Benzyl Methyl Ether Research Articles

Mechanism of the Deprotonation Reaction of Alkyl Benzyl Ethers withn-Butyllithium

Kinetic study of the α-lithiation of benzyl methyl ether (BME) by nBuLi has revealed that increasing the concentration of the organolithium compound does not necessarily increase the reactivity, and this is a consequence of the reactivities of the different nBuLi aggregates present in solution. We propose a dimer-based mechanism, in which a pre-complexation step is a key process for substrates bearing a donor oxygen atom that can interact with the lithium cation to form mixed dimers. For these studies, we have developed a system based on UV/Vis spectroscopy that allows kinetic measurements to be conducted at -80 °C under argon.

ChemInform Abstract: 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ)/tert‐Butyl Nitrite/Oxygen: A Versatile Catalytic Oxidation System.

A new catalytic oxidation system using catalytic amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tert-butyl nitrite with molecular oxygen serving as the environmentally benign, terminal oxidant has been developed. This aerobic catalytic system was established for the selective oxidation of non-sterically hindered benzylic alcohols and electron-rich benzyl methyl ethers, and successfully extended to an application in the oxidative deprotection of PMB ethers to the alcohols in high selectivity.

Theoretical investigation into the likely reaction mechanisms of benzyl alcohol with dimethyl carbonate over a faujasite zeolite catalyst

Benzyl methyl ether (BME) compounds are largely synthesized by the chemical 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 good methylating and carboxymethylating agent that is, in contrast to other such agents, a relatively non-toxic compound. In this study, the methylation and carboxymethylation reactions of benzyl alcohol over a 3T cluster of zeolite and a 36T extended framework was investigated by density functional theory (DFT) and the ONIOM approach, respectively. Both frameworks revealed two pathways for the methylation reaction, the first involving two transition states (TSs) and the second only a single TS. Methylation via the two-TS pathway was found to be more kinetically stable than the single-TS pathway whilst the methylation reaction is kinetically favored over the carboxymethylation reaction. The rate constants with the 36T cluster were increased 104–106 fold compared to the 3T quantum cluster.

7‐Arylnorbornanes: Model Compounds for the Study of CH···π and OH···π Interactions

AbstractPreorganised 7‐arylnorbornanes were selected as suitable model compounds for the study of CH···π and OH···π interactions. The most stable conformation of these derivatives favours such interactions by avoiding secondary hydrogen bonds between the oxygen atoms and the ortho‐H of the aryl rings in the planar conformation as well as by increasing the gauche/trans ratio for steric reasons. The rotational barriers of the studied compounds are higher when electron‐donor substituents are placed at the para position of the aryl ring. The trend of the electronic effects exerted by the substituents is in agreement with the existence of CH···π and OH···π interactions, which are favoured in electron‐rich aromatic systems. However, interestingly, DFT calculations show that the rotational barriers in these species are mainly governed by the occurrence of π(Cipso=C)→σ*(C–O) donations instead of the expected CH···π and OH···π hydrogen bonds. Both NMR and IR data support this hypothesis. Therefore, the assertion that the predominance of the gauche conformation is a proof of the presence of weak hydrogen bonds in benzyl alcohols and benzyl methyl ethers should be made with caution.

2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ)/tert‐Butyl Nitrite/Oxygen: A Versatile Catalytic Oxidation System

AbstractA new catalytic oxidation system using catalytic amounts of 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) and tert‐butyl nitrite with molecular oxygen serving as the environmentally benign, terminal oxidant has been developed. This aerobic catalytic system was established for the selective oxidation of non‐sterically hindered benzylic alcohols and electron‐rich benzyl methyl ethers, and successfully extended to an application in the oxidative deprotection of PMB ethers to the alcohols in high selectivity.

Two New Phenolic Compounds from the Rhizomes of Gastrodia elataBlume

AbstractPhytochemical investigation of the rhizomes of Gastrodia elata Blume (Orchidaceae) led to the isolation and identification of twelve compounds, including two new phenolic compounds, 4‐hydroxybenzyl vanillyl ether (=4‐{[(4‐hydroxyphenyl)methoxy]methyl}‐2‐methoxyphenol; 1) and 4‐{{4‐[4‐(methoxymethyl)phenoxy]benzyl}oxy}benzyl methyl ether (=1‐[4‐(methoxymethyl)phenoxy]‐4‐{[4‐(methoxymethyl)phenoxy]methyl}benzene; 2). The structures of 1 and 2 were elucidated by spectroscopic data analysis including 1D‐ and 2D‐NMR experiments.

Thiol‐ene clickable hyperscaffolds bearing peripheral allyl groups

AbstractRadical catalyzed thiol‐ene reaction has become a useful alternative to the Huisgen‐type click reaction as it helps to expand the variability in reaction conditions as well as the range of clickable entities. Thus, direct generation of hyperbranched polymers bearing peripheral allyl groups that could be clicked using a variety of functional thiols would be of immense value. A specifically designed AB2 type monomer, that carries two allyl benzyl ethers groups and one alcohol functionality, was shown to undergo self‐condensation under acid‐catalyzed melt‐transetherification to yield a hyperbranched polyether that carries numerous allyl end‐groups. Importantly, it was shown that the kinetics of polymerization is not dramatically affected by the change of the ether unit from previously studied methyl benzyl ether to an allyl benzyl ether. The peripheral allyl groups were readily clicked quantitatively, using a variety of thiols, to generate an hydrocarbon‐soluble octadecyl‐derivative, amphiphilic systems using 2‐mercaptoethanol and chiral amino acid (N‐benzoyl cystine) derivatized hyperbranched structures; thus demonstrating the versatility of this novel class of clickable hyperscaffolds. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Solvent-mediated fiber growth in organogels

We have investigated the decisive role of the solvent type in the gelation of an oligo(p-phenylene vinylene) molecule with OH functions on the terminal groups (OPVOH). We show that gels of “hub-like” morphology are obtained with benzyl alcohol, a solvent that mimics the chemical structure of the terminal groups, whereas a “randomly dispersed” morphology is obtained with trans-decahydronaphthalene and with benzyl methyl ether, a solvent very similar to benzyl alcohol except that the hydrogen of the OH function has been replaced by a CH3 group. Also, the thermodynamic behaviour, gel formation and gel melting are similar for benzyl methyl ether and trans-decahydronaphthalene but are significantly different in benzyl alcohol: the gel melting point is higher, and so is the melting enthalpy. Extrapolation of this parameter to 100% OPVOH gives a value significantly higher than that directly measured on pure OPVOH. Molecular organization as studied by X-ray diffraction and fluorescence properties follow the same trend. The occurrence of a molecular compound between OPVOH and benzyl alcohol is contemplated in an attempt to account for these outcomes.

Visible light flavin photo-oxidation of methylbenzenes, styrenes and phenylacetic acids

We report the photocatalytic oxidation of benzylic carbon atoms under mild conditions using riboflavin tetraacetate as photocatalyst and blue-emitting LEDs (440 nm) as light source. Oxygen is the terminal oxidant and hydrogen peroxide appears as the only byproduct in most cases. The process oxidizes toluene derivatives, stilbenes, styrenes and phenylacetic acids to their corresponding benzaldehydes. A benzyl methyl ether and acylated benzyl amines are oxidized directly to the corresponding methyl ester or benzylimides. The mechanism of the reactions has been investigated and the results indicate that oxygen addition to benzyl radicals is a key step of the oxidation process in the case of phenylacetic acids.

Exploration of New C−O Electrophiles in Cross-Coupling Reactions

Since their development in the 1970s, cross-coupling reactions catalyzed by transition metals have become one of the most important tools for constructing both carbon-carbon and carbon-heteroatom bonds. Traditionally, organohalides were widely studied and broadly used as the electrophile, both in the laboratory and in industry. Unfortunately, the high cost, environmental toxicity, and sluggish preparation often associated with aryl halides can make them undesirable for the large-scale syntheses of industrial applications. However, with the further development of catalytic systems, and particularly of the ligands contained therein, a variety of electrophiles have now been successfully applied to cross-coupling reactions. Oxygen-based electrophiles have attracted much attention due to their ready availability from phenol and carbonyl compounds. Initially, aryl and alkenyl triflates were used in cross-coupling reactions due to their high reactivity; however, low moisture stability and high cost hampered their application. Later, with the development of highly efficient catalytic systems, the less reactive sulfonates and phosphates were successfully employed in cross-coupling reactions. Although they have higher stability and can be easily prepared, low atom economy remains an obstacle to their broader utility. Our group has worked to directly apply the abundant and readily available oxygen-containing compounds, such as phenols, alcohols, ethers, and carbonyl compounds, to cross-coupling reactions. In this Account, we describe our recent efforts in transition-metal-catalyzed cross-coupling reactions of new O-based electrophiles via C-O bond activation. We began by developing the methylation of aryl methyl ethers and benzyl methyl ethers via Ni-catalyzed selective C-O bond cleavage. With the refined Ni-based catalytic system, we further applied aryl/alkenyl carboxylates and carbamates to Suzuki-Miyaura, Negishi, and Kumada-Tamao-Corriu reactions to construct various biaryl scaffolds and highly substituted alkenes. To further improve the carbon atom economy, we developed the diaryl sulfates as one-by-one electrophiles (that is, both aryl groups are used in the reaction). Most recently, we have achieved the first successful cross-coupling reaction of magnesium naphtholates with aryl Grignard reagents. These results extend aryl and benzyl ethers, aryl and alkenyl carboxylates/carbamates, and magnesium naphtholates as novel electrophiles in cross-coupling reactions. More importantly, these studies contribute to our better understanding the intrinsic nature of C-O bonds, which were traditionally considered "inert" but clearly show enormous synthetic potential with the proper catalysts.

ChemInform Abstract: An Oxidation of Benzyl Methyl Ethers with NBS that Selectively Affords Either Aromatic Aldehydes or Aromatic Methyl Esters.

AbstractIrradiation of benzylic methyl ethers in the presence of 2 equiv.

An Oxidation of Benzyl Methyl Ethers with NBS that Selectively Affords Either Aromatic Aldehydes or Aromatic Methyl Esters

Either mono- or dibromination of benzyl methyl ethers can be achieved by controlling the amount of NBS and the temperature. Elimination of methyl bromide from the monobrominated intermediates produces aromatic aldehydes, whereas hydrolysis of the dibrominated intermediates affords aromatic methyl esters in good yields.

Structural elaboration of the surprising ortho-zincation of benzyl methyl ether

Breaking with convention, the reaction of the sodium zincate, [(TMEDA)Na(mu-TMP)(mu-(t)Bu)Zn((t)Bu)] with benzyl methyl ether (PhCH(2)OMe) produces exclusively an ortho-zincated intermediate [(TMEDA)Na(mu-TMP)(mu-C(6)H(4)CH(2)OMe)Zn((t)Bu)] instead of the expected "thermodynamic" alpha-metallated product.

Probing the C−H Activation of Linear and Cyclic Ethers at (PNP)Ir

Interaction of the amido/bis(phosphine)-supported (PNP)Ir fragment with a series of linear and cyclic ethers is shown to afford, depending on substrate, products of α,α-dehydrogenation (carbenes), α,β-dehydrogenation (vinyl ethers), or decarbonylation. While carbenes are exclusively obtained from tert-amyl methyl ether, sec-butyl methyl ether (SBME), n-butyl methyl ether (NBME), and tetrahydrofuran (THF), vinyl ethers or their adducts are observed upon reaction with diethyl ether and 1,4-dioxane. Decarbonylation occurs upon interaction of (PNP)Ir with benzyl methyl ether, and a mechanism is proposed for this unusual transformation, which occurs via a series of C−H, C−O, and C−C bond cleavage events. The intermediates characterized for several of these reactions as well as the α,α-dehydrogenation of tert-butyl methyl ether (MTBE) are used to outline a reaction pathway for the generation of PNP-supported iridium(I) carbene complexes, and it is shown that the long-lived, observable intermediates are substrate-dependent and differ for the related cases of MTBE and THF. Taken together, these findings highlight the variety of pathways utilized by the electron-rich, unsaturated (PNP)Ir fragment to stabilize itself by transferring electron density to ethereal substrates through oxidative addition and/or the formation of π-acidic ligands.

Effect of alkali species on performance of MnO/γ-Al2O3 catalysts for the hydrogenation of methyl benzoate to benzaldehyde

Abstract The effect of alkali species on performance of MnO/γ-Al 2 O 3 catalysts for methyl benzoate hydrogenation was investigated in fixed-bed reactor. Doping alkali species on MnO/γ-Al 2 O 3 catalysts enhanced the selectivity of benzaldehyde significantly, toluene and benzyl methyl ether were greatly suppressed. The infrared spectra of adsorbed pyridine adsorption was acquired to study the surface acid properties, the results revealed that doping alkali species weakened the acid strength of MnO/γ-Al 2 O 3 catalysts, which lead to restrain from the formation of toluene and benzyl methyl ether.

Isolation and detection of steroids from human urine by molecularly imprinted solid-phase extraction and liquid chromatography

Naturally occurring steroids such as progesterone, testosterone and 17β-estradiol were analyzed in this study. These bio-identical molecules paradoxically can be either beneficial or harmful. Unfortunately as growth promoters can be toxic and cancerogenic at elevated levels. Due to difficulty in monitoring at trace quantities of these hormones in biological matrices specific adsorption materials molecularly imprinted polymers (MIPs) were used for preconcentration and clean up in sample preparation step. A non-covalent imprinting approach was used for bulk polymerization of progesterone, testosterone and 17β-estradiol imprinted polymers. Synthesis of MIPs was achieved by thermal, UV and γ irradiation initiated polymerization whereby were used methacrylic acid (MAA), 4-vinylpyridine (4-VP) as functional monomers, ethylene glycol dimethacrylate (EDMA), trimethylolpropane trimethacrylate (TRIM) as cross-linking agents and acetonitrile, isooctane–toluene (1:99, v/v) and chloroform as porogen solvents. It was also used as initiator 2,2′-azobis(2-methylpropionitrile) (AIBN) or benzyl methyl ether (BME). The MIPs were applied as selective sorbents in solid-phase extraction (SPE). Molecularly imprinted solid-phase extraction (MISPE) considered as hyphenated technique were applied in extraction step before HPLC-DAD analysis of steroids from human urine.

Collision‐induced loss of AgH from Ag+ adducts of alkylamines, aminocarboxylic acids and alkyl benzyl ethers leads exclusively to thermodynamically favored product ions

The loss of AgH from [M+Ag]+ precursor ions of tertiary amines, aminocarboxylic acids and aryl alkyl ethers is examined by deuterium labeling combined with collision activation (CA) dissociation experiments. It was possible to demonstrate that the AgH loss process is highly selective toward the hydride abstraction. For tertiary amines and aminocarboxylic acids, hydrogen originates from the alpha-methylene group carrying the nitrogen function (formation of an immonium ion). In all cases examined, the most stable, i.e. the thermodynamically favored product ion is formed. In the AgH loss process, a large isotope effect operates discriminating against the loss of D. The [M+Ag]+ ion of benzyl methyl ether loses a hydride ion exclusively from the benzylic methylene group supporting the experimental finding that the AgH loss reaction selectively cleaves the weakest C-H bond available.

A second generation synthesis of the cruentaren A core structure based on oxetane and oxirane opening reactions

A second generation synthesis of the core structure of the macrolactone cruentaren A, a potent FATPase inhibitor, involves the highly functionalized benzoic acid 36 and reaction of an aryl lithium intermediate with the terminal epoxide 30. A methyl benzyl ether in the aryl bromide served as a surrogate for a carboxyl function. Epoxide 30 originated from the aldol product 24. The alkyne of 30 was introduced via opening of an oxetane ring.

신화학물질 HS-1580 유도체(HS-1580 HS-1581 HS-1582)의 항염증 효과

HS-1580 series (HS-1580, HS-1581, HS-1582) can produce anti-imflammatory effects were synthesized from the marine algae extraction in 2,3,6-tribromo-4,5-dihydroxy benzyl methyl ether (TDB). Raw 264.7 cells were pre-treated with 1 μg/μl lipopolysaccharide (LPS) and later treated with HS-1580 series. These cells of inflammatory mediators were tested as well. Nitric oxide (NO) is related to autoimmune disease and is produced by inducible NOS (iNOS). When treated with HS-1580 series, the product of NO will reduce in a dose-dependent manner. HS-1580 series significantly inhibit the iNOS protein expression. Cyclooxygenase (COX) involves with the various physiologic events and catalyzes in prostaglandin. HS-1580 series also inhibit the COX-2 protein expression as well as pro-inflammatory cytokines production such as tumor necrosis factor-α (TNF-α) and interluekin-1β (IL-1β). These upcoming results suggest that HS-1580 series have anti-inflammatory effects in Raw 264.7 cells by inhibiting such as iNOS, COX-2, TNF-α and IL-1β as inflammatory mediators.

Anti-inflammatory action of phenolic compounds fromGastrodia elata root

Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The anti-inflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.