Alkylation of C- and N-aminotriazoles with α-iodoketones

C- and N-Amino-1,2,4-triazoles react with 1-iodopropan-2-one in the absence of bases and phasetransfer catalysts (40°C, 9-12 h) to furnish 3-amino-1,4-bis(2-oxo-propyl)-4H-1,2,4-triazolium triiodide and 4-amino-1-(2-oxopropyl)-4H-1,2,4-triazolium iodide. The alkylation of 1,2,4-triazol-4-amine with 1-iodopropan-2-one and 1,3-diiodopropan-2-one in the presence of elemental iodine led to the formation of 4-amino-1-(2-oxopropyl)-4H-1,2,4-triazolium triiodide and 2-oxopropane-1,3-diylbis(4-amino-4H-1,2,4-triazolium) bis(triiodide). Triiodides are oily fluids possessing electric conductivity of 1.1 × 10^?3 Ω m^?1 opening the route to new types of electroconducting ionic liquids.     

13C NMR spectra of some 1,2-disubstitutedN-vinyl-1H-1,2,4-triazoles

¹³C NMR spectra (20 and 75 MHz, in DMSO-d₆) of a series of 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)- and 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were registered. It was shown that the chemical shifts of both the carbon atom of the alkene group and C(3) reflect regio- and stereoisomerism of these compounds. Taking this into account the isomeric structures of several 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were identified and the configurations relative to the double bond of a number of 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were determined.     

Synthesis and structure of new ditopic ligands containing tetrazole and 3-nitro-1,2,4-triazole fragments

Alkylation of 3-nitro-1,2,4-triazole with haloalkyltetrazoles has afforded in high yields previously unknown 1-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-1H-tetrazole and 2-tert-butyl-5-(3-nitro-1H-1,2,4-triazol-1-ylmethyl)-2H-tetrazole. The molecular and crystal structure of these compounds has been established by X-ray diffraction analysis (XRD).     

Chiral 1,2,4-triazoles: stereoselective acylation and chlorination

Acyl groups are transferred from diverse N- and O-acyl derivatives of chiral 3,5-bis-(1-hydroxyethyl)-[1,2,4]-triazole to amino acid esters enantioselectively, with 7% to 68% ee, depending on the temperature conditions and nature of the reagents. Thionyl chloride replaced the hydroxyl groups of (S)-1-[4-amino-5-((S)-1-hydroxy-ethyl)-[1,2,4]-triazol-3-yl]-ethanol 3 stereospecifically with inversion, as confirmed by X-ray analysis, which also revealed unusual crystal structures with asymmetric units comprising three molecules of 4-amino-3,5-bis(R-1-chloroethyl)-1,2,4-triazole 5 and four of 3,5-bis((R)-1-chloroethyl)-1H-1,2,4-triazole 6.     

Intramolecular cyclization of 4-amino-3-alkylsulfanyl-1,2,4-triazoles as a method for annelation of thiadiazine and thiadiazole rings

4-Amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiols reacted with N-substituted isatins to give 2-oxo-3-[5-(pyridin-4-yl)-3-sulfanyl-4H-1,2,4-triazole-4-ylimino]-2,3-dihydro-1H-indoles which were treated with phenacyl bromides to obtain the corresponding S-phenacyl derivatives. The latter underwent base-catalyzed intramolecular cyclization with formation of 6,7-dihydro-5H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines spiro-fused to 2-oxo-2,3-dihydro-1H-indole fragment at C³. Analogous cyclization of 2,6-di-tert-butyl-4-[5-hetaryl-3-(2-aryl-2-oxoethylsulfanyl)-4H-1,2,4-triazole-4-ylimino]cyclohexa-2,5-dienones involved the imino nitrogen atom to produce the corresponding 6-aroyl-5-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hetaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles.     

First cross-coupling reactions on halogenated 1H-1,2,4-triazole nucleosides

The halogenated 1H-1,2,4-triazole glycosides 6-10 were synthesized by BF₃-activated glycosylation of 3(5)-chloro-1,2,4-triazole (2), 3,5-dichloro-1,2,4-triazole (3), 3,5-dibromo-1,2,4-triazole (4), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole (5) with 1,2,3,4-tetra-O-pivaloyl-β-d-xylopyranose (1). The β-anomeric major products 3-chloro-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (6β), 3,5-dichloro-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (7β), and 3,5-dibromo-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (8β) were used as starting materials for transition metal catalyzed C-C-coupling reactions. Arylations of the triazole ring of 7β, and 8β were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11-17). Moreover, a Cu-catalyzed perfluoroalkylation of 8β is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazole (18). Compound 18 was depivaloylated to the trihydroxy derivative 19. The copper-mediated reaction of 8β with Rupert's reagent gave the bis(3-bromo-1-(2,3,4-tri-O-pivaloyl-β-d-xylopyranosyl)-1,2,4-triazol-5-yl) (20).     

1,2,4-Triazoles—XXXIV: Photodimerization of some 1,2,4-triazo[4,3--]quinoline and 1,2,4-triazolo[3,4-a]isoquinoline derivatives

Irradiation of 1,2,4-triazolo[4,3-a]quinoline and several Me derivatives at 300 nm afforded the cisoid-fused, head-to-tail cyclobutane dimers 7bα,7cα,14bα,14cα - tetrahydro - 1,2,3a,8,9,10a - hexaazadibenzo [c,i]dicyclopenta[a,g]biphenylenes. However, 1,2,4 - triazolo[3,4-a]isoquinolines gave analogous cisoid-fused, head-to-head dimers except for the 5-Me derivative where the head-to-tail dimer was obtained.Codimerization occurred when 1 - methyl - 1,2,4 - triazolo[4,3-a]quinoline and 5 - methyl - 1,2,4 -triazolo[3,4-a]isoquinoline were irradiated at 300 nm, affording a cisoid-fused head-to-tail cyclobutane co-dimer as the single photoproduct. However, irradiation of their 5-Me substituted derivatives at 300 nm afforded the cisoid-fused, head-to-head, cyclobutane codimer and also a minor amount of the dimer derived from 5 - methyl -1,2,4- triazolo[4,3-a] quinoline. Irradiation of equimolar quantities of 2(1H)-quinolinone and 5 - methyl - 1,2,4 -triazolo [4,3-a]quinoline at 300 nm gave the known 2(1H)-quinolinone dimer and a minor amount of a cisoid-fused co-dimer of undetermined configuration.     

Base-induced rearrangement of 4-amidino-3-R-furoxans into 1-substituted 3-(1-nitroalkyl)-5-R-1H-1,2,4-triazoles

A new base-induced rearrangement of furoxans, viz., a recyclization of 4-amidino-3-Rfuroxans into 1-substituted 3-(1-nitroalkyl)-5-R-1H-1,2,4-triazoles in the presence of alkali metal alkoxides and into 3-acyl-5-R-1H-1,2,4-triazoles in aqueous alkaline solutions, was found.     

Reaction of 3-oxo-N-phenylbutanethioamide with 5-amino-1H-1,2,4-triazoles

Reactions of 3-oxo-N-phenylbutanethioamide with 3-substituted 5-amino-1H-1,2,4-triazoles in acetic acid led to the formation of 5-methyl-7,8-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thiones, 7-methyl-5,8-dihydrol[1,2,4]triazolo[1,5-a]pyrimidine-5-thiones and 7-methyl-5-phenylamino[1,2,4]triazolo[1,5-a]pyrimidines. The structure of the products was proved by the ¹H and ¹³C NMR spectra, X-ray diffraction data, and chemical transformations.     

Tautomerism of aza cycles: II. Synthesis and structure of 5-substituted 3-(2-hydroxyethylsulfanyl)-1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazoles and their salts. Preference of the 1H,4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazolium tautomers

New complexing agents, potentially tautomeric 3-(2-hydroxyethylsulfanyl)-1H-1,2,4-triazole, its 5-methyl-and 5-phenyl-substituted analogs, and some their salts, were synthesized, and their structure was discussed on the basis of the ¹H and ¹³C NMR, IR, and mass spectra, X-ray diffraction data, and published data. In keeping with the rule formulated previously for N-unsubstituted 1,2,4-triazoles having dissimilar substituents, the synthesized compounds were found to exist as 3-(2-hydroxyethylsulfanyl)-5-R-1H-1,2,4-triazole tautomers (3-R_A-5-R_D-1H-1,2,4-triazoly). They are protonated at the nitrogen atom in position 4 of the triazole ring. The ¹H and ¹³C NMR spectra of these compounds in trifluoroacetic acid suggest the presence of two forms due to equilibrium between the neutral and protonated species. Analysis of the crystallographic data for the triazolium salts and published data showed preference of the 1H,4H-1,2,4-triazolium tautomer.     

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their analogues

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their lactone analogues, prepared from (1R)-(+)-camphor, were studied. Catalytic hydrogenation selectively led to partial saturation of the [1,2,4]triazolo[4,3-x]azine residue, while in reactions with borane–methylsulfide coordination of borane to the 1-position of [1,2,4]triazolo[4,3-x]azine system took place. On the other hand, activation of the carbonyl group in (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones with boron trifluoride etherate followed by reaction with borane–methylsulfide furnished the corresponding isoborneols, stereoselectively. The structures of all representative compounds were confirmed by X-ray diffraction.     

Regioselective alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole

Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis-decarboxylation of 1,6-dimethyl-7-ethoxycarbonyl-pyrazolo[5,1-c][1,2,4]triazole yields a compound identical with that obtained by the direct methylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole. The 1-N-alkylation is confirmed by NMR spectroscopy and mass spectrometry.     

A novel trinuclear titanium(IV) complex with a C3 axis along Ti1–Ti2–Ti3 containing 3-[(1H-1,2,4-triazol-1-yl)methyl]-BINOLate ligands: synthesis,structure, and reactivity

A new modified BINOL, (S)-3-[(1H-1,2,4-triazol-1-yl)methyl]-1,1′-binaphthol, was prepared. In the presence of titanium tetraisopropoxide, this ligand showed moderate catalytic properties for the asymmetric addition of diethylzinc to aldehydes. By treating rac-3-[(1H-1,2,4-triazol-1-yl)methyl]-1,1′-binaphthol with excess titanium tetraisopropoxide, a novel trinuclear titanium(IV) complex was obtained. A C₃ axis along Ti1–Ti2–Ti3 is present in the molecule.     

Reaction of azolethiones with diacetylene

Reactions of 2,3-dihydro-1H-benzimidazole-2-thione, 2,3-dihydro-1H-1,2,4-triazole-3-thione, 4-amino-5-phenyl-3,4-dihydro-2H-1,2,4-triazole, and 6-aminopurine-2-thiol with diacetylene in DMSO gave the corresponding 1-(azolylsulfanyl)but-1-en-3-ynes having Z configuration of the double bond.     

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with NH-azoles

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with 3,5-dimethylpyrazole, 1,3-dimethyl-3,7-dihydropurine-2,6-dione, 3,5-dibromo-1,2,4-triazole, 2,4,5-tribromoimidazole, and 2-chlorobenzimidazole lead to the formation of 5-azolylmethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles. In the case of 8-bromo-1,3-dimethyl-3,7-dihydropurine-2,6-dione the intermediate thiolate anion undergoes cyclization into 7-[(3,5-dibromo-1,2,4-triazol-1-yl)methyl]-1,3-dimethyl-6,7-dihydrothiazolo[2,3-f]purine-2,4(1H,3H)-dione. The structure of reaction products depends on the relative rate of substitution of leaving groups in the reagents.     

Reaction of Imidazoles and Triazoles with 1-(Benzotriazol-1-yl)-2-iodoethanone

Reactions of 2-methyl-1H-imidazole, 1H-benzimidazole, 4H-1,2,4-triazole, and 1H-benzotriazole with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1-one in the absence of a base gave the corresponding N-mono- and N,N′-disubstituted derivatives. 4H-1,2,4-Triazole-3-thiol reacted with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1- one to afford 1-([1,3]thiazolo[2,3-c][1,2,4]triazol-5-yl)-1H-benzotriazolium triiodide.     

4-functionally substituted 3-hetarylpyrazoles: XX. Synthesis of derivatives of 5-(pyrasol-4-yl)-1,2,4-triazole and 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]oxazine

N-Methylimines of 3-aryl-1-phenylpyrazole-4-carbaldehyde react with ethyl 2-aryl-hydrazino-2-chloroacetate with the formation of ethyl 1-aryl-5-(pyrazole-4-yl)-4,5-dihydro-1H-1,2,4-triazolecarboxylates. Analogous reactions of pyrazol-4-carbaldehyde N-(2-hydroxy)ethylimines results in derivatives of 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]-oxazines.     

The structural and theoretical study of 1H-3,5-di-phenyl-1,2,4-diazaphosphole in the solid state

The N-, P-containing five-membered heterocyclic compound 1H-3,5-di-phenyl-1,2,4-diazaphosphole (1) was prepared in good yield and has been structurally characterized. 1H-3,5-Di-phenyl-1,2,4-diazaphosphole (1), crystallizing in two unexpected cyclic dimers with N-H?N hydrogen bonds, presents in the solid state a dynamic proton disorder implying a dynamic equilibrium within both dimers. The conformations of the phenyl rings, the disorder of the NH protons, and the intermolecular hydrogen bond of several 1,2,4-diazaphospholes (1-5) in the solid state have been rationalized by DFT [B3LYP/6-311++G(d,p)] calculations.     

Synthesis and properties of 1H-1,2,4-benzotriazepines

The synthesis of some N,N-disubstituted benzhydrazidoyl chlorides and their reaction with cyano compounds in the presence of a Lewis acid are described. Whereas N-methyl-N-phenylbenzhydrazidoyl chloride (1a) gave 1H-1,2,4-triazoles, N,N-diphenylbenzhydrazidoyl chloride (1b) afforded 1H-1,2,4-benzotriazepines (3b) and N,N-(2,2′-biphenylen)benzhydrazidoyl chloride (10) yielded the corresponding 1H-1,2,4-benzotriazepine (12) or a hydrolysis product (13). Properties of compounds 3b, specially their near-quantative acid hydrolysis to 1-phenylindazoles, are reported.     

Spectroscopic study of interaction of 1H-1,2,4-triazoline-3-thione with molecular iodine

The formation by 1H-1,2,4-triazoline-3-thiones in dilute chloroform solution of n-σ*-complex with molecular iodine of the composition C₂H₂N₃S·I₂ was studied by electronic spectroscopy in the UV and visible regions (log β = 2.14±0.05). By the XRD method the crystal and molecular structure of the product of chemical interaction of the thione with molecular iodine in ethanol, 1,2-di(1H-1,2,4-triazol-3-yl) disulfide, was determined.