Diphenyl Ether Derivatives Research Articles

Synthesis and Herbicidal Activity of Diphenyl Ether Derivatives Containing Unsaturated Carboxylates

A series of novel diphenyl ether derivatives containing unsaturated carboxylates were designed and synthesized. Their structures were identified by (1)H nuclear magnetic resonance and elemental analyses. The bioassays indicated that the compounds 5b and 5c exhibited good herbicidal activities against velvetleaf at a concentration of 30-40 g/hm(2). The relationship between structure and herbicidal activity was also discussed. Among unsaturated carboxylates group, butenoate is the most promising one. Amonst them, 4-ethoxy-4-oxobutenyl 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitrobenzoate 5b was identified as the most promising candidate due to its high protoporphyrinogen IX oxidase inhibition effect (pI(50) = 6.64) and good herbicidal activity against broadleaf weeds with selectivity to soybean and low toxicity to mammals.

Electrochemical Study of Diphenyl Ether Derivatives Used as Herbicides

The electrochemical behaviour of five nitro diphenyl ethers used as herbicides is investigated in acetonitrile. A detailed study by cyclic voltammetry and exhaustive electrolysis is carried out for the anodic oxidation of 2-Chloro-6-nitro-3-phenoxyaniline (aclonifen) and shows that the major oxidation product is a dimeric compound. A mechanistic scheme involving a coupling process is postulated for the electrochemical oxidation of this compound. Furthermore, the use of differential pulse voltammetry on a glassy carbon electrode permits the selective determination ofaclonifen. The limit of detection is 0.6 μg/mL.

ChemInform Abstract: The Synthesis of 1,8-Disubstituted 10,11-Dihydrodibenz(b,f)oxepin-10- ones. Analogues of Anaesthetic Steroids.

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Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem of TB control and clinical management prompted us to synthesize a novel series of heterocyclic substituted diphenyl ether derivatives and determine their activity against the H37Rv strain of Mycobacterium. All ten compounds inhibited the growth of the H37Rv strain of Mycobacterium at concentrations of 1 μg/mL. This activity was found to be comparable to the reference drugs rifampicin and isoniazid at the same concentration. While the antimicrobial activity of other diphenyl ether analogues, such as triclosan, is associated with the inhibition of enoyl-ACP reductase (ENR), the synthesised substituted diphenyl ether derivatives did not affect this enzyme activity in spite of their structural similarity with triclosan. Therefore, these compounds appear to have a novel mechanism of action against M. tuberculosis, and their structural features should be studied further for their potential as new antitubercular drugs.

Gold(i) halide complexes of bis(diphenylphosphine)diphenyl ether ligands: a balance of ligand strain and non-covalent interactions

A series of bis(gold(I) halide; halide = Cl, Br, I) complexes of di(phosphino)diphenyl ether derivatives (L = DPEphos, DBFphos, Xantphos, tBuXantphos) have been synthesized. The new complexes have been characterized by X-ray crystallography, multinuclear NMR, and elemental analysis. The compounds luminesce at room temperature in dichloromethane solution. Many such complexes undergo aurophilic Au...Au bonding, and have chiral structures as a result. In complexes of the tBuXantphos ligand, X-ray crystallography indicates that an ion pair forms where the diphosphine ligand chelates one gold atom, and the other is part of an [AuX(2)](-) counterion (X = Cl, Br, I). It appears that the observed conformations of the metal-coordinated ligands are a balance of ligand strain and non-covalent interactions, including aurophilicity, intramolecular pi-stacking, halide-halide repulsion, and intramolecular Au-O interactions. Together with previous investigations, this research shows that Xantphos and its derivatives form a robust set of coordination complexes with gold that are stable in air and amenable to further synthetic manipulation. It is anticipated that these materials will be suitable precursors for gold-carbon coupling reactions and gold-based catalysis.

Structure elucidation of three diphenyl ether derivatives from the mangrove endophytic fungus SBE‐14 from the South China Sea

Two new natural products, tenelate A (1) and B (2), together with the known compound, tenellic acid C (3), were isolated from the mangrove endophytic fungus Talaromyces sp. (SBE-14), from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR techniques.

Synthesis and Structure of 1-Chlorosulfonyl-2-(4′-Nitrophenoxy)-5-Methylbenzene

Diphenyl ethers are structural elements found in medicinally useful antibiotics such as vancomycin as well as in biological toxins in the environment such as dioxins. The purpose of this paper is to report the synthesis and characterization of the previously unreported 1-chlorosulfonyl-2-(4′-nitrophenoxy)-5-methylbenzene, a trisubstituted diphenyl ether derivative. 1H NMR (CDCl3) δ 2.45 (3H, methyl5, s), 7.07 (1H, H4, d, J ~8.27 Hz), 7.13 (2H, H2′, H6′, d, J ~9.0 Hz), 7.54 (1H, H3, d, J ~8.28 Hz), 7.87 (1H, H6, s), 8.22 (2H, H3′, H5′, J ~9 Hz); 13C NMR (CDCl3) δ 20.7, 118.2, 121.9, 126.0, 129.8, 135.2, 135.8, 137.8, 143.8, 150.3, 161.4. An X-ray analysis has provided valuable insight into the effect of steric factors on the three dimensional shape of this compound which serves as a useful advanced intermediate in the synthesis of these biologically active molecules. A multistep synthesis of this molecule has been designed by retrosynthetic analysis as part of an ongoing program aimed at a function-oriented, multi-step economical synthesis of vancomycin lead antibiotics. Crystals are triclinic, space group P-1, a = 7.6537(15), b = 8.976(2), c = 11.050(2) A, α = 67.645(11), β = 79.735(11), γ = 87.798(10)°, V = 690.5(2) A3, Z = 2. The synthesis and characterization of the previously unreported trisubstituted diphenyl ether derivative are reported. The phenyl rings form a dihedral angle of 64.49(4)° and the chlorosulfonyl group has a C–C–S–Cl torsion angle of 62.95(11)°.

Activation and inhibition of leukotriene A 4 hydrolase aminopeptidase activity by diphenyl ether and derivatives

The synthesis and biological evaluation of a series of diphenyl ether derivatives were described. The compounds can either activate or inhibit the aminopeptidase activity of leukotriene A 4 hydrolase, while at the same time do not influence the hydrolase activity. Further enzyme kinetics and molecular modeling investigation on these novel chemical activators revealed their possible activation mechanism. These compounds can be used as probes to regulate the aminopeptidase activity of leukotriene A 4 hydrolase.

Synthesis, antitubercular activity and docking study of novel cyclic azole substituted diphenyl ether derivatives

The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of heterocyclic o/ m/ p substituted diphenyl ether derivatives and determine their activity against H37Rv strain of Mycobacterium. All 10 compounds inhibited the growth of the H37Rv strain of mycobacterium at concentrations as low as 1 μg/mL. This level of activity was found comparable to the reference drugs rifampicin and isoniazid at the same concentration. Molecular modeling of the binding of the diphenyl ether derivatives on enoyl-ACP reductase, the molecular target site of triclosan, indicated that these compounds fit within the binding domain occupied by triclosan. Hence the diphenyl ether derivatives tested in this study were docked to ENR and the binding of the diphenyl ether derivatives was also estimated using a variety of scoring functions that have been compiled into the single consensus score. As the scores ranged from 47.27% to 65.81%, these bioactive compounds appear to have a novel mechanism of action against M. tuberculosis, and their structural features should be studied further for their potential use as new antitubercular drugs.

Synthesis and in vitro evaluation of new diphenyl ether derivatives as serotonin transporter ligands

For the development of new ligands as potential imaging agents for the serotonin transporter (SERT), a series of diphenyl ether derivatives have been synthesized, characterized, and evaluated for their in vitro binding affinities to the SERT. Among the above compounds, 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-bromobenzenamine (15) and 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-iodobenzene amine (16) show high binding affinities for the SERT with K i values of 0.28 and 0.20 nmol·L−1, respectively. They can be further labeled with carbon-11, fluorine-18, iodine-123 or bromine-76, and evaluated as useful imaging agents for the SERT. Moreover, the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands.

Photochemically induced nitration and hydroxylation of organic aromatic compounds in the presence of nitrate or nitrite in ice

The photochemistry of three model aromatic compounds (phenol, anisole, and 4-methoxyphenol; c = 10 −3 mol L −1) in frozen aqueous solutions containing sodium nitrite or nitrate ( c = 10 −2 to 10 −1 mol L −1) at −15 °C was investigated. Nitration, hydroxylation, and coupling reactions were found to be the principal chemical processes, presumably taking place in a layer covering the ice crystal surfaces where both hydrophobic organic and water-soluble inorganic compounds were accumulated prior to and during irradiation. While the primary photoproducts were identified at low reaction conversions, exhaustive (quartz- or Pyrex-filtered) UV-irradiation produced a very complex mixture of compounds. The photoreactions proceeded predominantly by the nitrite or nitrate photoexcitation but chemistry of the excited organic chromophores was also observed. Phenol and 4-methoxyphenol photolysis afforded the corresponding nitro- and hydroxycompounds, in addition to biphenyl and diphenylether derivatives. Qualitatively the same photoproducts were produced in the presence of nitrite as well as nitrate; therefore both anions were the source of the NO x or HO radicals. In contrast, irradiation of anisole under the same reaction conditions afforded phenol nearly exclusively. It is demonstrated that the OH group of phenols played an important role in the course of hydroxylation and nitration reactions. The results from this study may support assumptions according to which photolysis of nitrate in the snowpack is responsible for oxidation of organic precursors to their hydroxy or carbonyl derivatives.

Synthesis and characterization of halogen‐containing poly(ether ketone ketone)s

AbstractA series of novel poly(ether ketone ketone)s (PEKKs) were synthesized from diphenyl ether and isophthaloyl chloride derivatives such as 5‐halo‐ and 5‐tert‐butyl‐isophthaloyl chloride. The aromatic electrophilic substitution route to polyketones was a convenient route for the preparation of the polymers in high yields via precipitation polycondensation at a low temperature with aluminum trichloride as a catalyst. High molecular weight PEKKs were achieved with number‐average molecular weights of 15,000–100,000 g/mol for polymers that showed good solubility in organic solvents. The presence of substituents greatly modified the spectroscopic features in comparison with those of unsubstituted isophthaloyl poly(ether ketone ketone)s, particularly for the series containing halogens, for which significant variations of the chemical shifts in both 1H and 13C NMR spectra were observed; these shifts could be related to the nature of the halogen. Thermal properties were also affected by the presence of pendent substituents, with clear enhancements of the glass‐transition temperatures, which could be ascribed to the nature and bulkiness of the substituents. Thermogravimetric analyses showed that the new polymers had good thermal resistance, although an important drop in thermal resistance was observed for polymers bearing large halogen atoms, such as bromine and iodine. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2601–2608, 2002

A comparative study on the nonlinear optical properties of diphenyl ether and diphenyl sulfide compounds

Fourteen diphenyl ether and diphenyl sulfide compounds were synthesized and a comparative study on their second-order nonlinear optical properties was carried out. The results showed that these two kinds of compounds all had fairly large molecular first-order nonlinear optical hyperpolarizabilities β, but they have very different second harmonic generation (SHG). The diphenyl sulfide derivatives usually have strong SHG effects while almost all the diphenyl ether compounds have no SHG response, which can be attributed to their crystal structure. We found that the diphenyl sulfide compounds were easy to crystallize in a noncentrosymmetric style but the crystal structure of the diphenyl ether derivative was centrosymmetric, and therefore a zero χ(2) was produced. The atom O or S was the real origin of the difference in their crystal structures, and therefore of the SHG effect.

Tenellic acids A-D: new bioactive diphenyl ether derivatives from the aquatic fungus Dendrospora tenella.

Tenellic acids A-D (1-4) were isolated from cultures of the freshwater fungus Dendrospora tenella. The structures of these new diphenyl ether derivatives were determined primarily by analysis of NMR data. Compounds 1-4 display antimicrobial activity against Gram-positive bacteria.

Synthesis of amorphous poly(thioarylene)s via oxidative polymerization of diaryl disulfides

AbstractAmorphous poly(thioarylene)s containing a methyl substituent and/or an ether bond in the main chain were prepared via oxidative polymerization of diaryl disulfides using 2,3‐dichloro‐5,6‐dicyanobenzoquinone. The resulting poly(thio‐2,6‐dimethyl‐1,4‐phenyleneoxy‐1,4‐phenylene) having alternating ether and thioether bonds shows a better solvent solubility and has a higher glass transition temperature (Tg) (182°C) than non‐substituted poly(thio‐1,4‐phenylene). Polymerization of methyl substituted diphenyl ether derivatives with disulfur dichloride has been also developed for a one‐pot synthesis of amorphous poly(thioarylene)s.

Mono-, bi- and polynuclear complexes of dimethyldiphenylsilane, diphenylether and biphenyl with Cr, Co and Ru. Synthesis and 1H, 13C, 17O and 29Si NMR spectroscopic characterization

Mono- and bimetallic transition metal carbonyls of dimethyldiphenylsilane, Ph 2Si(CH 3) 2 (L1), diphenylether, Ph 2O (L2) and biphenyl, Ph 2 (L3): Ph 2Si(CH 3) 2Cr(CO) 3 ( 1), Ph 2Si(CH 3) 2[Cr(CO) 3] 2 ( 2), Ph 2Si(CH 3) 2Co 4(CO) 9 ( 3), Ph 2Si(CH 3) 2[Co 4(CO) 9] 2 ( 4), Ph 2Si(CH 3) 2Cr(CO) 3Co 4(CO) 9 ( 5), Ph 2OCr(CO) 3 ( 6), Ph 2OCo 4(CO) 9 ( 7), Ph 2ORu 6C(CO) 14 ( 8), Ph 2OCr(CO) 3Co 4(CO) 9 ( 9) and Ph 2Ru 6C(CO) 14 ( 10) have been prepared and characterized by means of 1H, 13C, 17O and 29Si NMR spectroscopy. The same order of the shielding effects induced by the transition metal (Co < Ru < Cr) on the 1H NMR chemical shifts of the η 6-coordinated ring as observed earlier for diphenylmethane is also valid for the present bisarene aromatic ligands containing hetero-atoms in their structures. Differing from the behaviour of the 1H NMR chemical shifts of methylene protons of the diphenylmethane complexes, δ( 1H) of Si(CH 3) 2 group in dimethyldiphenylsilane always shows deshielded values consistent with π-coordination. Similarly, δ( 29Si) of Si(CH 3) 2 group is monotonously deshielded with the increasing degree of the complexation. As for diphenylmethane derivatives, δ( 17OC) of the present chromium tricarbonyl derivatives always shows easy-to-detect spectral characteristics, the shifts varying between 372.8 and 374.5 ppm. The only value obtained for tetracobalt nonacarbonyl derivatives was that of 7, δ( 17OC) = 349 ppm. The same order of δ( 17OC) as observed for the mesitylene transition metal carbonyls (Co < Cr < Ru) is also valid for the present polyarene compounds. The inverse relation between δ( 13CO) and δ( 17OC) in Ru and Co derivatives can be explained by the effect of π-backbonding. Diphenylether derivatives were not thermally stable enough to determine accurately δ( 17O) of the ethereal oxygen for all derivatives prepared. From the synthetic point of view, the present bisarene ligands were not so easily transformed to their π-coordinated derivatives as diphenylmethane.

5,4′-dimethyl-2-methoxydiphenylether: a new product from the anodic oxidation of 4-methylanisole

Anodic oxidation of p-methylanisole (1a) in a solution of aqueous 0.05 m H2SO4/acetone cosolvent (1 : 1, v/v) on platinum gives 5,4′-dimethyl-2-methoxydiphenylether (3), a compound hitherto unexplored, in 50% yield at a temperature below 15°C. Polymer products are formed in significant amounts (up to 60%) besides the diphenylether derivative (3) when the electrolytic oxidation proceeds in a solution containing AcOH as cosolvent at room temperature. The reaction mechanism includes both side chain anodic oxidation and ring 6e oxidation leading to a reactive intermediate, probably 3-methyl-5-methoxy-1,2-benzoquinone (5), whose polymeric products were also isolated.

Synthese von Bryophyten-Inhaltsstoffen 3. Neue Synthesen der Perrottetine E, F und G

Efficient and expeditious syntheses of the Perrottetines E, F and G (4',5-bis(m-hydroxyphenethyl)diphenyl ether derivatives) are developed, which give rise to these biologically active linear bis(bibenzyl) derivatives on a preparative scale

The synthesis of 1,8-disubstituted 10,11-dihydrodibenz[b,f]oxepin-10-ones. analogues of anaesthetic steroids

1,8-Disubstituted 10,11-dihydrodibenz[b,f]oxepin-10-ones 4a, b and 5a, b have been synthesised as analogues of steroid anaesthetics 2 and 3 respectively. The novel partial Ullmann reaction between methyl 2,6-dichlorophenylacetate 7 and 4-substituted phenols 8e, b gave diphenyl ether derivatives 9a, b. The latter were then hydrolysed and cyclodehydrated to give 1,8-disubstituted 10,11-dihydrodibenz[b,f] oxepin-10-ones 11a, b which underwent selective functional group transformations to give 4a, 5a and 4b, 5b respectively. Lithium borohydride reduction of the ester 13b to the benzyl alcohol 14b proceeded without reduction of the enol ether function.

Computer-Aided Molecular Design and Structure-Activity Relationships of Pesticides

Recent developments of computational techniques such as theoretical calculations and computer graphics are providing tools for designing bioactive molecules. My coleagues and I have applied computational technique and quantitative structure-activity relationships (QSAR) to study on structure-activity profiles of insect juvenile hormone (JH) mimics and fungicidal imidazoles. In the QSAR analyses steric and hydrophobic properties were important for the JH activity of mimics having a 2, 4-dodicadienoate structure against Aedes aegypti and Tenebrio molitor. The steric and hydrophobic parameters in the analyses suggested strong effects of steric dimensions such as molecular length and shape on the JH activity. The optimum hydrophobicity was ca. 6.8 in terms of log P value. Based on the results of QSAR, various compounds having a terpenoid component were synthesized, among which some undecen-2-one oxime O-ethers and undecen-2-yl carbamates showed JH activity against Culex pipiens, Chilo suppressalis and Musca domestica. Replacement of the terpenoid component in the oxime O-ethers by diphenylether structure produced novel JH mimics as active as methoprene. In the conformational analyses and computer graphics studies the diphenylether derivatives and the terpenoid compounds were superimposable in stable conformations. Besides the superimposability, functional groups in the JH mimics had similar electrostatic properties in terms of electrostatic potentials. In the QSAR of triflumizole and related fungicidal imidazoles, steric, electronic and hydrophobic effects of substituents on the benzene ring were important for the fungicidal activity against cucumber powdery mildew. The effects of substituents on the imino carbon were expressed by steric and hydrophobic parameters as well as some indicator variables. Conformational analysis and computer graphics were employed to study the mode of interaction of triflumizole with cytochrome P-450, the target enzyme of fungicidal azoles. An energy minimum structure of triflumizole fitted the cavity of cytochrome P-450 so as to block the oxidation of lanosterol, the ergosterol precursor. The results of QSAR coincided with the computer graphics model with respect to steric and hydrophobic properties, showing that the physicochemical properties expressed by the parameters in QSAR were important to antagonize cytochrome P-450 and thus to inhibit the biosynthesis of ergosterol.