- An NMR, IR and theoretical investigation of the methyl effect on conformational isomerism in 3-fluoro-3-methyl-2-butanone and 1-fluoro-3,3-dimethyl-2-butanone
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The solvent dependence of the 1H and 13C NMR spectra of 3-fluoro-3-methyl-2-butanone (FMB) and 1-fluoro-3,3-dimethyl-2-butanone (FDMB) was examined and the 4JHF, 1JCF and 2JCF couplings are reported. Density functional theory (DFT) at the B3LYP/6-311 ++ G(2df, 2p) level with ZPE (zero point energy) corrections was used to obtain the conformer geometries. In both FMB and FDMB, the DFT method gave only two minima for cis (F - C - C = O, 0°) and trans (F - C - C = O, 180°) rotamers. Assuming the cis and trans forms, the observed couplings in FMB when analysed by solvation theory gave the energy difference Ecis - Etrans of 3.80 kcal mol-1 (1 kcal = 4.184 kJ) in the vapour phase (cf. the DFT value of 3.21 kcal mol-1), decreasing to 2.6 kcal mol-1 in CCl4 and to 0.27 kcal mol-1 in DMSO. In FDMB the observed couplings when analysed similarly by solvation theory gave Ecis - Etrans = 1.80 kcal mol-1 in the vapour phase, decreasing to 0.47 kcal mol-1 in CCl4 and to - 1.25 kcal mol-1 in DMSO. The introduction of a methyl group geminal to the fluorine atom shifts the conformational equilibrium towards the trans rotamer, in contrast to no significant effect when the methyl group is introduced at the α-carbon further from the fluorine atom. Copyright
- Tormena, Claudio F.,Rittner, Roberto,Abraham, Raymond J.
-
-
Read Online
- Base-Catalyzed Intramolecular Defluorination/O-Arylation Reaction for the Synthesis of 3-Fluoro-1,4-oxathiine 4,4-Dioxide
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A novel process involving base-catalyzed intramolecular defluorination/O-arylation of readily available α-fluoro-β-one-sulfones was realized and provided a series of 3-fluoro-1,4-oxathiine 4,4-dioxide derivatives in good to excellent yields. Unlike traditional defluorination reactions with stoichiometric base as the deacid reagent, this process is triggered by a catalytic amount of base (TMG: tetramethylguanidine) and molecular sieves serve as both an adsorbent to remove HF acid and an activator to assist C-F bond cleavage.
- Kang, Lei,Zhang, Jinlong,Yang, Huameng,Qian, Jinlong,Jiang, Gaoxi
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supporting information
p. 785 - 789
(2021/04/09)
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- Diastereoselective Synthesis of Z-Alkenyl Disulfides from α-Thiophosphorylated Ketones and Thiosulfonates
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We developed a simple and efficient method for the synthesis of functionalized unsymmetrical Z-alkenyl disulfides under mild conditions in moderate to good yields. The designed method is based on the reaction of α-thiophosphorylated carbonyl compounds with thiotosylates in the presence of a base. The developed method allows the preparation of unsymmetrical Z-alkenyl disulfides bearing additional hydroxy, carboxy, or ester functionalities. (Figure presented.).
- Musiejuk, Mateusz,Doroszuk, Justyna,J?drzejewski, Bartosz,Ortiz Nieto, Gregory,Marin Navarro, Marisol,Witt, Dariusz
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supporting information
p. 618 - 626
(2019/12/24)
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- Nickel-Catalyzed Asymmetric Addition of Aromatic Halides to Ketones: Highly Enantioselective Synthesis of Chiral 2,3-Dihydrobenzofurans Containing a Tertiary Alcohol
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A highly enantioselective and straightforward synthetic procedure to chiral 3-hydroxy-2,3-dihydrobenzofurans has been developed by nickel/bisoxazoline-catalyzed intramolecular asymmetric addition of aryl halides to unactivated ketones, giving 2,3-dihydrobenzofurans with a chiral tertiary alcohol at the C-3 position in good yields and excellent enantioselectivities (up to 92percent yield and 98percent ee). The gram-scale reaction also proceeded smoothly without a loss of yield and enantioselectivity.
- Li, Ying,Li, Wendian,Tian, Jiangyan,Huang, Guozheng,Lv, Hui
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supporting information
p. 5353 - 5357
(2020/07/14)
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- Atom-economical brominations with tribromide complexes in the presence of oxidants
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Bromination is an important transformation in organic synthesis, and novel efficient bromination techniques are still required. Herein, we demonstrate atom-economical brominations using (DMI)2HBr3, a novel tribromide complex, with oxidants such as DMSO and Oxone. Using this system, olefinic and aromatic brominations, as well as selective α-monobrominations of ketones proceeded well to afford the desired bromides in good yields. Importantly, in these reactions all of the bromine atoms in this complex are used to brominate.
- Yubata, Kotaro,Matsubara, Hiroshi
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supporting information
p. 1001 - 1004
(2019/03/13)
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- Synthesis and evaluation of various heteroaromatic benzamides as analogues of –ylidene-benzamide cannabinoid type 2 receptor agonists
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The CB2 receptor is an attractive target for the treatment of a wide range of diseases and pathological conditions. Compounds that selectively activate the CB2 receptor are desirable as this avoids CB1-mediated psychoactive effects. Heteroarylidene-benzamides have demonstrated efficacy as selective CB2 receptor agonists. We aimed to expand the structure-activity relationship studies of this series of compounds by investigating the heteroaromatic core via the synthesis and in vitro evaluation of a small library of various heteroaromatic benzamide analogues. As heteroaromatic amides are privileged scaffolds in drug design, methods to synthesise them are of interest. Concise and reliable synthetic strategies were developed to access these novel analogues. The –ylidene-benzamide moiety is shown to be essential for CB activity as all amide derivatives exhibit no functional activity at either CB2 or CB1 receptors.
- Moir, Michael,Boyd, Rochelle,Gunosewoyo, Hendra,Montgomery, Andrew P.,Connor, Mark,Kassiou, Michael
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supporting information
(2019/08/12)
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- Microwave synthesis of 1-aryl-1H-pyrazole-5-amines
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A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.
- Everson, Nikalet,Yniguez, Kenya,Loop, Lauren,Lazaro, Horacio,Belanger, Briana,Koch, Grant,Bach, Jordan,Manjunath, Aashrita,Schioldager, Ryan,Law, Jarvis,Grabenauer, Megan,Eagon, Scott
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supporting information
p. 72 - 74
(2018/11/30)
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- Preparation of a novel bromine complex and its application in organic synthesis
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Although molecular bromine (Br2) is a useful brominating reagent, it is not easy to handle. Herein, we describe the preparation of a novel air-stable bromine complex prepared from 1,3-dimethyl-2-imidazolidinone (DMI) and Br2, which was identified to be (DMI)2HBr3 by spectral and X-ray techniques. This complex was then used to brominate olefins, carbonyl compounds, and aromatics, as well as in the Hofmann rearrangement. Yields of reaction products using this complex were almost the same or superior to those using other bromine alternatives.
- Nishio, Yuya,Yubata, Kotaro,Wakai, Yutaro,Notsu, Kotaro,Yamamoto, Katsumi,Fujiwara, Hideki,Matsubara, Hiroshi
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p. 1398 - 1405
(2019/02/07)
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- A H2O2/HBr system-several directions but one choice: oxidation-bromination of secondary alcohols into mono- or dibromo ketones
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In this work we found that a H2O2-HBr(aq) system allows synthesis of α-monobromo ketones and α,α′-dibromo ketones from aliphatic and secondary benzylic alcohols with yields up to 91%. It is possible to selectively direct the process toward the formation of mono- or dibromo ketones by varying the amount of hydrogen peroxide and hydrobromic acid. The convenience of application, simple equipment, multifaceted reactivity, and compliance with green chemistry principles make the application of the H2O2-HBr(aq) system very attractive in laboratories and industry. The proposed oxidation-bromination process is selective in spite of known properties of ketones to be oxidized by the Baeyer-Villiger reaction or peroxidated with the formation of compounds with the O-O moiety in the presence of hydrogen peroxide and Bronsted acids.
- Nikishin, Gennady I.,Kapustina, Nadezhda I.,Sokova, Liubov L.,Bityukov, Oleg V.,Terent'ev, Alexander O.
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p. 28632 - 28636
(2018/08/31)
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- O,O,N-ligand trivalent bicyclic phosphide, synthetic method and catalysis application
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The invention relates to an O,O,N-ligand trivalent bicyclic phosphide as an organic catalyst, and a chemical structural formula of the above compound is shown as the specification, substituent R1 andR2 can be any one of alkyl or nitro group such as hydrogen or methyl or ethyl or isopropyl or t-butyl, nitro group, cyano group, carbonyl group, and trifluoromethyl group, and the substituent position, number and conjugate position are not fixed. The synthetic method takes conventional ketone as a raw material, the multiple steps of bromination, ammonification, reduction, and cyclisation are carried out, and the O,O,N-ligand trivalent bicyclic phosphide can be finally synthesized. The method is used for synthesizing the O,O,N-ligand trivalent bicyclic phosphide with a novel structure, and provides a novel synthesis route for the type of the phosphor compound, and successfully achieves the effective application of the O,O,N-ligand trivalent bicyclic phosphide, which can effectively catalyzean intermolecular Wittig reaction. The rear O,O,N-ligand trivalent bicyclic phosphide has obvious effect in catalysis of an organic reaction system, can effectively catalyze the intermolecular Wittigreaction, increases the reaction rate, and shortens the reaction time.
- -
-
Paragraph 0033; 0034; 0035
(2018/07/30)
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- N,N,N coordinated trivalent bicyclophosphide, synthetic method and catalytic application thereof
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The invention provides a N,N,N coordinated trivalent bicyclophosphide as an organic catalyst. The chemical structural formula of the compound is shown in the description. The final N,N,N coordinated trivalent bicyclophosphide is synthesized by adopting ketone as a raw material and multiple steps of bromination, ammoniation, reduction, imidization, hydrogenation and cyclization and the like in sequence. The N,N,N coordinated trivalent bicyclophosphide is characterized by synthesis of the N,N,N coordinated trivalent bicyclophosphide with an all-new structure and all-new synthetic route for preparing the phosphorus compound; simultaneously, the effective application of the N,N,N coordinated trivalent bicyclophosphide is successfully obtained, i.e., intramolecular aza Wittig reaction can be effectively catalyzed. Compared with the traditional transitional metal catalyst, the rare N,N,N coordinated trivalent bicyclophosphide has an obvious action in catalyzing an organic reaction system, and provides an all-new idea for the existing organic catalytic reaction. Compared with the traditional phosphine catalyst, the N,N,N coordinated trivalent bicyclophosphide has an obvious action in catalyzing the organic reaction system.
- -
-
Paragraph 0039; 0040; 0041; 0042
(2018/07/30)
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- Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of β-Acetylamino Vinylsulfides: An Approach to Chiral β-Acetylamino Sulfides
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Rh/DuanPhos-catalyzed asymmetric hydrogenation of challenging β-acetylamino vinylsulfides has been developed, affording chiral β-acetylamino sulfides with high yields and excellent ee's (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral β-acetylamino sulfides. The potential utility of this protocol in the synthesis of Apremilast has also been disclosed.
- Gao, Wenchao,Lv, Hui,Zhang, Xumu
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supporting information
p. 2877 - 2880
(2017/06/07)
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- Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
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Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity. Guided by molecular modeling, we synthesized and studied the structure-activity relationship of 40 compounds against clinically relevant EGFR mutants. We successfully improved the cellular EGFR inhibition down to the low nanomolar range with covalently binding inhibitors against a gefitinib resistant T790M mutant cell line. We identified additional noncovalent interactions, which allowed us to develop metabolically stable inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant.
- Günther, Marcel,Lategahn, Jonas,Juchum, Michael,D?ring, Eva,Keul, Marina,Engel, Julian,Tumbrink, Hannah L.,Rauh, Daniel,Laufer, Stefan
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supporting information
p. 5613 - 5637
(2017/07/22)
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- Palladium-Catalyzed Chemo- and Enantioselective C?O Bond Cleavage of α-Acyloxy Ketones by Hydrogenolysis
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A chemoselective C?O bond cleavage of the ester alkyl side-chain of α-acyloxy ketones was realized for the first time by a highly efficient palladium-catalyzed hydrogenolysis (S/C=6000, the highest catalytic efficiency by far). Furthermore, a kinetic resolution of α-acyloxy ketones was first developed by enantioselective hydrogenolysis with good yields and up to 99 % ee.
- Chen, Jianzhong,Zhang, Zhenfeng,Liu, Delong,Zhang, Wanbin
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supporting information
p. 8444 - 8447
(2016/07/19)
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- And its application epoxytriazole compd.
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PROBLEM TO BE SOLVED: To provide a novel compound useful as an active ingredient of a cell differentiation promoter such as a rooting promoter, and to provide a rooting method and a rooting medium using a cell differentiation promoter containing the compound for improving the productivity of clone seedlings by a cuttage method, a tissue culture method or the like. SOLUTION: This invention relates to: (±)-E-1-(benzo[d][1,3]dioxole-5-yl)-4,4-dimethyl-2-(1H-1,2,4-triazole-1-yl)penta-1-en-3-ol; a cell differentiation promoter and an auxin activity promoter containing the compound as an active ingredient; a rooting medium of plant shoots containing the cell differentiation promoter or the auxin activity promoter; and a method for producing clone seedlings using the cell differentiation promoter, the auxin activity promoter or the rooting medium. COPYRIGHT: (C)2013,JPOandINPIT
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Paragraph 0065; 0066
(2017/01/02)
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- Intermolecular N-H oxidative addition of ammonia, alkylamines, and arylamines to a planar σ3-phosphorus compound via an entropy-controlled electrophilic mechanism
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Ammonia, alkyl amines, and aryl amines are found to undergo rapid intermolecular N-H oxidative addition to a planar mononuclear ? 3-phosphorus compound (1). The pentacoordinate phosphorane products (1·[H][NHR]) are structurally robust, permitting full characterization by multinuclear NMR spectroscopy and single-crystal X-ray diffraction. Isothermal titration calorimetry was employed to quantify the enthalpy of the N-H oxidative addition of n-propylamine to 1 (nPrNH2 + 1 a? 1·[H][NHnPr], ?"H rxn298 = -10.6 kcal/mol). The kinetics of n-propylamine N-H oxidative addition were monitored by in situ UV absorption spectroscopy and determination of the rate law showed an unusually large molecularity (?= k[1][nPrNH2]3). Kinetic experiments conducted over the temperature range of 10-70 °C revealed that the reaction rate decreased with increasing temperature. Activation parameters extracted from an Eyring analysis (?"Ha§§ = -0.8 ± 0.4 kcal/mol, ?"Sa§§ = -72 ± 2 cal/(mol·K)) indicate that the cleavage of strong N-H bonds by 1 is entropy controlled due to a highly ordered, high molecularity transition state. Density functional calculations indicate that a concerted oxidative addition via a classical three-center transition structure is energetically inaccessible. Rather, a stepwise heterolytic pathway is preferred, proceeding by initial amine-assisted N-H heterolysis upon complexation to the electrophilic phosphorus center followed by rate-controlling N a? P proton transfer.
- McCarthy, Sean M.,Lin, Yi-Chun,Devarajan, Deepa,Chang, Ji Woong,Yennawar, Hemant P.,Rioux, Robert M.,Ess, Daniel H.,Radosevich, Alexander T.
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supporting information
p. 4640 - 4650
(2014/04/17)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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p. 2955 - 2965
(2013/09/02)
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- Bromination of ketones with the systems H2O2-LiBr- CeIII and H2O2-LiBr-CeIV
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A new method for the synthesis of α-bromoketones was suggested. The C5-C11 linear and branched ketones in the reaction with the systems H2O2-LiBr-CeIII and H 2O2-LiBr-CeIV in acetonitrile were brominated at α-position. The reaction is highly selective.
- Nikishin,Sokova,Kapustina
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p. 1214 - 1217
(2014/03/21)
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- Synthesis of an octa-tert-butylphthalocyanine: A low-aggregating and photochemically stable photosensitizer
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The synthesis of a new octa-tert-butylphthalocyanine is described. First, the 4,5-di-tert-butylphthalonitrile building block was synthesized in a six-step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties. The synthesis of a new octa-tert-butylphthalocyanine is described. First, the 4,5-di-tert-butylphthalonitrile building block was synthesized in a six-step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties. Copyright
- Gobo, Nicholas R. S.,Brocksom, Timothy J.,Zukerman-Schpector, Julio,De Oliveira, Kleber T.
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supporting information
p. 5028 - 5031
(2013/11/06)
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- Enamine rearrangement of pyridinium salts to indole ring: A combined experimental and molecular modeling study
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N-Alkyl pyridinium (II) and N-alkyl isoquinolinium salts V undergo cyclization reaction when heated with sodium bicarbonate to give the corresponding indolizine derivatives III and VI, respectively, which undergo ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding indole derivatives IV and IX, respectively. Molecular modeling tools including Molecular Mechanics using Augmented MM3 parameters followed by geometry optimization calculations in MO-G using PM3 parameters were performed to gain better understanding and more insights on the thermodynamic properties of the recyclization reactions of compounds IIa-g to the corresponding IIIa-g and IIIa-g to the corresponding IVa-g. The results were in excellent agreement with the experimental data and hence were proven to be a good tool in explaining different yields % because of the steric and electronic effects of electron-withdrawing groups on the reactivity of the pyridine ring for nucleophilic attack.
- Hosaan, Aisha,Fadda, Ahmed A.
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p. 638 - 644
(2013/07/19)
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- Main group redox catalysis: Reversible PIII/PV redox cycling at a phosphorus platform
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A planar, trivalent phosphorus compound is shown to undergo reversible two-electron redox cycling (PIII/PV) enabling its use as catalyst for a transfer hydrogenation reaction. The trivalent phosphorus compound activates ammonia-borane to furnish a 10-P-5 dihydridophosphorane, which in turn is shown to transfer hydrogen cleanly to azobenzene, yielding diphenylhydrazine and regenerating the initial trivalent phosphorus species. This result constitutes a rare example of two-electron redox catalysis at a main group compound and suggests broader potential for this nonmetal platform to support bond-modifying redox catalysis of the type dominated by transition metal catalysts.
- Dunn, Nicole L.,Ha, Minji,Radosevich, Alexander T.
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supporting information; experimental part
p. 11330 - 11333
(2012/09/05)
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- GLUCAGON RECEPTOR MODULATORS
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The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, A1, A2, A3, A4, L, B1, B2, B3 and B4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.
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Page/Page column 34
(2012/08/27)
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- Direct conversion of olefins into α-bromo ketones using O-iodoxybenzoic acid and tetraethylammonium bromide
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Utilizing full potential of IBX, a mild, selective, and facile method has been developed for the direct conversion of olefins into the corresponding α-bromo ketones by using 1.1 equivalents each of o-iodoxybenzoic acid and tetraethylammonium bromide. Georg Thieme Verlag Stuttgart - New York.
- Deshmukh, Swapnil S.,Chaudhari, Kiran H.,Akamanchi, Krishnacharya G.
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experimental part
p. 81 - 83
(2011/03/20)
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- Fast oxidation of secondary alcohols by the bromate-bromide system using cyclic microwave heating in acidic water
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We report an improved, gentle, cyclic microwave activation technique for the oxidation of secondary alcohols using nonhazardous hypobromous acid (BrOH) as the reagent in acidic water. Several aliphatic and aromatic secondary alcohols were successfully oxidized to the corresponding ketones using this technique in high yields and with only minor amounts of side products.
- P??kk?nen, Sanna,Pursiainen, Jouni,Lajunen, Marja
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scheme or table
p. 6695 - 6699
(2011/02/23)
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- Oxidation of secondary alkanols with the system cerium ammonium nitrate-lithium bromide into ketones, α-bromo ketones, and α,α -dibromo ketones
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Oxidation of secondary alkanols with the system Ce(NH4) 2(NO3)6-LiBr in aqueous acetonitrile gave ketones, α-bromo ketones, or α,α-dibromo ketones. The selectivity of the reaction under standard conditions depends only on the molar ratio of the reagents (alkanol : CeIV : LiBr).
- Nikishin,Sokova,Kapustina
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experimental part
p. 391 - 395
(2011/02/17)
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- The effects of C-S and C-Se bonds on torquoselectivity: stereoselective olefination of α-thio and α-selenoketones with ynolates
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Highly Z-selective olefination of acyclic α-thio and α-selenoketones with ynolates has been achieved, and the theoretical calculations of the transition states in the ring-opening of the intermediates, the β-lactone enolates, revealed that the torquoselectivity was controlled by the secondary orbital interactions between the σ orbital of the C-S bond or a lone pair orbital on the S and σ* orbitals of the breaking C-O bond, and the σ orbital of the breaking C-O bond or a lone pair orbital on the O on the ring and the σ* orbitals of the C-S bond. The synthetic applications of the resulting olefins are also shown.
- Yoshikawa, Takashi,Mori, Seiji,Shindo, Mitsuru
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experimental part
p. 8832 - 8838
(2010/04/06)
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- One-step synthesis of N-acetylcysteine and glutathione derivatives using the Ugi reaction
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Fully protected natural and unnatural N-acetylcysteine, dipeptide Cys-Gly, glutathione, and homoglutathione derivatives were synthesized by the Ugi four-component reaction using various benzylthio aldehydes and ketones as carbonyl building blocks. The scope and limitations of the method were investigated. Formation of imidazoline by-products in the Ugi reaction was discussed. 2,2,2-Trifluoroethanol was shown to be a superior reaction media than methanol in some reactions. Also, the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl derivative (OBO-ester) of isocyanoacetic acid was shown to be superior to use than ethyl isocyanoacetate as a peptide synthesis precursor in cases when higher reactivity of an isocyanide is required.
- Zhdanko, Alexander G.,Gulevich, Anton V.,Nenajdenko, Valentine G.
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experimental part
p. 4692 - 4702
(2009/10/02)
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- Discovery of imidazo[1,2-a]pyridines as potent MCH1R antagonists
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A series of imidazo[1,2-a]pyridine derivatives was identified and evaluated for MCH1R binding and antagonistic activity. Introduction of a methyl substituent at the 3-position of imidazo[1,2-a]pyridine provided compounds with a significant improvement in MCH1R affinity. Representative compounds in this series exhibited good potency and brain exposure in rats.
- Kishino, Hiroyuki,Moriya, Minoru,Sakuraba, Shunji,Sakamoto, Toshihiro,Takahashi, Hidekazu,Suzuki, Takao,Moriya, Ryuichi,Ito, Masahiko,Iwaasa, Hisashi,Takenaga, Norihiro,Ishihara, Akane,Kanatani, Akio,Sato, Nagaaki,Fukami, Takehiro
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scheme or table
p. 4589 - 4593
(2010/04/25)
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- Synthesis of (1′R,3S,4S)-3-[1′-(tert-butyldimethylsilyloxy) ethyl]-4-(cyclopropylcarbonyloxy)azetidin-2-one
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The novel carbapenem precursor 1e has been synthesized from L-threonine, cyclopropyl methyl ketone and benzhydrylamine (for the introduction of the azetidinone N-protecting group). Two independently prepared building blocks - sodium (2R,3R)-2,3-epoxybutyrate as a mixed salt with NaBr (2b) and N-(benzhydryl)aminomethyl cyclopropyl ketone (4e) - were coupled to give (2R,3R)-N-(benzhydryl)-N-(2-cyclopropyl-2-oxoethyl)-2,3-epoxybutyramide (8e). This key intermediate gave a regio- and stereoselective C3-C4 ring closure on LiHMDS treatment in THF at 0°C to yield (1′R,3S,4S)-4- cyclopropylcarbonyl-1-diphenylmethyl-3-(1-hydroxyethyl)azetidin-2-one (13e). N-Deprotection of 13e was performed by photochemical bromination and subsequent hydrolysis. The resulting (1′R,3S,4S)-4-(cyclopropylcarbonyl)-3-(1- hydroxyethyl)azetidin-2-one (23e) reacted in a Baeyer-Villiger oxidation with a total control of the regioselectivity (due to the poor migratory aptitude of the cyclopropyl group) to furnish (1′R,3S,4S)-3-(1-hydroxyethyl)-4- (cyclopropylcarbonyloxy)azetidin-2-one (24e), subsequent O-silylation achieving the total synthesis of 1e (title compound). Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Laurent, Mathieu,Ceresiat, Marcel,Marchand-Brynaert, Jacqueline
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p. 3755 - 3766
(2007/10/03)
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- TMS·OTf-Catalyzed α-bromination of carbonyl compounds by N-bromosuccinimide
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Various carbonyl compounds undergo α-bromination reaction under a mild and practical condition utilizing N-bromosuccinimide (NBS), catalyzed by trimethylsilyl trifluoromethanesulfonate (TMS·OTf). This method is also effective for the side-chain bromination of heteroaromatic carbonyl compounds without the ring brominations.
- Guha, Samar Kumar,Wu, Bo,Kim, Beom Soo,Baik, Woonphil,Koo, Sangho
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p. 291 - 293
(2007/10/03)
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- Asymmetric hydrogenation of tert-alkyl ketones
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A combined system of RuCl2(tolbinap)(pica) and an alkaline or organic phosphazene base catalyzes asymmetric hydrogenation of sterically congested tert-alkyl ketones (TolBINAP = 2,2-bis(di-4-tolylphosphino)-1,1-binaphthyl, PICA = α-picolylamine). Hydrogenation with RuH(η1-BH4)(tolbinap)(pica) does not require any strong base. Alcoholic solvents strongly affect the catalytic efficiency. The reaction proceeds smoothly in ethanol under 1-20 atm of H2 and at room temperature with a substrate to catalyst molar ratio of up to 100000. Various aliphatic, aromatic, heteroaromatic, and olefinic tert-alkyl ketones are convertible to the corresponding chiral carbinols in high enantiomeric purity. Olefinic and heteroaromatic functions are left intact. Certain cyclic ketones are also usable. The mode of enantioface selection is consistent and predictable. Copyright
- Ohkuma, Takeshi,Sandoval, Christian A.,Srinivasan, Rajagopal,Lin, Quinghong,Wei, Yinmao,Muniz, Kilian,Noyori, Ryoji
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p. 8288 - 8289
(2007/10/03)
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- Pentylpyridinium tribromide: A vapor pressure free room temperature ionic liquid analogue of bromine
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The synthesis and characterization of the room temperature ionic liquid pentylpyridinium tribromide (2) is described. Tribromide 2 was used as a vapor pressure free bromine analogue for the bromination of ketones, aromatics, alkenes, and alkynes. The brominations were carried out in the absence of organic solvents and in most cases the only extraction solvent needed was water. Selectivities and reactivities were shown to be superior to current protocols. The spent reagent pentylpyridinium bromide (1) was easily recycled.
- Salazar, José,Dorta, Romano
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p. 1318 - 1320
(2007/10/03)
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- Substrate activation: Indirect β-bromination of alcohols
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The reversible oxidation of an alcohol into a ketone provides access to enol/enolate chemistry. Preliminary results have applied this principle to the β-bromination of alcohols.
- Cami-Kobeci, Gerta,Williams, Jonathan M.J.
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p. 124 - 126
(2007/10/03)
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- Elaboration of 1-benzoyltetrahydroisoquinoline derivatives employing a Pictet-Spengler cyclization with α-chloro-α-phenylthioketones. Synthesis of O-methylvelucryptine
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The reaction of N-tosyl-β-phenethylamines with α-chloro-α-phenylthioketones, leading to 1-benzoyl- and 1-pivaloyl-tetrahydroisoquinolines under modified Pictet-Spengler conditions, is described. The synthesis of O-methylvelucryptine employing this transformation as a key step is reported.
- Silveira, Claudio C,Bernardi, Carmem R.,Braga, Antonio L.,Kaufman, Teodoro S.
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p. 8947 - 8950
(2007/10/03)
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- New lead compounds for brassinosteroid biosynthesis inhibitors
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The first brassinosteroid biosynthesis inhibitor is reported. Among newly synthesized triazole derivatives, 4-(4-chlorophenyl)-2-phenyl-3- (1,2,4-triazoyl)butan-2-ol (6) was found to inhibit the growth of cress seedlings, and this inhibition was recovered by the treatment of brassinolide, suggesting that compound 6 primarily inhibits brassinosteroid biosynthesis.
- Min, Yong Ki,Asami, Tadao,Fujioka, Shozo,Murofushi, Noboru,Yamaguchi, Isomaro,Yoshida, Shigeo
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p. 425 - 430
(2007/10/03)
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Photodegradation of Azole Fungicide Triadimefon
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To examine the photostability of the fungicide triadimefon [1-(4-chlorophenoxy)-3,3-dimethyl-1H-(1,2,4-triazol-1-yl)butan-2-one] in the field, model experiments with organic solvents were performed. Photolysis in methanol, hexane, and acetone resulted in considerable formation of 1-(4-chlorophenoxy)-3,3-dimethylbutan-2-one, 1-[(4-chlorophenoxy)methyl]-1H-1,2,4-triazole, 1H-(1,2,4-triazol-1-yl)-3,3-dimethylbutan-2-one, and 1-phenoxy-3,3-dimethyl-1H-(1,2,4-triazol-1-yl)butan-2-one. The rate of photodegradation in different solvents followed first-order rate kinetics with a significant correlation coefficient.
- Nag, Subir K.,Dureja, Prem
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p. 294 - 298
(2007/10/03)
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- Phototransformation of triadimefon on glass and soil surfaces
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Photodegradation of triadimefon has been studied on glass and soil surfaces. A number of photoproducts have been isolated and characterised by NMR, IR and MS. Photolysis resulted in considerable amounts of 1-(4- chlorophenoxymethyl)-1,2,4-triazole, 1-(4-chlorophenoxy)-2,2-dimethyl-1- (1,2,4-triazol-1-yl)propane, 1-(1,2,4-triazol-1-yl)-3,3-dimethylbutan-2-one and 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-ol. Rates of photodegradation on glass and soil surfaces under UV and sunlight followed first-order kinetics with a significant correlation coefficient. Photodegradation was greater on alluvial soil than on laterite soil.
- Nag,Dureja
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p. 247 - 252
(2007/10/03)
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- Synthesis, X-ray Structure and Reactions of (2-Oxoalkyl)triarylbismuthonium Salts
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Treatment of triarylbismuth difluorides 1 with silyl enol ethers 2 in the presence of boron trifluoride-diethyl ether or trimethylsilyl trifluoromethanesulfonate (triflate) gave (2-oxoalkyl)triarylbismuthonium tetrafluoroborates 3 and triflates 4 in good yields.A similar reaction of the difluorides 1 with hexamethyldisiloxane in the presence of the latter acid reagent led to the formation of oxybis(triarylbismuth) ditriflates 5.X-Ray crystallographic analyses of compounds 3a, 4a and 5a showed that the first two onium salts have a distorted tetrahedral geometry and the last, a μ-oxo type compound, has a distorted trigonal bipyramidal geometry around the bismuth centre.The stability of these bismuthonium salts may reasonably be attributed to the intramolecular coordinative interaction between the bismuth and oxygen atoms and also low nucleophilicity of the counter ions employed.The bismuthonium salt 3f readily underwent onium exchange with the phosphine 6 and the sulfide 9 to afford the corresponding phosphonium and sulfonium salts 7 and 10.The salts 3 and 4 also underwent coupling with a variety of nucleophiles such as the enolate 11, piperidine 13, the phenoxides 15, the thiolates 17, the sulfinate 19 and the halides 21 to afford the corresponding α-substituted ketones 12, 14, 16, 18, 20 and 22 in moderate to good yields, together with a good recovery of triphenylbismuthine 8.
- Matano, Yoshihiro,Azuma, Nagao,Suzuki, Hitomi
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p. 1739 - 1748
(2007/10/02)
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- SELECTIVE MONOBROMINATION OF KETONES BY BIS(DIMETHYLACETAMIDE)HYDROGEN TRIBROMIDE
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A unified procedure for the α-monobromination of ketones by bis(dimethylacetamide)hydrogen tribromide in methanol is proposed.Methyl aryl ketones with donating and moderately accepting substituents in the ring readily enter into the reaction. 1-Bromo ketones are mostly formed during the bromination of methyl alkyl ketones.
- Rodygin, M. Yu.,Mikhailov, V. A.,Savelova, V. A.
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p. 881 - 887
(2007/10/02)
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- Synthesis and reactivity of α-halomethyl ketimines
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The synthesis of N-(1-halo-2-alkylidene)amines, i.e. α-halomethyl ketimines, is described for the first time, utilizing the TiCl4-induced condensation of α-halomethyl ketones with primary amines. The reactivity of these new α-halomethylketimines was studied with respect to nucleophiles such as iodide, cyanide, alcohols, alkoxides, amines and thiolates. α-Halomethyl ketimines are powerful ambident electrophiles which underwent a variety of reactions leading to functionalized imines and heterocycles.
- De Kimpe,De Cock,Stevens
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p. 2739 - 2760
(2007/10/02)
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- The far-ultraviolet photochemistry of alkylcyclopropenes in solution
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The photochemistry of 1,3,3-trimethylcyclopropene and 1-tert-butyl-3,3-dimethylcyclopropene has been investigated in hydrocarbon, methanol, and 1-hexene solution with far-ultraviolet (185-228 nm) light.Direct photolysis of the two compounds affords allene, alkyne, and 1,3-diene derivatives, formally as a result of initial bond cleavage to yield vinylcarbene intermediates.Products derived from cleavage of the most substituted (C1-C3) cyclopropene bond account for 60-80percent of the observed mixture in each case.Results from the photolysis of 1,3,3-trimethylcyclopropene-1-13C suggest a second pathway for formation of alkyne products in cyclopropene photochemistry, which occurs in competition with (or by exclusion of) the vinylcarbene -hydrogen migration pathway.The data are consistent with the intermediacy of a vinylidene species, formed by -hydrogen migration/ring opening, although attempts to chemically trap this intermediate with methanol or alkene were unsuccessful.Key words: cyclopropene, photolysis, vinylmethylene, propenylidene, far-UV.
- Fahie, Brian J.,Leigh, William J.
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p. 1859 - 1867
(2007/10/02)
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- Synthesis of Bromoacetyl Derivatives by Use of Tetrabutylammonium Tribromide
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Orange ccrystalline tetrabutylammonium tribromide was prepared using a simple method.The reaction of acetyl dervivatives with an eqimolar amount of the tribromide in dichloromethane-methanol at room temperature bave bromoacetyl derivatives in fairly good yields.
- Kajigaeshi, Shoji,Kakinami, Takaaki,Okamoto, Tsuyoshi,Fujisaki, Shizuo
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p. 1159 - 1160
(2007/10/02)
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- Synthesis and Antifungal Activity of a Series of Novel 1,2-Disubstituted Propenones
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To find an antifungal agent other than those of the imidazole and triazole series, a new class of 1,2-disubstituted propenones I and II was prepared and tested for antifungal activity.Comparison of the structure-activity relationships showed that the conjugated structure of carbonyl and exomethylene groups in I and II plays an important role in potent antifungal acivity.However, it is noteworthy that compounds 53, 54, and 56, which have a hydroxymethyl or methoxymethyl group instead of an exo-methylene group in I, also showed potent activity.Although many compounds exhibited strong antifungal activity in vitro, none showed activity in vivo of oral efficacy against subacute systemic candidiasis in mice. '
- Ogata, Masaru,Matsumoto, Hiroshi,Kida, Shiro,Shimizu, Sumio,Tawara, Katsuya,Kawamura, Yoshimi
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p. 1497 - 1502
(2007/10/02)
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- Asymmetric Synthesis Using Chirally Modified Borohydrides. Part 3. Enantioselective Reduction of Ketones and Oxime Ethers with Reagents Prepared from Borane and Chiral Amino Alcohols
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The asymmetric reduction of aromatic and aliphatic ketones, halogeno ketones, keto esters, and ketone oxime ethers with reagents prepared from borane and chiral amino alcohols has been investigated.When α,α-diphenyl-β-amino alcohols, such as (2S,3R)-(-)-2-amino-3-methyl-1,1-diphenylpentanol (2d), were used as a chiral auxiliary, very high enantioselectivities (ca. 90percent e.e.) were obtained in the reduction of various ketones and oxime ethers.
- Itsuno, Shinichi,Nakano, Michio,Miyazaki, Koji,Masuda, Hirofumi,Ito, Koichi,et al.
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p. 2039 - 2044
(2007/10/02)
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- Thiadiazine herbicides
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N-(1,3,4-Thiadiazin-2-yl)-2,6-dialkoxybenzamide derivatives useful as herbicides.
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- Effet d'engrenage. VIII. Extension a des derives fonctionnels de l'alanine
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The gear effect has been discovered and studied for the first time on molecules where the interacting groups were alkyl substituents.In order to be closer to biochemical models, this effect has now been studied where one interacting group is asymmetric and functional.For this purpose eighteen new compounds derived from alanine have been prepared and studied by nmr and dynamic nmr.The gear effect is operating, and it appears to be a suitable means to modulate the interaction of two active functions.
- Blaive, Bruno,Roussel, Christian,Metzger, Jacques,Sandstroem, Jan
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p. 2212 - 2220
(2007/10/02)
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