Cyclic Ethers Research Articles

Extraction and Physicochemical Characterization of Pectin from Noni (Morinda citrifolia) Fruit

Noni (Morinda citrifolia) is a popular plant in Asian countries and has great potential as pectin source for thickening agents in food products. In general, ethanol has been widely used to precipitate pectin, but the proportion can affect the quality of the product. Therefore, this study aimed to characterize the physicochemical properties of pectin from noni fruit. Extraction was performed using 0.1 N HCl at pH 1.5 and heated at 80°C for 15 min, followed by precipitation with different proportions of 96% ethanol including A (1:1), B (1:2), and C (1:3) v/v, while commercial orange pectin was used as a reference. The results showed that all pectin extracted belonged to the high methoxyl category. The FTIR spectra confirmed the presence of important functional groups including OH-hydroxyl, CH3-saturated aliphatic methyl, C=O carbonyl, and -O- cyclic ether. Furthermore, the crystalline and amorphous structures of noni pectin were confirmed by X-ray diffraction observation. The highest yield was achieved using the proportion of 1:3, followed by 1:2, and 1:1 on a wet basis. The MeO and AUA content of sample B (1:2) were relatively similar to those of the reference. Based on extraction results, noni possesses good characteristics and has the potential for commercial pectin production.

Tuning Molecular Packing and Boosting Self-Assembling Properties via Ring Fusion Strategy in Naphthalimide-Based A-D-A Conjugated Systems.

Two fully fused acceptor-donor-acceptor (A-D-A) architecture conjugated derivatives (NPF and NCF) comprising an electron-withdrawing naphthalimide (NMI) and two different electron-donating cores, phenanthrene and carbazole, respectively, were conveniently synthesized by bismuth(III)-catalyzed selective cyclization of vinyl ethers. Compared with their corresponding single bond-linked A-D-A molecules NPS and NCS, both having a moderately twisted aromatic configuration, the ring fusion strategy leads to fully coplanar conjugated skeletons and greatly changes the electronic structures, photophysical properties, self-assembling behaviors, and molecular packing motifs. In particular, the naphthalimide/carbazole derivative NCF exhibits intriguing 2D brickwork packing and significantly enhanced self-assembling properties.

Electrochemical Deconstructive and Ring-Expansion Functionalization of Unstrained Cycloalkanols.

An efficient and sustainable electrochemical method for the synthesis of cyclic ethers and acyclic aldehydes from alkanols has been reported. This strategy has been successfully applied to cycloalkanols bearing different ring sizes and different types of nucleophiles. In addition, mechanistic investigations show that the reactions undergo sequential processes, including anodic oxidation, β-scission, and nucleophilic addition. This method provides a new synthetic approach to constructing cyclic ethers and terminal aldehydes from cycloalkanols and nucleophiles.

Copper‐Catalyzed Alkenylation and Alkenyloxylation with‐Alkenyl(phenyl)iodonium Salts

AbstractA Cu‐catalyzed vinylation method for alkenyl ethers has been developed. In this strategy, both chain and cyclic alkenyl ether substrates were applicable, and the target products were obtained in up to 95% yields and with the E/Z selectivities of >98:2. Furthermore, we have successfully applied this method to directly vinylate the C‐2 position of protected glucals, offering a valuable tool for their functionalization. Moreover, through the utilization of alkenyl alcohols as substrates, we accomplished a 1,2‐alkenyloxylation of alkenyl double bond, enabling the synthesis of functionalized cyclic ether compounds with five or six‐membered rings.

Blue- and Red-Shifting C-H⋯O Hydrogen Bonds of Cyclic Ethers with Haloforms: Effect of Ring-Size and Consistency with Bent's Rule.

A DFT-based computational study is carried out to delve into the interplay between hyperconjugation and rehybridization effects underlying the formation of blue- or red-shifting H-bonds (HBs) in 1 : 1 complexes of cyclic ethers (HB acceptor) of varying ring-size with haloforms, CHF3 and CHCl3 (HB donor). The calculations reveal that with decreasing angular strain (increasing ring-size) of the cyclic ethers, the extent of blue-shift increases for 1 : 1 complexes with CHF3, while a reverse sequence is observed with CHCl3, eventually leading to a red-shifting HB in the oxepane : CHCl3 complex. It is noted that the trend in the shift of C-H stretching fundamental is not mirrored by the C-H bond length or interaction energies for both the systems studied, that is, the low sensitivity of the changes on the strain on the O-atom of HB acceptor (cyclic ethers) is to be emphasized.

Kinetic Computation of Cyclization Reactions of Large Keto-Hydroperoxide Radicals in Low Temperature Combustion.

The cyclization reactions of keto-hydroperoxide (KHP) radicals leading to the formation of keto cyclic ethers and OH radicals play an important role in low temperature combustion for hydrocarbon fuels or oxygenated hydrocarbon fuels. However, due to the lack of kinetic data of cyclization reactions of KHP radicals, researchers often derive high-pressure-limit rate constants of cyclization reactions of KHP radicals from analogous cyclization reactions of hydroperoxyl alkyl radicals during construction of the combustion mechanism. This study aims to systematically investigate the kinetics of cyclization reactions of KHP radicals involving short-to-large-sized radicals. The studied reactions are divided into 7 reaction classes, according to the size of the cyclic transition state, the conjugative effect (whether KHP radicals are resonance-stabilized or not), and the position of the carbonyl group (whether the carbonyl group is inside or outside of the reaction center). The isodesmic reaction method, in conjunction with transition state theory, is utilized for each reaction class to compute the energy barriers and high-pressure-limit rate constants at the DFT level. The study revealed that energy barriers calculated at the DFT level with correction by the isodesmic reaction method are close to the results from the benchmark CCSD(T) method. To develop more accurate rate rules, these reaction classes are further divided into subclasses based on the relative site of the OOH group with the carbonyl group, the type of carbon atoms where the OOH group is located, and the type of carbon atoms where the radical site is located. For each subclass, high-pressure-limit rate rules are derived by averaging the rate constants of reactions in the subclass, and it is found that the maximum absolute deviation of the energy barrier and the ratio of the largest rate constant to the smallest rate constant among reactions in each subclass are within chemical accuracy limits, indicating acceptable use of the developed rate rules. A comparison of the rate constants for cyclization reactions of KHP radicals with the values of analogous cyclization reactions of hydroperoxyalkyl radicals as provided in reported mechanisms is made. Additionally, a comparison is drawn between our developed rate rules for subclasses of the cyclization reactions of KHP radicals and the rate rules for analogous subclasses of cyclization reactions of hydroperoxyl alkyl radicals. These comparisons demonstrate significant differences and highlight the necessity for improved rate rules for cyclization reactions of KHP radicals to enhance the automatically generated combustion mechanisms for hydrocarbon and oxygenated hydrocarbon fuels.

L-PTMI-co-L-PEI copolymers obtained through copolymerization of cyclic imino ethers and their chain modification: Antibacterial properties and cytotoxicity

Polymeric antimicrobial agents are intensively investigated as potential novel antibiotics. In this work we use copolymerization of 2-propyl-2-oxazine (PrOzi) and 2-methyl-2-oxazoline (MeOx) combined with hydrolysis of the polymer side chains as a tool to obtain various linear polymeric derivatives of polytrimethylenimines (L-PTMI) and polyethylenimine (L-PEI). To obtain well-defined polymers, initially we determined copolymerization rates, and subsequently, we investigated the hydrolytic rates of various repeating units, namely PrOzi, MeOx, and 2-methyl-2-oxazine (MeOzi) in both homo- and copolymers. We observed that the structure of the polymeric main chain significantly influences the rate of acidic hydrolysis. In particular, the protonated L–PEI repeating unit (r.u.) accelerates the hydrolytic cleavage of the amide bond more than the protonated L-PTMI r.u., due to the shorter distance between amine centers.The biological activity of the polymers was assessed against three model microorganisms, namely Escherichia coli, Staphylococcus aureus and Candida albicans, and benchmarked in toxicity test against human lung fibroblast cell line. The antibacterial activity of L-PTMI-co-L–PEI increases monotonically with the increasing content of PTMI r.u., indicating an additive effect of covalently bonded L-PTMI and L-PEI. The antimicrobial activity of the copolymers is almost identical to that of the tested polymer blends in the corresponding ratios.The introduction of up to 40 % of PrOzi r.u. into the polyamine structure of PTMI (PPrOzi–co-L-PTMI copolymer) does not decrease the antimicrobial activity, compared to L–PTMI. The molecule remains active, particularly against Staphylococcus aureus (MIC = 4 μg/mL). At the same time, the presence of amide r.u. reduces toxicity. The highest observable selectivity index can reach values as high as 20 (PPrOzi40%–co-L-PTMI60%).

Synthesis of Macrolactone Core of ent-Formosalide A via Regioselective Ether Cyclization.

Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate Prorocentrum sp, whose structure is characterized by functionalized 5- and 6-membered ether rings embedded in the macrolactone and an all cis-tetraene side chain. Here, we report the synthesis of the macrolactone core of ent-formosalide A. Our approach is highlighted by the Au-mediated 6-exo-dig cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner. Control experiments demonstrated that the acyclic protecting group of the C9,C10-diol was crucial for the desired 6-exo-dig cyclization. Theoretical studies were performed focusing on structural component analysis, which suggested that the C8-C9-C10-C11 dihedral angle induced by the protecting group controlled the regioselectivity. An additional 6 steps including Shiina macrolactone formation from the 6-membered ether ring completed the synthesis of the macrolactone core of ent-formosalide A.

Ring‐opening (co)polymerization strategies of selected oxacyclic monomers to control and provide tailored polymers with desired properties

AbstractRing‐opening polymerization (ROP) is a versatile synthetic method used to produce polymers from cyclic monomers, particularly oxacyclic monomers such as lactones and cyclic ethers. Oxacyclic monomers polymerize with anionic or cationic initiators. For selected monomers, such as glycidol, β‐butyrolactone and higher lactones, methods, and mechanisms of polymerization are presented, the understanding of which has allowed control of these processes. The use of appropriate polymerization techniques and methods, as well as conducting the copolymerization, mainly block copolymerization, makes it possible to control the architecture, molar mass, and end groups of the resulting polymers. These parameters determine the properties of macromolecules, such as solubility, ability to aggregate in aqueous solutions, thermoresponsiveness, and degradability. By carefully selecting monomers, catalysts, and polymerization conditions, ROP strategies can be tailored to produce polymers with precise molecular structures and desired properties for a wide range of applications. This review mainly focuses on precisely controlled syntheses that lead to well‐defined macromolecules consisting mostly of polyether and/or polyester chains.

Revealing the nitrogen migration mechanism during pyrolysis and steam gasification of biomass: A combined ReaxFF MD and DFT study

The biomass pyrolysis/gasification technology takes advantages of high efficiency and carbon neutrality, which is promising for high value-added products fabrication. However, biomass possesses relatively high amount of N especially for seaweeds and municipal sludge wastes, and the lack of N migration mechanism has resulted in emission of N-containing pollutants and limited its industrial application. In this work, a simulation investigation combining reactive force field molecular dynamic and density functional theory calculations was performed to study the conversion mechanisms of N-containing species in the pyrolysis/gasification of biomass processes. The glutamic acid and cellulose were selected as the model compounds of N-containing and typical compositions of biomass, respectively, and six models containing multiple mass ratios of glutamic acid to cellulose and steam to feedstock were constructed. The results show that the majority of nitrogen in the original model is converted towards NH3-N (62%) during glutamic acid pyrolysis by direct cleavage, hydrogen capture, deamination, and decarboxylation. The presence of cellulose effectively inhibits the decomposition of NH3 at high temperature range, thereby increasing the yield of NH3-N (up to 70%) and restraining the conversion of nitrogen into mesomolecules. The introduction of H2O provides a substantial amount of •H radicals, which facilitates the conversion of nitrogen into NH3-N. During DFT calculations, eight reaction pathways for the formation of N-containing products were proposed on the basis of distribution of pyrolysis products. The glutamic acid cleavage reaction achieves the lowest energy barrier, and the deamination of glutamic acid towards a ternary cyclic ether is found to be the most feasible pathway for the NH3 production. This work can provide theoretical support for nitrogen pollutants mitigation during pyrolysis and steam gasification of biomass processes.

Evaluation of oxidation stability for palm biodiesel with additives using Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography

This paper discusses the potential of tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA) and alpha-tocopherol (α-T) in preventing palm biodiesel oxidation over an extended storage period of twelve weeks. A combination of Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) analyses were carried out. The FTIR spectra showed no significant changes to the carbonyl band at 1740 cm−1 across the storage period for fuels with additives, but the control had increased band intensity, which implied that additives prevented the formation of byproducts which have carbonyl groups or cyclic ether rings. From GC-MS analyses, lower transmittance at C18 methyl esters region was evident of methyl oleate, methyl linoleate and methyl linolenate being consumed to the point where their concentrations dropped below those of methyl palmitate in the sample without additives. Furthermore, the analyses indicated that 3-octyl-oxiraneoctanoic acid ME, E−10,13,13-trimethyl-11-tetradecen-1-ol acetate and 17-octadecynoic acid ME were the major oxidation byproducts. Traces of acetal, carboxylic acid, oxirane and alkylnoic acid were also detected. It was shown through HPLC analyses that TBHQ, BHA and α-T were consumed with α-T samples having the highest consumption compared to TBHQ and BHA. Overall, the findings supported the important role of additives in stabilizing the fuel and preventing oxidation during extended storage.

A Fully Methylated Cyclic Ether Solvent Enables Graphite Anode Cycling at Low Temperatures.

Graphite anode suffers from great capacity loss and larger cell polarization under low-temperature conditions in lithium-ion batteries (LIBs), which are mainly caused by the high energy barrier for the Li+ desolvation process and sluggish Li+ transfer rate across the solid electrolyte interface (SEI). Regulating an electrolyte with an anion-dominated solvation structure could synchronously stabilize the interface and boost the reaction kinetics of the graphite anode. Herein, a highly ionic conductive electrolyte consisting of a fully methylated cyclic ether solvent of 2,2,4,4,5,5-hexamethyl-1,3-dioxolane (HMD) and fluoroethylene carbonate (FEC) cosolvent was designed. The high electron-donating effect and steric hindrance of -(CH3)2 in HMD endow the HMD-based electrolyte with high ionic conductivity but lower coordination numbers with Li+, and an anion-dominated solvation structure was formed. Such configuration can accelerate the desolvation process and induce the forming of a LiF-rich SEI film on the anode, avoiding the solvent coembedding into graphite and enhancing the ion migration rate under low temperatures. The assembled Li||graphite cell with the tame electrolyte outperformed the conventional carbonates-based cell, showing 93.8% capacity retention after 227 cycles for the DF-based cell compared to 64.7% after 150 cycles. It also exhibited a prolonged cycle life for 200 rounds with 81% capacity retention under -20 °C. Therefore, this work offers a valuable thought for solvent design and provides approaches to electrolyte design for low-temperature LIBs.

Fluorinated Cyclic Ether Diluent for High-Voltage Lithium Metal Batteries

Fluorinated Cyclic Ether Diluent for High-Voltage Lithium Metal Batteries

Reaction Pattern and Mechanistic Aspects of Iodine and Iodine-Based Reagents in Selenylation of Aliphatic, Aromatic, and (Hetero)Cyclic Systems.

Organoselenium compounds have been the subject of extensive research since the discovery of the biologically active compound ebselen. Ebselen has recently been found to show activity against the main protease of the virus responsible for COVID-19. Other organoselenium compounds are also well-known for their diverse biological activities, with such compounds exhibiting interesting physical properties relevant to the fields of electronics, materials, and polymer chemistry. In addition, the incorporation of selenium into various organic molecules has garnered significant attention due to the potential of selenium to enhance the biological activity of these molecules, particularly in conjunction with bioactive heterocycles. Iodine and iodine-based reagents play a prominent role in the synthesis of organoselenium compounds, being valued for their cost-effectiveness, non-toxicity, and ease of handling. These reagents efficiently selenylate a broad range of organic substrates, encompassing alkenes, alkynes, and cyclic, aromatic, and heterocyclic molecules. They serve as catalysts, additives, inducers, and oxidizing agents, facilitating the introduction of different functional groups at alternate positions in the molecules, thereby allowing for regioselective and stereoselective approaches. Specific iodine reagents and their combinations can be tailored to follow the desired reaction pathways. Here, we present a comprehensive review of the progress in the selenylation of organic molecules using iodine reagents over the past decade, with a focus on reaction patterns, solvent effects, heating, microwave, and ultrasonic conditions. Detailed discussions on mechanistic aspects, such as electrophilic, nucleophilic, radical, electrochemical, and ring expansion reactions via selenylation, multiselenylation, and difunctionalization, are included. The review also highlights the formation of various cyclic, heterocyclic, and heteroarenes resulting from the in situ generation of selenium intermediates, encompassing cyclic ketones, cyclic ethers, cyclic lactones, selenophenes, chromones, pyrazolines, pyrrolidines, piperidines, indolines, oxazolines, isooxazolines, lactones, dihydrofurans, and isoxazolidines. To enhance the reader's interest, the review is structured into different sections covering the selenylation of aliphatic sp2/sp carbon and cyclic sp2 carbon, and then is further subdivided into various heterocyclic molecules.

Enhanced performance of lithium metal batteries via cyclic fluorinated ether based electrolytes

To address the challenges associated with applying high-voltage cathodes in lithium metal batteries (LMBs) there is a need for new electrolytes enabling stable interphases at both electrodes. Here we attack this by using a dioxolane-derived cyclic fluorinated ether, 2,2-bis(trifluoromethyl)-1,3-dioxolane (BTFD), as a fluorinated diluent to a 1,2-dimethoxyethane (DME) based electrolyte. The cells using the resulting BTFD-based electrolytes exhibit higher Coulombic efficiencies for lithium stripping and plating as compared to those using the non-fluorinated ether-based electrolyte. This originates from the reduced formation of ‘dead Li’ at the anode, as shown by using electrochemical impedance spectroscopy (EIS). In practice, the BTFD-based electrolytes are shown to improve the performance of Li||NMC cells, which is due to the formation of a predominantly inorganic cathode electrolyte interphase (CEI) that suppresses the cathode degradation during cycling. We used X-ray photoelectron spectroscopy (XPS) and scanning transmission electron microscopy (STEM) to characterize the CEIs’ overall composition and structure. To obtain more details on the CEI speciation, Raman and nuclear magnetic resonance (NMR) spectroscopies were employed, assisted by molecular level computations. Overall, we demonstrate how the very design of the electrolyte composition influences the performance of LMBs.

Expanded Azahelicenes with Large Dissymmetry Factors.

Expanded azahelicenes, as heteroanalogues of helically chiral helicenes, hold significant potential for chiroptical materials. Nevertheless, their investigation and research have remained largely unexplored. Herein, we present the facile synthesis of a series of expanded azahelicenes NHn (n=1-5) consisting of 11, 19, 27, 35, and 43 fused rings, mainly by Suzuki coupling followed by Bi(OTf)3-mediated cyclization of vinyl ethers. The structures of NH2, NH3 and NH4 were confirmed through X-ray crystallography analysis, and their (P)- and (M)- enantiomers were also isolated with chiral high performance liquid chromatography. The enantiomers exhibit large absorption (abs) and luminescence (lum) dissymmetry factors, with |gabs|max=0.044; |glum|max=0.003 for NH2, |gabs|max=0.048; |glum|=0.014 for NH3, and |gabs|max=0.043; |glum|max=0.021 for NH4, which are superior to their respective all-carbon analogues.

Expanded Azahelicenes with Large Dissymmetry Factors

AbstractExpanded azahelicenes, as heteroanalogues of helically chiral helicenes, hold significant potential for chiroptical materials. Nevertheless, their investigation and research have remained largely unexplored. Herein, we present the facile synthesis of a series of expanded azahelicenes NHn (n=1–5) consisting of 11, 19, 27, 35, and 43 fused rings, mainly by Suzuki coupling followed by Bi(OTf)3‐mediated cyclization of vinyl ethers. The structures of NH2, NH3 and NH4 were confirmed through X‐ray crystallography analysis, and their (P)‐ and (M)‐ enantiomers were also isolated with chiral high performance liquid chromatography. The enantiomers exhibit large absorption (abs) and luminescence (lum) dissymmetry factors, with |gabs|max=0.044; |glum|max=0.003 for NH2, |gabs|max=0.048; |glum|=0.014 for NH3, and |gabs|max=0.043; |glum|max=0.021 for NH4, which are superior to their respective all‐carbon analogues.

Mechanism-Based Macrocyclic Inhibitors of Serine Proteases.

Protease inhibitor drug discovery is challenged by the lack of cellular and oral permeability, selectivity, metabolic stability, and rapid clearance of peptides. Here, we describe the rational design, synthesis, and evaluation of peptidomimetic side-chain-cyclized macrocycles which we converted into covalent serine protease inhibitors with the addition of an electrophilic ketone warhead. We have identified potent and selective inhibitors of TMPRSS2, matriptase, hepsin, and HGFA and demonstrated their improved protease selectivity, metabolic stability, and pharmacokinetic (PK) properties. We obtained an X-ray crystal structure of phenyl ether-cyclized tripeptide VD4162 (8b) bound to matriptase, revealing an unexpected binding conformation. Cyclic biphenyl ether VD5123 (11) displayed the best PK properties in mice with a half-life of 4.5 h and compound exposure beyond 24 h. These new cyclic tripeptide scaffolds can be used as easily modifiable templates providing a new strategy to overcoming the obstacles presented by linear acyclic peptides in protease inhibitor drug discovery.

Ruthenium Complexes with a Tridentate Anionic Bisfluoroalkoxy‐Carbene Ligand – Valuable Latent Olefin Metathesis Catalysts for Polymerisation Reactions

AbstractA Grubbs‐type ruthenium complex bearing a tridentate anionic bisfluoroalkoxy‐carbene was synthesised and fully characterised. Under standard conditions, it proved to be inactive in olefin metathesis reactions, but the addition of HCl triggers its activity and allows the synthesis of a series of cyclic olefins and ethers as well as a stereoregular polynorbornene with an unexpectedly high content of trans‐configured double bonds, as found in commercially available polynorbornene (Norsorex®). Detailed structural studies and DFT calculations showed that the complex enters the catalytic cycle, but instead of performing a full turnover, it is caught as a stable intermediate that does not undergo further reactions. The addition of HCl causes dissociation of the fluoroalkoxy units, resulting in a compound that behaves similarly to standard Grubbs‐type complexes. To further understand this phenomenon, the corresponding Hoveyda‐Grubbs complex was also obtained and studied in detail; due to the absence of the phosphine ligand, its behaviour was different from that of its Grubbs‐type counterpart.

Tuning the FEC‐Related Electrolyte Solvation Structures in Ether Solvents Enables High‐Performance Lithium Metal Anode

AbstractLithium metal is the most promising high‐energy‐density anode. However, it is incompatible with high‐voltage cathodes in ether solvents due to their narrow electrochemical window. Herein, fluoroethylene carbonate (FEC) co‐solvent is introduced to regulate the Li+ solvation structures in ether solvents, including cyclic ether (1,3‐dioxolane [DOL]) and linear glymes with different chain lengths (1,2‐dimethoxyethane [DME], diglyme [G2] and triglyme [G3]). The apparently different effects of ether solvents on solvation ability and interaction strength with FEC are revealed. FEC plays a diverse role and function in 1 m lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)‐ether/FEC electrolyte, thus relevant batteries perform distinct performances due to various ionic dynamics and solid‐electrolyte interphase. The Li+‐solvation structures are explored by Raman and nuclear magnetic resonance spectroscopies. Specifically, part of FEC molecules are inserted into the first solvation shell in 1 m LiTFSI‐DOL/FEC because of the weak solvation ability of DOL and strong interaction of DOL‐FEC, leading to few coordinated TFSI− and sluggish interfacial kinetics. In sharp contrast, FEC as a weak coordinated solvent almost exclusively occupies the second solvation sheath in 1 m LiTFSI‐glyme/FEC, favoring TFSI− coordination and rapid de‐solvation dynamics. Ultimately, the LiNi0.8Co0.1Mn0.1O2/Li battery in G2/FEC presents the most excellent performance, derived from abundant free‐FEC and rapid ionic kinetics.