- Methyl Hydrazinocarboxylate as a Practical Alternative to Hydrazine in the Wolff-Kishner Reaction
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Herein we describe a facile protocol for the reduction of aromatic ketones and aldehydes to the corresponding methylene unit. The procedure involves isolation of a carbomethoxyhydrazone intermediate that is easily decomposed to the reduced product without the requirement for large quantities of pernicious hydrazine.
- Cranwell, Philippa B.,Russell, Andrew T.,Smith, Christopher D.
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supporting information
p. 131 - 135
(2015/12/26)
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- Unusual ipso substitution of diaryliodonium bromides initiated by a single-electron-transfer oxidizing process
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(Chemical Equation Presented) Aromatic substitution: The treatment of diaryliodonium bromides 1 with aromatic nucleophiles 2, afforded a variety of heteroaryl-containing biaryls 3 in good yields. The ipso-substitution process at the heteroaryl ring in 1 occurs through the formation of aromatic cation radicals, which are initiated by the single-electron-transfer (SET) oxidation of 2. (HFIP = hexafluoroisopropanol)
- Dohi, Toshifumi,Ito, Motoki,Yamaoka, Nobutaka,Morimoto, Koji,Fujioka, Hiromichi,Kita, Yasuyuki
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supporting information; experimental part
p. 3334 - 3337
(2010/08/04)
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- Highly selective 5-substitution of 3-methylthiophene via directed lithiation
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(Chemical Equation Presented) Lithiation of 3-methylthiophene with lithium 2,2,6,6-tetramethylpiperidide (LiTMP) is highly selective at the 5-position, and reaction with a range of electrophiles gives high yields of the corresponding 2,4-disubstituted thiophenes, even when unhindered electrophiles are used.
- Smith, Keith,Barratt, Mark Lewis
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p. 1031 - 1034
(2008/02/04)
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- 1,3-bicyclo[1.1.1]pentanediyl: The shortest rigid linear connector of phenylated photochromic units and a 1,5-dimethoxy-9,10-di(phenylethynyl) anthracene fluorophore
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An excess of bis-1,3-(4-iodophenyl)bicyclo[1.1.1]pentane, prepared in 63% yield by iodination of 1.3-diphenylbicyclo[1.1.1]pentane, was selectively mono-coupled with 9-ethynyl-1,5-dimethoxy-10-phenylethynylanthracene (26), and subsequently with the zinc derivatives of 1-(2-methyl/methoxy-4-methyl-5- phenylthiophen-3-yl)-2-(2-methyl/methoxy-4-methylthiophen-3-yl) perfluorocyclopentenes (38-H-41-H). Regioselective synthesis of the 2-unsubslituted thiophenes 38-H-41-H required intermediate prepara tion of 2-trimethylsilyl-3,5-dimethyl-4-bromothiophene (37) or 2-trimethylsilyl-5- methoxy-3-methyl-4-bromothiophene (40). Protection of the α-position of the thiophene ring with a 2-trimethylsilyl group blocks the rearrangement of the 4-lithio derivatives into the corresponding 2-lithiated thiophenes. With the bicyclo[1.1.1]pentane frag ment linking the photochromic units 1-3 and 1,5-dimethoxy-9,10-di(phenylethynyl)anthracene as a fluorescent part, quantitative resonance energy transfer between the excited state of the fluorophore (donor) and the closed form of the photochromic units 1-3 (acceptors) was observed. The closed forms of the methoxy-substituted photochromic units 2 and 3 are less resistant to UV light (313 nm) than the closed form of 1.
- De Meijere, Armin,Ligang, Zhao,Belov, Vladimir N.,Bossi, Mariano,Noltemeyer, Matthias,Hell, Stefan W.
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p. 2503 - 2516
(2008/04/01)
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- PROCESS FOR PREPARING 2,5-DISUBSTITUTED 3-ALKYLTHIOPHENES
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The present invention relates to a process for preparing 2,5-disubstituted 3-alkyl-thiophenes and more particularly to a process for preparing them that comprises an acylation reaction in position 5 of 2-substituted 3-alkylthiophenes. This process does not need reagents which are difficult to handle and does not need anhydrous conditions or inert atmosphere. The resulting product is obtained in high purity.
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- 2-amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors
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The present invention relates to a compound of formula (I): wherein: R3 is selected from the group consisting of 1-napthyl, 2-napthyl and cycloalkylphenyl; and R4 and R5 taken together form a ring having from 5 to 10 carbon atoms. Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal subject, such as a human, wherein increased angiogenesis is desired, comprising administering to a mammal in need of such therapy an effective amount of the aforementioned thiophene selective adenosine A1 allosteric enhancer.
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- 2-Amino-3-aroyl-4,5-alkylthiophenes: Agonist allosteric enhancers at human a1 adenosine receptors
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2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A1 adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A1AR (hA1AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A1AR agonist [125I]ABA and membranes from CHO-K1 cells stably expressing the hA1AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A1AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)n- bridge, n = 3 1AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.
- Tranberg, C. Elisabet,Zickgraf, Andrea,Giunta, Brian N.,Luetjens, Henning,Figler, Heidi,Murphree, Lauren J.,Falke, Ruediger,Fleischer, Holger,Linden, Joel,Scammells, Peter J.,Olsson, Ray A.
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p. 382 - 389
(2007/10/03)
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- Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia
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This invention provides compounds of Formula I having the structure E is S, SO, SO2, O, or NR1c; X is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, CN, aryl, aralkyl of 6-12 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, hydroxyaralkyl of 6-12 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryloxy; arylalkoxy, nitro, amino, NR2R2a, NR2COR2a, cycloalkylamino of 3-8 carbon atoms, morpholino, alkylsulfanyl of 1-6 carbon atoms, arylsulfanyl, pyridylsulfanyl, 2-N,N-dimethylaminoethylsulfanyl, —OCH2CO2R2bor —COR2c; Z1and Z2are each, independently, hydrogen, halogen, CN, alkyl of 1-6 carbon atoms, aryl, aralkyl of 6-12 carbon atoms, cycloalkyl of 3-8 carbon atoms, nitro, amino, —NR1R1a, —NR1COR1a, cycloalkylamino of 3-8 carbon atoms, morpholino, or OR8, or Z1and Z2may be taken together as a diene unit having the formula —CH═CR9—CR10═CR11—; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
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- Novel synthesis of substituted thiophenes by palladium-catalyzed cycloisomerization of (Z)-2-En-4-yne-1-thiols
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(formula presented) The first example of palladium-catalyzed cycloisomerization of (Z)-2-en-4-yne-1-thiols 1 to give substituted thiophenes 2 is reported. Cycloisomerization reactions are carried out under nitrogen at 25-100 °C in N,N-dimethylacetamide as
- Gabriele, Bartolo,Salerno, Giuseppe,Fazio, Alessia
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p. 351 - 352
(2007/10/03)
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- Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
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This invention provides compounds of Formula I having the structure: wherein R1, R2, R3, R4, R5, R6, R7, R8, W, X, Y, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
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- Naphtho[2,3-B]heteroar-4-yl derivatives
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This invention provides compounds of Formula I having the structure wherein R1, R2, R3, R4, R5, W, R9, X, R6, p, Y, Z, R7, and R8 are as defined in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
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- The low affinity PCP sites in the rat cerebellum not only bind TCP-like but also BTCP-like structures
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Congeners of the potent dopamine (DA) re-uptake inhibitor l-[1-(2- benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the rat cerebellum, although this structure is devoid of dopaminergic nerve endings. In line with previous studies the hypothesis that they bind to low affinity PCP sites labelled with [3H]TCP in the rat cerebellum, even though they do not bind to the high affinity PCP sites in the forebrain, was considered. Analogues of l-[1-(2-thiophenyl)cyclohexyl]piperidine (TCP) and BTCP with a modified aromatic moiety and with O or S atoms substituted in the cyclohexyl ring were prepared and tested in competition experiments both in rat forebrain and cerebellum membranes labelled with [3H]TCP, and in rat striatum membranes labelled with [3H]BTCP. Results indicated that BTCP and congeners could bind to low affinity PCP sites labelled with [3H]TCP in the rat cerebellum with a decrease of the selectivity for the DA transporter. On the contrary, some TCP analogues displayed a very high selectivity for these low affinity sites: they might be important pharmacological tools to elucidate the nature and function at yet unknown of these sites. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
- Espaze, Florence,Hamon, Jacques,Hirbec, Helene,Vignon, Jacques,Kamenka, Jean-Marc
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p. 323 - 331
(2007/10/03)
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- Thallium(III) Trifluoroacetate-Trifluoroacetic Acid in the Chemistry of Polythiophenes. 2. Treatment of 3-Alkylthiophenes and Electron Paramagnetic Resonance Results
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The treatment of thiophene and 3-alkylthiophenes with thallium(III) trifluoroacetate (TTFA) in trifluoroacetic acid (TFA) gives insoluble and dark powdery solids with oxygen content and electrical conductivities ranging from 10-4 to 10-6 Ω-1 cm-1. Polar and short fractions are negligible. All of them show semiconductivity (10-3Ω-1 cm-1) when doped in iodine atmosphere. Electron paramagnetic resonance (EPR) spectra of either as-synthesized or I2-treated solids display characteristic single and broad lines (ΔHPP, 1.84-7.4 G) with Lorentzian shapes and g-values in the range 2.0028-2.0038. Infrared spectra show characteristic C-H out-of-plane deformations (780 cm-1 for polythiophene and 820-825 cm-1 for poly(3-alkylthiophenes)) in addition to a strong peak at 1650-1690 cm-1 which has not been conclusively assigned. EPR spectra of some disubstituted and tetrasubstituted 2,2′-bithiophene radical cations have been observed and their g-values and coupling constants assigned when the corresponding parent compounds are photolyzed with ultraviolet light in TFA. Photolysis of 3-alkylthiophenes in TFA in the EPR instrument gave the radical cations of 4,4′-dialkyl-2,2′-bithiophenes. In no case, were EPR signals of the isomeric 3,3′-dialkyl- or 3,4′-dialkyl-2,2′-bithiophene radical cations observed, indicating that dimerization of 3-alkylthiophenes occurs through the less sterically hindered 5-position. The presence of two doublet species corresponding to both conformers, syn and anti, in the radical cations is associated with a large barrier to rotation about the C(2)-C(2′) bond.
- Tormo, Jordi,Jesus Moreno,Ruiz, Jordi,Fajari, Lluis,Julia, Luis
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p. 878 - 884
(2007/10/03)
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- Synthetic Applications of Arenetricarbonylchromium(0) Complexes: the Synthesis of Polyfunctionalised Thiophenes
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Lithiation of thiophenetricarbonylchromium(0) complexes with butyllithium occurs preferentially at C-2/5 but when these are blocked, 3/4 lithiation is facile.Combinations of a bulky silyl (i-Pr3Si or t-BuMe2Si) blocking group at C-2/5 and remote lithiation/electrophilic quench of C-3/4 followed by desilylation/lithiation/electrophilic quench allowed the synthesis of 2,3-, 2,3,5- and 2,3,4,5-polysubstituted thiophene complexes and their derived free thiophenes.
- Loft, Michael S.,Mowlem, Timothy J.,Widdowson, David A.
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- Sulfonylureas: A new class of cancer chemotherapeutic agents
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This study summarizes the antitumor properties of a number of sulofenur thiophene analogs against subcutaneously implanted 6C3HED lymphosarcoma with structural modification of the aryl moiety of the sulfonamide portion of the diarylsulfonylureas. The spectrum of activity of N-(p-chlorophenyl)-N'-[(5- methoxy-2-thienyl)sulfonyl]urea in the HXGC3, VRC5, CX-1, and LX-1 cell lines is also presented.
- Mohamadi,Spees,Grindey
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p. 3012 - 3016
(2007/10/02)
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- Dye-Sensitized Photooxygenation of 2,3-Dihydrothiophenes: Formation of Stable 1,2-Dioxetanes from 4,5-Dialkyl-Substituted Derivatives
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Singlet oxygen reacts with 4,5-dimethyl- (1a), 4-ethyl-5-methyl- (1b), and 4-isopropyl-5-methyl-2,3-dihydrothiophene (1c) to give 1,2-dioxetanes 2a-c in high yields (> 90 percent). 2a-c represents the first examples of sulfur-substituted dioxetanes that could be isolated.Less than 5 percent of allylic hydroperoxides 3a, 4a, and 3b, identified by their 1H NMR spectra, and less than 5 percent of S-oxides 5a-c were formed in competing ene reactions and sulfoxide-producing steps, respectively.Due to its decreased rigidity, dioxetane 2a is less stable than its oxygen counterpart.Increased flexibility of dioxetanes derived from dihydrothiophenes and dihydrothiopyranes, as compared to those derived from dihydrofurans and dihydropyrans, causes dioxetanes 9 and 16, obtained from 4-carbomethoxy-5-methyl-2,3-dihydrothiophene (8) and 5,6-dimethyl-3,4-dihydro-2H-thiopyran (14), to cleave into dicarbonyl compounds readily at low temperatures.Sulfur-substituted allylic hydroperoxides are also less stable than their oxygen counterparts.Formation of the expected endocyclic allylic hydroperoxides 3a, 3b, and 10 is inferred from the appearance of their H2O2 elimination products, thiophenes 7a, 7b, and 13, respectively.
- Gollnick, Klaus,Knutzen-Mies, Karen
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p. 4027 - 4031
(2007/10/02)
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- Gas-phase heteroaromatic substitution. 14. Attack of dimethylfluoronium ion on 2- and 3-methyl-pyrroles, -furans, -and thiophenes
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The gas-phase methylation of 2- and 3-methyl-pyrroles (2P and 3P), -furans (2F and 3F), and thiophenes (2T and 3T) by (CH3)2F+ ions, from γ-radiolysis of CH3F, has been investigated at pressures ranging from 50 to 760 Torr, in the presence of a thermal radical scavenger (O2) and variable concentrations of an added base (NMe3: 0-10 Torr).The mechanism of the methylation process is discussed and the intrinsic positional selectivity of the (CH3)2F+ ions evaluated in the framework of the Charge and Frontier Orbital Control concept.Owing to the very large energy gap between the LUMO of (CH3)2F+ and the HOMOs of the selected heteroaromatic substrates, their gas-phase methylation is characterized by a distinct affinity of the ionic electrophile toward those substrates positions with the highest net negative charge, i.e., the C3 in 2P (100percent), the C4 in 3P (100percent), the heteroatom of 2F and 3F (>80percent), the C5 of 2T (32percent), and the C2 of 3T (47percent).Analysis of the methylated product distribution from 2F and 3F as a function of the experimental conditions reveals that the interaction of the (CH3)2F+ with the heteroatom of furans gives rise to the reversible formation of two sets of electrostatic adducts, i.e., a "chelate" adduct (III) and a single proton-bonded adduct (IV), the first rapidly evolving to the α-substituted heteroarenium intermediate by proximity effects and the latter slowly rearranging to the chelate structure III.Formation of these categories of electrostatic adducts from furans, which is much less extensive in the case of thiophenes and absent in pyrroles, accounts for the apparent pronounced affinity of gaseous alkylating electrophiles, irrespective of their LUMO energy, for the α carbons of furans. Key words: gas-phase ion chemistry, electrophilic aromatic substitution, radiolysis, dimethylfluoronium ions, methylated heteroarenes.
- Cecchi, Patrizio,Pizzabiocca, Adriano,Renzi, Gabriele,Sparapani, Cinzia,Speranza, Maurizio
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p. 2094 - 2103
(2007/10/02)
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- Equilibrium studies of thiophene exchange in (η-thiophene)Ru(η-C5H5)+: A model for thiophene adsorption on hydrodesulfurization catalysts
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Equilibrium constants (K′) for the displacement of the π- (i.e., η5-) thiophene (T) ligand in CpRu(T)+ by methyl-substituted thiophenes (Th′), CpRu(T)+ + Th′ ? CpRu(Th′)+ + T, increase as the number of methyl groups in Th′ increases: T (1) 2T (35) 2T (50) 3T(200) 3T (300) 4T (1300). The K′ values increase by a factor of approximately 6 for each methyl in the thiophene (Th′). That thiophenes also adsorb to a Co-Mo/Al2O3 hydrodesulfurization (HDS) catalyst more strongly as the number of methyl groups in the thiophene increases suggests that they are also π-bonded to the catalyst surface. The results suggest that trends in rates of deuterium exchange and hydrodesulfurization on HDS catalysts for a series of methyl-substituted thiophenes are determined by their relative strengths of adsorption to the catalyst surface.
- Hachgenci,Angelici
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- THE IDENTIFICATION OF 2,3-DIMETHYL-5-(2,6,10-TRIMETHYLUNDECYL)THIOPHENE, A NOVEL SULPHUR CONTAINING BIOLOGICAL MARKER
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The identification of 2,3-dimethyl-5-(2,6,10-trimethylundecyl)thiophene as a major constituent of certain petroleums and sediment extracts was confirmed by synthesis of the standard.
- Damste, J.S.Sinninghe,Kock-van Dalen, A.C.,de Leeuw, J.W.,Schenck, P.A.
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p. 957 - 960
(2007/10/02)
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- Reactions of Thiophene and Alkylthiophenes in Glow Discharge
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The glow discharge reaction of thiophene is shown to produce thioketene and carbon monosulfide along with other gaseous products.The dominant liquid product is ethynylthiophene.Methylthiophenes and especially dimethylthiophenes produce benzene as one of the major liquid products.
- Skramstad, Jan,Chaudhry, Mohammed Shoaib,Garvang, Arne
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p. 509 - 512
(2007/10/02)
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- Sulfonation of aromatic compounds in the presence of solvents
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A process for the sulfonation of aromatic compounds wherein an aromatic substance consisting of one or more aromatic compounds susceptible to the action of sulfur trioxide is formed into a reactant by admixture with one or more organic liquids, substantially inert to sulfur trioxide under the conditions of the process, which reactant is brought to boiling at a temperature not greater than 100° C under a pressure of from 0.1 mm Hg to atmospheric pressure, gaseous sulfur trioxide is introduced thereinto thereby causing it to continue to boil, the component or components of the reactant thus volatilized is or are reconverted to liquid in a heat-exchanger and recycled to the reaction chamber, and the pressure in the reaction chamber and the rate at which the gaseous sulfur trioxide is introduced into the reactant are controlled so as to ensure that there is always present in the reaction chamber an amount of volatilizable matter exceeding that amount volatilizable by the heat of reaction of the aromatic substance present in the reaction chamber with the gaseous sulfur trioxide in contact with said aromatic substance and that the temperature of the reaction mixture is a temperature of 100° C or below.
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