Anhydrous Diethyl Ether Research Articles

Synthesis of Pyrrolizinone and Pyrrolizino[1,2-a]pyrrolizin-5-one Skeletons Starting From Pyrrole through a Single-Step and Catalyst-Free Approach

Abstract1H-Pyrrole reacted with lactone-type 2,3-furandione derivatives in anhydrous diethyl ether at room temperature to give a series of derivatives of pyrrolizinone (which is among the most important alkaloid skeletons) in a single step without a catalyst. Pyrrolizinone derivatives with a variety of substituents, such as phenyl, substituted phenyl, thienyl, trifluoromethyl, naphthyl, biphenylyl, ester, or oxalate, were obtained. The reaction of an equimolar amount of pyrrole gave pyrrolizinones, whereas an excess of pyrrole gave pyrrolizino[1,2-a]pyrrolizin-5-ones containing a skeleton that had not previously been reported. The purified molecules were obtained in yields of up to 91%. One cyclization process was carried out on a gram scale, yielding 0.952 g (71%) of the corresponding product.

Callus of East Indian sandalwood co-cultured with fungus Colletotrichum gloeosporioides accumulates santalenes and bisabolene

The inducible accumulation of desired products via in vitro cultures provides an experimental system for researching secondary metabolism in woody plants. This system is convenient, because environmental conditions can be strictly controlled. This is particularly important for East Indian sandalwood (Santalum album L.), a tree with desired sandal oil products that are restricted to the heartwood. In this study, we established a method to induce and proliferate callus from sandalwood shoot explants. Thidiazuron (TDZ) (0.2–1.5 mg/l) could induce the formation of callus, which proliferated rapidly within a month following three successive subcultures in liquid shake culture on Murashige and Skoog (MS) basal medium supplemented with 0.8–1.0-mg/l TDZ. Callus cultured in this liquid medium for 7 days was co-cultured with fungi, either Colletotrichum gloeosporioides or Penidiella kurandae. Gas chromatography–mass spectrometry (GC–MS) analysis of the solvent extract by chemical anhydrous diethyl ether of callus co-cultured with C. gloeosporioides showed the presence of santalenes and bisabolene, which are the precursors of santalol. However, another fungus, P. kurandae, could not induce santalenes or bisabolene. This study provides an opportunity to further studies on the santalene and bisabolene biosynthetic signaling pathway and the fungal endophyte–plant interaction in sandalwood.

Effect of Citrus reticulata Blanco Essential Oil on Cryptolestes ferrugineus (Stephens) Adults

The rusty grain beetle, Cryptolestes ferrugineus (Stephens), is a major insect pest of stored products worldwide. In an effort to manage populations of C. ferrugineus in stored grains, the essential oil from Citrus reticulata Blanco peel was prepared by the Soxhlet method with anhydrous diethyl ether, and its contact activity, repellent activity, and fumigant activity were investigated against C. ferrugineus adults. C. reticulata peel essential oil had potent contact, repellent, and fumigant activity against C. ferrugineus adults, with activity significantly increasing with increasing exposure dosage during the same exposure time. Percent repellency values achieved >80.0% after 60 h of exposure. For contact toxicity, the corrected mortality of C. ferrugineus adults reached >99.0% after 48 h of exposure at the dosage of 2.0 μL/cm2. For fumigant toxicity, the corrected mortality of C. ferrugineus adults reached 89.0 and 100.0% at the dosages of 40 and 80 μL/L of air, respectively. These results suggest that the C. reticulata peel essential oil has strong potential for managing populations of C. ferrugineus in practice.

Potassium tert-Butoxide-Catalyzed Dehydrogenative Cross-Coupling of Heteroarenes with Hydrosilanes

A. 1-Methyl-2-(triethylsilyl)-1H-indole (2). An oven-dried 100-mL round-bottom Schlenk flask is equipped with a Teflon-coated magnetic stir bar (25 x 8 mm) and capped with a rubber septum (Note 1). The side arm of the flask is connected to Schlenk line and the flask is cooled to room temperature under vacuum and back-filled with nitrogen. Potassium tert-butoxide (1.34 g, 12.0 mmol, 0.2 equiv) is added to the flask under positive nitrogen flow (Notes 2 and 3), and then the flask is evacuated and back-filled with nitrogen three times. N-Methylindole (7.48 mL, 7.86 g, 60.0 mmol, 1.0 equiv) and triethylsilane (28.6 mL, 20.82 g, 179.5 mmol, 3.0 equiv) are added sequentially via syringe through the septum, resulting in a yellow heterogeneous mixture (Figure 1). After the septum is replaced with a glass stopper (Note 4), the reaction mixture is degassed (Note 5) and stirred at 45 oC for 76 h (Note 6), resulting in a dark purple solution. The heating bath is removed and the reaction mixture is allowed to cool to ambient temperature (~25 oC), then anhydrous diethyl ether (30 mL) is added slowly while stirring (Note 7).

Phenylboronic acid based polymeric micelles for mucoadhesive anterior segment ocular drug delivery.

Event Abstract Back to Event Phenylboronic acid based polymeric micelles for mucoadhesive anterior segment ocular drug delivery. Ben Muirhead1, Graeme Prosperi-Porta2 and Heather Sheardown1 1 McMaster University, Biomedical Engineering, Canada 2 University of Calgary, Cumming School of Medicine, Canada Introduction: Despite poor performance, topical drops are by far the most widely used therapy for many ocular diseases. Static barriers including tight junctions of the conjunctiva, the hydrophobic corneal epithelium and hydrophilic corneal stroma, and dynamic barriers including the rapid tear turnover, lacrimal drainage, and the vasculature and lymphatics of the conjunctiva all conspire to prevent the majority of topically applied therapeutics from reaching their site of action. Only 5% of topically administered drug reaches the anterior structures of the eye, while less than 1% reach the posterior[1]. Consequently, drugs delivered via eye drop are massively overdosed, resulting in undesirable systemic exposure and extreme waste (>99% for many glaucoma medications). We propose the use of mucoadhesive self-assembling micelles as a solution to the obvious problems facing topical ocular drug delivery. Phenylboronic acid (PBA) is a synthetic molecule with a strong affinity for mucin due to its ability to complex with 1,2-cis-diols. PBA has an extensive pedigree in biomedical engineering, including as part of an ocular delivery scheme for cyclosporine A (CycA)[2]. Thus, a series of block copolymer micelles incorporating mucoadhesive PBA into their outer shells was developed capable of targeted drug delivery to ocular tissues. Method and Materials: pLA-b-p(MAA-PBA) copolymers were synthesized by RAFT polymerization and contained a spectrum of PBA mole percentages. The resultant copolymer was isolated by precipitation into 10 times excess of cold anhydrous diethyl ether and further purified by repeated precipitation into diethyl ether from tetrahydrofuran two additional times. Copolymer composition and molecular weight were determined using proton nuclear magnetic resonance. Micelles were formed by precipitation into purified water from acetone. Micelle size was determined using dynamic light scattering. Mucoadhesion was determined using Surface Plasmon Resonance with bovine mucin and simulated tear fluid. CycA release from micelles was determined using high performance liquid chromatography (HPLC). Results: DLS determined the diameter and polydispersity (PDI) of the micelles. Micelle diameter is dependent on the PBA content in the micelle corona and ranges from 35nm to 65nm in diameter as the mole percentage of PBA is increased from 0% to 30%. The PDI in all cases was acceptable, with a maximum value of 0.29. CycA was entrapped within the LMP micelles by dissolving both components in acetone followed by addition into purified water at a ratio of 20 mg copolymer to 3 mg CycA. All micelles showed entrapment efficiencies greater than 99.8% and excellent release characteristics. SPR showed an unambiguous relationship between the molde percentage of PBA and mucoadhesion. After a standard battery of cell viability testing which showed no adverse reaction using human corneal epithelial cells, these micelles were tested in vivo using Sprague-Dawley rats by dropping their eyes for a period of 10 days, showing excellent biocompatibility. Conclusions: Mucoadhesive micelles offer significant potential to increase the efficacy of topically applied ophthalmic drugs by decrease the dosage, frequency of dose, and off-target systemic toxicity. We have synthesized a series of poly(L-lactide)-b-poly(methacrylic acid-co-phenylboronic acid) copolymer micelles with varying amounts of phenylboronic acid which show excellent mucoadhesivity, drug release characteristics, and biocompatibility.

Adducts of ruthenium(IV) thiolates with substituted pyridines. Syntheses and structures of [Ru(SMes)4(R-py)] (R = 4-Et, 4-tBu, and 3,5-Me2) and [{Ru(SMes)4}2(μ-4,4’-bipy)] (Mes = 2,4,6-trimethylphenyl)

Treatment of the trigonal-bipyramidal ruthenium(IV)–thiolate complex, [Ru(SMes)4(MeCN)] (Mes = 2,4,6-trimethylphenyl, 1), with an anhydrous diethyl ether solution of hydrogen chloride in THF afforded [Ru(SMes)3Cl(MeCN)] (2), whereas interaction of 1 with [Et4N]Cl in THF gave an anionic ruthenium(IV)–thiolate complex, [Et4N][Ru(SMes)4Cl] (3). Reaction of 1 with one equivalent of substituted pyridines in dichloromethane gave the corresponding pyridine-coordinated ruthenium(IV)–thiolate complexes, [Ru(SMes)4(R-py)] (R = 4-Et, 4; 4-tBu, 5; 3,5-Me2, 6), while reaction of 1 with 0.5 equiv. of 4,4’-bipy (4,4’-bipy = 4,4’-bipyridine) in dichloromethane resulted in the formation of a dinuclear ruthenium(IV)–thiolate complex [{Ru(SMes)4}2(μ-4,4’-bipy)] (7). Complexes 2–7 have been spectroscopically characterized along with their electrochemical analyses, and their structures have been determined by single-crystal X-ray diffraction.

Six-coordinate NbF5 and TaF5 complexes with tertiary mono-phosphine and -arsine ligands

The syntheses of the extremely moisture sensitive, neutral [MF5(PR3)] (M = Nb or Ta, R = Me or Ph) and [MF5(AsR′3)] (R′ = Me or Et), from reaction of the ligands with MF5 in anhydrous diethyl ether solution are reported. Attempts to isolate analogous complexes with SbMe3 were unsuccessful. The products are characterised by IR and mutinuclear NMR (1H, 19F{1H}, 31P{1H} and 93Nb) spectroscopic studies. These are the first examples of six-coordinate phosphine or arsine complexes of the Group 5 pentafluorides. The ionic species, trans-[MF4(PMe3)2][MF6], are obtained from diethyl ether solution of [MF5(PMe3)] containing excess PMe3 and similarly characterised. All complexes are extremely moisture and oxygen sensitive and decomposed by many common solvents. In solution in toluene the [MF5(PMe3)] (M = Nb or Ta) and [MF5(AsR′3)] are extensively dissociated at ambient temperatures. The [MF5(PPh3)] dissolve in CH2Cl2 with decomposition to form [PPh3H][MF6]. Attempts to isolate phosphine complexes of NbOF3 were unsuccessful.

Repellent and fumigant activity of Alpinia officinarum rhizome extract against Tribolium castaneum (Herbst)

The plant extract was prepared by Soxhlet method with anhydrous diethyl ether from Alpinia officinarum rhizome, a traditional Chinese herbal plant, and its repellent and fumigant activity was investigated against Tribolium castaneum (Herbst) adults. The A. officinarumrhizome extract had potent repellent activity against T. castaneum adults with over 80% repellency values at the tested concentration (A. officinarum extract: acetone = 1:10, v/v) during 48 h of exposure time. A. officinarum rhizome extract exhibited strong fumigant activity in a dosage-dependent manner against T. castaneum adults with 75% mortality at a dosage of 80 µl/l air after 48 h exposure. These naturally occurring plant extracts could be useful for managing populations of T. castaneum. Key words: Alpinia officinarum rhizome extract, Tribolium castaneum (Herbst), fumigant activity, repellent activity, plant extract.

A Liquid–Liquid Biphasic Homogeneous Organocatalytic Aldol Protocol Based on the Use of a Silica Gel Bound Multilayered Ionic Liquid Phase

AbstractAn innovative two stage liquid–liquid biphasic homogeneous protocol for the asymmetric organocatalytic aldol reaction is proposed, based on the use of the cis‐ion‐tagged proline 8 dissolved in the liquid film of a multilayered ionic liquid covalently bonded to silica gel 4. The resulting catalytically active material 9 is first soaked with cyclohexanone in the presence of water, resulting in a semi‐transparent gel, then the aldehyde is added and the mixture stirred at RT. In the first stage, 4 acts as a catalyst reservoir that delivers 8 to the cyclohexanone phase allowing the reaction to take place homogeneously. In the second stage, cyclohexanone is removed under vacuum and the resulting slurry is extracted with anhydrous diethylether. Now 4 acts as a catalyst sponge, redissolving 8. Product extraction is extremely selective; no trace of catalyst is detected in the product‐containing phase, and 9 can be easily reused several times with high cumulative productivity values (up to 523).

Vanadium(IV) tetrachloride catalyzed oxidative homo-coupling of aryl lithium under mild reaction condition

A novel efficient strategy to prepare symmetrical diaryls via VCl4 catalyzed homo-coupling of aryl lithium has been developed. In which, organometallic reagent n-BuLi was applied as the strong base to form aryl lithium from aryl halogen in anhydrous diethyl ether, then it was followed by the addition of catalytic amount of VCl4 at room temperature to afford diaryls. All the diaryls have been characterized by 1H and 13C NMR.

Structural complex of sterol 14α-demethylase (CYP51) with 14α-methylenecyclopropyl-Δ7-24, 25-dihydrolanosterol

Sterol 14α-demethylase (CYP51) that catalyzes the removal of the 14α-methyl group from the sterol nucleus is an essential enzyme in sterol biosynthesis, a primary target for clinical and agricultural antifungal azoles and an emerging target for antitrypanosomal chemotherapy. Here, we present the crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate analog 14α-methylenecyclopropyl-Δ7-24,25-dihydrolanosterol (MCP). This sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs, but it has a much stronger, mechanism-based inhibitory effect on I105-containing (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the conserved CYP51 binding cavity, the complex specifies the roles of the contact amino acid residues and sheds new light on CYP51 substrate specificity. It also provides an explanation for the effect of MCP on T. cruzi CYP51. Comparison with the ligand-free and azole-bound structures supports the notion of structural rigidity as the characteristic feature of the CYP51 substrate binding cavity, confirming the enzyme as an excellent candidate for structure-directed design of new drugs, including mechanism-based substrate analog inhibitors.

The Bioactivitiy of Essential Oil from <i>Ailanthus altissima</i> Swingle (Sapindales: Simaroubaceae) Bark on <i>Lasioderma serricorne</i>（Fabricius) (Coleoptera: Anobiidae)

The essential oil was extracted by Soxhlet method with anhydrous diethyl ether from Ailanthus altissima Swingle (Sapindales: Simaroubaceae) bark, a traditional Chinese herbal plant, and its repellent and its fumigant activity was investigated against Lasioderma serricorne （Fabricius）(Coleoptera: Anobiidae) adults. A. altissima bark oil had extremely strong repellent activity against L. serricorne adults with the percentage repellency 93.7, 87.8 and 76.1% after 24, 48, and 72 h exposure, respectively. A. altissima bark oil also possessed high fumigant activity against L. serricorne adults with the corrected percentage mortality 100% at 8 µL/L air within 48 h exposure.

Synthesis of 2-methyl-2-(3-phenoxybenzoyloxy)propionitrile

2-Methyl-2-(3-phenoxybenzoyloxy)propionitrile was obtained by the reaction of the 3-phenoxybenzoic acid chloride with acetone cyanohydrine in the anhydrous diethyl ether in the presence of triethylamine as the hydrogen chloride acceptor: The synthesis was performed at room temperature (20–25°С) under stirring for 1 h using the 3-phenoxybenzoic acid chloride–acetone cyanohydrine–triethylamine in a molar ratio 1:1.2:1.2.

Determination of Nimodipine in Human Plasma by HPLC-ESI-MS and Its Application to a Bioequivalence Study

A simple, specific, and precise liquid chromatographic-electrospray ionization mass spectrometric (LC-ESI-MS) method has been developed for determination of nimodipine concentration in human plasma. The method involves the addition of 200 microL of saturated sodium bicarbonate (NaHCO(3)) solution to plasma to improve the extraction recovery, liquid-liquid extraction of nimodipine from plasma samples with anhydrous diethyl ether, simple reversed-phase chromatography, and ESI mass spectrometric detection in negative ion selected ion monitoring mode (SIM) using target [M-] ions at m/z 417 and m/z 359 for nimodipine and nitrendipine (internal standard, IS), respectively. A complete analytical run was achieved within 3.5 min. The limit of quantification was 0.5 ng/mL. The method was validated within a linear range of 0.5-100 ng/mL. The correlation coefficient for the calibration regression line was 0.9995 or better. Intra- and inter-batch accuracy and precision were acceptable. Analyte was stable in a battery of stability studies. The method has been successfully used in a bioequivalence study.

Syntheses and Structures of Binaphthyl-bridged Schiff Bases

Abstract The reaction of dinaphthofuran with lithium in anhydrous diethyl ether led to a solution of the corresponding C,O-dilithiated intermediate which, upon treatment with DMF at −78°C, afforded, after hydrolysis, 2′-hydroxy-1,1′-binaphthyl-2-carbaldehyde in a good yield. Then binaphthyl-bridged Schiff bases were prepared by the condensation of 2′-hydroxy-1,1′-binaphthyl-2-carbaldehyde with the corresponding aromatic amines.

Synthesis and Structures of 1,1′‐Dinaphthopyrans.

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1-(2-ethoxy-2-oxoethyl)-5-methyl-1H-pyrazole-3-ethyl carboxylate

A mixture of 1 (6g; 39mmol) and potassium tert-butoxide (4.62g; 41.3mmol) in 120ml of anhydrous diethyl ether was refluxed for 75min.[...]

1-(2-ethoxy-2-oxoethyl)-5-methyl-1H-pyrazole-3-methyl carboxylate

A mixture of 1 (2g; 14.3mmol) and potassium tert-butoxide (1.68g; 15mmol) in 80ml of anhydrous diethyl ether was refluxed for 75min.[...]

A General Synthetic Route to Dibenzospiropyrans and Dinaphthospiropyrans from Dibenzofuran and Dinaphthofuran

The reaction of dibenzofuran or dinaphthofuran with lithium in anhydrous diethyl ether led to a solution of the corresponding C,O-dilithiated intermediate which, upon treatment with 1,3,3-trimethylindolin-2-one or different coumarin derivatives at -78 °C, afforded, after hydrolysis, dibenzospiropyrans and dinaphthospiropyrans in good yields. The structures of all new compounds were determined by single crystal X-ray analysis.

Synthesis and Structures of 1,1′-Dinaphthopyrans

The reaction of dinaphthofuran with lithium in anhydrous diethyl ether led to a solution of the corresponding C,O-di-lithiated intermediate which, upon treatment with a range of ketones or aldehydes at -78 °C afforded, after hydrolysis and dehydration, 1,1′-dinaphthopyrans in good yields. The reaction proceeds through reductive ring-opening and cyclization and an intermediate diol was isolated.