Six-membered Ring Research Articles

Structural Characterization of 4-(4-Nitrophenyl)thiomorpholine, a Precursor in Medicinal Chemistry

4-(4-nitrophenyl)thiomorpholine, the title compound, has been used as a precursor for the corresponding 4-thiomorpholinoaniline, which is a useful building block in medicinal chemistry. The crystal and molecular structures of the title compound, however, have not been described thus far. We synthesized the title compound by means of a nucleophilic aromatic substitution reaction of 4-fluoronitrobenzene and thiomorpholine and structurally characterized it by X-ray crystallography, DFT calculations, and Hirshfeld surface analysis. In the crystal, the molecule exhibits an approximately CS-symmetric structure, with the nitrogen-bound 4-nitrophenyl group in a quasi axial position on the six-membered thiomorpholine ring in a low-energy chair conformation. The solid-state structure of the title compound is markedly different from that of its morpholine analogue. This can be ascribed to the formation of centrosymmetric dimers through intermolecular C–H···O weak hydrogen bonds involving the methylene groups adjacent to the sulfur atom and face-to-face aromatic stacking.

Heterocycle compounds synthesized by amide ligand-promoted copper salt catalyzed construction of C-O(S) bonds.

We introduce a mild method for the ligand-promoted copper-catalyzed coupling of 2-halophenol to construct DBDO using cost-effective copper salts, ligands, and alkaline reagents. This method cleverly makes 2-bromophenol complete the Ullman reaction twice, achieves efficient C-O(S) bond coupling and intermolecular cyclization, and yields high amounts of oxygen(sulfur)-containing six-membered ring products. Less reactive 2-chlorophenol was also applied in this catalytic system. The application range of the copper-amide catalytic system was further expanded. Moreover, the success of a gram-scale reaction demonstrated that this operationally simple process is scalable.

Selective separation and recovery of boron from spent Nd-Fe-B magnets leaching solution

The accumulation of boron during the recovery of rare earth elements (REEs) from spent Neodymium-Iron-Boron (Nd-Fe-B) magnets affects the extraction of REEs and causes environmental pollution through the boron-containing wastewater. Given that boron is a globally scarce strategic resource, this study proposes a method for the selective separation and recovery of boron from spent Nd-Fe-B magnets leaching solution. The synergistic extraction of boron adopting 2-ethylhexanol (EHA) and 2-ethyl-1,3-hexanediol (EHD), and the extraction mechanism were investigated. Under optimized conditions (30 % EHA-20 % EHD-50 % sulfonated kerosene, 1:1O/A phase ratio, pH 3.3, 10 min), the two-stage countercurrent extraction achieved a remarkable 99.9 % extraction efficiency with minimal loss of REEs. Slope analysis, Raman, FT-IR, and NMR combined with DFT were used to elucidate the extraction mechanism. Specifically, some of the boric acid molecules complexed with the OH groups of EHD to form stable six-membered ring complexes, while another part bound with both EHA and EHD to form linear complexes containing six-membered rings. Employing 0.4 mol/L NaOH as the stripping agent, the two-stage countercurrent stripping process achieved a stripping efficiency of 99.8 %. Subsequently, borax pentahydrate products exceeding 99 % purity were obtained via evaporative crystallization from the stripping solution. Notably, the raffinate contained only ∼ 5 mg/L of boron, which could be further reduced below the discharge standard via the REEs recovery process, allowing for safe emission. This work offers a novel approach for the selective separation and recovery of boron from spent Nd-Fe-B magnets, eliminating its adverse effects on REEs extraction and the environment, while simultaneously recovering a valuable resource.

Hydrolysis mechanism of the cyclohexaborate anion: Unraveling the intricacies.

is a highly polymerized borate anion of three six-membered rings. Limited research on the hydrolysis mechanism under neutral solution conditions exists. Calculations based on density functional theory show that undergoes five steps of hydrolysis to form H3BO3 and . At the same time, there are a small number of borate ions with different degrees of polymerization during the hydrolysis process, such as triborate, tetraborate, and pentaborate anions. The structure of the borate anion and the coordination environment of the bridging oxygen atoms control the hydrolysis process. Finally, this work explains that in existing experimental studies, the reason for the low content in solution environments with low total boron concentrations is that it depolymerizes into other types of borate ions and clarifies the borate species. The conversion relationship provides a basis for identifying the possibility of various borate ions existing in the solution. This work also provides a certain degree of theoretical support for the cause of the "dilution to salt" phenomenon.

Upper Rim-Bridged Calix[4]arenes via Cyclization of meta Alkynyl Intermediates with Diphenyl Diselenide.

A Sonogashira coupling of meta-iodocalix[4]arene with various terminal acetylenes confirmed that the meta position of calixarene is well addressable, and that both thermal and microwave protocols led to good yields of alkynylcalixarenes. Alkynes thus obtained were subjected to the ferric chloride and diphenyl diselenide-promoted electrophilic closure. It turns out that the calix[4]arenes give completely different bridging products than those described for the non-macrocyclic starting compounds. This can be demonstrated not only by the isolation of products with a six-membered ring (6-exo-dig), but mainly by the smooth formation of the 5-endo-dig cyclization, which has never been observed in the aliphatic series. An attempt at electrocyclization led to a high yield of the 1,2-diketone (oxidation of the starting alkyne), again in contrast to the reaction described for the acyclic derivatives. The structures of the unexpected products were unequivocally established by X-ray analysis and clearly demonstrate how the preorganized macrocyclic skeleton favors a completely different regioselectivity of cyclization reactions compared to common aliphatic compounds.

A Route to Two-Dimensional Room-Temperature Organometallic Multiferroics: The Marriage of d-p Spin Coupling and Structural Inversion Symmetry Breaking.

Two-dimensional (2D) room-temperature multiferroic materials are highly desirable but still very limited. Herein, we propose a potential strategy to obtain such materials in 2D metal-organic frameworks (MOFs) by utilizing the d-p direct spin coupling in conjunction with center-symmetry-breaking six-membered heterocyclic rings. Based on this strategy, a screening of 128 2D MOFs results in the identification of three multiferroics, that is, Cr(1,2-oxazine)2, Cr(1,2,4-triazine)2, and Cr(1,2,3,4-trazine)2, simultaneously exhibiting room-temperature ferrimagnetism and ferroelectricity/antiferroelectricity. The room-temperature ferrimagnetic order (306-495 K) in these MOFs originates from the strong d-p direct magnetic exchange interaction between Cr cations and ligand anions. Specifically, Cr(1,2-oxazine)2 exhibits ferroelectric behavior with an out-of-plane polarization of 4.24 pC/m, whereas the other two manifest antiferroelectric characteristics. Notably, all three materials present suitable polarization switching barriers (0.18-0.31 eV). Furthermore, these MOFs are all bipolar magnetic semiconductors with moderate band gaps, in which the spin direction of carriers can be manipulated by electrical gating.

Enhanced adhesive and mechanically robust silicone-based coating with excellent marine anti-fouling and anti-corrosion performances.

Poly(dimethylsiloxane) (PDMS) is widely used in marine antifouling coatings due to its low surface energy property. However, certain drawbacks of PDMS coatings such as poor surface adhesion, weak mechanical properties, and inadequate static antifouling performance have hindered its practical applications. Herein, condensation polymerization is utilized to prepare PDMS-based polythiamine ester (PTUBAF) coatings that consist of PDMS, polytetrahydrofuran (PTMG), 2, 3, 5, 6-tetrafluoro-1, 4-benzenedimethanol (TBD) as the main chains and isobornyl acrylate(IBA) as the antifouling group. The surface adhesion to the substrate is enhanced due to the hydrogen bond between the coated carbamate group and the hydroxyl group on the surface of the substrate. Mechanical properties of PTUBAF are significantly improved due to the benzene ring and six-membered ring biphase hard structure. The strong synergistic effect of bactericidal groups and low surface energy surface endows the PTUBAF coating with outstanding antifouling performance. Due to the low surface energy surface, the PTUBAF coatings are also found to possess excellent anti-corrosion. Furthermore, since the PTUBAF coatings exhibit a visible light transmittance of 91 %, they can applied as protective films for smartphones. The proposed method has the potential to boost the production and practical applications of silicone-based coatings.

Holotrichones A and B, potent anti-leukemic lindenane-type sesquiterpene trimers with unprecedented complex carbon skeletons from a rare Chloranthus species

Two lindenane-type sesquiterpene (LDS) trimers with unprecedented carbon skeletons, holotrichones A (1) and B (2), were obtained from the whole plant of Chloranthus holostegius var. trichoneurus by a ultra performance liquid chromatography-photodiode array detector-mass spectrometry (UPLC-PDA-MS)-guided isolation strategy. Compound 1 represents the first LDS trimer incorporating a unique 3/5/6/6-fused framework, in which a lindenane-type monomer and the 2-methylbutyryl substituent of an LDS dimer is bridged by a six-membered ring system. Compound 2 is the first hetero-trimer fused by an LDS dimer with a p-benzoquinone-meroterpenoid, featuring an unusual 3/5/6/6/3/5/6/6/6 nonacyclic system fused by the sesquiterpenoid unit and a 2-geranyl-6-methyl-2,5-cyclohexadien-1,4-dione moiety. In compound 2, the dimeric LDS moiety is equipped with a rare oxaspiro[4.5]decane system. Their structures, including absolute configurations, were established by spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. The plausible biogenetic pathway speculation indicated that hetero- and homo-Diels-Alder additions may dominate the formation of these highly fused polycyclic frameworks. Both compounds 1 and 2 induced the human acute myeloid leukemia MV-4–11 cell death via apoptosis induction, which deserves further investigation on this new chemical class of LDS oligomers for their anti-leukemic potential.

Proansamycin B derivatives from the post-PKS modification gene deletion mutant of Amycolatopsis mediterranei S699.

Ten new proansamycin B congeners (1-10) together with one known (11) were isolated and characterized on the basis of 1D and 2D NMR spectroscopic and HRESIMS data from the Amycolatopsis mediterranei S699 ΔPM::rifR+rif-orf19 mutant. Compounds 8 and 9 featured with six-membered ring and five-membered ring hemiketal, respectively. Compounds 1, 2, and 9 displayed antibacterial activity against MRSA (methicillin-resistant Staphylococcus aureus), with the MIC (minimal inhibitory concentration) values of 64, 8, and 128 µg/mL, respectively. Compound 1 showed significant cytotoxicity against MDA-MB-231, HepG2 and Panc-1 cell lines with IC50 (half maximal inhibitory concentration) values of 2.3 ± 0.2, 2.5 ± 0.3 and 3.8 ± 0.5 μM, respectively.

Crystal structures of sulfonamide protected bicyclic guanidines: (S)-8-{[(tert-butyl-dimethyl-sil-yl)-oxy]meth-yl}-1-[(2,2,4,6,7-penta-methyl-2,3-di-hydro-benzo-furan-5-yl)sulfon-yl]-1,3,4,6,7,8-hexa-hydro-2H-pyrimido[1,2-a]pyrimidin-1-ium tri-fluoro-methane-sulfonate and (S)-8-(iodo-meth-yl)-1-tosyl-1,3,4,6,7,8-hexa-hydro-2H-pyrimido[1,2-a]pyrimidin-1-ium iodide.

Two compounds, (S)-8-{[(tert-butyl-dimethyl-sil-yl)-oxy]meth-yl}-1-[(2,2,4,6,7-penta-methyl-2,3-di-hydro-benzo-furan-5-yl)sulfon-yl]-1,3,4,6,7,8-hexa-hydro-2H-pyrimido[1,2-a]pyrimidin-1-ium tri-fluoro-methane-sulfonate, C27H46N3O4SSi+·CF3O3S-, (1) and (S)-8-(iodo-meth-yl)-1-tosyl-1,3,4,6,7,8-hexa-hydro-2H-pyrimido[1,2-a]pyrimidin-1-ium iodide, C15H21IN3O2S+·I-, (2), have been synthesized and characterized. They are bicyclic guanidinium salts and were synthesized from N-(tert-but-oxy-carbon-yl)-l-me-thio-nine (Boc-l-Met-OH). The guanidine is protected by a 2,2,4,6,7-penta-methyl-dihydro-benzo-furan-5-sulfonyl (Pbf, 1) or a tosyl (2) group. In the crystals of both compounds, the guanidinium group is almost planar and the N-H forms an intra-molecular hydrogen bond in a six-membered ring to the oxygen atom of the sulfonamide protecting group.

Molecular dynamics simulation of dodecyl dimethyl benzyl ammonium cation-intercalated montmorillonite

Abstract Dodecyl dimethyl benzyl ammonium (DDBA) is a novel cation surfactant used to modify clay minerals. DDBA-intercalated montmorillonite is formed by the ion exchange between DDBA cations in the solution and cations in the montmorillonite interlayers. By using molecular dynamics simulations, we investigated the basal spacings, interlayer structures and dynamics of DDBA-montmorillonites. The results showed that the calculated basal spacings agreed well with experimental values and that the layering behaviours of DDBA had been revealed. The ammonium groups of DDBA ions preferred staying close to the centre of Si–O six-member rings. The benzyl group and lauryl group were oriented in parallel in the monolayer state, whereas they were tilted in other states. DDBA ions have very low mobility in the interlayer region, indicating that the negatively charged montmorillonite surfaces can effectively fix this positively charged surfactant. The microscopic structures and dynamics obtained in the present study provide atomic-scale insights into the properties of DDBA-intercalated clay minerals.

Observation of the Water-HNSO2 Complex.

Sulfamic acid (NH2SO3H, SFA) is supposed to play an important role in aerosol new particle formation (NPF) in the atmosphere, and its formation mainly arises from the SO3-NH3 reaction system in which weakly bonded donor-acceptor complexes such as SO3···NH3 and isomeric HNSO2···H2O have been proposed as the key intermediates. In this study, we reveal the first spectroscopic observation of HNSO2···H2O in two forms in a solid Ar matrix at 10 K. The major form consists of two intermolecular H bonds by forming a six-membered ring structure with a calculated dissociation energy of 7.6 kcal mol-1 at the CCSD(T)-F12a/aug-cc-pVTZ level of theory. The less stable form resembles SO3···H2O in containing a pure chalcogen bond (S···O) with a dissociation energy of 7.2 kcal mol-1. The characterization of HNSO2···H2O with matrix-isolation IR spectroscopy is supported by D- and 18O-isotope labeling and quantum chemical calculations.

The use of simple structural parameters of energetic metal-organic frameworks to assess their density

A new method is presented for accurately estimating the density (D) of energetic material-organic frameworks (EMOFs), which has vital role in determining their performance. The experimental density data for 124 EMOFs, which are composed of five or six-membered heterocyclic rings, has been used to develop and analyze the model. The model is constructed based on simple structural parameters and can be easily applied to EMOFs with complex compositions and structures. The performance of the new model in estimating density has been compared to the Dalirandeh et al. model. The values of statistical factors comprising mean absolute error (MAE), maximum absolute error (AEmax), root mean square error (RMSE), mean absolute percent error (MAPE), and coefficient of determination (R2) for Dalirandeh et al./new model are 0.09/0.07, 0.33/0.23, 0.12/0.10, 4.21/3.50, and 0.94/0.96, respectively. Statistical validations and applicability domain (AD) assessments have confirmed that the new model provides high accuracy, precision, reliability, and goodness-of-fit.

Substitution Effect of a Single Nitrogen Atom on π-Electronic Systems of Linear Polycyclic Aromatic Hydrocarbons (PAHs): Theoretically Visualized Coexistence of Mono- and Polycyclic π-Electron Delocalization.

We theoretically investigated the nitrogen substitution effect on the molecular structure and π-electron delocalization in linear nitrogen-substituted polycyclic aromatic hydrocarbons (N-PAHs). Based on the optimized molecular structures and magnetic field-induced parameters of fused bi- and tricyclic linear N-PAHs, we found that the local π-electron delocalization of subcycles (e.g., mono- and bicyclic constituent moieties) in linear N-PAHs is preserved, despite deviation from ideal structures of parent monocycles. The introduction of a fused five-membered ring with a pyrrolic N atom (N-5MR) in linear N-PAHs significantly perturbs the π-electronic condition of the neighboring fused six-membered ring (6MR). Monocyclic pyrrole exhibits substantial bond length alternations, strongly influencing the π-electronic systems of both the fused N-5MR and 6MR in linear N-PAHs, depending on the location of shared covalent bonds. A fused six-membered ring with a graphitic N atom in an indolizine moiety cannot generate monocyclic π-electron delocalization but instead contributes to the formation of polycyclic π-electron delocalization. This is evidenced by bifurcated diatropic ring currents induced by an external magnetic field. In conclusion, the satisfaction of Hückel's 4n + 2 rule for both mono- and polycycles is crucial for understanding the overall π-electron delocalization. It is crucial to consider the unique characteristics of the three types of substituted N atoms and the spatial arrangement of 5MR and 6MR in N-PAHs.

Direct Band Gap Semiconductors with Two- and Three-Dimensional Triel-Phosphide Frameworks (Triel=Al, Ga, In).

Recently, several ternary phosphidotrielates and -tetrelates have been investigated with respect to their very good ionic conductivity, while less focus was pointed towards their electronic structures. Here, we report on a novel series of compounds, in which several members possess direct band gaps. We investigated the known compounds Li3AlP2, Li3GaP2, Li3InP2, and Na3InP2 and describe the synthesis and the crystal structure of novel Na3In2P3. For all mentioned phosphidotrielates reflectance UV-Vis measurements reveal direct band gaps in the visible light region with decreasing band gaps in the series: Li3AlP2 (2.45 eV), Li3GaP2 (2.18 eV), Li3InP2 (1.99 eV), Na3InP2 (1.37 eV), and Na3In2P3 (1.27 eV). All direct band gaps are confirmed by quantum chemical calculations. The unexpected property occurs despite different structure types. As a common feature all compounds contain EP4 tetrahedra, which share exclusively vertices for E=In and vertices as well as edges for E=Al and Ga. The structure of the novel Na3In2P3 is built up by a polyanionic framework of six-membered rings of corner-sharing InP4 tetrahedra. As a result, the newly designed semiconductors with direct band gaps are suitable for optoelectronic applications, and they can provide significant guidance for the design of new functional semiconductors.

Study on AEMs with Excellent Comprehensive Performance Prepared by Covalently Cross-Linked p-Triphenyl with SEBS Remotely Grafted Piperidine Cations.

A series of SEBS-C6-PIP-yPTP (y = 0-15%) AEMs with good mechanical and chemical stability were prepared by combining the strong rigidity of p-triphenyl, good toughness of SEBS, and excellent stability of PIP cations. After the introduction of a p-triphenyl polymer into the main chain, a clear hydrophilic-hydrophobic phase separation structure was constructed within the membrane, forming a continuous and interconnected ion transport channel to improve ion transport efficiency. Moreover, the molecular chains of the cross-linked AEMs change from chain-like to network-like, and the tighter binding between each molecule increases the tensile strength. The special structure of the six-membered ring makes PIP have a significant constraint effect; when nucleophilic substitution and Hoffman elimination occur at the α and β positions, the required transition state potential energy increases, making the reaction difficult to occur and improving the alkaline stability of the polymer membrane. The SEBS-C6-PIP-15%PTP membrane has the best mechanical properties (Ts = 38.79 MPa, Eb = 183.09% at 80 °C, 100% RH), the highest ion conductivity (102.02 mS. cm-1 at 80 °C), and the best alkaline stability (6.23% degradation at 80 °C in a 2 M NaOH solution for 1400 h). It can be seen that organic-organic covalent cross-linking is an effective means to improve the comprehensive performance of AEMs.

Crystal structure, Hirshfeld surface analysis, crystal voids, interaction energy calculations and energy frameworks and DFT calculations of ethyl 2-cyano-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-3-phenylpropanoate

The title compound, C16H17N3O3, is racemic as it crystallizes in a centrosymmetric space group (P\overline{1}), although the trans disposition of substituents about the central C—C bond is established. The five- and six-membered rings are oriented at a dihedral angle of 75.88 (8)°. In the crystal, N—H...N hydrogen bonds form chains of molecules extending along the c-axis direction that are connected by inversion-related pairs of O—H...N into ribbons. The ribbons are linked by C—H...π(ring) interactions, forming layers parallel to the ab plane. A Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H...H (45.9%), H...N/N...H (23.3%), H...C/C...H (16.2%) and H...O/O...H (12.3%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. The volume of the crystal voids and the percentage of free space were calculated to be 100.94 Å3 and 13.20%, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the electrostatic energy contributions in the title compound. Moreover, the DFT-optimized structure at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.

Green-Emitting Extended B3,N2-Doped Polycyclic Aromatic Hydrocarbon with Multiple Resonance Structure.

An air-stable B3,N2-PAH (B3N2; nine annulated six-membered rings) was synthesized from 1-X-2,6-di(azasilaanthryl)benzenes (X = Cl, I) via lithiation/borylation, electrophilic aromatic borylation, and Si/B exchange. The heteroatom distribution in B3N2 meets the requirements for multiple resonance thermally activated delayed fluorescence (MR-TADF). Indeed, B3N2 emits green light (λem = 523 nm; ΦPL = 85%; CHCl3) with a small fwhm of 0.15 eV. Lifetimes for prompt (7.8 ns) and delayed (60 μs) fluorescence were measured in PMMA.

Metal-Free Reversible Double Cyclization of Cyanuric Diazide to an Asymmetric Bitetrazolate via Cleavage of the Six-Membered Aromatic Ring.

Crystallization of the reaction mixture of 2-amino-4,6-diazido-1,3,5-triazine and excess tert-butylamine results in the isolation of tert-butylammonium N,N-[1'H-(1,5'-bitetrazol)-5-yl]cyanamidate, suggesting a complex decyclization/cyclization rearrangement involving breakage of the six-membered aromatic ring and the formation of two new five-membered azole rings mediated by deprotonation of the precursor by the amine. The addition of tert-butylamine to 2-amino-4,6-diazido-1,3,5-triazine gives spectroscopic indication of thermodynamically unfavorable reactivity in low-dielectric solvents, and high-level quantum chemical computations also suggest its formation to be unfavorable. A computed interconversion pathway describes the likely reaction mechanism and supports the general thermodynamic unfavorability of the reaction and the requirement for a high-dielectric environment to template formation of the ionic product and its trapping by crystallization.

(1E,3E)-1,4-Dinitro-1,3-butadiene-Synthesis, Spectral Characteristics and Computational Study Based on MEDT, ADME and PASS Simulation.

The chemistry of conjugated nitrodienes is becoming increasingly popular. These molecules are successfully applied in cycloaddition to synthesize six-membered rings in Diels-Alder reactions. Nitrodienes can be also applied to obtain bis-compounds in [3+2] cycloaddition. Moreover, the presence of a nitro group in the structure provides a possibility of further modification of the products. The simplest symmetrical representative of conjugated nitrodienes is (1E,3E)-1,4-dinitro-1,3-butadiene. Although the first mentions of the compound date back to the early 1950s, the compound has not yet been examined thoroughly enough. Therefore, in this article, a comprehensive study of (1E,3E)-1,4-dinitro-1,3-butadiene has been described. For this purpose, an experimental study including the synthesis process as well as an evaluation of the spectral characteristics has been conducted. So as to better understand the properties of this compound, a computational study of reactivity indices based on MEDT and also an assessment of pharmacokinetics and biological activity according to ADME and PASS methodologies have been made. On this basis, some future application trends of (1E,3E)-1,4-dinitro-1,3-butadiene have been proposed.