Pyrazolyl Moiety Research Articles

Reactivity of Mg(AlMe4)2 towards neutral tris(pyrazolyl)alkanes.

Various new tris(pyrazolyl)alkanes of the class R'CTp3-R (R' = Me, Et, nPr, iBu; R = Et, cyPr, Cy, p-tBuPh, Ph; cyPr = cyclopropyl, Cy = cyclohexyl, p-tBuPh = para-tert-butylphenyl) were synthesised and their reactivity towards Mg(AlMe4)2 was examined. Along with new examples of recurring structural motifs, such as separated ion pairs and "metal in a box" complexes, e.g., [(MeCTp3-Et)2Mg][AlMe4]2, several magnesium complexes with new structural features/compositions were obtained. Treatment of the "metal in a box" species [(MeCTp3-R)Mg][AlMe4]2 with THF donor gave the terminal methyl complex [(MeCTp3-cyPr)MgMe(thf)2][AlMe4]. Variation of the backbone alkyl substituent R' in the tris(pyrazolyl)alkane R'CTp3-Ph gave ionic liquids (R' = Et, nPr) and the methyl-bridged dimagnesium complex [({iBuCTp3-Ph}Mg{AlMe4})2(μ-Me)][AlMe4]. The bulky Cy and p-tBuPh moieties at the pyrazolyl 3 position gave the new structural motif [MeCTp3-RMg(ηn-AlMe4)][AlMe4] (η3, R = Cy; η2, R = p-tBuPh), stabilising a "[Mg(AlMe4)]+" entity. The AlMe3 group can be reversibly displaced under reduced pressure affording the new separated ion pair [(MeCTp3-p-tBuPh)MgMe][AlMe4] with a terminal "[MgMe]+" moiety. Moderate thermal treatment of both [(MeCTp3-p-tBuPh)MgMe][AlMe4] and [(MeCTp3-p-tBuPh)Mg(η2-AlMe4)][AlMe4] resulted in selective C-H-bond activation in the 5 position of one of the pyrazolyl moieties and the formation of an AlMe3-modified anionic tris(pyrazolyl)alkane and hence the neutral complex [MeC(pz3-p-tBuPh)2(pz3-p-tBuPh,5-AlMe3)]MgMe.

β-Carbolines as intermediates in indirect heteroarylation of tryptamines exemplified by the synthesis of 2-pyrazolyltryptamines

A cyclization–recyclization pathway for indirect 2-heteroarylation of tryptamines has been suggested by the example of introducing the pyrazolyl moiety. The process involves the intermediate cyclization of tryptamines into push–pull type β-carboline semi-products. The relative stability of the tautomeric forms of 2-pyrazolyltryptamines has been estimated using the DFT method.

Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides.

Five new compounds of benz[e]indole pyrazolyl-substituted amides (2a-e) were synthesised in low to good yields via the direct amide-coupling reaction between a pyrazolyl derivative containing a carboxylic acid and several amine substrates. The molecular structures were determined by various spectroscopic methods, such as NMR (1H, 13C and 19F), FT-IR and high-resolution mass spectrometry (HRMS). X-ray crystallographic analysis on the 4-fluorobenzyl derivative (2d) reveals the amide-O atom to reside to the opposite side of the molecule to the pyrazolyl-N and pyrrolyl-N atoms; in the molecular packing, helical chains feature amide-N‒H⋯N(pyrrolyl) hydrogen bonds. Density-functional theory (DFT) at the geometry-optimisation B3LYP/6-31G(d) level on the full series shows general agreement with the experimental structures. While the LUMO in each case is spread over the benz[e]indole pyrazolyl moiety, the HOMO spreads over the halogenated benzo-substituted amide moieties or is localised near the benz[e]indole pyrazolyl moieties. The MTT assay showed that 2e, exhibited the highest toxicity against a human colorectal carcinoma (HCT 116 cell line) without appreciable toxicity towards the normal human colon fibroblast (CCD-18Co cell line). Based on molecular docking calculations, the probable cytotoxic mechanism of 2e is through the DNA minor groove binding.

Synthesis, Molecular and Supramolecular Structures of Symmetric Dinuclear Cd(II) Azido Complex with bis-Pyrazolyl s-Triazine Pincer Ligand

A new dinuclear Cd(II)-azido complex of 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (PMT) pincer ligand is synthesized. Its single crystal X-ray structure reveals the dinuclear [Cd(PMT)(Cl)(N3)]2 formula. The triclinic crystal parameters are a = 9.323(4) Å, b = 10.936(5) Å, c = 11.312(6) Å, α = 112.637(10)°, β = 104.547(11)° and γ = 105.133(10)° while V = 944.1(8) Å3. Due to symmetry considerations, the asymmetric unit comprises a half [Cd(PMT)(Cl)(N3)]2 formula. The Cd(II) is hexa-coordinated with one tridentate PMT ligand in a pincer fashion mode in addition to one terminal chloride and two azide ions bridging the two Cd(II) centers in double μ(1,1) bridging mode. Unusually, the Cd-N(s-triazine) bond is not the shortest among the Cd-N interactions with the PMT pincer ligand. The supramolecular structure of the dinuclear [Cd(PMT)(Cl)(N3)]2 formula is controlled by a significant amount of Cl…H (16.4%), N…H (25.3%), H…C (9.8%) and H…H (37.2%) interactions based on Hirshfeld surface analysis. Careful inspection of the shape index map reveals the presence of some weak π-π stacking interactions between the s-triazine and pyrazolyl moieties. The percentage of C…C contacts is 1.9% where the C2…C8 (3.462 Å) is the shortest while the centroid–centroid distance is 3.686 Å. Natural charge analysis describes the charge transferences from the ligand groups to the Cd(II), while and atoms in molecules (AIM) give an indication on the properties of the Cd-N and Cd-Cl bonds.

Acid form of Trofimenko’s scorpionates, H(Tp<sup>R,R′</sup>); comments on synthesis and solid-state structure of H(Tp<sup><italic>t</italic>Bu,Me</sup>)

We report a re-examination of Trofimenko’s original protocol for the preparation of the acid form of his hydrotris(pyrazolyl)borates, H(Tp<sup>R,R′</sup>), by the treatment of M(Tp<sup>R,R′</sup>)with glacial acetic acid. It is concluded that the protocol is effective as long as the 3-substituent of the pyrazolyl moiety is sufficiently bulky to provide steric protection to the acidic N–H proton. The solid-state structure of H(Tp<sup><italic>t</italic>Bu,Me</sup>), the acid form of the popular Tp<sup><italic>t</italic>Bu,Me</sup> ligand is also presented.

Acid form of Trofimenko’s scorpionates, H(Tp

We report a re-examination of Trofimenko’s original protocol for the preparation of the acid form of his hydrotris(pyrazolyl)borates, H(TpR,R′), by the treatment of M(TpR,R′) with glacial acetic acid. It is concluded that the protocol is effective as long as the 3-substituent of the pyrazolyl moiety is sufficiently bulky to provide steric protection to the acidic N–H proton. The solid-state structure of H(TptBu,Me), the acid form of the popular TptBu,Me ligand is also presented.

Regioisomeric dipyrazolyl−anthracene luminophores: mechanochromic luminescence switch and mercury ion detection with ‘turn-off’ response

A series of regioisomeric luminophores L1–L8 with 1H-pyrazol-3-yl or 1H-pyrazol-4-yl substituents at the different positions of anthracene core have been synthesised and characterised. According to the photophysical properties and related frontier orbital features of these compounds, the ‘site-effect’ of pyrazolyl substituent on an anthracene unit can be found, demonstrating the dependence of the properties of the compound on the position of substitution of the pyrazolyl moieties connecting to the anthracene core. Moreover, the target luminophores present reversible mechanochromism properties. The most significant mechanochromism luminescence is achieved for luminophores L1 and L2 with pyrazolyl substituents at the 9-and 10-positions of the anthracene unit. Upon grinding the pristine powder sample, a colour change from light yellow to yellow-green is observed. In addition, the target luminophores L2, L4, L6 and L8 demonstrate sensing properties of Hg2+ ions with high selectivity and exceptional sensitivity. These findings suggest that these anthracene-centred luminophores are promising functional platforms with fluorescence and selective heavy metal sensor arrays.

Cyclooctadiene Rh(I) Bis- and Tris(pyrazolyl)aluminate Complexes and Their Catalytic Activity on the Polymerization of Phenylacetylene.

In this work, we report the transfer of alkyl bis- and tris(pyrazolyl)aluminates metalloligands to an electron-rich organotransition metal center. The 16-electron heterobimetallic complexes of rhodium [Rh(COD){Al(Ph2pz)2Me2}] (3) and [Rh(COD){Al(Ph2pz)3Me}] (4) were obtained by metathesis reaction of the sodium bis- (1) and tris(pyrazolyl)aluminate (2) with [RhCl(COD)]2. For 3, 1H and 13C NMR in solution along with DFT calculations are consistent with a κ2-coordination mode of the bis(pyrazolyl)aluminate to a square-planar Rh(I) center. The X-ray structure of 4 shows a similar κ2-coordination mode of the tris(pyrazolyl)aluminate to Rh(I) with a pendant pyrazolyl moiety. The attempted synthesis of aluminate-rhodium complexes with R = CF3, tBu on the pyrazolate ring afforded [Rh(R2pz)(COD)]2 and [R2pzAlMe2]2. Complexes 3 and 4 were investigated as homogeneous catalysts in the polymerization of phenylacetylene (PA). Both complexes showed enhanced catalytic activity compared to analogous rhodium poly(pyrazolyl)borates. Optimized gas-phase DFT geometries of 3, 4, [Rh(COD){B(Ph2pz)2Me2}], and [Rh(COD){B(Ph2pz)3Me}] were used to compare bite angles, while DFT geometries of 3-CO, 4-CO, [Rh(CO)2{B(Ph2pz)2Me2}], and [Rh(CO)2{B(Ph2pz)3Me}] were employed to probe the electronic situation of the rhodium center through IR CO stretching modes. The wider bite angles and the less electron-rich rhodium center of the poly(pyrazolyl)aluminates compared with their borate analogues could be implicated in the better performance of the active catalytic species during polymerization of PA.

Hydrogen-Bonded and Halogen-Bonded: Orthogonal Interactions for the Chloride Anion of a Pyrazolium Salt.

In the hydrochloride of a pyrazolyl-substituted acetylacetone, the chloride anion is hydrogen-bonded to the protonated pyrazolyl moiety. Equimolar co-crystallization with tetrafluorodiiodobenzene (TFDIB) leads to a supramolecular aggregate in which TFDIB is situated on a crystallographic center of inversion. The iodine atom in the asymmetric unit acts as halogen bond donor, and the chloride acceptor approaches the -hole of this TFDIB iodine subtending an almost linear halogen bond, with Cl···I = Å and Cl···I–C = 179.32(6)°. This contact is roughly orthogonal to the N–H···Cl hydrogen bond. An analysis of the electron density according to Bader’s Quantum Theory of Atoms in Molecules confirms bond critical points (bcps) for both short contacts, with = 0.129 for the halogen and e for the hydrogen bond. Our halogen-bonded adduct represents the prototype for a future class of co-crystals with tunable electron density distribution about the -hole contact.

N-Donor-Functionalized Acetylacetones for Heterobimetallic Coordination Polymers, the Next Episode: Trimethylpyrazoles

The ditopic molecule 3-(1,3,5-trimethyl-4-1H-pyrazolyl)acetylacetone (HacacMePz) combines an acetylacetone group suitable for deprotonation and O,O′ coordination to a Pearson hard cation with a softer N-donor site. Both binding modes were employed individually: the pyrazolyl moiety was coordinated to ZnII, HgII, and AgI, and with trivalent iron the tris-chelating O,O′ complex [Fe(acacMePz)3] was isolated. The CuII derivative shows shorter O,O′ chelation and N coordination in the more distant Jahn–Teller sites and exists in two alternative crystal forms: namely, as a tetranuclear discrete complex and as a chain polymer. The different Pearson hardnesses of the coordination sites of acacMePz– allow for the design of well-ordered mixed-metal solids. Selective complexation to a hard and soft cations was achieved in coordination polymers combining hard FeIII and softer HgII or AgI. Even slight differences in Pearson hardness based on different oxidation states of the same cation imply sufficient selectivity, as shown by the successful synthesis of a mixed-valence CuII/CuI chain polymer. A synopsis of all structurally characterized compounds confirms that HacacMePz represents a bridging ligand with restricted conformational freedom. No full rotation about the single bond between the pyrazolyl and acetylacetone fragments occurs, and dihedral angles between these moieties are limited to values of 90 ± 17°.

Regulating Spin Dynamics of Nitronyl Nitroxide Biradical Lanthanide Complexes through Introducing Different Transition Metals.

Four biradical-Ln complexes with different transition metal ions, namely [LnM(hfac)5 (NITPh-PyPzbis)] (MII =MnII and LnIII =Gd 1, Dy 2; MII =NiII and LnIII =Tb 3, Dy 4), were prepared by the reaction of Ln(hfac)3 ⋅ 2H2 O, Mn(hfac)2 ⋅ 2H2 O or Ni(hfac)2 ⋅ 2H2 O with NITPh-PyPzbis biradical (hfac=hexafluoroacetylacetonate, NITPh-PyPzbis=5-(3-(2-pyridinyl)-1H-pyrazol-1-yl)-1,3-bis(1'-oxyl-3'-oxido- 4',4',5',5'-tetramethyl-4,5-hydro-1H-imidazol-2-yl)benzene). In complexes 1-4, the NITPh-PyPzbis biradical chelates one LnIII ion by means of its aminoxyl moieties and the transition metal ion is introduced through the two N donors from the pyridyl pyrazolyl moiety. Magnetic investigations indicate that complex 4 displays visible maxima in frequency/temperature-dependent χ'' signals with two-step relaxation processes, but complex 2 exhibits no slow magnetization relaxation. The comparison of structure parameters of both Dy complexes indicates that the symmetries of coordination spheres of two Dy ions are D2d for 2 and C2v for 4, which thus probably results in different magnetic relaxation behaviors. This work provides new insight for improving properties of Ln-biradical based SMMs.

Silver(I)‐mediated hetero base pairs of 6‐pyrazolylpurine and its deaza derivatives

AbstractA series of antiparallel‐stranded and parallel‐stranded DNA duplexes containing hetero base pairs of the artificial nucleobases 6‐(1H‐pyrazol‐1‐yl)‐9H‐purine (6PP), 1‐deaza‐6PP (1D6PP), 7‐deaza‐6PP (7D6PP), and 1,7‐dideaza‐6PP (1,7D6PP) were investigated with respect to their ability to form silver(I)‐mediated base pairs. A close examination of the duplex melting temperatures in the absence and in the presence of silver(I) ions shows a strong sequence‐dependence of the stability of the resulting silver(I)‐mediated base pairs. The most stable silver(I)‐mediated base pairs are formed when 1,7D6PP is located in a purine‐rich strand opposite either 6PP or 7D6PP. This indicates that the silver(I) ions are coordinated via the Watson‐Crick edge of the latter nucleobase, whereas they bind to the pyrazolyl moiety of the former. As a result, a [2+1] coordination environment is proposed for the silver(I) ions.

Silver(I) Coordination in Silver(I)-Mediated Homo Base Pairs of 6-Pyrazolylpurine in DNA Duplexes Involves the Watson-Crick Edge.

DNA duplexes comprising 6‐(1H‐pyrazol‐1‐yl)‐9H‐purine (6PP), 1‐deaza‐6PP (1D6PP), 7‐deaza‐6PP (7D6PP) and 1,7‐dideaza‐6PP (1,7D6PP) 2′‐deoxyribonucleosides, respectively, were investigated towards their ability to form metal‐mediated base pairs in the presence of AgI. In 6PP and 7D6PP, the AgI ion can coordinate to the nucleobase via the endocyclic N1 nitrogen atom, that is, via the Watson–Crick edge. In contrast, this nitrogen atom is not available in 1D6PP and 1,7D6PP, so that in 1D6PP an AgI coordination is only possible via the Hoogsteen edge (N7). Reference duplexes with either adenine:adenine mispairs or canonical adenine:thymine base pairs were used to investigate the impact of the pyrazolyl moiety on the AgI‐binding properties. To determine the thermal and structural duplex stabilities in the absence or presence of AgI, all duplexes were examined by UV and circular dichroism spectroscopic studies. These investigations shed light on the question of whether N1‐ or N7‐coordination is preferred in purine‐based metal‐mediated base pairs.

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions.

The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.

Synthesis and reactions of 4H-3,1-benzoxazin-4-one derivative bearing pyrazolyl moiety as antimicrobial and antioxidant agents

Ring opening of 4-aryl-2-phenyloxazol-5-one 1 with 2-aminobenzoic acid in acetic acid and n-butanol gave compounds 2 and 3, respectively. The 4H-3,1-benzoxazin-4-one derivative 4 was synthesized by refluxing of compound 2 in acetic anhydride. Then it reacted with different nitrogen nucleophiles such as hydrazine hydrate, phenylhydrazine, cyclohexylamine, piperidine, ethylenediamine, ethanolamine, semicarbazide hydrochloride, cyanoacetohydrazide and methyl glycinate hydrochloride to give compounds 5–14 in order to study the behavior of these nucleophilic reagents on the performed ring system. All the structures of the newly prepared compounds were characterized by their IR, 1H-, 13C-NMR and MS spectral data. Some of the synthesized compounds were screened for their antimicrobial and antioxidant activities. Compound 5 showed remarkable activity upon this screening.

Green, effective and chromatography free synthesis of benzoimidazo[1,2-a]pyrimidine and tetrahydrobenzo [4,5]imidazo [1,2-d]quinazolin-1(2H)-one and their pyrazolyl moiety using Fe3O4@SiO2@l-proline reusable catalyst in aqueous media

l-proline-functionalized silica-coated Fe3O4 nanoparticle was synthesized and characterized using Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), Zeta potential and a vibrating sample magnetometer (VSM). The Fe3O4@SiO2@l-proline nanoparticles in aqeous media have been used as a green avenue for the mild and efficient multicomponent synthesis of new derivatives of benzoimidazo[1,2-a]pyrimidines and tetrahydrobenzo [4,5]imidazo-[1,2-d]quinazolin-1(2H)-ones in excellent yields. Furthermore, the recovery and reuse of the catalyst was demonstrated 10 times without a detectible loss in activity. Eco-friendliness, high purity of the desired products, short reaction time and easy workup can be mentioned as the other advantages of this method.

Design, Synthesis, and Application of NNN Pincer Ligands Possessing a Remote Hydroxyl Group for Ruthenium-Catalyzed Transfer Hydrogenation of Ketones

A new family of pyridyl-based NNN pincer ligands bearing a remote pendent OH group were developed. Considerable acceleration effects on the activity of Ru-catalyzed transfer hydrogenation of ketones were imparted by the pendent OH group, and importantly, introducing a CH2OH group to the 4′-position of the pyrazolyl moiety is an appropriate choice. The results present a general strategy for exploring bifunctional ligands to construct effective catalysts.

Above room temperature spin crossover in thioamide-functionalised 2,6-bis(pyrazol-1-yl)pyridine iron(ii) complexes

This work describes the synthesis of two novel functionalised 2,6-bis(pyrazol-1-yl)pyridine (bpp) ligands, namely 2,6-bis(pyrazol-1-yl)pyridine-4-carbothioamide (bppCSNH2) and N-methyl-2,6-bis(pyrazol-1-yl)pyridine-4-carbothioamide (bppCSNHMe). The corresponding solvated or non-solvated Fe(ii) salts, [Fe(bppCSNH2)2]X2 and [Fe(bppCSNHMe)2]X2 (X = BF4- or ClO4-) were synthesised and their properties measured by SQUID magnetometry, Evans NMR, differential scanning calorimetry and single crystal X-ray diffraction. In the solid state [Fe(bppCSNH2)2]2+ salts persist in the low spin state below 350 K. The structure of [Fe(bppCSNH2)2](BF4)2·2MeNO2 shows a network of intermolecular interactions responsible for the low spin state stabilisation, relative to the prototypical [Fe(bpp)2]2+ spin crossover (SCO) salts. By contrast the complexes of bppCSNHMe both display abrupt SCO above 300 K. [Fe(bppCSNHMe)2](BF4)2·MeNO2 requires solvent loss before SCO can be observed centred at 332 K. The non-solvated [Fe(bppCSNHMe)2](ClO4)2 shows SCO centred at 325 K. Analysis of solvated and non-solvated crystal structures suggests that cooperativity is facilitated by thioamide-group interactions with neighbouring pyrazolyl and pyridyl moieties.

Design, synthesis and antiproliferative activity in cancer cells of novel dihydropyrazolyl and pyrazolyl artemisinin-phenyl ethers

To explore potent anticancer agent based on artemisinin scaffold, a series of 10-O-phenyl ethers derivatives containing dihydropyrazolyl or pyrazolyl moiety have been designed and synthesized. Their structures were determined by LC-MS and ¹H-NMR date. Inhibitory effects of the target compounds in human breast cancer MCF-7, MCF/Adr, MDA-MB-231 cells and prostate cell line PC-3 were determined by MTT assay. Those derivatives displayed good antiproliferative activity against the tested cancer cells. Particularly, target compounds exhibited significant cytotoxicity against drug-resistance cells MCF/Adr, which was worthy for further investigation.

Unconventional Single-Molecule Conductance Behavior for a New Heterocyclic Anchoring Group: Pyrazolyl.

Electrical conductance across a molecular junction is strongly determined by the anchoring group of the molecule. Here we highlight the unusual behavior of 1,4-bis(1H-pyrazol-4-ylethynyl)benzene that exhibits unconventional junction current versus junction-stretching distance curves, which are peak-shaped and feature two conducting states of 2.3 × 10-4 G0 and 3.4 × 10-4 G0. A combination of theory and experiments is used to understand the conductance of single-molecule junctions featuring this new anchoring group, i.e., pyrazolyl. These results demonstrate that the pyrazolyl moiety changes its protonation state and contact binding during junction evolution and that it also binds in either end-on or facial geometries with gold contacts. The pyrazolyl moiety holds general interest as a contacting group, because this linkage leads to a strong double anchoring of the molecule to the gold electrode, resulting in enhanced conductance values.