Benzyl Methyl Ether Research Articles

Intramolecular Hydrogen Bonding Rigidifying Flexible Bridge for Solution- and Vacuum-Processed TSCT-TADF Emitters.

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

Sustainable Electrochemical Benzylic C-H Oxidation Using MeOH as an Oxygen Source.

New methods and strategies for the direct oxidation of benzylic C-H bonds are highly desirable, owing to the importance of ketone motifs in significant organic transformations and the synthesis of valuable molecules, including pharmaceuticals, pesticides, and fine chemicals. Herein, we describe an electrochemical benzylic C-H oxidation strategy for the synthesis of ketones using MeOH as an oxygen source. Inexpensive and safe KBr serves as both an electrolyte and a bromide radical precursor in the reaction. This transformation also offers several advantages such as mild conditions, broad functional group tolerance, and operational simplicity. Mechanistic investigations by control experiments, radical scavenging experiments, electron paramagnetic resonance (EPR), kinetic studies, cyclic voltammetry (CV), and in-situ Fourier transform infrared (FTIR) spectroscopy support a pathway involving the formation and transformation of benzyl methyl ether via hydrogen atom transfer (HAT) and single-electron transfer (SET). The practical application of our strategy is highlighted by the successful synthesis of five pharmaceuticals, namely lenperone, melperone, diphenhydramine, cinnarizine, and flunarizine.

Selective C-H Bond Cleavage with a High-Spin FeIV-Oxido Complex.

Non-heme Fe monooxygenases activate C-H bonds using intermediates with high-spin FeIV-oxido centers. To mimic these sites, a new tripodal ligand [pop]3- was prepared that contains three phosphoryl amido groups that are capable of stabilizing metal centers in high oxidation states. The ligand was used to generate [FeIVpop(O)]-, a new FeIV-oxido complex with an S = 2 spin ground state. Spectroscopic measurements, which included low-temperature absorption and electron paramagnetic resonance spectroscopy, supported the assignment of a high-spin FeIV center. The complex showed reactivity with benzyl alcohol as the external substrate but not with related compounds (e.g., ethyl benzene and benzyl methyl ether), suggesting the possibility that hydrogen bonding interaction(s) between the substrate and [FeIVpop(O)]- was necessary for reactivity. These results exemplify the potential role of the secondary coordination sphere in metal-mediated processes.

Spectroscopic and Theoretical Studies on Conformational Stability of Benzyl Methyl Ether.

Conformer-selected electronic and vibrational spectra of benzyl methyl ether and its terminal methyl group-substituted derivative in a supersonic jet have been measured using ultraviolet (UV)-UV hole burning and fluorescence-detected infrared spectroscopy to investigate the conformational stability of flexible molecules. Various quantum chemical calculations as well as experimental observations reveal the coexistence of three conformers with different CCOC dihedral angles and side-chain orientations relative to the benzene ring plane. Vibrational analysis in the excited state with time-dependent density functional theory and IR simulations containing anharmonic coupling sufficiently reproduce the experimental results, suggesting that these three conformers can be distinguished into one gauche-conformer and two trans-ones with respect to the CCOC dihedral angle. We also observe that the gauche conformer exhibits higher-frequency CH2 modes. The natural bond orbital analysis indicates that this phenomenon is attributed to the electron delocalization from the non-bonding orbitals and the C-O orbitals associated with the neighboring oxygen atom, which leads to a conformer dependence of the methylene C-H bond strength.

Update to RIFM fragrance ingredient safety assessment, benzyl methyl ether, CAS Registry Number 538-86-3.

• Benzyl methyl ether; a safety assessment based on RIFM's criteria. • A safety assessment based on 7 human health endpoints plus environmental. • All endpoints were cleared using target data, read-across, and/or TTC.

Metal-Free Hyper-Cross-Linked Polymers from Benzyl Methyl Ethers: A Route to Polymerization Catalyst Recycling

New routes to porous materials can help lower production costs, improve sustainability, and broaden design options. Here, we use a selection of organic acids as catalysts in the synthesis of organic hyper-cross-linked polymers from benzyl methyl ether compounds. This approach provides a new route to metal-free porous organic polymers and addresses one of the largest setbacks of hyper-cross-linked polymers by allowing the simple recovery and recycling of a nonmetallic catalyst. By use of p-toluenesulfonic acid, a solid at room temperature, catalyst recovery rates of >80% were easily achieved. The catalyst was then reused as recovered in the further production of hyper-cross-linked polymers. Three rounds of catalyst recycling are demonstrated on two different aromatic systems, with no apparent detriment to the chemical or textural properties of the resulting networks.

Network pharmacology study on the mechanism of Qiangzhifang in the treatment of panic disorder.

BackgroundPanic disorder (PD) is a kind of mental illness characterized by the symptom of recurring panic attacks. Qiangzhifang (QZF) is a novel decoction developed by Professor Zhaojun Yan based on a unique system of syndrome differentiation and clinical experience. It has achieved remarkable results after long-term clinical practice, but its mechanism of action is still unclear. This study aims to use network pharmacology and molecular docking to explore the mechanism of QZF in the treatment of PD.MethodsWe used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a literature search, and Encyclopedia of Traditional Chinese Medicine (ETCM) to find active ingredients and targets of QZF. We searched for PD targets in GeneCards, Online Mendelian Inheritance in Man (OMIM), the Comparative Toxicogenomics Database (CTD), and DrugBank. We established a PD target database, constructed a protein-protein interaction (PPI) network, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis in order to screen possible pathways of action and analyze the mechanism.ResultsThis study identified 84 effective components of QZF, 691 potential targets, 357 PD targets, and 97 intersectional targets. Enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that QZF was associated with 118 biological processes (BPs), 18 cellular components (CCs), 35 molecular functions (MFs) [false discovery rate (FDR) <0.01], and 62 pathways (FDR <0.01). QZF mainly acts on its targets AKT1, FOS, and APP through active ingredients such as quercetin, β-sitosterol, 4-(4'-hydroxybenzyloxy)benzyl methyl ether, harmine, 1,7-dimethoxyxanthone, and 1-hydroxy-3,7-dimethoxyxanthone to regulate serotonin, gamma-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and other signal pathways to treat PD.ConclusionsThrough network pharmacology and molecular docking technology, we predicted the possible mechanism of QZF in the treatment of PD, revealed the interaction targets and potential value of QZF, and provided a basis for its clinical application.

Molecular characterization of primary humic-like substances in fine smoke particles by thermochemolysis–gas chromatography–mass spectrometry

In this study, the molecular structures of primary humic-like substances (HULIS) in fine smoke particles emitted from the combustion of biomass materials (including rice straw, corn straw, and pine branches) and coal, and atmospheric HULIS were determined by off-line tetramethylammonium hydroxide thermochemolysis coupled with gas chromatography and mass spectrometry (TMAH-GC/MS). A total of 89 pyrolysates were identified by the thermochemolysis of primary and atmospheric HULIS. The main groups were polysaccharide derivatives, N-containing compounds, lignin derivatives, aromatic acid methyl ester, aliphatic acid methyl ester, and diterpenoid derivatives. Both the type and distribution of pyrolysates among primary HULIS were comparable to those in atmospheric HULIS. This indicates that primary HULIS from combustion processes are important contributors to atmospheric HULIS. Some distinct differences were also observed. The aromatic compounds, including lignin derivatives and aromatic acid methyl ester, were the major pyrolysates (53.0%–84.9%) in all HULIS fractions, suggesting that primary HULIS significantly contributed aromatic structures to atmospheric HULIS. In addition, primary HULIS from biomass burning (BB) contained a relatively high abundance of lignin and polysaccharide derivatives, which is consistent with the large amounts of lignin and cellulose structures contained in biomass materials. Aliphatic acid methyl ester and benzyl methyl ether were prominent pyrolysates in atmospheric HULIS. Moreover, some molecular markers of specific sources were obtained from the thermochemolysis of primary and atmospheric HULIS. For example, polysaccharide derivatives, pyridine and pyrrole derivatives, and lignin derivatives can be used as tracers of fresh HULIS emitted from BB. Diterpenoid derivatives are important markers of HULIS from pine wood combustion sources. Finally, the differences in pyrolysate types and the distributions between primary and atmospheric HULIS suggested that the primary HULIS would undergo many atmospheric processes to reconstruct the macromolecular organic matter in atmospheric aerosols.

Benzyl methyl ether production from benzyl alcohol and methanol in carbonic water

Synthesis of benzyl methyl ether from benzyl alcohol and methanol in high-temperature carbonic water was studied in a batch reactor. Benzyl methyl ether formation was not observed by reacting benzyl alcohol with only methanol under supercritical conditions at 573K. On the other hand, benzyl methyl ether was formed by the treatment of benzyl alcohol in an aqueous methanol solution at 573K. 12% of benzyl methyl ether yield was obtained in aqueous methanol solution (methanol to water molar ratio of 0.025mol/0.11mol) at 573K in 60min and the yield enhanced to 33% by the addition of 18MPa of carbon dioxide to the aqueous solution. As the etherification is an acid catalyzed reaction, the protons derived from the dissociation of water molecules could be responsible for the etherification of benzyl alcohol in an aqueous methanol solution at 573K. The enhancement of benzyl methyl ether yield by the addition of carbon dioxide in aqueous methanol solution is caused by the increase of the number of protons derived from carbonic acid, which is formed in high-temperature liquid water under high-pressured carbon dioxide.

A Mild and Ligand-Free Ni-Catalyzed Silylation via C-OMe Cleavage.

Metal-catalyzed transformations that forge carbon-heteroatom bonds are of central importance in organic synthesis. Despite the formidable potential of aryl methyl ethers as coupling partners, the scarcity of metal-catalyzed C-heteroatom bond formations via C-OMe cleavage is striking, with isolated precedents requiring specialized, yet expensive, ligands, high temperatures, and π-extended backbones. We report an unprecedented catalytic ipso-silylation of aryl methyl ethers under mild conditions and without recourse to external ligands. The method is distinguished by its wide scope, which includes the use of benzyl methyl ethers, vinyl methyl ethers, and unbiased anisole derivatives, thus representing a significant step forward for designing new C-heteroatom bond formations via C-OMe scission. Applications of this transformation in orthogonal silylation techniques as well as in further derivatizations are also described. Preliminary mechanistic experiments suggest the intermediacy of Ni(0)-ate complexes, leaving some doubt that a canonical catalytic cycle consisting of an initial oxidative addition of the C-OMe bond to Ni(0) species comes into play.

ChemInform Abstract: Diisobutylaluminum Hydride‐Promoted Cyclization of Benzyl and Phenylsilyl Ethers Bearing a 2‐(Trimethylsilyl)ethynyl Group: Syntheses of Indenes and Benzosiloles.

Abstract The reaction of o -[2-(trimethylsilyl)ethynyl]benzyl methyl ethers with diisobutylaluminum hydride (DIBAL-H) gave 2-(trimethylsilyl)indenes in good yields. This cyclization proceeds by regio- and stereoselective hydroalumination of the alkyne moiety followed by intramolecular nucleophilic substitution. o -[2-(Trimethylsilyl)ethynyl]phenylsilyl methyl ethers also underwent the DIBAL-H promoted-cyclization to be converted into 2-(trimethylsilyl)benzosiloles in good yields. This approach provides straightforward and efficient way to construct benzosiloles from readily available organosilanes.

Diisobutylaluminum hydride-promoted cyclization of benzyl and phenylsilyl ethers bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes and benzosiloles

The reaction of o-[2-(trimethylsilyl)ethynyl]benzyl methyl ethers with diisobutylaluminum hydride (DIBAL-H) gave 2-(trimethylsilyl)indenes in good yields. This cyclization proceeds by regio- and stereoselective hydroalumination of the alkyne moiety followed by intramolecular nucleophilic substitution. o-[2-(Trimethylsilyl)ethynyl]phenylsilyl methyl ethers also underwent the DIBAL-H promoted-cyclization to be converted into 2-(trimethylsilyl)benzosiloles in good yields. This approach provides straightforward and efficient way to construct benzosiloles from readily available organosilanes.

ChemInform Abstract: 1,3‐Dicyclohexylimidazol‐2‐ylidene as a Superior Ligand for the Nickel‐Catalyzed Cross‐Couplings of Aryl and Benzyl Methyl Ethers with Organoboron Reagents.

AbstractThe developed reaction system is inapplicable to secondary benzylic ethers other than 2‐[methoxy(phenyl)methyl]naphthalene (IX).

1,3-Dicyclohexylimidazol-2-ylidene as a superior ligand for the nickel-catalyzed cross-couplings of aryl and benzyl methyl ethers with organoboron reagents.

A new catalytic system has been developed involving the use of Ni(cod)2 in conjunction with 1,3-dicyclohexylimidazol-2-ylidene for the cross-coupling of aryl and benzyl methyl ethers with organoboron reagents. This method not only allows for the use of readily available methyl ethers as halide surrogates but also provides a functional group tolerant method for the late-stage derivatization of complex molecules.

ChemInform Abstract: Chemoselective and Direct Functionalization of Methyl Benzyl Ethers and Unsymmetrical Dibenzyl Ethers by Using Iron Trichloride.

AbstractFor the first time azidation, alkynylation, and cyanation with methoxy and benzyloxy functionalities as leaving groups is presented using FeCl3 as inexpensive catalyst.

QM/MM Study for the Reaction Mechanisms of Benzyl Alcohol with Dimethyl Carbonate over a Faujasite Zeolite Catalyst

Benzyl methyl ether (BME) compounds are largely synthesized by the industry for use as a starting material for the synthesis of other organic compounds. In order to achieve the target of green chemistry, BME can be synthesized from benzyl alcohol and dimethyl carbonate (DMC) using a zeolite catalyst. DMC is a non toxic compound and a good methylating and carboxymethylating agent. The methylation and carboxymethylation reactions of benzyl alcohol over a 36T extended framework was investigated by ONIOM(HF/3-21g:UFF). Two pathways for the methylation reaction were found, where the first involving two transition states (TS) and the second only a single TS. Methylation via the two-TS pathway has a lower activation energy compared to the single-transition state pathway. Also, the methylation reaction is kinetically more favorable than the carboxymethylation reaction and this finding agrees well with the previous experimental results. The rate constant for the studied reactions were calculated by using the transition state theory and the rate determining step was determined.

Chemoselective and Direct Functionalization of Methyl Benzyl Ethers and Unsymmetrical Dibenzyl Ethers by Using Iron Trichloride

Methyl and benzyl ethers are widely utilized as protected alcohols due to their chemical stability, such as the low reactivity of the methoxy and benzyloxy groups as leaving groups under nucleophilic conditions. We have established the direct azidation of chemically stable methyl and benzyl ethers derived from secondary and tertiary benzyl alcohols. The present azidation chemoselectively proceeds at the secondary or tertiary benzylic positions of methyl benzyl ethers or unsymmetrical dibenzyl ethers and is also applicable to direct allylation, alkynylation, and cyanation reactions, as well as the azidation. The present methodologies provide not only a novel chemoselectivity but also the advantage of shortened synthetic steps, due to the direct process without the deprotection of the methyl and benzyl ethers.

Trends in electron–ion dissociative recombination of benzene analogs with functional group substitutions: Positive Hammett σpara constants

An in-depth study of the effects of functional group substitution on benzene's electron–ion dissociative recombination (e-IDR) rate constants has been conducted. The e-IDR rate constants for nitrobenzene, benzonitrile, acetophenone, benzyl methyl ether, and phenyl isothiocyanate have been measured using a flowing afterglow equipped with an electrostatic Langmuir probe (FALP). A trend has been indicated between the associated positive Hammett σpara constant for each functional group substitution and the e-IDR rate constants for the protonated form of the benzene analog. Such a plot has indicated that protonated benzene analogs which have functional groups substitutions with a positive Hammett σpara constant value have approximately the same e-IDR rate constant of 4.6×10−7cm3s−1. Implications of the observed trends to the predictions of e-IDR rate constants for unmeasured benzene analogs are discussed.

ChemInform Abstract: Antimony(V) Chloride as an Efficient Reagent for Deprotection of Methyl Ethers.

This paper proposes a new and efficient method for the deprotection of methyl ethers using antimony pentachloride at ambient temperature. The procedure described here is a facile and practical method for the removal of the methyl group from aryl and benzyl methyl ethers. High selectivity was observed for the removal of the methyl group from dimethoxyarenes. The notable advantages of this protocol are mild reaction conditions, high yields, and the ­facility of workup procedure. The mechanism of the ether cleavage is proposed to explain this new reaction.

Antimony(V) Chloride as an Efficient Reagent for Deprotection of Methyl Ethers

This paper proposes a new and efficient method for the deprotection of methyl ethers using antimony pentachloride at ambient temperature. The procedure described here is a facile and practical method for the removal of the methyl group from aryl and benzyl methyl ethers. High selectivity was observed for the removal of the methyl group from dimethoxyarenes. The notable advantages of this protocol are mild reaction conditions, high yields, and the ­facility of workup procedure. The mechanism of the ether cleavage is proposed to explain this new reaction.