Pyrazole NH Research Articles

Multi-channel anion sensing behaviour of a Ru(II)-bipyridine complex based on benzothiazolyl pyrazole ligand: Experimental and implication of machine learning tools for data prediction

Multi-channel anion sensing characteristics of a Ru(II) complex of the form [(bpy)2Ru (Hpzbzth)](ClO4)2 (1) {bpy = 2,2′-bipyridine and Hpzbzth = 3,5-bis(benzthiazol-2-yl)pyrazole} has been carried out in this work and analyzed through multiple machine learning tools. The complex possesses one pyrazole NH proton in its outer sphere which upon interaction with specific anions yields considerable change in its photo-redox behaviours. The anion sensing aspect of the complex is systematically investigated in acetonitrile through absorption, steady state and time-resolved emission spectroscopy as well as by square-wave (SWV) voltammetry. In absence of anions, the complex displays emission and represents the “on-state”, while complete quenching of emission takes place in presence of basic anions and designates the “off-state” of the system. The initial state of the complex could also be restored upon addition of acid and the process is reversible. Essentially, the complex acts as anion- and acid-induced molecular switches. The absorption, emission and electrochemical outputs of the complex in presence of anions and acid are employed to mimic different types of Boolean and Fuzzy logic (FL) functions. Additionally, we implemented herein different deep learning tools such as artificial neural networks (ANNs) and adaptive neuro-fuzzy inference system (ANFIS) to envisage the full anion sensing aspects of the complex. The outcomes of the three models are compared and also tallied with the experimental results.

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

Mechanistic Study on Catalytic Disproportionation of Hydrazine by a Protic Pincer‐Type Iron Complex through Proton‐Coupled Electron Transfer

Density functional theory calculations have been performed for the proposal of a plausible reaction pathway for disproportionation of hydrazine catalyzed by an iron complex bearing a multiproton‐responsive pincer‐type bis(pyrazole) ligand. The pyrazole arms in this ligand are capable of serving as both Brønsted acid and base. At the first stage of the catalytic cycle, a hydrazine molecule bound to the iron center is converted into two molecules of ammonia by two successive protonation steps from the pyrazole NH groups. The deprotonated pyrazolate arms later abstract two protons from another hydrazine molecule to afford an iron–diazene complex, which is a possible intermediate leading to formation of dinitrogen and ammonia. This bidirectional proton transfer (pyrazole arm ↔ hydrazine) is coupled with electron shuttling along a different pathway (iron center ↔ hydrazine). Overall energy profiles of the proposed mechanism calculated in different spin states elucidate the importance of the spin‐state flexibility of this iron complex.

Iron and ruthenium complexes having a pincer-type ligand with two protic amidepyrazole arms: Structures and catalytic application

This paper describes the iron and ruthenium complexes ligated by 2,6-di(5-pivalamido-1H-pyrazol-3-yl)pyridine (amide-LH2) bearing electron-withdrawing NHCOBut groups on the two protic pyrazole arms. Treatment of FeCl2·4H2O with an equimolar amount of amide-LH2 followed by addition of two trimethylphosphine and an excess of sodium triflate gave the pincer-type iron complex [Fe(MeCN)(amide-LH2)(PMe3)2](OTf)2 (1b; OTf=OSO2CF3). Impact of the amido groups in 1b on the reactions with hydrazines was evaluated. Complex 1b catalyzed disproportionation of hydrazine into ammonia and dinitrogen, although the catalytic activity was lower than that of the But-LH2 analogue 1a. X-ray analysis of 1b as well as the ruthenium complex [{RuCl2(PPh3)2}2(μ2-amide-LH2)2] (2b) revealed that the pendant carboxamide groups along with the pyrazole NH units are engaged in hydrogen bonds in the second coordination sphere.

The Suzuki-Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction.

The efficient Suzuki-Miyaura cross-coupling reaction of halogenated aminopyrazoles and their amides or ureas with a range of aryl, heteroaryl, and styryl boronic acids or esters has been developed. The method allowed incorporation of problematic substrates: aminopyrazoles bearing protected or unprotected pyrazole NH, as well as the free amino or N-amide group. Direct comparison of the chloro, bromo, and iodopyrazoles in the Suzuki-Miyaura reaction revealed that Br and Cl derivatives were superior to iodopyrazoles, as a result of reduced propensity to dehalogenation. Moreover, the mechanism and factors affecting the undesired dehalogenation side reaction were revealed.

Stereoselective synthesis of chlorido–phosphine ruthenium complexes bearing a pyrazole-based protic tripodal amine ligand

Octahedral ruthenium(II) complexes bearing a tripodal amine ligand featuring three ionizable pyrazole NH groups, tris((5-mesitylpyrazol-3-yl)methyl)amine (LH3), have been synthesized in a stereoselective manner. Treatment of the chlorido complex [{RuCl(LH3)}2(μ2-Cl)]Cl (1) with triphenylphosphine in methanol and subsequent anion exchange with potassium hexafluorophosphate resulted in the clean formation of the phosphine complex cis(P,Namine)-[RuCl(PPh3)(LH3)]PF6 (cis(P,Namine)-2), in which the phosphine ligand lies in the position cis to the amine nitrogen atom. Similarly, diphosphines Ph2P(CH2)nPPh2 reacted with 1 under the same conditions to give the diphosphine-bridged dinuclear ruthenium complexes cis(P,Namine)-[{RuCl(LH3)}2{μ2-Ph2P(CH2)nPPh2}](PF6)2 (3a: n=4; 3b: n=3; 3c: n=2). The cis-selectivity is in marked contrast with the reaction in toluene, which affords the trans isomer exclusively (Yamagishi et al., Inorg. Chem. 54 (2015) 11584.). On the other hand, a related chlorido–(dimethyl sulfoxide) complex trans(S,Namine)-[RuCl(Me2SO-S)(LH3)]Cl (4) was synthesized by the reaction of cis-[RuCl2(Me2SO)4] with LH3. Detailed structures of cis(P,Namine)-2, 3a, and 4 have been determined by X-ray crystallography.

Supramolecular dimeric structures of pyrazole-containing meso-oxo carbaphlorin analogues

Synthesis and properties of a novel meso-oxo carbaphlorin analogue embedded with an N-free pyrazole moiety are described. The N-benzyl precursor was prepared by a [3 + 1]-MacDonald condensation of N-benzyl pyrazole dialdehyde and β-alkyl-substituted tripyrrane dicarboxylic acid and subsequent oxidation by ferric chloride. Upon deprotection of the benzyl group, the resulting N-free oxophlorin analogue formed a unique supramolecular dimer through mutual hydrogen bonding interactions between the pyrazole NH and meso-carbonyl group. The assembled behaviour was characterised by various spectroscopies, X-ray crystallographic analysis and vapour pressure osmometry. Under the similar reaction conditions, the condensation of meso-phenyl-substituted tripyrrane derivative afforded an unprecedented tetrapyrrolic macrocycle fused with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone unit at their α-pyrrolic positions. The X-ray crystallographic analysis of the macrocycle revealed a twisted core structure, and nonaromatic nature was elucidated.

Efficient and chromatography-free methodology for the modular synthesis of oligo-(1H-pyrazol-4-yl)-arenes with controllable size, shape and steric bulk

A novel methodology to synthesise oligo-(1H-pyrazol-4-yl)-arenes with controllable size, shape and steric bulk from 1-trityl-1H-pyrazol-4-ylboronate pinacol esters. This straightforward and efficient procedure can be applied to a variety of brominated aromatic precursors in a manner which leaves the pyrazole NH intact for further modification or coordination to metal ions. This will enable the synthesis of novel bioactive molecules and molecular material precursors, all achievable without any purification techniques beyond standard extraction and trituration.

“Scorpionate-like” complexes that are held together by hydrogen bonds: Crystallographic and spectroscopic studies of (3-NH(t-butyl)-5-methyl-pyrazole)nMX2 (M = Zn, Ni, Co, Mn; n = 3, 4; X = Cl, Br)

The hydrogen bonding ligand, 3-NH(t-butyl)-5-methyl-pyrazole, forms “scorpionate-like” first row transition metal complexes that are held together by hydrogen bonds rather than covalent bonds. The formulae of these complexes are (LH)nMX2, where n=3, 4; X=Cl, Br; and LH=3-NH(t-butyl)-5-methyl-pyrazole. The amino-substituted pyrazole can hydrogen bond via both the amino group and the pyrazole NH to form intramolecular NH to halide hydrogen bonds. These complexes have been well characterized and show a 3:1 ratio of ligand to metal for zinc and cobalt (1 and 2), and a 4:1 ratio of ligand to metal for manganese and nickel (3 and 4). The hydrogen bonding interactions appear to be stronger for the 3:1 complexes. The crystallographic and spectroscopic studies (EPR and NMR) have shown that these hydrogen-bonding interactions are strong enough to perturb metal halogen bond distances and, with non-hydrogen bonding solvents, the hydrogen bonds appear to hold these complexes together in solution.

Synthesis and Structures of Ruthenium and Iron Complexes Bearing an Unsymmetrical Pincer‐type Ligand with Protic Pyrazole and Tertiary Aminoalkyl Arms

AbstractA protic pyrazole‐armed NNN‐type pincer ligand 2‐(5‐tert‐butylpyrazol‐3‐yl)‐6‐(diethylaminomethyl)pyridine (LH) with a tertiary aminomethyl tether was synthesized as a new template for metal‐ligand bifunctional catalysts furnished with proton‐responsive pyrazole and hemilabile amine as the cooperating units. Treatment of LH with trans‐[RuCl2(Me2SO)4] and anhydrous FeCl2 led to the formation of the pincer‐type ruthenium complex [RuCl2(Me2SO‐S)(LH)] (2) and iron complex [FeCl2(LH)] (3), respectively. Detailed structures of 2·CH2Cl2 and 3 were determined by X‐ray crystallography. The Brønsted acidic pyrazole NH group proved to be engaged in intra‐ or intermolecular hydrogen bonding. Catalytic hydrogenation of acetophenone with the protic pincer‐type complexes 2 and 3 was also investigated.

Optimization of Bipyridinyl Pyrazole Scaffolds via Design, Synthesis and Screening of a New Series of ROS1 Kinase‐modulating Compounds

A series of rationally designed ROS1 tyrosine kinase inhibitors 6a–9b with bipyridinyl pyrazole scaffold was synthesized and screened. The scaffold itself has showed an exclusive selectivity profile over ROS1 closely related kinases, ALK and c‐Met. The aim of this study was to further explore the structure–activity relationships (SAR) of the bipyridinyl pyrazole core structure, and to improve its ROS1 inhibitory potency. The rational of this study was to explore the nature of the proposed binding site for the pyrazole NH substituents. Careful selections of pyrazole NH substituent groups along with their regioisomers were considered. The compounds exhibited high degree of potency, IC50 values of 21–159 nM. A detailed SAR of bipyridinyl pyrazole scaffold has been finally well established and the virtual screening strategy, through molecular docking, has been performed for this type of ROS1 kinase inhibitors and the docked poses along with the activity data have gone in consistent with SAR specifications.

Packing forces in dichloridobis(3,5-diphenyl-1H-pyrazole-κN(2))cobalt(II) dichloromethane hemisolvate.

The title compound, [CoCl2(C15H12N2)2]·0.5CH2Cl2, was crystallized from a binary mixture of dichloromethane and hexane and a dimeric supramolecular structure was isolated. The Co(II) centre exhibits a distorted tetrahedral geometry, with two independent pyrazole-based ligands occupying two coordination sites and two chloride ligands occupying the third and fourth coordination sites. The supramolecular structure is supported by complementary hydrogen bonding between the pyrazole NH group and the chloride ligand of an adjacent molecule. This hydrogen-bonding motif yields a ten-membered hydrogen-bonded ring. Density functional theory (DFT) simulations at the PBE/6-311G level of theory were used to probe the solid-state structure. These simulations suggest that the chelate undergoes a degree of conformational distortion from the lowest-energy geometry to allow for optimal hydrogen bonding in the solid state.

A novel trinuclear μ3-hydroxido-bridged Cu(II) compound; a molecular cluster, stabilized by hydrogen bonding, bridging pyrazolates, terminal pyrazoles, water and nitrate anions

The synthesis, together with molecular structure and characterization of μ3-hydroxidobis(nitrato)tris(μ-pyrazolato)tetrakis(pyrazole)tricopper(II) monohydrate ([Cu3(OH)(pz)3(Hpz)4(NO3)2](H2O)) is presented and discussed, also in comparison with some related pyrazole nitrate compounds. The peculiar intramolecular hydrogen-bond stabilization for the cluster with as many as 6 intramolecular hydrogen bonds is considered in detail. The non-bonding water solvate bridges between a coordinating nitrate and hydroxide, and intermolecularly with the pyrazole NH from a neighboring unit. Ligand-field, EPR and infrared spectra are discussed in the context of the trinuclear Cu unit. Low-temperature magnetic susceptibility shows a strong antiferromagnetic exchange, resulting in a spin of S=1/2 at low T, similar to earlier reported related compounds.

Synthesis, structures, and reactivities of iron, cobalt, and manganese complexes bearing a pincer ligand with two protic pyrazole arms

This paper describes systematic synthesis of iron, cobalt, and manganese complexes with a pincer-type ligand featuring two ionizable pyrazole NH groups, 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (LH2) and derivatization of these complexes. Treatment of LH2 with divalent cobalt and manganese chlorides resulted in the formation of the dichlorido complexes [MCl2(LH2)] (1b, M=Co; 1c, M=Mn). The cobalt complex 1b as well as the iron analogue [FeCl2(MeOH)(LH2)] (1a′) reacted with silver triflate to afford the high-spin di(triflato) complexes [M(OTf)2(MeCN)(LH2)] (2a, M=Fe; 2b, M=Co; OTf=OSO2CF3), which were further converted to the low-spin phosphine complexes [M(MeCN)(PMe3)2(LH2)](OTf)2 (4a, M=Fe; 4b, M=Co) by the reactions with trimethylphosphine in acetonitrile. The nitrile ligand in 4 was replaced by carbon monoxide to yield the carbonyl complexes [M(CO)(PMe3)2(LH2)](OTf)2 (5a, M=Fe; 5b, M=Co). In addition, the (triflato)iron complex 2a reacted with dioxygen to give the oxo-bridged dinuclear iron(III) complex [{Fe(OTf)2(LH2)}2(μ-O)] (3). Detailed structures of 1c·2EtOH, 2a, 2b, 3·2CH2Cl2, 4b, 5a, and 5b have been determined by X-ray crystallography.

1-{3-[1-(Hydroxyimino)ethyl]-4-methyl-1H-pyrazol-5-yl}ethanone

In the title compound, C8H11N3O2, the oxime and the acetyl groups adopt a transoid conformation, while the pyrazole H atom is localized in the proximity of the acetyl group and is cis with respect to the acetyl O atom. In the crystal, dimers are formed as the result of hydrogen-bonding inter­actions involving the pyrazole NH group of one mol­ecule and the carbonyl O atom of another. The dimers are associated into sheets via O—H⋯N hydrogen bonds involving the oxime hydroxyl and the unprotonated pyrazole N atom, generating a macrocyclic motif with six mol­ecules.

(1H-Pyrazole-κN2)(2,2′:6′,2′′-terpyridine-κ3N,N′,N′′)platinum(II) bis(perchlorate) nitromethane monosolvate

The reaction between [PtCl(terpy)]·2H(2)O (terpy is 2,2':6',2''-terpyridine) and pyrazole in the presence of two equivalents of AgClO(4) in nitromethane yields the title compound, [Pt(C(3)H(4)N(2))(C(15)H(11)N(3))](ClO(4))(2)·CH(3)NO(2), as a yellow crystalline solid. Single-crystal X-ray diffraction shows that the dicationic platinum(II) chelate is square planar with the terpyridine ligand occupying three sites and the pyrazole ligand occupying the fourth. The torsion angle subtended by the pyrazole ring relative to the terpyridine chelate is 62.4 (6)°. Density functional theory calculations at the LANL2DZ/PBE1PBE level of theory show that in vacuo the lowest-energy conformation has the pyrazole ligand in an orientation perpendicular to the terpyridine ligand (i.e. 90°). Seemingly, the stability gained by the formation of hydrogen bonds between the pyrazole NH group and the perchlorate anion in the solid-state structure is sufficient for the chelate to adopt a higher-energy conformation.

New Hexanuclear Group 11 Pyrazolate Complexes: Synthesis and Photophysical Features

The treatment of 2,2'-di(1,2-pyrazol-3-yl)-1,1'-binaphthyl with two equivalents of appropriate monovalent group 11 precursors in the presence of a base leads to a complete exchange of the pyrazole NH protons with M(+) cations. Structural characterisation of the copper(I) complex revealed a hexanuclear complex with a pelton-wheel-like arrangement of the binaphthyl unit. As indicated by their spectroscopic data, all three complexes are isostructural. The complexes show a complex fluorescence behaviour that can be partially related to the ligand system and also to the metal sites, as indicated by the position of the fluorescence peaks and their temperature dependence and lifetimes.

A highly selective fluorescent sensor for fluoride anion based on pyrazole derivative: Naked eye “no–yes” detection

A new pyrazole-based fluorescent sensor, 5-amino-3-(5-phenyl-1H-pyrrol-2-yl)-1H-pyrazole-4-carboxamide (compound 1), was studied for fluoride anion (F −) detection in organic or water-containing solution. This compound displayed both changes in UV–vis absorption and fluorescence emission spectra upon addition of F −. With increasing of F −, blue emission intensity increases drastically and reaches saturation with 607-fold enhancement at 424 nm. The results indicate that compound 1 has highly selectivity for fluoride detection over other anions, such as Cl −, Br −, I −, HSO 4 −, H 2PO 4 − and AcO − in DMSO or aqueous DMSO solutions. 1H NMR titration and other experiments confirm that the sensing process is mainly from the deprotonation of the pyrazole–NH in compound 1.

Methyl 3-[3-(ethoxycarbonyl)thioureido]-1H-pyrazole-5-carboxylate

The title compound, C9H12N4O4S, was proven to be the product of the reaction of methyl 5-amino-1H-pyrazole-3-carboxyl­ate with ethyl isothio­cyanato­carbonate. All non-H atoms of the mol­ecule are planar, the mean deviation from the least squares plane being 0.048 Å. The intra­molecular N—H⋯O bond involving the NH-group, which links the thio­urea and pyrazole fragments, closes a six-membered pseudo-heterocyclic ring, and two more hydrogen bonds (N—H⋯O with the participation of the pyrazole NH group and N—H⋯S involving the second thio­urea NH group) link the mol­ecules into infinite chains running along [10].

Metal complexes derived from hydrazoneoxime ligands: IV. Molecular and supramolecular structures of some nickel(II) complexes derived from diacetylmonoxime S-benzyldithiocarbazonate

Four new nickel(II) complexes, [{Ni(L)} 2], [NiL · HPyr], [NiL · HIm] and [Ni(HL) 2] · H 2O, derived from diacetylmonoxime- S-benzyldithiocarbazonate (H 2L) have been synthesized and characterized by elemental analyses, field desorption and electrospray ionization mass spectra, UV–Vis, infrared absorption spectra, as well as 1H NMR spectra. X-ray molecular structures showed that the Ni(II) in both [NiL · HPyr] and [NiL · HIm] are in a distorted square planar environment and is coordinated to the dianionic NNS tridentate hydrazoneoxime ligand via deprotonated oximate nitrogen, hydrazone imine nitrogen, and thiolate sulphur. The fourth coordination sites are occupied, respectively, by the pyrazole and imidazole nitrogens. The oximate O1 of [NiL · HPyr] is involved in intramolecular hydrogen bond with the pyrazole NH proton as well as intermolecular hydrogen bond pyrazole C6H proton, forming a helical chain propagating along the b-axis. The structure is stabilized by a set of π⋯π and CH⋯π interactions. The molecular units in [NiL · HIm] are linked together by hydrogen bond formation between the oximate oxygen and imidazole NH proton, giving rise to an infinite zigzag chain extended along the a-axis. The chains are interconnected by π⋯π and CH⋯O interactions. In [Ni(HL) 2] · H 2O, the Ni(II) is in a distorted octahedral environment. The two mononegative hydrazoneoxime ligands are coordinated in the meridional configuration where the two thiol sulphur atoms and the two oxime nitrogen atoms are cis to each other, while the imine nitrogen atoms are trans. The oxime proton O2H is involved in a reciprocal bifurcated hydrogen bond formation with both N2 and S3 of the adjacent molecule giving rise to hydrogen bonded dimer. This dimeric structure is further stabilized by a pair of reciprocal CH⋯O interactions. A one dimensional chain of alternating dimeric unit and water molecule propagating along the c-axis is formed via hydrogen bond formation between the oxime O1 oxygen and the bridged water molecule proton.