Syntheses and Structural Investigations of Penta-Coordinated Co(II) Complexes with Bis-Pyrazolo-S-Triazine Pincer Ligands,and Evaluation of Their Antimicrobial and Antioxidant Activities

Two penta-coordinated [Co(^MorphBPT)Cl₂]; 1 and [Co(^PipBPT)Cl₂]; 2 complexes with the bis-pyrazolyl-s-triazine pincer ligands ^MorphBPT and ^PipBPT were synthesized and characterized. Both ^MorphBPT and ^PipBPT act as NNN-tridentate pincer chelates coordinating the Co(II) center with one short Co-N(s-triazine) and two longer Co-N(pyrazole) bonds. The coordination number of Co(II) is five in both complexes, and the geometry around Co(II) ion is a distorted square pyramidal in 1, while 2 shows more distortion. In both complexes, the packing is dominated by Cl…H, C-H…π, and Cl…C (anion-π stacking) interactions in addition to O…H interactions, which are found only in 1. The UV-Vis spectral band at 564 nm was assigned to metal–ligand charge transfer transitions based on TD-DFT calculations. Complexes 1 and 2 showed higher antimicrobial activity compared to the respective free ligand ^MorphBPT and ^PipBPT, which were not active. MIC values indicated that 2 had better activity against S. aureus, B. subtilis, and P. vulgaris than 1. DPPH free radical scavenging assay revealed that all the studied compounds showed weak to moderate antioxidant activity where the nature of the substituent at the s-triazine core has a significant impact on the antioxidant activity.     

Novel one-dimensional polymeric Cu(II) complexes via Cu(II)-assisted hydrolysis of the 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine pincer ligand: Synthesis,structure, and antimicrobial activities

Two unexpected one-dimensional coordination polymers, [Cu(PT)(H₂O)Cl]_n 1 and [Cu₂(BPT)(ClO₄)₃(H₂O)₄]_n·2nH₂O 2 , of symmetrical triazine-based ligands were synthesized by Cu(II)-mediated hydrolysis of the 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine ( MBPT ) pincer ligand. The reaction of Cu(ClO₄)₂·6H₂O with MBPT proceeded via hydrolysis of the methoxy group to produce the dicompartmental 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2(1H)-one ligand ( HBPT ) that then undergoes in situ complexation with Cu(II) to afford 2 . In case of CuCl₂, the reaction proceeds further with C–N cleavage of one pyrazolyl unit leading to the formation of 6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4(1H,3H)-dione ligand ( HPT ) that also undergoes in situ complexation with Cu(II) affording 1 . The role of Cu(II) is to increase the Lewis acid reactivity of the water molecule where similar hydrolytic reactions for MBPT were observed in acidic medium in presence of an aqueous HCl (1:1 v/v) solution. The molecular and supramolecular structures of complexes 1 and 2 were investigated using X-ray diffraction of single crystal, Hirshfeld analysis, and density functional theory calculations. The Cl…H (11.7%) and O…H (24.7%) contacts are the most important in 1 , whereas the molecular packing of 2 is controlled mainly by the O…H (58.7%) hydrogen bonds. Complex 2 showed better activity against Escherichia coli, Bacillus subtilis, and Candida albicans compared with the standard antibiotics amoxicillin, tetracycline, and ampicillin. In general, complexes 1 and 2 showed good antimicrobial activity than these antibiotics and have the advantage to be used as both antibacterial and antifungal agents.     

Synthesis,Structure and Biological Evaluations of Zn(II) Pincer Complexes Based on S-Triazine Type Chelator

2,4-bis (3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (BPMT) pincer ligand was used to synthesize the new [Zn(BPMT)(NCS)₂] (1) and [Zn(BPMT)(Br)₂] (2) complexes by a reaction with Zn(NO₃)₂·6H₂O in the presence of either KSCN or KBr, respectively. The structure of complex 1 has been exclusively confirmed using single crystal X-ray diffraction. In this neutral heteroleptic complex, the BPMT is a pincer chelate coordinating the Zn(II) ion via three interactions with the two pyrazole moieties and the s-triazine core. Hence, BPMT is a tridentate NNN-chelate. The coordination environment of Zn(II) is completed by two strong interactions with two terminal SCN⁻ ions via the N-atom. Hence, the Zn(II) is penta-coordinated with a distorted square pyramidal coordination geometry. Hirshfeld analysis indicated the predominance of H…H, H…C and N…H intermolecular interactions. Additionally, the S…H, S…C and S…N contacts are the most significant. The free ligand has no or weak antimicrobial, antioxidant and anticancer activities while the studied Zn(II) complexes showed interesting biological activity. Complex 1 has excellent antibacterial activity against B. subtilis (2.4 μg/mL) and P. vulgaris (4.8 μg/mL) compared to Gentamycin (4.8 μg/mL). Additionally, complex 1 (78.09 ± 4.23 µg/mL) has better antioxidant activity than 2 (365.60 ± 20.89 µg/mL). In addition, complex 1 (43.86 ± 3.12 µg/mL) and 2 (30.23 ± 1.26 µg/mL) have 8 and 12 times the anticancer activity of the free BPMT ligand (372.79 ± 13.64 µg/mL).     

New N-pyrazole, P-phosphinite hybrid ligands and corresponding Rh(I) complexes: X-ray crystal structures of complexes with [Rh, N, P-phosphinite, Cl, (CO)] core

Two new N-pyrazole, P-phosphinite hybrid ligands 3-(3,5-dimethyl-1H-pyrazol-1-yl)propyldiphenylphosphinite (L³) and 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyldiphenylphosphinite (L⁴) are presented. The reactivity of these ligands and two other ligands reported in the literature (3,5-dimethyl-1H-pyrazol-1-yl)methyldiphenylphosphinite (L¹) and 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyldiphenylphosphinite (L²) towards [RhCl(CO)₂]₂ (1) have been studied and complexes [RhCl(CO)L] (L = L² (2), L³ (3) and L⁴ (4)) have been obtained. For L¹ only decomposition products have been achieved. All complexes were fully characterised by analytical and spectroscopic methods and the resolution of the crystalline structure of complexes 2 and 3 by single-crystal X-ray diffraction are also presented. In these complexes, the ligands are coordinated via κ²(N,P) to Rh(I), forming metallocycles of seven (2 and 4) or eight (3) members and finish its coordination with a carbonyl monoxide and a trans-chlorine to phosphorus atom. In both complexes, weak intermolecular interactions are present. NMR studies of complexes 2-4 show the chain N-(CH₂)_x-O becomes rigid and the protons diastereotopic.     

Replacement of dimethylpyrazolyl group in 1,2,4,5-tetrazines by aliphatic alcohols and water

Reactions of 3,6-bis(4-R-3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazines and 3-amino-6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazines with aliphatic alcohols and water in the presence of a base involved replacement of the dimethylpyrazolyl group and resulted in the formation of mono- and dialkoxy-1,2,4,5-tetrazines and 6-substituted 3-hydroxy-1,2,4,5-tetrazines. Dissociation constants of the latter were determined by potentiometric titration.     

Dipotassium Hydrogen Phosphate Powder-Catalyzed Stereoselective Synthesis of N-Vinyl Pyrazoles in Solvent-Free Conditions

Protonation of the highly reactive 1:1 intermediates, which are produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, by 3,5-dimethylpyrazol leads to vinyltriphenylphosphonium salts, which undergo a Michael addition reaction with a conjugate base to produce dialkyl 2-(3,5-dimethyl1H-pyrazol-1-yl)-3-(triphenylphosphoranylidene)butanedioates. Dipotassium hydrogen phosphate powder was found to catalyze the stereoselective conversion of dialkyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-3-(triphenylphosphoranylidene) butanedioates to dialkyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-butenedioates in solvent-free conditions under microwave (0.6 KW, 3 min) and thermal (90°C, 60 min) conditions.     

Complexes of copper(II) and cobalt(II) halides with 4-(3,5-dimethyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-6-methyl-2-phenylpyrimidine: Synthesis,structures, and properties

Copper(II) and cobalt(II) complexes with 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-2-phenylpyrimidine (L) of the general formula MLX₂ (M = Cu(II), X = Cl and Br; M = Co(II), X = Cl, Br, and I) were obtained. According to X-ray diffraction data, CuLBr₂ and CoLX₂ (X = Cl, Br, and I) are mononuclear molecular complexes. The ligand L is coordinated to the metal atom in a chelating bidentate fashion through the N atoms of the pyrimidine and pyrazole rings. The coordination polyhedron of the metal atom is extended to a distorted tetrahedron by two halide ions. In solution, CuLBr₂ undergoes slow transformation into CuL_(1?x)L′ _x Br₂ and the binuclear (X-ray diffraction data) Cu(I) complex [CuL_(1?x)L′ _x Br]₂ (L′ is 4-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-2-phenylpyrimidine). The complexes MLX₂ show weak antiferromagnetic interactions between the M²⁺ ions.     

Synthesis and evaluation of bipyrazolic derivatives as inhibitors of corrosion of C38 steel in molar hydrochloric acid

Methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino) acetate, BT36, and methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)-3-(1H-indol-3-yl)propanoate, BT 43, have been synthesized. Investigation by weight-loss measurement and use of electrochemical techniques revealed the compounds are very effective inhibitors of corrosion of C38 steel in 1 M HCl solutions—percentage protection exceeded 95 % for BT43 at concentrations as low as 10^?2 M. An impedance study in the absence and presence of these compounds revealed the mechanism of protection was cathodic inhibition by polarization and charge-transfer. The Langmuir adsorption isotherm was obeyed. Quantum chemical data calculated by use of DFT at the B3LYP/6-31G* level of theory revealed a good correlation between inhibition efficiency and the molecular structure of BT36 and BT43. The highest occupied molecular orbital, the lowest unoccupied molecular orbital, the separation energy (ΔE), and the dipole moment (μ) from the inhibitor to the metal surface explain the experimental data well.     

Fragmentation of pyrazolecarbaldehyde thio- and dithioacetals under electron impact and chemical ionization

The mass spectra of 1-substituted 3,5-dimethyl-1H-pyrazole-4-carbaldehyde bis(2-hydroxyethyl) dithioacetals and thioacetals were studied for the first time. The main fragmentation pathways of their molecular ions generated under electron impact and chemical ionization were similar. Primary decomposition of the molecular ions of bis(2-hydroxyethyl) dithioacetals involves elimination of 2-sulfanylethanol molecule with formation of the corresponding 1,3-oxathiolane radical cation. Fragmentation of the molecular ions [M]⁺ · and [M + H]⁺ derived from 2-(3,5-dimethyl-1H-pyrazol-4-yl)-1,4,6-oxadithiocanes includes cleavage of the eight-membered heteroring and elimination of C₄H₉OS ·. Substituents in the heteroring of pyrazolecarbaldehydes inhibit decomposition processes related to the aldehyde group.     

Vilsmeier-Haak formylation of 3,5-dimethylpyrazoles

Formylation of N-alkyl-3,5-dimethyl-1H-pyrazoles according to Vilsmeier-Haak led to the formation of the corresponding 4-formyl derivatives. 3,5-Dimethyl-1H-pyrazole having no substituent on the nitrogen atom failed to undergo formylation at the 4 position under analogous conditions. 3,5-Dimethyl-1H-pyrazole-4-carbaldehyde was synthesized by alkaline hydrolysis of methyl β-(4-formyl-3,5-dimethyl-1H-pyrazol-1-yl)propionate and subsequent heating of the acid thus formed.     

Linker extension through hard-soft selective metal coordination for the construction of a non-rigid metal-organic framework

A metal-organic framework (MOF) has been obtained by using a linker extension strategy. Three di-anions of 4-(3,5-dimethyl-1H-pyrazol-4-yl)-benzoic acid coordinate to three Cu(I) ions forming an extended trigonal planar ligand, which links three di-copper paddlewheel units giving rise to a Pt₃O₄ net.     

Synthesis,characterization, and catalytic application of a zinc(II) complex bearing a pyrazole-based ligand

The reaction between ZnCl₂ and N,N-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-1-phenylethylamine (bdmppea) affords [(bdmppea)ZnCl₂], whose structure has been determined by X-ray crystallography. The [(bdmppea)ZnEt₂] complex in situ prepared by the reaction between [bdmppea] and ZnEt₂ exhibited high activity toward the polymerization reaction of rac-lactide at room temperature. However, its activity decreased sharply with decreasing temperature. Stereospecificity of this catalyst characterized by heterotacticity (P_r) was determined by homonuclear decoupled NMR spectroscopy, which value was ∼0.58.     

Complex formation of PdCl<Subscript>2</Subscript> with 1-substituted 3,5-dimethylpyrazoles

Herein the synthesis of 3-(3,5-Dimethyl-1H-pyrazol-1-yl)butanal oxime (L) and its complex formation with PdCl₂ is studied. IR and 1Н NMR spectroscopic methods as well as X-ray diffraction analysis (СIF file CCDC no. 1531058) elucidate that the nitrogen atoms N(4) and N(15) from pyrazole and imine group of oxime respectively, participate in coordination with PdCl₂. Moreover, primarily thermal stability test shows that [PdCl₂(L)] complex (I) is quite stable at moderate temperatures and intense decomposition of latter occurs ca 200–210°C. As a consequence of thermal decomposition, both volatile ligand and its dehydration by-product 3-(3,5-dimethyl-1H-pyrazol-1-yl)butanenitrile are formed. Afterwards, the anticonvulsant properties of PdCl₂, L, and I are of interest and well studied in this section.     

Synthesis of ditopic ligands containing bis(1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-methane fragments

New approaches have been proposed for the synthesis of compounds containing two bis(1H-pyrazol-1-yl)methane fragments. Nucleophilic replacement of the halogen atoms in appropriate tetrabromo derivatives by pyrazoles in the superbasic system KOH-DMSO gave ditopic chelating ligands: 1,1,2,2-tetrakis(1H-pyrazol-1-yl)ethane, 1,4-bis[bis(1H-pyrazol-1-yl)methyl]benzene, and 1,4-bis[bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl]benzene. 1,4-Bis[bis(1H-pyrazol-1-yl)methyl]benzene was also synthesized by reaction of 1H-pyrazole with terephthalaldehyde in the presence of thionyl chloride. 1,1,2,2-Tetrakis(1H-pyrazol-1-yl)ethane was converted into the corresponding tetraiodo and tetranitro derivatives.     

Utilization of DmbNHNH2 in the synthesis of amino-substituted 4-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenols

(2,4-Dimethoxybenzyl)hydrazine (DmbNHNH₂) was utilized in the synthesis of Dmb-protected 4-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenols. This unambiguous protection of the pyrazole endocyclic nitrogen atom enabled the preparation of amino-substituted 4-((3,5-diamino-1H-pyrazol-4yl)diazenyl)phenols that were inaccessible through direct substitution. The Boc group could be selectively cleaved in the presence of the Dmb group.     

Synthesis and luminescent properties of neutral Eu(III) and Gd(III) complexes with 1-(1,5-dimethyl-1h-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione

Neutral [EuL₃Phen] complexes were synthesized by the reaction of EuCl₃ with heterocyclic diketones-1-(1,5-dimethyl-1H-pyrazol-4-yl)-4,4,4-trifluoro-1,3-butanedione and 4,4,5,5,6,6,6-heptafluoro-1-(1-methyl-1H-pyrazol-4-yl)-1,3-hexanedione—and 1,10-phenanthroline (Phen) in an aqueous alcohol solution in the presence of NaOH. The reaction of GdCl₃ with the same diketones under analogous conditions, but without adding 1,10-phenanthroline, yielded [GdL₃(H₂O)₂] complexes. The composition of the complexes was determined by elemental analysis, and their optical and luminescent properties were examined.     

A novel one-pot oxidative cyclization of 2′-amino and 2′-hydroxychalcones employing FeCl3·6H2O-methanol. Synthesis of 4-alkoxy-2-aryl-quinolines and flavones

A simple, inexpensive, and efficient oxidative cyclization of 2′-amino and 2′-hydroxychalcones has been carried out by employing FeCl₃·6H₂O-methanol under mild conditions. This method has been investigated for the synthesis of 2-(1,3-diphenyl-1H-pyrazol-4-yl)-4-methoxyquinolines.     

Efficient and Reusable Iron Catalyst to Convert CO2 into Valuable Cyclic Carbonates

The production of cyclic carbonates from CO₂ cycloaddition to epoxides, using the C-scorpionate iron(II) complex [FeCl₂{κ³-HC(pz)₃}] (pz = 1H-pyrazol-1-yl) as a catalyst, is achieved in excellent yields (up to 98%) in a tailor-made ionic liquid (IL) medium under mild conditions (80 °C; 1–8 bar). A favorable synergistic catalytic effect was found in the [FeCl₂{κ³-HC(pz)₃}]/IL system. Notably, in addition to exhibiting remarkable activity, the catalyst is stable during ten consecutive cycles, the first decrease (11%) on the cyclic carbonate yield being observed during the 11th cycle. The use of C-scorpionate complexes in ionic liquids to afford cyclic carbonates is presented herein for the first time.     

Facile microwave-assisted synthesis of bis-pyrazol pyrimidine derivatives via an <Emphasis Type="Italic">N</Emphasis>-alkylation reaction

Abstract  

We present herein a new and efficient method for synthesis of bis-pyrazol pyrimidine derivatives by N-alkylation using a microwave-assisted synthetic process. Two new compounds, N-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl nicotinonitrile and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-4-methyl nicotinonitrile, were synthesized by the N-alkylation reaction. The novel compounds were characterized by Fourier transform infrared spectrometry, ultraviolet spectroscopy, elemental analysis, and nuclear magnetic resonance spectroscopy, etc. The microwave-assisted procedures have noteworthy advantages in terms of thermal efficiency over those carried out by conventional heating methods.     

Nitropyrazoles: XII. Transformations of the 4-Methyl Group in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization of the Transformation Products

A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl- (dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitropyrazol- 4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl- 3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K₂CO₃ to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K₂CO₃ in acetonitrile; in the reaction with K₂CO₃ in ethanol, the 5-nitro group was replaced by ethoxy.