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An efficient approach to the gram-scale synthesis of 3(5)-substituted, 1,3- and 1,5-disubstituted 1,2,4-triazole-derived building blocks is described. The key synthetic precursors - 1,2,4-triazole-3(5)-carboxylates (20 examples, 35-89% yield) were prepared from readily available acyl hydrazides and ethyl 2-ethoxy-2-iminoacetate hydrochloride. Further transformations were performed following the convergent synthetic strategy and allowed the preparation of 1,3- and 1,5-disubstituted 1,2,4-triazole-derived esters (16 examples, 25-75% yield), 3(5)-substituted, 1,3- and 1,5-disubstituted carboxylate salts (18 examples, 78-93% yield), amides (5 examples, 82-93% yield), nitriles (5 examples, 30-85% yield), hydrazides (6 examples, 84-89% yield), and hydroxamic acids (3 examples, 73-78% yield). Considering wide applications of the 1,2,4-triazole motif in medicinal chemistry, these compounds are valuable building blocks for lead-oriented synthesis; they have also great potential for coordination chemistry.The online version contains supplementary material available at 10.1007/s10593-022-03064-z.

A series of 2-(1H-1,2,4-triazol-3-yl)acetates, as well as 4-mono- and 4,4-disubstituted 5-amino-2,4-dihydro-3H-pyrazol-3-ones (including spirocyclic derivatives) have been synthesized using the Pinner reaction strategy. α-Mono- and α,α-disubstituted ethyl cyanoacetates were converted into the corresponding carboxyimidate salts that served as the key intermediates. Their further reaction with formylhydrazide or hydrazine hydrate provided triazolylacetates or aminopyrazolones (including spirocyclic derivatives), depending on the structure of the starting Pinner salt and the nature of the nucleophile. The scope and limitations of the developed synthetic method have been established.

In the title compound [Fe

The structure of complex cis-Pd(HLMe)Cl2 was studied both in solution and in solid state using multinuclear (1H, 13C, 15N) NMR spectroscopy and X-ray structural analysis. Complex was evaluated for cytotoxic activity. Thus, the results showed that cis-Pd(HLMe)Cl2 has a pronounced cytotoxicity toward human leukemic lymphoblast’s CCRF-CEM and cervix adenocarcinoma HeLa cells. Moreover, it was found that cis-Pd(HLMe)Cl2 is more toxic than cisplatin: its IC50 value at 24 h incubation was lower by more than an order for CCRF-CEM cells and by three orders for HeLa cells as compared with cisplatin IC50. Depending on the concentration, cis-Pd(HLMe)Cl2 is accelerated or slowed hemolysis of erythrocytes. Observed differential biological effects of cis-Pd(HLMe)Cl2 suggest the dependence of the agent’s interactions with cells on the molecular structure of palladium ligand and the cell type.

Two new copper(II) complexes [Cu2(L)2(OAc)2(H2O)2] (1) (L = 3-methyl-5-pyridin-2-yl-1,2,4-triazole) and [CuL2] (2) were prerared and thoroughly studied. The complexes are able to selectively catalyze the oxidation of styrene towards benzaldehyde and of cyclohexane to KA oil. The 2D coordination polymer 1 showed an antiferromagnetic behaviour attributed to the intrachain magnetic coupling.

A procedure has been developed for the synthesis of a zinc complex with chelating li-gand 3-(2-pyridyl)-5-(3,4,5-trimethoxyphenyl)-1,2,4-triazole. Within the framework of the density functional method, with the B3LYP functional in the SBKJC basis, the equilibrium geometry of the ground electronic state of the ligand molecule and zinc complex was determined. The physicochemical properties of the ligand were also characterized: logP = 4.1±0.1, рКf1 = 3.31±0.05, рКf2 = 10.2±0.1, ε275 ≈ 1·105 l·mol–1·cm–1. It was shown that complexation is accompanied by an increase in fluorescence intensity, for the complex λemmax ≈ 458 nm. The absorption spectrum of the complex is characterized by two bands with maxima at 278 nm (ε278 ≈ 1.3·104 l·mol–1·cm–1) and 322 nm (ε322 ≈ 1.2·104 l·mol–1·cm–1).

Two new uranyl complexes with the molecular formula [(UO 2 )(H 2 L 1 )](СH 3 OH) and [(UO 2 )(H 3 L 2 )](СH 3 OH) { H 4 L 1 = 2-[5-[[5-[[5-(2-pyridyl)-1H-1,2,4-triazol-3‑yl]methyl]-1H-1,2,4-triazol-3-yl]methyl]-1H-1,2,4-triazol-3-yl]phenol and H 5 L 2 = 2-[5-[[5-[[5-[[5-(2-pyridyl)-1H-1,2,4‑triazol-3-yl]methyl]-1H-1,2,4-triazol-3-yl]methyl]-1H-1,2,4-triazol-3-yl]methyl]-1H-1,2,4-triazol-3-yl]phenol)} have been synthesized. All compounds have been characterized by NMR and IR spectroscopy. With H 4 L 1 and H 5 L 2 uranyl ion forms mononuclear complexes. In [(UO 2 )(H 3 L 2 )](СH 3 OH) pyridyl nitrogen was uncoordinated and bonding of H 5 L 2 was realized only through phenol oxygen and N 4 -nitrogens of triazole cycles.

Methods of the synthesis of 2-(5-(1,2,4)triazol-1-ylmethyl-1H-(1,2,4)-triazol-3-yl)-pyridine and a binuclear copper complex are described. The structure of the complex is established by X-ray structural analysis. The complex is a centrosymmetric [Cu2(L)2(NO3)2·2H2O]·H2O dimer. The Cu-Cu distance is 4.0408 (3) Å. In the complex the ligand is in a deprotonated state. Due to this, the triazole fragment acts as a bridge between the two metal centers. Copper ions are in an octahedral environment. The equatorial plane is formed by three triazole nitrogen atoms and one pyridyl nitrogen atom. The axial positions are occupied by a water molecule and a nitrate ion. Isotropic patterns corresponding to binuclear copper particles of the [Cu2L2-H]+ composition were registered in the ESI mass spectra of the solution of the [Cu2(L)2(NO3)2(H2O)2]·H2O complex. These data confirm the presence of a binuclear complex in solution. The catecholoxidase activity of the binuclear copper (II) complex based on 2-(5-(1,2,4)triazol-1-ylmethyl-1H-(1,2,4)-triazol-3-yl)-pyridine was studied. The kinetics of model reactions of the catecholase type were investigated by the method of initial velocities using a model substrate of 3,5-di-tert-butyl catechol (3,5-DTBK). At low concentrations of 3,5-DTBK, the dependence of the initial oxidation rate on the concentration of the substrate is linear, which corresponds to the first order of the reaction on the substrate. However, the dependence graph at higher concentrations of 3,5-DTBK is nonlinear and indicates the saturation of the catalyst with the substrate. The form of the dependence of the initial reaction rate on the substrate concentration is explained within the framework of the Michaelis-Menten model, which well describes the behavior of natural metaloenzymes.

A combined FTIR matrix isolation and theoretical B3LYP/6-311++G(2d,2p) study of 2-(tetrazol-5-yl)benzoic acid isolated in solid nitrogen was performed. Out of fifteen stable isomers of this molecule located on the singlet potential energy surface the most stable one, comprising the intramolecular N H⋯O hydrogen bond, was detected experimentally in nitrogen matrices after deposition. Upon irradiation with λ = 305 nm a new conformer of the precursor was generated and upon λ = 280 nm radiation a reverse photorotamerization reaction was induced. Simultaneously with the photoisomerizations, a cleavage of the tetrazole ring with dinitrogen elimination was observed proceeding with a very small rate and leading to formation of a carbodiimide derivative.

A series of palladium(II) complexes with 3-(2-pyridyl)-5R-1,2,4-triazoles Pd(LR)2 (R = ethyl (4a), n-propyl (4b), i-propyl (4c) and t-butyl (4d)) have been synthesised and characterised by NMR, IR, UV-vis spectroscopy, ESI and MALDI-TOF mass spectrometry. Single-crystal X-ray diffraction study of 4a–d revealed a square-planar coordination geometry, in which the N^N chelating monoanionic ligands adopt a trans-configuration around Pd(II) and show notable intraligand C–H⋯N hydrogen bonding within the complex. The solid state emission and excitation spectra of 4a–d showed vibronic structure of the spectra at room temperature. The TG/DTA curves of 4a–c revealed that the complexes are stable up to ca. 250 °C, whereas 4d starts to decompose at 230 °C. Compounds 4a–d efficiently catalyse the nitroaldol (Henry) reaction of benzaldehyde with nitroethane in water, methanol and ethanol with appreciable diastereoselectivity in favour of the syn-isomer (syn : anti up to 81 : 19). In addition, 4a–d catalyse the microwave-assisted Suzuki–Miyaura cross-coupling reaction of bromoanisole with phenyl boronic acid, in the presence of a base. Moreover, these heterogeneous catalysts can be recovered and reused without losing activity for several consecutive cycles.

The development of new fluorescent reagents for determination of trace amounts of zinc in biological samples is an actual issue. Efficient reagents should characterized by high hydrophobicity, low sensitivity to media acidity and intense fluorescence in the long-wavelength region of the spectrum. Therefore, the using of a rigid π-conjugated molecule of 3-(2-pyridyl)-5-(2-hydroxyphenyl)-1,2,4-triazole as a fluorescent probe for the determination of zinc micro-quantities in biological samples is considered as a rational choice. 3-(2-pyridyl)-5-(2-hydroxyphenyl)-1,2,4-triazole is a highly hydrophobic ligand (logP=3.0±0.1). Dissociation of the protonated nitrogen atom in the pyridine cycle of the ligand occurs at pH = 4, рКа1= 3.98±0.05. The pKa2 value is equal to 8.74 ± 0.03 and corresponds to the dissociation of the N-H group of the triazole fragment. The absorption spectrum of the ligand solution in DMSO is characterized by two bands with maximum at 272 nm and 320 nm due to intraligand π-π * transitions. The values of the molar absorption coefficient for these bands are 1.18·104 l·mol-1·cm-1 and 1.36·104 l·mol-1·cm-1, respectively. Two bands at 402 nm and 535 nm are also observed on the fluorescence spectra of the ligand. The high fluorescence intensity in the long-wavelength region of the spectrum indicates the promising use of this ligand as an analytical reagent at a creation of new fluoresce techniques. 3-(2-pyridyl)-5-(2-hydroxyphenyl)-1,2,4-triazole as chelating ligand can form two complex compounds in DMSO solution with composition ML and ML2. Complex formation is accompanied by the appearance of a third absorption band in the visible regions of the spectrum at 440 nm (ε440≈ 6,5·103 l·mol-1·cm-1) due to LMCT transitions. In addition, the complex formation leads to fluorescence quenching. Developed fluorescent techniques for determination of zinc quantities in a sample of hair and in a tablet of vitamins "Duovit" are characterized by satisfactory precision and accuracy. The range of zinc concentrations determining in the hair sample is 71–286 μg/g, Sr=0.033 (n=3, P=0.95). The zinc content that was found in the "Duovit" tablet is well correlated with the declared content. This indicates the good selectivity of ligand in relation to the accompanying microelements.

A series of 2-(1H-1,2,4-triazol-3-yl)acetates, as well as 4-mono- and 4,4-disubstituted 5-amino-2,4-dihydro-3H-pyrazol-3-ones (including spirocyclic derivatives) have been synthesized using the Pinner reaction strategy. α-Mono- and α,α-disubstituted ethyl cyanoacetates were converted into the corresponding carboxyimidate salts that served as the key intermediates. Their further reaction with formylhydrazide or hydrazine hydrate provided triazolylacetates or aminopyrazolones (including spirocyclic derivatives), depending on the structure of the starting Pinner salt and the nature of the nucleophile. The scope and limitations of the developed synthetic method have been established.

Zinc and cadmium complexes, ML2(NO3)2 (L = N-methyl-C-(2-pyridyl)nitrone) were synthesized and characterized by means of X-ray diffraction crystallography and IR and NMR spectroscopy. The organic ligands in the complexes are coordinated via the oxygen atom of the nitrone group and the nitrogen atom of the pyridine moiety. The coordination environment of the central atoms is a distorted octahedron. The bond lengths and angles of the complexes were calculated using the DFT method with B3LYP functional. Theoretical studies revealed that the geometric parameters are in agreement with the experimental data. The fluorescent properties for the zinc and cadmium complexes were investigated at room temperature.

The structure of four new palladium complexes [Pd(HL 2 )Cl 2 and Pd(L 1–3 ) 2 ] with 3-(2-pyridyl)-5-R-1,2,4-triazoles (R=H, CH3, Ph respectively HL 1 , HL 2 , HL 3 ) was proposed based on IR, NMR, UV spectroscopy and MALDI mass spectrometry data analysis. It is found that the complexation of HL 2 and HL 3 with Pd2+ ions results in a decrease of their fluorescence intensity and it is vice versa in case of HL 1 . Furthermore, the influence of the substituent (R) in the 3-(2-pirydyl)-5-R-1,2,4-triazoles on the fluorescent and protolytic properties of HL 1–3 was investigated.

Phototransformations of 2-(1,2,4-triazol-3-yl)benzoic acid induced by tunable UV laser were studied in low temperature matrices by FTIR spectroscopy. Out of 36 possible isomers of this molecule the most stable one, comprising the intramolecular N-H···O hydrogen bond, was detected experimentally in argon and xenon matrices after deposition. Upon irradiation with λ = 325 nm, two new conformers of the precursor were formed. The corresponding reverse photorotamerizations were also detected at 250 nm partly reproducing the initial molecules. In addition to the conformational changes, an interesting photoisomerization took place in the studied matrices leading to a proton transfer from N atom of the triazole ring to the carbonyl oxygen of the carboxylic group. As a result of this reaction, a new product with two OH groups was identified for the first time. The experimental studies were supported by DFT calculations in both ground and excited electronic states.

Structure of three new uranyl complexes with 3-(2-hydroxyphenyl)-5-(2-pyridyl)-1,2,4-triazoles was proposed basing on IR, UV spectroscopy, NMR and MALDI mass spectrometry data analysis. It was shown prospective using of triazoles as analytical reagents for fluorescence determination of uranyl ion.

Easily accessible carboxylic acid hydrazides undergo cyclocondensation with ethyl carbethoxyformimidate, giving 5-substituted ethyl 1,2,4-triazole-3-carboxylates. These are important building blocks in organic synthesis. The approach we used to obtain title compounds made possible synthesis of 3-(2-aminophenyl)-1,2,4-triazole.

The synthesis, spectral characterization and luminescent properties of palladium(II) complexes with 3-(2-pyridyl)-1H-1,2,4-triazole-5-acetic acid ethyl ester (HL) have been described. The compounds Pd(L)2 and Pd4(L)4Cl4·2DMF were prepared by refluxing Pd(HL)Cl2 in DMF. The pathways of their formation were investigated using 1H NMR spectroscopy. The molecular and crystal structures of Pd4(L)4Cl4·2DMF were determined by means of single crystal X-ray diffraction analysis. The triazoles in Pd4(L)4Cl4·2DMF were found to act as bidentate ligands bridging two palladium centers in two different ways, so the molecular structure consists of tetranuclear units of palladium ions. The luminescence properties of the ligand and its complexes were discussed.

Facile methods of the preparation of heterocyclic analogues of Salen and Vanen are reported. The azamethine fragments of Schiff bases were replaced by 1,2,4-triazoles. The method of synthesis described may afford to prepare the series of ligand systems with different substituents with high overall yields relatively to the hydrazide. Unlike Schiff's bases, all synthesized compounds are chemically stable and resistant to oxidizing and reducing agents. The molecules are entirely conjugate to the π-systems, which is likely to be reflected in the electronic properties of coordination compounds. Obtained ligand systems could maintain great interest in the synthesis of various transition metal coordination compounds. These could be concluded from the fact that coordination behavior of synthesized ligands is expected to be similar to that is observed for Salen an Vanen type ligands respectively. The resulting compounds have the same donor centers from Salen and Vanen, having a similar planar structure and coordination behavior. All ligands are tetradentate, may leave vacant positions in the coordination sphere of transition metals and form five- and six-membered cycles. The Vanen analogues are capable of forming binuclear complex compounds, since they have internal N2O2 (for coordination with 3d metal ions) and external O2O2 (for exo-coordination of ions of lantanides) donor centers. The compounds obtained are capable of forming coordination compounds with antibacterial, antifungal, anticancer, antioxidant, anti-inflammatory, antimalarial, antiviral activities and also as homogeneous and heterogeneous catalysts in polymerization, epoxidation, hydrosilylation reactions, sensors etc. The analogues were analyzed by NMR and IR spectroscopy.

Alkylation of 3-(2-pyridyl)-1,2,4-triazole-5-acetic acid with iodomethane leads to formation of 3-(2-pyridyl)-N1-methyl-1,2,4-triazole-5-acetic acid ethyl ester (L1) and 3-(2-pyridyl)-N2-1,2,4-triazole-5-acetic acid ethyl ester (L2). It was also managed to identify the compound ethyl ester 3-(2-pyridyl)-N2-methyl-1,2,4-triazol-5-yl-α-propionic acid (L3) which is the product of alkylation of L2 in the methylene group. L1-3 were used for synthesis of palladium(II) complexes PdL1Cl2, PdL2Cl2 and PdL3Cl2. The composition and structure of obtained compounds were proposed on the basis of IR and 1H NMR spectroscopy data and elemental analysis. IR spectra of synthesized ligands have a lot in common, due to their structure similarity. As a result of coordination all signals in the IR spectra are shifted besides bands of ester groups. 1H NMR spectra of obtained ligands is bit similar, this is due to their structure. Signals of pyridine ring protons 3-(2-pyridyl)-N1-methyl-1,2,4-trazole-5-acetic acid ethyl ester shifted to 0.11–0.13 ppm in a weak field in compare with izomers. N1–CH3 signals are shifted to lower field than N2–CH3, it can be explained by the influence of negative magnetic anisotropy of pyridine ring. Methyl and methylene signals of ester group are located nearly in the same field in L1–3. Coordination of all ligands occurs through the nitrogen atom of pyridine ring and N4-triazole. In this case all L1, L2 and L3 signals of pyridine protons suffer shift to a low field. Methyl and methylene signals of ester group almost no shifted what indicate that no coordination through oxygen atom.

The synthesis, crystal structure, spectroscopic and magnetic properties of binuclear [Cu2(L)2(SO4)(H2O)3]·3H2O (4a) and tetranuclear [Cu4(HL)2(L)4(DMF)2(SO4)2]·DMF (4b) copper(II) complexes were reported (where HL is 3-(pyridine-2-yl)-1,2,4-triazole). Potentiometric titrations, ESI-MS and spectrophotometric studies of complex formation in MeOH/H2O solutions indicated the presence of monomeric [CuHL]2+, dinuclear [Cu2L2]2+ and [Cu2L2(OH)]+, and trinuclear [Cu2L3]+ and [Cu2L3(OH)] species. The small N,N-nucleating ligand HL leads to a supramolecular formation of the complexes. The ligand comprises a triazole moiety substituted by pyridine group, strategically located to form chelate metalocycles. The basis of both complexes is two metal centres bridged via N1–N2 diazine grouping of a triazole ring. For complex 4b two HL coordinate in acidoform via NPy and N4 of azole moiety as well. There are significant differences in the polyhedrons, namely nuclearity and Cu…Cu separations. Complexes were characterized by elemental analysis, mass-spectrometry, IR- spectroscopy and X-ray analysis. Magnetic measurements revealed that both compounds exhibit antiferromagnetic interaction. The magnetic susceptibility data were interpreted on the basis of the spin Hamiltonian in the temperature range (2–300 K) using the dinuclear (4a: J1 = −52.41 cm−1) and tetranuclear (4b: J1 = −53.10 cm−1 to J2 = −0.14 cm−1) models.

The article is devoted to investigation of coordination compounds of palladium (II) with 3-(2-pyridyl)-1,2,4-triazole derivatives containing amino groups. We syntesized 4 ligands and 4 new coordination compounds. An interesting after removing of BOC-protection, NH2-group is still uncoordinated. In 1H NMR spectra of complexes was a significant shift of the ortho-pyridine proton in a low-field area, which prove proposed structure. This may be due to its closeness to the lone electron pair of the nitrogen cycle of the second triazole ligand.

The UVI atom exhibits a penta­gonal–bipyramidal N2O5 coordination environment. In the complex, the 1,2,4-triazole ligand is coordinated in a tridentate manner., In the title compound, [U(C13H9N4O)(NO3)O2(H2O)]·CH3CN·H2O, the UVI atom is seven-coordinated in a distorted penta­gonal–bipyramidal N2O5 manner by one tridentate triazole ligand, one monodentate nitrate anion and one water mol­ecule in the equatorial plane and by two uran­yl(VI) O atoms in the axial positions. In the crystal, the UVI complex mol­ecule is linked to the water and aceto­nitrile solvent mol­ecules through N—H⋯N, O—H⋯O and O—H⋯N hydrogen bonds, forming a sheet structure parallel to the bc plane. The sheets are further linked by an additional O—H⋯O hydrogen bond, forming a three-dimensional network.

The regioselective cyclocondensation of aminoethyl-1,2,4-triazoles and glyoxal provides pentacyclic heterocycles in which two 7,8-dihydro-5H-6λ2-[1,2,4]triazolo[1,5-c]pyrimidine systems are connected through CH(OH) bridges generating a central piperazine-2,5-diol ring. The structure of the new compounds was elucidated based on 1H, 13C and 15N NMR spectroscopic methods. The molecular structure of the parent compound generated from aminoethyl-1,2,4-triazole was established by single crystal X-ray diffraction.

The cyclocondensation of aminomethyl-1,2,4-triazoles and glyoxal gives hexahydropyrazino[2,3- e ]pyrazines in good yields. 1 H and 13 C NMR spectra of the title compounds are described and the molecular structure of 4a,5,6,10a,11,12-hexahydro-(4a R ,10a R )-[1,2,4]triazolo[1,5- a ][1,2,4]triazolo[1′,5′:1,6]pyrazino[2,3- e ]pyrazine was established by single crystal X-ray analysis.

Methods of the synthesis of the copper(II) containing 3-(2-pyridinyl)-1H-1,2,4-triazole complexes are reported. Systematic studies were devoted to the investigating an importance of triethylamine towards the сomplexation. The various coordination modes that have been observed in complexes were discussed. We noticed the correlations of coordination complexes structure and the metal-ligand correlation. Two mononuclear complexes and one dinuclear complex of a 2:2 composition were obtained. The deprotonation of the ligand in the complex namely [Cu(L)2](H2O)2 was eased by adding triethylamine. The octahedral complex [Cu(HL)2(NO3)](NO3) was synthesized without triethylamine. In excess of ligands, mononuclear coordination compounds formed mostly. By adding the equal to ligand amount of triethylamine we obtained complex in a lower tetragonal symmetry. Deprotonated triazole is the high field ligand, therefore, due to the Jahn–Teller effect, square coordination is more desirable. In all coordination compounds formation of the 5-membered chelate cycle realizes through a pyridine-triazole binding site.The structures of three complexes have been determined by single crystal X-ray diffraction.

The structure of the title compound, [U(C14H9N3O2)O2(CH3OH)2]·CH3OH, is the first to be reported for an actinide complex including triazole ligands. The UVIatom exhibits a pentagonal–bipyramidal NO6coordination environment, involving two axial oxide ligands [U=O = 1.766 (3) and 1.789 (3) Å], four equatorial O atoms [U—O = 2.269 (3)–2.448 (3) Å] from the ligand and the two coordinated methanol molecules, and one equatorial N atom [U—N = 2.513 (4) Å] from the ligand. In the crystal structure, the complex molecules are linkedviaintermolecular N—H...O and O—H...O hydrogen bonds to form a two-dimensional structure.