- 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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- VERSATILE SYNTHESIS OF AN INTERMEDIATE FOR THE 1β-METHYLCARBAPENEM SYNTHESIS
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A 1β-methylcarboxylate (1) which is a requisite intermediate for the synthesis of the 1β-methylcarbapenem was obtained in an efficient manner by the coupling reaction of a Z(O)-pyridylthiosilyl enol ether and a 4-acetoxyazetidinone derivative in the presence of ZnCl2 in CH2Cl2.The reactive silyl enol ether was prepared by the reverse addition method in high yield.
- Hirai, Koichi,Iwano, Yuji,Mikoshiba, Isamu,Koyama, Hiroo,Nishi, Takahide
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- Methyl ketone derivative, and preparation method and applications thereof
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The invention discloses a methyl ketone derivative, and a preparation method and applications thereof. The preparation method comprises following steps: a ketone derivative and an organic peroxide are dissolved in a solvent, and reaction is carried out at 80 to 130 DEG C so as to obtain methyl pyrimidone and a methyl pyrimidone derivative. According to the preparation method, the ketone derivative is taken as a starting material; the raw materials are easily and widely available; products of different kinds can be obtained via the preparation method, and can be used directly or used in other further reaction. No metal is involved, so that the preparation method is suitable to be applied in pharmaceutical preparation technology. The preparation method is short in route, mild in reaction conditions, simple in reaction operation and postprocessing process, and high in yield, and is suitable for large-scale production.
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Paragraph 0036; 0037
(2017/08/28)
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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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- (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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- (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors
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The invention encompasses the novel compound of Formula A that is useful in the treatment of cyclooxygenase-2 mediated diseases. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula A.
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- 3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to COX-2 inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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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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- ANTIPSYCHOTIC CYCLIC IMIDE DERIVATIVES OF 2-(4-BUTYLPIPERAZIN-1-YL) PYRIDINES, COMPOSITIONS AND USE
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Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is a substituted pyridin-2-yl ring and the second substituent is a butylene chain attached to cyclic imide heterocycles such as azaspiro 4.5!decanedione, dialkylglutarimide, thiazolidinedione, spirocyclopentylthiazolidinedione, or morpholine-2,6-dione. The compounds have psychotropic properties and 2-4-4-(2,4-dioxo-1-thia-3-azaspiro 4. 5!nonane-3-yl)butyl!-1-piperazinyl!-pyridine-3-carboxaldehyde is a typical embodiment having selective antipsychotic activity.
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- ANTIPSYCHOTIC CYCLIC IMIDE DERIVATIVES OF 2-(4-BUTYLPIPERAZIN-1-YL)PYRIDINES, COMPOSITIONS AND USE
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Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is a substituted pyridin-2-yl ring and the second substituent is a butylene chain attached to cyclic imide heterocycles such as azaspiro 4.5!decanedione, dialkylglutarimide, thiazolidinedione, spirocyclopentylthiazolidinedione, or morpholine-2,6-dione. The compounds have psychotropic properties and 2-4-4-(2,4-dioxo-1-thia-3-azaspiro 4. 5!nonane-3-yl)butyl!-1-piperazinyl!pyridine-3-carboxaldehyde is a typical embodiment having selective antipsychotic activity.
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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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