- Interplay of method development and mechanistic studies - From aerobic oxidative coupling to radical reactions via alkenyl peroxides
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This account summarizes how scientific advances were made in the authors' research group by combining method development in organic synthesis with detailed mechanistic studies. The discovery of an unexpected autoxidative coupling reaction led, by virtue of an ever increased understanding of its mechanism, to a strategy for green C-H functionalization reactions, novel modes of radical generation, addition reactions of ketones to alkenes and new insights into an old reaction, the Baeyer-Villiger oxidation. 1 Introduction 2 Aerobic Oxidative Coupling Reactions with Benzylic C-H Bonds 2.1 The Autoxidative Coupling with Xanthene 2.2 With a Little Help from Light - CHIPS 2.3 Related Autoxidative Coupling Reactions 3 How Does the Autoxidative Coupling Work? 3.1 An Excursion: Formation of Alkenyl Peroxides from Criegee Intermediates in the Atmosphere 3.2 How do Alkenyl Peroxides Form in Solution? Meet Criegee Again 3.3 The Full Mechanism of the Autoxidative Coupling Reaction 4 Previous Indications for Solution Chemistry of Alkenyl Peroxides 4.1 What Might Alkenyl Peroxides be Good for? 5 Concluding Remarks.
- Klussmann, Martin,Schweitzer-Chaput, Bertrand
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- Chemoselective Demethylation of Methoxypyridine
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A chemoselective demethylation method for various methoxypyridine derivatives has been developed. Treatment of 4-methoxypyridine with L-selectride in THF for 2 h at reflux temperature afforded 4-hydroxypyridine in good yield; no reaction to anisole occurred. The utility of our method was demonstrated by the efficient synthesis of the metabolic substances of the antiulcer agent omeprazole. Chemoselective demethylation at the site of 3,5-dimethyl-4-methoxypyridine in the presence of 4-methoxybenzimidazole was achieved.
- Makino, Kosho,Hasegawa, Yumi,Inoue, Takahide,Araki, Koji,Tabata, Hidetsugu,Oshitari, Tetsuta,Ito, Kiyomi,Natsugari, Hideaki,Takahashi, Hideyo
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p. 951 - 954
(2019/05/10)
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- Asymmetric Homogeneous Hydrogenation of 2-Pyridones
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An asymmetric homogeneous hydrogenation of 2(1H)-pyridones has been developed, using a ruthenium complex bearing two chiral N-heterocyclic carbene (NHC) ligands. To the best of our knowledge, the presented reaction is the first example of a homogeneous asymmetric conversion of 2-pyridones into the corresponding enantioenriched 2-piperidones.
- Wysocki, Jedrzej,Schlepphorst, Christoph,Glorius, Frank
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supporting information
p. 1557 - 1562
(2015/06/30)
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- OXAZOLE AND THIAZOLE DERIVATIVES AS SELECTIVE PROTEIN KINASE INHIBITORS (C-KIT)
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The present invention relates to compounds of formula I or pharmaceutically acceptable salts thereof: wherein R1, R2, R3, A, Q, W and X are as defined in the description. These compounds selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant proteine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective native and/or mutant c-kit inhibitors.
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Page/Page column 77-78
(2013/03/26)
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- PROCESS FOR PRODUCTION OF 2-HYDROXY-4-SUBSTITUTED PYRIDINES
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A process for preparing a 2-hydroxy-4-substituted pyridine compound using a microbiological method, a novel microorganism, and a novel compound are provided. According to the process, a function of a microorganism or a product obtained therefrom is exerted on a 4-substituted pyridine of the general formula (1): wherein R is a methyl group, a carboxyl group, a carbamoyl group, a hydroxyiminomethyl group or a cyano group, to obtain the corresponding 2-hydroxy-4-substituted pyridine compound. The novel microorganisms are the Delftia species YGK-A649 (FERM BP-10389), Delftia species YGK-C217 (FERM BP-10388), or Acidovorax species YGK-A854 (FERM BP-10387) and the novel compound is a 2-hydroxy-4-pyridinaldoxime.
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Page/Page column 10-11
(2008/06/13)
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- Azetidinone compounds useful in the preparation of carbapenem antibiotics and process for preparing carbapenem and penem compounds
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Compounds of formula (I): STR1 wherein: R1 is hydrogen or a hydroxy-protecting group; R2 is alkyl, alkoxy, halogen, optionally substituted phenyl or optionally substituted phenoxy; R3 is optionally substituted pyridyl, optionally substituted quinolyl or phenyl group which has a substituent of formula --CYNR5 R6, where Y is oxygen or sulfur, and R5 and R6 are each alkyl, aryl or aralkyl, or R5 and R6 and the nitrogen to which they are attached together form a heterocyclic group; is R4 hydrogen or an amino-protecting group; and Z is sulfur or oxygen; are valuable intermediates in the preparation of carbapenem compounds and retain a desirable configuration during conversion to such carbapenem compounds. Penem and carbapenem compounds having a group of formula --SA' are prepared from a corresponding compound having a substituted thio, sulfinyl or sulfonyl group at this position by reaction with a compound A'SH (where A' is an organic group) in the presence of a salt of a metal of Group II or III of the Periodic Table.
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- OXYGENATION OF THE UNACTIVATED PYRIDINE SYSTEM BY ACETYL HYPOFLUORITE MADE DIRECTLY FROM F2
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Acetyl hypofluorite was found capable of activating the usually unreactive pyridine by substituting the hydrogen at the 2 position by an acetoxy group which then was hydrolyzed to the corresponding pyridinone.Substitutents at 3, 4 or 5 position do not interfere with the reaction, but compounds with substituents at 2 (with the exception of aromatic ones) either do not react or produce tars.The reaction conditions are very mild and the yields are very good for this kind of substitution.Quinolines and pyrazines also react very satisfactorily.
- Rozen, Shlomo,Hebel, David
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p. 249 - 258
(2007/10/02)
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- Synthesis of 2-Substituted 4-Pyridylpropionates. Part 2. Alkylation Approach
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A synthesis of methyl 3-(2-methoxy-4-pyridyl)propionate (2), a key intermediate in the synthesis of the potent long-acting histamine H2-receptor antagonist SK&F 93574 (1), is described.The key step in the synthesis of compound (1) involves alkylation of 2-methoxy-4-methylpyridine (5) with sodium chloroacetate in the presence of sodamide.The scope and limitations of the alkylation is investigated using a variety of electrophiles.The application of this reaction to other 2-substituted 4-methylpyridines is also discussed.
- Adger, Brian M.,Ayrey, Peter,Bannister, Robin,Forth, Michael A.,Hajikarimian, Yousef,et al.
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p. 2791 - 2796
(2007/10/02)
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- Carbon Dioxide: A Reagent for the Simultaneous Protection of Nucleophilic Centres and the Activation of Alternative Locations to Electrophilic Attack. Part 8. A Novel Synthetic Route to 4-Substituted-2-pyridones
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2-Pyridone, using the one-pot protection method, is lithiated specifically in the 4-position.In this way, a range of 4-substituted 2-pyridones was prepared.Their orientation of substitution was proved by X-ray analysis.
- Katritzky, Alan R.,Fan, Wei-Qiang,Koziol, Anna E.,Palenik, Gus J.
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p. 2343 - 2348
(2007/10/02)
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- The Effect of Acid Concentration on the Pyridine Nitramine Rearrangement: an N.M.R. Study
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The rearrangement of 2- and 4-nitraminopyridines in 70-95percent sulfuric acid has been investigated by n.m.r.Ring nitration is favoured by conditions leading to initial dissociation of the nitramine, and the results provide no support for an intramolecul
- Deady, Leslie W.,Korytsky, Olga L.
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p. 1159 - 1166
(2007/10/02)
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- The Mechanisms of Thermal Eliminations. Part 11. Rate Data for Pyrolysis of 2-Alkoxypyridines to 2-Pyridone, and of 2-Ethoxypicolines to 2-Picolones: Nature and Polarity of the Transition State
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The rates of thermal elimination of 2-ethoxy-, 2-isopropoxy-, 2-t-butoxy-pyridine to 2-pyridone and the corresponding alkene, and of the 2-ethoxy derivatives of 3-, 4-, 5-, and 6-methylpyridines to ethylene and the corresponding 2-picolines have been measured over at least 50 deg for each compound, between 585.1 and 721.1 K.The respective log (A/s-1) and Ea/kJ mol-1 values for the former three compounds are 12.20, 196.5; 12.68, 187.6; and 12.33, 161.0, and these are similar to those for the corresponding acetates.The relative rates of the first-order unimolecular decomposition at 600 K are: Et(1.0), Pri(18.0), But(1645) compared with 1.0:28.8:3316 for the acetates.The polarity of the transition state is thus less than for ester elimination.The difference in the rate ratios k(Pri)/k(Et) for alkoxypyridine and acetate pyrolyses is greater than the difference in the k(But)/k(Pri) ratios and is interpreted in terms of the difference in polarity of the transition states for primary, secondary, and tertiary elimination.Methyl substituents in the 3-, 4-, 5-, and 6-positions of the pyridine ring change the rate at 600 K by factors of 1.57, 1.02, 0.74, and 1.08, respectively.These show the decomposition does not take place via N-alkylpyridone tautomers, and that the reaction is, like ester pyrolysis, sterically accelerated.
- Al-Awadi, Nouria,Ballam, John,Hemblade, Paul R.,Taylor, Roger
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p. 1175 - 1178
(2007/10/02)
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- SYNTHESIS OF PYRIDINE N-OXIDE-SbCl5 COMPLEXES AND THEIR INTRAMOLECULAR AND OXYGEN-TRANSFER REACTION
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Mixing with equimolar solutions of pyridine N-oxide or its homologs and SbCl5 in CCl4 deposited 1:1 complexes as colorless crystals in high yield.On thermolysis, these complexes underwent intramolecular oxygen transfer to give selectively the corresponding 2-pyridone derivatives.N,N-Dimethylaniline N-oxide and SbCl5 also gave a crystalline 1:1 complex which on termolysis yield o-dimethylaminophenol in good yield.
- Yamamoto, Jiro,Imagawa, Masahiro,Yamauchi, Sigeyuki,Nakazava, Osamu,Umezu, Masahiro,et al.
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p. 1871 - 1873
(2007/10/02)
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- Kinetic Study of the Acid-Promoted Hydrolysis of Some Representative 2-Fluoro Nitrogen Heterocycles
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The acid-promoted hydrolysis of the 2-fluoro derivatives of pyridine, the four isomeric picolines, quinoline, pyrimidine, 4-methylpyrimidine, and 4,6-dimethylpyrimidine have been studied in hydrochloric acid over the concentration range of 0.05-8.0 F HCl.At each acid concentration, the reactions followed pseudo-first-order kinetics, and at low concentrations of acid, the rate of reaction increased linearly with h0.However, at higher acid concentrations negative deviations from linearity were observed for all the substrates and rate maxima for all but the pyrimidines.These results were correlated with the decline in water activity by means of the Bunnett ω and ω* relationships, as well as the Bunnett-Olsen LFER.The slopes of these correlations were suggestive of a proton transfer role for water in the reactions of the less activated 2-fluoropyridines and of 2-fluoroquinoline, while the correlations indicate a nucleophilic role for water in the reactions of the more highly activated pyrimidines.Entropies of activation, calculated both from the pseudo-first-order rate constants, and from the values of k2* obtained from the intercepts of the LFER plot, were significantly more negative for the pyridine and quinoline systems for the pyrimidines.The above results are interpreted as consistent with nucleophilic attack by water in the rate-determining step for the reaction of the pyrimidines, while for the less activated substrates nucleophilic attack may be assisted by proton transfer to additional water molecules.
- Clark, H. R.,Beth, L. D.,Burton, R. M.,Garrett, D. L.,Miller, A. L.,Muscio, O. J.
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p. 4363 - 4369
(2007/10/02)
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