Alkoxy Research Articles

Synthesis of 1,3-Dibromopyrene as Precursor of 1-, 3-, 6-, and 8-Substituted Long-Axially Symmetric Pyrene Derivatives.

Pyrene derivatives bearing substituents at positions 1, 3, 6, and 8 find numerous applications, as exemplified by their use in lasers, sensors, and bioimaging probes. However, these derivatives typically have point-symmetric or short-axially symmetric structures, whereas long-axially symmetric derivatives remain underexplored because of the difficulty in obtaining their precursor, 1,3-dibromopyrene. To address this problem, we herein synthesized 1,3-dibromopyrene from 1-methoxypyrene in an overall yield (71 % over four steps) considerably exceeding those of existing methods. 1,3-Dibromopyrene was converted into 13OPA, a long-axially symmetric pyrene dye with electron-donor (alkoxy) groups at positions 1 and 3 and electron-acceptor (formyl) groups at positions 6 and 8. 13OPA exhibited photophysical properties distinct from those of its point-symmetric and short-axially symmetric isomers, featuring a broad and strongly redshifted absorption, strong fluorescence with reduced sensitivity to protic solvents, and small dipole moment change upon photoexcitation. The derivatization of 13OPA into a Schiff base and its functionalization via Lewis acid-base pairing were also demonstrated. Thus, our work expands the design scope of pyrene-based molecules, particularly those used as emitters.

Synthesis of liquid crystalline compounds containing thiol groups at both ends as reactive substituents and their immobilization on a gold substrate

In this study, we synthesized four bifunctional compounds containing two alkoxy groups, at which reactive thiol groups were introduced. Among these compounds, a compound with four and five methylene units in each alkyl chain did not exhibit a liquid crystalline phase. The other three compounds exhibit one or two liquid crystalline phases, and the number of liquid crystalline phases depends on the number of methylene units in their alkyl chains. These liquid crystalline compounds were oriented in one direction using a rubbed alignment film, and the oriented compounds were transferred onto a gold substrate. Using these gold substrates as working electrodes, cyclic voltammetry (CV) was performed with potassium ferricyanide as the redox probe. As the deposition time increased, the current intensities of a pair of redox waves gradually decreased. This trend suggests that with longer deposition times, a larger amount of the liquid crystalline compound was transferred to the gold substrate surface. These findings shed light on the relationship among the structures of bifunctional compounds, their liquid crystalline behavior, and their alignment properties on gold substrates, thereby offering valuable insights for potential applications in nanotechnology and materials science.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Nickel‐Catalyzed Branch Selective C‐H Alkylation of Indoles and Azoles with Alkenes: An Additive‐ and Solvent‐Free Approach

The development of sustainable protocols for the synthesis of alkylated heteroarenes is crucial owing to their widespread existence in medicinally relevant and bioactive natural products. Herein, we describe an efficient, additive‐ and solvent‐free approach for the regioselective C−H alkylation of indoles and azoles with alkenes using a nickel catalyst, which proceeds through a chelation‐assistance strategy. The reaction exclusively provided branched alkylated products with the compatibility of alkyl, alkoxy, fluoro, trifluoromethyl, alkene, cyano, ester, and carbonyl groups. This protocol is applicable to other heteroarenes, such as imidazoles and benzimidazoles, providing the desired alkylated products with exclusive Markovnikov selectivity. The synthetic utility and scale‐up of the reaction are demonstrated, and the protocol is in concord with the principles of green chemistry. Alkylation proceeds through facile and reversible C−H nickelation and alkene insertion processes, presumably involving rate‐limiting reductive elimination.

A highly crystalline face-on π-conjugated polymer based on alkoxythiophene-flanked benzobisthiazole for organic photovoltaics

The use of noncovalent intramolecular interactions constitutes a powerful design strategy for preparing π-conjugated polymers featuring high backbone coplanarities and thereby high crystallinities. Herein, we report the design and synthesis of an alkoxythiophene-flanked benzobisthiazole (BBTz) as a new building unit for π-conjugated polymers, which was subsequently copolymerized to give a simple BBTz-bithiophene copolymer with alkyl and alkoxy groups (PDBTz2). Owing to the S···O noncovalent intramolecular interactions between the alkoxy oxygens and thiazole sulfurs in BBTz, PDBTz2 showed greater coplanarity and crystallinity than its alkyl counterpart, PDBTz1. Interestingly, the backbone orientation was completely altered from the edge-on orientation observed for PDBTz1 to a face-on orientation for PDBTz2, which is preferable for organic photovoltaics (OPVs). In addition, the electron-donating nature of the alkoxy group increased the HOMO energy level of PDBTz2 compared to that of PDBTz1, which enabled photoinduced hole transfer from a nonfullerene acceptor, Y6, to the polymer. As a result, the short-circuit current density of an organic photovoltaic cell based on PDBTz2 and Y6 was significantly greater than that of a cell based on PDBTz1 and Y6. This study confirmed that alkoxythiophene-flanked BBTz is a promising building unit for high-performance π-conjugated polymers.

Treatment of Organophosphorus Poisoning with 6-Alkoxypyridin-3-ol Quinone Methide Precursors: Resurrection of Methylphosphonate-Aged Acetylcholinesterase.

Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.2 min, so immediate recovery (resurrection) of OP-aged AChE is needed. In 2018, we showed pyridin-3-ol-based quinone methide precursors (QMPs) can resurrect OP-aged electric eel AChE in vitro, achieving 2% resurrection after 24 h of incubation (pH 7, 4 mM). We prepared 50 unique 6-alkoxypyridin-3-ol QMPs with 10 alkoxy groups and five amine leaving groups to improve AChE resurrection. These compounds are predicted in silico to cross the blood-brain barrier and treat AChE in the central nervous system. This library resurrected 7.9% activity of OP-aged recombinant human AChE after 24 h at 250 μM, a 4-fold increase from our 2018 report. The best QMP (1b), with a 6-methoxypyridin-3-ol core and a diethylamine leaving group, recovered 20.8% (1 mM), 34% (4 mM), and 42.5% (predicted maximum) of methylphosphonate-aged AChE activity over 24 h. Seven QMPs recovered activity from AChE aged with Soman and a VX degradation product (EA-2192). We hypothesize that QMPs form the quinone methide (QM) to realkylate the phosphylated serine residue as the first step of resurrection. We calculated thermodynamic energetics for QM formation, but there was no trend with the experimental biochemical data. Molecular docking studies revealed that QMP binding to OP-aged AChE is not the determining factor for the observed biochemical trends; thus, QM formation may be enzyme-mediated.

Nematogenic homologous series of coumarin derivatives containing azomethine-ester linkages: synthesis, characterisation, photophysical and mesomorphic properties

ABSTRACT Novel Homologous series of coumarin based Schiff’s base derivatives derived from 4’-formyl phenyl 7-n-alkoxycoumarin-3-carboxylate and 4-n-(decyloxy)aniline have been synthesised. The proposed structures of all the newly prepared compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and elemental analysis. The photophysical properties of the coumarin based Schiff’s base derivatives have been studied. The textures of coumarin based Schiff’s base derivatives and their transition temperature were observed and recorded under a polarising optical microscope. The enthalpy change data were measured using Differential Scanning Calorimetry. By varying the alkoxy group (n = 1–10, 12, 14, 16) at the terminal position at one end of the moiety, the nematic phase was observed on heating as well as cooling. The thermal stability of all the compounds was recorded using thermal gravimetry analysis.

Alkoxylated Fluoranthene-Fused [3.3.3]Propellanes: Facile Film Formation against High π-Core Content.

Solid-state assembling modes are as crucial as the chemical structures of single molecules for real applications. In this work, solid-state structures and phase-transition temperatures are investigated for a series of fluoranthene-fused [3.3.3]propellanes consisting of a rigid three-dimensional (3D) π-core and varying lengths of alkoxy groups. Compounds in this series with n-butoxy or longer alkoxy groups take an amorphous state at room temperature. In these molecules, rotatable biaryl-type bonds are not incorporated and high D3h molecular symmetry is retained. Therefore, π-fused [3.3.3]propellanes present a unique platform for amorphous molecular materials with low ratios of flexible alkoxy atoms to rigid π-core ones.

Ligand-Induced Intramolecular Redox Diversity in Titanium Complexes with Acenaphthene-1,2-diimine.

A series of the chlorido and alkoxychlorido titanium complexes of the general formula (dpp-Bian)Ti(OiPr)nCl3-n, where dpp-Bian = 1,2-bis[(2,6-iPr2C6H3)imino]acenaphthene n = 0 (2), 1 (3), 2 (4), as well as (dpp-Bian)Ti(OiPr)2 (5) and (dpp-Bian)Ti(OiPr)Cl3 (3-Cl), were isolated and characterized using single-crystal X-ray diffraction analysis and spectroscopic studies combined with density functional theory (DFT) calculations. In the solid state, compounds 2-4 reveal a square-pyramidal geometry at the metal center supported with monoanionic dpp-Bian, whereas 3-Cl with a neutral diimine ligand and 5 bearing a dianionic enebisamide dpp-Bian show, respectively, an octahedral and tetrahedral coordination surrounding the metal ion. Paramagnetic complexes 2-4 exhibit electron paramagnetic resonance spectra in both toluene solution and solid state, confirming the transfer of spin density from the metal ion to the dpp-Bian ligand as the number of alkoxy groups increases. The increase in polarity of the Ti-N bonds in the row 2 < 3 < 4 contributes to enhanced stability of the metal complexes with respect to O-donor molecules. Thus, in tetrahydrofuran (THF), compounds 2 and 3 undergo reversible solvolysis, whereas complex 4 is stable. The charge and spin density distributions as well as molecular orbital energies in 2-4 were analyzed on the basis of DFT calculations which also provided information on the electronic transition energies, absorption band assignments, and thermodynamic parameters of the reactions between the complexes and THF.

Polymer-Metal Bilayer with Alkoxy Groups for Antibacterial Improvement.

Many bio-applicable materials, medical devices, and prosthetics combine both polymer and metal components to benefit from their complementary properties. This goal is normally achieved by their mechanical bonding or casting only. Here, we report an alternative easy method for the chemical grafting of a polymer on the surfaces of a metal or metal alloys using alkoxy amine salt as a coupling agent. The surface morphology of the created composites was studied by various microscopy methods, and their surface area and porosity were determined by adsorption/desorption nitrogen isotherms. The surface chemical composition was also examined by various spectroscopy techniques and electrokinetic analysis. The distribution of elements on the surface was determined, and the successful bonding of the metal/alloys on one side with the polymer on the other by alkoxy amine was confirmed. The composites show significantly increased hydrophilicity, reliable chemical stability of the bonding, even interaction with solvent for thirty cycles, and up to 95% less bacterial adhesion for the modified samples in comparison with pristine samples, i.e., characteristics that are promising for their application in the biomedical field, such as for implants, prosthetics, etc. All this uses universal, two-step procedures with minimal use of energy and the possibility of production on a mass scale.

Tuning Fluorescence and Singlet Oxygen Quantum Yields of Subporphyrazines by Axial Functionalization.

The axial functionalization of Subporphyrazines (SubPzs) with unreported alkoxy groups, carboxy and carboperoxy rests, as well as sulfanyl, aryl and amino groups, forming B-O, B-S, B-C, and B-N bonds, respectively, has been investigated. The studied oxygen nucleophiles include aromatic and sterically demanding aliphatic alcohols, along with carboxylic acids and peracids. In general, direct substitution of the chloro-SubPz by oxygen nucleophiles of diverse nature proceeds smoothly, with yields of the isolated alkoxy and carboxy-substituted SubPzs ranging from 49 to 100 %. Conversely, direct substitution with sulphur, carbon and nitrogen nucleophiles do not afford the corresponding substituted SubPzs. In these cases, a stepwise procedure involving an axial triflate-SubPz intermediate was employed, affording only the phenyl-SubPz in 8 % yield. The major compound under these conditions was the unreported SubPz μ-oxo dimer, presumably arising from substitution of the triflate-SubPz by the in situ generated hydroxy-SubPz. This result indicates a quite low reactivity of the TfO-SubPz intermediate with carbon, sulphur and nitrogen nucleophiles. All SubPzs prepared in this work exhibited fluorescence at 510-515 nm with quantum yields ranging from 0.1 to 0.24. Additionally, all SubPzs generated singlet oxygen, with ΦΔ values ranging from 0.15 to 0.57, which show no apparent correlation with the axial substituents.

Benzimidazolium quaternary ammonium salts: synthesis, single crystal and Hirshfeld surface exploration supported by theoretical analysis.

Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea.

Alkoxy-Functionalized Hydroxamate/Zinc Metal-Organic Frameworks and the Effects of Substituents and Acid Addition on Their Structures.

Single crystals of alkoxy-functionalized hydroxamate/zinc metal-organic frameworks (MOFs) were obtained by fixating the hydroxamate moiety via intramolecular hydrogen bonding. The resulting MOF structures depend on the steric demand of the alkoxy groups, whereby the incorporation of bulky isopropyl groups affords porous hydroxamate/zinc MOFs. The topological structures of the isopropyl-substituted MOFs could be controlled by adding acid.

Catalytic synthesis of β-lactam derivatives by carbonylative cycloaddition of acylsilanes with imines via a palladium Fischer-carbene intermediate

AbstractFischer-type carbene complexes are characterized by the presence of a π-donating group, such as an alkoxy group on the carbene carbon. Despite the notable progress that has been made in synthetic methods that involve the use of Fischer-type carbene complexes, stoichiometric amounts of carbene complexes are still required for such reactions and catalytic variants remain elusive. This limitation primarily stems from the lack of suitable carbene precursors, which is in sharp contrast to the fact that carbene complexes bearing an electron-withdrawing group can be readily generated from the corresponding diazo esters. Here we report that acylsilanes can function as a precursor for a Fischer-carbene complex by the action of a palladium catalyst. This system can be used in catalytic carbonylative cycloaddition reactions with imines to form densely substituted β-lactam derivatives. A key siloxycarbene–palladium intermediate complex was isolated and successfully characterized by X-ray crystallography.

Structural evolution and redox chemistry of robust ternary layered oxide cathode for sodium-ion batteries

Nickel/manganese-based O3-type layered oxides have been widely deemed to be a family of promising cathode materials for sodium-ion batteries (SIBs) owing to the large theoretical specific capacity and low manufacturing cost, but being usually challenged by unsatisfied electrochemical performance. In this study, a novel ternary layered oxide NaNi1/2Mn1/4Ti1/4O2 is reported as a robust high-capacity cathode for SIBs, and its structural evolution and redox chemistry in the potential range of 1.5–4.2 V (vs Na+/Na) are carefully explored by coupling X-ray diffraction technique, X-ray photoelectron spectroscopy, transmission electron microscope, FTIR spectroscopy, and galvanostatic measurement. Experimental facts reveal that the material undergoes multiple structural phase evolutions involving two solid-solution regions and one two-phase region based on the redox chemistry of Ni2+/Ni3+ and Ni3+/Ni4+ couples. It exhibits excellent electrochemical performance with a high reversible capacity of 145.2 mAh g−1 and an impressive capacity retention of 85.1% after 100 cycles due to the unique structure with robust ternary composition and stable coating interface. The coating interface is mainly related with formation of the amorphous carbonate layer at preparation step and the CEI film containing alkoxy group during the first charge. In addition, initial Na extraction from the material suffers from a “potential jump” phenomenon owing to severe electrochemical polarization caused by large interfacial impedance and charge-transfer impedance. This work provides new insights on interfacial change, structural evolution and redox reaction of high-capacity O3-type layered oxide cathode during Na extraction/insertion.

Tuning the Structure of 4‐Aminopyridine Catalysts for Improved Activity and Selectivity in Functionalization of Alcohols

AbstractSeeking to improve the site selectivity in the catalytic phosphorylation and acylation of a model amphiphilic substrate, further increasing the preference for the apolar domain, which we recently disclosed, we attempted to augment the nucleophilicity of the 4‐aminopyridine core unit used in our catalysts, while simultaneously preserving or even increasing the density of their lipophilic outer‐sphere components. Of the three approaches to the new catalyst design, the most promising, in the case of phosphorylation, was that placing two benzyl moieties, substituted with long apolar alkoxy groups in the ortho positions, on the amine nitrogen of the core. This modification also substantially improved the activity of the catalyst in both reactions. Although this approach reduced the selectivity in the acylation reaction, we demonstrated that by altering the geometry of the benzyl substituents (e. g., by restricting the degree of their freedom), the higher selectivity can be regained.

Microflow Synthesis of Unsymmetrical H-Phosphonates via Sequential and Direct Substitution of Chlorine Atoms in Phosphorus Trichloride with Alkoxy Groups.

Unsymmetrical H-phosphonates were synthesized by a rapid (<15 s) and mild (20 °C) process in a microflow reactor as the first example of the sequential direct substitution of the chlorine atoms in PCl3 with alkoxyl/aryloxy groups using equivalent amounts of PCl3 and alcohols. The optimal base concentration differed in each step, presumably attributed to differences in the Brønsted basicity of the electrophilic intermediates. Phosphite hydrolysis was observed, and the structure-hydrolysis relationship was quantitatively evaluated.

Palladium-catalyzed electrochemical C(sp3)-H acetoxylation of alcohol derivatives with an exo-directing group.

Palladium-catalyzed electrochemical C(sp3)-H acetoxylation to prepare 1,2-diol derivatives was achieved using oxime ethers as exo-directing groups. Various substrates containing alkoxy groups with a methyl branch at the α-position as well as norbornan-2-ol derivative were acetoxylated only using a catalytic amount of Pd(OAc)2 along with NaOAc/Ac2O/AcOH under anodic oxidation conditions.

Synthesis, Insecticidal Activities, and Structure-Activity Relationship Studies of Novel Diamide Compounds Containing (Halogenated) Alkoxy Group

Synthesis, Insecticidal Activities, and Structure-Activity Relationship Studies of Novel Diamide Compounds Containing (Halogenated) Alkoxy Group

Electrophilic aromatic substitution of electron-rich arenes with N-fluorobenzenesulfonimide (NFSI) as an electrophile.

An efficient amidation of electron-rich arenes using NFSI as a nitrogen source has been successfully disclosed. This amidation process can be easily conducted at elevated temperatures, without the need for catalysts or additives. A wide range of arenes substituted with hydroxy, alkoxy, or carbonyl groups were found to be compatible, yielding the desired amination products. Computational study shows that the amidation proceeds via an electrophilic aromatic substitution pathway, comprising a three-step process that includes substitution, addition, and elimination, which differs slightly from the classical mechanism.