to react faster than PYRROC and SYPCO in the [3+2] cycloaddition with benzyl azide.

SYNTHESIS AND PROPERTIES OF 5-HYDROXY-1-TOLYL(BENZYL)-1,2,3-TRIAZOLES

1-Benzyl- N -tolyl-1,2,3-triazole-4-carboxamide was accessed via rearrangement of N -benzyl-1-tolyl-1,2,3-triazole-4-carboxamide. It is shown that by boiling in various solvents an equilibrium between isomeric triazoles and diazomalondiamides is established, and that the equilibrium is shifted toward 1-benzyl-1,2,3-triazole. The two isomeric triazoles are shown to undergo alkylation reactions. For 5-hydroxy-1-tolyl-1,2,3-triazole, the alkylation occurs at position 3 of the heterocycle to form a mesoionic triazol-5-olate, whereas for 1benzyl-5-hydroxy-1,2,3-triazole, alkylation leads to the formation of a 5-alkoxy derivative. Authors: Yulia I. Nein, Tatiana V. Glukhareva, Ksenia A. Sadovskova, Yuri Yu. Morzherin*

Synthesis and properties of 5-hydroxy-1-tolyl(benzyl)-1,2,3-triazoles

1-Benzyl-N-tolyl-1,2,3-triazole-4-carboxamide was accessed via rearrangement of N-benzyl-1-tolyl-1,2,3-triazole-4-carboxamide. It is shown that by boiling in various solvents an equilibrium between isomeric triazoles and diazomalondiamides is established, and that the equilibrium is shifted toward 1-benzyl-1,2,3-triazole. The two isomeric triazoles are shown to undergo alkylation reactions. For 5-hydroxy-1-tolyl-1,2,3-triazole, the alkylation occurs at position 3 of the heterocycle to form a mesoionic triazol-5-olate, whereas for 1-benzyl-5-hydroxy-1,2,3-triazole, alkylation leads to the formation of a 5-alkoxy derivative.

New Facile Route to Synthesize Furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives

A new facile route for synthesis of 3-(aryl)-8,9-diphenylfuro[3,2-e][1,2,4]triazolo pyrimidines derivative from the same starting material, 2-amino-4,5-diphenylfuran-3-carbonitrile, has been developed through heterocyclization of the corresponding arylidene-hydrazono-5,6-diphenylfuro[2,3-d]pyrimidine and N-(arylmethylene)-4-imino-5,6-diphenylfuro[2,3-d]pyrimidin-3(4H)-amine under refluxing condition with acetic anhydride followed by air oxidation. The products were obtained in good yield with an easy workup along with the purification of products by a nonchromatographic method. This general synthetic procedure can be extended to the preparation of a wide range of isomeric triazoles using 2-amino 3-carbonitrile bifunctional derivatives.

ChemInform Abstract: New Heterocyclic Systems Based on 5,6,7,8‐Tetrahydroisoquinolines

Abstractsynthesis and characterization

New heterocyclic systems based on 5,6,7,8-tetrahydroisoquinolines

A method has been developed for the synthesis of new 8-amino-substituted 5-propyl(isobutyl)-1,2,3,4-tetra-hydropyrimido[4',5':4,5]furo[2,3-c]isoquinolines from 3-oxo derivatives of 5,6,7,8-tetra-hydroisoquinolines. Isomeric triazoles, condensed at the edge [c] of the pyrimidine ring, have been obtained from the 8-hydrazino derivatives. A Dimroth rearrangement was carried out in acidic medium.

Cu(II) Coordination Architectures with Two Positionally Isomeric Triazole–Bipyridine Ligands

The Cu(II) coordination polymer, {[Cu( p-bdc)(4,4′-bpt)]}n shows a 2D layer structure bridged by a p-bdc anion and the polymer {[Cu(H2btc)(3,3′-bpt)2(H2O)2]·2H2O}n, whose thermal stability has been briefly investigated, shows a 1D chain structure bridged by an H2btc anion. [ p-H2bdc = 1,4-benzenedicarboxylate acid, H4btc = 1,2,4,5-benzenetetracarboxylic acid, 4,4′-bpt = 1H-3,5-bis(4-pyridyl)-1,2,4-triazole, 3,3′-bpt = 1H-3,5-bis(3-pyridyl)-1,2,4-triazole] Both complexes have been prepared by the reaction of the relevant carboxylate acid and positional isomeric triazole–bipyridine ligand with Cu(II) salts under hydrothermal conditions. Both structures are further extended through intermolecular interaction to form 3D supramolecular frameworks.

Cobalt(II) coordination polymers built on isomeric dipyridyl triazole ligands with pyromellitic acid: Synthesis, characterization and their effects on the thermal decomposition of ammonium perchlorate

Three new cobalt(II) coordination compounds, [Co(3,3′-Hbpt)2(H2pm)(H2O)2]·2H2O (1), [Co(4,4′-Hbpt)(pm)0.5(H2O)]·3H2O (2) and [Co(3,4′-Hbpt)(pm)0.5(H2O)3]·2H2O (3) (3,3′-Hbpt = 3,5-bis(3-pyridyl)-1H-1,2,4-triazole; 4,4′-bpt = 3,5-bis(4-pyridyl)-1H-1,2,4-triazole, 3,4′-Hbpt = 3-(3-pyridyl)-5-(4′-pyridyl)-1H-1,2,4-triazole and H4pm = pyromellitic acid) have been synthesized by hydrothermal reactions. Single-crystal X-ray diffraction reveals that compound 1 has a one-dimensional (1D) chain network, 2 exhibits a four-connected three-dimensional (3D) structure with 1D open channels encapsulated by water molecules, while 3 displays a regular two-dimensional (2D) architecture connected through 1D metal helical chains. In addition, the efficacy of compounds 1–3 as additives to promote the thermal decomposition of ammonium perchlorate (AP) is explored by differential scanning calorimetry (DSC).

Nonchromatographic Isolation of 2-Alkyl-2H-1,2,3-Triazoles in the Synthesis of NK3 Receptor Antagonists

A nonchromatographic isolation of a 2-alkyl-2H-triazole from a 1:1 mixture with the corresponding 1-alkyl-1H isomer was developed in a scalable synthesis of a synthetic intermediate for NK3 receptor antagonists. Based on the fundamental nucleophilicity difference in the isomeric triazoles, this method could be used as a general tactic in the isolation of 2H-triazoles.

Oligosaccharide Analogues of Polysaccharides

The α- and γ-CD analogues 6 and 18, which possess a hexa-2,5-diyne-1,6-dioxy unit, were synthesised by intramolecular coupling of the bis-O-propargylated maltohexaoside 4, or the analogous maltooctaoside 16, followed by deprotection. The dialkynylated linear oligosaccharides were obtained by glycosidation of propargyl alcohol with the thioglycosides 1 and 13, reductive cleavage of the benzylidene acetal, and propargylation of the terminal HO−C(4) group, respectively. The β-CD analogues 23 and 25, which possess a penta-1,3-diyn-1-yl-5-oxy unit, were similarly obtained by intramolecular oxidative coupling of 20 and 21, respectively. The linear dialkynylated oligosaccharides 20 and 21 were obtained by two consecutive glycosylations, first with the maltohexaosyl-S-glycoside 1 as donor, and then by glycosylation of the resulting propargyl maltohexoside with the C(4)-ethynylated donor 19. The proximity of the terminal units of maltooligosaccharides allowed a facile intramolecular cycloaddition of the azido alkyne 29 to the isomeric triazoles 30 and 31, which were deprotected to 32 and 33, respectively. Analysis of the intramolecular H-bonds in 6, 23, 25, 32, and 33 showed that insertion of a noncarbohydrate link interrupts a single flip-flop H-bond.

Antitumour polycyclic acridines. Part 3.1 A two-step conversion of 9-azidoacridine to 7H-pyrido[4,3,2-kl ]acridines by Graebe–Ullmann thermolysis of substituted 9-(1,2,3-triazol-1-yl)acridines

9-Azidoacridine 5 reacted with a series of alkynes to form mixtures of regioisomeric 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridines 6, except for the reaction with trimethylsilylacetylene which gave a single regioisomer. Structural assignments have been confirmed by 1H NMR and NOE experiments and the X-ray structure of 9-(4-butyl-1,2,3-triazol-1-yl)acridine 6a corroborates the positioning of the butyl group and shows that the plane of the triazole ring intersects that of the acridine moiety by 65.97(5)° in the crystal structure. Graebe–Ullmann fragmentation of the triazolylacridines was monitored by differential scanning calorimetry and preparative thermolytic conversion to 2- or 3-substituted 7H-pyrido[4,3,2-kl]acridines 8 was performed in hot diphenyl ether. Whereas 9-[4-(3-chloropropyl)-1,2,3-triazol-1-yl]acridine 11 cyclised to 3-(3-chloropropyl)-7H-pyrido[4,3,2-kl]acridine 13, the isomeric triazole 12 afforded the pentacyclic salt 1H,8H-2,3-dihydroindolizino[7,6,5-kl]acridinium chloride 15.

Structure‐Activity Relations for Imidazo‐pyridine‐Type Inhibitors of β‐D‐Glucosidases

AbstractThe triazole 7 and the known gluco‐ and manno‐configurated imidazoles 10 and 11 have been prepared by annulation of the azole ring to the aldonothiolactam 14 in a Hg(OAc)2‐promoted reaction with either hydrazine‐carbaldehyde or aminoacetaldehyde dimethyl acetal. Depending upon the reaction conditions, the synthesis of the imidazoles yielded mostly the gluco‐imidazole 19 or a mixture of the gluco/manno epimers 19/20. In contrast to the triazole 4, the isomeric triazole 7 proved a good inhibitor of retaining β‐glucosidases from sweet almonds and from Caldocellum saccharolyticum. This observation and the qualitative correlation between basicity and inhibitory power of the tetrahydropyridoazoles provide further evidence for the hypothesis of the ‘lateral protonation’ of glycosides by (some) retaining β‐glucosidases.

Cycloaddition des Méthylazide et Phénylazide au β‐Nitrostyrène et au Nitropropène Homologue

AbstractPhenylazide and methylazide reacts with title olefines and gives two isomeric triazoles without nitro group, and 4‐nitro‐1,2,3 triazole. The isomerisation of starting alkenes explains the formation of isomeric triazoles. Oxydation of amino‐nitro‐diazocompounds in equilibrium with 1,2,3 triazolines leads to 4‐nitro‐1,2,3 triazoles.

Mass-spectrometric study of the cyclization of diazo compounds. 10. 2-Diazomalonic acid amides. Mass spectra of the negative ions

The mass spectra of the negative ions of the dissociative resonance capture of electrons of diazo amides and the isomeric triazoles were studied. The molecular negative ions of these compounds are unstable and do not undergo interisomerization. The principal fragmentation process involves the elimination of a molecule of nitrogen and transformation of the resulting [M-N2]− ions to the heterocyclic form, which is the same for the two isomers.

ChemInform Abstract: CONFORMATIONAL STUDIES BY DYNAMIC NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY. PART 27. KINETICS AND MECHANISM OF ANNULAR TAUTOMERISM IN ISOMERIC TRIAZOLES

Chemischer InformationsdienstVolume 15, Issue 37 Article ChemInform Abstract: CONFORMATIONAL STUDIES BY DYNAMIC NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY. PART 27. KINETICS AND MECHANISM OF ANNULAR TAUTOMERISM IN ISOMERIC TRIAZOLES L. LUNAZZI, L. LUNAZZISearch for more papers by this authorF. PARISI, F. PARISISearch for more papers by this authorD. MACCIANTELLI, D. MACCIANTELLISearch for more papers by this author L. LUNAZZI, L. LUNAZZISearch for more papers by this authorF. PARISI, F. PARISISearch for more papers by this authorD. MACCIANTELLI, D. MACCIANTELLISearch for more papers by this author First published: September 11, 1984 https://doi.org/10.1002/chin.198437077Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue37September 11, 1984 RelatedInformation

Conformational studies by dynamic nuclear magnetic resonance spectroscopy. Part 27. Kinetics and mechanism of annular tautomerism in isomeric triazoles

The rates for the prototropic shift of the NH hydrogen in the two isomeric triazoles [(1)= 1,2,4- and (2)= 1,2,3-triazole] have been measured at low temperature by 1H n.m.r. (100 and 300 MHz). Only the less symmetric (cs) of the two possible annular tautomers was found to be populated in the case of (1), whereas both (cs and c2v) were detected in (2). The relative proportions in the latter compound are dramatically dependent on temperature, concentration, and solvent. In either triazoles the kinetic process appears to be intramolecular and the mechanism corresponds to a 1,2 prototropic shift. The parameters of activation yielded similar ΔH‡(5.8 and 6.5 kcal mol–1) and quite negative ΔS‡(–29 and –19 cal mol–1 K–1) values, thus indicating a relatively low probability of attaining the ordered (three-membered) cyclic transition state.

Reactions of α,β-unsaturated acyl isothiocyanates with phenylhydrazine

3-(2-Furyl)propenoyl isothiocyanate or 3-phenylpropenoyl isothiocyanate react with phenylhydrazine to give an isomeric mixture of 1,4- and 2,4-disubstituted thiosemicarbazides which cyclize under alkaline conditions to the corresponding 1,3-disubstituted Δ3-1,2,4-triazoline-5-thiones and 1,5-disubstituted 3-mercapto-1,2,4-triazoles, respectively. The structure of the prepared substances was confirmed by independent syntheses. Methylation of isomeric triazoles as well as methylation followed by cyclization of the corresponding thiosemicarbazides afforded, respectively, 1,5-disubstituted 3-methylthio-1,2,4-triazoles and 1,3-disubstituted 5-methylthio-1,2,4-triazoles. The structure of the synthesized products is discussed on the basis of their IR, 1H-NMR and mass spectra.

Formation of 1,2,4-triazoles by the action of angeli's salt on secondary amines and alkylhydrazones

Two years ago we reported [1] the presence of one of the isomeric triazoles C6H11N3 — apparently 3,5-dimethyl-1-ethyl-1,2,4-triazole — in the products of the reaction of Angeli's salt with diethylamine.

Synthesis of D-ribofuranosyl derivatives of methyl propiolate as C-nucleoside precursors

The synthesis of methyl 4,7-anhydro-5,6,8-tri-O-benzyl-2,3-dideoxy-D-allo-oct-2-ynoate (2) and its D-altro isomer (5) is reported; the ester (5) reacts with benzyl azide to give two isomeric triazoles (10) and (11).

Mechanism of the pyrolysis of 1,2,3-triazoles. 1H-Azirines as intermediates

The isomeric triazoles 4-methyl-5-phenyl-1-phthalimido-1,2,3-triazole (1) and 5-methyl-4-phenyl-1-phthalimido-1,2,3-triazole (2) have been pyrolysed in the vapour phase at 400–500°, and give the same products, which involve the antiaromatic 1H-azirine derivative, 2-methyl-3-phenyl-1-phthalimido-1H-azirine (3), as a common intermediate.