Single-crystal X-ray Structure Research Articles

Unexpected Side Products in the Large-Scale Preparation of 2,3-Dihydro-1,1,2,2,3,3-hexamethyl-1H-indene

AbstractDuring the development of an optimized procedure for the synthesis of 2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene significant amounts of 5-tert-butyl-2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene were formed, along with 5-tert-hexyl-2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene under certain conditions. The structures of 5-tert-hexyl-2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene and 5-tert-butyl-2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene were established by spectroscopic means and confirmed by X-ray single-crystal structure determinations. The mechanism for the formation of 5-tert-butyl-2,3-dihydro-1,1,2,2,3,3-hexamethyl-1H-indene is discussed.

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide.

C1 chemistry has a central role in the efficient utilization of single-carbon molecules, contributing significantly to sustainability, innovation and economic growth across various sectors. In this study, we present an efficient and rapid method for synthesizing a variety of heteroannulated pyrimidones using cyanoacetamide-based multicomponent reaction (MCR) chemistry. By utilizing specific MCR-based scaffolds as precursors and employing the abundant and inexpensive formamide as a C1 feedstock under neat conditions, we were able to efficiently access substituted thieno-, quinolino- and indolopyrimidones without the need of column chromatography. Further, a single-crystal X-ray structure was obtained, revealing certain geometrical features.

Ligand-free palladium-catalyzed synthesis of 3-(2,2-dialkyl-2H-chromen-4-yl)-2-phenylimidazo[1,2-a]pyridine derivatives: molecular docking investigation of their potential as DNA gyrase inhibitors and evaluation of their antibacterial activities.

Palladium-catalyzed reactions between imidazo[1,2-a]pyridine derivatives and 4-bromo-2,2-dialkyl-substituted 2H-chromenes under microwave irradiation at 100 W, 120 °C for 20-30 min provided a series of new 3-(2,2-dialkyl-2H-chromen-4-yl)-2-phenylimidazo[1,2-a]pyridine derivatives in good to excellent yields. The structures of the synthesized compounds were confirmed through spectroscopic techniques (NMR and HRMS). The X-ray single-crystal structure of compound 16e was also determined. Shorter reaction time, high yield and good substrate scope were the major advantages of this method. All these compounds were further investigated in vitro for the evaluation of their antibacterial potency using the agar well diffusion method against human pathogenic Gram-negative E. coli and Gram-positive S. aureus bacteria, with the determination of their minimum inhibitory concentration (MIC) values. Indeed, compound 16h strongly inhibited DNA gyrase in silico with a binding affinity of -8.7 kcal mol-1 and exhibited zone of inhibition (ZI) values of 19 mm and MIC values of 10 μg mL-1 in both Gram-negative E. coli and Gram-positive S. aureus, relative to the standard drug gentamicin. By analyzing the structure-activity relationships based on the molecular docking results and the potent antibacterial activities, it could be concluded that these new phenylimidazo[1,2-a]pyridine-chromene derivatives have the potential to be effective druggable antibacterial agents.

Concise Synthesis of (-)-Veratramine and (-)-20-iso-Veratramine via Aromative Diels-Alder Reaction.

A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-iso-veratramine has been accomplished. A Horner-Wadsworth-Emmons olefination joins two chiral building blocks of approximately equal complexity and a transition-metal catalyzed intramolecular Diels-Alder cycloaddition-aromatization cascade constructs the tetrasubstituted arene. Other key steps include a highly diastereoselective crotylation of an N-sulfonyl iminium ion and an Eschenmoser fragmentation. The chiral building blocks developed for this synthesis could be used to access a range of additional isosteroidal alkaloids using our diversifiable strategy. Our work shows that 20-iso-veratramine is not identical with a natural product proposed to have that structure. The single crystal X-ray structures of veratramine and 20-iso-veratramine are reported.

Hydrogen-Bonded Di(hydroperoxy)alkane Adducts of the Type Cy3P=O·(HOO)2CHR (R = Alkyl).

Five representatives of a novel type of di(hydroperoxy)alkane adducts of phosphine oxides have been synthesized and fully characterized, including their solubility in organic solvents. The phosphine oxide Cy3PO (1) has been used in combination with the corresponding aldehydes to create the adducts Cy3PO·(HOO)2CHCH3 (2), Cy3PO·(HOO)2CHCH2CH3 (3), Cy3PO·(HOO)2CH(CH2)2CH3 (4), Cy3PO·(HOO)2CH(CH2)3CH3 (5), and Cy3PO·(HOO)2CH(CH2)7CH3 (6). All adducts crystallize easily and contain the peroxide and phosphine oxide hydrogen-bonded in 1:1 ratios. The single crystal X-ray structures of 2-6 and their unique features are discussed. The 31P NMR spectra of the adducts 2-6 show downfield-shifted signals as compared to Cy3PO. In the IR spectra, the ν(P=O) wavenumbers of the adducts have smaller values than the neat phosphine oxide. All spectroscopic results of 2-6 show that the P=O bond is weakened by hydrogen-bonding to the di(hydroperoxy)alkane moieties. Adduct 6 selectively oxidizes PPh3 to OPPh3 within minutes, and nonanal is reformed in the process. The easy synthesis, handling, and administration of these stable, solid, and soluble peroxides with well-defined composition will have a positive impact on synthetic chemistry.

Synthesis and Structure of Methylated Acetylenic Nitriles.

Cyanoacetylene and dicyanoacetylene react in the ternary methylation system CH3F/SbF5/SO2 under the formation of its corresponding N-monomethylated and N,N'-dimethylated species, respectively. Additionally, in the case of dicyanoacetylene, an N,N'-dimethylated HF-addition product was obtained. The salts were characterized by low-temperature vibrational spectroscopy. In the case of [C4H4N][SbF6], [C5H3N2][SbF6]·SO2, and [C6H8N2F2][SbF6]2, single-crystal X-ray structures are reported. Surprisingly, all of the obtained salts are room-temperature stable. The experimental data are discussed, together with quantum chemical calculations at the M06-2X/aug-cc-pVTZ level of theory.

Chloride, Alkoxide, or Silicon: The Bridging Ligand Dictates the Spin State in Dicobalt Expanded Pincer Complexes.

We report the synthesis and characterization of a series of high- and low-spin dicobalt complexes of the tBuPNNP expanded pincer ligand. Reacting this dinucleating ligand in its neutral form with two equiv of CoCl2(tetrahydrofuran)1.5 yields a high-spin dicobalt complex featuring one Co inside and one Co outside of the dinucleating pocket. Performing the same reaction in the presence of two equivalents of KOtBu provides access to a high-spin dicobalt complex wherein both Co centers are bound within the PNNP pocket, and this complex also features a bridging OtBu ligand. Reacting either of the high-spin complexes with excess diethyl silane affords a low-spin dicobalt complex containing two unusual bridging Si-based ligands. These complexes were investigated using NMR spectroscopy, XAS, single crystal X-ray structure determination, and computational methods, showing that the Si-based ligands are best described as base-stabilized silylenes.

Expression of concern: Synthesis and characterization of a novel copper carboxylate complex and a copper complex-coated polyether sulfone membrane for efficient degradation of methylene blue dye under UV irradiation: the single crystal X-ray structure of the copper carboxylate complex.

Expression of concern for 'Synthesis and characterization of a novel copper carboxylate complex and a copper complex-coated polyether sulfone membrane for efficient degradation of methylene blue dye under UV irradiation: the single crystal X-ray structure of the copper carboxylate complex' by Rupy Dhir et al., Dalton Trans., 2024, 53, 9441-9451, https://doi.org/10.1039/D4DT00871E.

Synthesis and Redox Chemistry of Co3E4 (E=P, As) Clusters.

The synthesis of the cluster complexes [(Cp'''Co)3(μ3,η2:η2:η2-E3)(μ3-E)] (E=P (3), As (4)) starting from the anionic triple-decker complexes [K(18cr6)(dme)2][(Cp'''Co)2(μ,η4:η4-E4)] (E=P (1), As (2)) by electrophilic quenching with the Co dimer [(Cp'''CoCl)2] is reported. Both complexes show a distinct redox chemistry, which was first investigated by cyclic voltammetry. Subsequently, the monoanions [K(L)(sol)n][(Cp'''Co)3(μ3,η2:η2:η2-E3)(μ3-E)] (E=P, L=18cr6, sol=dme, n=2 (5), E=As, L=2,2,2-crypt, n=0 (6)), the monocations [(Cp'''Co)3(μ3,η2:η2:η2-E3)(μ3-E)][FAl] (E=P (7), As (8)) and the dications [(Cp'''Co)3(μ3,η3:η3:η3-E4)][TEF]2 (E=P (9), As (10)) could be realized experimentally and isolated in moderate to good yields. All compounds were characterized by single crystal X-ray structure analysis, NMR and EPR spectroscopy, mass spectrometry and elemental analysis.

Ni(II)-Dithiocarbamate and -diphosphine coordination complexes as pre-catalysts for electrochemical OER activity.

Electrochemical water oxidation holds immense potential for sustainable energy generation, splitting water into clean-burning hydrogen and life-giving oxygen. However, a key roadblock lies in the sluggish nature of the oxygen evolution reaction (OER). Finding stable, cost-effective, and environmentally friendly catalysts with high OER efficiency is crucial to unlock this technology's full potential. Here, we have synthesized four new cationic heteroleptic Ni(II) complexes having the formula [Ni(S^S)(P^P)]PF6 (1-4) where S^S represents bidentate dithiocarbamate ligands (N,N-bis(benzyl)dithiocarbamate and N-benzyl-N-3-picolyldithiocarbamate) and P^P represents diphosphine ligands (1,2-bis(diphenylphosphino)ethane (dppe) and 1,1-bis(diphenylphosphino)ferrocene (dppf)). The complexes were characterized by UV-Vis, FT-IR, and multinuclear NMR spectroscopic techniques. Single crystal X-ray structures of all complexes are also reported. The molecular structures showed a distorted square planar geometry around the Ni(II) center defined by a bidentate S^S dithiolate chelating ligand and a P^P diphosphine chelating ligand. Interestingly, the complexes exhibit weak non-covalent interactions, contributing to the overall supramolecular structures. The role of complexes in water oxidation has been investigated electrochemically in a 1.0 M KOH solution after immobilization onto the surface of activated carbon cloth (CC). Detailed analyses revealed that the complexes are promising precatalysts for generating active Ni(OH)2/NiO(OH) as a true oxygen evolution reaction (OER) catalyst at CC upon anodic activation. Notably, the catalyst derived from complex 4@CC exhibited the highest OER activity with a Tafel slope of 93 mV per decade and reaching a current density of 10 mA cm-2 at a low overpotential of 250 mV in a 1.0 M KOH solution. This study reveals the significance of dithiocarbamate and diphosphine ligands in facilitating the conversion of Ni(II) complexes into highly active OER catalysts.

Strongly yellow photo- and electroluminescent palladium(II) complexes via metal-assisted thermally activated delayed fluorescence

Two luminescent palladium(II) complexes, namely PdBO and DPdBO, featuring metal-perturbed intraligand charge-transfer (MPICT) excited states have been designed and synthesized. Single-crystal X-ray structures of both complexes indicate the presence of...

“Coordination caps” of graded electron-donor capacity

Abstract An efficient synthesis of the novel {6-[1,1-di(pyridin-2-yl)ethyl]pyridine-2-yl}2-methyl-1,3-propanediamine (2) is reported, as well as a reliable large-scale synthesis (of the order of 100 g) of previously known 2,2’-[1-(6-chloropyridin-2-yl)ethane-1,1-diyl]dipyridine (4); the latter is the starting material for the preparation of the former, as well as a multitude of other polypodal polyamine/polyimine ligands. Both materials, as well as the intermediates in their multi-step syntheses, have been fully characterised. Ligand 2, in conjunction with ligands 2,2’-(pyridine-2,6-diyl)bis(2-methylpropane-1,3-diamine) (1) and 2,6-bis(1,1-di(pyridin-2-yl)ethyl)pyridine (3), establishes a series of tetrapodal pentadentate N5 ligands L of like scaffold, and thus coordination geometry, but graded primary amine/imine donor atom ratios. The iron(II) complexes [Fe(L)NCCH3](OTf)2 (L = 1: A; L = 2: B; L = 3: C; OTf = triflate) have been prepared and fully characterised, including X-ray single-crystal structure analyses. The metal-centred one-electron oxidation/reduction potential (FeII/FeIII) depends sensitively on the electron donor capacity of the capping ligand used, as demonstrated by cyclic voltammetry. Whereas the acetonitrile ligand in A and C is readily exchanged for a methanol ligand in methanol solution, the resulting complexes showing variable-temperature spin crossover (SCO) in solution, B has been found to be inert to this type of ligand exchange.

Dimeric Copper(I) Complex with a Disulfonamide-Bridged Core.

Pyridine-2-yl-sulfonyl-quinolin-8-yl-amide (psq) has produced the first sulfonamidato-bridged dicopper(I) complex, {Cu[κ4-(μ-κN:κN-psq)]}2 containing the rhombic Cu(I)2N2 core. The single crystal X-ray structure of this complex shows that two anionic psq ligands straddle the metal atoms via bridging sulfonamide N atoms to give a Cu···Cu distance of 2.9593(8) Å. When it is dissolved in chloroform [Cu(psq)]2 activates C-Cl bonds as demonstrated through the rapid formation of [CuCl(psq)]2. While the solid orange compound is stable for weeks under N2. Acetonitrile solutions of [Cu(psq)]2 are rapidly oxidized in air. A 1D-carbonato-bridged coordination polymer, {Cu2[κ4-(μ-κO:κN-psq)]2[μ3-CO3][H2O]}, and the bis-homoleptic complex [Cu(κ3-psq)(κ2-psq)] are concurrently isolated in high yield without evidence of ligand oxidation with H2O2 detected as a side product. This implicit O2 activation was harnessed in the oxidation of phenol substrates. 2,6-Di-tert-butylphenol is catalytically converted to the coupled dione product with 100% yield. If a para-blocked phenol is used, the reaction become stoichiometric and an O2-derived hydroperoxide group is installed into the ortho position. In contrast, nitrophenol is not oxidized and the result is metal-based oxidation and isolation of [Cu(OC6H4NO2)(psq)]2. This is rationalized by this more acidic phenol acting as a proton donor, rather than a H atom donor to a putative O2 adduct.

LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development.

Estrogen effects in tissue are mediated in part through activation of the surface estrogen receptor GPER, a broadly expressed G protein-coupled receptor that impacts a wide range of normal and pathologic processes, including metabolism, vascular health, inflammation, and cancer. A commonly used synthetic and specific GPER agonist, named G-1, antagonizes tumors by promoting cellular differentiation and enhancing tumor immunogenicity. G-1 is a racemic compound, and since its discovery, the question of whether both enantiomers display agonist activity or the agonist activity resides primarily in a single enantiomer has never been fully resolved. Herein, we disclose the isolation of the pure enantiomers of G-1 and determine that the desirable activity resides exclusively in 1 enantiomer, named LNS8801, whose configuration we have unambiguously determined by single crystal x-ray structure analysis. Using preclinical models, we show that LNS8801 suppresses cancer in a GPER-dependent manner and that LNS8801 is efficacious when administered orally. Further, we show that GPER is widely, but not ubiquitously, expressed in both normal and malignant human tissues. In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response.

Redox Noninnocent Copper(I) Complex Where Metal Is a Spectator and Ligand Is an Actor in the Glaser Coupling Reaction of Alkynes.

An extended trisazo dipyridyl ligand, L, and its copper(I) complex, [1]+, were synthesized and fully characterized. Complex [1]+ has five coordination geometry satisfied by ligand L. L has a low-lying π* orbital; thus, [1]+ showed very facile multiple ligand-based redox events. Moreover, due to the strong π-acceptor nature of L, the Cu(II)/Cu(I) redox potential of [1]+ was anodic (0.62 V). The redox events of both L and [1]+ were characterized using various spectroscopic studies and density functional theory (DFT) calculations. Taking advantage of the multiple facile ligand-based reductions in [1]+, the Glaser coupling reaction of terminal alkynes was explored. Various kinds of alkynes were found to be effective when using [1]+ as a precatalyst. The mechanism of the reaction was investigated thoroughly by several controlled experiments, isolation, and characterization of the intermediates using various spectroscopic studies as well as by single-crystal X-ray structure determination. These studies showed that the L in [1]+ acted not only in the electron transfer events but also as a locus for binding the substrate, breaking and forming bonds, and, finally, releasing the product. Thus, here, the metal mainly acted as a spectator and ligand L acted as an actor.

A novel layered structure of the heterometallic oxalate compound [NH2(CH3)2]2[NaFe(C2O4)3]·0.33NH(CH3)2·0.33H2O: synthesis, crystal structure and thermal decomposition.

The synthesis, single-crystal X-ray structure determination and thermal analysis are reported for a novel heteronuclear oxalate compound synthesized from a mixture of Fe and Na salts, oxalic acid and N,N-dimethylformamide (DMF) in aqueous solution. The new metallooxalate compound was obtained and identified as a dimethylammonium tris(oxalato)ferrate(III), namely, poly[[bis(dimethylammonium) [tri-μ-oxalato-sodium(I)iron(III)]]-dimethylamine-water (3/1/1)], [NH2(CH3)2]2[NaFe(C2O4)3]·0.33NH(CH3)2·0.33H2O, which crystallizes in the orthorhombic noncentrosymmetric space group C2221. In this novel structure, each Fe atom is hexacoordinated by three non-equivalent bidentate oxalate ligands, while the four Na atoms adopt different coordination numbers, i.e. 6, 7 and 8. The structure consists of bimetallic anionic A layers, {[NaFe(C2O4)3]2-}n, displaying a layered structure with infinitely linked Fe2Na2 tetramers on the ab plane. Two kinds of bimetallic parallel layers (A1 and A2) are present alternately and are found to be staggered, while only the A2 layer is crossed by a twofold axis parallel to the a axis through two Na atoms. The [NH2(CH3)2]+ (HDMA) cations occupy the voids between the anionic layers, while the free molecules, i.e. NH(CH3)2 (DMA) and H2O, are located between two different anionic layers. In addition to ionic bonds, the stability of the structure is ensured by hydrogen-bond interactions involving the oxalate ligands and the nitrogenous and water molecules. The layered structure appears to be different in the family of oxalate-bridged NaI-FeIII compounds. It is in agreement with the predicted 2D or layered structure of bimetallic complexes containing anionic tris(oxalato)metallate(III) with the [XR4]+ counter-ion template (X= N, P or S, and R= alkyl group or H). The thermal decomposition of the compound shows the final residual product to be NaFeO2.

Covalent Folding of Fluorinated Polyphenylene by Sulfur Fluorine Annulative Substitution.

We report that fluorinated polyphenylene P50 undergoes folding-like sulfur fluorine annulative substitution (SFAS) to form a well-defined tubular helix H50. This is achieved with atomic precision in an exceptionally efficient manner, involving the simultaneous transformation of 98 C-F bonds with the yield per reaction site approaching 99.9%. The desired product H50 features a fully fused dibenzothiophene skeleton of 5.8 helical turns in total. It is truly monodisperse (Đ = 1.0) in nature, allowing for thorough spectroscopic characterizations. Unambiguous single crystal X-ray structure, distinct chiroptical properties, and intriguing through-cavity threading complexation are described. These results, in addition to those of H50's lower congeners, H34 and H18, illustrate the great potential of folding-like SFAS in shaping random-coiled polymer chains into higher-order functional structures.

Utilizing MEDT analysis of [3 + 2] cycloaddition reaction: x-ray crystallography of spirooxindole linked with thiophene/furan heterocycles and triazole framework

Hybridization of spirooxindole with different pharmacophores such as triazole and heterocycle such as thiophene and furan moiety was achieved by the [3 + 2] cycloaddition (32CA) reaction approach. Structural investigations of the compounds 4a and 4b were performed using X-ray single crystal structure determinations and Hirshfeld analysis. Both compounds crystallized in monoclinic crystal system. The space group is P21/c for 4a and P21/n for 4b. The crystal parameters are a = 10.2619(3) Å, b = 13.6776(3) Å, c = 10.9318(3), β = 116.640(4)° for the former while a = 13.0012(1) Å, b = 14.9692(1) Å, c = 14.1178(1) Å, β = 97.101(1)° for the latter. In both compounds, the aryl group and the triazole moieties are twisted from one another. The twist angle is 84.75˚for 4a while 86.64˚ for 4b. Based on Hirshfeld calculations, the Cl…H, O…H, N…H and C…H non-covalent interactions in 4a while the O…H interactions in 4b are the most important. The molecular mechanism of the key 32CA reaction between the in situ generated azomethine ylides and the corresponding chalcones has been studied within the Molecular Electron Density Theory (MEDT). The MEDT study reveals that the low activation energies and high experimental selectivity are the result of the supernucleophilic character of the ylides and the strong electrophilicity of the chalcones, which favour the process through a high polar character. This high polar character accounts for the total endo selectivity experimentally found.

Borenium Ion Equivalents Stabilized by BICAAC and Their Implementation as Catalysts in Hydrosilylation of Carbonyls.

Hydride abstraction from the borane adduct, (BICAAC) ⋅ BH3 afforded the hydride bridged dinuclear borenium ion equivalent complexes 1 and 2 that have been characterized by various spectroscopic and spectrometric techniques followed by the assessment of Lewis acidity using the Gutmann-Beckett method. The single crystal X-ray structure of complex 2 revealed the presence of discrete ions in the solid state. The complex (BICAAC) ⋅ BH2(OTf) (3), obtained from the reaction of (BICAAC) ⋅ BH3 with MeOTf, formed the corresponding boronium cations [(BICAAC) ⋅ BH2(L)]+(OTf)- on reaction with Lewis bases (L= pyridine (4) and DMAP (5)). Complexes 1 and 2 demonstrated notable catalytic activity in the hydrosilylation of a diverse array of carbonyls using 1.0 mol % catalyst loading (achieving the highest turnover frequency (TOFmax) of up to 1200 h-1 with benzaldehyde. A broad substrate scope has been presented for aldehydes and ketones decorated with various electron-donating and withdrawing substituents along with this the hydrosilylation of a few para-quinone methides has also been presented.

Cold and Liquid Crystal Properties of Square-Planar Copper(II) Versus Nickel(II)- Iminophenolate/Naphthalen-2-Olate Schiff Base Complexes.

Reaction of the phenolate or naphthalen-2-olate based Schiff base ligands, (E)-1-((2-ethylphenylimino)methyl)phenol (HL1) or (E)-1-((2-ethylphenylimino)methyl)naphthalen-2-ol (HL2) with nickel(II) and copper(II) acetate provides the complexes bis[(E)-1-((2-ethylphenylimino)methyl)phenolato-ĸ2N,O]Ni/Cu(II), [Ni(L1)2] (1) and [Cu(L1)2] (2), or bis[(E)-1-((2-ethylphenylimino)methyl)naphthalen-2-olato-ĸ2N,O]Ni/Cu(II), [Ni(L2)2] (3) and [Cu(L2)2] (4), respectively. Single crystal X-ray structure determinations for 1, 3 and 4 reveal N2,O2-metal coordination of two chelating Schiff base ligands in a square-planar geometry. Powder X-ray diffractograms confirm the phase purity of the bulk microcrystalline samples. Thermal analyses by differential scanning calorimetry (DSC) and polarized light microscopic (PLM) indicate the copper(II) complexes to exhibit cold crystal (2) and liquid crystal (4) property. Cyclic voltammograms suggest an irreversible electrochemical process with two one electron charge transfer processes in N,N-dimethylformamide. Variable temperature magnetic measurements at the solid-state prove the diamagnetic nature of the low-spin Ni2+ centres in 1 or 3, as expected from the square-planar coordination geometry with rather strong ligands. The complexes expose medium level of antioxidant activity in methanol. Optimized geometry and excited state property by DFT/TD-DFT correspond well to the experimental results of the electronic and molecular structure at the ground state.